Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight

Abstract

Osteocalcin (OC) is a vitamin K-dependent protein found in bone and in circulation. High serum g-carboxylated OC reflects a high, and high uncarboxylated OC (ucOC) reflects a low vitamin K status. A revolutionary hypothesis is that ucOC acts as a hormone improving glucose handling and reducing fat mass. The objective was to test the logical extrapolation of the ucOC hormone hypothesis to humans that elevated ucOC is associated with higher body weight, BMI and fat mass. In a cross-sectional analysis, the associations of vitamin K status with circulating adiponectin and body composition were investigated in 244 postmenopausal women (study I). The effects of vitamin K treatment on adiponectin, body weight and BMI were investigated in archived samples from forty-two young men and women who received varying doses of menaquinone-7 during 12 weeks (study II) and from a cohort of 164 postmenopausal women who participated in a 3-year placebo-controlled trial on 45 mg menaquinone-4 (MK-4) (study III). No association was found between vitamin K status and circulating adiponectin before or after vitamin K supplementation. A higher carboxylation of OC was significantly correlated with lower body weight, BMI and fat mass of the trunk. Women taking MK-4 maintained their baseline body weight and BMI, whereas women taking placebo showed significant increases in both indices. These findings demonstrate that a high vitamin K status of bone has no effect on circulating adiponectin in healthy people and long-term vitamin K supplementation does not increase weight in healthy postmenopausal women.

The role of osteocalcin in human glucose metabolism: marker or mediator?

“…124 In studies using high doses of menaquinone-4, no effect on body weight was observed despite the reduction in the percentage of undercarboxylated osteocalcin. 125,126 In those studies that measured glucose metabolism, administration of both menaquinone-4 and phylloquinone reduced the percentage of undercarboxylated osteocalcin and HOMA-IR and improved insulin in men (Table 2). 120,125 Similar findings, however, were not noted in women.…”

VKORC1L1, an Enzyme Rescuing the Vitamin K 2,3-Epoxide Reductase Activity in Some Extrahepatic Tissues during Anticoagulation Therapy

“…The number of dispensed outpatient prescriptions for warfarin increased by 45%, from 21 million in 1998 to nearly 31 million in 2004 (19). Nevertheless, arterial calcifications were observed in human only after many years of VKA treatment (20,21). In laboratory animals, ectopic calcifications were observed in mice ApoE Ϫ/Ϫ treated by warfarin (20).…”

Serum Osteocalcin Is Not Associated with Glucose but Is Inversely Associated with Leptin across Generations of Nondiabetic Women

“…On average, 10% of circulating osteocalcin is undercarboxylated in mice. In contrast, undercarboxylated osteocalcin (ucOC) in humans can account for up to 40% (14,15), or even more (16), of circulating osteocalcin, depending on the methodology used for ucOC determination. Animal studies suggest that only the ucOC mediates the metabolic functions (2).…”