Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial.

Randomized, double-blind, placebo-controlled, 3-arm trial conducted at a single center in Denmark in 76 middle-aged obese men with metabolic syndrome. Participants were assigned 1:1:1 to high-dose resveratrol, low-dose resveratrol, or placebo and followed for 16 weeks; 66 completed the study, including 21 in each resveratrol arm.

Oral trans-resveratrol tablets were given for 16 weeks in two active regimens: 500 mg twice daily (1,000 mg/day) in the high-dose arm and 75 mg twice daily (150 mg/day) in the low-dose arm, compared with placebo.

High-dose resveratrol showed the clearest benefit, with a dose-dependent rise in bone alkaline phosphatase and an improvement in lumbar spine trabecular bone density. Bone alkaline phosphatase increased in the high-dose group versus placebo by 16.4 4.2% at week 4, 16.5 4.1% at week 8, and 15.2 3.7% at week 16, with a dose-response association of R 0.471, P .001. Lumbar spine trabecular vBMD increased by 2.6 1.3% versus placebo after 16 weeks (P .043) and by 2.6 0.9% from baseline (P .009); P1NP also increased at week 8 by 8.0 4.5% versus placebo (P .049). Low-dose resveratrol produced smaller, mostly nonsignificant changes, and hip outcomes, resorption markers, and inflammation-related measures were not consistently improved.

This was a small, single-center trial in obese men with metabolic syndrome, which limits generalizability. Follow-up was only 16 weeks, so durability of the bone effects is unknown. Several outcomes were null or site-specific, with no consistent hip benefit and no clear inflammatory mechanism, and some analyses had incomplete data availability.