Vitamin K finds its moment for bone health, cardio health, and more

Leon ShurgersBelow is the full interview Functional Ingredients conducted with Leon Schurgers, PhD, a renowned research scientist specialising in the role of vitamin K in the field of bone health and cardiovascular health. Dr Schurgers is one of the chief researchers and an honorary senior scientist at the division on vitamin K research at the Cardiovascular Research Institute (CARIM), the largest research institute of the University of Maastricht in The Netherlands.

Dr. Schurgers is also the Vice President and Scientific Director of VitaK,, a research company with a long expertise in all aspects of vitamin K and vitamin K-dependent proteins at the University. He is a member of the American Heart Association, the American Society of Bone and Mineral Research, and the International Society of Thrombosis and Haemostasis. Finally, Dr. Schurgers is also a board member of KEQAS, the worldwide vitamin K external quality assurance scheme.

He is widely published, with papers in respected journals such as the Journal Blood (the official publication of the American Society of Hematology), Journal of Thombosis and Haemostasis, Lab Investigations, Journal of Vascular Research, Atherosclerosis, Osteoporosis International, Pediatric Research and others in 2007 alone!

Fi. As evidence begins to accumulate, it is suggested that high intakes are required to provide optimal effect. Does the long-chain menaquinone-7 (MK-7) solve this over the synthetic short-chain vitamin K1?

L.S. All K-vitamins have a similar function, but since their pharmacokinetic behavior and tissue distribution following absorption vary greatly, it is obvious that adequate supply to different tissues not only depends on the amount of vitamin K taken, but also on which type of vitamin K which was ingested. It has been reported that the uptake of K1 from green vegetables (which form the main dietary source of K1) varies between 5 and 15 per cent.

Although K2 vitamins comprise only some 10 per cent of our total dietary vitamin-K intake, they may form half of the total vitamin K absorbed; this because of the much better, nearly complete absorption and also significantly longer biological half-life of the long-chain menaquinones. It seems, therefore, that these long-chain menaquinones (eg MK-7) are the main contributors to the vitamin-K status in humans.

In conclusion: high intakes are required for K-vitamins with short half-life in the circulation. This problem can be solved by supplementing with the K2 vitamin MK7, which when given on a daily basis results in high steady state vitamin K-levels at a relative low intake.

Measurements of vitamin K-dependent proteins such as osteocalcin (ucOC), which is vital for bone health, and MGP (ucMGP), the most potent inhibitor of vascular calcification known, in the majority of the healthy adult population suggests sub-clinical vitamin K deficiency in large parts of the population.

Fi. Describe the mechanism of action for K2 being able to take calcium from arteries and place it in bones.

L.S. The action of K2 is putting calcium at the right place; stimulates calcification were needed (bones) and prevents precipitation ectopically (arteries). The commonality is that both rely upon vitamin K-dependent proteins. The role of vitamin K has for the past decade been linked to two of the most important health issues, osteoporosis and cardiovascular disease. This link specifically centers on calcium utilisation, whereby inadequate metabolism of calcium can result in concurrent arterial calcification and osteoporosis. This is called the Calcium Paradox.

The Calcium Paradox is explained simply as getting calcium in the right place — ie into the bone structures and out of the arterial vessel walls. These events are dependent upon the synthesis of the vitamin K-dependent proteins Osteocalcin and Matrix Gla Protein in a process called carboxylation. This reaction is essential for optimal and healthy utilization of calcium.

Without adequate Vitamin K, our bodies do not use calcium correctly! Vitamin K carboxylates, or "activates" a K-dependent protein called osteocalcin that is necessary to use calcium to build healthy bone tissue.

Vitamin K also activates a protein called matrix GLA protein, or MGP, that is necessary for the vascular tissues to make use of and then remove excess calcium. Natural vitamin K2 is a form of vitamin K that has been linked to this activity.

In a cross-sectional analysis among 5,000 participants of the Rotterdam study, Geleijnse et al. reported a strong correlation between long-term nutritional vitamin K2 (mainly long-chain menaquinone) intake and aortic calcification and cardiovascular death. After subdivision of the cohort into tertiles according to dietary vitamin K2 intake, and using the lowest tertile of intake as a reference, the cardiovascular mortality risk was 50 per cent lower in the highest tertile for vitamin K2 intake, whereas the all-cause mortality risk was 25 per cent lower! For vitamin K1 the observed associations were not significant.

Fi. Are there any other ingredients that do either of K2's actions — take calcium from arteries or place it in bones?

L.S. The action of vitamin K, activating vitamin K-depending proteins, is unique. No other vitamins, micronutrients or structures can do this. Therefore, nothing can replace the action of vitamin K. The inactivity of osteocalcin and matrix Gla-protein has been linked by many studies to poor bone quality and stiffened arteries. Therefore, nothing can replace vitamin K.

Fi. Does the evidence show that higher levels, 50mcg/day, MK-7 could interfere with oral anticoagulation treatment in a clinically relevant way?

L.S. For many years medical doctors advise their patients who are on oral anticoagulant treatment (OAC) not to consume vitamin-K rich diets because of the interference between oral anticoagulant treatment and vitamin K. However, we know that vitamin K is necessary for other functions in the body. In fact, the medical community is now debating the use of vitamin K concurrently with anticoagulants that are vitamin K antagonists — the most common are warfarin, phenprocoumon, and acenocoumarol. We believe natural vitamin K2 as menaquinone-7 is the ideal form to use, however, any K supplementation for a person using OAC therapy MUST be coordinated with their physician.

Our group has conducted human studies with OAC to determine what levels of vitamin K could interact negatively. The conclusions are as follows: supplementation of K1 below 150ug/day is unlikely to interfere, while supplementation of menaquinone-7 below 50mcg per day is unlikely to clinically interfere. At this moment we are testing the interaction of lower doses (10, 20 and 45mcg) of menaquinone-7 on oral anticoagulant treatment.

However, any supplement containing K vitamins should also have a warning on its label regarding the potential interaction.

Fi. What other health benefits is emerging with K2 — rheumatoid arthritis, etc?

L.S. Recently a study conducted by our colleague Dr Booth at Tuffs University in Boston showed in the Framingham cohort that 50 per cent of the patients with rheumatoid arthritis were vitamin K-deficient, as measured by plasma levels. The study clearly demonstrated a putative function for vitamin K in rheumatoid arthritis.

Interestingly, K2 vitamins have also a second function not related to vitamin-K activity. We and others have shown that the side chain of K2 vitamins may be regarded as a geranylgeranyl derivative, which inhibits osteoclast activation most likely via the inhibition of the mevalonate pathway. K vitamins and K-dependent proteins in recent research have been linked to the incidence and severity of varicose veins, glial cells (brain), tissue calcification (bone and arteries).

Fi. Are there other nutrients that have a synergistic effect with K2 — vitamin D, etc?

L.S. Vitamin D3 and omega-3 fatty acids are recommended to be taken with K2 for bone health and CV health.

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