A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects.

Randomized placebo-controlled trial in obese, insulin-resistant, sedentary adult men at Aarhus University Hospital in Aarhus, Denmark. Participants were Caucasian men with BMI > 30 kg/m2.

Nicotinamide riboside (NIAGEN) was given orally at 1000 mg twice daily for 12 weeks, for a total dose of 2000 mg/day. Capsules were identical to placebo.

Nicotinamide riboside was safe over 12 weeks, but it did not improve insulin sensitivity or whole-body glucose metabolism in obese, insulin-resistant men. The primary insulin sensitivity outcome was unchanged (M-value interaction P = 0.71), and hepatic lipid content fell slightly in the NR group versus placebo but was not significant (−2% vs −0.2%, P = 0.13). NR increased urinary NR- and NAD-derived metabolites versus placebo (P < 0.01), but fasting glucose, HbA1c, total cholesterol, HDL, LDL, and ALT were not meaningfully improved. No serious adverse events occurred; minor adverse reactions were reported in 4 participants in the NR group.

The trial was short at 12 weeks and studied a restricted population of sedentary, obese, insulin-resistant Caucasian men, which limits generalizability. The single-center design and lack of benefit on the primary metabolic endpoint also limit confidence in broader clinical effects.