Vitamin K: the effect on health beyond coagulation – an overview

April 2021
Cees Vermeer

Abstract

Vitamin K is essential for the synthesis of proteins belonging to the Gla-protein family. To the members of this family belong four blood coagulation factors, which all are exclusively formed in the liver. The importance of vitamin K for hemostasis is demonstrated from the fact that vitamin K-deficiency is an acute, life-threatening condition due to excessive bleeding. Other members of the Gla-protein family are osteocalcin, matrix Gla-protein (MGP), and Gas6 that play key functions in maintaining bone strength, arterial calcification inhibition, and cell growth regulation, respectively.

In total 17 Gla-proteins have been discovered at this time. Recently, it was observed that the dietary vitamin K requirement for the synthesis of the coagulation factors is much lower than for that of the extra-hepatic Gla-proteins. This forms the basis of the triage theory stating that during poor dietary supply, vitamins are preferentially utilized for functions that are important for immediate survival.

This explains why in the healthy population all clotting factors are synthesized in their active form, whereas the synthesis of other Gla-proteins is sub-optimal in non-supplemented subjects. Prolonged sub-clinical vitamin K deficiency is a risk factor for osteoporosis, atherosclerosis, and cancer. Present recommendations for dietary intake are based on the daily dose required to prevent bleeding. Accumulating scientific data suggests that new, higher recommendations for vitamin K intake should be formulated.

Safety

Since the primary deficiency disease associated with vitamin K is bleeding due to impaired blood clotting, it is often thought that high intake of vitamin K may increase thrombosis risk. This is evidently not true. Full carboxylation (and thus: maximal procoagulant activity) of the vitamin K-dependent clotting factors is essential, and vitamin K metabolism has been designed to meet that goal with highest priority.

Excess vitamin K intake cannot result in more clotting factor carboxylation. This has also been demonstrated within our institute in thousands of subjects taking high doses of vitamin K during several years. Even when monitored with the most sensitive techniques (endogenous thrombin potential, ETP), an increased thrombosis tendency was not found in any of the participants.

An exception is formed by patients receiving oral anticoagulants like warfarin or acenocoumarol that act as vitamin K-antagonists. Obviously excess vitamin K intake will interfere with this medication. On the other hand it is becoming increasingly clear that the long-term use of these drugs is associated with accelerated bone loss, low bone mass, and widespread valvular and arterial calcifications (26), thus demonstrating once more the importance of vitamin K for bone and vascular health.