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Scientific Research on Vitamin K2: Current State of Knowledge and Future Directions

As new roles for vitamin K in health and disease emerge, so has interest in the relative contribution of different vitamin K forms to human health, including bone and heart health.

Vitamin K is a term that refers to multiple forms of structurally-similar compounds, all of which have an enzymatic role in the function of vitamin K-dependent proteins. While the best known vitamin K-dependent proteins are clotting proteins, other vitamin K-dependent proteins have been implicated in many chronic diseases. As new roles for vitamin K in health and disease emerge, so has interest in the relative contribution of different vitamin K forms to human health, including bone and heart health.

Dietary forms of vitamin K fall into two general categories: phylloquinone (vitamin K1) and menaquinones (collectively referred to as vitamin K2). There are at least 10 individual menaquinones, all of which differ from phylloquinone by their side chain. Not all menaquinones are the same; hence, the use of the term “vitamin K2" can be misleading. For example, menaquinone-4 is unique among the menaquinones in that it is not produced by bacteria. Instead, it is concentrated in animal meats and dairy products, and can be formed in the body from dietary phylloquinone. It is also a common vitamin K form used in dietary supplements. In contrast, menaquinones with longer side chains are of bacterial origin, and are primarily concentrated in animal meats and fermented foods. There is also substantial bacterial production of menaquinones in the human gut. Menaquinone-7 is an emerging vitamin K form also used in dietary supplements. Little is known about the other bacterially-produced menaquinones. Even less is known about the contribution of menaquinones produced by the gut bacteria to human health.

Dietary recommendations for vitamin K vary globally, and do not differentiate phylloquinone intake from menaquinone intake. However, the current vitamin K recommendations are based on phylloquinone, for which most of the food composition data are available. There is insufficient scientific knowledge at this time to determine an independent dietary recommendation for menaquinones.

Higher intakes of menaquinones are reported to be associated with less subclinical and clinical cardiovascular disease (CVD), metabolic syndrome and some forms of cancer. However, the difference in total menaquinone intake between the highest and lowest categories of intake is narrow, and the potential protective influence of narrow differences of intake is uncertain, and merits further research. It is also important to consider the food sources of menaquinones. It is plausible that menaquinone intake tracks intake of other nutrients and/or fatty acids found in foods that have also been associated with protective effects against cardiovascular disease. Therefore, alternative approaches to evaluating the role of menaquinones in human health are needed.

Menaquinones are generally not detected in circulation unless supplements are taken or large quantities of menaquinone-rich foods are consumed. As a result, there are no other biomarkers available that differentiate menaquinone intake from phylloquinone intake, so population studies are to date limited in elucidating the relative contribution of individual vitamin K forms to health. Randomized clinical trials are currently the optimal approach but, to date, are limited to the studies of menaquinone-4 and menaquinone-7 and bone and heart health. While promising results have been reported for menaquinone-7, more trials need to be conducted to determine generalizability. In addition, comparative trials are required to address the question of relative contribution of individual forms of vitamin K to human health.

Sarah Booth, Ph.D., will discuss what’s currently known about vitamin K2, as well as future directions, during the Understandings and Market Opportunities Around Vitamin K2 workshop on Saturday, Oct. 8, at SupplySide West 2016.

Sarah L. Booth, Ph.D., serves as associate director of the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University and directs its vitamin K laboratory. She is also a professor of nutrition at the Friedman School of Nutrition Science and Policy. An expert in vitamin K, Booth’s main scientific interests include the absorption, transport and metabolism of vitamin K and the role of its metabolism in the prevention of chronic disease. She uses research from animal studies and human clinical trials to develop an evidence base toward the possibility of setting an estimated average requirement (EAR) of vitamin K for adults.

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