Vitamin K supplementation reduces serum concentrations of under-γ-carboxylated osteocalcin in healthy young and elderly adults

Abstract

Background: Subclinical vitamin K insufficiency, manifested by under-γ-carboxylation of the bone matrix protein osteocalcin, may be common. Objective: Our objective was to delineate the prevalence of submaximal γ-carboxylation as assessed by response to phylloquinone supplementation and to evaluate the effect of this intervention on skeletal turnover in healthy North American adults. Design: Healthy subjects (n = 219), approximately equally distributed by sex and age (18–30 y and ≥65 y), received daily phylloquinone (1000 μg) or placebo for 2 wk. Serum undercarboxylated osteocalcin (ucOC) and total osteocalcin, N-telopeptides of type I collagen (NTx), bone-specific alkaline phosphatase (BSAP), and phylloquinone concentrations were measured at baseline and after weeks 1 and 2. Results: At baseline, the mean serum phylloquinone concentration was lower in the young than in the old group; there was no effect of sex. Concomitantly, baseline %ucOC was highest in the young and lowest in the old men (P < 0.0001) but did not differ significantly by age in women. After supplementation, serum phylloquinone concentration increased ≈10-fold (P < 0.0001) at week 1 (from 0.93 ± 0.08 to 8.86 ± 0.70 nmol/L, x̄ ± SEM); this was sustained through week 2. Among all supplemented groups, mean %ucOC decreased from 7.6% to 3.4% without significant differences by age or sex; 102 of 112 subjects had a >1% decrease. Phylloquinone supplementation reduced serum osteocalcin but did not alter NTx or BSAP concentration. Conclusions: Usual dietary practices in this population did not provide adequate vitamin K for maximal osteocalcin carboxylation. Phylloquinone supplementation reduced serum osteocalcin concentration but did not alter other markers of serum bone turnover.