A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects.
What this study found
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…
- Study & population
- Randomized placebo-controlled trial in obese, insulin-resistant, sedentary adult men at Aarhus University Hospital in Aarhus, Denmark.
- Intervention
- Nicotinamide riboside (NIAGEN) was given orally at 1000 mg twice daily for 12 weeks, for a total dose of 2000 mg/day.
- Key limitation
- The trial was short at 12 weeks and studied a restricted population of sedentary, obese, insulin-resistant Caucasian men, which limits generalizability.
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Open PDFOriginal abstract
Background Animal studies suggest a positive role for nicotinamide riboside (NR) on insulin sensitivity and hepatic steatosis in models of obesity and type 2 diabetes. NR, an NAD+ precursor, is a member of the vitamin B-3 family now available as an over-the-counter supplement. Although data from preclinical trials appear consistent, potential effects and safety need to be evaluated in human clinical trials. Objective The aim of this study was to test the safety of dietary NR supplementation over a 12-wk period and potential to improve insulin sensitivity and other metabolic parameters in obese, insulin-resistant men. Design In an investigator-initiated randomized, placebo-controlled, double-blinded, and parallel-group designed clinical trial, forty healthy, sedentary men with a body mass index (BMI) > 30 kg/m2, age-range 40-70 y were randomly assigned to 12 wk of NR (1000 mg twice daily) or placebo. We determined the effects of NR supplementation on insulin sensitivity by a hyperinsulinemic euglycemic clamp and substrate metabolism by indirect calorimetry and labeled substrates of tritiated glucose and palmitate. Body composition and fat mass distribution were determined by whole-body dual-energy X-ray absorptiometry (DXA) and MRI scans, and measurements of intrahepatic lipid content were obtained by MR spectroscopy. Results Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR supplementation. Similarly, NR supplementation had no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition. No serious adverse events due to NR supplementation were observed and safety blood tests were normal. Conclusion 12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men. This trial was registered at clinicaltrials.gov as NCT02303483.