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In the news: Role of Vitamin K in Vascular Health

Low Awareness of Vitamin D & K Relationship

The importance of vitamin D in maintaining bone mineral density and in modulating the immune system is well known. However, fewer are aware of the role vitamin K2 plays in vitamin D and calcium metabolism.

Case in point, a recent study(1) by dermatologists from the University of Kansas and Baylor College of Medicine found that of 50 patients counseled to take vitamin D supplements due to recommended sun protection, only 4 of the 50 surveyed understood the relationship of vitamins K2 and D – a finding of potential importance since most people consuming a typical Western diet do not obtain sufficient K2.

Vitamin K is the generic name for a family of structurally similar compounds that include phylloquinone (vitamin K1) and a series of menaquinones (vitamin K2), designated MK-4 through MK-13, based on the length of their side chain.

Evidence supports a synergistic effect of vitamin K2 on vitamin D, potentially explaining “the calcium paradox” – i.e., that supplemental calcium promotes bone mineral density and strength, but may also raise the risk for heart disease by accelerating the deposit of calcium in blood vessel walls and soft tissue. In short, vitamin D promotes calcium absorption, while vitamin K directs calcium to bone and reduces artery calcification.

Vitamin K functions as a coenzyme for a vitamin K-dependent enzyme that synthesizes the protein osteocalcin. Osteocalcin produced by bone cells (osteoblasts) helps take calcium from the circulation and bind it to the bone matrix for mineralization.

Vitamin K is also required for the synthesis of the protein matrix GLA which is produced by cells of vascular smooth muscles and helps regulate the accumulation of calcium in blood vessel walls.

Growing Importance of Vitamin K2

Both vitamin K1 and K2 forms are important and can activate osteocalcin and matrix GLA. However, K1 is considered much less efficient as it is transported to the liver first to activate coagulation proteins.

The results from population-based studies lend credence to the relationship of vitamin K2 and cardiovascular (CV) health. For example, a population-based study(2) with 16,000 healthy women followed for 8 years reports that high intake of dietary vitamin K2 is linked to protection against CV events. For every 10 mcg of dietary K2 as MK-7, -8 and -9, CHD risk was reduced by 9%.

In long-term clinical trials, supplemental vitamin K2 as MK-7 has been found to improve both bone health and cardiovascular health as measured by ultrasound and pulse-wave velocity(3,4).

Role for vitamin K in Retinal Health?

Studies suggesting that active matrix GLA helps maintain the integrity of kidney and myocardial microcirculation have prompted researchers to ask whether vitamin K has a role to play in preserving the retinal microcirculation as well.

A recent study, for instance, found that a marker for poor vitamin K status (inactive matrix GLA) is a long-term predictor of smaller retinal arteriolar diameters in the general population5. And, interestingly, in an animal model of glaucoma, supplemental vitamin K1 has been reported to protect against damage of retinal ganglion cells6.

When trying to achieve adequate calcium and vitamin D intakes, it’s important not to overlook K. Vitamin K1 is found primarily in green leafy vegetables such as kale, spinach and collards. Fermented foods like natto and cheeses are the best source of vitamin K2, while meat, dairy, and eggs contain low K1 and modest K2 levels. Since both vitamins K1 and K2 can activate coagulation factors, those on warfarin should check with their prescribing physicians before increasing dietary or supplemental vitamin K.

References

1. Abouodh H, et al. Vitamin K2 awareness in sun-protected patients supplementing with vitamin D. J Drugs Derm 20:228-9, 2021.
2. Gast CG, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cadiovasc Dis 19:504-10, 2009.
3. Knappen MH, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost 113(5):1135-44, 2015.
4. Wei FF, et al. Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans. Nature. 8:15088, 2018.
5. Deng C et al. The effect of dietary K1 supplementation on trabecular meshwork and retina in a chronic ocular hypertensive rat model. IOVS. 61:40, 2020.