Medical Advisory Board: Dr. Ram Dandillaya, Clinical Chief, Cardiology, Cedars-Sinai; Dr. Antonio J. Forte, Faculty, Mayo Clinic; Dr. John J. Lee, Faculty, Harvard Medical School; Dr. Daniel Kahneman, Nobel Prize Laureate. OpenEvidence is a Mayo Clinic Platform Accelerate Company.

Answered on June 5, 2023

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD) precursor vitamin that has gained attention for its potential health benefits. Studies have demonstrated its safety and efficacy in increasing NAD levels, which may provide protective effects against various pathological conditions.[1] In a randomized, double-blind, placebo-controlled clinical trial, long-term administration of NR at doses of 100, 300, and 1000 mg showed dose-dependent increases in whole blood NAD levels without significant adverse events or dysregulation of 1-carbon metabolism.[2] Another study found that 12 weeks of NR supplementation at 2000 mg/day appeared safe, although it did not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men.[3]
The European Food Safety Authority concluded that NR is safe for use in food supplements for the healthy adult population, excluding pregnant and lactating women, at levels up to 300 mg/day. For pregnant and lactating women, an intake of up to 230 mg/day is considered safe.[4] A 90-day oral toxicity study in rats determined the no-observed-adverse-effect-level (NOAEL) for systemic toxicity of a high-purity, synthetic NR to be 500 mg/kg/day for males and 1,200 mg/kg/day for females.[5]
Overall, current evidence supports the safety of NR supplementation in healthy adults, with some limitations for pregnant and lactating women. However, further research is needed to fully understand its potential health benefits and long-term safety profile.

References

1.Sharma C, Donu D, Cen Y. Emerging Role of Nicotinamide Riboside in Health and Diseases. Nutrients. 2022;14(19):3889. doi:10.3390/nu14193889.
3.Dollerup OL, Christensen B, Svart M, et al. A Randomized Placebo-Controlled Clinical Trial of Nicotinamide Riboside in Obese Men: Safety, Insulin-Sensitivity, and Lipid-Mobilizing Effects. The American Journal of Clinical Nutrition. 2018;108(2):343-353. doi:10.1093/ajcn/nqy132.
4.Turck D, Castenmiller J, de Henauw S, et al. Safety of Nicotinamide Riboside Chloride as a Novel Food Pursuant to Regulation (EU) 2015/2283 and Bioavailability of Nicotinamide From This Source, in the Context of Directive 2002/46/Ec. EFSA Journal. European Food Safety Authority. 2019;17(8):e05775. doi:10.2903/j.efsa.2019.5775.
5.Marinescu AG, Chen J, Holmes HE, et al. Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. International Journal of Toxicology. 2020 Jul/Aug;39(4):307-320. doi:10.1177/1091581820927406.

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