Nicotinamide riboside (NR), a form of vitamin B₃, is one of the most studied precursors of nicotinamide adenine dinucleotide (NAD+). Discovered in 1906, NAD+ plays a key role in the body’s oxidation-reduction reactions. Its levels deplete due to stress, aging, DNA damage, oxidative stress, inflammation, and enzyme consumption. This depletion can be countered by synthesizing NAD+ from tryptophan or other precursors, including NR.
NR converts to NAD+ in a two- or three-step process, which is significantly faster than tryptophan-based synthesis, which involves eight steps. In fact, a single 1,000 mg dose of NR can lead to a 2.7-fold increase in NAD+ levels in human whole blood. Natural sources of NR include yeast-derived food products and dairy products, such as cow milk and whey. Supplementation with NR initially began in mouse models on high-fat diets. Researchers observed that NR helped protect the mice from weight gain, improved their insulin sensitivity, and increased mitochondrial content in their skeletal muscle.
Further animal studies revealed that NR activated the SIRT1 gene, which plays a key role in healthy aging, cell survival, and metabolic control. By activating SIRT1, NR protected against cardiac hypertrophy and reduced systolic blood pressure in mouse models. Supplementation with NR in animal models of Alzheimer’s disease improved cognition and reduced brain degeneration by inhibiting amyloid-beta accumulation in the brain. NR’s ability to increase NAD+ levels helps combat oxidative stress and promotes DNA repair. Some researchers suggest that neurodegenerative disorders involving DNA-repair defects, like ataxia telangiectasia and xeroderma pigmentosum, may benefit from NR supplementation in the future.
NR also contributes to liver health. It promotes hepatocyte replication, increases hepatic ATP content, and reduces lipid accumulation in the liver. NR achieves these effects by decreasing NLRP3 inflammasome activity, which promotes inflammation, and by inducing the mitochondrial unfolded protein response. Clinical trials are currently investigating the impact of NR supplementation on muscle composition, inflammation, and Parkinson’s disease.
