Category Archive Nutrition

How Much Vegetables I Have Needed In A Day

How Much Vegetables I have Needed In A Day/Vegetables are parts of plants that are consumed by humans or other animals as food. The original meaning is still commonly used and is applied to plants collectively to refer to all edible plant matter, including the flowers, fruits, stems, leaves, roots, and seeds. An alternate definition of the term is applied somewhat arbitrarily, often by culinary and cultural tradition. It may exclude foods derived from some plants that are fruits, flowers, nuts, and cereal grains, but include savory fruits such as tomatoes and courgettes, flowers such as broccoli, and seeds such as pulses.

A diet rich in vegetables and fruits can lower blood pressure, reduce the risk of heart disease and stroke, prevent some types of cancer, lower risk of eye and digestive problems, and have a positive effect upon blood sugar, which can help keep appetite in check. Eating non-starchy vegetables and fruits like apples, pears, and green leafy vegetables may even promote weight loss. Their low glycemic loads prevent blood sugar spikes that can increase hunger.

At least nine different families of fruits and vegetables exist, each with potentially hundreds of different plant compounds that are beneficial to health. Eat a variety of types and colors of produce in order to give your body the mix of nutrients it needs. This not only ensures greater diversity of beneficial plant chemicals but also creates eye-appealing meals.

These are general recommendations by age. Find the right amount for you by getting your

Daily Recommendation*
Toddlers 12 to 23 months ⅔ to 1 cup
Children 2-4 yrs 1 to 2 cups
5-8 yrs 1½ to 2½ cups
Girls 9-13 yrs 1½ to 3 cups
14-18 yrs 2½ to 3 cups
Boys 9-13 yrs 2 to 3½ cups
14-18 yrs 2½ to 4 cups
Women 19-30 yrs 2½ to 3 cups
31-59 yrs 2 to 3 cups
60+ yrs 2 to 3 cups
Men 19-30 yrs 3 to 4 cups
31-59 yrs 3 to 4 cups
60+ yrs 2½ to 3½ cups

The amount that counts as 1 cup of vegetables

The amount that counts as 1 cup of vegetables
Dark-Green Vegetables Broccoli 1 cup, chopped or florets, fresh or frozen
Bitter melon leaves, chrysanthemum leaves, escarole, lambs quarters, nettles, poke greens, taro leaves, turnip greens 1 cup, cooked
Amaranth leaves, beet greens, bok choy, broccoli raab (rapini), chard, collards (collard greens), cress, dandelion greens, kale, mustard greens, spinach, Swiss chard, watercress 1 cup, cooked

2 cups, fresh

Raw leafy greens: Arugula (rocket), basil, cilantro,  dark green leafy lettuce, endive, escarole, mixed greens, mesclun, romaine 2 cups, fresh
Red and Orange Vegetables Carrots 2 medium carrots

1 cup, sliced or chopped, fresh, cooked, or frozen

1 cup baby carrots

Pimento/Pimiento 3 whole

1 cup

Pumpkin, calabaza 1 cup, mashed, cooked
Red and orange bell peppers 1 large bell pepper

1 cup, chopped, fresh, or cooked

Red chili peppers ¾ cup
Sweet potato 1 large sweet potato, baked

1 cup, sliced or mashed, cooked

Tomatoes 1 large tomato

2 small tomatoes

1 cup, chopped or sliced, fresh, canned, or cooked

100% vegetable juice 1 cup
Winter squash (acorn, butternut, hubbard, kabocha) 1 cup, cubed, cooked
Beans, Peas, and Lentils Dry beans and peas and lentils (such as bayo, black, brown, fava, garbanzo, kidney, lima, mung, navy, pigeon, pink, pinto, soy, or white beans, or black-eyed peas (cow peas) or split peas, and red, brown, and green lentils) 1 cup, whole or mashed, cooked
Starchy Vegetables Breadfruit 1 ½ cups, cooked
Cassava ¾ cup, cooked
Corn, yellow or white 1 large ear of corn

1 cup corn kernels, fresh or frozen

Green peas 1 cup fresh or frozen
Hominy 1 cup, cooked
Plantains ¾ cup, cooked
White potatoes 1 medium white potato, boiled or baked

1 cup, diced, mashed, fresh or frozen

Other Vegetables Avocado 1 avocado
Bamboo shoots 1 cup
Bean sprouts 1 cup, cooked
Cabbage, green, red, napa, savoy 1 cup, chopped or shredded raw or cooked
Cactus pads (nopales) 5 pads

1 cup sliced

Cauliflower 1 cup, pieces or florets raw or cooked, fresh or frozen
Celery 1 cup, diced or sliced, raw or cooked

2 large stalks (11″ to 12″ long)

Cucumbers 1 cup, raw, sliced or chopped
Green or wax beans 1 cup, cooked
Green bell peppers 1 large bell pepper

1 cup, chopped, raw or cooked, fresh or frozen

Lettuce, iceberg or head 2 cups, raw, shredded or chopped
Mushrooms 1 cup, raw or cooked
Okra 1 cup, cooked
Onions 1 cup, chopped, raw or cooked
Summer squash or zucchini 1 cup, cooked, sliced or diced

Health Benefits

All food and beverage choices matter – focus on variety, amount, and nutrition.

  • As part of an overall healthy diet, eating foods such as vegetables that are lower in calories per cup instead of some other higher-calorie food may be useful in helping to lower calorie intake.
  • Eating a diet rich in vegetables and fruits as part of an overall healthy diet may reduce risk for heart disease, including heart attack and stroke.
  • Eating a diet rich in some vegetables and fruits as part of an overall healthy diet may protect against certain types of cancers.
  • Adding vegetables can help increase intake of fiber and potassium, which are important nutrients that many Americans do not get enough of in their diet.

Vegetables are well-known for being good for your health. Most vegetables are low in calories but high in vitamins, minerals and fiber. However, some vegetables stand out from the rest with additional proven health benefits, such as the ability to fight inflammation or reduce the risk of disease.

Which Kind Of Vegetables Are Best According To My Age

1. Spinach

  • This leafy green tops the chart as one of the healthiest vegetables, thanks to its impressive nutrient profile.
  • One cup (30 grams) of raw spinach provides 56% of your daily vitamin A needs plus your entire daily vitamin K requirement — all for just 7 calories (rx).
  • Spinach also boasts a lot of antioxidants, which can help reduce the risk of chronic disease.
  • One study found that dark green leafy vegetables like spinach are high in beta-carotene and lutein, two types of antioxidants that have been associated with a decreased risk of cancer (rx).
  • In addition, a 2015 study found that spinach consumption may be beneficial for heart health, as it may lower blood pressure (rx).

SUMMARY:Spinach is rich in antioxidants that may reduce the risk of chronic disease, as it may reduce risk factors such as high blood pressure.

2. Carrots

  • Carrots are packed with vitamin A, providing 428% of the daily recommended value in just one cup (128 grams) (rx).
  • They contain beta-carotene, an antioxidant that gives carrots their vibrant orange color and could help in cancer prevention (rx).
  • In fact, one study revealed that for each serving of carrots per week, participants’ risk of prostate cancer decreased by 5% (rx).
  • Another study showed that eating carrots may reduce the risk of lung cancer in smokers as well. Compared to those who ate carrots at least once a week, smokers who did not eat carrots had a three times greater risk of developing lung cancer (rx).
  • Carrots are also high in vitamin C, vitamin K and potassium (rx).

SUMMARY:Carrots are especially high in beta-carotene, which can turn into vitamin A in the body. Their high antioxidant content may help reduce the risk of lung and prostate cancer.

3. Broccoli

  • Broccoli belongs to the cruciferous family of vegetables.
  • It is rich in a sulfur-containing plant compound known as glucosinolate, as well as sulforaphane, a by-product of glucosinolate (rx).
  • Sulforaphane is significant in that it has been shown to have a protective effect against cancer.
  • In one animal study, sulforaphane was able to reduce the size and number of breast cancer cells while also blocking tumor growth in mice (rx).
  • Eating broccoli may help prevent other types of chronic disease, too.
  • A 2010 animal study found that consuming broccoli sprouts could protect the heart from disease-causing oxidative stress by significantly lower levels of oxidants (rx).
  • In addition to its ability to prevent disease, broccoli is also loaded with nutrients.
  • A cup (91 grams) of raw broccoli provides 116% of your daily vitamin K needs, 135% of the daily vitamin C requirement and a good amount of folate, manganese and potassium (rx).

SUMMARY:Broccoli is a cruciferous vegetable that contains sulforaphane, a compound that may prevent cancer growth. Eating broccoli may also help reduce the risk of chronic disease by protecting against oxidative stress.

4. Garlic

  • Garlic has a long history of use as a medicinal plant, with roots tracing all the way back to ancient China and Egypt (rx).
  • The main active compound in garlic is allicin, a plant compound that is largely responsible for garlic’s variety of health benefits (rx).
  • Several studies have shown that garlic can regulate blood sugar as well as promote heart health.
  • In one animal study, diabetic rats were given either garlic oil or diallyl trisulfide, a component of garlic. Both garlic compounds caused a decrease in blood sugar and improved insulin sensitivity (rx).
  • Another study fed garlic to participants both with and without heart disease. Results showed that garlic was able to decrease total blood cholesterol, triglycerides, and LDL cholesterol while increasing HDL cholesterol in both groups (rx).
  • Garlic may be useful in the prevention of cancer as well. One test-tube study demonstrated that allicin induced cell death in human liver cancer cells (rx).
  • However, further research is needed to better understand the potential anti-cancer effects of garlic.

SUMMARY:Studies show that garlic may help lower blood triglyceride levels. Some studies have also found that it could decrease blood sugar levels and may have an anti-cancer effect, although more research is needed.

5. Brussels Sprouts

  • Like broccoli, Brussels sprouts are a member of the cruciferous family of vegetables and contain the same health-promoting plant compounds.
  • Brussels sprouts also contain kaempferol, an antioxidant that may be particularly effective in preventing damage to cells (rx).
  • One animal study found that kaempferol protected against free radicals, which cause oxidative damage to cells and can contribute to chronic disease (rx).
  • Brussels sprout consumption can help enhance detoxification as well.
  • One study showed that eating Brussels sprouts led to a 15–30% increase in some of the specific enzymes that control detoxification, which could decrease the risk of colorectal cancer (rx).
  • Additionally, Brussels sprouts are very nutrient-dense. Each serving provides a good amount of many vitamins and minerals, including vitamin K, vitamin A, vitamin C, folate, manganese and potassium (rx).

SUMMARY:Brussels sprouts contain an antioxidant called kaempferol, which may protect against oxidative damage to cells and prevent chronic disease. They may also help enhance detoxification in the body.

6. Kale

  • Like other leafy greens, kale is well-known for its health-promoting qualities, including its nutrient density and antioxidant content.
  • A cup (67 grams) of raw kale contains plenty of B vitamins, potassium, calcium and copper.
  • It also fulfills your entire daily requirement for vitamins A, C, and K (rx).
  • Due to its high amount of antioxidants, kale may also be beneficial in promoting heart health.
  • In a 2008 study, 32 men with high cholesterol drank 150 ml of kale juice daily for 12 weeks. By the end of the study, HDL cholesterol increased by 27%, LDL cholesterol decreased by 10% and antioxidant activity was increased (rx).
  • Another study showed that drinking kale juice can decrease blood pressure and may be beneficial in reducing both blood cholesterol and blood sugar (rx).

SUMMARY:Kale is high in vitamins A, C and K as well as antioxidants. Studies show that drinking kale juice could reduce blood pressure and LDL cholesterol while increasing HDL cholesterol.

7. Green Peas

  • Peas are considered starchy vegetables. This means they have a higher amount of carbs and calories than non-starchy vegetables and may impact blood sugar levels when eaten in large amounts.
  • Nevertheless, green peas are incredibly nutritious.
  • One cup (160 grams) of cooked green peas contains 9 grams of fiber, 9 grams of protein and vitamins A, C and K, riboflavin, thiamin, niacin and folate (rx).
  • Because they are high in fiber, peas support digestive health by enhancing the beneficial bacteria in your gut and promoting regular bowel movements (rx).
  • Moreover, peas are rich in saponins, a group of plant compounds known for their anti-cancer effects (rx).
  • Research shows that saponins may help fight cancer by reducing tumor growth and inducing cell death in cancer cells (rx).

SUMMARY:Green peas contain a good amount of fiber, which helps support digestive health. They also contain plant compounds called saponins, which may have anti-cancer effects.

8. Swiss Chard

  • Swiss chard is low in calories but high in many essential vitamins and minerals.
  • One cup (36 grams) contains just 7 calories yet 1 gram of fiber, 1 gram of protein and lots of vitamins A, C and K, manganese and magnesium (rx).
  • Swiss chard is especially known for its potential to prevent damage caused by diabetes mellitus.
  • In one animal study, chard extract was found to reverse the effects of diabetes by decreasing blood sugar levels and preventing cell damage from disease-causing free radicals (rx).
  • Other animal studies have shown that the antioxidant content of chard extract can protect the liver and kidneys from the negative effects of diabetes (rx, rx).

SUMMARY:Some animal studies show that Swiss chard could protect against the negative effects of diabetes and may decrease blood sugar levels.

9. Ginger

  • Ginger root is used as a spice in everything from vegetable dishes to desserts.
  • Historically, ginger has also been used as a natural remedy for motion sickness (rx).
  • Several studies have confirmed the beneficial effects of ginger on nausea. In a review comprised of 12 studies and nearly 1,300 pregnant women, ginger significantly reduced nausea compared to a placebo (rx).
  • Ginger also contains potent anti-inflammatory properties, which can be helpful in treating inflammation-related disorders like arthritis, lupus or gout (rx).
  • In one study, participants with osteoarthritis who were treated with a concentrated ginger extract experienced reduced knee pain and relief from other symptoms (rx).
  • Further research suggests that ginger could aid in the treatment of diabetes as well.
  • A 2015 study looked at the effects of ginger supplements on diabetes. After 12 weeks, ginger was found to be effective in decreasing blood sugar levels (rx).

SUMMARY:Studies show that ginger could reduce nausea and alleviate inflammation. Ginger supplements may also help decrease blood sugar.

10. Asparagus

  • This spring vegetable is rich in several vitamins and minerals, making it an excellent addition to any diet.
  • Just half a cup (90 grams) of asparagus provides one-third of your daily folate needs.
  • This amount also provides plenty of selenium, vitamin K, thiamin, and riboflavin (rx).
  • Getting enough folate from sources like asparagus can offer protection from disease and can prevent neural tube birth defects during pregnancy (rx, rx).
  • Some test-tube studies also show that asparagus may benefit the liver by supporting its metabolic function and protecting it against toxicity (rx).

SUMMARY:Asparagus is especially high in folate, which may help prevent neural tube birth defects. Test-tube studies have also found that asparagus can support liver function and reduce the risk of toxicity.

11. Red Cabbage

  • This vegetable belongs to the cruciferous family of vegetables and, much like its relatives, is brimming with antioxidants and health-promoting properties.
  • One cup (89 grams) of raw red cabbage contains 2 grams of fiber as well as 85% of the daily vitamin C requirement (rx).
  • Red cabbage is also rich in anthocyanins, a group of plant compounds that contribute to its distinct color as well as a whole host of health benefits.
  • In a 2012 animal study, rats were fed a diet designed to increase cholesterol levels and increase plaque buildup in the arteries. The rats were then given red cabbage extract.
  • The study found that red cabbage extract was able to prevent increases in blood cholesterol levels and protect against damage to the heart and liver (rx).
  • These results were supported by another animal study in 2014 showing that red cabbage could reduce inflammation and prevent liver damage in rats fed a high-cholesterol diet (rx).

SUMMARY:Red cabbage contains a good amount of fiber, vitamin C and anthocyanins. Certain studies show that it may decrease blood cholesterol levels, reduce inflammation and lower the risk of heart and liver damage.

12. Sweet Potatoes

  • Classified as a root vegetable, sweet potatoes stand out for their vibrant orange color, sweet taste and impressive health benefits.
  • One medium sweet potato contains 4 grams of fiber, 2 grams of protein and a good amount of vitamin C, vitamin B6, potassium and manganese (rx).
  • It’s also high in a form of vitamin A called beta-carotene. In fact, one sweet potato fulfills 438% of your daily vitamin A needs (rx).
  • Beta-carotene consumption has been linked to a significant decrease in the risk of certain types of cancer, including lung and breast cancer (rx, rx).
  • Specific types of sweet potatoes may also contain additional benefits. For example, Caiapo is a type of white sweet potato that may have an anti-diabetic effect.
  • In one study, people with diabetes were given 4 grams of Caiapo daily over 12 weeks, leading to a reduction in both blood sugar and blood cholesterol levels (rx).

SUMMARY:Sweet potatoes are high in beta-carotene, which may decrease the risk of some types of cancer. White sweet potatoes could also help reduce blood cholesterol and blood sugar levels.

13. Collard Greens

  • Collard greens are a very nutrient-rich vegetable.
  • One cup (190 grams) of cooked collard greens contains 5 grams of fiber, 4 grams of protein and 27% of your daily calcium needs (rx).
  • In fact, collard greens are one of the best plant sources of calcium available, along with other leafy greens, broccoli and soybeans.
  • Adequate calcium intake from plant sources can promote bone health and has been shown to decrease the risk of osteoporosis (rx).
  • Collard greens are also high in antioxidants and could even reduce your risk of developing certain diseases.
  • One study found that eating more than one serving of collard greens per week was associated with a 57% decreased risk of glaucoma, an eye condition that can lead to blindness (rx).
  • Another study showed that a high intake of vegetables in the Brassica family, which includes collard greens, may decrease the risk of prostate cancer (rx).

SUMMARY:Collard greens are high in calcium, which could reduce the risk of osteoporosis. The regular intake of collard greens has also been associated with a reduced risk of glaucoma and prostate cancer.

14. Kohlrabi

  • Also known as the turnip cabbage or German turnip, kohlrabi is a vegetable related to the cabbage that can be eaten raw or cooked.
  • Raw kohlrabi is high in fiber, providing 5 grams in each cup (135 grams). It’s also full of vitamin C, providing 140% of the daily value per cup (rx).
  • Studies have shown that the antioxidant content of kohlrabi makes it a powerful tool against inflammation and diabetes (rx).
  • In one animal study, kohlrabi extract was able to decrease blood sugar levels by 64% within just seven days of treatment (rx).
  • Though there are different types of kohlrabi available, studies show that red kohlrabi has nearly twice the amount of phenolic antioxidants and displays stronger anti-diabetic and anti-inflammatory effects (rx).

SUMMARY:Kohlrabi is rich in both fiber and vitamin C. Animal studies show that kohlrabi could potentially cause a reduction in blood sugar.

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Which Kind Of Vegetables Are Best According To My Age

Which Kind Of Vegetables Are Best According To My Age/Vegetables are parts of plants that are consumed by humans or other animals as food. The original meaning is still commonly used and is applied to plants collectively to refer to all edible plant matter, including the flowers, fruits, stems, leaves, roots, and seeds. An alternate definition of the term is applied somewhat arbitrarily, often by culinary and cultural tradition. It may exclude foods derived from some plants that are fruits, flowers, nuts, and cereal grains, but include savory fruits such as tomatoes and courgettes, flowers such as broccoli, and seeds such as pulses.

A diet rich in vegetables and fruits can lower blood pressure, reduce the risk of heart disease and stroke, prevent some types of cancer, lower risk of eye and digestive problems, and have a positive effect upon blood sugar, which can help keep appetite in check. Eating non-starchy vegetables and fruits like apples, pears, and green leafy vegetables may even promote weight loss. Their low glycemic loads prevent blood sugar spikes that can increase hunger.

At least nine different families of fruits and vegetables exist, each with potentially hundreds of different plant compounds that are beneficial to health. Eat a variety of types and colors of produce in order to give your body the mix of nutrients it needs. This not only ensures greater diversity of beneficial plant chemicals but also creates eye-appealing meals.

These are general recommendations by age. Find the right amount for you by getting your

Daily Recommendation*
Toddlers 12 to 23 months ⅔ to 1 cup
Children 2-4 yrs 1 to 2 cups
5-8 yrs 1½ to 2½ cups
Girls 9-13 yrs 1½ to 3 cups
14-18 yrs 2½ to 3 cups
Boys 9-13 yrs 2 to 3½ cups
14-18 yrs 2½ to 4 cups
Women 19-30 yrs 2½ to 3 cups
31-59 yrs 2 to 3 cups
60+ yrs 2 to 3 cups
Men 19-30 yrs 3 to 4 cups
31-59 yrs 3 to 4 cups
60+ yrs 2½ to 3½ cups

The amount that counts as 1 cup of vegetables

The amount that counts as 1 cup of vegetables
Dark-Green Vegetables Broccoli 1 cup, chopped or florets, fresh or frozen
Bitter melon leaves, chrysanthemum leaves, escarole, lambs quarters, nettles, poke greens, taro leaves, turnip greens 1 cup, cooked
Amaranth leaves, beet greens, bok choy, broccoli raab (rapini), chard, collards (collard greens), cress, dandelion greens, kale, mustard greens, spinach, Swiss chard, watercress 1 cup, cooked

2 cups, fresh

Raw leafy greens: Arugula (rocket), basil, cilantro,  dark green leafy lettuce, endive, escarole, mixed greens, mesclun, romaine 2 cups, fresh
Red and Orange Vegetables Carrots 2 medium carrots

1 cup, slices or chopped, fresh, cooked or frozen

1 cup baby carrots

Pimento/Pimiento 3 whole

1 cup

Pumpkin, calabaza 1 cup, mashed, cooked
Red and orange bell peppers 1 large bell pepper

1 cup, chopped, fresh, or cooked

Red chili peppers ¾ cup
Sweet potato 1 large sweet potato, baked

1 cup, sliced or mashed, cooked

Tomatoes 1 large tomato

2 small tomatoes

1 cup, chopped or sliced, fresh, canned, or cooked

100% vegetable juice 1 cup
Winter squash (acorn, butternut, hubbard, kabocha) 1 cup, cubed, cooked
Beans, Peas, and Lentils Dry beans and peas and lentils (such as bayo, black, brown, fava, garbanzo, kidney, lima, mung, navy, pigeon, pink, pinto, soy, or white beans, or black-eyed peas (cow peas) or split peas, and red, brown, and green lentils) 1 cup, whole or mashed, cooked
Starchy Vegetables Breadfruit 1 ½ cups, cooked
Cassava ¾ cup, cooked
Corn, yellow or white 1 large ear of corn

1 cup corn kernels, fresh or frozen

Green peas 1 cup fresh or frozen
Hominy 1 cup, cooked
Plantains ¾ cup, cooked
White potatoes 1 medium white potato, boiled or baked

1 cup, diced, mashed, fresh or frozen

Other Vegetables Avocado 1 avocado
Bamboo shoots 1 cup
Bean sprouts 1 cup, cooked
Cabbage, green, red, napa, savoy 1 cup, chopped or shredded raw or cooked
Cactus pads (nopales) 5 pads

1 cup sliced

Cauliflower 1 cup, pieces or florets raw or cooked, fresh or frozen
Celery 1 cup, diced or sliced, raw or cooked

2 large stalks (11″ to 12″ long)

Cucumbers 1 cup, raw, sliced or chopped
Green or wax beans 1 cup, cooked
Green bell peppers 1 large bell pepper

1 cup, chopped, raw or cooked, fresh or frozen

Lettuce, iceberg or head 2 cups, raw, shredded or chopped
Mushrooms 1 cup, raw or cooked
Okra 1 cup, cooked
Onions 1 cup, chopped, raw or cooked
Summer squash or zucchini 1 cup, cooked, sliced or diced

Health Benefits

All food and beverage choices matter – focus on variety, amount, and nutrition.

  • As part of an overall healthy diet, eating foods such as vegetables that are lower in calories per cup instead of some other higher-calorie food may be useful in helping to lower calorie intake.
  • Eating a diet rich in vegetables and fruits as part of an overall healthy diet may reduce risk for heart disease, including heart attack and stroke.
  • Eating a diet rich in some vegetables and fruits as part of an overall healthy diet may protect against certain types of cancers.
  • Adding vegetables can help increase intake of fiber and potassium, which are important nutrients that many Americans do not get enough of in their diet.

Vegetables are well-known for being good for your health. Most vegetables are low in calories but high in vitamins, minerals and fiber. However, some vegetables stand out from the rest with additional proven health benefits, such as the ability to fight inflammation or reduce the risk of disease.

Which Kind Of Vegetables Are Best According To My Age

1. Spinach

  • This leafy green tops the chart as one of the healthiest vegetables, thanks to its impressive nutrient profile.
  • One cup (30 grams) of raw spinach provides 56% of your daily vitamin A needs plus your entire daily vitamin K requirement — all for just 7 calories (rx).
  • Spinach also boasts a lot of antioxidants, which can help reduce the risk of chronic disease.
  • One study found that dark green leafy vegetables like spinach are high in beta-carotene and lutein, two types of antioxidants that have been associated with a decreased risk of cancer (rx).
  • In addition, a 2015 study found that spinach consumption may be beneficial for heart health, as it may lower blood pressure (rx).

SUMMARY:Spinach is rich in antioxidants that may reduce the risk of chronic disease, as it may reduce risk factors such as high blood pressure.

2. Carrots

  • Carrots are packed with vitamin A, providing 428% of the daily recommended value in just one cup (128 grams) (rx).
  • They contain beta-carotene, an antioxidant that gives carrots their vibrant orange color and could help in cancer prevention (rx).
  • In fact, one study revealed that for each serving of carrots per week, participants’ risk of prostate cancer decreased by 5% (rx).
  • Another study showed that eating carrots may reduce the risk of lung cancer in smokers as well. Compared to those who ate carrots at least once a week, smokers who did not eat carrots had a three times greater risk of developing lung cancer (rx).
  • Carrots are also high in vitamin C, vitamin K and potassium (rx).

SUMMARY:Carrots are especially high in beta-carotene, which can turn into vitamin A in the body. Their high antioxidant content may help reduce the risk of lung and prostate cancer.

3. Broccoli

  • Broccoli belongs to the cruciferous family of vegetables.
  • It is rich in a sulfur-containing plant compound known as glucosinolate, as well as sulforaphane, a by-product of glucosinolate (rx).
  • Sulforaphane is significant in that it has been shown to have a protective effect against cancer.
  • In one animal study, sulforaphane was able to reduce the size and number of breast cancer cells while also blocking tumor growth in mice (rx).
  • Eating broccoli may help prevent other types of chronic disease, too.
  • A 2010 animal study found that consuming broccoli sprouts could protect the heart from disease-causing oxidative stress by significantly lower levels of oxidants (rx).
  • In addition to its ability to prevent disease, broccoli is also loaded with nutrients.
  • A cup (91 grams) of raw broccoli provides 116% of your daily vitamin K needs, 135% of the daily vitamin C requirement and a good amount of folate, manganese and potassium (rx).

SUMMARY:Broccoli is a cruciferous vegetable that contains sulforaphane, a compound that may prevent cancer growth. Eating broccoli may also help reduce the risk of chronic disease by protecting against oxidative stress.

4. Garlic

  • Garlic has a long history of use as a medicinal plant, with roots tracing all the way back to ancient China and Egypt (rx).
  • The main active compound in garlic is allicin, a plant compound that is largely responsible for garlic’s variety of health benefits (rx).
  • Several studies have shown that garlic can regulate blood sugar as well as promote heart health.
  • In one animal study, diabetic rats were given either garlic oil or diallyl trisulfide, a component of garlic. Both garlic compounds caused a decrease in blood sugar and improved insulin sensitivity (rx).
  • Another study fed garlic to participants both with and without heart disease. Results showed that garlic was able to decrease total blood cholesterol, triglycerides, and LDL cholesterol while increasing HDL cholesterol in both groups (rx).
  • Garlic may be useful in the prevention of cancer as well. One test-tube study demonstrated that allicin induced cell death in human liver cancer cells (rx).
  • However, further research is needed to better understand the potential anti-cancer effects of garlic.

SUMMARY:Studies show that garlic may help lower blood triglyceride levels. Some studies have also found that it could decrease blood sugar levels and may have an anti-cancer effect, although more research is needed.

5. Brussels Sprouts

  • Like broccoli, Brussels sprouts are a member of the cruciferous family of vegetables and contain the same health-promoting plant compounds.
  • Brussels sprouts also contain kaempferol, an antioxidant that may be particularly effective in preventing damage to cells (rx).
  • One animal study found that kaempferol protected against free radicals, which cause oxidative damage to cells and can contribute to chronic disease (rx).
  • Brussels sprout consumption can help enhance detoxification as well.
  • One study showed that eating Brussels sprouts led to a 15–30% increase in some of the specific enzymes that control detoxification, which could decrease the risk of colorectal cancer (rx).
  • Additionally, Brussels sprouts are very nutrient-dense. Each serving provides a good amount of many vitamins and minerals, including vitamin K, vitamin A, vitamin C, folate, manganese and potassium (rx).

SUMMARY:Brussels sprouts contain an antioxidant called kaempferol, which may protect against oxidative damage to cells and prevent chronic disease. They may also help enhance detoxification in the body.

6. Kale

  • Like other leafy greens, kale is well-known for its health-promoting qualities, including its nutrient density and antioxidant content.
  • A cup (67 grams) of raw kale contains plenty of B vitamins, potassium, calcium and copper.
  • It also fulfills your entire daily requirement for vitamins A, C, and K (rx).
  • Due to its high amount of antioxidants, kale may also be beneficial in promoting heart health.
  • In a 2008 study, 32 men with high cholesterol drank 150 ml of kale juice daily for 12 weeks. By the end of the study, HDL cholesterol increased by 27%, LDL cholesterol decreased by 10% and antioxidant activity was increased (rx).
  • Another study showed that drinking kale juice can decrease blood pressure and may be beneficial in reducing both blood cholesterol and blood sugar (rx).

SUMMARY:Kale is high in vitamins A, C and K as well as antioxidants. Studies show that drinking kale juice could reduce blood pressure and LDL cholesterol while increasing HDL cholesterol.

7. Green Peas

  • Peas are considered starchy vegetables. This means they have a higher amount of carbs and calories than non-starchy vegetables and may impact blood sugar levels when eaten in large amounts.
  • Nevertheless, green peas are incredibly nutritious.
  • One cup (160 grams) of cooked green peas contains 9 grams of fiber, 9 grams of protein and vitamins A, C and K, riboflavin, thiamin, niacin and folate (rx).
  • Because they are high in fiber, peas support digestive health by enhancing the beneficial bacteria in your gut and promoting regular bowel movements (rx).
  • Moreover, peas are rich in saponins, a group of plant compounds known for their anti-cancer effects (rx).
  • Research shows that saponins may help fight cancer by reducing tumor growth and inducing cell death in cancer cells (rx).

SUMMARY:Green peas contain a good amount of fiber, which helps support digestive health. They also contain plant compounds called saponins, which may have anti-cancer effects.

8. Swiss Chard

  • Swiss chard is low in calories but high in many essential vitamins and minerals.
  • One cup (36 grams) contains just 7 calories yet 1 gram of fiber, 1 gram of protein and lots of vitamins A, C and K, manganese and magnesium (rx).
  • Swiss chard is especially known for its potential to prevent damage caused by diabetes mellitus.
  • In one animal study, chard extract was found to reverse the effects of diabetes by decreasing blood sugar levels and preventing cell damage from disease-causing free radicals (rx).
  • Other animal studies have shown that the antioxidant content of chard extract can protect the liver and kidneys from the negative effects of diabetes (rx, rx).

SUMMARY:Some animal studies show that Swiss chard could protect against the negative effects of diabetes and may decrease blood sugar levels.

9. Ginger

  • Ginger root is used as a spice in everything from vegetable dishes to desserts.
  • Historically, ginger has also been used as a natural remedy for motion sickness (rx).
  • Several studies have confirmed the beneficial effects of ginger on nausea. In a review comprised of 12 studies and nearly 1,300 pregnant women, ginger significantly reduced nausea compared to a placebo (rx).
  • Ginger also contains potent anti-inflammatory properties, which can be helpful in treating inflammation-related disorders like arthritis, lupus or gout (rx).
  • In one study, participants with osteoarthritis who were treated with a concentrated ginger extract experienced reduced knee pain and relief from other symptoms (rx).
  • Further research suggests that ginger could aid in the treatment of diabetes as well.
  • A 2015 study looked at the effects of ginger supplements on diabetes. After 12 weeks, ginger was found to be effective in decreasing blood sugar levels (rx).

SUMMARY:Studies show that ginger could reduce nausea and alleviate inflammation. Ginger supplements may also help decrease blood sugar.

10. Asparagus

  • This spring vegetable is rich in several vitamins and minerals, making it an excellent addition to any diet.
  • Just half a cup (90 grams) of asparagus provides one-third of your daily folate needs.
  • This amount also provides plenty of selenium, vitamin K, thiamin, and riboflavin (rx).
  • Getting enough folate from sources like asparagus can offer protection from disease and can prevent neural tube birth defects during pregnancy (rx, rx).
  • Some test-tube studies also show that asparagus may benefit the liver by supporting its metabolic function and protecting it against toxicity (rx).

SUMMARY:Asparagus is especially high in folate, which may help prevent neural tube birth defects. Test-tube studies have also found that asparagus can support liver function and reduce the risk of toxicity.

11. Red Cabbage

  • This vegetable belongs to the cruciferous family of vegetables and, much like its relatives, is brimming with antioxidants and health-promoting properties.
  • One cup (89 grams) of raw red cabbage contains 2 grams of fiber as well as 85% of the daily vitamin C requirement (rx).
  • Red cabbage is also rich in anthocyanins, a group of plant compounds that contribute to its distinct color as well as a whole host of health benefits.
  • In a 2012 animal study, rats were fed a diet designed to increase cholesterol levels and increase plaque buildup in the arteries. The rats were then given red cabbage extract.
  • The study found that red cabbage extract was able to prevent increases in blood cholesterol levels and protect against damage to the heart and liver (rx).
  • These results were supported by another animal study in 2014 showing that red cabbage could reduce inflammation and prevent liver damage in rats fed a high-cholesterol diet (rx).

SUMMARY:Red cabbage contains a good amount of fiber, vitamin C and anthocyanins. Certain studies show that it may decrease blood cholesterol levels, reduce inflammation and lower the risk of heart and liver damage.

12. Sweet Potatoes

  • Classified as a root vegetable, sweet potatoes stand out for their vibrant orange color, sweet taste and impressive health benefits.
  • One medium sweet potato contains 4 grams of fiber, 2 grams of protein and a good amount of vitamin C, vitamin B6, potassium and manganese (rx).
  • It’s also high in a form of vitamin A called beta-carotene. In fact, one sweet potato fulfills 438% of your daily vitamin A needs (rx).
  • Beta-carotene consumption has been linked to a significant decrease in the risk of certain types of cancer, including lung and breast cancer (rx, rx).
  • Specific types of sweet potatoes may also contain additional benefits. For example, Caiapo is a type of white sweet potato that may have an anti-diabetic effect.
  • In one study, people with diabetes were given 4 grams of Caiapo daily over 12 weeks, leading to a reduction in both blood sugar and blood cholesterol levels (rx).

SUMMARY:Sweet potatoes are high in beta-carotene, which may decrease the risk of some types of cancer. White sweet potatoes could also help reduce blood cholesterol and blood sugar levels.

13. Collard Greens

  • Collard greens are a very nutrient-rich vegetable.
  • One cup (190 grams) of cooked collard greens contains 5 grams of fiber, 4 grams of protein and 27% of your daily calcium needs (rx).
  • In fact, collard greens are one of the best plant sources of calcium available, along with other leafy greens, broccoli and soybeans.
  • Adequate calcium intake from plant sources can promote bone health and has been shown to decrease the risk of osteoporosis (rx).
  • Collard greens are also high in antioxidants and could even reduce your risk of developing certain diseases.
  • One study found that eating more than one serving of collard greens per week was associated with a 57% decreased risk of glaucoma, an eye condition that can lead to blindness (rx).
  • Another study showed that a high intake of vegetables in the Brassica family, which includes collard greens, may decrease the risk of prostate cancer (rx).

SUMMARY:Collard greens are high in calcium, which could reduce the risk of osteoporosis. The regular intake of collard greens has also been associated with a reduced risk of glaucoma and prostate cancer.

14. Kohlrabi

  • Also known as the turnip cabbage or German turnip, kohlrabi is a vegetable related to the cabbage that can be eaten raw or cooked.
  • Raw kohlrabi is high in fiber, providing 5 grams in each cup (135 grams). It’s also full of vitamin C, providing 140% of the daily value per cup (rx).
  • Studies have shown that the antioxidant content of kohlrabi makes it a powerful tool against inflammation and diabetes (rx).
  • In one animal study, kohlrabi extract was able to decrease blood sugar levels by 64% within just seven days of treatment (rx).
  • Though there are different types of kohlrabi available, studies show that red kohlrabi has nearly twice the amount of phenolic antioxidants and displays stronger anti-diabetic and anti-inflammatory effects (rx).

SUMMARY:Kohlrabi is rich in both fiber and vitamin C. Animal studies show that kohlrabi could potentially cause a reduction in blood sugar.

Metabolism of Nutrients – Types, Structure, Functions

Metabolism of Nutrients defines the molecular fate of nutrients and other dietary compounds in humans, as well as outlining the molecular basis of processes supporting nutrition, such as chemical sensing and appetite control. It focuses on the presentation of nutritional biochemistry, and the reader is given a clear and specific perspective on the events that control the utilization of dietary compounds. Slightly over 100 self-contained chapters cover all essential and important nutrients as well as many other dietary compounds with relevance for human health. An essential read for healthcare professionals and researchers in all areas of health and nutrition who want to access the wealth of nutrition knowledge available today in one single source.

Connecting Other Sugars to Nutrient Metabolism

Sugars, such as galactose, fructose, and glycogen, are catabolized into new products in order to enter the glycolytic pathway.

Key Points

When blood sugar levels drop, glycogen is broken down into glucose -1-phosphate, which is then converted to glucose-6-phosphate and enters glycolysis for ATP production.

In the liver, galactose is converted to glucose-6-phosphate in order to enter the glycolytic pathway.

Fructose is converted into glycogen in the liver and then follows the same pathway as glycogen to enter glycolysis.

Sucrose is broken down into glucose and fructose; glucose enters the pathway directly while fructose is converted to glycogen.

Key Terms

  • disaccharide: A sugar, such as sucrose, maltose, or lactose, consisting of two monosaccharides combined together.
  • glycogen: A polysaccharide that is the main form of carbohydrate storage in animals; converted to glucose as needed.
  • monosaccharide: A simple sugar such as glucose, fructose, or deoxyribose that has a single ring.

You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways.

Metabolic pathways should be thought of as porous; that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Like sugars and amino acids, the catabolic pathways of lipids are also connected to the glucose catabolism pathways.

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Glycogen Pathway: Glycogen from the liver and muscles, hydrolyzed into glucose-1-phosphate, together with fats and proteins, can feed into the catabolic pathways for carbohydrates.

Glycogen, a polymer of glucose, is an energy-storage molecule in animals. When there is adequate ATP present, excess glucose is shunted into glycogen for storage. Glycogen is made and stored in both the liver and muscles. The glycogen is hydrolyzed into the glucose monomer, glucose-1-phosphate (G-1-P), if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into G-1-P and converted into glucose-6-phosphate (G-6-P) in both muscle and liver cells; this product enters the glycolytic pathway.

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Glycogen Structure: Schematic two-dimensional cross-sectional view of glycogen: A core protein of glycogen is surrounded by branches of glucose units. The entire globular granule may contain around 30,000 glucose units.

Galactose is the sugar in milk. Infants have an enzyme in the small intestine that metabolizes lactose to galactose and glucose. In areas where milk products are regularly consumed, adults have also evolved this enzyme. Galactose is converted in the liver to G-6-P and can thus enter the glycolytic pathway.

Fructose is one of the three dietary monosaccharides (along with glucose and galactose) which are absorbed directly into the bloodstream during digestion. Fructose is absorbed from the small intestine and then passes to the liver to be metabolized, primarily to glycogen. The catabolism of both fructose and galactose produces the same number of ATP molecules as glucose.

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Fructose Metabolism: Although the metabolism of fructose and glucose share many of the same intermediate structures, they have very different metabolic fates in human metabolism.

Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage. The catabolism of sucrose breaks it down to monomers of glucose and fructose. The glucose can directly enter the glycolytic pathway while fructose must first be converted to glycogen, which can be broken down to G-1-P and enter the glycolytic pathway as described above.

Connecting Proteins to Glucose Metabolism Nutrient Metabolism

Excess amino acids are converted into molecules that can enter the pathways of glucose catabolism.

Key Points

Amino acids must be deaminated before entering any of the pathways of glucose catabolism: the amino group is converted to ammonia, which is used by the liver in the synthesis of urea.

Deaminated amino acids can be converted into pyruvate, acetyl CoA, or some components of the citric acid cycle to enter the pathways of glucose catabolism.

Several amino acids can enter the glucose catabolism pathways at multiple locations.

Key Terms

  • catabolism: Destructive metabolism, usually including the release of energy and breakdown of materials.
  • keto acid: Any carboxylic acid that also contains a ketone group.
  • deamination: The removal of an amino group from a compound.

Metabolic pathways should be thought of as porous; that is, substances enter from other pathways and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Proteins are a good example of this phenomenon. They can be broken down into their constituent amino acids and used at various steps of the pathway of glucose catabolism.

Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are recycled into the synthesis of new proteins or are used as precursors in the synthesis of other important biological molecules, such as hormones, nucleotides, or neurotransmitters. However, if there are excess amino acids, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism.

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Connection of Amino Acids to Glucose Metabolism Pathways: The carbon skeletons of certain amino acids (indicated in boxes) are derived from proteins and can feed into pyruvate, acetyl CoA, and the citric acid cycle.

Each amino acid must have its amino group removed (deamination) prior to the carbon chain’s entry into these pathways. When the amino group is removed from an amino acid, it is converted into ammonia through the urea cycle. The remaining atoms of the amino acid result in a keto acid: a carbon chain with one ketone and one carboxylic acid group. In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste product in mammals produced from the nitrogen originating in amino acids; it leaves the body in urine. The keto acid can then enter the citric acid cycle.

When deaminated, amino acids can enter the pathways of glucose metabolism as pyruvate, acetyl CoA, or several components of the citric acid cycle. For example, deaminated asparagine and aspartate are converted into oxaloacetate and enter glucose catabolism in the citric acid cycle. Deaminated amino acids can also be converted into another intermediate molecule before entering the pathways. Several amino acids can enter glucose catabolism at multiple locations.

Oxidation of Carbohydrates, Proteins, and Fats Converge on the Tricarboxylic Acid Cycle

This circular diagram depicts the chemical reactions of the tricarboxylic acid cycle. In a series of eight reactions, the acetyl group of acetyl-coA is completely oxidized to carbon dioxide (CO2), oxaloacetate is regenerated, and the coenzymes NAD+ and FAD are reduced to NADH and FADH2, respectively.

The reactions catalyzed by the dehydrogenases that result in NAD+ and FAD reduction are highlighted. The reaction catalyzed by succinyl-CoA synthetase (in which GTP synthesis occurs) is an example of substrate-level phosphorylation.

Interconversion of energy between reduced coenzymes and O2 directs ATP synthesis, but how (and where) are NADH and FADH2 reduced? In aerobic respiration or aerobiosis, all products of nutrients’ degradation converge to a central pathway in the metabolism, the TCA cycle. In this pathway, the acetyl group of acetyl-CoA resulting from the catabolism of glucose, fatty acids, and some amino acids is completely oxidized to CO2 with concomitant reduction of electron transporting coenzymes (NADH and FADH2). Consisting of eight reactions, the cycle starts with condensing acetyl-CoA and oxaloacetate to generate citrate. The next seven reactions regenerate oxaloacetate and include four oxidation reactions in which energy is conserved with the reduction of NAD+ and FAD coenzymes to NADH and FADH2, whose electrons will then be transferred to O2 through the ETS. In addition, a GTP or an ATP molecule is directly formed as an example of substrate-level phosphorylation. In this case, the hydrolysis of the thioester bond of succinyl-CoA with concomitant enzyme phosphorylation is coupled to the transfer of an enzyme-bound phosphate group to GDP or ADP. Importantly, although O2 does not participate directly in this pathway, the TCA cycle only operates in aerobic conditions because the oxidized NAD+ and FAD are regenerated only in the ETS. Also noteworthy is that TCA cycle intermediates may also be used as the precursors of different biosynthetic processes.The TCA cycle is also known as the Krebs cycle, named after its discoverer, Sir Hans Kreb. Krebs based his conception of this cycle on four main observations made in the 1930s. The first was the discovery in 1935 of the sequence of reactions from succinate to fumarate to malate to oxaloacetate by Albert Szent-Gyorgyi, who showed that these dicarboxylic acids present in animal tissues stimulate O2 consumption. The second was the finding of the sequence from citrate to α-ketoglutarate to succinate, in 1937, by Carl Martius and Franz Knoop. Next was the observation by Krebs himself, working on muscle slice cultures, that the addition of tricarboxylic acids even in very low concentrations promoted the oxidation of a much higher amount of pyruvate, suggesting a catalytic effect of these compounds. And the fourth was Krebs’s observation that malonate, an inhibitor of succinate dehydrogenase, completely stopped the oxidation of pyruvate by the addition of tricarboxylic acids and that the addition of oxaloacetate in the medium in this condition generated citrate, which accumulated, thus elegantly showing the cyclic nature of the pathway.

Pathways for Nutrient Degradation that Converge onto the TCA Cycle

Glycolysis

A linear diagram depicts the chemical reactions of the glycolysis pathway. In a series of ten chemical reactions, a glucose molecule is converted to pyruvate, resulting in the synthesis of energy in the form of ATP.

Glycolysis is the pathway in which one glucose molecule is degraded into two pyruvate molecules. Interestingly, during the initial phase, energy is consumed because two ATP molecules are used up to activate glucose and fructose-6-phosphate. Part of the energy derived from the breakdown of the phosphoanhydride bond of ATP is conserved in the formation of phosphate-ester bonds in glucose-6-phosphate and fructose-1,6-biphosphate (Figure 4).In the second part of glycolysis, the majority of the free energy obtained from the oxidation of the aldehyde group of glyceraldehyde 3-phosphate (G3P) is conserved in the acyl-phosphate group of 1,3- bisphosphoglycerate (1,3-BPG), which contains high free energy. Then, part of the potential energy of 1,3BPG, released during its conversion to 3-phosphoglycerate, is coupled to the phosphorylation of ADP to ATP. The second reaction where ATP synthesis occurs is the conversion of phosphoenolpyruvate (PEP) to pyruvate. PEP is a high-energy compound due to its phosphate-ester bond, and therefore the conversion reaction of PEP to pyruvate is coupled with ADP phosphorylation. This mechanism of ATP synthesis is called substrate-level phosphorylation.

For complete oxidation, pyruvate molecules generated in glycolysis are transported to the mitochondrial matrix to be converted into acetyl-CoA in a reaction catalyzed by the multienzyme complex pyruvate dehydrogenase (Figure 5). When Krebs proposed the TCA cycle in 1937, he thought that citrate was synthesized from oxaloacetate and pyruvate (or a derivative of it). Only after Lipmann’s discovery of coenzyme A in 1945 and the subsequent work of R. Stern, S. Ochoa, and F. Lynen did it become clear that the molecule acetyl-CoA donated its acetyl group to oxaloacetate. Until this time, the TCA cycle was seen as a pathway to carbohydrate oxidation only. Most high school textbooks reflect this period of biochemistry knowledge and do not emphasize how the lipid and amino acid degradation pathways converge on the TCA cycle.

The Fatty Acid Oxidation Pathway Intersects the TCA Cycle

In 1904, Knoop, in a classic experiment, decisively showed that fatty acid oxidation was a process by which two-carbon units were progressively removed from the carboxyl end fatty acid molecule. The process consists of four reactions and generates acetyl-CoA and the acyl-CoA molecule shortened by two carbons, with the concomitant reduction of FAD by enzyme acyl-CoA dehydrogenase and of NAD+ by β-hydroxy acyl-CoA dehydrogenase. This pathway is known as β-oxidation because the β-carbon atom is oxidized prior to when the bond between carbons β and α is cleaved (Figure 6). The four steps of β-oxidation are continuously repeated until the acyl-CoA is entirely oxidized to acetyl-CoA, which then enters the TCA cycle. In the 1950s, a series of experiments verified that the carbon atoms of fatty acids were the same ones that appeared in the acids of the TCA cycle.

Amino Acid Transamination/Deamination Contributes to the TCA Cycle

Two points must be considered regarding the use of amino acids as fuels in energy metabolism. The first is the presence of nitrogen in amino acid composition, which must be removed before amino acids become metabolically useful. The other is that there are at least twenty different amino acids, each of which requires a different degradation pathway. For our purpose here, it is important to mention two kinds of reactions involving amino acids: transamination and deamination. In the first kind of reaction, the enzyme aminotransferases convert amino acids to their respective α-ketoacids by transferring the amino group of one amino acid to an α-ketoacid. This reaction allows the amino acids to be interconverted. The second kind of reaction, deamination, removes the amino group of the amino acid in the form of ammonia. In the liver, the oxidative deamination of glutamate results in α-ketoglutarate (a TCA cycle intermediate) and ammonia, which is converted into urea and excreted. Deamination reactions in other organs form ammonia that is generally incorporated into glutamate to generate glutamine, which is the main transporter of amino groups in blood. Hence, all amino acids through transamination/deamination reactions can be converted into intermediates of the TCA cycle, directly or via conversion to pyruvate or acetyl-CoA (Figure 5).

Function

Role in Glucose Metabolism

The homeostasis of glucose metabolism is carried out by 2 signaling cascades: insulin-mediated glucose uptake (IMGU) and glucose-stimulated insulin secretion (GSIS). The IMGU cascade allows insulin to increase the uptake of glucose from skeletal muscle and adipose tissue and suppresses glucose generation by hepatic cells. Activation of the insulin cascade’s downstream signaling begins when insulin extracellularly interacts with the insulin receptor’s alpha subunit. This interaction leads to conformational changes in the insulin-receptor complex, eventually leading to tyrosine kinase phosphorylation of insulin receptor substrates and subsequent activation of phosphatidylinositol-3-kinase. These downstream events cause the desired translocation of the GLUT-4 transporter from intracellular to extracellular onto skeletal muscle cell’s plasma membrane. Intracellularly, GLUT4 is present within vesicles. The rate at which these GLUT4-vesicles are exocytosed increases due to insulin’s actions or exercise. Thus, by increasing GLUT-4’s presence on the plasma membrane, insulin allows for glucose entry into skeletal muscle cells for metabolism into glycogen.

Role in Glycogen Metabolism

In the liver, insulin affects glycogen metabolism by stimulation of glycogen synthesis. Protein phosphatase I (PPI) is the key molecule in the regulation of glycogen metabolism. Via dephosphorylation, PPI slows the rate of glycogenolysis by inactivating phosphorylase kinase and phosphorylase A. In contrast, PPI accelerates glycogenesis by activating glycogen synthase B.  Insulin serves to increase PPI substrate-specific activity on glycogen particles, in turn stimulating the synthesis of glycogen from glucose in the liver.

There are a variety of hepatic metabolic enzymes under the direct control of insulin through gene transcription. This affects gene expression in metabolic pathways. In gluconeogenesis, insulin inhibits gene expression of the rate-limiting step, phosphoenolpyruvate carboxylase, as well as fructose-1,6-bisphosphatase and glucose-6-phosphatase. In glycolysis, gene expression of glucokinase and pyruvate kinase increases. In lipogenesis, the expression is increased of fatty acid synthase, pyruvate dehydrogenase, and acetyl-CoA carboxylase.

Role in Lipid Metabolism

As previously mentioned, insulin increases the expression of some lipogenic enzymes. This is due to glucose stored as a lipid within adipocytes. Thus, an increase in a fatty acid generation will increase glucose uptake by the cells. Insulin further regulates this process by dephosphorylating and subsequently inhibiting hormone-sensitive lipase, leading to inhibition of lipolysis. Ultimately, insulin decreases serum free fatty acid levels.

Role in Protein Metabolism

Protein turnover rate is regulated in part by insulin. Protein synthesis is stimulated by insulin’s increase in intracellular uptake of alanine, arginine, and glutamine (short-chain amino acids) and gene expression of albumin and muscle myosin heavy chain alpha. Regulation of protein breakdown is affected by insulin’s downregulation of hepatic and muscle cell enzymes responsible for protein degradation. The impacted enzymes include ATP-ubiquitin-dependent proteases, and ATP-independent lysosomal proteases, and hydrolases.

Role in Inflammation and Vasodilation

Insulin’s actions within endothelial cells and macrophages have an anti-inflammatory effect on the body. Within endothelial cells, insulin stimulates the expression of endothelial nitric oxide synthase (eNOS).  eNOS functions to release nitric oxide (NO), which leads to vasodilation. Insulin suppresses nuclear factor-kappa-B (NF-kB) found intracellularly in endothelial cells. Endothelial NF-KB activates the expression of adhesion molecules, E-selectin, and ICAM-1, which release soluble cell adhesion molecules into the circulation. Studies have linked the presence of cell adhesion molecules on vascular endothelium to the development of atherosclerotic arterial plaques.

Insulin suppresses the generation of O2 radicals and reactive oxygen species (ROS). Within the macrophage, insulin inhibits NADPH oxidase expression by suppressing one of its key components, p47phox.  NADPH oxidase aids in generating oxygen radicals, which activate the inhibitor of NF-kB kinase beta (IKKB). IKKB phosphorylates IkB, leading to its degradation. This degradation releases NF-kB, allowing for its translocation in the macrophage’s nucleus. Once in the nucleus, NF-kB stimulates gene transcription of pro-inflammatory proteins that are released into the circulation, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein (MCP-1), and matrix metalloproteinase (MMP)

References

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Nutrients – Types, Mechanism, Health Benefit

Nutrients are chemical substances required by the body to sustain basic functions and are optimally obtained by eating a balanced diet. There are six major classes of nutrients essential for human health: carbohydrates, lipids, proteins, vitamins, minerals, and water. Carbohydrates, lipids, and proteins are considered macronutrients and serve as a source of energy. Water is required in large amounts but does not yield energy. Vitamins and minerals are considered micronutrients and play essential roles in metabolism. Vitamins are organic micronutrients classified as either water-soluble or fat-soluble. The essential water-soluble vitamins include vitamins B1, B2, B3, B5, B6, B7, B9, B12, and C. The essential fat-soluble vitamins include vitamins A, E, D, and K. Minerals are inorganic micronutrients. Minerals can classify as macrominerals or microminerals. Macrominerals are required in amounts greater than 100 mg per day and include calcium, phosphorous, magnesium, sodium, potassium, and chloride. Sodium, potassium, and chloride are also electrolytes. Microminerals are those nutrients required in amounts less than 100 mg per day and include iron, copper, zinc, selenium, and iodine. This article will review the following biochemical aspects of the essential nutrients: fundamentals, cellular, molecular, function, testing, and clinical significance.

Digestive Systems and Nutrition

Animals use the organs of their digestive systems to extract important nutrients from food they consume, which can later be absorbed.

Key Points

Animals obtain lipids, proteins, carbohydrates, essential vitamins, and minerals from the food they consume.

The digestive system is composed of a series of organs, each with a specific, yet related function, that work to extract nutrients from food.

Organs of the digestive system include the mouth, esophagus, stomach, small intestine, and the large intestine.

Accessory organs, such as the liver and pancreas, secrete digestive juices into the gastrointestinal tract to assist with food breakdown.

Key Terms

  • digestion: the process, in the gastrointestinal tract, by which food is converted into substances that can be utilized by the body
  • macromolecule: a very large molecule, especially used in reference to large biological polymers (e.g. nucleic acids and proteins)
  • alimentary canal: the organs of a human or an animal through which food passes; the digestive tract

All living organisms need nutrients to survive. While plants can obtain the molecules required for cellular function through the process of photosynthesis, most animals obtain their nutrients by the consumption of other organisms. At the cellular level, the biological molecules necessary for animal function are amino acids, lipid molecules, nucleotides, and simple sugars. The food consumed consists of protein, fat, and complex carbohydrates, but the requirements of each are different for each animal.

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Balanced human diet: For humans, fruits and vegetables are important in maintaining a balanced diet. Both of these are an important source of vitamins and minerals, as well as carbohydrates, which are broken down through digestion for energy.

Animals must convert these macromolecules into the simple molecules required for maintaining cellular functions, such as assembling new molecules, cells, and tissues. The conversion of the food consumed to the nutrients required is a multi-step process involving digestion and absorption. During digestion, food particles are broken down to smaller components which will later be absorbed by the body.

Digestive System

The digestive system is one of the largest organ systems in the human body. It is responsible for processing ingested food and liquids. The cells of the human body all require a wide array of chemicals to support their metabolic activities, from organic nutrients used as fuel to the water that sustains life at the cellular level. The digestive system not only effectively chemically reduces the compounds in food into their fundamental building blocks, but also acts to retain water and excrete undigested materials. The functions of the digestive system can be summarized as follows: ingestion (eat food), digestion (breakdown of food), absorption (extraction of nutrients from the food), and defecation (removal of waste products).

The digestive system consists of a group of organs that form a closed tube-like structure called the gastrointestinal tract (GI tract) or the alimentary canal. For convenience, the GI tract is divided into upper GI tract and lower GI tract. The organs that make up the GI tract include the mouth, the esophagus, the stomach, the small intestine, and the large intestine. There are also several accessory organs that secrete various enzymes into the GI tract. These include the salivary glands, the liver, and the pancreas.

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Generalized animal digestive system: This diagram shows a generalized animal digestive system, detailing the different organs and their functions.

Challenges to Human Nutrition

One of the challenges in human nutrition is maintaining a balance between food intake, storage, and energy expenditure. Imbalances can have serious health consequences. For example, eating too much food while not expending much energy leads to obesity, which in turn will increase the risk of developing illnesses such as type-2 diabetes and cardiovascular disease. The recent rise in obesity and related diseases means that understanding the role of diet and nutrition in maintaining good health is more important than ever.

Carbohydrates: Sources, Uses in the Body, and Dietary Requirements

Carbohydrates, which break down to glucose, are a major source of energy for humans but are not essential nutrients.

Key Points

Carbohydrates include such items as fruits, grains, beans, and potatoes, along with sugars and sugared foods.

While fat is a better source of energy, the brain cannot burn fat and instead requires glucose.

Polysaccharides (complex carbs) are difficult for humans to break down but are useful as fiber to enhance the digestive process.

Government agencies recommend a dietary intake of 45–65% or 55–75% of carbohydrates to meet daily energy needs.

Of daily carbohydrate intake, only 10% should be simple carbs or sugars.

Key Terms

  • glucose: A simple monosaccharide (sugar) with a molecular formula of C6H12O6; it is a principle source of energy for cellular metabolism.
  • carbohydrate: A sugar, starch, or cellulose that is a food source of energy for an animal or plant; a saccharide.
  • saccharide: The unit structure of carbohydrates, of general formula CnH2nOn. Either the simple sugars or polymers such as starch and cellulose. The saccharides exist in either a ring or short chain conformation, and typically contain five or six carbon atoms.

EXAMPLES

Daily food intake that includes 8–10 fruit and vegetable servings (not starchy potatoes or grains, such as corn and rice) will not only provide plenty of energy but will also keep glucose levels in balance.

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Carbohydrates are a class of macromolecule: Grain products are rich sources of carbohydrates.

Foods high in carbohydrates include fruits, sweets, soft drinks, bread, pasta, beans, potatoes, bran, rice, and cereals. Carbohydrates are a common source of energy in living organisms, however, carbohydrate is not an essential nutrient in humans.

Carbohydrates are not necessary building blocks of other molecules, and the body can obtain all its energy from protein and fats. The brain and neurons generally cannot burn fat for energy but use solely glucose or ketones. Humans can synthesize some glucose (in a set of processes known as “gluconeogenesis”) from specific amino acids or from the glycerol backbone in triglycerides and, in some cases, from fatty acids. Carbohydrates and protein contain 4 kilocalories per gram, while fats contain 9 kilocalories per gram. In the case of protein, this is somewhat misleading as only some amino acids are able to undergo conversion into useful energy forms.

Organisms typically cannot metabolize all types of carbohydrates to yield energy. Glucose is a nearly universal and accessible source of calories. Many organisms also have the ability to metabolize other monosaccharides and disaccharides, though glucose is preferred. Polysaccharides are also common sources of energy. Even though these complex carbohydrates are not very digestible, they may comprise important dietary elements for humans. Called “dietary fiber,” these carbohydrates enhance digestion, among other benefits.

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Glucose Molecule: Image of a glucose molecule containing a fixed ratio of carbon, hydrogen and oxygen.

Based on the effects on risk of heart disease and obesity, the Institute of Medicine (IOM) recommends that American and Canadian adults get between 45–65% of dietary energy from carbohydrates. The Food and Agriculture Organization (FAO) and World Health Organization (WHO) jointly recommend that national dietary guidelines set a goal of 55–75% of total energy from carbohydrates, but only 10% directly from sugars (their term for simple carbohydrates).

Lipids: Sources, Uses in the Body, and Dietary Requirements

Fats store energy, facilitate absorption of fat-soluble vitamins, aid brain growth and development, and protect against many diseases.

Key Points

Vitamins A, D, E, and K should be taken with some dietary fat in order to facilitate their absorption and activity.

Humans cannot synthesize omega-6 and omega-3 fatty acids, so these fats must be obtained from the diet.

Omega-6 fatty acids are found in many foods, while omega-3 fatty acids are found in walnuts and are especially abundant in fatty fish.

Omega-3 fatty acids have many positive health benefits including reduced rates of cancer, cardiovascular disease, mental illness, and dementia.

Studies of dietary fat intake have found no link between the percentage of calories obtained from fats and the risk of cancer, heart disease, or obesity.

Trans fats, such as those present in partially hydrogenated vegetable oils, are a risk factor for cardiovascular disease.

Key Terms

  • phospholipids: Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers.
  • trans fats: Trans fats are unsaturated fats generated by physical agents such as heat or pressure that can lead to a variety of health problems.
  • fatty acid: Fatty acids can be saturated or unsaturated and are usually derived from triglycerides or phospholipids.

EXAMPLES

College students require optimal brain function, which is supported by fatty fish and walnuts.

Most of the fats found in food are triglycerides, cholesterol, and phospholipids. Some dietary fat is necessary for the absorption of fat-soluble vitamins (A, D, E, and K) and carotenoids. Humans and other mammals require fatty acids such as linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid), because they cannot be synthesized from simple precursors in the diet.

Both omega-6 and omega-3 are 18-carbon polyunsaturated fatty acids that differ in the number and position of their double bonds. Most vegetable oils (safflower, sunflower, and corn oils) are rich in linoleic acid. Alpha-linolenic acid is found in the green leaves of plants, selected seeds, nuts, and legumes, and particularly in flax, rapeseed, walnut, and soy. Fish oils are especially rich in the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Numerous studies have shown that the consumption of omega-3 fatty acids has positive benefits in terms of infant development, cancer, cardiovascular disease, and mental illnesses such as depression, attention-deficit hyperactivity disorder, and dementia. In contrast, the consumption of trans fats, such as those present in partially hydrogenated vegetable oils, are now known to be a risk factor for cardiovascular disease.

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Omega-3 Fatty Acid: Docosahexaenoic acid (DHA) is an omega-3 fatty acid. It is essential for the proper functioning of the brain in both adults and infants. DHA concentrations in breast milk ranged from 0.07-1.0% of total fatty acids and are influenced by the amount of fatty fish in the mother’s diet. In the U.S., infant formula has been supplemented with DHA since 2001. Research suggests that DHA contributes to numerous nervous system functions such as visual acuity, neurogenesis, and synaptogenesis and that it lowers the risk for cardiovascular disease. It is highly concentrated in the brain and eye.

Several studies have suggested that total dietary fat intake is linked to obesity and diabetes. However, influential studies like the Women’s Health Initiative Dietary Modification Trial (an eight-year study of 49,000 women), as well as the Nurses’ Health Study and the Health Professionals Follow-up Study, have revealed no such link between the percentage of calories from fat and risk of cancer, heart disease, or weight gain. The Nutrition Source, a website maintained by the Department of Nutrition at the Harvard School of Public Health, summarizes the current evidence on the impact of dietary fat as follows: “Detailed research—much of it done at Harvard—shows that the total amount of fat in the diet isn’t really linked with weight or disease.”

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Salmon: Salmon is an excellent source of omega-3 fatty acids.

Proteins: Sources, Uses in the Body, and Dietary Requirements

Proteins are composed of 20 different amino acids, about half of which are essential, meaning they must be obtained from the diet.

Key Points

Protein-based foods (plant and animal) provide amino acids; however, the best source of essential amino acids is animal.

If the diet does not provide adequate protein, the body will obtain what it needs from itself, especially from its own muscles.

While adequate protein is required for building skeletal muscle and other tissues, there is ongoing debate regarding the use and necessity of high-protein diets in anaerobic exercise, in particular weight training and bodybuilding.

This use of protein as a fuel is particularly important under starvation conditions as it allows the body’s own proteins to be used to support life.

Key Terms

  • amino acid: Any of the twenty naturally occurring α-amino acids (having the amino, and carboxylic acid groups on the same carbon atom), and a variety of side chains, that combine, via peptide bonds, to form proteins.
  • denaturation: Denaturation is a process in which proteins or nucleic acids lose their tertiary and secondary structure which is present in their native state, by application of some external stress or compound such as a strong acid or base, a concentrated inorganic salt, an organic solvent (e.g., alcohol or chloroform), or heat.
  • protein: Any of numerous large, complex naturally-produced molecules composed of one or more long chains of amino acids, in which the amino acid groups are held together by peptide bonds.

Most microorganisms and plants can biosynthesize all 20 standard amino acids, while animals (including humans) must obtain some of the amino acids from the diet. The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids. Key enzymes that synthesize certain amino acids are not present in animals. One example is aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate.

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Amino Acid: Ball-and-stick model of the cystine molecule, an amino acid formed from two cysteine molecules.

In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are then broken down into amino acids through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases. Some ingested amino acids are used for protein biosynthesis, while others are converted to glucose through gluconeogenesis, or fed into the citric acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the body’s own proteins to be used to support life, particularly those found in muscle. Amino acids are also an important dietary source of nitrogen.

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Protein: Muscle meat, such as steak, is an excellent source of the essential amino acids the body needs to create all necessary proteins.

A high-protein diet is often recommended by bodybuilders and nutritionists to help efforts to build muscle and lose fat. It should not be confused with low-carb diets, such as the Atkins Diet, which are not calorie-controlled and which often contain large amounts of fat. While adequate protein is required for building skeletal muscle and other tissues, there is ongoing debate regarding the use and necessity of high-protein diets in anaerobic exercise in particular weight training and bodybuilding. Extreme protein intake (in excess of 200g per day), coupled with an inadequate intake of other calorie sources (fat or carbohydrates), can cause a form of metabolic disturbance and death commonly known as rabbit starvation.

Relatively little evidence has been gathered regarding the effect of long-term high intake of protein on the development of chronic diseases. Increased load on the kidney is a result of an increase in the reabsorption of NaCl. This causes a decrease in the sensitivity of tubuloglomerular feedback, which, in turn, results in an increased glomerular filtration rate. This increases pressure in glomerular capillaries. When added to any additional renal disease, this may cause permanent glomerular damage.

Food Requirements and Essential Nutrients

Essential nutrients are those that cannot be created by an animal’s metabolism and need to be obtained from the diet.

Key Points

The animal diet needs to be well-balanced in order to ensure that all necessary vitamins and minerals are being obtained.

Vitamins are important for maintaining bodily health, making bones strong, and seeing in the dark.

Water-soluble vitamins are not stored by the body and need to be consumed more regularly than fat-soluble vitamins, which build up within body tissues.

Essential fatty acids need to be consumed through the diet and are important building blocks of cell membranes.

Nine of the 20 amino acids cannot be synthesized by the body and need to be obtained from the diet.

Key Terms

  • nutrient: a source of nourishment, such as food, that can be metabolized by an organism to give energy and build tissue
  • catabolism: destructive metabolism, usually including the release of energy and breakdown of materials
  • vitamin: any of a specific group of organic compounds essential in small quantities for healthy human growth, metabolism, development, and body function

Food Requirements

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A balanced diet: For humans, a balanced diet includes fruits, vegetables, grains, and protein. Each of these food sources provides different nutrients the body cannot make for itself. These include vitamins, omega 3 fatty acids, and some amino acids.

What are the fundamental requirements of the animal diet? The animal diet should be well balanced and provide nutrients required for bodily function along with the minerals and vitamins required for maintaining structure and regulation necessary for good health and reproductive capability.

Organic Precursors

The organic molecules required for building cellular material and tissues must come from food. Carbohydrates or sugars are the primary sources of organic carbons in the animal body. During digestion, digestible carbohydrates are ultimately broken down into glucose and used to provide energy through metabolic pathways. The excess sugars in the body are converted into glycogen and stored in the liver and muscles for later use. Glycogen stores are used to fuel prolonged exertions, such as long-distance running, and to provide energy during food shortages. Excess digestible carbohydrates are stored by mammals in order to survive famine and aid in mobility.

Another important requirement is that of nitrogen. Protein catabolism provides a source of organic nitrogen. Amino acids are the building blocks of proteins and protein breakdown provides amino acids that are used for cellular function. The carbon and nitrogen derived from these become the building block for nucleotides, nucleic acids, proteins, cells, and tissues. Excess nitrogen must be excreted, as it is toxic. Fats add flavor to food and promote a sense of satiety or fullness. Fatty foods are also significant sources of energy because one gram of fat contains nine calories. Fats are required in the diet to aid the absorption of fat-soluble vitamins and the production of fat-soluble hormones.

Essential Nutrients

While the animal body can synthesize many of the molecules required for function from the organic precursors, there are some nutrients that need to be consumed from food. These nutrients are termed essential nutrients: they must be eaten as the body cannot produce them.

Vitamins and minerals are substances found in the food we eat. Your body needs them to be able to work properly and for growth and development. Each vitamin has its own special role to play. For example, vitamin D (added to whole milk or naturally occurring in sardines), helps make bones strong, while vitamin A (found in carrots) helps with night vision. Vitamins fall into two categories: fat-soluble and water-soluble. The fat-soluble vitamins dissolve in fat and can be stored in your body, whereas the water-soluble vitamins need to dissolve in water before your body can absorb them; therefore, the body cannot store them.

Fat-soluble vitamins are found primarily in foods that contain fat and oil, such as animal fats, vegetable oils, dairy foods, liver, and fatty fish. Your body needs these vitamins every day to enable it to work properly. However, you do not need to eat foods containing these every day. If your body does not need these vitamins immediately, they will be stored in the liver and fat tissues for future use. This means that stores can build up; if you have more than you need, fat-soluble vitamins can become harmful. Some fat-soluble vitamins include vitamin A, vitamin K, vitamin D, and vitamin E. Unlike the other fat-soluble vitamins, vitamin D is difficult to obtain in adequate quantities in a normal diet; therefore, supplementation may be necessary.

Water-soluble vitamins are not stored in the body; therefore, you need to have them more frequently. If you have more then you need, the body rids itself of the extra vitamins during urination. Because the body does not store these vitamins, they are generally not harmful. Water-soluble vitamins are found in foods that include fruits, vegetables, and grains. Unlike fat-soluble vitamins, they can be destroyed by heat. This means that sometimes these vitamins can often be lost during cooking. This is why it is better to steam or grill these foods rather then boil them. Some water-soluble vitamins include vitamin B6, vitamin B12, vitamin C, biotin, folic acid, niacin, and riboflavin.

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Sea buckthorn seed oil: Sea buckthorn seed oil contains many vital nutrients.

The omega-3 alpha-linolenic acid and the omega-6 linoleic acid are essential fatty acids needed to synthesize some membrane phospholipids. Many people take supplements to ensure they are obtaining all the essential fatty acids they need. Sea buckthorn contains many of these fatty acids and is also high in vitamins. Sea buckthorn can be used to treat acne and promote weight loss and wound healing.

Minerals are inorganic essential nutrients that must also be obtained from food. Among their many functions, minerals help in cell structure and regulation; they are also considered co-factors. In addition to vitamins and minerals, certain amino acids must also be procured from food and cannot be synthesized by the body. These amino acids are the “essential” amino acids. The human body can synthesize only 11 of the 20 required amino acids. The rest must be obtained from food.

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Amino Acids: There are 20 known amino acids. Animals can make only 11, so the others must be obtained through the diet. Meats are the best source of amino acids, although some amino acids can also be obtained from vegetables and grains.

Fundamentals Nutrition

Carbohydrates

Carbohydrates are essential macronutrients that are the primary source of energy for humans; 1 gram of carbohydrate contains 4 kcal of energy. Carbohydrates also play roles in gut health and immune function. Carbohydrates are present in plant-based foods like grains, fruits, vegetables, and milk. Carbohydrates are ingested in the form of simple carbohydrates, like monosaccharides and disaccharides, or complex carbohydrates, like oligosaccharides and polysaccharides. Monosaccharides are the basic building blocks of all carbohydrates and include glucose, fructose, and galactose. Glucose is the primary form to which carbohydrates become metabolized in humans. Disaccharides contain two sugar units and include lactose, sucrose, and maltose. Lactose is a carbohydrate found in milk, and sucrose is basic table sugar. Oligosaccharides consist of 3 to 10 sugar units and include raffinose and stachyose, which are in legumes. Polysaccharides include greater than ten sugar units and consist of starches, glycogen, and fibers, like pectin and cellulose. Starches like amylose are in grains, starchy vegetables, and legumes and consist of glucose monomers. Glycogen is the storage form of glucose in animals and is present in the liver and muscle, but there is little to none in the diet. Fibers are plant polysaccharides like pectin and cellulose found in whole grains, fruits, vegetables, and legumes but are not digestible by humans. However, they play a major role in gut health and function and can be digested by microbiota in the large intestine. For healthy children and adults, carbohydrates should make up approximately 45 to 65% of energy intake based on the minimum required glucose for brain function. The recommended fiber intake is greater than 38 g for men and 25 g for women, which is the intake that research has observed to lower the risk of coronary artery disease. Some carbohydrates are more nutritious than others. Optimal carbohydrate intake consists of fiber-rich, nutrient-dense whole grains, fruits, vegetables, legumes, and added sugar.

Proteins

Proteins are essential macronutrients that contribute to structural and mechanical function, regulate processes in the cells and body, and provide energy if necessary. Proteins are composed of amino acids and are available in food sources like meats, dairy foods, legumes, vegetables, and grains. 1 gram of protein contains 4 kcal of energy. The recommended protein intake is 0.8 to 1 gram per kilogram of body weight per day. For healthy children ages 1 to 3, ages 4 to 18, and adults, approximately 5 to 20%, 10 to 30%, and 10 to 35% of daily energy intake should come from protein, respectively, based on the adequate amount needed for nitrogen equilibrium.

Lipids

Lipids are essential macronutrients that are the main source of stored energy in the body, contribute to cellular structure and function, regulate temperature, and protect body organs. Lipids are found in fats, oils, meats, dairy, and plants and consumed mostly in the form of triglycerides. One gram of fat contains 9 kcal of energy. For healthy children ages 1 to 3, ages 4 to 18, and adults, approximately 30 to 40%, 25 to 15%, and 20 to 35% of daily energy intake should come from fat, respectively. Approximately 5 to 10% and 0.6 to 1.2% of the daily fat energy intake should consist of n-6 polyunsaturated fatty acids (linoleic acid) and n-3 polyunsaturated fatty acids (α-linolenic acid), respectively.

Vitamin

  • Vitamin B1 (Thiamin) – Thiamin, or vitamin B1, is an essential water-soluble vitamin that acts as a coenzyme in carbohydrate and branched-chain amino acid metabolism. Thiamin is in food sources such as enriched and whole grains, legumes, and pork. The RDA (Recommended Dietary Allowance) of thiamin for adults is 1.1 mg/day for women and 1.2 mg/day for men.
  • Vitamin B2 (Riboflavin) – Riboflavin, or vitamin B2, is an essential water-soluble vitamin that acts as a coenzyme in redox reactions. Riboflavin is present in food sources such as enriched and whole grains, milk and dairy products, leafy vegetables, and beef. The RDA of riboflavin for adults is 1.1 mg/day for women and 1.3 mg/day for men.
  • Vitamin B3 (Niacin) – Niacin, or vitamin B3, is an essential water-soluble vitamin that acts as a coenzyme to dehydrogenase enzymes in the transfer of the hydride ion and an essential component of the electron carriers NAD and NADP. Niacin is present in enriched and whole grains and high protein foods like meat, milk, and eggs. The RDA of niacin for adults is 14 mg/day of NEs (niacin equivalents) for women and 16 mg/day of NEs for men.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid, or vitamin B5, is an essential water-soluble vitamin that acts as a key component of coenzyme A and phosphopantetheine, which are crucial to fatty acid metabolism. Pantothenic acid is widespread in foods. The AI (adequate intake) of pantothenic acid for adults is 5 mg/day.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6, or pyridoxine, is an essential water-soluble vitamin that acts as a coenzyme for amino acid, glycogen, and sphingoid base metabolism. Vitamin B6 is widespread among food groups. The RDA for vitamin B6 for adults is 1.3 mg/day.
  • Vitamin B7 (Biotin) – Biotin, or vitamin B7, is an essential water-soluble vitamin that acts as a coenzyme in carboxylation reactions dependent on bicarbonate. Biotin is found widespread in foods, especially egg yolks, soybeans, and whole grains. The AI of biotin for adults is 30 mcg/day.
  • Vitamin B9 (Folate)  – Folate, or vitamin B9, is an essential water-soluble vitamin that acts as a coenzyme in single-carbon transfers in nucleic acid and amino acid metabolism. Folate is in enriched and fortified grains, green leafy vegetables, and legumes. The RDA of folate for adults is 400 mcg/day of DFEs. The recommendation is that women of childbearing age consume an additional 400 mcg/day of folic acid from supplements or fortified foods to decrease the risk of neural tube defects.
  • Vitamin B12 (Cobalamin) – Vitamin B12, or cobalamin, is an essential water-soluble vitamin that acts as coenzymes for the crucial methyl transfer reaction in converting homocysteine to methionine and the isomerization reaction that occurs in the conversion of L-methylmalonyl-CoA to succinyl-CoA. Vitamin B12 is only present in animal products because it is a product of bacteria synthesis. Many foods are also fortified with synthetic vitamin B12. The RDA of vitamin B12 for adults is 2.4 mcg/day. It is recommended for older adults to meet their RDA with fortified foods or supplements because many are unable to absorb naturally occurring vitamin B12.
  • Vitamin C (Ascorbic Acid) – Vitamin C, or ascorbic acid, is an essential water-soluble vitamin that acts as a reducing agent in enzymatic reactions and nonenzymatically as a soluble antioxidant. Vitamin C is found primarily in fruits and vegetables, except for animal organs like the liver and kidneys. The RDA of vitamin C for adult women and men is 75 mg/day and 90 mg/day, respectively. Smokers require an additional 35 mg/day of vitamin C.
  • Vitamin A (Retinol) – Vitamin A, or retinol, is an essential fat-soluble vitamin that plays numerous roles in vision, cellular differentiation, gene expression, growth, the immune system, bone development, and reproduction. Vitamin A is found primarily in animal products. Fruits and vegetables are a source of provitamin A carotenoids that can be converted to retinol in the body at a lesser amount. The RDA for vitamin A for adults is 900 mcg/day for males and 700 mcg/day for females.
  • Vitamin D (Cholecalciferol) –Vitamin D, or cholecalciferol, is an essential fat-soluble vitamin that plays an essential role in calcium metabolism, cell growth and development, and bone health. Vitamin D can be found in fish oils and in small amounts in plants in its less biologically active form. Interestingly, vitamin D synthesis occurs in the skin with exposure to UV light making dietary sources unnecessary in certain cases. The RDA for vitamin D for adults is 10 to 15 mcg/day.
  • Vitamin E (Tocopherol) – Vitamin E, or tocopherol, is a fat-soluble vitamin that is an antioxidant and may play roles in cell signaling, platelet aggregation, and vasodilation. Vitamin E, in the form of α-tocopherol, is found in certain vegetable oils, including sunflower, safflower, canola, and olive oil, whole grains, nuts, and green leafy vegetables. The RDA for vitamin E for adults is 15 mg/day.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K is an essential fat-soluble vitamin that is the coenzyme in the carboxylation of glutamic acid to form γ-carboxyglutamic acid reaction, which is essential to the proteins involved in blood coagulation. Vitamin K is present in green leafy vegetables, canola oil, and soybean oil. The RDA of vitamin K for adults is 120 mcg/day for men and 90 mcg/day for women.

Mineral

  • Calcium – Calcium is an essential macromineral responsible for numerous structural components such as bones and teeth and physiological mechanisms in the body. Calcium exists in dietary sources such as dairy, cereals, legumes, and vegetables. The RDA for calcium for adults is 1,000 mg/day.
  • Magnesium – Magnesium is an essential macromineral responsible for numerous functions in the body, including signaling pathways, energy storage, and transfer, glucose metabolism, lipid metabolism, neuromuscular function, and bone development. Magnesium is present in food sources such as fruits, vegetables, whole grains, legumes, nuts, dairy, meat, and fortified foods like cereal. The adult RDA for magnesium is 400 mg/day.
  • Phosphorus – Phosphorus is an essential macromineral that is a structural component of bones and teeth, DNA, RNA, and plasma membrane of cells. It is also critical metabolically to produce and store energy. Phosphorus is pervasive throughout food sources, with the greatest contributors being milk, dairy, meat, and poultry. Phosphorus is also an additive in processed foods as a preservative. The RDA for phosphorus for adults is 700 mg/day.
  • Sodium – Sodium is an essential macromineral and electrolyte that plays critical roles in cellular membrane transport, water balance, nerve innervation, and muscle contraction as the most abundant extracellular cation. Sodium is available in dietary sources such as salt, processed foods, meat, milk, eggs, and vegetables. The AI for sodium for adults is 1,500 mg/day; however, the average sodium intake in industrialized nations is 2 or 3 fold by comparison, at 3,000 to 4,500 mg/day.
  • Potassium – Potassium is an essential macromineral and electrolyte that plays critical roles in muscle contraction, nerve innervation, blood pH balance, and water balance as the most abundant intracellular cation. Potassium is obtainable in dietary sources such as fruits and vegetables. The AI for potassium is for adults is 4,700 mg/day.
  • Chloride – Chloride is an essential macromineral and electrolyte that plays critical roles in digestion, muscular activity, water balance, and acid-base balance as the most abundant extracellular anion in the body. Dietary chloride is almost always present in dietary sources associated with sodium in the form of NaCl or table salt. Chloride is in processed foods, meat, milk, eggs, and vegetables. The AI for chloride for adults is 1,500 mg/day.
  • Iron – Iron is an essential trace mineral that has a critical role in oxygen transport and energy metabolism. Dietary iron is from sources such as meat, fortified grains, and green leafy vegetables. Animal foods contain a more bioavailable form of iron called heme iron, while plant foods and fortified grains contain a less bioavailable form called non-heme iron. The RDA for iron for adults is 8 to 18 mg/day.
  • Zinc – Zinc is an essential trace mineral that functions structurally in proteins and catalytically as a component of over 300 different enzymes. Zinc appears in a variety of foods, especially shellfish and red meat. The RDA for zinc for adults is 10 mg/day.
  • Copper – Copper is an essential trace mineral that acts as a component of numerous proteins, including many important enzymes. Copper is in a variety of food sources but the highest concentrations in organ meats, nuts, seeds, chocolate, and shellfish. The RDA for copper for adults is 1 mg/day.
  • Iodine – Iodine is an essential trace mineral necessary for thyroid hormone synthesis. Iodine is present in meats and plant foods based on the soil content of the food production region. Otherwise, iodized salt is the main food source of iodine in regions with low soil iodine content. The adult RDA for iodine is 150 mcg/day.
  • Selenium – Selenium is an essential trace mineral that is an essential component of selenoproteins that play biological roles in antioxidant defense and anabolic processes in the human body. Selenium occurs in grains and vegetables, but the amounts vary based on the selenium content in the soil that the grains and vegetables were grown in. Brazil nuts are known for having high concentrations of selenium. The RDA for selenium for adults is 55 mcg/day.

Cellular

Carbohydrates

Carbohydrate digestion occurs in the mouth and small intestine with salivary amylase, pancreatic amylase, and brush border enzymes. Human carbohydrate digesting enzymes catalyze hydrolysis reactions that break the bonds between monomers. However, given fibers have beta bonds, they are indigestible by human enzymes, so some end up getting digested by bacterial enzymes in the large intestine, and the remainder is excreted in the feces. In the mouth, salivary amylase begins to break down the polysaccharide starch into the disaccharide maltose, which both contain monomers of glucose. Carbohydrate digestion bypasses the stomach and continues in the small intestine via pancreatic amylase and brush border enzymes on the microvilli. Pancreatic amylase continues to break down starches into maltose. The brush border enzymes include maltase, sucrase, and lactase. Maltase hydrolyzes maltose into two glucose monomers. Sucrase hydrolyzes sucrose into glucose and fructose. Lactase hydrolyzes lactose into glucose and galactose.

Monosaccharides pass through intestinal epithelial cells via facilitated diffusion and active transport to enter the bloodstream. Fructose is absorbed via facilitated diffusion by GLUT5 and released via facilitated diffusion by GLUT2. Glucose and galactose are absorbed along with sodium via active transport by the symporter sodium-glucose transporter 1 and are released via facilitated diffusion by GLUT2. The monomers enter the portal vein and travel to the liver. When fructose and galactose enter the liver, they must first be converted to glucose to be metabolized for energy. These can be converted into intermediates of the glycolysis pathway, glucose-6-phosphate or fructose-6-phosphate, to directly enter the glycolysis pathway or the substrate of glycogenesis, glucose-1-phosphate, to be stored as glycogen.

Glucose metabolism requires the following B vitamins to act as coenzymes: thiamine (B1), riboflavin (B2), and niacin (B3). Glucose metabolism begins in the cytoplasm of cells with the anaerobic process of glycolysis when one 6-carbon glucose molecule is partially oxidized into two 3-carbon pyruvate molecules. During the process, there is a net yield of two ATP and two NADH, where they will carry the electrons to the electron transport chain, eventually producing ATP. NADH is derived from niacin. ATP is the main source of cellular energy due to its high energy bonds between phosphate groups, which are released when broken via hydrolysis.

In the absence of oxygen, which can happen during strenuous exercise or in cells without mitochondria, lactate dehydrogenase catalyzes the conversion of pyruvate to lactate, which can then go back to the liver to be converted back to pyruvate and undergo gluconeogenesis to create glucose. Then, the glucose can go back to the muscle cells and go through glycolysis, again releasing two ATP molecules. This is called the Cori cycle and shows how lactate, the waste product of skeletal muscles, can be converted to glucose in hepatocytes and then be used for energy back in the skeletal muscles.

In the presence of oxygen, pyruvate will travel to the mitochondrial matrix, where pyruvate dehydrogenase will catalyze the oxidation and decarboxylation of two 3-carbon molecules of pyruvate from glycolysis into two 2-carbon molecules of acetyl-CoA. Pyruvate dehydrogenase uses thiamine pyrophosphate, or TPP, as a coenzyme. In addition, two carbon dioxide molecules and two NADH molecules are produced, and the NADH molecules will carry electrons to the electron transport chain to ultimately produce ATP. Pyruvate decarboxylation is the link between glycolysis and the citric acid cycle.

The citric acid cycle, also known as the TCA cycle and the Krebs cycle, occurs in the mitochondrial matrix where the 2-carbon acetyl-CoA will join 4-carbon oxalate to produce 6-carbon citrate, which gets degraded to produce the energetic molecules GTP, NADH, and FADH2. The cycle will continue so long as there is an input of acetyl-CoA because citrate eventually gets converted back to oxalate. Two pyruvates from glycolysis will release 2 GTP, 6 NADH, and 2 FADH molecules. FADH is derived from riboflavin. NADH and FADH2 will travel to the electron transport chain, where ATP will be synthesized via oxidative phosphorylation.

Oxidative phosphorylation begins at the electron transport chain along the inner membrane of the mitochondrion. Four protein complexes I-IV are embedded along the membrane and function to pump protons from the mitochondrial matrix to the intermembrane space to create an electrochemical gradient through a chain of redox reactions. Protein complex I receive electrons from NADH to pump hydrogen across the inner membrane. FADH2 drops electrons off at protein complex II, and protons get pumped across at protein complex III. One molecule of NADH generates three ATP molecules, while one molecule of FADH2 only generates two molecules of ATP.  When enough protons fill up the intermembrane space, an electrochemical gradient occurs. At protein complex IV, oxygen acts as the final electron acceptor, forming water. Through chemiosmosis, protons will flow from the intermembrane space through the hydrophilic tunnel of ATP synthase back to the matrix. The proton motive force generates energy that allows ATP synthase to condense ADP + Pi into high-energy ATP. Overall, this process generates 34 ATP molecules per molecule of glucose and is by far the most efficient way to produce energy.

Proteins

Protein digestion begins in the stomach, where they are broken down by the protease enzyme pepsin. First, gastric parietal cells will release hydrochloric acid, which will denature proteins and convert inactive pepsinogen to active pepsin. Pepsin digests proteins by hydrolyzing peptide bonds between amino acids to form large polypeptides or oligopeptides. Protein digestion continues in the small intestine. In response to the acidic chyme from the stomach, the hormones cholecystokinin and secretin are synthesized in the duodenum. These hormones trigger pancreatic cells to secrete bicarbonate and proenzymes into the intestine. The proenzymes trypsinogen, procarboxypeptidase, and chymotrypsinogen are converted into their active enzyme forms trypsin, carboxypeptidase, and chymotrypsin in a cascade of enzymatic reactions. Trypsin, carboxypeptidase, and chymotrypsin digest polypeptides into tripeptides, dipeptides, and free amino acids that can be absorbed in the small intestine.

Peptide and amino acid absorption occur across epithelial cells in the small intestine via transporters. Some amino acids can travel across the epithelium paracellularly, while others require amino acid transporters that vary based on the specific amino acid and mechanism in which they transport. Tripeptides and dipeptides are transported into the epithelial cell via PEPT1 coupled with the electrochemical gradient produced by the Na+/H+ exchanger on the brush border membrane. Intracellular peptides finish breaking down tripeptides and dipeptides into free amino acids. Free amino acids will exit the basolateral membrane of the epithelial cell and enter the bloodstream at the portal vein to the liver.

Amino acids can be metabolized via transamination for amino acid interconversion or deamination for the oxidation of the carbon skeleton for energy or excretion. For amino acid interconversion, pyridoxine (B6), cobalamin (B12), and folate (B9) are required. For amino acid oxidation, pyridoxine (B6), cobalamin (B12), and biotin (B7) are required. Amino acids can undergo transamination to enter the TCA cycle in glucose metabolism. Certain amino acids like alanine can be transaminated by an aminotransferase enzyme with the coenzyme PLP, which is derived from pyridoxine, to form pyruvate. Other amino acids can be transaminated by an aminotransferase enzyme with PLP to form α-ketoglutarate, an intermediate in the TCA cycle. Some amino acids can be transaminated by an aminotransferase enzyme with PLP to form oxaloacetate, which is an intermediate in the TCA cycle. Other amino acids can be oxidized with enzymes that require biotin and vitamin B12 as coenzymes or from succinyl-CoA, which is an intermediate in the TCA cycle. When the carbon skeletons of amino acids become degraded for energy, they are deaminated, and the nitrogen group is excreted in the form of urea.

Lipids

Limited digestion of lipids occurs in the mouth and stomach with the enzymes lingual lipase and gastric lipase, respectively. However, most ingested lipids arrive at the duodenum of the small intestine undigested. The presence of lipids in the duodenum stimulates the release of enzymes from the pancreas and bile from the gallbladder. Bile emulsifies that lipids preparing them for digestion by pancreatic lipase. Pancreatic lipase hydrolyzes triglycerides to monoglycerides and free fatty acids. Lipids are absorbed via simple diffusion. Short-chain fatty acids and glycerol move directly into the portal circulation and bind to albumin. Long-chain fatty acids, mono/diglycerides, cholesterol, and phospholipids combine with bile to form micelles allowing them to be soluble in the hydrophilic environment and then leave the micelle and enter the intestinal mucosa cell. In the intestinal cell, long-chain fatty acids are re-esterified to form triglycerides. Triglycerides combine with cholesterol, phospholipids, and other proteins to form chylomicrons. The chylomicrons will leave the intestinal cell and enter the lymph system, eventually entering the bloodstream through the thoracic duct.

Lipoproteins carry lipids throughout the bloodstream, and the enzyme lipoprotein lipase frees up fatty acids to be taken up by cells. In the bloodstream, the chylomicrons can deliver the dietary fatty acids to body cells, where they will form triglycerides and the remaining lipids to the liver to travel to other cells or be excreted. In the liver, triglycerides, cholesterol, phospholipids, and proteins will combine to form VLDL, which will leave the liver to deliver lipids, mainly in the form of triglycerides, to cells in the bloodstream. As VLDL delivers triglycerides to cells, it begins to shrink and become LDL. LDL continues to carry lipids to cells, but the lipids are mainly in the form of cholesterol. LDL binds to LDL receptors of cells for cholesterol to be taken up. The remaining lipids will leave cells in the form of HDL, where they will carry lipids back to the liver for either reuse or excretion. In the cells, lipids can be metabolized for energy by entering at different points of the glucose metabolism pathway. Triglycerides are broken down into glycerol and free fatty acids. Glycerol can be converted to pyruvate and catabolized for energy. Free fatty acids can be oxidized to acetyl-CoA to enter the citric acid cycle.

  • Vitamin B1 (Thiamin) – Thiamin absorption occurs mainly in the jejunum of the small intestine. Higher concentrations are absorbed via passive diffusion, while lower concentrations are absorbed via an active, carrier-mediated system that involves phosphorylation. In the blood, thiamin is transported in the erythrocytes and plasma. A small percentage of thiamin is absorbed, while the remainder is excreted in the urine.
  • Vitamin B2 (Riboflavin) – Thiamin is mainly consumed as FMN and FAD bound to a food protein. In the stomach, the acidic environment releases the coenzymes FMN and FAD from the protein. Most absorption of riboflavin occurs in the small intestine via an active or facilitated transport system. FMN and FAD must first be hydrolyzed to riboflavin by nonspecific pyrophosphatases to be absorbed. Riboflavin is transported in the plasma mainly bound to albumin and is excreted in the urine.
  • Vitamin B3 (Niacin) – At low concentrations, niacin is absorbed in the small intestine via sodium-ion-dependent facilitated diffusion. At high concentrations, niacin is absorbed in the small intestine via passive diffusion. Niacin can be transported freely in the blood in the forms of nicotinic acid or nicotinamide. Cells and tissues can take up niacin via passive diffusion or with the use of transporters. Niacin is excreted in urine as 1-methyl nicotinamide or NAM.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid is absorbed via active transport at low concentrations and passive transport at high concentrations in the small intestine. Pantothenate kinase catalyzes the synthesis of CoA from pantothenate. CoA plays an important role in the citric acid cycle in the forms of acetyl-CoA and succinyl-CoA. CoA can be hydrolyzed to pantothenate for excretion. Pantothenic acid is excreted in the urine.
  • Vitamin B6 (Pyridoxine)  – The main dietary form of vitamin B6 is pyridoxal phosphate or PLP. For PLP to be absorbed in the small intestine, it must first undergo phosphatase-mediated hydrolysis to enter the small intestine in its nonphosphorylated form. Pyridoxal, or PL, crosses the enterocyte via passive diffusion to enter the bloodstream to the liver. In the liver, PL is converted back to PLP by the enzyme PL kinase. PLP is the main circulating form of vitamin B6 and is transported in the blood bound to albumin. The majority of PLP in the body is found in the muscle. Vitamin B6 is excreted in the urine in the form of 4-pyridoxic acid.
  • Vitamin B7 (Biotin) – Biotin can be ingested as free biotin or protein-bound biotin. In the small intestine, an enzyme called biotinidase releases biotin from its covalent bond to the protein allowing it to be absorbed. Biotin is absorbed in the small intestine through a sodium-dependent transporter. Biotin is transported through the bloodstream to the liver, mostly unbound as free biotin. Biotin and biotin metabolites are excreted in the urine.
  • Vitamin B9 (Folate)  – Food folates are polyglutamate derivatives and must be hydrolyzed to the monoglutamate forms before absorption. The monoglutamate form of folate is absorbed in the small intestine via active transport. Pharmacological doses of folic acid from supplements or fortified foods are absorbed via passive transport. Folate is transported in the bloodstream to the liver in the form of 5-methyl-tetrahydrofolate. Folate is mostly bound to albumin in the bloodstream. Most ingested folate is used or stored. Any dietary folate not absorbed is excreted in feces.
  • Vitamin B12 (Cobalamin)  – Small amounts of vitamin B12 are absorbed through a coordinated process of the GI tract, given naturally occurring B12 is bound to a protein that must be released for absorption. First, in the stomach, the presence of acid and pepsin causes the dissociation of food-bound vitamin B12 from its proteins. Then R-proteins or haptocorrins, secreted by the salivary glands, bind to vitamin B12 to protect it from stomach acid. In the small intestine, pancreatic proteases degrade R-proteins to allow B-12 to bind to intrinsic factor, which is secreted by gastric parietal cells. Intrinsic factor attaches B12 to specific ileal mucosa receptors allowing the complex to be internalized by endocytosis into the enterocyte and released into the bloodstream where it is bound to transcobalamin I, II, or III. 50% of transcobalamin II bound B12 is taken up by the liver, where it is stored while the remainder is transported to other tissues. B12 is excreted in bile, but most of it ends up reabsorbed.
  • Vitamin C (Ascorbic Acid) – The absorption, tissue distribution, and excretion of vitamin C are tightly regulated by tissue-specific active transporters SVCT-1 and SCVT-2. Ascorbic acid is absorbed into the enterocyte by SVCT-1 and enters the bloodstream via SVCT-2. Other tissues take up ascorbic acid via SVCT-1 and/or SCVT-2. Vitamin C is excreted in the urine at intakes greater than 400 mg/day. Vitamin C is most concentrated in the brain, eyes, and adrenal gland.
  • Vitamin A (Retinol) – Vitamin A is ingested both in the form of retinol and provitamin A carotenoids. In the small intestine, retinol and provitamin A carotenoids enter the mucosal cell after combining with bile to form a micelle. Retinol binds to cellular retinol-binding protein (CRBP) II within the intestinal mucosal cells to form a retinol-CRBP II complex. Then, lecithin retinol aminotransferase esterifies CRBP II retinol with a fatty acid to form CRBP-retinyl palmitate. The retinol esters will be incorporated with other lipids and apoproteins to form a chylomicron. The chylomicron will leave the intestinal cell and enter the lymph system and eventually enter the blood. β-carotene, a provitamin A carotenoid, is converted to retinoic acid inside the intestinal cells and is able to directly enter the bloodstream where it attaches to albumin to be transported to the liver.
  • Vitamin D (Cholecalciferol) – Vitamin D is obtained mainly through UV-B-induced production in the skin. A minor amount of vitamin D is obtained through dietary intake. In the skin, vitamin D3, or cholecalciferol, is synthesized when 7-dehydrocholesterol is exposed to UV-B light from the sun. Vitamin D3 is transferred to the liver to be further metabolized. Through dietary intake, vitamin D3 is absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporate into chylomicrons to leave the intestinal cells to enter the lymph system and eventually enter circulation the thoracic duct. In the liver, vitamin D3 enters a hepatocyte and is hydroxylated into 25-OH vitamin D3, which is catalyzed by the enzyme 25-hydroxylase. Then, 25-OH vitamin D3 bind to vitamin D-binding protein, or DBP, to leave the hepatocytes and be transported to the kidney for an additional hydroxylation reaction. In the kidney, 25-OH vitamin D3 is hydroxylated to 1,25-(OH)2 vitamin D3, which is catalyzed by the enzyme 1-hydroxylase. 1,25-(OH)2 vitamin D3 is also known as calcitriol, which is considered the active form of vitamin D. 1,25-(OH)2 vitamin D3 bound to DBP is released to the bone, immune cells, and liver cells.
  • Vitamin E (Tocopherol) – Through dietary intake, vitamin E is absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporate into a chylomicron to leave the intestinal cells and enter the lymph system and eventually enter circulation the thoracic duct. Vitamin E is transported in remnant chylomicrons to the liver, where it is taken up by a hepatocyte. In the hepatocyte, α-tocopherol transfer protein incorporates α-tocopherols into very low-density lipoproteins, or VLDLs, to transport to peripheral tissues. In circulation, lipoprotein lipase (LPL) catalyzes the conversion of VLDL to LDL to HDL. The cellular uptake of α-tocopherol takes place with the uptake of lipoproteins via receptor-mediated endocytosis. Most α-tocopherol is stored in adipose tissue. The remaining tocopherols and tocotrienols are excreted with bile in feces.
  • Vitamin K (Phylloquinone; Menaquinone) – Through dietary intake, vitamin K1 and K2 are absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporation into a chylomicron to leave the intestinal cells and enter the lymph system and eventually enter circulation at the thoracic duct. Vitamin K1 and K2 are transported in remnant chylomicrons to the liver where it is taken up by a hepatocyte. In the hepatocyte, vitamin K1 and K2 are incorporated into very low-density lipoproteins, or VLDLs, to transport to peripheral tissues. In circulation, lipoprotein lipase (LPL) catalyzes the conversion of VLDL to LDL to HDL. The cellular uptake of vitamin K1 and K2 takes place with the uptake of lipoproteins via receptor-mediated endocytosis. Vitamin K is stored predominantly in the liver in the form of menaquinone and is excreted in the urine and feces.
  • Calcium – The intestine, kidney, bone, and parathyroid gland work together to tightly regulate calcium balance in the body. The majority of calcium is absorbed in the small intestine via paracellular diffusion. The remainder of calcium is absorbed transcellular through the calcium channel TRPV6 when luminal calcium levels are low. Calcium is transported in the bloodstream in three forms: 48% ionized as free Ca2+, 46% bound to the protein albumin, and 7% complexed with citrate, phosphate, or sulfate. In low blood calcium concentration conditions, the parathyroid gland is stimulated to release parathyroid hormone (PTH). PTH then stimulates the kidneys to increase calcium reabsorption in the proximal convoluted tubule. PTH also stimulates the kidneys to convert 25-OH D3 into 1,25(OH)2 D3, or calcitriol. The increased calcitriol and PTH in the blood travel to the bone and stimulate the resorption of calcium and phosphorus from the bone. Calcitriol also stimulates the small intestine to increase calcium absorption. As a result, blood calcium is increased. In high blood calcium conditions, the thyroid gland releases the hormone calcitonin, preventing calcium mobilization from the bone, thus reducing blood calcium levels. 99% of the calcium in the body is found in the bones and teeth, while the remainder is found in soft tissues and plasma both intracellularly and extracellularly. Most calcium is reabsorbed in the kidney, but the remainder is excreted in urine and feces.
  • Magnesium – Magnesium is absorbed in the small intestine through paracellular diffusion and transcellular active transport via TRPM6 and TRMP7. At normal magnesium intakes, 30% of intestinal magnesium absorption occurs via transcellular transport. When magnesium intakes are lower, more magnesium is absorbed via transcellular transport. When magnesium intakes are higher, more magnesium is absorbed through paracellular diffusion. Magnesium is transported in the blood as free Mg2+(60%), protein-bound (30%), and complexed to citrate, phosphate, or sulfate (10%). The kidneys control magnesium homeostasis. About 70% of serum magnesium is available for glomerular filtration, and 96% of the filtered magnesium is reabsorbed in the kidneys through several mechanisms in the proximal tubule, ascending limb, and distal tubule. The remaining magnesium is excreted in the urine. 99% of magnesium in the body is stored intracellularly in bone, muscle, and soft tissues, while 1% of magnesium in the body is found in extracellular fluid.
  • Phosphorus –  The phosphorus is absorbed in the small intestine into the enterocyte via two processes: active transport by the apical Na+ phosphate transporter NaPi-IIb and paracellular diffusion. Phosphorous leaves the enterocyte to enter the bloodstream via facilitated diffusion. The kidney plays a role in phosphorus homeostasis through the reabsorption of inorganic phosphate from the glomerular filtrate in the proximal convoluted tubule. Approximately 75 to 85% of phosphorus is reabsorbed per day, and the remainder is excreted in the urine. Phosphorus homeostasis can also be regulated secondary to that of calcium with resorption from the bone due to high PTH and calcitriol levels. Throughout the body, phosphorus is distributed 85% in the skeleton, 0.4% in the teeth, 14% in the soft tissue, 0.3% in the blood, and 0.3% in the extravascular fluid.
  • Sodium – Sodium is absorbed in the small intestine across the brush border membrane of the enterocyte via sodium-glucose cotransporter 1 (SGLT1). SGLT 1 is an active transporter that absorbs 2 sodium ions and 1 glucose across the brush border membrane of the enterocyte. Sodium is then transported out of the enterocyte into the bloodstream across the basolateral membrane via the sodium-potassium pump, or ATPase. The sodium-potassium pump uses ATP to transport 3 sodium ions out of the enterocyte and 2 potassium ions into the enterocyte. Sodium and water balance are closely linked and maintained by the kidneys. Half of the sodium in the body is found in extracellular fluid, while around 10% is found in intracellular fluid. The remaining 40% of sodium is found in the skeleton. Small losses of sodium can occur through urine, feces, and sweat.
  • Potassium – Most of the dietary potassium is absorbed in the small intestine via passive transport. The kidney maintains potassium homeostasis. About 90% of the potassium consumed is excreted in the urine, with the remaining small amount excreted in stool and sweat. Most of the potassium content in the body is found in the intracellular space of the skeletal muscle.
  • Chloride – Chloride absorption occurs in the lumen of the small intestine via three distinct mechanisms: paracellularly through passive transport, the coupling of Na+/H+ and Cl−/HCO3− exchangers, and HCO3−-dependent Cl− absorption. Chloride is principally found in extracellular fluid. The kidneys regulate chloride concentration. Around 99% of chloride is reabsorbed in the proximal tubule of the kidneys both paracellularly and transcellular via the Cl−/HCO3− exchanger. The remainder of chloride can be excreted in urine, feces, or sweat.
  • Iron – Iron consumed from food can be present in two forms: heme and nonheme iron. 90% of dietary iron consists of nonheme iron, which is far less bioavailable than heme iron. Iron is absorbed in the small intestine in the duodenum. Given nonheme iron is often present in the form of ferric iron, it must be reduced to the ferrous form prior to enterocyte uptake with the ferric reductase enzyme DCYTB. The apical surface of the enterocyte contains divalent metal transporter 1 (DMT1), which transports ferrous iron into the enterocyte. On the basolateral membrane of the enterocyte, ferroportin releases ferrous iron to hephaestin, which oxidizes ferrous iron to ferric iron so it can bind to the transporting protein transferrin in portal circulation. Ferroportin is the main regulatory point of entry for iron in the body. Iron is stored in the liver bound to ferritin, where it can be sequestered to bone marrow for erythropoiesis or red blood cell formation. Macrophages in the reticuloendothelial system of the liver, spleen, and bone marrow can ingest old red blood cells to recycle iron to be stored in the liver. There is no specific excretory system for iron. Iron loss can only occur secondary to the exfoliation of epithelial cells in the skin and gastrointestinal tract in addition to red blood cell loss from the gastrointestinal tract.
  • Zinc – Zinc is absorbed in the small intestine via carrier-mediated transport, with ZIP4 taking zinc up into the intestinal cell and ZNT1 releasing it into the bloodstream. Zinc is bound to albumin in circulation. Zinc transporters are pervasive throughout tissues in the body and play a role in maintaining zinc homeostasis. Zinc is excreted in feces.
  • Copper – Copper absorption mainly occurs in the small intestine. Copper is taken up by enterocytes with copper transporter 1 (CTR1), which is a copper importer located at the apical membrane of intestinal cells and most tissues. Copper is exported from the enterocytes into the blood by the exporter ATP7A. In portal circulation, most of the copper is bound to the transporter protein ceruloplasmin. Copper is taken up by the liver when copper-bound ceruloplasmin binds to ceruloplasmin receptors. In the hepatocytes, protein metallochaperones serve to assign and transport copper to specific pathways throughout the body. Copper is exported from the hepatocyte via the exporter ATP7B. Excess copper is secreted in the bile, which gets excreted in the feces.
  • Iodine – Iodine can be ingested in many chemical forms. Iodide is rapidly and almost completely absorbed in the stomach and small intestine. Iodate, which is used in iodized salt, is reduced in the gut and then absorbed as iodide. In circulation, iodine is taken up mainly by the thyroid gland and kidney. Iodine uptake by the thyroid depends on iodine intake, whereas uptake by the kidney remains fairly constant. Iodine is excreted in the urine. Most of the body’s iodine is stored in the thyroid to be used in thyroid hormone synthesis.
  • Selenium – The mechanism of selenium absorption is not well known. Selenium absorption occurs in the small intestine via mechanisms dependant upon the form of selenium. The absorption of inorganic selenate occurs through active transport with a sodium pump. The absorption of inorganic selenite occurs via passive diffusion. Organic selenomethionine and selenocysteine are absorbed via an active transport mechanism similar to that of neutral amino acids like methionine. Selenium is absorbed into the portal bloodstream from the enterocyte and is transported to the liver in multiple forms. Selenite is taken up by erythrocytes and reduced by glutathione reductase to selenide, which is transported in the plasma bound to albumin. Selenium can also be transported in the form of selenoprotein P. Sometimes, selenium may bind to LDL and VLDL. Selenium is stored in tissues in the form of selenomethionine with variable densities in the liver, muscle, kidney, plasma, and other organs. Selenium excretion via urine in the form of methylselenol.

Molecular

Carbohydrates

Carbohydrates are organic molecules made up of carbon, hydrogen, and oxygen. Carbohydrates are classified based on their chemistry: individual monomer characteristics, degree of polymerization, and type of linkages (α or β). Given this classification, carbohydrates subdivide into three main groups: sugars (degree of polymerization = 1 to 2), oligosaccharides (degree of polymerization = 3 to 10), and polysaccharides (degree of polymerization more than 10). Sugars include monosaccharides and disaccharides. The most common monosaccharides are glucose, fructose, and galactose. The most common disaccharides are sucrose, lactose, and maltose. Examples of oligosaccharides include maltodextrins, raffinose, and polydextrose. Polysaccharides include starches and non-starch polysaccharides. Starches include digestible amylose due to its alpha-linked monosaccharides. Non-starch polysaccharides include non-digestible cellulose due to their β-linked monosaccharides.

Proteins

Proteins are polymers of amino acids. Amino acids are organic molecules composed of carbon, hydrogen, oxygen, and nitrogen. The general structure of an amino acid consists of a central carbon surrounded by hydrogen, an amino group, a carboxylic acid group, and a side chain “R.” Each amino acid has a unique side chain. Nine essential amino acids must come from dietary sources: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The body can make eleven non-essential amino acids from precursors: alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine. There are four structure levels in a protein: primary, secondary, tertiary, and quaternary. The primary structure of a protein is a chain of amino acids connected by peptide bonds; this determines the subsequent structures and biological functions of the protein. The secondary structure of a protein consists of hydrogen bonding within amino acid chains that create either an α-helix or β-sheet conformation. The tertiary structure of a protein derives from attractions between α-helices and β-sheets of a polypeptide resulting in a three-dimensional arrangement of a protein. The quaternary structure of an amino acid consists of a spatial arrangement of multiple polypeptides in a protein.

Lipids

Lipids are organic molecules that share the common property of being hydrophobic. Dietary lipids are often in the forms of triglycerides, phospholipids, cholesterol, and fatty acids. Fatty acids are classified as saturated or containing no carbon-carbon double bonds, or unsaturated, or containing at least one carbon-carbon double bond. Saturated fatty acids have higher melting points than unsaturated fatty acids, making them solid at room temperature, unlike liquid unsaturated fatty acids. Triglycerides are composed of one 3-carbon glycerol backbone and three fatty acids. Phospholipids contain a phosphate head connected to a glycerol molecule, connected to two fatty acids. Cholesterol is a sterol that is composed of a hydrocarbon ring structure.

  • Vitamin B1 (Thiamin) – Thiamin consists of pyrimidine and thiazole rings that are linked by a methylene bridge. Thiamin exists in a variety of phosphorylated forms. Its main form is thiamin pyrophosphate or TPP.
  • Vitamin B2 (Riboflavin) – The basic chemical structure of riboflavin consists of a flavin group formed by the tricyclic heterocyclic isoalloxazine and a ribitol sugar group. The main coenzyme forms of riboflavin are flavin mononucleotide or FMN and flavin adenine dinucleotide, or FAD.
  • Vitamin B3 (Niacin) – Niacin refers to nicotinamide, nicotinic acid, and other derivatives. The basic chemical structure of nicotinic acid consists of a pyridine ring with a substituted carboxylic acid group. The chemical structure of nicotinamide consists of a pyridine ring with a substituted amide group. The main coenzyme forms of niacin are nicotinamide adenine dinucleotide or NAD and nicotinamide adenine dinucleotide phosphate or NADP.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid is a water-soluble vitamin synthesized from the condensation reaction of pantoic acid and β-alanine in only plants and bacteria. Pantothenic acid serves to transfer and carry acyl groups.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6 is a generic term for six related compounds: pyridoxal (PL), pyridoxamine (PM, pyridoxine (PN), and their respective 5’-phosphatase forms (PLP, PMP, and PNP). The major forms of vitamin B6 in animal tissues are PLP and PMP.
  • Vitamin B7 (Biotin) – Biotin’s chemical structure consists of a heterobicyclic ring of radio and thiophene with a valeric acid side chain.
  • Vitamin B9 (Folate) – Folate is the generic term for the different forms of vitamin B9 that function in single-carbon transfers. The most oxidized and stable form of folate called folic acid is in vitamin supplements. It consists of a p-aminobenzoic acid molecule bound to a pteridine ring on one side and a glutamic acid molecule on the other side. Naturally occurring folates found in food, called food folate, are pteroylpolyglutamates, which contain between one and six additional glutamate molecules connected by a peptide linkage to glutamate’s γ-carboxyl.
  • Vitamin B12 (Cobalamin) – Cobalamin, or vitamin B12, is a generic term for a group of cobalt-containing compounds with a corrin ring attached to 5,6-dimethylbenzimidazole, a sugar ribose, and a phosphate. The two cobalamins that are active in human metabolism as coenzymes are methylcobalamin and 5-deoxyadenosylcobalamin.
  • Vitamin C (Ascorbic Acid) – Vitamin C, or ascorbic acid, chemically is a simple carbohydrate with an ene-diol structure that makes it an essential water-soluble electron donor. The main form of vitamin C found in foods is its reduced form – ascorbic acid. Ascorbate is the main circulating form of vitamin C in the body.
  • Vitamin A (Retinol) – Vitamin A is a generic descriptor for compounds that exhibit the biological activity of retinol and provitamin A carotenoids. Retinol is an unsaturated 20-carbon cyclic alcohol. Provitamin A carotenoids exhibit a 40-carbon basal structure with cyclic end groups and a conjugated system of double bonds.
  • Vitamin D (Cholecalciferol) – Vitamin D3, or cholecalciferol, had a chemical structure that contains three steroid rings and an eight-carbon side chain. The structure derives from cholesterol.
  • Vitamin E (Tocopherol) – The term vitamin E encompasses eight lipophilic compounds that include four tocopherols and four tocotrienols, each of which has a designation as α-, β-, γ-, and δ-. Each of these compounds contains a chromanol ring and a lipophilic tail. Tocotrienols differ from tocopherols with their unsaturated side chains. α-tocopherol is the only form of vitamin E that is known to reverse deficiency symptoms.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K occurs naturally in two main forms: K1, or phylloquinone, and K2, or menaquinone, which has many different forms. Also, vitamin K occurs in the synthetic form of vitamin K3, or menadione, which contains only the 2-methyl-1, a 4-naphthoquinone nucleus common to all forms of vitamin K. The natural forms differ by the number of isoprenoid units in their isoprenoid side chains.
  • Calcium – Calcium is an alkaline earth metal cation found in the form of Ca2+. Calcium is a critical divalent cation in intracellular and extracellular fluid.
  • Magnesium – Magnesium is an alkaline earth metal cation found in the form of Mg2+. Magnesium is the second most abundant intracellular cation in the body.
  • Phosphorus – Phosphorous is a multivalent nonmetal that occurs in both inorganic and organic forms throughout the body. The organic forms of phosphorus include phospholipids and various phosphate esters. The inorganic forms of phosphorus include phosphate ions, protein-bound phosphate, and calcium, sodium, or magnesium-bound phosphate. Most phosphorus exists in the form of an inorganic free phosphate ion (PO42- or PO43-).
  • Sodium – Sodium is an alkali metal cation found in the form of Na+. Sodium is the major extracellular cation in the body.
  • Potassium – Potassium is an alkali metal cation found in the form of K+. Potassium is the major intracellular cation in the body.
  • Chloride – Chloride is a nonmetal anion found in the form of Cl-. Chloride is the body’s principal anion making up 70% of the body’s total anion content and serves as the most important extracellular anion in the body.
  • Iron – Iron is a transition metal element. Iron exists in two main oxidation states: Fe2+ and Fe3+. The more bioavailable form of iron is its reduced form ferrous iron, or Fe2+, due to its solubility. The less bioavailable form of iron is its oxidized form ferric iron, or Fe3+, due to its lack of solubility. Heme iron is contained in the protoporphyrin ring of hemoglobin, myoglobin, and cytochromes and is highly bioavailable. Nonheme iron can be found in molecules like iron-sulfur enzymes and ferritin and is less bioavailable.
  • Zinc – Zinc is a metal that exists in the form of Zn2+. With the 2+ charge, zinc is a strong electron acceptor in biological systems.
  • Copper – Copper is a transition metal that exists in the forms of Cu+ and Cu2+. Cu+ is the cuprous reduced form of copper. Cu2+ is the cupric oxidized form of copper. Copper is absorbed into cells in its reduced form but is ingested and travels through the bloodstream in its oxidized form.
  • Iodine – Iodine is a nonmetal element identified by its distinct violet vapor. Iodine is consumed and absorbed in its reduced form of iodide (I-). Iodine is also consumable in its oxidized form of iodate (IO3-), as well as when it is organically bound to thyroxine (T4) and triiodothyronine (T3).
  • Selenium – Selenium is present in nature in both organic and inorganic forms. The main organic forms of selenium are selenomethionine and selenocysteine. The inorganic forms of selenium are selenite (SeO32-), selenide (Se2−), selenate (SeO42-), and selenium element (Se).

Function

Macronutrients – Carbohydrates, Proteins, Lipids

Macronutrients mainly function to supply energy. Carbohydrates function as the main source of cellular energy from the human diet and are particularly essential to supply energy to the glucose-dependent brain and nervous system. Fiber plays a role in lowering cholesterol by binding to bile and promoting gut health. Proteins function less favorably as a source of energy because they play crucial roles in regulating body processes and contributing majorly to cell and body structure. Proteins particularly function as hormones, enzymes, transporters, and antibodies. Lipids function as a source of stored energy, contribute to cell function and structure and protects body organs. Water acts as a solvent for chemical reactions, a medium for nutrient transport, and a thermoregulator.

  • Vitamin B1 (Thiamin) – The coenzyme form of thiamin, or TPP, is involved in the following types of metabolic reactions: decarboxylation of α-keto acids and transmetalation. These occur in carbohydrate and branched-chain amino acids metabolism.
  • Vitamin B2 (Riboflavin) – Riboflavin functions as a component of the metabolically essential coenzymes FMN and FAD. FMN and FAD can serve as intermediates in electron transfer in redox reactions. As coenzymes, FAD and FMN are often bound to enzymes that are oxidases and dehydrogenases.
  • Vitamin B3 (Niacin) – Niacin functions as a component of the metabolically essential coenzymes NAD and NADP. These coenzymes act as hydride ion acceptors or donors in biological redox reactions. They also serve as coenzymes for dehydrogenases.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid functions as a supporter of the synthesis and maintenance of coenzyme A, a cofactor and acyl group carrier for other enzymes, and an acyl protein carrier in the fatty acid synthase complex.
  • Vitamin B6 (Pyridoxine) – Vitamin B6, in the form of PLP, is a coenzyme for over 100 enzymes involved in amino acid metabolism. PLP is a coenzyme for aminotransferases, decarboxylases, racemases, and dehydratases. PLP is a coenzyme in the first step of heme biosynthesis and the transsulfuration of homocysteine to cysteine.
  • Vitamin B7 (Biotin) – Biotin functions in metabolism as a coenzyme for transferring single-carbon units in the form of carbon dioxide for the following carboxylases: pyruvate carboxylase, propionyl-CoA carboxylase, acetyl-CoA carboxylase, and β-methylcrotonyl-CoA carboxylase. These enzymes play roles in gluconeogenesis, citric acid cycle, fatty acid synthesis, and leucine degradation.
  • Vitamin B9 (Folate)  – Folate functions in nucleic and amino acid metabolism as a coenzyme in single-carbon transfers. Folate functions as a coenzyme in nucleic acid metabolism in the processes of DNA synthesis in purine and pyrimidine nucleotide biosynthesis.  Folate functions as a coenzyme in amino acid metabolism in amino acid interconversions, including the conversion of homocysteine to methionine, which serves as the major source of methionine for the formation of the major methylating agent S-adenosyl-methionine.
  • Vitamin B12 (Cobalamin)  – Cobalamin functions as a coenzyme for two enzymes in human metabolism: methionine synthase and L-methylmalonyl-CoA mutase. Vitamin B12, in the form of methylcobalamin, is required as a coenzyme to methionine synthase for the methyl transfer reaction from methyltetrahydrofolate to homocysteine resulting in the formation of methionine and tetrahydrofolate. Vitamin B12, in the form of adenosylcobalamin, is required as a coenzyme to  L-methylmalonyl-CoA mutase in the isomerization reaction that results in the conversion of L-methylmalonyl-CoA to succinyl-CoA.
  • Vitamin C (Ascorbic Acid) – Vitamin C, in the form of ascorbate, has both enzymatic and nonenzymatic functions in the body. Ascorbate functions as a coenzyme as a reducing agent in the synthesis reactions of collagen, carnitine, neurotransmitters, and tyrosine. Ascorbate functions nonenzymatically as a powerful water-soluble antioxidant with the ability to reduce free radicals and reactive oxygen species. Ascorbate notably reduces glutathione radicals produced by the electron transport chain.
  • Vitamin A (Retinol) – Vitamin A functions metabolically in vision, cellular differentiation, gene expression, growth, immune system, and reproduction. In the form of 11-cis-retinal, Vitamin A is the chromophore group of rhodopsin found in the rod cells of the retina and is essential for night vision. In the form of retinoic acid, Vitamin A is required for the differentiation of certain cells like keratinocytes to epidermal cells and squamous epithelial keratinizing cells to mucous-secreting cells. Vitamin A can regulate gene expression by acting as transcription factors when bound to RAR and RXR. Vitamin A protects against xerophthalmia by maintaining normal growth of the conjunctival membranes of the eye. Vitamin A plays roles in processes involved in innate and adaptive immunity, including cell differentiation and hematopoiesis. Vitamin A plays a vital role in spermatogenesis in reproduction.
  • Vitamin D (Cholecalciferol) – Vitamin D, in its active form 1,25-(OH)2 vitamin D3, can function as a hormone by binding to receptors on target tissues to activate a signal transduction pathway and a regulator of gene expression by binding to a nuclear receptor to affect transcription. One of the most important functions of 1,25-(OH)2 vitamin D3 is to work with parathyroid hormone to maintain blood calcium homeostasis. 1,25-(OH)2 vitamin D3 functions to increase the absorption of calcium in the small intestine and reabsorption of calcium in the kidneys in response to low blood calcium. It also works with parathyroid hormone to stimulate the resorption of calcium from the bone to increase blood calcium levels. 1,25-(OH)2 vitamin D3 can also bind to various nuclear vitamin D receptors, or VDRs, in the bones, intestines, kidneys, and skin to stimulate the transcription of genes. This process is key to osteoclast maturation.
  • Vitamin E (Tocopherol) – Vitamin E is best known to function as a chain-breaking antioxidant that neutralizes the lipid peroxyl radicals during lipid peroxidation to prevent cyclic propagation of lipid peroxidation. This process is key in protecting the polyunsaturated fatty acids within the phospholipids of plasma membranes and plasma lipoproteins.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K mainly functions in the synthesis of several blood coagulation factors. It also plays a role in bone mineralization. Vitamin K performs these functions by enabling the carboxylation of glutamic acid residues in proteins to form γ-glutamic carboxyl (Gla) residues. Gla residues enable proteins to bind with calcium and interact with other proteins, which is necessary for blood coagulation and bone mineralization.
  • Calcium – 99% of the calcium in the body is in bone and teeth as a structural component. The remaining calcium in the body is found in intracellular and extracellular spaces and plays key roles in innervation, muscle contraction, blood coagulation, hormone secretion, and intracellular adhesion.
  • Magnesium – Magnesium is an important intracellular cation for numerous functions throughout the body. Magnesium plays a key role in metabolic reactions such as energy storage, glucose metabolism, and nucleic acid and protein synthesis. Magnesium also functions in oxidative reactions, immune function, and bone development. Magnesium plays a role in stabilizing excitable membranes by maintaining electrolyte balance and homeostasis of calcium, sodium, and potassium. Magnesium acts as a calcium channel antagonist and plays a role in vasodilation.
  • Phosphorus – Phosphorus has various structural and metabolic functions throughout the body. Structurally, phosphorus functions to form the structure of bone and teeth along with calcium, the phosphate backbone of DNA and RNA, and the phospholipid bilayer of cell membranes. Metabolically, phosphorus functions to create and store energy in phosphate bonds of ATP, regulate acid/base balance in the blood as a buffer, regulate gene transcription, regulate enzyme activity, and enable signal transduction of numerous regulatory pathways.
  • Sodium – As an extracellular cation, sodium functions to regulate blood volume, blood pressure, osmotic equilibrium, and pH. Sodium and potassium ions function together to create an action potential maintained by ion pumps that allow for neurotransmission, muscle contraction, and heart function. Sodium also plays a critical role in the transport of nutrients across the plasma membrane.
  • Potassium – Potassium is critical for normal cellular function. Sodium and potassium ions function together to create an action potential maintained by Na+-K+ ATPase, allowing for neurotransmission, muscle contraction, and heart function. Potassium also works alongside sodium to maintain intracellular and extracellular osmotic pressure.
  • Chloride – As the most important extracellular anion in the body, chloride functions to maintain fluid balance, acid-base balance, electrolyte balance, electrical neutrality, and muscle function throughout the body. Chloride works with sodium to maintain fluid balance. Chloride also works with bicarbonate to maintain acid-base balance.
  • Iron – Iron’s functions are essential for oxygen transport and cell proliferation—iron functions as the core of heme proteins like myoglobin, hemoglobin, and cytochromes. Myoglobin and hemoglobin are essential for oxygen storage and transport, while cytochromes are essential for electron transport chain reactions in energy metabolism. Iron is also critical in its nonheme form in iron-sulfur enzymes like succinate dehydrogenase and NADH dehydrogenase in oxidative metabolism.
  • Zinc – Zinc functions structurally as a component of proteins and catalytically as a component of >300 enzymes in the body. Zinc’s functions are pervasive throughout the body and crucial to growth, immunity, cognitive function, and bone health.
  • Copper – Copper functions as a critical cofactor to a group of cellular transporters called cuproenzymes. Copper is essential for the proper function of human organs and metabolic processes such as hemoglobin synthesis, neurotransmitter synthesis, iron oxidation, cellular respiration, antioxidant peptide amidation, pigment formation, and connective tissue formation.
  • Iodine – The primary function of iodine is its role in the synthesis of thyroid hormones thyroxine (T4) and triiodothyronine (T3). At the apical surface of the thyrocyte, iodide is oxidized by the enzymes thyroperoxidase (TPO) and hydrogen peroxide to attach it to tyrosyl residues on thyroglobulin to produce the precursors of thyroid hormones: monoiodotyrosine (MIT) and diiodotyrosine (DIT). TPO then catalyzes the formation of a diether bridge between the phenyl groups of iodotyrosine to create thyroid hormones. The linkage of two DITs produces T4, while the linkage of MIT and DIT produces T3. T3 and T4  are almost structurally identical, but T3 has one less iodine than T4. Thyroid hormones function to regulate fetal cell growth, postnatal growth, and basal metabolic rate.
  • Selenium – Selenium functions as an essential component of selenoproteins that play major roles in dense against oxidation, thyroid hormone formation, DNA synthesis, reproduction, and fertility. The functions of most selenoproteins are unknown, but the known functions involve participation in antioxidant and anabolic processes. A family of antioxidant enzymes named glutathione peroxidases is dependent upon selenium to function to neutralize hydrogen peroxide and organic hyperoxides in both intracellular and extracellular compartments. Deiodinases are a group of three selenoenzymes responsible for converting T4 to T3 in thyroid hormone activation. Selenoprotein-P is the most abundant selenoprotein found in plasma and plays a major role in the transport and homeostasis of selenium in tissues.

Testing

Carbohydrates

Measuring the amount of glucose in plasma is one of the most important ways to screen for and manage diabetes. To clinically test and monitor blood glucose, blood is drawn from a vein, usually when the patient has fasted for at least 8 hours. The level of glucose is measured in milligrams of glucose per deciliter plasma. A healthy fasting blood glucose level is less than or equal to 99 mg/dL. Someone who has an increased risk for diabetes, or prediabetes, falls in the range of fasting blood glucose of 100 to 125 mg/dL. If a patient has a fasting blood glucose of 126 mg/dL or greater on two separate occasions, they can receive a diagnosis of diabetes.

Proteins

Nitrogen balance is the gold standard for testing the protein status of the body. Nitrogen balance can serve as a marker of adequate nutrition and physiological stress. Nitrogen balance is equal to the grams of nitrogen consumed minus the grams of nitrogen excreted. The grams of nitrogen consumed is calculated by the grams of protein consumed divided by 6.25 grams of protein per 1 gram of nitrogen. The grams of nitrogen excreted is calculated by extrapolating losses with grams of nitrogen in urinary urea plus 4 grams, which accounts for losses in feces, sweat, skin, and wounds. Under normal conditions, an individual should be at nitrogen equilibrium, or nitrogen balance equals zero. Critically ill patients often have negative nitrogen, so the goal with them is to increase the protein intake to achieve a positive nitrogen balance for healing.

Lipids

To test the amount of lipids in the body, a sample of blood is taken via venipuncture in tubes and analyzed for serum or plasma total cholesterol, triglycerides, and lipoproteins. Cholesterol levels remain fairly constant so that sampling is possible at any time. In contrast to cholesterol levels, triglyceride levels fluctuate throughout the day, so blood collection should occur after a 12-hour fasting period because, at that point, chylomicrons should have cleared from the circulation. To separate and quantify lipoproteins from the plasma sample, ultracentrifugation, precipitation, and electrophoresis are performed. High vs. low plasma lipid levels are determined based on the bell-shaped distribution of the general population. Cholesterol levels are determined based on the risk for coronary atherosclerosis. Cholesterol levels below 200 mg/dl are considered desirable, levels from 200 to 239 mg/dl are considered borderline high cholesterol, and levels of 240 mg/dl or greater are considered high cholesterol.

  • Vitamin B1 (Thiamin) – Thiamin status is measurable via urinary thiamin excretion, erythrocyte thiamin, and erythrocyte transketolase activity. Erythrocyte transketolase activity is considered the gold standard functional test of thiamin status.
  • Vitamin B2 (Riboflavin) – Riboflavin status is measured via erythrocyte glutathione reductase activity, erythrocyte flavin, and urinary flavin. Erythrocyte glutathione reductase activity is the most common method to determine riboflavin status.
  • Vitamin B3 (Niacin) – Niacin status can be measured using urinary 1-methyl nicotinamide excretion, plasma concentrations of 2-pyridone, erythrocyte pyridine nucleotides, and transfer of adenosine diphosphate ribose as a functional measurement. Urinary 1-methyl nicotinamide is the most reliable and sensitive measure of niacin status.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid status can be measured using urinary pantothenic acid excretion and whole blood pantothenic acid concentration.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6 status assessment is best with plasma PLP. A plasma PLP of <20 nmol/L indicates a vitamin B6 deficiency.
  • Vitamin B7 (Biotin) – Biotin status is measurable with urinary biotin and 3-hydroxyisovalerate excretion. Decreased urinary excretion of biotin along with increased urinary excretion of 3-hydroxyisovalerate indicates biotin deficiency.
  • Vitamin B9 (Folate)  – The primary test used to measure folate status is erythrocyte folate. Given folate is taken up by developing erythrocytes in the bone marrow, erythrocyte folate concentration is an ideal indicator of long-term folate status. Plasma homocysteine can also be useful as an indicator of folate status given in inadequate quantities of folate; not as much homocysteine can undergo conversion to methionine. Serum folate can also be tested as an indicator of dietary folate intake but is limited and should be used in conjunction with additional folate status indicators.
  • Vitamin B12 (Cobalamin)  – The primary test to measure vitamin B12 status is serum vitamin B12, reflecting both intake and stores. The lower limit of serum vitamin B12 for adults is 170 to 250 pg/mL. Serum methylmalonic acid concentration is another specific and functional indicator of vitamin B12 status because serum methylmalonic acid concentrations become elevated during vitamin B12 deficiency. Serum total homocysteine concentration is a functional but non-specific indicator of vitamin B12 status due to elevation during vitamin B12 deficiency.
  • Vitamin C (Ascorbic Acid – Vitamin C status testing is via plasma vitamin C and leukocyte vitamin C. Plasma vitamin C concentration is sensitive to a recent diet, while leukocyte vitamin C reflects tissue stores. A plasma vitamin C concentration of less than 0.2 mg/dL is considered deficient.
  • Vitamin A (Retinol) – The gold standard for testing vitamin A status is through a liver biopsy because the liver is vitamin A’s major storage organ. However, this measure is not very feasible in humans. Retinol status is testable with plasma retinol concentration, but it only indicates low status if there is a severe deficiency. Vitamin A status may also be tested with a relative dose-response test, which measures the magnitude of increased RBP following supplementation.
  • Vitamin D (Cholecalciferol) – Vitamin D status is tested by using serum 25-hydroxyvitamin D concentrations. A serum 25-hydroxyvitamin D concentration that is less than 20 ng/mL represents a vitamin D deficiency and a need for supplementation.
  • Vitamin E (Tocopherol) – Vitamin E status is difficult to test because serum concentrations of vitamin E are largely age-dependent and are influenced by blood lipids. In the general population, α-tocopherol plasma levels can range from 19.9 micromoles/L to 34.2 micromoles. More research needs to be done to adjust specific requirements to an individual’s bioavailability.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K status is difficult to assess due to its being lipophilic and not very abundant. However, functional tests such as prothrombin time or Gla protein measurement can be useful to assess vitamin K status indirectly.
  • Calcium – Calcium status is difficult to assess in individuals because there is no reliable indicator that can establish a relationship between calcium and a particular disease state. Total body calcium is not useful to assess calcium intake because the body regulates calcium in a very tight range and will adapt to conserve it. Bone-mass measurements may indicate long-term calcium status by assessing changes in bone density.
  • Magnesium – Magnesium status can be tested with serum magnesium. Serum magnesium is maintained at a tight range of 1.7 to 2.6 mg/dL. A serum value of under 1.7 mg indicates a magnesium deficiency. A serum value of over 2.6 mg/dL indicates magnesium toxicity.
  • Phosphorus – Serum phosphorus is the most common way to assess phosphorus status. Serum phosphorus is maintained in a relatively narrow range of 2.5 to 4.5 mg/dL. Although serum phosphorus does not reflect the full body stores, serum phosphorus is crucial for various cellular processes in the body. Serum phosphorus below or above the normal range can indicate a deficiency and toxicity, respectively.
  • Sodium – Sodium balance is tested via plasma sodium concentration. A plasma sodium concentration greater than 150 mmol/L indicates sodium toxicity or hypernatremia. A plasma sodium concentration of less than 136 mmol/L indicates sodium deficiency or hyponatremia.
  • Potassium – Potassium balance is tested via serum potassium. The body maintains normal serum potassium levels in a narrow range of 3.5 to 5.5 mmol/L. Potassium toxicity, or hyperkalemia, occurs at serum potassium concentrations greater than 5.5 mmol/L. Potassium deficiency, or hypokalemia, occurs at concentrations less than 3.5 mmol/L.
  • Chloride – Since chloride serves as an important diagnostic indicator for various diseases, it can be tested for in serum, sweat, urine, and feces. Serum and urine chloride concentrations are used in the diagnosis of acid-base and osmolar disorders and used in formulas like the anion gap, strong anion gap, strong ion difference, and chloride/sodium ratio. Sweat chloride concentration is used in the diagnosis of cystic fibrosis when it is above 60 mmol/L.
  • Iron  – Iron is tested via serum-based indicators of iron status, such as hemoglobin, plasma ferritin, and plasma transferrin saturation. Hemoglobin is routinely measured to indicate anemia but is not specific for iron. Plasma ferritin is the gold standard of iron status because it is the most specific indicator of iron stores. A plasma ferritin concentration of less than 20 ng/L indicates iron deficiency. High plasma ferritin values can indicate iron overload. Transferrin saturation indicates the ratio of iron to transferrin to reflect transport iron. Transferrin saturation is low-cost but shows a pronounced diurnal variation.
  • Zinc – Zinc status testing is via serum zinc. A concentration of zinc below the lower value of the reference range of 10 to 18 micromol/L is considered a deficiency.
  • Copper – Copper status evaluation is via serum copper or serum ceruloplasmin. A concentration of serum copper below the lower value of the reference range of 12 to 20 micromol/L is considered a deficiency.
  • Iodine – Iodine status can be assessed with four different methods: urinary iodine concentration, goiter rate, serum TSH, and serum Tg. Urinary iodine, serum Tg, and goiter rate are complementary tests given urinary iodine are sensitive to recent iodine intake in a matter of days, serum Tg shows an intermediate response in a matter of weeks or months, and goiter rate changes reflect iodine nutrition in a matter of months or years. TSH can be used to assess iodine status reflecting on the level of circulating thyroid hormone but is a relatively insensitive indicator of iodine status in adults. However, TSH is a sensitive indicator of iodine status in newborns.
  • Selenium – Selenium status is tested via serum selenium. A concentration of selenium below the lower value of the reference range of 0.75 to 1.85 micromol/L is considered a deficiency.

Clinical Significance

Carbohydrates

Diabetes refers to a group of metabolic diseases of disordered glucose metabolism. Diabetes is characterized by hyperglycemia, or high blood sugar, and premature vascular disease. Symptoms of diabetes-related hyperglycemia include polydipsia, polyuria, weight loss, polyphagia, and blurred vision. Acute and life-threatening complications of uncontrolled diabetes include hyperglycemia with diabetic ketoacidosis or nonketotic hyperosmolar syndrome. Long-term complications of uncontrolled diabetes include macrovascular and microvascular complications that lead to loss of vision, renal failure, neuropathy, and cardiovascular disease. There are three types of diabetes: type 1, type 2, and gestational. Type 1 diabetes occurs in 5 to 10% of cases and is characterized by absolute insulin deficiency and pancreatic beta-cell destruction. Insulin is a hormone produced by pancreatic beta cells that stimulate sugar uptake in the blood by cells. Insulin therapy is required to treat type 1 diabetes. Type 2 diabetes occurs in 90 to 95% of cases and is characterized by insulin resistance and impaired beta-cell function. In some individuals with type 2 diabetes, blood glucose control can be managed with lifestyle changes like diet, weight reduction, and exercise, and/or oral glucose-lowering medications. However, some individuals may need insulin therapy. Gestational diabetes occurs in 9% of pregnant women during the second or third trimester of pregnancy. Glucose tolerance usually returns to normal after delivery, but this increases the risk for type 2 diabetes later in life.

Proteins

Protein-energy malnutrition is a problem for children in developing and developed countries around the world and contributes to acute and chronic childhood illness. In cases of extreme protein-energy malnutrition, marasmus and kwashiorkor are the two main clinical syndromes seen. Marasmus is more common and is characterized by muscle wasting and depletion of subcutaneous fat stores without edema as a result of deprivation of calories and nutrients. In addition, there is poor growth, little disease resistance, slowed metabolism, and impaired brain development. This usually occurs in children under the age of 5 due to their increased caloric requirements. Kwashiorkor is characterized by normal weight with edema, poor growth, low blood albumin, little disease resistance, and apathy resulting from a diet with an adequate caloric intake but inadequate protein. This commonly occurs in older infants or toddlers who are displaced from breastfeeding due to the birth of a younger sibling and have to wean rapidly but are unable to increase protein intake enough.

Lipids

Lipids in abnormal concentrations attract clinical attention. Abnormal lipid levels can occur due to abnormalities in the synthesis, degradation, and transport of lipoprotein particles. Hyperlipidemia is defined as elevated levels of lipids or lipoproteins in the blood. Hyperlipidemia is very clinically relevant due to its association with an increased risk of atherosclerotic cardiovascular disease. Other clinical manifestations of hyperlipidemia include ischemic vascular disease, acute pancreatitis, and visible accumulations of lipid deposits. Increased plasma lipid levels can be related to genetic disorders, dietary factors, certain drugs, and as a secondary symptom of certain diseases.

Vitamin B1 (Thiamin)

Thiamin deficiency is historically known as a disease called beriberi. Currently, in developed nations, thiamin deficiency mainly occurs with chronic alcoholism and is called Wernicke-Korsakoff syndrome. Symptoms of thiamin deficiency are nonspecific and include anorexia, weight loss, apathy, short-term memory issues, confusion, irritability, muscular weakness, and enlargement of the heart.

Vitamin B2 (Riboflavin)

The symptoms of riboflavin deficiency include sore throat, angular stomatitis, glossitis, dermatitis, and weakness. It is rare but can occur with diseases such as cancer, diabetes, cardiac disease, and alcoholism.

Vitamin B3 (Niacin)

The classic clinical manifestation of severe niacin deficiency is a disease called pellagra. Pellagra is characterized by a symmetrical, pigmented rash that develops in sunlight exposed areas, GI symptoms such as vomiting, constipation, diarrhea, a bright red tongue, and neurological problems such as depression and fatigue, apathy, headache, and loss of memory. Pellagra was common in the United States and Europe in areas where corn was a dietary staple in the early twentieth century. Pellagra has disappeared from developed countries except for cases of chronic alcoholism. It persists in parts of India, China, and Africa.

Vitamin B5 (Pantothenic Acid)

Pantothenic acid deficiencies are extremely rare but have been shown in individuals fed diets devoid of pantothenic acid. Symptoms of deficiency include irritability, fatigue, apathy, sleep disturbances, GI complaints, numbness, paresthesias, muscle cramps, and hypoglycemia with increased insulin sensitivity.

Vitamin B6 (Pyridoxine) 

Vitamin B6 deficiency is rare in healthy individuals. Symptoms of vitamin B6 deficiency include seborrheic dermatitis, microcytic anemia, convulsions, and confusion. Microcytic anemia occurs due to PLP’s role as a cofactor in the first step in heme biosynthesis.

Vitamin B7 (Biotin)

Biotin deficiency is rare but can occur in specific scenarios. Biotin deficiency can occur in people who ingest raw eggs due to the protein avidin, which inhibits biotin absorption. It can also occur in people with genetic defects in the enzyme biotinidase. Symptoms of biotin deficiency include thinning of hair, loss of hair color, dermatitis, depression, lethargy, and hallucinations.

Vitamin B9 (Folate) 

Folate deficiency results in impaired synthesis of DNA and RNA, which can manifest clinically megaloblastic anemia and developmental disorders in utero. Megaloblastic or macrocytic anemia occurs when red blood cell development is halted in the early erythroblast stage due to a lack of folate, allowing DNA synthesis to continue and erythroblasts to divide and mature. Early erythroblasts are large and do not contain much hemoglobin. Inadequate maternal folate status during pregnancy can result in neural tube defects such as spina bifida and anencephaly. Neural tube defect risk reduction has been achieved with daily supplementation of 400 mcg of folate in women of childbearing age. In addition, there is some evidence that might suggest folate reduces the risk of cardiovascular disease, certain cancers, and psychiatric disorders.

Vitamin B12 (Cobalamin) 

The major cause of clinical effects of vitamin B12 deficiency is pernicious anemia, which is caused by a lack of functional intrinsic factor in the stomach due to autoimmune destruction of gastric parietal cells. Malabsorption of food-bound vitamin B12 can also occur due to non-autoimmune atrophic gastritis, which causes loss of stomach acid and mainly affects the elderly. The hematological effects of vitamin B12 deficiency are clinically indistinguishable from those of folate deficiency causing macrocytic, or megaloblastic, anemia. Vitamin B12 deficiency can also result in impaired neurological function and increased neural tube defect risk.

Vitamin C (Ascorbic Acid)

Vitamin C deficiency is clinically and historically known as scurvy. Vitamin C deficiency is currently rare and only seen in malnourished populations with chronic conditions, poor diet, malabsorption, or substance dependency. Symptoms of vitamin C deficiency include gingival inflammation, fatigue, petechiae, bruising, and joint pain.

Vitamin A (Retinol)

Vitamin A deficiency affects 20-40 million children worldwide in regions with low-fat, plant-based diets and protein-calorie malnutrition. Vitamin A deficiency more commonly causes death than blindness in children in high-risk regions due to its role in the immune system. Vitamin A deficiency can also cause an increased risk of respiratory and diarrheal infections, decreased growth rate, slow bone development, and decreased survival from a serious illness.

Vitamin D (Cholecalciferol)

Vitamin D deficiency can lead to rickets and osteomalacia due to its critical role in bone and mineral metabolism. Rickets occurs in infants and children as a result of the failure of the bone to mineralize. The symptoms of rickets include growth retardation and bowing of the long bones of the legs. Osteomalacia occurs in adults; as a result, inadequate amounts of calcium and phosphate causing demineralization of the bone. Vitamin D may have extraskeletal effects and play a role in cardiovascular diseases, autoimmune diseases, neurological diseases, cancer, asthma, and pregnancy complications.

Vitamin E (Tocopherol)

Vitamin E deficiency is very rare but can occur in certain individuals. Symptoms of vitamin E deficiency include oxidative damage of tissues, membrane damage of cells, neurological abnormalities such as peripheral neuropathy, muscular, functional abnormalities like ataxia, and hemolytic anemia. Vitamin E deficiency most commonly occurs in premature babies of very low birthweight, people with fat-malabsorption disorders like Crohn’s disease and cystic fibrosis, and those who have a rare neurodegenerative disease called ataxia with vitamin E deficiency (AVED) that is caused by mutations in the gene for αβ-tocopherol transfer protein.

Vitamin K (Phylloquinone; Menaquinone)

Vitamin K deficiency is uncommon in healthy adults but may be seen in those with gastrointestinal malabsorptive disorders. However, newborns are at high risk for vitamin K deficiency. Newborns are at risk given milk is low in vitamin K, their stores are low since vitamin K does not pass the placenta, and their intestines are not yet populated with vitamin K synthesizing bacteria. Infants born in the United States and Canada routinely receive 0.5 to 1 mg of intramuscular phylloquinone within 6 hours of birth to prevent vitamin K deficiency bleeding, or VKDB. VKDB can affect infants up to 3 to 4 months of age and cause intracranial hemorrhage, central nervous system damage, and liver damage.

Calcium

Hypocalcemia, or calcium deficiency, can result from inadequate calcium intake, poor calcium absorption, or excessive calcium losses. Poor calcium absorption can occur due to inadequate vitamin D status. Excessive calcium losses can occur due to a lack of PTH. Symptoms of hypocalcemia can include muscle spasms, cramps, paresthesia, tetany, and seizures. Long-term hypocalcemia can impact bone health and result in reduced bone mass and osteoporosis. Hypercalcemia can occur due to increased bone resorption, increased intestinal absorption, and decreased renal excretion of calcium. Syndromes that increase PTH production can result in excessive calcium reabsorption and calcitriol production in the kidney. Excess PTH and calcitriol production can result in increased bone resorption. Excess calcitriol also can increase intestinal absorption. Symptoms of hypercalcemia include fatigue, confusion, polydipsia, frequent urination, upset stomach, bone pain, muscle weakness, and cardiac arrhythmia.

Magnesium

Magnesium deficiency, or hypomagnesemia, can occur due to chronic inadequate magnesium intake, chronic diarrhea, magnesium malabsorption, alcoholism, and medications like diuretics, antacids, proton pump inhibitors, and aminoglycoside antibiotics. Symptoms of hypomagnesemia are nonspecific and include muscle weakness, cramps, spasms, and tremors. Magnesium toxicity, or hypermagnesemia, can occur with supplemental magnesium, especially in intestinal or renal disease. Symptoms of hypermagnesemia include diarrhea, nausea, vomiting, headaches, lethargy, and flushing. At very high serum concentrations of magnesium, cardiac and electrocardiogram changes can occur, as well as coma, respiratory depression, and cardiac arrest.

Phosphorus

Phosphorus deficiency, or hypophosphatemia, is relatively rare in healthy individuals. However, hypophosphatemia can occur due to conditions that cause a shift of phosphorous from extracellular fluid to intracellular fluid, decreased intestinal absorption of phosphorus, or increased renal excretion of phosphorus. Hypophosphatemia may also occur in individuals with rare genetic disorders that decrease renal reabsorption and increase phosphorus excretion. Hypophosphatemia can appear asymptomatic until serum levels reach <1.5 mg/dL, where symptoms of anorexia, confusion, seizures, and paralysis can present. Respiratory depression can occur at serum levels <1 mg/dL. Treatment of hypophosphatemia includes oral or intravenous supplementation, depending on the severity of deficiency. Phosphorus toxicity, or hyperphosphatemia, can occur in those with chronic kidney disease due to decreased phosphorus excretion. Hyperphosphatemia is associated with increased death from cardiovascular disease due to vascular calcification in individuals with and without chronic kidney disease. Hyperphosphatemia is treated first by dietary restriction of phosphate, protein restriction, and dialysis if the latter fails. Hyperphosphatemia can also be treated with oral phosphate binders that block dietary phosphorus absorption.

Sodium

Given the pervasiveness of sodium in various foods, sodium deficiency is highly unlikely in healthy individuals. Sodium deficiency, or hyponatremia, can only occur in pathological conditions such as adrenal insufficiency, kidney disease that results in excessive sodium losses, excessive burns, diabetic ketoacidosis, and additional conditions that cause excessive sodium losses such as vomiting, diarrhea, prolonged sweating, and excessive diuretic use. Symptoms of hyponatremia include hypovalemia, lethargy, confusion, and weakness. Sodium toxicity, or hypernatremia, can occur with dehydration, hyperaldosteronemia, and renal failure. Symptoms of hypernatremia include hypervolemia, hypertension, convulsions, or coma. Even under normal conditions, continuous excessive intake of sodium can result in hypertension in certain individuals.

Potassium

Potassium is considered to be a shortfall nutrient in the American diet according to the 2010 Dietary Guidelines for American’s Advisory Committee because most Americans are unable to consume the AI of 4,700 mg/day. There is moderate evidence of an association between blood pressure reduction and potassium intake in adults, which influences cardiovascular disease risk. Hypokalemia usually occurs due to inadequate potassium intake and/or excessive potassium losses. Hypokalemia can clinically manifest in symptoms such as muscle weakness, smooth muscle dysfunction, cardiac complications, and glucose intolerance. Hyperkalemia usually occurs due to impaired renal excretion. Hyperkalemia will manifest in excitatory tissues and present symptoms such as neuromuscular symptoms such as paresthesias and fasciculations, cardiac arrest, and impaired renal function.

Chloride

Hypochloremia, or chloride deficiency, is related to clinical situations that cause excessive chloride losses due to gastrointestinal or renal conditions such as vomiting and renal failure. When serum chloride levels fall, bicarbonate reabsorption increases proportionately, resulting in metabolic alkalosis. Symptoms of hypochloremia are concurrent with those of metabolic alkalosis and include confusion, apathy, cardiac arrhythmias, and neuromuscular irritability. Hyperchloremia, or chloride toxicity, is related to clinical situations that cause excessive gastrointestinal or renal bicarbonate losses, such as severe diarrhea and medications that promote bicarbonate excretion. When serum bicarbonate levels fall, chloride reabsorption increases proportionately, resulting in metabolic acidosis.

Iron

The World Health Organization (WHO) indicates iron deficiency to be the most common form of malnutrition globally, affecting 25% of the global population. Iron deficiency is highly prevalent in both developing and developed countries. Iron deficiency is most commonly caused by inadequate dietary iron intake, inadequate iron utilization due to diseases, impaired iron absorption, or excess iron loss. Iron deficiency can often be avoided and reversed with iron supplementation and/or reducing iron losses. Untreated iron deficiency can result in microcytic anemia, poor cognitive performance, impaired immune function, impaired growth in children, poor pregnancy outcomes, and reduced endurance capacity. On the other hand, iron overload can be caused by a disease called hereditary hemochromatosis due to a C282Y mutation in the HFE gene. Hereditary hemochromatosis can be treated with iron removal therapy.

Zinc

Zinc deficiency can present clinically with symptoms such as dermatitis, alopecia, decreased appetite, frequent diarrhea, frequent upper respiratory infection, stunted growth in children, and hypogonadism. Zinc deficiency can occur due to diarrheal illness, kidney failure, and genetic diseases acrodermatitis enteropathica (AE). AE is a fatal disease of zinc malabsorption due to a mutation in the ZIP4 gene, which encodes the major intestinal zinc uptake protein. AE is treated with lifelong zinc supplementation of 100 mg/kg per day. Zinc toxicity is rare due to the tight regulation of zinc concentrations in the body. However, long-term zinc supplementation above the tolerable upper intake level of 40 mg/day can decrease copper absorption and cause copper deficiency. This occurs because zinc induced the formation of the intestinal cell protein metallothionein, which binds to metals and prevents their absorption by trapping them in the intestinal cell. Metallothionein has a stronger affinity for copper than zinc, thus trapping copper in the intestinal cell and halting absorption.

Copper

Copper deficiency generally manifests in systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system. Copper deficiency causes symptoms such as fatigue and weakness. Copper deficiency can occur due to excessive zinc supplementation and the genetic disorder of copper malabsorption called Menkes disease. Menkes disease is caused by a mutation in the ATP7A gene, which causes copper to accumulate in the enterocyte, making it unable to reach the blood or any other organ system. Another genetic disease of copper metabolism is Wilson disease, which is a genetic disease of accumulation of copper mainly in the liver and the brain due to a mutation in the ATP7B gene responsible for the ATP7B exporter.

Iodine

Iodine deficiency will cause a compensatory response of the thyroid gland. When iodine intake falls below approximately 100 mcg/day, the pituitary increases secretion of TSH, which increases plasma iodine clearance by the thyroid. Thus, plasma iodine levels decrease, and thyroid hormone synthesis decreases, resulting in hypothyroidism. The increase in TSH also increases the thyroid cell number and cell size resulting in an enlarged thyroid gland or goiter. The goiter can be treated with iodine supplementation, gradually reducing the size or a thyroidectomy. If left untreated, the goiter may cause tracheal and esophageal pressure. Thyroid deficiency during pregnancy can lead to neurological cretinism in the offspring.

Selenium

Selenium deficiency has been known to appear in humans after severe and prolonged cases of selenium deprivation. Selenium deficiency is known as Keshan disease and occurs in areas where selenium content in the soil is low, like China. Symptoms of Keshan disease include cardiomyopathy, peripheral myopathy, decreased muscle tone and function, hair thinning, opacification of nails, and anemia.

References

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Nutrition – Types, Mechanism, Functions, Health Benefits

Nutrition are chemical substances required by the body to sustain basic functions and are optimally obtained by eating a balanced diet. There are six major classes of nutrients essential for human health: carbohydrates, lipids, proteins, vitamins, minerals, and water. Carbohydrates, lipids, and proteins are considered macronutrients and serve as a source of energy. Water is required in large amounts but does not yield energy. Vitamins and minerals are considered micronutrients and play essential roles in metabolism. Vitamins are organic micronutrients classified as either water-soluble or fat-soluble. The essential water-soluble vitamins include vitamins B1, B2, B3, B5, B6, B7, B9, B12, and C. The essential fat-soluble vitamins include vitamins A, E, D, and K. Minerals are inorganic micronutrients. Minerals can classify as macrominerals or microminerals. Macrominerals are required in amounts greater than 100 mg per day and include calcium, phosphorous, magnesium, sodium, potassium, and chloride. Sodium, potassium, and chloride are also electrolytes. Microminerals are those nutrients required in amounts less than 100 mg per day and include iron, copper, zinc, selenium, and iodine. This article will review the following biochemical aspects of the essential nutrients: fundamentals, cellular, molecular, function, testing, and clinical significance.

Digestive Systems and Nutrition

Animals use the organs of their digestive systems to extract important nutrients from food they consume, which can later be absorbed.

Key Points

Animals obtain lipids, proteins, carbohydrates, essential vitamins, and minerals from the food they consume.

The digestive system is composed of a series of organs, each with a specific, yet related function, that work to extract nutrients from food.

Organs of the digestive system include the mouth, esophagus, stomach, small intestine, and the large intestine.

Accessory organs, such as the liver and pancreas, secrete digestive juices into the gastrointestinal tract to assist with food breakdown.

Key Terms

  • digestion: the process, in the gastrointestinal tract, by which food is converted into substances that can be utilized by the body
  • macromolecule: a very large molecule, especially used in reference to large biological polymers (e.g. nucleic acids and proteins)
  • alimentary canal: the organs of a human or an animal through which food passes; the digestive tract

All living organisms need nutrients to survive. While plants can obtain the molecules required for cellular function through the process of photosynthesis, most animals obtain their nutrients by the consumption of other organisms. At the cellular level, the biological molecules necessary for animal function are amino acids, lipid molecules, nucleotides, and simple sugars. The food consumed consists of protein, fat, and complex carbohydrates, but the requirements of each are different for each animal.

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Balanced human diet: For humans, fruits and vegetables are important in maintaining a balanced diet. Both of these are an important source of vitamins and minerals, as well as carbohydrates, which are broken down through digestion for energy.

Animals must convert these macromolecules into the simple molecules required for maintaining cellular functions, such as assembling new molecules, cells, and tissues. The conversion of the food consumed to the nutrients required is a multi-step process involving digestion and absorption. During digestion, food particles are broken down to smaller components which will later be absorbed by the body.

Digestive System

The digestive system is one of the largest organ systems in the human body. It is responsible for processing ingested food and liquids. The cells of the human body all require a wide array of chemicals to support their metabolic activities, from organic nutrients used as fuel to the water that sustains life at the cellular level. The digestive system not only effectively chemically reduces the compounds in food into their fundamental building blocks, but also acts to retain water and excrete undigested materials. The functions of the digestive system can be summarized as follows: ingestion (eat food), digestion (breakdown of food), absorption (extraction of nutrients from the food), and defecation (removal of waste products).

The digestive system consists of a group of organs that form a closed tube-like structure called the gastrointestinal tract (GI tract) or the alimentary canal. For convenience, the GI tract is divided into upper GI tract and lower GI tract. The organs that make up the GI tract include the mouth, the esophagus, the stomach, the small intestine, and the large intestine. There are also several accessory organs that secrete various enzymes into the GI tract. These include the salivary glands, the liver, and the pancreas.

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Generalized animal digestive system: This diagram shows a generalized animal digestive system, detailing the different organs and their functions.

Challenges to Human Nutrition

One of the challenges in human nutrition is maintaining a balance between food intake, storage, and energy expenditure. Imbalances can have serious health consequences. For example, eating too much food while not expending much energy leads to obesity, which in turn will increase the risk of developing illnesses such as type-2 diabetes and cardiovascular disease. The recent rise in obesity and related diseases means that understanding the role of diet and nutrition in maintaining good health is more important than ever.

Carbohydrates: Sources, Uses in the Body, and Dietary Requirements

Carbohydrates, which break down to glucose, are a major source of energy for humans but are not essential nutrients.

Key Points

Carbohydrates include such items as fruits, grains, beans, and potatoes, along with sugars and sugared foods.

While fat is a better source of energy, the brain cannot burn fat and instead requires glucose.

Polysaccharides (complex carbs) are difficult for humans to break down but are useful as fiber to enhance the digestive process.

Government agencies recommend a dietary intake of 45–65% or 55–75% of carbohydrates to meet daily energy needs.

Of daily carbohydrate intake, only 10% should be simple carbs or sugars.

Key Terms

  • glucose: A simple monosaccharide (sugar) with a molecular formula of C6H12O6; it is a principle source of energy for cellular metabolism.
  • carbohydrate: A sugar, starch, or cellulose that is a food source of energy for an animal or plant; a saccharide.
  • saccharide: The unit structure of carbohydrates, of general formula CnH2nOn. Either the simple sugars or polymers such as starch and cellulose. The saccharides exist in either a ring or short chain conformation, and typically contain five or six carbon atoms.

EXAMPLES

Daily food intake that includes 8–10 fruit and vegetable servings (not starchy potatoes or grains, such as corn and rice) will not only provide plenty of energy but will also keep glucose levels in balance.

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Carbohydrates are a class of macromolecule: Grain products are rich sources of carbohydrates.

Foods high in carbohydrates include fruits, sweets, soft drinks, bread, pasta, beans, potatoes, bran, rice, and cereals. Carbohydrates are a common source of energy in living organisms, however, carbohydrate is not an essential nutrient in humans.

Carbohydrates are not necessary building blocks of other molecules, and the body can obtain all its energy from protein and fats. The brain and neurons generally cannot burn fat for energy but use solely glucose or ketones. Humans can synthesize some glucose (in a set of processes known as “gluconeogenesis”) from specific amino acids or from the glycerol backbone in triglycerides and, in some cases, from fatty acids. Carbohydrates and protein contain 4 kilocalories per gram, while fats contain 9 kilocalories per gram. In the case of protein, this is somewhat misleading as only some amino acids are able to undergo conversion into useful energy forms.

Organisms typically cannot metabolize all types of carbohydrates to yield energy. Glucose is a nearly universal and accessible source of calories. Many organisms also have the ability to metabolize other monosaccharides and disaccharides, though glucose is preferred. Polysaccharides are also common sources of energy. Even though these complex carbohydrates are not very digestible, they may comprise important dietary elements for humans. Called “dietary fiber,” these carbohydrates enhance digestion, among other benefits.

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Glucose Molecule: Image of a glucose molecule containing a fixed ratio of carbon, hydrogen and oxygen.

Based on the effects on risk of heart disease and obesity, the Institute of Medicine (IOM) recommends that American and Canadian adults get between 45–65% of dietary energy from carbohydrates. The Food and Agriculture Organization (FAO) and World Health Organization (WHO) jointly recommend that national dietary guidelines set a goal of 55–75% of total energy from carbohydrates, but only 10% directly from sugars (their term for simple carbohydrates).

Lipids: Sources, Uses in the Body, and Dietary Requirements

Fats store energy, facilitate absorption of fat-soluble vitamins, aid brain growth and development, and protect against many diseases.

Key Points

Vitamins A, D, E, and K should be taken with some dietary fat in order to facilitate their absorption and activity.

Humans cannot synthesize omega-6 and omega-3 fatty acids, so these fats must be obtained from the diet.

Omega-6 fatty acids are found in many foods, while omega-3 fatty acids are found in walnuts and are especially abundant in fatty fish.

Omega-3 fatty acids have many positive health benefits including reduced rates of cancer, cardiovascular disease, mental illness, and dementia.

Studies of dietary fat intake have found no link between the percentage of calories obtained from fats and the risk of cancer, heart disease, or obesity.

Trans fats, such as those present in partially hydrogenated vegetable oils, are a risk factor for cardiovascular disease.

Key Terms

  • phospholipids: Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers.
  • trans fats: Trans fats are unsaturated fats generated by physical agents such as heat or pressure that can lead to a variety of health problems.
  • fatty acid: Fatty acids can be saturated or unsaturated and are usually derived from triglycerides or phospholipids.

EXAMPLES

College students require optimal brain function, which is supported by fatty fish and walnuts.

Most of the fats found in food are triglycerides, cholesterol, and phospholipids. Some dietary fat is necessary for the absorption of fat-soluble vitamins (A, D, E, and K) and carotenoids. Humans and other mammals require fatty acids such as linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid), because they cannot be synthesized from simple precursors in the diet.

Both omega-6 and omega-3 are 18-carbon polyunsaturated fatty acids that differ in the number and position of their double bonds. Most vegetable oils (safflower, sunflower, and corn oils) are rich in linoleic acid. Alpha-linolenic acid is found in the green leaves of plants, selected seeds, nuts, and legumes, and particularly in flax, rapeseed, walnut, and soy. Fish oils are especially rich in the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Numerous studies have shown that the consumption of omega-3 fatty acids has positive benefits in terms of infant development, cancer, cardiovascular disease, and mental illnesses such as depression, attention-deficit hyperactivity disorder, and dementia. In contrast, the consumption of trans fats, such as those present in partially hydrogenated vegetable oils, are now known to be a risk factor for cardiovascular disease.

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Omega-3 Fatty Acid: Docosahexaenoic acid (DHA) is an omega-3 fatty acid. It is essential for the proper functioning of the brain in both adults and infants. DHA concentrations in breast milk ranged from 0.07-1.0% of total fatty acids and are influenced by the amount of fatty fish in the mother’s diet. In the U.S., infant formula has been supplemented with DHA since 2001. Research suggests that DHA contributes to numerous nervous system functions such as visual acuity, neurogenesis, and synaptogenesis and that it lowers the risk for cardiovascular disease. It is highly concentrated in the brain and eye.

Several studies have suggested that total dietary fat intake is linked to obesity and diabetes. However, influential studies like the Women’s Health Initiative Dietary Modification Trial (an eight-year study of 49,000 women), as well as the Nurses’ Health Study and the Health Professionals Follow-up Study, have revealed no such link between the percentage of calories from fat and risk of cancer, heart disease, or weight gain. The Nutrition Source, a website maintained by the Department of Nutrition at the Harvard School of Public Health, summarizes the current evidence on the impact of dietary fat as follows: “Detailed research—much of it done at Harvard—shows that the total amount of fat in the diet isn’t really linked with weight or disease.”

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Salmon: Salmon is an excellent source of omega-3 fatty acids.

Proteins: Sources, Uses in the Body, and Dietary Requirements

Proteins are composed of 20 different amino acids, about half of which are essential, meaning they must be obtained from the diet.

Key Points

Protein-based foods (plant and animal) provide amino acids; however, the best source of essential amino acids is animal.

If the diet does not provide adequate protein, the body will obtain what it needs from itself, especially from its own muscles.

While adequate protein is required for building skeletal muscle and other tissues, there is ongoing debate regarding the use and necessity of high-protein diets in anaerobic exercise, in particular weight training and bodybuilding.

This use of protein as a fuel is particularly important under starvation conditions as it allows the body’s own proteins to be used to support life.

Key Terms

  • amino acid: Any of the twenty naturally occurring α-amino acids (having the amino, and carboxylic acid groups on the same carbon atom), and a variety of side chains, that combine, via peptide bonds, to form proteins.
  • denaturation: Denaturation is a process in which proteins or nucleic acids lose their tertiary and secondary structure which is present in their native state, by application of some external stress or compound such as a strong acid or base, a concentrated inorganic salt, an organic solvent (e.g., alcohol or chloroform), or heat.
  • protein: Any of numerous large, complex naturally-produced molecules composed of one or more long chains of amino acids, in which the amino acid groups are held together by peptide bonds.

Most microorganisms and plants can biosynthesize all 20 standard amino acids, while animals (including humans) must obtain some of the amino acids from the diet. The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids. Key enzymes that synthesize certain amino acids are not present in animals. One example is aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate.

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Amino Acid: Ball-and-stick model of the cystine molecule, an amino acid formed from two cysteine molecules.

In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are then broken down into amino acids through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases. Some ingested amino acids are used for protein biosynthesis, while others are converted to glucose through gluconeogenesis, or fed into the citric acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the body’s own proteins to be used to support life, particularly those found in muscle. Amino acids are also an important dietary source of nitrogen.

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Protein: Muscle meat, such as steak, is an excellent source of the essential amino acids the body needs to create all necessary proteins.

A high-protein diet is often recommended by bodybuilders and nutritionists to help efforts to build muscle and lose fat. It should not be confused with low-carb diets, such as the Atkins Diet, which are not calorie-controlled and which often contain large amounts of fat. While adequate protein is required for building skeletal muscle and other tissues, there is ongoing debate regarding the use and necessity of high-protein diets in anaerobic exercise in particular weight training and bodybuilding. Extreme protein intake (in excess of 200g per day), coupled with an inadequate intake of other calorie sources (fat or carbohydrates), can cause a form of metabolic disturbance and death commonly known as rabbit starvation.

Relatively little evidence has been gathered regarding the effect of long-term high intake of protein on the development of chronic diseases. Increased load on the kidney is a result of an increase in the reabsorption of NaCl. This causes a decrease in the sensitivity of tubuloglomerular feedback, which, in turn, results in an increased glomerular filtration rate. This increases pressure in glomerular capillaries. When added to any additional renal disease, this may cause permanent glomerular damage.

Food Requirements and Essential Nutrients

Essential nutrients are those that cannot be created by an animal’s metabolism and need to be obtained from the diet.

Key Points

The animal diet needs to be well-balanced in order to ensure that all necessary vitamins and minerals are being obtained.

Vitamins are important for maintaining bodily health, making bones strong, and seeing in the dark.

Water-soluble vitamins are not stored by the body and need to be consumed more regularly than fat-soluble vitamins, which build up within body tissues.

Essential fatty acids need to be consumed through the diet and are important building blocks of cell membranes.

Nine of the 20 amino acids cannot be synthesized by the body and need to be obtained from the diet.

Key Terms

  • nutrient: a source of nourishment, such as food, that can be metabolized by an organism to give energy and build tissue
  • catabolism: destructive metabolism, usually including the release of energy and breakdown of materials
  • vitamin: any of a specific group of organic compounds essential in small quantities for healthy human growth, metabolism, development, and body function

Food Requirements

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A balanced diet: For humans, a balanced diet includes fruits, vegetables, grains, and protein. Each of these food sources provides different nutrients the body cannot make for itself. These include vitamins, omega 3 fatty acids, and some amino acids.

What are the fundamental requirements of the animal diet? The animal diet should be well balanced and provide nutrients required for bodily function along with the minerals and vitamins required for maintaining structure and regulation necessary for good health and reproductive capability.

Organic Precursors

The organic molecules required for building cellular material and tissues must come from food. Carbohydrates or sugars are the primary sources of organic carbons in the animal body. During digestion, digestible carbohydrates are ultimately broken down into glucose and used to provide energy through metabolic pathways. The excess sugars in the body are converted into glycogen and stored in the liver and muscles for later use. Glycogen stores are used to fuel prolonged exertions, such as long-distance running, and to provide energy during food shortages. Excess digestible carbohydrates are stored by mammals in order to survive famine and aid in mobility.

Another important requirement is that of nitrogen. Protein catabolism provides a source of organic nitrogen. Amino acids are the building blocks of proteins and protein breakdown provides amino acids that are used for cellular function. The carbon and nitrogen derived from these become the building block for nucleotides, nucleic acids, proteins, cells, and tissues. Excess nitrogen must be excreted, as it is toxic. Fats add flavor to food and promote a sense of satiety or fullness. Fatty foods are also significant sources of energy because one gram of fat contains nine calories. Fats are required in the diet to aid the absorption of fat-soluble vitamins and the production of fat-soluble hormones.

Essential Nutrients

While the animal body can synthesize many of the molecules required for function from the organic precursors, there are some nutrients that need to be consumed from food. These nutrients are termed essential nutrients: they must be eaten as the body cannot produce them.

Vitamins and minerals are substances found in the food we eat. Your body needs them to be able to work properly and for growth and development. Each vitamin has its own special role to play. For example, vitamin D (added to whole milk or naturally occurring in sardines), helps make bones strong, while vitamin A (found in carrots) helps with night vision. Vitamins fall into two categories: fat-soluble and water-soluble. The fat-soluble vitamins dissolve in fat and can be stored in your body, whereas the water-soluble vitamins need to dissolve in water before your body can absorb them; therefore, the body cannot store them.

Fat-soluble vitamins are found primarily in foods that contain fat and oil, such as animal fats, vegetable oils, dairy foods, liver, and fatty fish. Your body needs these vitamins every day to enable it to work properly. However, you do not need to eat foods containing these every day. If your body does not need these vitamins immediately, they will be stored in the liver and fat tissues for future use. This means that stores can build up; if you have more than you need, fat-soluble vitamins can become harmful. Some fat-soluble vitamins include vitamin A, vitamin K, vitamin D, and vitamin E. Unlike the other fat-soluble vitamins, vitamin D is difficult to obtain in adequate quantities in a normal diet; therefore, supplementation may be necessary.

Water-soluble vitamins are not stored in the body; therefore, you need to have them more frequently. If you have more then you need, the body rids itself of the extra vitamins during urination. Because the body does not store these vitamins, they are generally not harmful. Water-soluble vitamins are found in foods that include fruits, vegetables, and grains. Unlike fat-soluble vitamins, they can be destroyed by heat. This means that sometimes these vitamins can often be lost during cooking. This is why it is better to steam or grill these foods rather then boil them. Some water-soluble vitamins include vitamin B6, vitamin B12, vitamin C, biotin, folic acid, niacin, and riboflavin.

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Sea buckthorn seed oil: Sea buckthorn seed oil contains many vital nutrients.

The omega-3 alpha-linolenic acid and the omega-6 linoleic acid are essential fatty acids needed to synthesize some membrane phospholipids. Many people take supplements to ensure they are obtaining all the essential fatty acids they need. Sea buckthorn contains many of these fatty acids and is also high in vitamins. Sea buckthorn can be used to treat acne and promote weight loss and wound healing.

Minerals are inorganic essential nutrients that must also be obtained from food. Among their many functions, minerals help in cell structure and regulation; they are also considered co-factors. In addition to vitamins and minerals, certain amino acids must also be procured from food and cannot be synthesized by the body. These amino acids are the “essential” amino acids. The human body can synthesize only 11 of the 20 required amino acids. The rest must be obtained from food.

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Amino Acids: There are 20 known amino acids. Animals can make only 11, so the others must be obtained through the diet. Meats are the best source of amino acids, although some amino acids can also be obtained from vegetables and grains.

Fundamentals Nutrition

Carbohydrates

Carbohydrates are essential macronutrients that are the primary source of energy for humans; 1 gram of carbohydrate contains 4 kcal of energy. Carbohydrates also play roles in gut health and immune function. Carbohydrates are present in plant-based foods like grains, fruits, vegetables, and milk. Carbohydrates are ingested in the form of simple carbohydrates, like monosaccharides and disaccharides, or complex carbohydrates, like oligosaccharides and polysaccharides. Monosaccharides are the basic building blocks of all carbohydrates and include glucose, fructose, and galactose. Glucose is the primary form to which carbohydrates become metabolized in humans. Disaccharides contain two sugar units and include lactose, sucrose, and maltose. Lactose is a carbohydrate found in milk, and sucrose is basic table sugar. Oligosaccharides consist of 3 to 10 sugar units and include raffinose and stachyose, which are in legumes. Polysaccharides include greater than ten sugar units and consist of starches, glycogen, and fibers, like pectin and cellulose. Starches like amylose are in grains, starchy vegetables, and legumes and consist of glucose monomers. Glycogen is the storage form of glucose in animals and is present in the liver and muscle, but there is little to none in the diet. Fibers are plant polysaccharides like pectin and cellulose found in whole grains, fruits, vegetables, and legumes but are not digestible by humans. However, they play a major role in gut health and function and can be digested by microbiota in the large intestine. For healthy children and adults, carbohydrates should make up approximately 45 to 65% of energy intake based on the minimum required glucose for brain function. The recommended fiber intake is greater than 38 g for men and 25 g for women, which is the intake that research has observed to lower the risk of coronary artery disease. Some carbohydrates are more nutritious than others. Optimal carbohydrate intake consists of fiber-rich, nutrient-dense whole grains, fruits, vegetables, legumes, and added sugar.

Proteins

Proteins are essential macronutrients that contribute to structural and mechanical function, regulate processes in the cells and body, and provide energy if necessary. Proteins are composed of amino acids and are available in food sources like meats, dairy foods, legumes, vegetables, and grains. 1 gram of protein contains 4 kcal of energy. The recommended protein intake is 0.8 to 1 gram per kilogram of body weight per day. For healthy children ages 1 to 3, ages 4 to 18, and adults, approximately 5 to 20%, 10 to 30%, and 10 to 35% of daily energy intake should come from protein, respectively, based on the adequate amount needed for nitrogen equilibrium.

Lipids

Lipids are essential macronutrients that are the main source of stored energy in the body, contribute to cellular structure and function, regulate temperature, and protect body organs. Lipids are found in fats, oils, meats, dairy, and plants and consumed mostly in the form of triglycerides. One gram of fat contains 9 kcal of energy. For healthy children ages 1 to 3, ages 4 to 18, and adults, approximately 30 to 40%, 25 to 15%, and 20 to 35% of daily energy intake should come from fat, respectively. Approximately 5 to 10% and 0.6 to 1.2% of the daily fat energy intake should consist of n-6 polyunsaturated fatty acids (linoleic acid) and n-3 polyunsaturated fatty acids (α-linolenic acid), respectively.

Vitamin

  • Vitamin B1 (Thiamin) – Thiamin, or vitamin B1, is an essential water-soluble vitamin that acts as a coenzyme in carbohydrate and branched-chain amino acid metabolism. Thiamin is in food sources such as enriched and whole grains, legumes, and pork. The RDA (Recommended Dietary Allowance) of thiamin for adults is 1.1 mg/day for women and 1.2 mg/day for men.
  • Vitamin B2 (Riboflavin) – Riboflavin, or vitamin B2, is an essential water-soluble vitamin that acts as a coenzyme in redox reactions. Riboflavin is present in food sources such as enriched and whole grains, milk and dairy products, leafy vegetables, and beef. The RDA of riboflavin for adults is 1.1 mg/day for women and 1.3 mg/day for men.
  • Vitamin B3 (Niacin) – Niacin, or vitamin B3, is an essential water-soluble vitamin that acts as a coenzyme to dehydrogenase enzymes in the transfer of the hydride ion and an essential component of the electron carriers NAD and NADP. Niacin is present in enriched and whole grains and high protein foods like meat, milk, and eggs. The RDA of niacin for adults is 14 mg/day of NEs (niacin equivalents) for women and 16 mg/day of NEs for men.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid, or vitamin B5, is an essential water-soluble vitamin that acts as a key component of coenzyme A and phosphopantetheine, which are crucial to fatty acid metabolism. Pantothenic acid is widespread in foods. The AI (adequate intake) of pantothenic acid for adults is 5 mg/day.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6, or pyridoxine, is an essential water-soluble vitamin that acts as a coenzyme for amino acid, glycogen, and sphingoid base metabolism. Vitamin B6 is widespread among food groups. The RDA for vitamin B6 for adults is 1.3 mg/day.
  • Vitamin B7 (Biotin) – Biotin, or vitamin B7, is an essential water-soluble vitamin that acts as a coenzyme in carboxylation reactions dependent on bicarbonate. Biotin is found widespread in foods, especially egg yolks, soybeans, and whole grains. The AI of biotin for adults is 30 mcg/day.
  • Vitamin B9 (Folate)  – Folate, or vitamin B9, is an essential water-soluble vitamin that acts as a coenzyme in single-carbon transfers in nucleic acid and amino acid metabolism. Folate is in enriched and fortified grains, green leafy vegetables, and legumes. The RDA of folate for adults is 400 mcg/day of DFEs. The recommendation is that women of childbearing age consume an additional 400 mcg/day of folic acid from supplements or fortified foods to decrease the risk of neural tube defects.
  • Vitamin B12 (Cobalamin) – Vitamin B12, or cobalamin, is an essential water-soluble vitamin that acts as coenzymes for the crucial methyl transfer reaction in converting homocysteine to methionine and the isomerization reaction that occurs in the conversion of L-methylmalonyl-CoA to succinyl-CoA. Vitamin B12 is only present in animal products because it is a product of bacteria synthesis. Many foods are also fortified with synthetic vitamin B12. The RDA of vitamin B12 for adults is 2.4 mcg/day. It is recommended for older adults to meet their RDA with fortified foods or supplements because many are unable to absorb naturally occurring vitamin B12.
  • Vitamin C (Ascorbic Acid) – Vitamin C, or ascorbic acid, is an essential water-soluble vitamin that acts as a reducing agent in enzymatic reactions and nonenzymatically as a soluble antioxidant. Vitamin C is found primarily in fruits and vegetables, except for animal organs like the liver and kidneys. The RDA of vitamin C for adult women and men is 75 mg/day and 90 mg/day, respectively. Smokers require an additional 35 mg/day of vitamin C.
  • Vitamin A (Retinol) – Vitamin A, or retinol, is an essential fat-soluble vitamin that plays numerous roles in vision, cellular differentiation, gene expression, growth, the immune system, bone development, and reproduction. Vitamin A is found primarily in animal products. Fruits and vegetables are a source of provitamin A carotenoids that can be converted to retinol in the body at a lesser amount. The RDA for vitamin A for adults is 900 mcg/day for males and 700 mcg/day for females.
  • Vitamin D (Cholecalciferol) –Vitamin D, or cholecalciferol, is an essential fat-soluble vitamin that plays an essential role in calcium metabolism, cell growth and development, and bone health. Vitamin D can be found in fish oils and in small amounts in plants in its less biologically active form. Interestingly, vitamin D synthesis occurs in the skin with exposure to UV light making dietary sources unnecessary in certain cases. The RDA for vitamin D for adults is 10 to 15 mcg/day.
  • Vitamin E (Tocopherol) – Vitamin E, or tocopherol, is a fat-soluble vitamin that is an antioxidant and may play roles in cell signaling, platelet aggregation, and vasodilation. Vitamin E, in the form of α-tocopherol, is found in certain vegetable oils, including sunflower, safflower, canola, and olive oil, whole grains, nuts, and green leafy vegetables. The RDA for vitamin E for adults is 15 mg/day.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K is an essential fat-soluble vitamin that is the coenzyme in the carboxylation of glutamic acid to form γ-carboxyglutamic acid reaction, which is essential to the proteins involved in blood coagulation. Vitamin K is present in green leafy vegetables, canola oil, and soybean oil. The RDA of vitamin K for adults is 120 mcg/day for men and 90 mcg/day for women.

Mineral

  • Calcium – Calcium is an essential macromineral responsible for numerous structural components such as bones and teeth and physiological mechanisms in the body. Calcium exists in dietary sources such as dairy, cereals, legumes, and vegetables. The RDA for calcium for adults is 1,000 mg/day.
  • Magnesium – Magnesium is an essential macromineral responsible for numerous functions in the body, including signaling pathways, energy storage, and transfer, glucose metabolism, lipid metabolism, neuromuscular function, and bone development. Magnesium is present in food sources such as fruits, vegetables, whole grains, legumes, nuts, dairy, meat, and fortified foods like cereal. The adult RDA for magnesium is 400 mg/day.
  • Phosphorus – Phosphorus is an essential macromineral that is a structural component of bones and teeth, DNA, RNA, and plasma membrane of cells. It is also critical metabolically to produce and store energy. Phosphorus is pervasive throughout food sources, with the greatest contributors being milk, dairy, meat, and poultry. Phosphorus is also an additive in processed foods as a preservative. The RDA for phosphorus for adults is 700 mg/day.
  • Sodium – Sodium is an essential macromineral and electrolyte that plays critical roles in cellular membrane transport, water balance, nerve innervation, and muscle contraction as the most abundant extracellular cation. Sodium is available in dietary sources such as salt, processed foods, meat, milk, eggs, and vegetables. The AI for sodium for adults is 1,500 mg/day; however, the average sodium intake in industrialized nations is 2 or 3 fold by comparison, at 3,000 to 4,500 mg/day.
  • Potassium – Potassium is an essential macromineral and electrolyte that plays critical roles in muscle contraction, nerve innervation, blood pH balance, and water balance as the most abundant intracellular cation. Potassium is obtainable in dietary sources such as fruits and vegetables. The AI for potassium is for adults is 4,700 mg/day.
  • Chloride – Chloride is an essential macromineral and electrolyte that plays critical roles in digestion, muscular activity, water balance, and acid-base balance as the most abundant extracellular anion in the body. Dietary chloride is almost always present in dietary sources associated with sodium in the form of NaCl or table salt. Chloride is in processed foods, meat, milk, eggs, and vegetables. The AI for chloride for adults is 1,500 mg/day.
  • Iron – Iron is an essential trace mineral that has a critical role in oxygen transport and energy metabolism. Dietary iron is from sources such as meat, fortified grains, and green leafy vegetables. Animal foods contain a more bioavailable form of iron called heme iron, while plant foods and fortified grains contain a less bioavailable form called non-heme iron. The RDA for iron for adults is 8 to 18 mg/day.
  • Zinc – Zinc is an essential trace mineral that functions structurally in proteins and catalytically as a component of over 300 different enzymes. Zinc appears in a variety of foods, especially shellfish and red meat. The RDA for zinc for adults is 10 mg/day.
  • Copper – Copper is an essential trace mineral that acts as a component of numerous proteins, including many important enzymes. Copper is in a variety of food sources but the highest concentrations in organ meats, nuts, seeds, chocolate, and shellfish. The RDA for copper for adults is 1 mg/day.
  • Iodine – Iodine is an essential trace mineral necessary for thyroid hormone synthesis. Iodine is present in meats and plant foods based on the soil content of the food production region. Otherwise, iodized salt is the main food source of iodine in regions with low soil iodine content. The adult RDA for iodine is 150 mcg/day.
  • Selenium – Selenium is an essential trace mineral that is an essential component of selenoproteins that play biological roles in antioxidant defense and anabolic processes in the human body. Selenium occurs in grains and vegetables, but the amounts vary based on the selenium content in the soil that the grains and vegetables were grown in. Brazil nuts are known for having high concentrations of selenium. The RDA for selenium for adults is 55 mcg/day.

Cellular

Carbohydrates

Carbohydrate digestion occurs in the mouth and small intestine with salivary amylase, pancreatic amylase, and brush border enzymes. Human carbohydrate digesting enzymes catalyze hydrolysis reactions that break the bonds between monomers. However, given fibers have beta bonds, they are indigestible by human enzymes, so some end up getting digested by bacterial enzymes in the large intestine, and the remainder is excreted in the feces. In the mouth, salivary amylase begins to break down the polysaccharide starch into the disaccharide maltose, which both contain monomers of glucose. Carbohydrate digestion bypasses the stomach and continues in the small intestine via pancreatic amylase and brush border enzymes on the microvilli. Pancreatic amylase continues to break down starches into maltose. The brush border enzymes include maltase, sucrase, and lactase. Maltase hydrolyzes maltose into two glucose monomers. Sucrase hydrolyzes sucrose into glucose and fructose. Lactase hydrolyzes lactose into glucose and galactose.

Monosaccharides pass through intestinal epithelial cells via facilitated diffusion and active transport to enter the bloodstream. Fructose is absorbed via facilitated diffusion by GLUT5 and released via facilitated diffusion by GLUT2. Glucose and galactose are absorbed along with sodium via active transport by the symporter sodium-glucose transporter 1 and are released via facilitated diffusion by GLUT2. The monomers enter the portal vein and travel to the liver. When fructose and galactose enter the liver, they must first be converted to glucose to be metabolized for energy. These can be converted into intermediates of the glycolysis pathway, glucose-6-phosphate or fructose-6-phosphate, to directly enter the glycolysis pathway or the substrate of glycogenesis, glucose-1-phosphate, to be stored as glycogen.

Glucose metabolism requires the following B vitamins to act as coenzymes: thiamine (B1), riboflavin (B2), and niacin (B3). Glucose metabolism begins in the cytoplasm of cells with the anaerobic process of glycolysis when one 6-carbon glucose molecule is partially oxidized into two 3-carbon pyruvate molecules. During the process, there is a net yield of two ATP and two NADH, where they will carry the electrons to the electron transport chain, eventually producing ATP. NADH is derived from niacin. ATP is the main source of cellular energy due to its high energy bonds between phosphate groups, which are released when broken via hydrolysis.

In the absence of oxygen, which can happen during strenuous exercise or in cells without mitochondria, lactate dehydrogenase catalyzes the conversion of pyruvate to lactate, which can then go back to the liver to be converted back to pyruvate and undergo gluconeogenesis to create glucose. Then, the glucose can go back to the muscle cells and go through glycolysis, again releasing two ATP molecules. This is called the Cori cycle and shows how lactate, the waste product of skeletal muscles, can be converted to glucose in hepatocytes and then be used for energy back in the skeletal muscles.

In the presence of oxygen, pyruvate will travel to the mitochondrial matrix, where pyruvate dehydrogenase will catalyze the oxidation and decarboxylation of two 3-carbon molecules of pyruvate from glycolysis into two 2-carbon molecules of acetyl-CoA. Pyruvate dehydrogenase uses thiamine pyrophosphate, or TPP, as a coenzyme. In addition, two carbon dioxide molecules and two NADH molecules are produced, and the NADH molecules will carry electrons to the electron transport chain to ultimately produce ATP. Pyruvate decarboxylation is the link between glycolysis and the citric acid cycle.

The citric acid cycle, also known as the TCA cycle and the Krebs cycle, occurs in the mitochondrial matrix where the 2-carbon acetyl-CoA will join 4-carbon oxalate to produce 6-carbon citrate, which gets degraded to produce the energetic molecules GTP, NADH, and FADH2. The cycle will continue so long as there is an input of acetyl-CoA because citrate eventually gets converted back to oxalate. Two pyruvates from glycolysis will release 2 GTP, 6 NADH, and 2 FADH molecules. FADH is derived from riboflavin. NADH and FADH2 will travel to the electron transport chain, where ATP will be synthesized via oxidative phosphorylation.

Oxidative phosphorylation begins at the electron transport chain along the inner membrane of the mitochondrion. Four protein complexes I-IV are embedded along the membrane and function to pump protons from the mitochondrial matrix to the intermembrane space to create an electrochemical gradient through a chain of redox reactions. Protein complex I receive electrons from NADH to pump hydrogen across the inner membrane. FADH2 drops electrons off at protein complex II, and protons get pumped across at protein complex III. One molecule of NADH generates three ATP molecules, while one molecule of FADH2 only generates two molecules of ATP.  When enough protons fill up the intermembrane space, an electrochemical gradient occurs. At protein complex IV, oxygen acts as the final electron acceptor, forming water. Through chemiosmosis, protons will flow from the intermembrane space through the hydrophilic tunnel of ATP synthase back to the matrix. The proton motive force generates energy that allows ATP synthase to condense ADP + Pi into high-energy ATP. Overall, this process generates 34 ATP molecules per molecule of glucose and is by far the most efficient way to produce energy.

Proteins

Protein digestion begins in the stomach, where they are broken down by the protease enzyme pepsin. First, gastric parietal cells will release hydrochloric acid, which will denature proteins and convert inactive pepsinogen to active pepsin. Pepsin digests proteins by hydrolyzing peptide bonds between amino acids to form large polypeptides or oligopeptides. Protein digestion continues in the small intestine. In response to the acidic chyme from the stomach, the hormones cholecystokinin and secretin are synthesized in the duodenum. These hormones trigger pancreatic cells to secrete bicarbonate and proenzymes into the intestine. The proenzymes trypsinogen, procarboxypeptidase, and chymotrypsinogen are converted into their active enzyme forms trypsin, carboxypeptidase, and chymotrypsin in a cascade of enzymatic reactions. Trypsin, carboxypeptidase, and chymotrypsin digest polypeptides into tripeptides, dipeptides, and free amino acids that can be absorbed in the small intestine.

Peptide and amino acid absorption occur across epithelial cells in the small intestine via transporters. Some amino acids can travel across the epithelium paracellularly, while others require amino acid transporters that vary based on the specific amino acid and mechanism in which they transport. Tripeptides and dipeptides are transported into the epithelial cell via PEPT1 coupled with the electrochemical gradient produced by the Na+/H+ exchanger on the brush border membrane. Intracellular peptides finish breaking down tripeptides and dipeptides into free amino acids. Free amino acids will exit the basolateral membrane of the epithelial cell and enter the bloodstream at the portal vein to the liver.

Amino acids can be metabolized via transamination for amino acid interconversion or deamination for the oxidation of the carbon skeleton for energy or excretion. For amino acid interconversion, pyridoxine (B6), cobalamin (B12), and folate (B9) are required. For amino acid oxidation, pyridoxine (B6), cobalamin (B12), and biotin (B7) are required. Amino acids can undergo transamination to enter the TCA cycle in glucose metabolism. Certain amino acids like alanine can be transaminated by an aminotransferase enzyme with the coenzyme PLP, which is derived from pyridoxine, to form pyruvate. Other amino acids can be transaminated by an aminotransferase enzyme with PLP to form α-ketoglutarate, an intermediate in the TCA cycle. Some amino acids can be transaminated by an aminotransferase enzyme with PLP to form oxaloacetate, which is an intermediate in the TCA cycle. Other amino acids can be oxidized with enzymes that require biotin and vitamin B12 as coenzymes or from succinyl-CoA, which is an intermediate in the TCA cycle. When the carbon skeletons of amino acids become degraded for energy, they are deaminated, and the nitrogen group is excreted in the form of urea.

Lipids

Limited digestion of lipids occurs in the mouth and stomach with the enzymes lingual lipase and gastric lipase, respectively. However, most ingested lipids arrive at the duodenum of the small intestine undigested. The presence of lipids in the duodenum stimulates the release of enzymes from the pancreas and bile from the gallbladder. Bile emulsifies that lipids preparing them for digestion by pancreatic lipase. Pancreatic lipase hydrolyzes triglycerides to monoglycerides and free fatty acids. Lipids are absorbed via simple diffusion. Short-chain fatty acids and glycerol move directly into the portal circulation and bind to albumin. Long-chain fatty acids, mono/diglycerides, cholesterol, and phospholipids combine with bile to form micelles allowing them to be soluble in the hydrophilic environment and then leave the micelle and enter the intestinal mucosa cell. In the intestinal cell, long-chain fatty acids are re-esterified to form triglycerides. Triglycerides combine with cholesterol, phospholipids, and other proteins to form chylomicrons. The chylomicrons will leave the intestinal cell and enter the lymph system, eventually entering the bloodstream through the thoracic duct.

Lipoproteins carry lipids throughout the bloodstream, and the enzyme lipoprotein lipase frees up fatty acids to be taken up by cells. In the bloodstream, the chylomicrons can deliver the dietary fatty acids to body cells, where they will form triglycerides and the remaining lipids to the liver to travel to other cells or be excreted. In the liver, triglycerides, cholesterol, phospholipids, and proteins will combine to form VLDL, which will leave the liver to deliver lipids, mainly in the form of triglycerides, to cells in the bloodstream. As VLDL delivers triglycerides to cells, it begins to shrink and become LDL. LDL continues to carry lipids to cells, but the lipids are mainly in the form of cholesterol. LDL binds to LDL receptors of cells for cholesterol to be taken up. The remaining lipids will leave cells in the form of HDL, where they will carry lipids back to the liver for either reuse or excretion. In the cells, lipids can be metabolized for energy by entering at different points of the glucose metabolism pathway. Triglycerides are broken down into glycerol and free fatty acids. Glycerol can be converted to pyruvate and catabolized for energy. Free fatty acids can be oxidized to acetyl-CoA to enter the citric acid cycle.

  • Vitamin B1 (Thiamin) – Thiamin absorption occurs mainly in the jejunum of the small intestine. Higher concentrations are absorbed via passive diffusion, while lower concentrations are absorbed via an active, carrier-mediated system that involves phosphorylation. In the blood, thiamin is transported in the erythrocytes and plasma. A small percentage of thiamin is absorbed, while the remainder is excreted in the urine.
  • Vitamin B2 (Riboflavin) – Thiamin is mainly consumed as FMN and FAD bound to a food protein. In the stomach, the acidic environment releases the coenzymes FMN and FAD from the protein. Most absorption of riboflavin occurs in the small intestine via an active or facilitated transport system. FMN and FAD must first be hydrolyzed to riboflavin by nonspecific pyrophosphatases to be absorbed. Riboflavin is transported in the plasma mainly bound to albumin and is excreted in the urine.
  • Vitamin B3 (Niacin) – At low concentrations, niacin is absorbed in the small intestine via sodium-ion-dependent facilitated diffusion. At high concentrations, niacin is absorbed in the small intestine via passive diffusion. Niacin can be transported freely in the blood in the forms of nicotinic acid or nicotinamide. Cells and tissues can take up niacin via passive diffusion or with the use of transporters. Niacin is excreted in urine as 1-methyl nicotinamide or NAM.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid is absorbed via active transport at low concentrations and passive transport at high concentrations in the small intestine. Pantothenate kinase catalyzes the synthesis of CoA from pantothenate. CoA plays an important role in the citric acid cycle in the forms of acetyl-CoA and succinyl-CoA. CoA can be hydrolyzed to pantothenate for excretion. Pantothenic acid is excreted in the urine.
  • Vitamin B6 (Pyridoxine)  – The main dietary form of vitamin B6 is pyridoxal phosphate or PLP. For PLP to be absorbed in the small intestine, it must first undergo phosphatase-mediated hydrolysis to enter the small intestine in its nonphosphorylated form. Pyridoxal, or PL, crosses the enterocyte via passive diffusion to enter the bloodstream to the liver. In the liver, PL is converted back to PLP by the enzyme PL kinase. PLP is the main circulating form of vitamin B6 and is transported in the blood bound to albumin. The majority of PLP in the body is found in the muscle. Vitamin B6 is excreted in the urine in the form of 4-pyridoxic acid.
  • Vitamin B7 (Biotin) – Biotin can be ingested as free biotin or protein-bound biotin. In the small intestine, an enzyme called biotinidase releases biotin from its covalent bond to the protein allowing it to be absorbed. Biotin is absorbed in the small intestine through a sodium-dependent transporter. Biotin is transported through the bloodstream to the liver, mostly unbound as free biotin. Biotin and biotin metabolites are excreted in the urine.
  • Vitamin B9 (Folate)  – Food folates are polyglutamate derivatives and must be hydrolyzed to the monoglutamate forms before absorption. The monoglutamate form of folate is absorbed in the small intestine via active transport. Pharmacological doses of folic acid from supplements or fortified foods are absorbed via passive transport. Folate is transported in the bloodstream to the liver in the form of 5-methyl-tetrahydrofolate. Folate is mostly bound to albumin in the bloodstream. Most ingested folate is used or stored. Any dietary folate not absorbed is excreted in feces.
  • Vitamin B12 (Cobalamin)  – Small amounts of vitamin B12 are absorbed through a coordinated process of the GI tract, given naturally occurring B12 is bound to a protein that must be released for absorption. First, in the stomach, the presence of acid and pepsin causes the dissociation of food-bound vitamin B12 from its proteins. Then R-proteins or haptocorrins, secreted by the salivary glands, bind to vitamin B12 to protect it from stomach acid. In the small intestine, pancreatic proteases degrade R-proteins to allow B-12 to bind to intrinsic factor, which is secreted by gastric parietal cells. Intrinsic factor attaches B12 to specific ileal mucosa receptors allowing the complex to be internalized by endocytosis into the enterocyte and released into the bloodstream where it is bound to transcobalamin I, II, or III. 50% of transcobalamin II bound B12 is taken up by the liver, where it is stored while the remainder is transported to other tissues. B12 is excreted in bile, but most of it ends up reabsorbed.
  • Vitamin C (Ascorbic Acid) – The absorption, tissue distribution, and excretion of vitamin C are tightly regulated by tissue-specific active transporters SVCT-1 and SCVT-2. Ascorbic acid is absorbed into the enterocyte by SVCT-1 and enters the bloodstream via SVCT-2. Other tissues take up ascorbic acid via SVCT-1 and/or SCVT-2. Vitamin C is excreted in the urine at intakes greater than 400 mg/day. Vitamin C is most concentrated in the brain, eyes, and adrenal gland.
  • Vitamin A (Retinol) – Vitamin A is ingested both in the form of retinol and provitamin A carotenoids. In the small intestine, retinol and provitamin A carotenoids enter the mucosal cell after combining with bile to form a micelle. Retinol binds to cellular retinol-binding protein (CRBP) II within the intestinal mucosal cells to form a retinol-CRBP II complex. Then, lecithin retinol aminotransferase esterifies CRBP II retinol with a fatty acid to form CRBP-retinyl palmitate. The retinol esters will be incorporated with other lipids and apoproteins to form a chylomicron. The chylomicron will leave the intestinal cell and enter the lymph system and eventually enter the blood. β-carotene, a provitamin A carotenoid, is converted to retinoic acid inside the intestinal cells and is able to directly enter the bloodstream where it attaches to albumin to be transported to the liver.
  • Vitamin D (Cholecalciferol) – Vitamin D is obtained mainly through UV-B-induced production in the skin. A minor amount of vitamin D is obtained through dietary intake. In the skin, vitamin D3, or cholecalciferol, is synthesized when 7-dehydrocholesterol is exposed to UV-B light from the sun. Vitamin D3 is transferred to the liver to be further metabolized. Through dietary intake, vitamin D3 is absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporate into chylomicrons to leave the intestinal cells to enter the lymph system and eventually enter circulation the thoracic duct. In the liver, vitamin D3 enters a hepatocyte and is hydroxylated into 25-OH vitamin D3, which is catalyzed by the enzyme 25-hydroxylase. Then, 25-OH vitamin D3 bind to vitamin D-binding protein, or DBP, to leave the hepatocytes and be transported to the kidney for an additional hydroxylation reaction. In the kidney, 25-OH vitamin D3 is hydroxylated to 1,25-(OH)2 vitamin D3, which is catalyzed by the enzyme 1-hydroxylase. 1,25-(OH)2 vitamin D3 is also known as calcitriol, which is considered the active form of vitamin D. 1,25-(OH)2 vitamin D3 bound to DBP is released to the bone, immune cells, and liver cells.
  • Vitamin E (Tocopherol) – Through dietary intake, vitamin E is absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporate into a chylomicron to leave the intestinal cells and enter the lymph system and eventually enter circulation the thoracic duct. Vitamin E is transported in remnant chylomicrons to the liver, where it is taken up by a hepatocyte. In the hepatocyte, α-tocopherol transfer protein incorporates α-tocopherols into very low-density lipoproteins, or VLDLs, to transport to peripheral tissues. In circulation, lipoprotein lipase (LPL) catalyzes the conversion of VLDL to LDL to HDL. The cellular uptake of α-tocopherol takes place with the uptake of lipoproteins via receptor-mediated endocytosis. Most α-tocopherol is stored in adipose tissue. The remaining tocopherols and tocotrienols are excreted with bile in feces.
  • Vitamin K (Phylloquinone; Menaquinone) – Through dietary intake, vitamin K1 and K2 are absorbed in the small intestine via incorporation into a micelle to enter the intestinal cells and incorporation into a chylomicron to leave the intestinal cells and enter the lymph system and eventually enter circulation at the thoracic duct. Vitamin K1 and K2 are transported in remnant chylomicrons to the liver where it is taken up by a hepatocyte. In the hepatocyte, vitamin K1 and K2 are incorporated into very low-density lipoproteins, or VLDLs, to transport to peripheral tissues. In circulation, lipoprotein lipase (LPL) catalyzes the conversion of VLDL to LDL to HDL. The cellular uptake of vitamin K1 and K2 takes place with the uptake of lipoproteins via receptor-mediated endocytosis. Vitamin K is stored predominantly in the liver in the form of menaquinone and is excreted in the urine and feces.
  • Calcium – The intestine, kidney, bone, and parathyroid gland work together to tightly regulate calcium balance in the body. The majority of calcium is absorbed in the small intestine via paracellular diffusion. The remainder of calcium is absorbed transcellular through the calcium channel TRPV6 when luminal calcium levels are low. Calcium is transported in the bloodstream in three forms: 48% ionized as free Ca2+, 46% bound to the protein albumin, and 7% complexed with citrate, phosphate, or sulfate. In low blood calcium concentration conditions, the parathyroid gland is stimulated to release parathyroid hormone (PTH). PTH then stimulates the kidneys to increase calcium reabsorption in the proximal convoluted tubule. PTH also stimulates the kidneys to convert 25-OH D3 into 1,25(OH)2 D3, or calcitriol. The increased calcitriol and PTH in the blood travel to the bone and stimulate the resorption of calcium and phosphorus from the bone. Calcitriol also stimulates the small intestine to increase calcium absorption. As a result, blood calcium is increased. In high blood calcium conditions, the thyroid gland releases the hormone calcitonin, preventing calcium mobilization from the bone, thus reducing blood calcium levels. 99% of the calcium in the body is found in the bones and teeth, while the remainder is found in soft tissues and plasma both intracellularly and extracellularly. Most calcium is reabsorbed in the kidney, but the remainder is excreted in urine and feces.
  • Magnesium – Magnesium is absorbed in the small intestine through paracellular diffusion and transcellular active transport via TRPM6 and TRMP7. At normal magnesium intakes, 30% of intestinal magnesium absorption occurs via transcellular transport. When magnesium intakes are lower, more magnesium is absorbed via transcellular transport. When magnesium intakes are higher, more magnesium is absorbed through paracellular diffusion. Magnesium is transported in the blood as free Mg2+(60%), protein-bound (30%), and complexed to citrate, phosphate, or sulfate (10%). The kidneys control magnesium homeostasis. About 70% of serum magnesium is available for glomerular filtration, and 96% of the filtered magnesium is reabsorbed in the kidneys through several mechanisms in the proximal tubule, ascending limb, and distal tubule. The remaining magnesium is excreted in the urine. 99% of magnesium in the body is stored intracellularly in bone, muscle, and soft tissues, while 1% of magnesium in the body is found in extracellular fluid.
  • Phosphorus –  The phosphorus is absorbed in the small intestine into the enterocyte via two processes: active transport by the apical Na+ phosphate transporter NaPi-IIb and paracellular diffusion. Phosphorous leaves the enterocyte to enter the bloodstream via facilitated diffusion. The kidney plays a role in phosphorus homeostasis through the reabsorption of inorganic phosphate from the glomerular filtrate in the proximal convoluted tubule. Approximately 75 to 85% of phosphorus is reabsorbed per day, and the remainder is excreted in the urine. Phosphorus homeostasis can also be regulated secondary to that of calcium with resorption from the bone due to high PTH and calcitriol levels. Throughout the body, phosphorus is distributed 85% in the skeleton, 0.4% in the teeth, 14% in the soft tissue, 0.3% in the blood, and 0.3% in the extravascular fluid.
  • Sodium – Sodium is absorbed in the small intestine across the brush border membrane of the enterocyte via sodium-glucose cotransporter 1 (SGLT1). SGLT 1 is an active transporter that absorbs 2 sodium ions and 1 glucose across the brush border membrane of the enterocyte. Sodium is then transported out of the enterocyte into the bloodstream across the basolateral membrane via the sodium-potassium pump, or ATPase. The sodium-potassium pump uses ATP to transport 3 sodium ions out of the enterocyte and 2 potassium ions into the enterocyte. Sodium and water balance are closely linked and maintained by the kidneys. Half of the sodium in the body is found in extracellular fluid, while around 10% is found in intracellular fluid. The remaining 40% of sodium is found in the skeleton. Small losses of sodium can occur through urine, feces, and sweat.
  • Potassium – Most of the dietary potassium is absorbed in the small intestine via passive transport. The kidney maintains potassium homeostasis. About 90% of the potassium consumed is excreted in the urine, with the remaining small amount excreted in stool and sweat. Most of the potassium content in the body is found in the intracellular space of the skeletal muscle.
  • Chloride – Chloride absorption occurs in the lumen of the small intestine via three distinct mechanisms: paracellularly through passive transport, the coupling of Na+/H+ and Cl−/HCO3− exchangers, and HCO3−-dependent Cl− absorption. Chloride is principally found in extracellular fluid. The kidneys regulate chloride concentration. Around 99% of chloride is reabsorbed in the proximal tubule of the kidneys both paracellularly and transcellular via the Cl−/HCO3− exchanger. The remainder of chloride can be excreted in urine, feces, or sweat.
  • Iron – Iron consumed from food can be present in two forms: heme and nonheme iron. 90% of dietary iron consists of nonheme iron, which is far less bioavailable than heme iron. Iron is absorbed in the small intestine in the duodenum. Given nonheme iron is often present in the form of ferric iron, it must be reduced to the ferrous form prior to enterocyte uptake with the ferric reductase enzyme DCYTB. The apical surface of the enterocyte contains divalent metal transporter 1 (DMT1), which transports ferrous iron into the enterocyte. On the basolateral membrane of the enterocyte, ferroportin releases ferrous iron to hephaestin, which oxidizes ferrous iron to ferric iron so it can bind to the transporting protein transferrin in portal circulation. Ferroportin is the main regulatory point of entry for iron in the body. Iron is stored in the liver bound to ferritin, where it can be sequestered to bone marrow for erythropoiesis or red blood cell formation. Macrophages in the reticuloendothelial system of the liver, spleen, and bone marrow can ingest old red blood cells to recycle iron to be stored in the liver. There is no specific excretory system for iron. Iron loss can only occur secondary to the exfoliation of epithelial cells in the skin and gastrointestinal tract in addition to red blood cell loss from the gastrointestinal tract.
  • Zinc – Zinc is absorbed in the small intestine via carrier-mediated transport, with ZIP4 taking zinc up into the intestinal cell and ZNT1 releasing it into the bloodstream. Zinc is bound to albumin in circulation. Zinc transporters are pervasive throughout tissues in the body and play a role in maintaining zinc homeostasis. Zinc is excreted in feces.
  • Copper – Copper absorption mainly occurs in the small intestine. Copper is taken up by enterocytes with copper transporter 1 (CTR1), which is a copper importer located at the apical membrane of intestinal cells and most tissues. Copper is exported from the enterocytes into the blood by the exporter ATP7A. In portal circulation, most of the copper is bound to the transporter protein ceruloplasmin. Copper is taken up by the liver when copper-bound ceruloplasmin binds to ceruloplasmin receptors. In the hepatocytes, protein metallochaperones serve to assign and transport copper to specific pathways throughout the body. Copper is exported from the hepatocyte via the exporter ATP7B. Excess copper is secreted in the bile, which gets excreted in the feces.
  • Iodine – Iodine can be ingested in many chemical forms. Iodide is rapidly and almost completely absorbed in the stomach and small intestine. Iodate, which is used in iodized salt, is reduced in the gut and then absorbed as iodide. In circulation, iodine is taken up mainly by the thyroid gland and kidney. Iodine uptake by the thyroid depends on iodine intake, whereas uptake by the kidney remains fairly constant. Iodine is excreted in the urine. Most of the body’s iodine is stored in the thyroid to be used in thyroid hormone synthesis.
  • Selenium – The mechanism of selenium absorption is not well known. Selenium absorption occurs in the small intestine via mechanisms dependant upon the form of selenium. The absorption of inorganic selenate occurs through active transport with a sodium pump. The absorption of inorganic selenite occurs via passive diffusion. Organic selenomethionine and selenocysteine are absorbed via an active transport mechanism similar to that of neutral amino acids like methionine. Selenium is absorbed into the portal bloodstream from the enterocyte and is transported to the liver in multiple forms. Selenite is taken up by erythrocytes and reduced by glutathione reductase to selenide, which is transported in the plasma bound to albumin. Selenium can also be transported in the form of selenoprotein P. Sometimes, selenium may bind to LDL and VLDL. Selenium is stored in tissues in the form of selenomethionine with variable densities in the liver, muscle, kidney, plasma, and other organs. Selenium excretion via urine in the form of methylselenol.

Molecular

Carbohydrates

Carbohydrates are organic molecules made up of carbon, hydrogen, and oxygen. Carbohydrates are classified based on their chemistry: individual monomer characteristics, degree of polymerization, and type of linkages (α or β). Given this classification, carbohydrates subdivide into three main groups: sugars (degree of polymerization = 1 to 2), oligosaccharides (degree of polymerization = 3 to 10), and polysaccharides (degree of polymerization more than 10). Sugars include monosaccharides and disaccharides. The most common monosaccharides are glucose, fructose, and galactose. The most common disaccharides are sucrose, lactose, and maltose. Examples of oligosaccharides include maltodextrins, raffinose, and polydextrose. Polysaccharides include starches and non-starch polysaccharides. Starches include digestible amylose due to its alpha-linked monosaccharides. Non-starch polysaccharides include non-digestible cellulose due to their β-linked monosaccharides.

Proteins

Proteins are polymers of amino acids. Amino acids are organic molecules composed of carbon, hydrogen, oxygen, and nitrogen. The general structure of an amino acid consists of a central carbon surrounded by hydrogen, an amino group, a carboxylic acid group, and a side chain “R.” Each amino acid has a unique side chain. Nine essential amino acids must come from dietary sources: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The body can make eleven non-essential amino acids from precursors: alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine. There are four structure levels in a protein: primary, secondary, tertiary, and quaternary. The primary structure of a protein is a chain of amino acids connected by peptide bonds; this determines the subsequent structures and biological functions of the protein. The secondary structure of a protein consists of hydrogen bonding within amino acid chains that create either an α-helix or β-sheet conformation. The tertiary structure of a protein derives from attractions between α-helices and β-sheets of a polypeptide resulting in a three-dimensional arrangement of a protein. The quaternary structure of an amino acid consists of a spatial arrangement of multiple polypeptides in a protein.

Lipids

Lipids are organic molecules that share the common property of being hydrophobic. Dietary lipids are often in the forms of triglycerides, phospholipids, cholesterol, and fatty acids. Fatty acids are classified as saturated or containing no carbon-carbon double bonds, or unsaturated, or containing at least one carbon-carbon double bond. Saturated fatty acids have higher melting points than unsaturated fatty acids, making them solid at room temperature, unlike liquid unsaturated fatty acids. Triglycerides are composed of one 3-carbon glycerol backbone and three fatty acids. Phospholipids contain a phosphate head connected to a glycerol molecule, connected to two fatty acids. Cholesterol is a sterol that is composed of a hydrocarbon ring structure.

  • Vitamin B1 (Thiamin) – Thiamin consists of pyrimidine and thiazole rings that are linked by a methylene bridge. Thiamin exists in a variety of phosphorylated forms. Its main form is thiamin pyrophosphate or TPP.
  • Vitamin B2 (Riboflavin) – The basic chemical structure of riboflavin consists of a flavin group formed by the tricyclic heterocyclic isoalloxazine and a ribitol sugar group. The main coenzyme forms of riboflavin are flavin mononucleotide or FMN and flavin adenine dinucleotide, or FAD.
  • Vitamin B3 (Niacin) – Niacin refers to nicotinamide, nicotinic acid, and other derivatives. The basic chemical structure of nicotinic acid consists of a pyridine ring with a substituted carboxylic acid group. The chemical structure of nicotinamide consists of a pyridine ring with a substituted amide group. The main coenzyme forms of niacin are nicotinamide adenine dinucleotide or NAD and nicotinamide adenine dinucleotide phosphate or NADP.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid is a water-soluble vitamin synthesized from the condensation reaction of pantoic acid and β-alanine in only plants and bacteria. Pantothenic acid serves to transfer and carry acyl groups.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6 is a generic term for six related compounds: pyridoxal (PL), pyridoxamine (PM, pyridoxine (PN), and their respective 5’-phosphatase forms (PLP, PMP, and PNP). The major forms of vitamin B6 in animal tissues are PLP and PMP.
  • Vitamin B7 (Biotin) – Biotin’s chemical structure consists of a heterobicyclic ring of radio and thiophene with a valeric acid side chain.
  • Vitamin B9 (Folate) – Folate is the generic term for the different forms of vitamin B9 that function in single-carbon transfers. The most oxidized and stable form of folate called folic acid is in vitamin supplements. It consists of a p-aminobenzoic acid molecule bound to a pteridine ring on one side and a glutamic acid molecule on the other side. Naturally occurring folates found in food, called food folate, are pteroylpolyglutamates, which contain between one and six additional glutamate molecules connected by a peptide linkage to glutamate’s γ-carboxyl.
  • Vitamin B12 (Cobalamin) – Cobalamin, or vitamin B12, is a generic term for a group of cobalt-containing compounds with a corrin ring attached to 5,6-dimethylbenzimidazole, a sugar ribose, and a phosphate. The two cobalamins that are active in human metabolism as coenzymes are methylcobalamin and 5-deoxyadenosylcobalamin.
  • Vitamin C (Ascorbic Acid) – Vitamin C, or ascorbic acid, chemically is a simple carbohydrate with an ene-diol structure that makes it an essential water-soluble electron donor. The main form of vitamin C found in foods is its reduced form – ascorbic acid. Ascorbate is the main circulating form of vitamin C in the body.
  • Vitamin A (Retinol) – Vitamin A is a generic descriptor for compounds that exhibit the biological activity of retinol and provitamin A carotenoids. Retinol is an unsaturated 20-carbon cyclic alcohol. Provitamin A carotenoids exhibit a 40-carbon basal structure with cyclic end groups and a conjugated system of double bonds.
  • Vitamin D (Cholecalciferol) – Vitamin D3, or cholecalciferol, had a chemical structure that contains three steroid rings and an eight-carbon side chain. The structure derives from cholesterol.
  • Vitamin E (Tocopherol) – The term vitamin E encompasses eight lipophilic compounds that include four tocopherols and four tocotrienols, each of which has a designation as α-, β-, γ-, and δ-. Each of these compounds contains a chromanol ring and a lipophilic tail. Tocotrienols differ from tocopherols with their unsaturated side chains. α-tocopherol is the only form of vitamin E that is known to reverse deficiency symptoms.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K occurs naturally in two main forms: K1, or phylloquinone, and K2, or menaquinone, which has many different forms. Also, vitamin K occurs in the synthetic form of vitamin K3, or menadione, which contains only the 2-methyl-1, a 4-naphthoquinone nucleus common to all forms of vitamin K. The natural forms differ by the number of isoprenoid units in their isoprenoid side chains.
  • Calcium – Calcium is an alkaline earth metal cation found in the form of Ca2+. Calcium is a critical divalent cation in intracellular and extracellular fluid.
  • Magnesium – Magnesium is an alkaline earth metal cation found in the form of Mg2+. Magnesium is the second most abundant intracellular cation in the body.
  • Phosphorus – Phosphorous is a multivalent nonmetal that occurs in both inorganic and organic forms throughout the body. The organic forms of phosphorus include phospholipids and various phosphate esters. The inorganic forms of phosphorus include phosphate ions, protein-bound phosphate, and calcium, sodium, or magnesium-bound phosphate. Most phosphorus exists in the form of an inorganic free phosphate ion (PO42- or PO43-).
  • Sodium – Sodium is an alkali metal cation found in the form of Na+. Sodium is the major extracellular cation in the body.
  • Potassium – Potassium is an alkali metal cation found in the form of K+. Potassium is the major intracellular cation in the body.
  • Chloride – Chloride is a nonmetal anion found in the form of Cl-. Chloride is the body’s principal anion making up 70% of the body’s total anion content and serves as the most important extracellular anion in the body.
  • Iron – Iron is a transition metal element. Iron exists in two main oxidation states: Fe2+ and Fe3+. The more bioavailable form of iron is its reduced form ferrous iron, or Fe2+, due to its solubility. The less bioavailable form of iron is its oxidized form ferric iron, or Fe3+, due to its lack of solubility. Heme iron is contained in the protoporphyrin ring of hemoglobin, myoglobin, and cytochromes and is highly bioavailable. Nonheme iron can be found in molecules like iron-sulfur enzymes and ferritin and is less bioavailable.
  • Zinc – Zinc is a metal that exists in the form of Zn2+. With the 2+ charge, zinc is a strong electron acceptor in biological systems.
  • Copper – Copper is a transition metal that exists in the forms of Cu+ and Cu2+. Cu+ is the cuprous reduced form of copper. Cu2+ is the cupric oxidized form of copper. Copper is absorbed into cells in its reduced form but is ingested and travels through the bloodstream in its oxidized form.
  • Iodine – Iodine is a nonmetal element identified by its distinct violet vapor. Iodine is consumed and absorbed in its reduced form of iodide (I-). Iodine is also consumable in its oxidized form of iodate (IO3-), as well as when it is organically bound to thyroxine (T4) and triiodothyronine (T3).
  • Selenium – Selenium is present in nature in both organic and inorganic forms. The main organic forms of selenium are selenomethionine and selenocysteine. The inorganic forms of selenium are selenite (SeO32-), selenide (Se2−), selenate (SeO42-), and selenium element (Se).

Function

Macronutrients – Carbohydrates, Proteins, Lipids

Macronutrients mainly function to supply energy. Carbohydrates function as the main source of cellular energy from the human diet and are particularly essential to supply energy to the glucose-dependent brain and nervous system. Fiber plays a role in lowering cholesterol by binding to bile and promoting gut health. Proteins function less favorably as a source of energy because they play crucial roles in regulating body processes and contributing majorly to cell and body structure. Proteins particularly function as hormones, enzymes, transporters, and antibodies. Lipids function as a source of stored energy, contribute to cell function and structure and protects body organs. Water acts as a solvent for chemical reactions, a medium for nutrient transport, and a thermoregulator.

  • Vitamin B1 (Thiamin) – The coenzyme form of thiamin, or TPP, is involved in the following types of metabolic reactions: decarboxylation of α-keto acids and transmetalation. These occur in carbohydrate and branched-chain amino acids metabolism.
  • Vitamin B2 (Riboflavin) – Riboflavin functions as a component of the metabolically essential coenzymes FMN and FAD. FMN and FAD can serve as intermediates in electron transfer in redox reactions. As coenzymes, FAD and FMN are often bound to enzymes that are oxidases and dehydrogenases.
  • Vitamin B3 (Niacin) – Niacin functions as a component of the metabolically essential coenzymes NAD and NADP. These coenzymes act as hydride ion acceptors or donors in biological redox reactions. They also serve as coenzymes for dehydrogenases.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid functions as a supporter of the synthesis and maintenance of coenzyme A, a cofactor and acyl group carrier for other enzymes, and an acyl protein carrier in the fatty acid synthase complex.
  • Vitamin B6 (Pyridoxine) – Vitamin B6, in the form of PLP, is a coenzyme for over 100 enzymes involved in amino acid metabolism. PLP is a coenzyme for aminotransferases, decarboxylases, racemases, and dehydratases. PLP is a coenzyme in the first step of heme biosynthesis and the transsulfuration of homocysteine to cysteine.
  • Vitamin B7 (Biotin) – Biotin functions in metabolism as a coenzyme for transferring single-carbon units in the form of carbon dioxide for the following carboxylases: pyruvate carboxylase, propionyl-CoA carboxylase, acetyl-CoA carboxylase, and β-methylcrotonyl-CoA carboxylase. These enzymes play roles in gluconeogenesis, citric acid cycle, fatty acid synthesis, and leucine degradation.
  • Vitamin B9 (Folate)  – Folate functions in nucleic and amino acid metabolism as a coenzyme in single-carbon transfers. Folate functions as a coenzyme in nucleic acid metabolism in the processes of DNA synthesis in purine and pyrimidine nucleotide biosynthesis.  Folate functions as a coenzyme in amino acid metabolism in amino acid interconversions, including the conversion of homocysteine to methionine, which serves as the major source of methionine for the formation of the major methylating agent S-adenosyl-methionine.
  • Vitamin B12 (Cobalamin)  – Cobalamin functions as a coenzyme for two enzymes in human metabolism: methionine synthase and L-methylmalonyl-CoA mutase. Vitamin B12, in the form of methylcobalamin, is required as a coenzyme to methionine synthase for the methyl transfer reaction from methyltetrahydrofolate to homocysteine resulting in the formation of methionine and tetrahydrofolate. Vitamin B12, in the form of adenosylcobalamin, is required as a coenzyme to  L-methylmalonyl-CoA mutase in the isomerization reaction that results in the conversion of L-methylmalonyl-CoA to succinyl-CoA.
  • Vitamin C (Ascorbic Acid) – Vitamin C, in the form of ascorbate, has both enzymatic and nonenzymatic functions in the body. Ascorbate functions as a coenzyme as a reducing agent in the synthesis reactions of collagen, carnitine, neurotransmitters, and tyrosine. Ascorbate functions nonenzymatically as a powerful water-soluble antioxidant with the ability to reduce free radicals and reactive oxygen species. Ascorbate notably reduces glutathione radicals produced by the electron transport chain.
  • Vitamin A (Retinol) – Vitamin A functions metabolically in vision, cellular differentiation, gene expression, growth, immune system, and reproduction. In the form of 11-cis-retinal, Vitamin A is the chromophore group of rhodopsin found in the rod cells of the retina and is essential for night vision. In the form of retinoic acid, Vitamin A is required for the differentiation of certain cells like keratinocytes to epidermal cells and squamous epithelial keratinizing cells to mucous-secreting cells. Vitamin A can regulate gene expression by acting as transcription factors when bound to RAR and RXR. Vitamin A protects against xerophthalmia by maintaining normal growth of the conjunctival membranes of the eye. Vitamin A plays roles in processes involved in innate and adaptive immunity, including cell differentiation and hematopoiesis. Vitamin A plays a vital role in spermatogenesis in reproduction.
  • Vitamin D (Cholecalciferol) – Vitamin D, in its active form 1,25-(OH)2 vitamin D3, can function as a hormone by binding to receptors on target tissues to activate a signal transduction pathway and a regulator of gene expression by binding to a nuclear receptor to affect transcription. One of the most important functions of 1,25-(OH)2 vitamin D3 is to work with parathyroid hormone to maintain blood calcium homeostasis. 1,25-(OH)2 vitamin D3 functions to increase the absorption of calcium in the small intestine and reabsorption of calcium in the kidneys in response to low blood calcium. It also works with parathyroid hormone to stimulate the resorption of calcium from the bone to increase blood calcium levels. 1,25-(OH)2 vitamin D3 can also bind to various nuclear vitamin D receptors, or VDRs, in the bones, intestines, kidneys, and skin to stimulate the transcription of genes. This process is key to osteoclast maturation.
  • Vitamin E (Tocopherol) – Vitamin E is best known to function as a chain-breaking antioxidant that neutralizes the lipid peroxyl radicals during lipid peroxidation to prevent cyclic propagation of lipid peroxidation. This process is key in protecting the polyunsaturated fatty acids within the phospholipids of plasma membranes and plasma lipoproteins.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K mainly functions in the synthesis of several blood coagulation factors. It also plays a role in bone mineralization. Vitamin K performs these functions by enabling the carboxylation of glutamic acid residues in proteins to form γ-glutamic carboxyl (Gla) residues. Gla residues enable proteins to bind with calcium and interact with other proteins, which is necessary for blood coagulation and bone mineralization.
  • Calcium – 99% of the calcium in the body is in bone and teeth as a structural component. The remaining calcium in the body is found in intracellular and extracellular spaces and plays key roles in innervation, muscle contraction, blood coagulation, hormone secretion, and intracellular adhesion.
  • Magnesium – Magnesium is an important intracellular cation for numerous functions throughout the body. Magnesium plays a key role in metabolic reactions such as energy storage, glucose metabolism, and nucleic acid and protein synthesis. Magnesium also functions in oxidative reactions, immune function, and bone development. Magnesium plays a role in stabilizing excitable membranes by maintaining electrolyte balance and homeostasis of calcium, sodium, and potassium. Magnesium acts as a calcium channel antagonist and plays a role in vasodilation.
  • Phosphorus – Phosphorus has various structural and metabolic functions throughout the body. Structurally, phosphorus functions to form the structure of bone and teeth along with calcium, the phosphate backbone of DNA and RNA, and the phospholipid bilayer of cell membranes. Metabolically, phosphorus functions to create and store energy in phosphate bonds of ATP, regulate acid/base balance in the blood as a buffer, regulate gene transcription, regulate enzyme activity, and enable signal transduction of numerous regulatory pathways.
  • Sodium – As an extracellular cation, sodium functions to regulate blood volume, blood pressure, osmotic equilibrium, and pH. Sodium and potassium ions function together to create an action potential maintained by ion pumps that allow for neurotransmission, muscle contraction, and heart function. Sodium also plays a critical role in the transport of nutrients across the plasma membrane.
  • Potassium – Potassium is critical for normal cellular function. Sodium and potassium ions function together to create an action potential maintained by Na+-K+ ATPase, allowing for neurotransmission, muscle contraction, and heart function. Potassium also works alongside sodium to maintain intracellular and extracellular osmotic pressure.
  • Chloride – As the most important extracellular anion in the body, chloride functions to maintain fluid balance, acid-base balance, electrolyte balance, electrical neutrality, and muscle function throughout the body. Chloride works with sodium to maintain fluid balance. Chloride also works with bicarbonate to maintain acid-base balance.
  • Iron – Iron’s functions are essential for oxygen transport and cell proliferation—iron functions as the core of heme proteins like myoglobin, hemoglobin, and cytochromes. Myoglobin and hemoglobin are essential for oxygen storage and transport, while cytochromes are essential for electron transport chain reactions in energy metabolism. Iron is also critical in its nonheme form in iron-sulfur enzymes like succinate dehydrogenase and NADH dehydrogenase in oxidative metabolism.
  • Zinc – Zinc functions structurally as a component of proteins and catalytically as a component of >300 enzymes in the body. Zinc’s functions are pervasive throughout the body and crucial to growth, immunity, cognitive function, and bone health.
  • Copper – Copper functions as a critical cofactor to a group of cellular transporters called cuproenzymes. Copper is essential for the proper function of human organs and metabolic processes such as hemoglobin synthesis, neurotransmitter synthesis, iron oxidation, cellular respiration, antioxidant peptide amidation, pigment formation, and connective tissue formation.
  • Iodine – The primary function of iodine is its role in the synthesis of thyroid hormones thyroxine (T4) and triiodothyronine (T3). At the apical surface of the thyrocyte, iodide is oxidized by the enzymes thyroperoxidase (TPO) and hydrogen peroxide to attach it to tyrosyl residues on thyroglobulin to produce the precursors of thyroid hormones: monoiodotyrosine (MIT) and diiodotyrosine (DIT). TPO then catalyzes the formation of a diether bridge between the phenyl groups of iodotyrosine to create thyroid hormones. The linkage of two DITs produces T4, while the linkage of MIT and DIT produces T3. T3 and T4  are almost structurally identical, but T3 has one less iodine than T4. Thyroid hormones function to regulate fetal cell growth, postnatal growth, and basal metabolic rate.
  • Selenium – Selenium functions as an essential component of selenoproteins that play major roles in dense against oxidation, thyroid hormone formation, DNA synthesis, reproduction, and fertility. The functions of most selenoproteins are unknown, but the known functions involve participation in antioxidant and anabolic processes. A family of antioxidant enzymes named glutathione peroxidases is dependent upon selenium to function to neutralize hydrogen peroxide and organic hyperoxides in both intracellular and extracellular compartments. Deiodinases are a group of three selenoenzymes responsible for converting T4 to T3 in thyroid hormone activation. Selenoprotein-P is the most abundant selenoprotein found in plasma and plays a major role in the transport and homeostasis of selenium in tissues.

Testing

Carbohydrates

Measuring the amount of glucose in plasma is one of the most important ways to screen for and manage diabetes. To clinically test and monitor blood glucose, blood is drawn from a vein, usually when the patient has fasted for at least 8 hours. The level of glucose is measured in milligrams of glucose per deciliter plasma. A healthy fasting blood glucose level is less than or equal to 99 mg/dL. Someone who has an increased risk for diabetes, or prediabetes, falls in the range of fasting blood glucose of 100 to 125 mg/dL. If a patient has a fasting blood glucose of 126 mg/dL or greater on two separate occasions, they can receive a diagnosis of diabetes.

Proteins

Nitrogen balance is the gold standard for testing the protein status of the body. Nitrogen balance can serve as a marker of adequate nutrition and physiological stress. Nitrogen balance is equal to the grams of nitrogen consumed minus the grams of nitrogen excreted. The grams of nitrogen consumed is calculated by the grams of protein consumed divided by 6.25 grams of protein per 1 gram of nitrogen. The grams of nitrogen excreted is calculated by extrapolating losses with grams of nitrogen in urinary urea plus 4 grams, which accounts for losses in feces, sweat, skin, and wounds. Under normal conditions, an individual should be at nitrogen equilibrium, or nitrogen balance equals zero. Critically ill patients often have negative nitrogen, so the goal with them is to increase the protein intake to achieve a positive nitrogen balance for healing.

Lipids

To test the amount of lipids in the body, a sample of blood is taken via venipuncture in tubes and analyzed for serum or plasma total cholesterol, triglycerides, and lipoproteins. Cholesterol levels remain fairly constant so that sampling is possible at any time. In contrast to cholesterol levels, triglyceride levels fluctuate throughout the day, so blood collection should occur after a 12-hour fasting period because, at that point, chylomicrons should have cleared from the circulation. To separate and quantify lipoproteins from the plasma sample, ultracentrifugation, precipitation, and electrophoresis are performed. High vs. low plasma lipid levels are determined based on the bell-shaped distribution of the general population. Cholesterol levels are determined based on the risk for coronary atherosclerosis. Cholesterol levels below 200 mg/dl are considered desirable, levels from 200 to 239 mg/dl are considered borderline high cholesterol, and levels of 240 mg/dl or greater are considered high cholesterol.

  • Vitamin B1 (Thiamin) – Thiamin status is measurable via urinary thiamin excretion, erythrocyte thiamin, and erythrocyte transketolase activity. Erythrocyte transketolase activity is considered the gold standard functional test of thiamin status.
  • Vitamin B2 (Riboflavin) – Riboflavin status is measured via erythrocyte glutathione reductase activity, erythrocyte flavin, and urinary flavin. Erythrocyte glutathione reductase activity is the most common method to determine riboflavin status.
  • Vitamin B3 (Niacin) – Niacin status can be measured using urinary 1-methyl nicotinamide excretion, plasma concentrations of 2-pyridone, erythrocyte pyridine nucleotides, and transfer of adenosine diphosphate ribose as a functional measurement. Urinary 1-methyl nicotinamide is the most reliable and sensitive measure of niacin status.
  • Vitamin B5 (Pantothenic Acid) – Pantothenic acid status can be measured using urinary pantothenic acid excretion and whole blood pantothenic acid concentration.
  • Vitamin B6 (Pyridoxine)  – Vitamin B6 status assessment is best with plasma PLP. A plasma PLP of <20 nmol/L indicates a vitamin B6 deficiency.
  • Vitamin B7 (Biotin) – Biotin status is measurable with urinary biotin and 3-hydroxyisovalerate excretion. Decreased urinary excretion of biotin along with increased urinary excretion of 3-hydroxyisovalerate indicates biotin deficiency.
  • Vitamin B9 (Folate)  – The primary test used to measure folate status is erythrocyte folate. Given folate is taken up by developing erythrocytes in the bone marrow, erythrocyte folate concentration is an ideal indicator of long-term folate status. Plasma homocysteine can also be useful as an indicator of folate status given in inadequate quantities of folate; not as much homocysteine can undergo conversion to methionine. Serum folate can also be tested as an indicator of dietary folate intake but is limited and should be used in conjunction with additional folate status indicators.
  • Vitamin B12 (Cobalamin)  – The primary test to measure vitamin B12 status is serum vitamin B12, reflecting both intake and stores. The lower limit of serum vitamin B12 for adults is 170 to 250 pg/mL. Serum methylmalonic acid concentration is another specific and functional indicator of vitamin B12 status because serum methylmalonic acid concentrations become elevated during vitamin B12 deficiency. Serum total homocysteine concentration is a functional but non-specific indicator of vitamin B12 status due to elevation during vitamin B12 deficiency.
  • Vitamin C (Ascorbic Acid – Vitamin C status testing is via plasma vitamin C and leukocyte vitamin C. Plasma vitamin C concentration is sensitive to a recent diet, while leukocyte vitamin C reflects tissue stores. A plasma vitamin C concentration of less than 0.2 mg/dL is considered deficient.
  • Vitamin A (Retinol) – The gold standard for testing vitamin A status is through a liver biopsy because the liver is vitamin A’s major storage organ. However, this measure is not very feasible in humans. Retinol status is testable with plasma retinol concentration, but it only indicates low status if there is a severe deficiency. Vitamin A status may also be tested with a relative dose-response test, which measures the magnitude of increased RBP following supplementation.
  • Vitamin D (Cholecalciferol) – Vitamin D status is tested by using serum 25-hydroxyvitamin D concentrations. A serum 25-hydroxyvitamin D concentration that is less than 20 ng/mL represents a vitamin D deficiency and a need for supplementation.
  • Vitamin E (Tocopherol) – Vitamin E status is difficult to test because serum concentrations of vitamin E are largely age-dependent and are influenced by blood lipids. In the general population, α-tocopherol plasma levels can range from 19.9 micromoles/L to 34.2 micromoles. More research needs to be done to adjust specific requirements to an individual’s bioavailability.
  • Vitamin K (Phylloquinone; Menaquinone) – Vitamin K status is difficult to assess due to its being lipophilic and not very abundant. However, functional tests such as prothrombin time or Gla protein measurement can be useful to assess vitamin K status indirectly.
  • Calcium – Calcium status is difficult to assess in individuals because there is no reliable indicator that can establish a relationship between calcium and a particular disease state. Total body calcium is not useful to assess calcium intake because the body regulates calcium in a very tight range and will adapt to conserve it. Bone-mass measurements may indicate long-term calcium status by assessing changes in bone density.
  • Magnesium – Magnesium status can be tested with serum magnesium. Serum magnesium is maintained at a tight range of 1.7 to 2.6 mg/dL. A serum value of under 1.7 mg indicates a magnesium deficiency. A serum value of over 2.6 mg/dL indicates magnesium toxicity.
  • Phosphorus – Serum phosphorus is the most common way to assess phosphorus status. Serum phosphorus is maintained in a relatively narrow range of 2.5 to 4.5 mg/dL. Although serum phosphorus does not reflect the full body stores, serum phosphorus is crucial for various cellular processes in the body. Serum phosphorus below or above the normal range can indicate a deficiency and toxicity, respectively.
  • Sodium – Sodium balance is tested via plasma sodium concentration. A plasma sodium concentration greater than 150 mmol/L indicates sodium toxicity or hypernatremia. A plasma sodium concentration of less than 136 mmol/L indicates sodium deficiency or hyponatremia.
  • Potassium – Potassium balance is tested via serum potassium. The body maintains normal serum potassium levels in a narrow range of 3.5 to 5.5 mmol/L. Potassium toxicity, or hyperkalemia, occurs at serum potassium concentrations greater than 5.5 mmol/L. Potassium deficiency, or hypokalemia, occurs at concentrations less than 3.5 mmol/L.
  • Chloride – Since chloride serves as an important diagnostic indicator for various diseases, it can be tested for in serum, sweat, urine, and feces. Serum and urine chloride concentrations are used in the diagnosis of acid-base and osmolar disorders and used in formulas like the anion gap, strong anion gap, strong ion difference, and chloride/sodium ratio. Sweat chloride concentration is used in the diagnosis of cystic fibrosis when it is above 60 mmol/L.
  • Iron  – Iron is tested via serum-based indicators of iron status, such as hemoglobin, plasma ferritin, and plasma transferrin saturation. Hemoglobin is routinely measured to indicate anemia but is not specific for iron. Plasma ferritin is the gold standard of iron status because it is the most specific indicator of iron stores. A plasma ferritin concentration of less than 20 ng/L indicates iron deficiency. High plasma ferritin values can indicate iron overload. Transferrin saturation indicates the ratio of iron to transferrin to reflect transport iron. Transferrin saturation is low-cost but shows a pronounced diurnal variation.
  • Zinc – Zinc status testing is via serum zinc. A concentration of zinc below the lower value of the reference range of 10 to 18 micromol/L is considered a deficiency.
  • Copper – Copper status evaluation is via serum copper or serum ceruloplasmin. A concentration of serum copper below the lower value of the reference range of 12 to 20 micromol/L is considered a deficiency.
  • Iodine – Iodine status can be assessed with four different methods: urinary iodine concentration, goiter rate, serum TSH, and serum Tg. Urinary iodine, serum Tg, and goiter rate are complementary tests given urinary iodine are sensitive to recent iodine intake in a matter of days, serum Tg shows an intermediate response in a matter of weeks or months, and goiter rate changes reflect iodine nutrition in a matter of months or years. TSH can be used to assess iodine status reflecting on the level of circulating thyroid hormone but is a relatively insensitive indicator of iodine status in adults. However, TSH is a sensitive indicator of iodine status in newborns.
  • Selenium – Selenium status is tested via serum selenium. A concentration of selenium below the lower value of the reference range of 0.75 to 1.85 micromol/L is considered a deficiency.

Clinical Significance

Carbohydrates

Diabetes refers to a group of metabolic diseases of disordered glucose metabolism. Diabetes is characterized by hyperglycemia, or high blood sugar, and premature vascular disease. Symptoms of diabetes-related hyperglycemia include polydipsia, polyuria, weight loss, polyphagia, and blurred vision. Acute and life-threatening complications of uncontrolled diabetes include hyperglycemia with diabetic ketoacidosis or nonketotic hyperosmolar syndrome. Long-term complications of uncontrolled diabetes include macrovascular and microvascular complications that lead to loss of vision, renal failure, neuropathy, and cardiovascular disease. There are three types of diabetes: type 1, type 2, and gestational. Type 1 diabetes occurs in 5 to 10% of cases and is characterized by absolute insulin deficiency and pancreatic beta-cell destruction. Insulin is a hormone produced by pancreatic beta cells that stimulate sugar uptake in the blood by cells. Insulin therapy is required to treat type 1 diabetes. Type 2 diabetes occurs in 90 to 95% of cases and is characterized by insulin resistance and impaired beta-cell function. In some individuals with type 2 diabetes, blood glucose control can be managed with lifestyle changes like diet, weight reduction, and exercise, and/or oral glucose-lowering medications. However, some individuals may need insulin therapy. Gestational diabetes occurs in 9% of pregnant women during the second or third trimester of pregnancy. Glucose tolerance usually returns to normal after delivery, but this increases the risk for type 2 diabetes later in life.

Proteins

Protein-energy malnutrition is a problem for children in developing and developed countries around the world and contributes to acute and chronic childhood illness. In cases of extreme protein-energy malnutrition, marasmus and kwashiorkor are the two main clinical syndromes seen. Marasmus is more common and is characterized by muscle wasting and depletion of subcutaneous fat stores without edema as a result of deprivation of calories and nutrients. In addition, there is poor growth, little disease resistance, slowed metabolism, and impaired brain development. This usually occurs in children under the age of 5 due to their increased caloric requirements. Kwashiorkor is characterized by normal weight with edema, poor growth, low blood albumin, little disease resistance, and apathy resulting from a diet with an adequate caloric intake but inadequate protein. This commonly occurs in older infants or toddlers who are displaced from breastfeeding due to the birth of a younger sibling and have to wean rapidly but are unable to increase protein intake enough.

Lipids

Lipids in abnormal concentrations attract clinical attention. Abnormal lipid levels can occur due to abnormalities in the synthesis, degradation, and transport of lipoprotein particles. Hyperlipidemia is defined as elevated levels of lipids or lipoproteins in the blood. Hyperlipidemia is very clinically relevant due to its association with an increased risk of atherosclerotic cardiovascular disease. Other clinical manifestations of hyperlipidemia include ischemic vascular disease, acute pancreatitis, and visible accumulations of lipid deposits. Increased plasma lipid levels can be related to genetic disorders, dietary factors, certain drugs, and as a secondary symptom of certain diseases.

Vitamin B1 (Thiamin)

Thiamin deficiency is historically known as a disease called beriberi. Currently, in developed nations, thiamin deficiency mainly occurs with chronic alcoholism and is called Wernicke-Korsakoff syndrome. Symptoms of thiamin deficiency are nonspecific and include anorexia, weight loss, apathy, short-term memory issues, confusion, irritability, muscular weakness, and enlargement of the heart.

Vitamin B2 (Riboflavin)

The symptoms of riboflavin deficiency include sore throat, angular stomatitis, glossitis, dermatitis, and weakness. It is rare but can occur with diseases such as cancer, diabetes, cardiac disease, and alcoholism.

Vitamin B3 (Niacin)

The classic clinical manifestation of severe niacin deficiency is a disease called pellagra. Pellagra is characterized by a symmetrical, pigmented rash that develops in sunlight exposed areas, GI symptoms such as vomiting, constipation, diarrhea, a bright red tongue, and neurological problems such as depression and fatigue, apathy, headache, and loss of memory. Pellagra was common in the United States and Europe in areas where corn was a dietary staple in the early twentieth century. Pellagra has disappeared from developed countries except for cases of chronic alcoholism. It persists in parts of India, China, and Africa.

Vitamin B5 (Pantothenic Acid)

Pantothenic acid deficiencies are extremely rare but have been shown in individuals fed diets devoid of pantothenic acid. Symptoms of deficiency include irritability, fatigue, apathy, sleep disturbances, GI complaints, numbness, paresthesias, muscle cramps, and hypoglycemia with increased insulin sensitivity.

Vitamin B6 (Pyridoxine) 

Vitamin B6 deficiency is rare in healthy individuals. Symptoms of vitamin B6 deficiency include seborrheic dermatitis, microcytic anemia, convulsions, and confusion. Microcytic anemia occurs due to PLP’s role as a cofactor in the first step in heme biosynthesis.

Vitamin B7 (Biotin)

Biotin deficiency is rare but can occur in specific scenarios. Biotin deficiency can occur in people who ingest raw eggs due to the protein avidin, which inhibits biotin absorption. It can also occur in people with genetic defects in the enzyme biotinidase. Symptoms of biotin deficiency include thinning of hair, loss of hair color, dermatitis, depression, lethargy, and hallucinations.

Vitamin B9 (Folate) 

Folate deficiency results in impaired synthesis of DNA and RNA, which can manifest clinically megaloblastic anemia and developmental disorders in utero. Megaloblastic or macrocytic anemia occurs when red blood cell development is halted in the early erythroblast stage due to a lack of folate, allowing DNA synthesis to continue and erythroblasts to divide and mature. Early erythroblasts are large and do not contain much hemoglobin. Inadequate maternal folate status during pregnancy can result in neural tube defects such as spina bifida and anencephaly. Neural tube defect risk reduction has been achieved with daily supplementation of 400 mcg of folate in women of childbearing age. In addition, there is some evidence that might suggest folate reduces the risk of cardiovascular disease, certain cancers, and psychiatric disorders.

Vitamin B12 (Cobalamin) 

The major cause of clinical effects of vitamin B12 deficiency is pernicious anemia, which is caused by a lack of functional intrinsic factor in the stomach due to autoimmune destruction of gastric parietal cells. Malabsorption of food-bound vitamin B12 can also occur due to non-autoimmune atrophic gastritis, which causes loss of stomach acid and mainly affects the elderly. The hematological effects of vitamin B12 deficiency are clinically indistinguishable from those of folate deficiency causing macrocytic, or megaloblastic, anemia. Vitamin B12 deficiency can also result in impaired neurological function and increased neural tube defect risk.

Vitamin C (Ascorbic Acid)

Vitamin C deficiency is clinically and historically known as scurvy. Vitamin C deficiency is currently rare and only seen in malnourished populations with chronic conditions, poor diet, malabsorption, or substance dependency. Symptoms of vitamin C deficiency include gingival inflammation, fatigue, petechiae, bruising, and joint pain.

Vitamin A (Retinol)

Vitamin A deficiency affects 20-40 million children worldwide in regions with low-fat, plant-based diets and protein-calorie malnutrition. Vitamin A deficiency more commonly causes death than blindness in children in high-risk regions due to its role in the immune system. Vitamin A deficiency can also cause an increased risk of respiratory and diarrheal infections, decreased growth rate, slow bone development, and decreased survival from a serious illness.

Vitamin D (Cholecalciferol)

Vitamin D deficiency can lead to rickets and osteomalacia due to its critical role in bone and mineral metabolism. Rickets occurs in infants and children as a result of the failure of the bone to mineralize. The symptoms of rickets include growth retardation and bowing of the long bones of the legs. Osteomalacia occurs in adults; as a result, inadequate amounts of calcium and phosphate causing demineralization of the bone. Vitamin D may have extraskeletal effects and play a role in cardiovascular diseases, autoimmune diseases, neurological diseases, cancer, asthma, and pregnancy complications.

Vitamin E (Tocopherol)

Vitamin E deficiency is very rare but can occur in certain individuals. Symptoms of vitamin E deficiency include oxidative damage of tissues, membrane damage of cells, neurological abnormalities such as peripheral neuropathy, muscular, functional abnormalities like ataxia, and hemolytic anemia. Vitamin E deficiency most commonly occurs in premature babies of very low birthweight, people with fat-malabsorption disorders like Crohn’s disease and cystic fibrosis, and those who have a rare neurodegenerative disease called ataxia with vitamin E deficiency (AVED) that is caused by mutations in the gene for αβ-tocopherol transfer protein.

Vitamin K (Phylloquinone; Menaquinone)

Vitamin K deficiency is uncommon in healthy adults but may be seen in those with gastrointestinal malabsorptive disorders. However, newborns are at high risk for vitamin K deficiency. Newborns are at risk given milk is low in vitamin K, their stores are low since vitamin K does not pass the placenta, and their intestines are not yet populated with vitamin K synthesizing bacteria. Infants born in the United States and Canada routinely receive 0.5 to 1 mg of intramuscular phylloquinone within 6 hours of birth to prevent vitamin K deficiency bleeding, or VKDB. VKDB can affect infants up to 3 to 4 months of age and cause intracranial hemorrhage, central nervous system damage, and liver damage.

Calcium

Hypocalcemia, or calcium deficiency, can result from inadequate calcium intake, poor calcium absorption, or excessive calcium losses. Poor calcium absorption can occur due to inadequate vitamin D status. Excessive calcium losses can occur due to a lack of PTH. Symptoms of hypocalcemia can include muscle spasms, cramps, paresthesia, tetany, and seizures. Long-term hypocalcemia can impact bone health and result in reduced bone mass and osteoporosis. Hypercalcemia can occur due to increased bone resorption, increased intestinal absorption, and decreased renal excretion of calcium. Syndromes that increase PTH production can result in excessive calcium reabsorption and calcitriol production in the kidney. Excess PTH and calcitriol production can result in increased bone resorption. Excess calcitriol also can increase intestinal absorption. Symptoms of hypercalcemia include fatigue, confusion, polydipsia, frequent urination, upset stomach, bone pain, muscle weakness, and cardiac arrhythmia.

Magnesium

Magnesium deficiency, or hypomagnesemia, can occur due to chronic inadequate magnesium intake, chronic diarrhea, magnesium malabsorption, alcoholism, and medications like diuretics, antacids, proton pump inhibitors, and aminoglycoside antibiotics. Symptoms of hypomagnesemia are nonspecific and include muscle weakness, cramps, spasms, and tremors. Magnesium toxicity, or hypermagnesemia, can occur with supplemental magnesium, especially in intestinal or renal disease. Symptoms of hypermagnesemia include diarrhea, nausea, vomiting, headaches, lethargy, and flushing. At very high serum concentrations of magnesium, cardiac and electrocardiogram changes can occur, as well as coma, respiratory depression, and cardiac arrest.

Phosphorus

Phosphorus deficiency, or hypophosphatemia, is relatively rare in healthy individuals. However, hypophosphatemia can occur due to conditions that cause a shift of phosphorous from extracellular fluid to intracellular fluid, decreased intestinal absorption of phosphorus, or increased renal excretion of phosphorus. Hypophosphatemia may also occur in individuals with rare genetic disorders that decrease renal reabsorption and increase phosphorus excretion. Hypophosphatemia can appear asymptomatic until serum levels reach <1.5 mg/dL, where symptoms of anorexia, confusion, seizures, and paralysis can present. Respiratory depression can occur at serum levels <1 mg/dL. Treatment of hypophosphatemia includes oral or intravenous supplementation, depending on the severity of deficiency. Phosphorus toxicity, or hyperphosphatemia, can occur in those with chronic kidney disease due to decreased phosphorus excretion. Hyperphosphatemia is associated with increased death from cardiovascular disease due to vascular calcification in individuals with and without chronic kidney disease. Hyperphosphatemia is treated first by dietary restriction of phosphate, protein restriction, and dialysis if the latter fails. Hyperphosphatemia can also be treated with oral phosphate binders that block dietary phosphorus absorption.

Sodium

Given the pervasiveness of sodium in various foods, sodium deficiency is highly unlikely in healthy individuals. Sodium deficiency, or hyponatremia, can only occur in pathological conditions such as adrenal insufficiency, kidney disease that results in excessive sodium losses, excessive burns, diabetic ketoacidosis, and additional conditions that cause excessive sodium losses such as vomiting, diarrhea, prolonged sweating, and excessive diuretic use. Symptoms of hyponatremia include hypovalemia, lethargy, confusion, and weakness. Sodium toxicity, or hypernatremia, can occur with dehydration, hyperaldosteronemia, and renal failure. Symptoms of hypernatremia include hypervolemia, hypertension, convulsions, or coma. Even under normal conditions, continuous excessive intake of sodium can result in hypertension in certain individuals.

Potassium

Potassium is considered to be a shortfall nutrient in the American diet according to the 2010 Dietary Guidelines for American’s Advisory Committee because most Americans are unable to consume the AI of 4,700 mg/day. There is moderate evidence of an association between blood pressure reduction and potassium intake in adults, which influences cardiovascular disease risk. Hypokalemia usually occurs due to inadequate potassium intake and/or excessive potassium losses. Hypokalemia can clinically manifest in symptoms such as muscle weakness, smooth muscle dysfunction, cardiac complications, and glucose intolerance. Hyperkalemia usually occurs due to impaired renal excretion. Hyperkalemia will manifest in excitatory tissues and present symptoms such as neuromuscular symptoms such as paresthesias and fasciculations, cardiac arrest, and impaired renal function.

Chloride

Hypochloremia, or chloride deficiency, is related to clinical situations that cause excessive chloride losses due to gastrointestinal or renal conditions such as vomiting and renal failure. When serum chloride levels fall, bicarbonate reabsorption increases proportionately, resulting in metabolic alkalosis. Symptoms of hypochloremia are concurrent with those of metabolic alkalosis and include confusion, apathy, cardiac arrhythmias, and neuromuscular irritability. Hyperchloremia, or chloride toxicity, is related to clinical situations that cause excessive gastrointestinal or renal bicarbonate losses, such as severe diarrhea and medications that promote bicarbonate excretion. When serum bicarbonate levels fall, chloride reabsorption increases proportionately, resulting in metabolic acidosis.

Iron

The World Health Organization (WHO) indicates iron deficiency to be the most common form of malnutrition globally, affecting 25% of the global population. Iron deficiency is highly prevalent in both developing and developed countries. Iron deficiency is most commonly caused by inadequate dietary iron intake, inadequate iron utilization due to diseases, impaired iron absorption, or excess iron loss. Iron deficiency can often be avoided and reversed with iron supplementation and/or reducing iron losses. Untreated iron deficiency can result in microcytic anemia, poor cognitive performance, impaired immune function, impaired growth in children, poor pregnancy outcomes, and reduced endurance capacity. On the other hand, iron overload can be caused by a disease called hereditary hemochromatosis due to a C282Y mutation in the HFE gene. Hereditary hemochromatosis can be treated with iron removal therapy.

Zinc

Zinc deficiency can present clinically with symptoms such as dermatitis, alopecia, decreased appetite, frequent diarrhea, frequent upper respiratory infection, stunted growth in children, and hypogonadism. Zinc deficiency can occur due to diarrheal illness, kidney failure, and genetic diseases acrodermatitis enteropathica (AE). AE is a fatal disease of zinc malabsorption due to a mutation in the ZIP4 gene, which encodes the major intestinal zinc uptake protein. AE is treated with lifelong zinc supplementation of 100 mg/kg per day. Zinc toxicity is rare due to the tight regulation of zinc concentrations in the body. However, long-term zinc supplementation above the tolerable upper intake level of 40 mg/day can decrease copper absorption and cause copper deficiency. This occurs because zinc induced the formation of the intestinal cell protein metallothionein, which binds to metals and prevents their absorption by trapping them in the intestinal cell. Metallothionein has a stronger affinity for copper than zinc, thus trapping copper in the intestinal cell and halting absorption.

Copper

Copper deficiency generally manifests in systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system. Copper deficiency causes symptoms such as fatigue and weakness. Copper deficiency can occur due to excessive zinc supplementation and the genetic disorder of copper malabsorption called Menkes disease. Menkes disease is caused by a mutation in the ATP7A gene, which causes copper to accumulate in the enterocyte, making it unable to reach the blood or any other organ system. Another genetic disease of copper metabolism is Wilson disease, which is a genetic disease of accumulation of copper mainly in the liver and the brain due to a mutation in the ATP7B gene responsible for the ATP7B exporter.

Iodine

Iodine deficiency will cause a compensatory response of the thyroid gland. When iodine intake falls below approximately 100 mcg/day, the pituitary increases secretion of TSH, which increases plasma iodine clearance by the thyroid. Thus, plasma iodine levels decrease, and thyroid hormone synthesis decreases, resulting in hypothyroidism. The increase in TSH also increases the thyroid cell number and cell size resulting in an enlarged thyroid gland or goiter. The goiter can be treated with iodine supplementation, gradually reducing the size or a thyroidectomy. If left untreated, the goiter may cause tracheal and esophageal pressure. Thyroid deficiency during pregnancy can lead to neurological cretinism in the offspring.

Selenium

Selenium deficiency has been known to appear in humans after severe and prolonged cases of selenium deprivation. Selenium deficiency is known as Keshan disease and occurs in areas where selenium content in the soil is low, like China. Symptoms of Keshan disease include cardiomyopathy, peripheral myopathy, decreased muscle tone and function, hair thinning, opacification of nails, and anemia.

References

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Causes, Symptoms of Adenomyosis – Treatment

Symptoms of Adenomyosis/Adenomyosis is a uterine condition that is histologically characterized by the presence of ectopic endometrial glands and stroma within the myometrium, surrounded by hypertrophic and hyperplastic myometrial changes . For several decades, the diagnosis of adenomyosis was made in hysterectomy specimens either coincidentally, or in women treated surgically for chronic pelvic pain and/or abnormal uterine bleeding.

Adenomyosis is a medical condition characterized by the growth of cells that build up the inside of the uterus (endometrium) atypically located within the cells that put up the uterine wall (myometrium),[rx] as a result, thickening of the uterus occurs. As well as being misplaced in patients with this condition, endometrial tissue is completely functional. The tissue thickens, sheds, and bleeds during every menstrual cycle.[rx]

Causes of Adenomyosis

  • Adenomyosis and endometriosis are usually regarded as closely related, but
    • Microscopic appearance, and probably their pathogenesis, are somewhat different
    • They may occur independently of each other
    • Adenomyosis mostly is made up of nonfunctional (basal) endometrium and is frequently connected with the mucosa (vs. endometriosis, composed of functional layers)
    • Adenomyosis may represent a unique form of endometrial diverticulosis
  • Hypothetical mechanisms include (Crum: Diagnostic Gynecologic and Obstetric Pathology, 2nd Edition, 2011)
    • Instillation of endometrium within the myometrium
    • In situ metaplasia of pluripotent stem cells retained in myometrium or
    • Improper partitioning of the endometrium from the myometrium
  • Of note, del(7) (q21.2q31.2), a deletion found in typical leiomyoma, has been found in three cases of adenomyosis, suggesting some pathobiology overlap between leiomyomata and adenomyosis (Cancer Genet Cytogenet 1995;80:118)
  • Invasive tissue growth – Some experts believe that endometrial cells from the lining of the uterus invade the muscle that forms the uterine walls. Uterine incisions made during an operation such as a cesarean section (C-section) might promote the direct invasion of the endometrial cells into the wall of the uterus.
  • Developmental origins  – Other experts suspect that endometrial tissue is deposited in the uterine muscle when the uterus is first formed in the fetus.
  • Uterine inflammation related to childbirth –  Another theory suggests a link between adenomyosis and childbirth. Inflammation of the uterine lining during the postpartum period might cause a break in the normal boundary of cells that line the uterus.
  • Stem cell origins – A recent theory proposes that bone marrow stem cells might invade the uterine muscle, causing adenomyosis.

Symptoms of Adenomyosis

Adenomyosis can vary widely in the type and severity of symptoms that it causes, ranging from being entirely asymptomatic 33% of the time to being a severe and debilitating condition in some cases. Women with adenomyosis typically first report symptoms when they are between 40 and 50, but symptoms can occur in younger women.[rx][rx]

Symptoms and the estimated percent affected may include:[rx]

  • Chronic pelvic pain (77%)
  • Heavy menstrual bleeding (40-60%), which is more common in women with deeper adenomyosis. Blood loss may be significant enough to cause anemia, with associated symptoms of fatigue, dizziness, and moodiness.
  • Abnormal uterine bleeding
  • Painful cramping menstruation (15-30%)
  • Painful vaginal intercourse (7%)
  • A ‘bearing’ down feeling
  • Pressure on bladder
  • Dragging sensation down thighs and legs
  • Uterine enlargement (30%), which in turn can lead to symptoms of pelvic fullness.
  • Tender uterus
  • Infertility or sub-fertility (11-12%) – In addition, adenomyosis is associated with an increased incidence of preterm labor and premature rupture of membranes.[rx][rx]

Women with adenomyosis are also more likely to have other uterine conditions, including:

  • Uterine fibroids (50%)
  • Endometriosis (11%)
  • Endometrial polyp (7%)
  • Nonneoplastic condition presenting with palpably enlarged uterus
  • Symptoms are nonspecific: dysmenorrhea, menorrhagia, abnormal uterine bleeding, dyspareunia, chronic pelvic pain associated with the menstrual period and infertility (Eur J Obstet Gynecol Reprod Biol 2009;143:103N Engl J Med 2010;362:2389)
  • Associated with deep infiltrating endometriosis, parity, intense dysmenorrhea and increasing age (Eur J Obstet Gynecol Reprod Biol 2014;181:289)
  • Tends to regress after menopause (Hum Reprod 2012;27:3432)
  • When extensive, it confers a potential risk of infarction and thrombosis and exacerbates menorrhagia via activation of coagulation and fibrinolysis during menstruation (Eur J Obstet Gynecol Reprod Biol 2016;204:99)
  • Painful menstrual cramps (dysmenorrhea).
  • Heavy menstrual bleeding (menorrhagia).
  • Abnormal menstruation.
  • Pelvic pain.
  • Painful intercourse (dyspareunia).
  • Infertility.
  • Enlarged uterus.


Diagnosis of Adenomyosis

Histopathology

  • The diagnosis of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus.[rx] These tissue samples can come from a uterine biopsy or directly following a hysterectomy. Uterine biopsies can be obtained by either a laparoscopic procedure through the abdomen or hysteroscopy through the vagina and cervix.[rx]
  • The diagnosis is established when the pathologist finds invading clusters of endometrial tissue within the myometrium. Several diagnostic criteria can be used, but typically they require either the endometrial tissue to have invaded greater than 2% of the myometrium, or a minimum invasion depth between 2.5 to 8mm.[rx] Histopathological image of uterine adenomyosis observed in the hysterectomy specimen. Hematoxylin & eosin stain.
Gross Findings
  • Enlarged uterus
  • Thickened uterine wall with a trabeculated appearance
  • Hemorrhagic pinpoint or cystic spaces throughout wall[rx]
Microscopic Findings
  • Endometrial glands and stroma haphazardly distributed throughout the myometrium
  • Concentric myometrial hyperplasia frequent around adenomyotic foci
  • Variants: Gland-poor, stroma-poor, intravascular[rx]
Laboratory Evaluation

Laboratory testing is useful to rule out other disease entities included in the differential diagnosis, in addition to identifying certain complicating features such as anemia due to heavy menstruation. While some biomarkers due exist, none are specific for adenomyosis.

Imaging

Adenomyosis can vary widely in the extent and location of its invasion within the uterus. As a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. Nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment.[rx] Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis.[rx]

Ultrasound

Transvaginal ultrasound is the preferred diagnostic imaging modality for adenomyosis. The characteristic findings reflect the histopathologic changes of the disease process and can be broken down into three categories:

  • Endometrial infiltration – echogenic striations and nodules, myometrial cysts, and “lollipop” diverticula (cystic striations)
  • Smooth muscle proliferation – focal or diffuse myometrial thickening with indistinct borders more commonly involving the posterior fundus and heterogenous echotexture manifesting as “Venetian blind” appearance of thin linear shadows
  • Vascularity – color Doppler demonstrating an increased number of tortuous vessels throughout the involved myometrium as opposed to leiomyomas which displace vessels

A number of mimics can have similar findings on the ultrasound exam, including tamoxifen use, prior endometrial ablation, endometriosis, uterine contractions, vascular malformations, leiomyomas, and cancer. Certain techniques such as low-frequency, coronal reconstructions, 3-D ultrasound, cine-clips, color Doppler, and saline infusion sonohysterography (SIS) can be used to differentiate between these entities.

MRI

Characteristic findings on MRI parallel the same features seen on ultrasound:

  • On T2-weighted imaging, uterine enlargement characterized by ill-defined, low-signal-intensity regions within the junctional zone is reflective of smooth muscle hyperplasia (junctional zone thicker than 12mm is generally accepted as diagnostic)
  • T2 hyperintense myometrial cysts reflecting regions of ectopic endometrial tissue (can also have increased intrinsic T1 signal or increased susceptibility in hemorrhagic foci)
  • Contrast enhancement is generally not reliable for assessment of vascularity as compared to a color Doppler ultrasound
  • Similar to ultrasound, a variety of mimics ranging from co-existing gynecologic pathologies to physiologic variants exist. Susceptibility weighted imaging, diffusion-weighted imaging, MR spectroscopy, cine MR imaging, and increased 3T field strength are all problem-solving strategies.
  • It is important to obtain the MRI in the late proliferative or secretory phase (days 7 to 28) due to the decreased signal of normal myometrium during the early proliferative phase (days 1 to 6).

Transvaginal ultrasonography

  • Transvaginal ultrasound of the uterus, showing the endometrium as a hyperechoic (brighter) area in the middle, with linear striations extending upwards from it.
  • Transvaginal ultrasonography is a cheap and readily available imaging test that is typically used early during the evaluation of gynecologic symptoms.[rx] Ultrasound imaging, like MRI, does not use radiation and is safe for the examination of the pelvis and female reproductive organs.[rx] Overall, it is estimated that transvaginal ultrasonography has a sensitivity of 79% and specificity of 85% for the detection of adenomyosis.[rx]

Common transvaginal ultrasound findings in patients with adenomyosis include the following:[rx][rx][rx]

  • globular, enlarged, and/or asymmetric uterus
  • abnormally dense or especially varied density within the myometrium
  • myometrial cysts – pockets of fluid within the smooth muscle of the uterus
  • linear, acoustic shadowing without the presence of a uterine fibroid
  • echogenic linear striations – bright lines or stripes
  • anterior/posterior wall asymmetry
  • the diffuse spread of small vessels within the myometrium
  • Lack of contour abnormality
  • Absence of mass effect
  • Ill-defined margins between a normal and abnormal myometrium

Others Study

  • The power Doppler or Doppler ultrasonography function – can be used during transvaginal ultrasonography to help differentiate adenomyomas from uterine fibroids.[rx][rx][rx] This is because uterine fibroids typically have blood vessels circling the fibroid’s capsule. In contrast, adenomyomas are characterized by widespread blood vessels within the lesion.[rx] Doppler ultrasonography also serves to differentiate the static fluid within myometrial cysts from flowing blood within vessels.[rx]
  • The junction zone (JZ) – or a small distinct hormone-dependent region at the endometrial-myometrial interface, may be assessed by three-dimensional transvaginal ultrasound (3D TVUS) and MRI. Features of adenomyosis are disruption, thickening, enlargement or invasion of the junctional zone.[rx]
  • Sagittal MRI of a woman’s pelvis – showing a uterus with adenomyosis in the posterior wall. Gross enlargement of the posterior wall is noted, with many foci of hyperintensity.
  • Shear Wave Elastography – A recent study also showed that using Aixplorer (Supersonic Imagine, France) scanner with the application of shear wave elastography during transvaginal scanning may improve the diagnostic accuracy of adenomyosis [rx]. This study found that adenomyosis was associated with a significant increase of the myometrial stiffness estimated with shear wave elastography. Further studies are required to verify the clinical usefulness of such an approach.
  • Hysterosalpingography – Hysterosalpingography is seldom used to diagnose adenomyosis. However, in patients undergoing infertility assessment, the occasional finding of speculations measuring 1–4 mm in length, arising from the endometrium towards the myometrium, or a uterus with the “tuba erecta” finding may be suggestive of adenomyosis [rx].
  • Hysteroscopy – Several hysteroscopic appearances have been found to be associated with adenomyosis, including irregular endometrium with endometrial defects or superficial openings, hypervascularization, strawberry pattern, or cystic hemorrhagic lesions [rx]. Nevertheless, there is limited data available on the diagnostic accuracy of these various features.
  • Hysteroscopic and Laparoscopic Myometrial Biopsy – The study found that the depth of adenomyosis was correlated with the severity of menorrhagia. Of the 90 patients studied, 50 patients had normal hysteroscopy in which 55% of them had significant adenomyosis (greater than 1 mm) when compared to controls (0.8 mm).
  • Laparoscopic Myometrial Biopsy – In a prospective, nonrandomized study conducted by Jeng et al. [rx] evaluating 100 patients with clinical signs and symptoms strongly suggestive of adenomyosis, the sensitivity of myometrial biopsy were 98% and the specificity 100%; the positive predictive value was 100% and the negative predictive value 80%, which were superior to those of transvaginal sonography, serum CA-125 determination, or the combination of both. The group suggested that a laparoscopy-guided myometrial biopsy is a valuable tool in the diagnosis of diffuse adenomyosis in women presenting with infertility, dysmenorrhea, or chronic pelvic pain.
Important features in the diagnosis of myoma and adenomyosis FIGO (International Federation of Gynaecology and Obstetrics).
Feature Typical myoma Adenomyosis
The serosal contour of the uterus Lobulated or regular Globally enlarged uterus
Definition of lesion Well-defined Ill-defined in diffuse adenomyosis
(Maybe well-defined in adenomyoma)
The symmetry of uterine wall Asymmetrical in presence of a well-defined lesion Myometrial anteroposterior asymmetry
Lesion Well-defined outline Round/oval/lobulated
Smooth contour
Hypo/hyperechogenic rim
Edge/internal shadow
Uniform (hypo or hyperechogenic)
Non-uniform (mixed echogenicity)
Circumferential flow
Ill-defined outline
Ill-defined shape
Irregular/ill-defined contour
No rim
No edge shadow, fan-shaped shadowing
Non-uniform (mixed echogenicity)
Cysts, hyperechogenic islands
Subendometrial lines and buds
Translesional flow
Junctional zone (JZ) JZ not thickened (regular or not visible)
Interrupted JZ in areas with lesions types (1-3)
Thickened (irregular or ill-defined)
Interrupted JZ (even in absence of localized lesions)

Treatment of Adenomyosis

Adenomyosis can only be cured definitively with surgical removal of the uterus. As adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. For women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding.


Medications

  • NSAIDs – Nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, are commonly used in conjunction with other therapies for pain relief. NSAIDs inhibit the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase. Prostaglandins have been shown to be primarily responsible for dysmenorrhea or the cramping pelvic pain associated with menses.
  • Analgesic – Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the cyclooxygenase (COX-1 and COX-2) and decreasing the production of prostaglandins. NSAIDs have been proved to be effective in the treatment of primary dysmenorrhea by Gambone et al. [rx]. It is usually the first-line treatment for symptomatic pain relief for adenomyosis.
  • Oral Contraceptive Pills (OCPs) Combined oral contraceptive pills work by inhibiting ovulation by suppressing the release of gonadotropins. Many studies have shown that they are effective in the treatment of dysmenorrhea. A prospective observational trial showed that continuous low-dose OCP was more effective than cyclical low-dose OCP in controlling symptoms in patients after surgical treatment for endometriosis [rx].
  • Danazol  Danazol is an isoxazole derivative of 12 alpha-ethinyl testosterone. It causes a hypogonadal state and thus is widely used for the treatment of endometriosis and abnormal uterine bleeding [rx]. However, data on its use in adenomyosis remains limited. This may be due to its unwanted adverse effects after systemic treatment.
  • Dienogest – Dienogest is a selective synthetic oral progestin that combines the pharmacological properties of 17-alpha-progesterone and 19 nor-progesterone with a pronounced local effect on endometrial tissue. Dienogest has been shown to be effective in the treatment of endometriosis-associated pelvic pain. A prospective clinical trial has shown dienogest to be a valuable alternative to depot triptorelin acetate for the treatment of premenopausal pelvic pains in women with uterine adenomyosis. [rx]
  • Levonorgestrel-Releasing Intrauterine Device (LNG-IUD) – LNG-IUD is an intrauterine device, which releases 20 micrograms of levonorgestrel per day. It has been shown to be an effective treatment for abnormal uterine bleeding. LNG-IUD acts locally and causes decidualization of the endometrium and adenomyotic deposits. LNG-IUD alleviates dysmenorrhea by improving uterine contractility and reducing local prostaglandin production within the endometrium. LNG-IUD appears to be an effective method in relieving dysmenorrhea associated with adenomyosis [rx] and more effective than the combined OC pill [rx], improved the quality of life [rx], and appears to be a promising alternative treatment to hysterectomy.
  • LNG-IUD – may be used in conjunction with other treatment modalities such as GnRH analog [rx] or transcervical resection of the endometrium (TCRE) [rx]. In the latter study, it was found that TCRE combined with LNG-IUD was more effective in reducing menstrual flow compared with the LNG-IUD alone although there was no significant difference in the amount of pain reduction between the two treatment strategies.
  • GnRH Agonists  GnRH agonists are effective in alleviating dysmenorrhea and relieving menorrhagia associated with adenomyosis [rx]. However, due to the undesirable climacteric side effects and risk of osteoporosis, treatment with GnRH agonists is usually restricted to a short duration of 3–6 months although the duration of use may be extended if add-back estrogen therapy is employed [rx]. Discontinuation of treatment usually leads to regrowth of the lesions and recurrence of symptoms.
  • Selective Estrogen Receptor Modulator (SERM) – Selective estrogen receptor modulators like tamoxifen or raloxifene have been tried in the treatment of endometriosis [rx] based on observations that SERMs may reduce endometriosis lesion in mouse [rx]; however, their value in the treatment of adenomyoma has not been formally explored.
  • Aromatase Inhibitors  Like endometriosis, adenomyotic deposits are estrogen-dependent. Aromatase inhibitors inhibit the conversion of estrogen from androgens, thereby lowering the synthesis of estrogen. A prospective randomized controlled study found that the efficacy of aromatase inhibitors (letrozole 2.5 mg/day) in reducing the volume of adenomyoma as well as improving adenomyosis symptoms was similar to that of GnRH agonists (goserelin 3.6 mg/month) [rx] [rx].
  • Ulipristal Acetate  Ulipristal acetate (UPA) is a potent selective progesterone receptor modulator. There is good evidence to suggest that it can be used to shrink fibroid and control menorrhagia [rx, rx]. It is possible that it may be similarly effective in the treatment of adenomyoma but literature data is lacking.
  • Antiplatelet Therapy – There is new evidence to suggest the role of antiplatelet therapy in treating adenomyosis. Emerging evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Adenomyotic lesions are thought to have similar pathogenesis to that of endometriosis. A recent study in mice suggests that antiplatelet treatment may suppress myometrial infiltration, improve generalized hyperalgesia, and reduce uterine hyperactivity [rx].
  • Uterine Artery Embolization – Uterine artery embolization (UAE) has been used to treat symptomatic fibroids since the 1990s. There is increasing evidence to suggest that it is also effective in the treatment of the management of adenomyosis. [rx][rx].
  • High-Intensity Focused Ultrasound – High intensity focused ultrasound (HIFU) is another nonsurgical treatment for uterine fibroids that focuses high-intensity ultrasound on the target lesion causing coagulative necrosis and shrinkage of the lesion. Both MRI and USG can be used for guidance for the procedure. MRI has better real-time thermal mapping during the HIFU treatment. [rx, rx] [rx].
  • Endomyometrial Ablation or Resection – There is a limited report on the use of laparoscopic or hysteroscopic endometrial in treating adenomyosis in the literature. The success rate of myometrial electrocoagulation ranges from 55 to 70% as reported [rx]. [rx]MRI treated with laparoscopic bipolar coagulation, having significant reduction or the resolution of dysmenorrhea or heavy menstrual bleeding.
  • GnRH Analogue Therapy before In Vitro Fertilization – Several studies have shown that pretreatment with GnRH analog before IVF treatment improved pregnancy outcome. Zhou et al. [rx] analyzed the clinical efficacy of leuprorelin acetate in the treatment of uterine adenomyosis with infertility. They found that, after 2–6 months of leuprorelin acetate therapy, the mean uterine volume was significantly reduced from 180 ± 73 cm3 to 86 ± 67 cm3, leading to an improvement in embryo implantation and clinical pregnancy rates.
  • Stimulation Protocol – In women without pre-IVF GnRH analog therapy as described above, a long GnRH analog protocol should be considered as it helps to induce decidualization of the adenomyotic deposits rendering the disease inactive. Tao et al. [rx] showed that GnRH antagonist protocol appears to be inferior to GnRH agonist long protocol cycle, and the latter appeared to be associated with increased pregnancy and decreased miscarriage rates.
  • Two-Staged In Vitro Fertilization – In women with adenomyosis, a two-staged in vitro fertilization could be considered. Patients can undergo ovarian stimulation, oocyte retrieval, and fertilization followed by frozen-thawed embryo transfer (FET) at a later stage. Prior to the FET, GnRH analog suppression therapy for 3 months or so leads to shrinkage of the adenomyosis. FET in the first HRT cycle following GnRH analog suppression therapy, before the adenomyosis lesion regrows to its pretreatment size and exerts its adverse impact on implantation, may improve the result.
  • Mock Embryo Transfer – Performing a mock embryo transfer is desirable in women with adenomyosis, as it may help to assess the uterine cavity length and position, choose the correct transfer catheter, and alert the clinicians any extra precautions (e.g., use of tenaculum or cervical dilatation). Mock embryo transfer is particularly desirable in those with an enlarged uterus or distorted uterine cavity.
  • Single Embryo Transfer – Adenomyosis has been reported to be associated with an increased incidence of preterm delivery, preeclampsia, and second-trimester miscarriage when compared with the control group [rx]. Consequently, multiple pregnancies should be avoided and so single embryo transfer should be advised. Women who had adenomyomectomy prior to IVF should also be advised to have SET to avoid multiple pregnancies with a view to minimizing the risk of scar rupture.
  • HRT Protocol in Frozen-Thawed Embryo Transfer (FET) Cycle – GnRH agonist pretreatment to suppress the pituitary ovarian axis prior to hormone replacement therapy to prepare the endometrium in FET cycles appeared to improve the outcome compared with hormone replacement therapy without downregulation. In a study including 339 patients with adenomyosis, 194 received long-term GnRH agonist plus HRT (downregulation + HRT) and 145 with HRT alone. [rx].
  • Uterine Contractility and Atosiban Therapy – Several functional studies showed that excessive uterine contractility (>5 contractions per minute) has been demonstrated in approximately 30% of patients undergoing embryo transfer and this may have a significant adverse impact on subsequent embryo implantation and clinical pregnancy rates [rx]. The incidence of abnormal contractility appeared to be higher in women with adenomyosis [rx] which may in part explain the higher incidence of reproductive failure observed in this group of women. Recurrent Implantation Failure – Recurrent implantation failure is diagnosed when there is a failure to achieve a clinical pregnancy after the transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years [rx]. It is known that adenomyosis is associated with recurrent implantation failure [rx]. Women with recurrent implantation failure should be offered a 3D scan or MRI to establish if there is adenomyosis; if adenomyosis is present, the above management strategies should be adopted to improve the outcome.

Hormones and hormone modulators

  • Levonorgestrel-releasing intrauterine devices or hormonal IUDs – such as the Mirena, are an effective treatment for adenomyosis.[rx] They reduce symptoms by causing decidualization of the endometrium, reducing or eliminating menstrual flow.[rx] Additionally, by helping downregulate estrogen receptors, hormonal IUDs shrink the clusters of endometrial tissue within the myometrium. This leads to reduced menstrual blood flow, helps the uterus contract more properly, and helps to reduce menstrual pain. The use of hormonal IUDs in patients with adenomyosis has been proven to reduce menstrual bleeding, improve anemia and iron levels, reduce pain, and even result in an improvement of adenomyosis with a smaller uterus on medical imaging.[rx][rx] 
  • Oral contraceptives  – reduce the menstrual pain and bleeding associated with adenomyosis. This may require taking continuous hormone therapy to reduce or eliminating menstrual flow. Oral contraceptives may even lead to short-term regression of adenomyosis.
  • Progesterone or Progestins – Progesterone counteracts estrogen and inhibits the growth of endometrial tissue. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.
  • Gonadotropin-releasing hormone (GnRH) – agonists and danazol have been tried in order to relieve adenomyosis related symptoms and show some effect, but the studies are few, mainly with a retrospective study design and have small sample sizes.[rx] Long-time use of GnRH-analogues is often associated with heavy side effects, loss of bone density and increased risk of cardiovascular events, and therefore not feasible for young women. Furthermore, all present treatment options are irrelevant options for women trying to conceive. Exogenous progestogenic treatments have been found to be ineffective.[rx] In IVF-settings long down-regulation prior to IVF might have a positive effect on pregnancy rates.[rx]


Surgery

Uterine-sparing procedures
  • Uterine artery embolization (UAE) – In this minimally-invasive procedure, doctors intentionally block two large arteries that supply the uterus, called the uterine arteries. This is performed in order to dramatically reduce the blood supply to the uterus. By doing so, there is insufficient blood and thus oxygen present for the adenomyosis to develop and spread.  57-75% of women who undergo UAE for adenomyosis typically report long-term improvement in their menstrual pain and bleeding. However, there is a recurrence rate of symptoms in 35% of women following a UAE. 
  • Myometrium or adenomyoma resection – In this procedure, surgeons remove a focal consolidation of adenomyosis known as an adenomyoma. To be successful this procedure requires that the adenomyosis is relatively focally isolated and with a minimal diffuse spread. Unfortunately, adenomyosis is commonly diffuse and the operation is successful only 50% of the time. The procedure is performed with either a laparoscope or hysteroscope.[rx]
  • Myometrial electrocoagulation[rx]
  • Myometrial reduction[tx]
  • MRI-guided focused ultrasound surgery[rx]

Endometrial ablation and resection

  • Endometrial ablation techniques –  are only for women who have completed their childbearing. The techniques either include physical resection and removal of the endometrium through a hysteroscope or focus on ablating or killing the endometrial layer of the uterus without its immediate removal. Endometrial ablation and resection techniques are most appropriate for shallow adenomyosis. The efficacy of the procedures is reduced if the adenomyosis is too widespread or deep. Furthermore, deep adenomyosis may become trapped behind a scarred region that was ablated, leading to further bleeding and pain. Endometrial resection is also limited to relatively shallow adenomyosis as significant bleeding may result from damage to large arteries that are present 5 mm deep within the myometrium.[rx]
  • Non-hysteroscopic procedures – These techniques do not require a hysteroscope are relatively fast, and many can be performed as an outpatient procedure.
  • Thermal balloon – Using a thin expanding balloon placed within the uterus, providers can introduce heated fluid and ablate the endometrium. This procedure has been shown to result in amenorrhea or complete cessation of menstrual bleeding for 12 months in 23% of patients. 16% of patients eventually experience treatment failure with pain or bleeding requiring additional treatments or a hysterectomy. [9]
  • Cryo-endometrial ablation (CEA) – A form of cryotherapy whereby using a small probe, providers can directly apply sub-zero temperatures within the uterus to freeze and ablate the endometrium.
  • Circulating Hot Water – Heated water directly introduced into the uterus is used to thermally ablate the endometrium.
  • Microwave ablation – Using a small probe introduced into the uterus, a provider uses microwave energy to ablate the endometrium.
  • High-energy radiofrequency ablation – Using a small expandable mesh placed within the uterus, providers use high-energy radio waves to ablate the endometrium.
  • Hysteroscopic procedures: These techniques all require the use of a hysteroscope to perform.
    • Wire-loop resection – Under direct visualization through a hysteroscope, a wire loop instrument charged with an electric current permits a provider to carefully remove the endometrium in strips.
    • Laser ablation – Under direct visualization through a hysteroscope, lasers are used to vaporize and ablate the endometrium.
    • Rollerball ablation – Under direct visualization through a hysteroscope, a metallic ball on the end of a probe is charged with electricity and rolled across the surface of the endometrium. This has been shown to have a coagulative effect to the depth of 2–3 mm into the myometrium. This destroys the endometrium and the nearby growth of dysfunctional smooth muscle. Deeper adenomyosis escapes this coagulative effect.[9]

References

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Water Based Vacuum Pump Work For Penis Enlargement

Water-Based Vacuum Pump Work For Penis Enlargement/Penis Enlargement or male enhancement is any technique aimed to increase the size of a human penis? Some methods aim to increase total length, others the shaft’s girth, and yet others the glans size. Techniques include surgery, supplements, ointments, patches, and physical methods like pumping, jelqing, and traction.

Inflatable penile prosthetic (IPP) devices have been available and used for more than four decades. Often times, medical conditions causing erectile dysfunction also cause penis shortening, causing the decreased patient quality of life. To identify and review all available penis lengthening procedures that can be performed at the time of IPP insertion. An extensive, systematic literature review was performed using PubMed searching for key terms penis lengthening, inflatable penis prosthesis, penile girth, clitoroplasty, glans augmentation, and penis enhancement; all articles with subjective or objective penis length outcomes were reviewed.

Anatomy of Penis Enlargement

Lateral cross-section of the penis.

Water-Based Vacuum Pump Work For Penis Enlargement

Parts

  • The root of the penis (radix): It is the attached part, consisting of the bulb of the penis in the middle and the crus of the penis, one on either side of the bulb. It lies within the superficial perineal pouch.
  • Body of the penis (corpus): It has two surfaces: dorsal (posterosuperior in the erect penis), and ventral or urethral (facing downwards and backward in the flaccid penis). The ventral surface is marked by a groove in a lateral direction.
  • Epithelium of the penis consists of the shaft skin, the foreskin, and the preputial mucosa on the inside of the foreskin and covering the glans penis. The epithelium is not attached to the underlying shaft so it is free to glide to and fro.[rx]

Structure

The human penis is made up of three columns of tissue –  two corpora cavernosa lie next to each other on the dorsal side and one corpus spongiosum lies between them on the ventral side.[rx]

The enlarged and bulbous-shaped end of the corpus spongiosum forms the glans penis with two specific types of sinusoids, which supports the foreskin, or prepuce, a loose fold of skin that in adults can retract to expose the glans.[rx] The area on the underside of the penis, where the foreskin is attached, is called the frenum, or frenulum. The rounded base of the glans is called the corona. The perineal raphe is the noticeable line along the underside of the penis.

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Comparison of mean body weight, mean testicular weight, mean plasma testosterone and mean IGF-1 among experimental groups.

C MP G Testosterone GT
Bodyweight (g, s.d.) 588 (34) 579 (28) 575 (39) 552 (44) 567 (45)
Testis volume (mL, s.d.) 1.36 (0.11) 0.97 (0.05)b 1.26 (0.08)a 0.83 (0.06)ab 1.10 (0.09)a,b
Tibial length (mm) 38.4 (2.6) 36.6 (3.1) 39.1 (2.2) 35.5 (3.3) 36.8 (2.9)
Plasma testosterone (ng/mL, s.d.) 3.72 (1.91)a 0.44 (0.05)b 2.08 (0.51)a 27.5a,b 29.2a,b
Plasma IGF-1 (ng/mL, s.d.) 1445 (155) 1432 (232) 1704 (116)a,b 628 (206)a,b 1197 (126)a,b

denotes statistical significance (P < 0.05) compared to MP; denotes statistical significance (P < 0.05) compared to C.

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Disorders of Penis Enlargement

Water-Based Vacuum Pump Work For Penis Enlargement

  • Paraphimosis – is an inability to move the foreskin forward over the glans. It can result from fluid trapped in a foreskin left retracted, perhaps following a medical procedure, or accumulation of fluid in the foreskin because of friction during vigorous sexual activity.
  • In Peyronie’s disease – anomalous scar tissue grows in the soft tissue of the penis, causing curvature. Severe cases can be improved by surgical correction.
  • A thrombosis can occur during periods of frequent and prolonged sexual activity – especially fellatio. It is usually harmless and self-corrects within a few weeks.
  • Infection with the herpes virus can occur after sexual contact with an infected carrier –  this may lead to the development of herpes sores.
  • Pudendal nerve entrapment – is a condition characterized by pain on sitting and the loss of penile sensation and orgasm. Occasionally there is a total loss of sensation and orgasm. The pudendal nerve can be damaged by narrow, hard bicycle seats and accidents. This can also occur in the clitoris of females.
  • Penile fracture – can occur if the erect penis is bent excessively. A popping or cracking sound and pain is normally associated with this event. Emergency medical assistance should be obtained as soon as possible. Prompt medical attention lowers the likelihood of permanent penile curvature.
  • In diabetes – peripheral neuropathy can cause tingling in the penile skin and possibly reduced or completely absent sensation. The reduced sensations can lead to injuries for either partner and their absence can make it impossible to have sexual pleasure through stimulation of the penis. Since the problems are caused by permanent nerve damage, preventive treatment through good control of diabetes is the primary treatment. Some limited recovery may be possible through improved diabetes control.
  • Erectile dysfunction is the inability to develop and maintain an erection sufficiently firm for satisfactory sexual performance. Diabetes is a leading cause, as is natural aging. A variety of treatments exist, most notably including the phosphodiesterase type 5 inhibitor drugs (such as sildenafil citrate, marketed as Viagra), which work by vasodilation.
  • Priapism – is a painful and potentially harmful medical condition in which the erect penis does not return to its flaccid state. Priapism lasting over four hours is a medical emergency. The causative mechanisms are poorly understood but involve complex neurological and vascular factors. Potential complications include ischemia, thrombosis, and impotence. In serious cases, the condition may result in gangrene, which may result in amputation. However, that is usually only the case if the organ is broke out and injured because of it. The condition has been associated with a variety of drugs including prostaglandin. Contrary to common knowledge, sildenafil (Viagra) will not cause it.[rx]
  • Lymphangiosclerosis – is a hardened lymph vessel, although it can feel like a hardened, almost calcified or fibrous, vein. It tends not to share the common blue tint with a vein, however. It can be felt as a hardened lump or “vein” even when the penis is flaccid and is even more prominent during an erection. It is considered a benign physical condition. It is fairly common and can follow a particularly vigorous sexual activity for men, and tends to go away if given rest and more gentle care, for example by use of lubricants.
  • Carcinoma of the penis – is rare with a reported rate of 1 person in 100,000 in developed countries. Some sources state that circumcision can protect against this disease, but this notion remains controversial among medical circles.[rx]

Developmental Disorders

Hypospadias
  • Hypospadias is a developmental disorder where the meatus is positioned wrongly at birth. Hypospadias can also occur iatrogenically by the downward pressure of an indwelling urethral catheter.[rx] It is usually corrected by surgery.
  • A micropenis is a very small penis caused by developmental or congenital problems.
  • Diphallia, or penile duplication (PD), is the condition of having two penises. However, this disorder is extremely rare.

Alleged and observed psychological disorders

  • Penis panic (koro in Malaysian/Indonesian) – delusion of shrinkage of the penis and retraction into the body. This appears to be culturally conditioned and largely limited to Ghana, Sudan, China, Japan, Southeast Asia, and West Africa.
  • In April 2008, the Kinshasa Democratic Republic of Congo, West Africa’s ‘Police arrested 14 suspected victims (of penis snatching) and sorcerers accused of using black magic or witchcraft to steal (make disappear) or shrink men’s penises to extort cash for cure, amid a wave of panic. Arrests were made in an effort to avoid bloodshed seen in Ghana a decade before when 12 penis snatchers were beaten to death by mobs.[rx]
  • Penis envy—the contested Freudian belief of all women inherently envying men for having penises.

The technique of Penis Enlargement


Physical Techniques

  • Physical techniques involve extension devices, hanging weights, and vacuum pressure. There is also significant overlap between techniques intended to enlarge the penis and techniques intended to achieve other, related objectives, such as reversing impotence, extending the duration of erections, or enhancing sexual climax.

Pumping

  • Water-based vacuum pump commonly called a “penis pump”, a vacuum erection device, or VED, creates negative pressure that expands and thereby draws blood into the penis.[rx][rx] Medically approved VEDs, which treat erectile dysfunction, limit maximum pressure, whereas the pumps commonly bought by consumers seeking penis enlargement can reach dangerous pressure, damaging penis tissue.[rx]
  • To retain tumescence after breaking the device’s airtight seal, one must constrict the penis’ base, but constriction worn over 30 minutes can permanently damage the penis and cause erectile dysfunction.[rx] Although vacuum therapy can treat erectile dysfunction sufficiently to prevent penis deterioration and shrinkage,[rx] clinical trials have not found it effective for penis enlargement.[rx][rx]


Jelqing

  • Performed on the halfway tumescent penis, jelqing is a manual manipulation of simultaneous squeezing and stroking the shaft from base to corona. Also called “milking”,[rx] the technique has ancient Arab origins.[rx] Despite many anecdotal reports of success, medical evidence is absent.[rx]
  • Journalists have dismissed the method as biologically implausible,[rx] or even impossible, albeit unlikely to seriously damage the penis.[rx] Still, if done excessively or harshly, jelqing could conceivably cause ruptures, scarring, disfigurement, and desensitization.[rx][rx]

Traction

  • Traction is a nonsurgical method to lengthen the penis by employing devices that pull at the glans of the penis for extended periods of time. As of 2013, the majority of research investigating the use of penile traction focuses on treating the curvature and shrinkage of the penis as a result of Peyronie’s disease, although some literature exists on the impact on men with short penises.[rx] Scientific evidence supports some elongation by prolonged traction.[rx]

Jelqing exercises

  • Jelqing is an exercise that some people use to try to naturally increase the size of their penis. It involves using a hand-over-hand rolling motion to move blood to the head of your penis and stretch it. It’s sometimes called “milking.”
  • There aren’t enough medical studies to suggest that jelqing can actually increase your penis size. It’s a fairly safe practice, but it may lead to pain, irritation, or scar tissue formation if you do it too often or aggressively.

Clamps and rings

  • Some people use a clamp or ring to try to stretch and elongate their penis. To use one of these devices, you place it around the base of your penis after you’ve developed an erection. It’s meant to prevent blood from flowing out of your penis.
  • Wearing one of these devices may temporarily enlarge your penis. But wearing it for more than 30 minutes can cut off blood flow and cause damage to your penile tissue.

Diet, Exercise, and Lifestyle

  • The sad truth is that in a significant number of cases, erectile dysfunction is a condition we bring upon ourselves. Even when these things aren’t the outright cause of ED, they’re almost certain to be contributing factors that make your condition worse. This is a big, expansive category that covers a lot of ground, but in a nutshell, here’s what you need to know.
  • Eating lots of leafy greens, whole grains, oysters, watermelon, and blueberries (most any fruit will work, really) will help you give your body all that it needs to improve the quality of your erections while cutting out processed foods, cigarettes and alcohol will provide further benefits. Add in a healthy dose of exercise at least three times per week, and you’re well on your way to better sexual health!

References

Water-Based Vacuum Pump Work For Penis Enlargement

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What Are The Benefits of Riboflavin, Indications

What Are The Benefits of Riboflavin/Riboflavin is an essential human nutrient that is a heat-stable and water-soluble flavin belonging to the vitamin B family? Riboflavin is a precursor of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These coenzymes are of vital importance in normal tissue respiration, pyridoxine activation, tryptophan to niacin conversion, fat, carbohydrate, and protein metabolism, and glutathione reductase-mediated detoxification. Riboflavin may also be involved in maintaining erythrocyte integrity. This vitamin is essential for healthy skin, nails, and hair.

Riboflavin is d-Ribitol in which the hydroxy group at position 5 is substituted by a 7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-aryl moiety. It is a nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables, but the richest natural source is yeast. The free form occurs only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as flavin mononucleotide and flavin-adenine dinucleotide. It has a role as a photosensitizing agent, a metabolite, a B vitamin, a food coloring, an Escherichia coli metabolite, and a mouse metabolite. It is conjugate acid of riboflavin(1-).

Riboflavin is yellow and naturally fluorescent when exposed to ultraviolet light. Moreover, ultraviolet and visible light can rapidly inactivate riboflavin and its derivatives. Because of this sensitivity, lengthy light therapy to treat jaundice in newborns or skin disorders can lead to riboflavin deficiency. The risk of riboflavin loss from exposure to light is the reason why milk is not typically stored in a glass container

Deficiency Symptoms of Riboflavin/vitamin B2

Riboflavin deficiency is also known as ariboflavinosis.

  • Primary riboflavin deficiency happens when the person’s diet is poor in vitamin B2
  • Secondary riboflavin deficiency happens for another reason, maybe because the intestines cannot absorb the vitamin properly, or the body cannot use it, or because it is being excreted too rapidly
  • Angular cheilitis, or cracks at the corners of the mouth
  • Cracked lips
  • Dry skin
  • Nerve damage
  • A sluggish metabolism
  • Mouth or lip sores or cracks
  • Skin inflammation and skin disorders, especially around the nose and face
  • Inflamed mouth and tongue
  • Inflammation of the lining of the mouth
  • Inflammation of the tongue
  • Mouth ulcers
  • Red Lips
  • Sore throat
  • Scrotal dermatitis
  • Fluid in mucous membranes
  • Iron-deficiency anemia
  • Eyes may be sensitive to bright light, and they may be itchy, watery, or bloodshot
  • Weakness or fatigue
  • Change in mood
  • Skin cracking
  • Dermatitis
  • Anemia
  • Throat swelling/soreness
  • Swollen tongue
  • Skin cracking (including cracked corners of the mouth)
  • Dermatitis
  • Blurred vision and itching, watering, sore, or bloodshot eyes
  • Eyes becoming light-sensitive and easily fatigued

Riboflavin deficiency (also called ariboflavinosis) results in stomatitis including painful red tongue with a sore throat, chapped and fissured lips (cheilosis), and inflammation of the corners of the mouth (angular stomatitis). There can be oily scaly skin rashes on the scrotum, vulva, philtrum of the lip, or the nasolabial folds. The eyes can become itchy, watery, bloodshot and sensitive to light. Due to interference with iron absorption, even mild to moderate riboflavin deficiency results in an anemia with normal cell size and normal hemoglobin content (i.e. normochromic normocytic anemia). This is distinct from anemia caused by a deficiency of folic acid (B9) or cyanocobalamin (B12), which causes anemia with large blood cells (megaloblastic anemia). Deficiency of riboflavin during pregnancy can result in birth defects including congenital heart defects and limb deformities.

The stomatitis symptoms are similar to those seen in pellagra, which is caused by niacin (B3) deficiency. Therefore, riboflavin deficiency is sometimes called “pellagra sine pellagra” (pellagra without pellagra), because it causes stomatitis but not widespread peripheral skin lesions characteristic of niacin deficiency. Riboflavin deficiency prolongs recovery from malaria, despite preventing the growth of Plasmodium (the malaria parasite).

Daily Requirement of Riboflavin/vitamin B2

Intake recommendations for riboflavin and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include:

  • Recommended Dietary Allowance (RDA) –  Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
  • Adequate Intake (AI) – Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
  • Estimated Average Requirement (EAR) – Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
  • Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

Table 1 lists the current RDA for riboflavin. For infants from birth to 12 months, the FNB established an AI for riboflavin that is equivalent to the mean intake of riboflavin in healthy, breastfed infants.

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Recommended Dietary Allowances (RDAs) for Riboflavin 
Age Male Female Pregnancy Lactation
Birth to 6 months* 0.3 mg 0.3 mg
7–12 months* 0.4 mg 0.4 mg
1–3 years 0.5 mg 0.5 mg
4–8 years 0.6 mg 0.6 mg
9–13 years 0.9 mg 0.9 mg
14–18 years 1.3 mg 1.0 mg 1.4 mg 1.6 mg
19-50 years 1.3 mg 1.1 mg 1.4 mg 1.6 mg
51+ years 1.3 mg 1.1 mg

About 95% of riboflavin in the form of FAD or FMN from food is bioavailable up to a maximum of about 27 mg of riboflavin per meal or dose. The bioavailability of free riboflavin is similar to that of FAD and FMN. Because riboflavin is soluble in water, about twice as much riboflavin content is lost in cooking water when foods are boiled as when they are prepared in other ways, such as by steaming or microwaving.

 Selected Food Sources of Riboflavin 
Food Milligrams
(mg) per
serving
Percent
DV*
Beef liver, pan-fried, 3 ounces 2.9 171
Breakfast cereals, fortified with 100% of the DV for riboflavin, 1 serving 1.7 100
Oats, instant, fortified, cooked with water, 1 cup 1.1 65
Yogurt, plain, fat-free, 1 cup 0.6 35
Milk, 2% fat, 1 cup 0.5 29
Beef, tenderloin steak, boneless, trimmed of fat, grilled, 3 ounces 0.4 24
Clams, mixed species, cooked, moist heat, 3 ounces 0.4 24
Mushrooms, portabella, sliced, grilled, ½ cup 0.3 18
Almonds, dry roasted, 1 ounce 0.3 18
Cheese, Swiss, 3 ounces 0.3 18
Rotisserie chicken, breast meat only, 3 ounces 0.2 12
Egg, whole, scrambled, 1 large 0.2 12
Quinoa, cooked, 1 cup 0.2 12
Bagel, plain, enriched, 1 medium (3½”–4” diameter) 0.2 12
Salmon, pink, canned, 3 ounces 0.2 12
Spinach, raw, 1 cup 0.1 6
Apple, with skin, 1 large 0.1 6
Kidney beans, canned, 1 cup 0.1 6
Macaroni, elbow-shaped, whole wheat, cooked, 1 cup 0.1 6
Bread, whole wheat, 1 slice 0.1 6
Cod, Atlantic, cooked, dry heat, 3 ounces 0.1 6
Sunflower seeds, toasted, 1 ounce 0.1 6
Tomatoes, crushed, canned, ½ cup 0.1 6
Rice, white, enriched, long-grain, cooked, ½ cup 0.1 6
Rice, brown, long-grain, cooked, ½ cup 0 0

DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for riboflavin is 1.7 mg for adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.

The U.S. Department of Agriculture’s (USDA’s) National Nutrient Database for Standard Reference website lists the nutrient content of many foods and provides a comprehensive list of foods containing riboflavin arranged by nutrient content and food name.

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Natural Food Source

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United States
Age group (years) RDA for riboflavin (mg/d) Tolerable upper intake level
Infants 0–6 months 0.3* ND
Infants 6–12 months 0.4*
1–3 0.5
4–8 0.6
9–13 0.9
Females 14–18 1.0
Males 14–18 1.3
Females 19+ 1.1
Males 19+ 1.3
Pregnant females 14–50 1.4
Lactating females 14–50 1.6
European Food Safety Authority
Age group (years) Adequate Intake of riboflavin (mg/d) Tolerable upper limit
7–11 months 0.4 ND
1–3 0.6
4–6 0.7
7–10 1.0
11–14 1.4
15–17 1.6
18+
Australia and New Zealand
Age group (years) Adequate Intake of riboflavin (mg/d) Upper level of intake
0–6 months 0.3* ND
7–12 months 0.4*
1–3 0.5
4–8 0.6
9–13 0.9
Females 14–70 1.1
Males 14–70 1.3
Females >70 1.3
Males >70 1.6
Pregnant females 14–50 1.4
Lactating females 14–50 1.6
* Adequate intake for infants, no RDA/RDI yet established

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Uses & Health Benefit

  • Prevent riboflavin deficiency and to treat ariboflavinosis – Whenever possible, poor dietary habits should be corrected, and many clinicians recommend administration of multivitamin preparations containing riboflavin in patients with vitamin deficiencies since poor dietary habits often result in concurrent deficiencies.
  • Riboflavin – may be useful in treating microcytic anemia that occurs in patients with a familial metabolic disease associated with splenomegaly and glutathione reductase deficiency. Although riboflavin has not been shown by well-controlled trials to have any therapeutic value, the drug also has been used for the management of acne, congenital methemoglobinemia, muscle cramps, and burning feet syndrome.
  • People undergoing hemodialysis – or peritoneal dialysis and those with severe malabsorption are likely to require extra riboflavin. Women who are carrying more than one fetus or breastfeeding more than one infant are also likely to require more riboflavin. It is possible that individuals who are ordinarily extremely physically active may also have increased needs for riboflavin.
  • Preventing and treating low riboflavin levels (riboflavin deficiency) – In adults and children who have too little riboflavin in their body, taking riboflavin by mouth can increase levels of riboflavin in the body.
  • Cataracts – People who eat more riboflavin as part of their diet seem to have a lower risk of developing cataracts. Also, taking supplements containing riboflavin plus niacin seems to help prevent cataracts.
  • High amounts of homocysteine in the blood (hyperhomocysteinemia) – Taking riboflavin by mouth for 12 weeks decrease levels of homocysteine by up to 40% in some people. Also, taking riboflavin along with folic acid and pyridoxine seems to lower homocysteine levels by 26% in people with high homocysteine levels caused by drugs that are used to prevent seizures.
  • Migraine headaches – Taking high-dose riboflavin by mouth seems to reduce the number of migraine headache attacks, by about 2 attacks per month. Taking riboflavin in combination with other vitamin and minerals seems to also reduce the amount of pain experienced during a migraine.

Possibly Ineffective for

  • Stomach cancer – Taking riboflavin along with niacin does help prevent gastric cancer.
  • Malnutrition caused by too little protein in the diet (kwashiorkor) – Some research suggests that taking riboflavin, vitamin E, selenium, and N-acetyl cysteine by mouth does not reduce fluid, increase height or weight, or decrease infections in children at risk for kwashiorkor.
  • Lung cancer -Taking riboflavin by mouth along with niacin does not help prevent lung cancer.
  • Malaria – Taking riboflavin along with iron, thiamine, and vitamin C by mouth does not reduce the number or seriousness of malaria infections in children at risk of being exposed to malaria.
  • High blood pressure during pregnancy (pre-eclampsia) – In women that are 4 months pregnant, starting to take riboflavin by mouth does reduce the risk of pre-eclampsia during pregnancy.
  •  Early research shows that taking riboflavin by mouth might be helpful for treating lactic acidosis caused by drugs called nucleoside analog reverse transcriptase inhibitors (NRTIs) in patients with acquired immunodeficiency syndrome (AIDS).
  • Increasing intake of riboflavin from dietary and supplement sources, along with thiamine, folic acid, and vitamin B12, might decrease the risk of developing cervical cancer.
  • Research on the effects of riboflavin for preventing esophageal cancer is conflicting. Some research shows that taking riboflavin by mouth may decrease the risk of getting esophageal cancer, while other research shows that it has no effect.
  • Early research shows that taking riboflavin by mouth in certain patients at higher risk of high blood pressure due to genetic differences may lower blood pressure when used in addition to prescribed blood pressure medications.
  • Early research shows that taking riboflavin and niacin by mouth might reduce the risk of liver cancer in people less than 55 years old. However, it does not seem to reduce the risk of liver cancer in older people.
  • Early research shows that taking riboflavin by mouth for 6 months does not improve disability in patients with multiple sclerosis.
  • Early research shows that low levels of riboflavin in the blood are linked with an increased risk of oral leukoplakia. However, taking riboflavin supplements by mouth for 20 months does not seem to prevent or treat oral leukoplakia.
  • Early research shows that taking riboflavin, iron, and folic acid by mouth does not increase iron levels in pregnant women more than taking just iron and folic acid.
  • Early research shows that taking riboflavin by mouth for 8 weeks increases iron levels in people with low iron levels due to sickle cell disease.
  • Early research shows that taking riboflavin and niacin by mouth does not prevent stroke-related death in people at risk for stroke.
  • Acne.
  • Aging.
  • Boosting the immune system.
  • Canker sores.
  • Maintaining healthy skin and hair.
  • Memory loss including Alzheimer’s disease.
  • Muscle cramps.

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Drug Warnings

Riboflavin may cause urine to have a more yellow color than normal, especially if large doses are taken. This is to be expected and is no cause for alarm. Usually, however, riboflavin does not cause any side effects.

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References

 

http://rxharun.com/rx-dietary-supplements-beverages/health-benefits-vitamin-e-side-effects-dosage/?php


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How Do I Treat Tennis Elbow at Home, Exercise

How Do I Treat Tennis Elbow at Home/Tennis elbow is also known as lateral epicondylalgia (LE) and often referred to as epicondylitis or tendinopathy clinically, has complex underlying pathophysiology which is not well understood but is characterized by uncomplicated signs of localized pain over the lateral epicondyle which is made worse with resisted wrist extension and grip. The term epicondylitis has recently been considered a misnomer because of a lack of inflammatory signs.  The pain may also extend into the back of the forearm and grip strength may be weak.[rx][rx] Onset of symptoms is generally gradual.[rx] Golfer’s elbow is a similar condition that affects the inside of the elbow.[rx]

Lateral epicondylitis also is known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature.

Tennis-Elbow-

 

Tennis Elbow 

Obviously, this condition earned its name because whacking tennis balls around a lot was the original main cause, but these days it is much more commonly caused by computer usage. And heavy computer users outnumber serious tennis players at least a thousand to one.

Tennis-Elbow

Today, this condition would be better-called computer elbow.

  • (1) Electrohydraulic – electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic lateral epicondylitis (CLE) of the elbow (elbow tendonitis or tennis elbow). These waves may help to accelerate the healing process via an unknown mechanism.
  • (2) Results from randomized – controlled trials have been conflicting. Half of the studies showed statistically significant improvement in pain in the treatment group, and half of the studies had data showing no benefit over placebo for any measured outcomes.
  • (3) Limited evidence shows that ESWT – is cheaper than arthroscopic surgery, open surgery, and other conservative therapies, such as steroid infiltrations and physiotherapy, that continue for more than six weeks.
  • (4) The lack of convincing evidence – regarding its effectiveness does not support the use of ESWT for CLE.

Causes of Tennis Elbow

Tennis-Elbow-