Vitamin K is a group of structurally similar, fat-soluble vitamins that the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation (K from Koagulation, Danish for “coagulation”) and which the body also needs for controlling binding of calcium in bones and other tissues. The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise. Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. Preliminary clinical research indicates that deficiency of vitamin K may weaken bones, potentially leading to osteoporosis, and may promote calcification of arteries and other soft tissues.
Chemically, the vitamin K family comprises 2-methyl-1,4-naphthoquinone (3-) derivatives. Vitamin K includes two natural vitamers: vitamin K1 and vitamin K2. Vitamin K2, in turn, consists of a number of related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms.
Phylloquinone is present primarily in green leafy vegetables and is the main dietary form of vitamin K . Menaquinones, which are predominantly of bacterial origin, are present in modest amounts in various animal-based and fermented foods . Almost all menaquinones, in particular the long-chain menaquinones, are also produced by bacteria in the human gut . MK-4 is unique in that it is produced by the body from phylloquinone via a conversion process that does not involve bacterial action .
Types of Vitamin K
Now that we’ve established what Vitamin K is, we’re going start getting more specific. The food sources, actions and benefits of the Vitamin K variations are different, so it’s important to distinguish between them.
There are three types of Vitamin K
- Vitamin K1: Phylloquinones
- Vitamin K2 MK-4: Menaquinone-4
- Vitamin K2 MK-7: Menaquinone-7
Phylloquinones or K1
Vitamin K1 are called phylloquinones or phytonadiones (although phytonadione or phytomenadione are often used to describe synthetic K1 given as a treatment). It has a monounsaturated tail with four carbon groups. Vitamin K1 prevents bleeding through the blood clotting (coagulation) cascade. The most well-known function of Vitamin K1 in animals is as a blood clotting agent in the liver, where it forms blood clotting factors such as prothrombin (II), VII, IX and X.
Menaquinones or K2
The Vitamin K2 group are menaquinones (MK), which have polyunsaturated tails. The tails can be of 15 different lengths, which is indicated by the following number. MK-4, for instance, has a tail of four carbon groups while MK-7 has – you’ve guessed it – a tail of seven carbon groups. There are up to fifteen types of menaquinones (eg. MK-9 Mk-11), but less is known about these. So we’ll stick to MK-4 and MK-7. Both MK-4 and MK-7 activate a set of proteins called GLA proteins. The reaction is called carboxylation. We say that vitamin K2 ‘carboxylates’ proteins.
The two proteins are
Osteocalcin (Bone-GLA protein) – Responsible for laying down calcium in bones and teeth.
Matrix-GLA protein (Matrix-GLA protein) – Responsible for mopping up calcium from soft tissues including the heart, kidneys, and brain.The roles of these Vitamin-K2-dependent proteins are explored in Part III of this series.
Vitamin K1 & MK-7 -> MK-4 – The conversion of K1 to K2 isn’t well understood. Best evidence suggests you need to obtain Vitamin K2 MK-4 from your diet.
Role and benefits of Vitamin K2 MK-4 – MK-4 is the most readily absorbed in the tissue. It seems to be the most potent or quickly used form of Vitamin K2.After absorption in the intestines, the body positions MK-4s on the outer layers of your blood cholesterols. Vitamin K2 MK-4 is unloaded from blood cholesterols first. It is therefore distributed to the tissues like kidneys, lungs and muscles. Here, it activates matrix-GLA protein to prevent calcium buildup in organs and vessels. Vitamin K2 MK-4 is also most active in regulating genes that may prevent cancer and as an antioxidant in the brain.
Role and benefits of Vitamin K2 MK-7 – Vitamin K2 MK-7 is positioned closer to the center of lipoproteins or blood cholesterols. After MK-4 is cleaved off and used up quickly by the body, MK-7 is then available to be used in one of three ways:
- Delivered to bones
- Delivered to liver (for liver function, with K1)
- Repackaged in the liver to be sent to bones
MK-7 is more readily absorbed into bone. Here, it activates osteocalcin and provides skeletal benefits.
Symptoms of Vitamin K
Symptoms include bruising, petechiae, hematomas, oozing of blood at surgical or puncture sites, stomach pains; risk of massive uncontrolled bleeding; cartilage calcification; and severe malformation of developing bone or deposition of insoluble calcium salts in the walls of arteries. In infants, it can cause some birth defects such as underdeveloped face, nose, bones, and fingers.
Vitamin K is changed to its active form in the liver by the enzyme Vitamin K epoxide reductase. Activated vitamin K is then used to gamma carboxylate (and thus activate) certain enzymes involved in coagulation: Factors II, VII, IX, X, and protein C and protein S. Inability to activate the clotting cascade via these factors leads to the bleeding symptoms mentioned above.Notably, when one examines the lab values in Vitamin K deficiency [see below] the prothrombin time is elevated, but the partial thromboplastin time is normal or only mildly prolonged. This may seem counterintuitive given that the deficiency leads to decreased activity in factors of both the intrinsic pathway (F-IX) which is monitored by PTT, as well as the extrinsic pathway (F-VII) which is monitored by PT. However, factor VII has the shortest half-life of all the factors carboxylated by vitamin K; therefore, when deficient, it is the PT that rises first, since the activated Factor VII is the first to “disappear.” In later stages of deficiency, the other factors (which have longer half lives) are able to “catch up,” and the PTT becomes elevated as well.
Recommended Intakes of Vitamin K
Intake recommendations for vitamin K 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 gender, 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.
Insufficient data were available to establish an EAR for vitamin K, so the FNB established AIs for all ages that are based on vitamin K intakes in healthy population groups . Table 1 lists the current AIs for vitamin K in micrograms (mcg). The AIs for infants are based on the calculated mean vitamin K intake of healthy breastfed infants and the assumption that infants receive prophylactic vitamin K at birth as recommended by American and Canadian pediatric societies .
|Birth to 6 months||2.0 mcg||2.0 mcg|
|7–12 months||2.5 mcg||2.5 mcg|
|1–3 years||30 mcg||30 mcg|
|4–8 years||55 mcg||55 mcg|
|9–13 years||60 mcg||60 mcg|
|14–18 years||75 mcg||75 mcg||75 mcg||75 mcg|
|19+ years||120 mcg||90 mcg||90 mcg||90 mcg|
Several food sources of vitamin K are listed in Table 2. All values in this table are for phylloquinone content, except when otherwise indicated, because food composition data for menaquinones are limited .
|Natto, 3 ounces (as MK-7)||850||1,062|
|Collards, frozen, boiled, ½ cup||530||662|
|Turnip greens, frozen, boiled ½ cup||426||532|
|Spinach, raw, 1 cup||145||181|
|Kale, raw, 1 cup||113||141|
|Broccoli, chopped, boiled, ½ cup||110||138|
|Soybeans, roasted, ½ cup||43||54|
|Carrot juice, ¾ cup||28||34|
|Soybean oil, 1 tablespoon||25||31|
|Edamame, frozen, prepared, ½ cup||21||26|
|Pumpkin, canned, ½ cup||20||25|
|Pomegranate juice, ¾ cup||19||24|
|Okra, raw, ½ cup||16||20|
|Salad dressing, Caesar, 1 tablespoon||15||19|
|Pine nuts, dried, 1 ounce||15||19|
|Blueberries, raw, ½ cup||14||18|
|Iceberg lettuce, raw, 1 cup||14||18|
|Chicken, breast, rotisserie, 3 ounces (as MK-4)||13||17|
|Grapes, ½ cup||11||14|
|Vegetable juice cocktail, ¾ cup||10||13|
|Canola oil, 1 tablespoon||10||13|
|Cashews, dry roasted, 1 ounce||10||13|
|Carrots, raw, 1 medium||8||10|
|Olive oil, 1 tablespoon||8||10|
|Ground beef, broiled, 3 ounces (as MK-4)||6||8|
|Figs, dried, ¼ cup||6||8|
|Chicken liver, braised, 3 ounces (as MK-4)||6||8|
|Ham, roasted or pan-broiled, 3 ounces (as MK-4)||4||5|
|Cheddar cheese, 1½ ounces (as MK-4)||4||5|
|Mixed nuts, dry roasted, 1 ounce||4||5|
|Egg, hard boiled, 1 large (as MK-4)||4||5|
|Mozzarella cheese, 1½ ounces (as MK-4)||2||3|
|Milk, 2%, 1 cup (as MK-4)||1||1|
|Salmon, sockeye, cooked, 3 ounces (as MK-4)||0.3||0|
|Shrimp, cooked, 3 ounces (as MK-4)||0.3||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 vitamin K is 80 mcg for adults and children age 4 and older. However, the FDA does not require food labels to list vitamin K content unless a food has been fortified with this nutrient. 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) Nutrient Database website lists the nutrient content of many foods and provides comprehensive lists of foods containing vitamin K (phylloquinone) arranged by nutrient content and by food name, and of foods containing vitamin K (MK-4) arranged by nutrient content and food name.
|Kale, cooked||1⁄2 cup||531||Parsley, raw||1⁄4 cup||246|
|Spinach, cooked||1⁄2 cup, 77g||444||Spinach, raw||1 cup||145|
|Collards, cooked||1⁄2 cup||418||Collards, raw||1 cup||184|
|Swiss chard, cooked||1⁄2 cup||287||Swiss chard, raw||1 cup||299|
|Mustard greens, cooked||1⁄2 cup||210||Mustard greens, raw||1 cup||279|
|Turnip greens, cooked||1⁄2 cup||265||Turnip greens, raw||1 cup||138|
|Broccoli, cooked||1 cup||220||Broccoli, raw||1 cup||89|
|Brussels sprouts, cooked||1 cup||219||Endive, raw||1 cup||116|
|Cabbage, cooked||1⁄2 cup||82||Green leaf lettuce||1 cup||71|
|Asparagus||4 spears||48||Romaine lettuce, raw||1 cup||57|
|Table from “Important information to know when you are taking: Warfarin (Coumadin) and Vitamin K”, Clinical Center, National Institutes of Health Drug Nutrient Interaction Task Force.|
Uses & Health Benefit of Vitamin K
- Giving vitamin K1 by mouth or as an injection into the muscles can prevent bleeding problems in newborns.
- Taking vitamin K1 by mouth or as an injection into the vein can prevent and treat bleeding problems in people with low levels of prothrombin due to using certain medications.
- Taking vitamin K by mouth or injecting it intravenously (by IV) helps prevent bleeding in individuals with VKCFD.
- Taking vitamin K1 by mouth or as in injection into the vein can counteract too much anticoagulation caused by warfarin. However, injecting vitamin K1 under the skin does not seem to be effective.
- Taking vitamin K along with warfarin also seems to help stabilize blood clotting time in people taking warfarin, especially those who have low vitamin K levels.
- Giving vitamin K to women at risk for very preterm births might reduce the severity of intraventricular hemorrhage in preterm infants. However, it does not seem to prevent intraventricular hemorrhage nor the brain injuries associated with intraventricular hemorrhage.
Insufficient Evidence for
- Population research suggests that higher dietary intake of vitamin K2 is linked with a lower risk of developing breast cancer.
- Population research suggests that higher dietary intake of vitamin K2 is linked with a lower risk of cancer-related death. However, it does not seem to be linked with a lower risk of developing cancer. Higher dietary intake of vitamin K1 does not seem to be linked with a lower risk of cancer or cancer-related death.
- Research suggests that higher dietary intake of vitamin K2 is associated with a lower risk of coronary calcification, which occurs when the inner lining of the coronary arteries develops a layer of plaque, as well as a lower risk of death caused by coronary heart disease. Dietary vitamin K2 can be obtained from cheese, other milk products, and meat. Dietary intake of vitamin K1 does not seem to have an effect on heart disease risk. However supplementation with vitamin K1 seems to prevent or reduce the advancement of coronary calcification.
- People with cystic fibrosis can have low levels of vitamin K due to problems digesting fat. Taking a combination of vitamins A, D, E, and K seems to improve vitamin K levels in people with cystic fibrosis who have trouble digesting fat. Also, early research suggests that taking vitamin K by mouth for can enhance the production of osteocalcin, which plays a role in the body’s bone-building and metabolic regulation. However, there is no reliable evidence suggesting it improves overall health in people with cystic fibrosis.
- Early research suggests that taking a multivitamin fortified with vitamin K1 does not lower the risk of developing diabetes compared to taking a regular multivitamin.
- There is early evidence that vitamin K2 might lower cholesterol in people on dialysis with high cholesterol levels.
- Taking vitamin K2 does not seem to prevent liver cancer from recurring after curative or possibly curative treatment. However, some early research suggests that vitamin K2 might prevent the development of liver cancer in people with liver cirrhosis.
- Early research suggests that higher dietary intake of vitamin K2 is linked with a reduced risk of lung cancer and lung cancer-related death. Dietary intake of vitamin K1 does not seem to be linked with a reduced risk of these events.
- So far, research results on the effects of vitamin K on bone strength and fracture risk in people with osteoporosis don’t agree.
- Early research suggests that higher dietary intake of vitamin K2, but not vitamin K1, is linked with a reduced risk of prostate cancer.
- Population research suggests that dietary intake of vitamin K1 is not linked with a reduced risk of stroke.
- Spider veins
- Stretch marks
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