Vitamin K nutrition and postmenopausal osteoporosis.

Editorial The key question of vitamin K nutrition in humans may be how much is enough. As with other vitamins, the answer could depend on which biological effect is observed. Vitamin K was first discovered as an antihemorrhagic factor, and it is now known to be required for the synthesis of several proteins involved in blood coagulation (prothrombin; Factors VII, IX, and X; proteins S and C). One measure of vitamin K nutritional status is therefore the time it takes blood to clot. By this measure vitamin K nutritional deficiency in the U.S. population is largely limited to neonatal infants. Other measures of vitamin K nutritional status have arisen from an understanding ofthe molecular mechanism ofvitamin K action. Vitamin K is now known to be a cofactor for the posttranslational modification of specific glutamic acid residues to form the Ca2" binding amino acid, y-carboxyglutamic acid (Gla). Since Gla is not metabolized further in humans, urinary Gla levels provide a measure ofthe total turnover ofall Gla-containing proteins in an individual. If dietary levels of vitamin K are low, the extent of the vitamin K-dependent formation of some or all Gla residues in these proteins should be reduced and less Gla should appear in urine. In the study by Ferland et al. (1), vitamin K deficiency was induced in young and old healthy human subjects by restricting vitamin K1 intake to 10 ,g/d, a level which is below the 80 Ag/d recommended daily allowance for the vitamin. Plasma levels ofvitamin K fell over sixfold within 3 d ofdietary restriction in both the young and old subjects. Although this level of vitamin K1 depletion had no effect on blood coagulation time or on the activity of Factor VII or protein C, it did reduce urinary Gla levels by a consistent 10% in the younger group. How can urinary Gla decline if the synthesis of the vitamin K-dependent coagulation factors is normal? It is clear that other Gla proteins must contribute to urinary Gla levels, and that the normal synthesis of these proteins must be reduced at levels ofvitamin K which are adequate for normal blood coagu-lation. The authors estimate that these other Gla proteins contribute 36% of urinary Gla, and consequently a 10% drop in urinary Gla translates to a 28% decrease in synthesis of these other Gla proteins. Although a number of novel Gla-containing proteins may remain to be discovered, only two …