Vitamin K nutrition, metabolism, and requirements: current concepts and future research

Abstract

In 2001, the US Food and Nutrition Board concluded that there were insufficient data with which to establish a RDA for vitamin K, in large part because of a lack of robust endpoints that reflected adequacy of intake. Knowledge of the relative bioavailability of multiple vitamin K forms was also poor. Since then, stable isotope methodologies have been applied to the assessment of the bioavailability of the major dietary form of vitamin K in its free state and when incorporated into a plant matrix. There is a need for stable isotope studies with enhanced sensitivity to expand knowledge of the bioavailability, absorption, disposition, and metabolism of different molecular forms of vitamin K. Another area for future research stems from evidence that common polymorphisms or haplotypes in certain key genes implicated in vitamin K metabolism might affect nutritional requirements. Thus far, much of this evidence is indirect via effects on warfarin dose requirements. In terms of clinical endpoints, vitamin K deficiency in early infancy continues to be a leading cause of intracranial bleeding even in developed countries and the reasons for its higher prevalence in certain Asian countries has not been solved. There is universal consensus for the need for vitamin K prophylaxis in newborns, but the effectiveness of any vitamin K prophylactic regimen needs to be based on sound nutritional principles. In contrast, there is still a lack of suitable biomarkers or clinical endpoints that can be used to determine vitamin K requirements among adults.

Figure 1

Intestinal absorption of dietary phylloquinone (K₁) and MK-7. In the intestinal lumen, K₁ and MK-7 are incorporated into mixed micelles comprising bile salts, the products of pancreatic lipolysis, and other dietary lipids. Mixed micelles are taken up by intestinal enterocytes of the small intestine and are incorporated into nascent CM, which have apoA and apoB-48 on their surface. CM are secreted from within the intestinal villi into the lymphatic capillaries (lacteals), which join larger lymphatic vessels and empty into the blood circulation via the thoracic duct. In the bloodstream, CM acquire apoC and apoE from HDL. CM enter the capillary beds of peripheral tissues where they lose much of their TG cargo through the action of LPL, at the same time losing apoA and C. The resulting CR that reenter the circulation are smaller and have a central lipid core with surface apoB-48 and apoE. CM, chylomicron; LPL, lipoprotein lipase; MK, menaquinone.

Figure 2

Uptake of phylloquinone (K₁) and MK-7 by liver and by bone. It is likely that a major fraction of dietary K₁ and MK-7 is delivered to the liver and bone within the CR, which have apoB-48 and apoE on their surface. CR can interact with cell surface lipoprotein receptors (e.g., LDLR and LRP) and are taken up by target cells by receptor-mediated endocytosis. There is evidence that K₁ and especially MK-7 are incorporated into LDL through the hepatic export of VLDL (bearing surface apoB-100, C, and E) followed by their subsequent dilapidation in capillaries to VLDL remnants (IDL) and further catabolism to LDL (bearing surface apoB-100). It is known that human osteoblasts express the LDLR and LRP1 and that LRP1 plays a predominant role in the uptake of CR by osteoblasts, including the ability to utilize K₁-rich CR for γ-carboxylation of osteocalcin. CR, chylomicron remnant; LDLR, LDL receptor; LRP, LDL receptor-related protein; MK, menaquinone.