Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial

Undercarboxylated osteocalcin (ucOC) is reported to function as an endocrine hormone, affecting glucose metabolism in mice (1,2). Vitamin K, which converts ucOC to carboxylated osteocalcin (cOC), has been suggested to regulate glucose metabolism by modulating osteocalcin and/or proinflammatory pathway (3–5). We studied whether modulation of ucOC via vitamin K2 supplementation for 4 weeks affects β-cell function and/or insulin sensitivity in healthy young male subjects. Forty-two healthy young male volunteers received vitamin K2 (menatetrenone; 30 mg; Eisai Co., Japan) or placebo t.i.d. for 4 weeks. Frequently sampled intravenous glucose tolerance test was performed to determine insulin sensitivity index ( S i), acute insulin response to glucose (AIRg), and disposition index (DI) before and after treatment. Adiponectin, interleukin (IL)-6, C-reactive protein (CRP), ucOC, and cOC …