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-␥-carboxylation of the bone matrix protein osteocalcin, may be common. Objective: Our objective was to delineate the prevalence of submaximal ␥-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 g) 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 Ϸ10-fold (P < 0.0001) at week 1 (from 0.93 ± 0.08 to 8.86 ± 0.70 nmol/L, x -± 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.

Dietary acid–base balance and intake of bone-related nutrients in Cambridge teenagers

“…, 2001), to take into account the higher requirement for carboxylation of bone osteocalcin. Various studies suggest that current intakes of vitamin K in the US (Feskanich et al, 1999;Binkley et al, 2000;McKeown et al, 2002) and the Netherlands (Vermeer et al, 1995) are associated with a high proportion of under-carboxylated osteocalcin. However, it is not known whether adolescent vitamin K requirements are also higher since bone turnover is approximately 10-20 times that found in healthy adults (Szulc et al, 2000).…”

A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption

“…It is therefore possible that current recommended intakes, although adequate to maintain full carboxylation of vitamin K-dependent coagulation proteins (Suttie et al, 1988), are insufficient to maintain other VKD proteins, including osteocalcin, in the fully carboxylated state (Binkley et al, 2000(Binkley et al, , 2002Booth et al, 2003b). Partly in recognition of this, recommended intakes in the United States have recently been increased to 90 and 120 mg/day for women and men, respectively (Institute of Medicine, 2001).…”

Oral anticoagulant treatment and risk for bone fractures in uremic hemodialysed patients

“…In addition, vitamin K might directly reduce bone resorption due to decreased prostaglandin E2 synthesis and osteoclastlike cell formation, while vitamin K treatment has been shown to decrease urinary excretions of hydroxyproline which is a marker of bone resorption in post-menopausal women. 4,[6][7][8] The clinical characteristics of our 4 hemodialysed patients with bone fracture are as follows: Patients were exposed to oral anticoagulation for more than 2 years; are uremic hemodialysed; and elderly. As mentioned above, these categories of patients present poor vitamin K status.…”