Vitamin K’s role in age-related bone loss: A critical review

Abstract

Vitamin K is a group of structurally similar vitamers that all function as an enzymatic cofactor in the conversion of specific glutamic acid (Glu) residues to gamma (γ)-carboxyglutamic acid (Gla) residues in certain proteins. The common feature of these proteins is that the Gla residues are essential for binding calcium. While the most commonly known vitamin K-dependent (VKD) proteins function in coagulation, several VKD proteins are present in extra-hepatic tissue, including bone. There are two naturally occurring form of vitamin K that share a common chemical structure-a 2-methyl-1,4-napthoquinone (Fig. 29.1) and are capable of carboxylating VKD proteins. The primary dietary form, phylloquinone (vitamin K1), which has a phytyl group at the 3-position, is found in green leafy vegetables and vegetable oils. Phylloquinone contributes up to 60 % of total dietary vitamin K intakes. Menaquinones, collectively known as vitamin K2, differ structurally from phylloquinone by their 3'-substituted unsaturated multiprenyl group side chain. Menaquinone-4 (MK-4) is primarily found in poultry and pork products because a synthetic precursor to MK-4, menadione (vitamin K3) is abundant in animal feed. Physiologically, phylloquinone can also be converted to MK-4. While phylloquinone is the predominate form of vitamin K in circulation and in bone, MK-4 concentrations are higher than phylloquinone in other extrahepatic tissues. Unlike other menaquinones, MK-4 is not formed from bacterial synthesis. Therefore the common usage of the term, vitamin K2, to include all menaquinones is misleading as there are different origins and potential functions within this large group of vitamers. Longer-chain menaquinones [menaquinone-7 (MK-7)-menaquinone-10] originate from bacterial synthesis, and are primarily found in fermented dairy products and fermented plant-based foods. Natto, for example, is a fermented soy food traditionally eaten in Japan and is rich in MK-7. However, menaquinones generally contribute less to total vitamin K intakes of Western diets than phylloquinone. The role of long-chain menaquinones to human health is complicated by the fact that they are also synthesized by bacteria in the lower intestine. Not all intestinal bacteria synthesize menaquinones and the intestinally synthesized menaquinones are not well-absorbed, so their contribution to vitamin K nutritional status is uncertain. For the purpose of this review, we will focus on vitamin K intakes from food and/or supplements, and will assume that circulating vitamin K concentrations are derived primarily from intakes.