Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men With Obesity

Objective: Augmenting nicotinamide adenine dinucleotide (NAD(+)) metabolism through dietary provision of NAD(+) precursor vitamins translates to improved glucose handling in rodent models of obesity and diabetes. Preclinical evidence suggests that the NAD(+)/SIRT1 axis may be implicated in modulating important gut-related aspects of glucose regulation. We sought to test whether NAD(+) precursor supplementation with nicotinamide riboside (NR) affects beta-cell function, alpha-cell function, and incretin hormone secretion as well as circulating bile acid levels in humans. Design: A 12-week randomized, double-blind, placebo-controlled, parallel-group trial in 40 males with obesity and insulin resistance allocated to NR at 1000 mg twice daily (n = 20) or placebo (n = 20). Two-hour 75-g oral glucose tolerance tests were performed before and after the intervention, and plasma concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were determined. beta-Cell function indices were calculated based on glucose, insulin, and C-peptide measurements. Fasting plasma concentrations of bile acids were determined. Results: NR supplementation during 12 weeks did not affect fasting or postglucose challenge concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, or GIP, and beta-cell function did not respond to the intervention. Additionally, no changes in circulating adipsin or bile acids were observed following NR supplementation. Conclusion: The current study does not provide evidence to support that dietary supplementation with the NAD(+) precursor NR serves to impact glucose tolerance, beta-cell secretory capacity, alpha-cell function, and incretin hormone secretion in nondiabetic males with obesity. Moreover, bile acid levels in plasma did not change in response to NR supplementation.