A new study about the safety of Nicotinamide Riboside was published in the Human and Experimental Toxicology (HET) journal. HET is an international peer reviewed journal that is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology.
Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 present in trace amounts in some foods and believed to provide a multitude of health benefits. Like niacin, which is on the market for much longer, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NADþ).
The researchers used Niagen, which is a synthetic form of NR for this analyses. They applied a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay and acute, 14-day and 90-day rat toxicology studies to come to their conclusions. They found that NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Additionally based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day. They also compared that to the safety assessment of an equimolar dose of nicotinamide at 1260 mg/kg/day as a reference. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was found at 1000 mg/kg/day, and there were no observed adverse effects at a level of 300 mg/kg/day. Unfortunately the researchers did not test at more granular levels than these.
These tests were done in rats and therefore the doses need to be first translated to human equivalent doses to form more perspective on the safety. The FDA has specified guidelines for this conversion to Human Equivalent Dose (HED). They also stipulated an extra minimum safety factor of 10 to be used to indicate safe human doses. So starting from the 300mg/kg/day dose in rats in which no adverse side effects were observed we calculate a HED of 48mg/kg/day. Without safety factor that translates into 48 x 60 = 2880mg / day for a person weighing 60kg. Applying the 10 fold FDA safety factor that results in 288mg/day as indication for safe dosing for a 60kg person. This appears to be in range of the recommended dosing for supplements on the market.
It should be also noted that the research mentions the safety profile to be similar to nicotinamide (also called niacinamide). Nicotinamide is typically rated as LIKELY SAFE with the note that at dosing above 3 grams / day serious side effect can occur: liver problems, gout, ulcers of the digestive tract, loss of vision, high blood sugar, irregular heartbeat, and other serious problems. On a molar mass basis 3 grams or nicotinamide / day equals roughly to a dosing of 7 grams / day of Nicotinamide Riboside. That is 28 x more than the recommended daily dosing for supplements on the market.