A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men
Dollerup OL, Christensen B, Svart M, et al.
Key finding
12 weeks of 2 g/day NR in obese but otherwise healthy men did not improve insulin sensitivity, ectopic lipid, or body composition vs. placebo.
Summary
Randomized, double-blind, placebo-controlled trial of NR in 40 sedentary obese but otherwise healthy men (BMI 30-40). Participants received 1 g NR twice daily (2 g/day total) or placebo for 12 weeks. Primary endpoint was insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Secondary endpoints included body composition (DXA), hepatic and intramyocellular lipid content (MRS), and muscle mitochondrial function (ex vivo respirometry). Contrary to preclinical expectations based on rodent high-fat-diet studies, NR at this dose produced no statistically significant improvement in insulin sensitivity, ectopic lipid, body composition, or resting energy expenditure vs. placebo. Safety was excellent with no serious adverse events. The trial is an important counterpoint to optimistic rodent extrapolations: even at doubled doses for three times the duration of early NR safety studies, metabolic endpoints in otherwise-healthy obese men did not improve. The study highlighted the rodent-to-human translation gap and sharpened focus on populations with greater baseline NAD+ deficit as more likely responders.
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