Vitamin K2 update: Health benefits, daily dose and side effects

Although identification of vitamin K2 might be in later but use of the vitamin was not new. Centuries back Samurai warriors in Japan used to consume a fermented soybean dish called natto an extremely rich source of vitamin K2. Change of food habit, industrialization might diminish the presence of vitamin K2 in diet. The initial discovery of vitamin K can be attribute to Danish scientist Henrik Dam described a fat‑soluble factor that reduced bleeding. A few years later, American biochemist Edward Adelbert Doisy determined the chemical structure of vitamin K. For their work, Henrik Dam and Adelbert Doisy shared the 1943 Nobel Prize in Medicine. Years later scientist discovered presence of vitamin K2. (1,2)Here our subject is Vitamin K2 update: Health benefits, daily dose and side effects 

Earlier vitamin K was thought as a nutrient involved in blood clotting. Major progress in understanding of the mechanisms of action of vitamin K came with the discovery of Gla proteins, vitamin K dependent protien activation of which depend on vitamin K, sphingolipid synthesis. That followed the discovery of additional vitamin K dependent proteins showing wide tissue distribution and functional scope.(3)So vitamin K is further distributed into two groups phylloquinone (vitamin K1) and a series of menaquinones (vitamin K2. While major role of vitamin K1 involves in blood clotting, health benefits of vitamin K2 appear as myriad. 

Vitamin K2 update: Health benefits, daily dose and side effects 

Improve heart, bone, teeth health

In our earlier article we talked about how vitamin K2 plays crucial roles in heart and bone health. We also discussed risk of calcium supplementation with or without vitamin D as well as association of low vitamin D and K level with risk of hypertension or high blood pressure.

For more read about health benefits of vitamin K2 for heart and bone health and combination

 Matrix Gla protein(MGP) inhibits calcium deposition in artery that circulates through your blood. But for that purpose MGP needs vitamin K2 for its activation. Inactive MGP leads to calcium deposition in artery not in bone.

In bones a protein called osteocalcin promotes the accumulation of calcium in your bones as well as teeth. Again vitamin K2 activates osteocalcin and thus helps in placing calcium in right place i.e. in your bone as well as teeth not in artery.

Prevent kidney stone

From the earlier data probably you can imagine vitamin K2 has role in kidney function also. The kidneys have high concentration vitamin K2 that activates MGP and so accumulates calcium in circulation and remove from there. Thus vitamin K2 plays important roles in preventing development of kidney stone. (4)

Study published in the American Journal of Kidney diseases confirms that most hemodialysis patients have a functional vitamin K deficiency as well as higher inactive MGP. They also showed that vitamin K(2) supplementation can lower inactive MGP levels markedly. (5)Similar results were observed in other studies also and found vitamin K(2) supplementation reduces inactive MGP as well as improves arterial stiffness in patients of kidney transplant. (6,7)

Health of Brain and Nervous system

Research also identified vitamin K as an important nutrient for the nervous system. K2 presents in all brain regions, although concentration can vary according to regions with highest concentrations in the midbrain and pons medulla. Sphingolipids a group of complex lipids present in all mammalian cells as a major components of cell membranes. They are major lipid signaling molecules that have a role in motor and cognitive behavior and now viewed as key players in important cellular events such as proliferation, differentiation, senescence, cell–cell interaction, and transformation. Therefore decline or alteration in sphingolipid metabolism is associated with aging process and neurological degeneration.

Also in recent years, studies have linked alterations in sphingolipid metabolism to age-related cognitive decline and neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging data and growing evidence also point to protective actions of Vitamin K2 against oxidative stress as well as inflammation.

And certain sphingolipids are highly correlated with K2 in the brain. Also in addition to vitamin K dependent proteins vitamin K participates in sphingolipid metabolism in brain. Vitamin K2 has positive correlations with a major lipid called sulfatides abundant in the brain. Sulfatide has multifunctional rules in various biological fields including the nervous system. Thus, abnormal metabolism or expression change of sulfatide could cause various diseases. Another vitamin K dependent protein Gas6 is also closely associated with the nervous system activation of which requires vitamin K. (8,9,10,11, 12)

Cancer Prevention

Researchers also observed growth inhibitory effects of vitamin K in a variety of cancer cell lines.  EPIC-Heidelberg studies conducted on 11 319 and 24,340 participants, suggest intake of K2 has inverse relation with risk of incident and also with fatal cancer, prostate cancer. (13,14)

Among the vitamin K group vitamin K2 has the highest potential against cancer than K1. Several in vitro studies had also certified the anticancer effect of VK2 against several neoplastic cell lines, including hepatocellular carcinoma, leukemia, cholangiocarcinoma, ovarian cancer, pancreatic cancer, and colorectal cancer.

K2 can inhibit the proliferation of cancer cells by inducing the cell-cycle arrest of cancer cells, in which inhibition of nuclear factor-κB (NF-κB) activity has a crucial role.  Although more investigations are yet to come, review indicated that induction of the cell-cycle arrest, cell differentiation, apoptosis, and autophagy is crucial for VK2-dependent suppression of cancer cell growth. Review also suggests that the combination of VK2 with other chemotherapeutics, such as sorafenib, can exert a synergistic effect and reduce adverse drug reactions. (15)

Skin Health

Vitamin K2 also appears to have beneficial effect for skin health. Just like vitamin K2 inhibits calcification of arteries and other soft tissues it can also prevent excessive calcium in the elastin in the skin. And that way, K2 may help maintain skin elasticity as well as prevent wrinkles.  In study severity of facial wrinkles had significant inverse correlation with the bone density. (16) Japanese women have youthful skin and also consume natto.

May improve insulin sensitivity

Vitamin K2 also may improve insulin sensitivity through metabolism of vitamin K-dependent-protein osteocalcin, anti-inflammatory properties, and lipid-lowering effects. Vitamin K2 had a better effect than vitamin K1 on T2DM.(17,18)However these need more data.

Which Form of K2 ?

Vitamin K2 or menaquinones are characterized by the number of isoprenoid residues in their side chains. Generally MK-n represents menaquinones of vitamin K2.  Where M represents menaquinone, the K stands for vitamin K, and the n represents the number of isoprenoid side chain residues. MK-4 and MK-7 are the most well-studied as well as commonly used menaquinones or vitamin K2.

While circulation removes majority of vitamin K1 and MK-4 within 24 hr of ingestion MK-7 last for longer period and doesn’t appear to be completely removed from circulation after 72-96 hr. (19)Likely due to its longer side chain conferring greater liposolubility, MK-7 has a much longer half-life than MK-4. Menaquinone-7 appears to offer a number of practical benefits over menaquinone-4 in terms of lower dosing and single daily dosing instead of multiple doses.(20) But MK-4 has higher tissue presence than MK-7. So we have updated this part to our next article MK-4 VS MK-7.

Food Source

Vitamin K1 (phylloquinone): Found source includes plant foods like leafy greens.

Vitamin K2 (menaquinone): Natto a Japanese fermented soy food as major source of MK-7, other sources includes animal foods, dairy and fermented foods. Also some gut bacteria produces long chain K2.

Food sources are very limited and also the amounts available are very less in most food sources in present environment. Read more about food source database.

Daily Dose

Although it is not updated widely till now, research suggests daily as 45-50mcg for child and as up to 180 mcg for adults as safest upper limit.(19) We have updated this for osteoporosis with our article MK-4 VS MK-7.

How Safe vitamin K2 is?

Vitamin K appears as safe because of its low potential for toxicity. There is no documented case of toxicity or adverse effects with vitamin K consumption from food as well as supplements have been reported in humans or animals till date. (21)

Interaction with others

Vitamin K can have serious interaction with anticoagulants drug such as warfarin and tends to suppress the effects of warfarin. These drugs antagonize the activity of vitamin K, leading to the depletion of vitamin K-dependent clotting factors. Hence people taking warfarin and similar anticoagulants drug need to maintain a consistent intake of vitamin K from food and supplements because sudden changes in vitamin K intakes can increase or decrease the anticoagulant effect. If you are taking anticoagulants drug you should consult with your healthcare provider before taking vitamin K.

Antibiotics can destroy vitamin K-producing gut bacteria, so potentially decreasing vitamin K level. Bile acid sequestrants used to reduce cholesterol may also reduce the absorption of vitamin K and other fat-soluble vitamins. Orlistat a weight-loss drug also available as over-the-counter as well as prescription reduces the body’s absorption of dietary fat and thus can also reduce the absorption of fat-soluble vitamins including vitamin K.(21)

Final Word

This earlier overlooked vitamin having late attention and showing many crucial health benefits with its regulatory properties. More data yet to come.

 
Disclaimer: Information provided here are generalized information for 
educational purpose only,  not intended to provide one to one health 
consultation or replace practice of a qualified practitioner. Different 
people may have different health condition and may have different reaction 
to the same food. Hence it has been advised to consult with health care 
provider before application of any of above guidelines. 

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