Nicotinamide riboside supplementation is not associated with altered methylation homeostasis in Parkinson's disease

Replenishing nicotinamide adenine dinucleotide (NAD) via supplementation of nicotinamide riboside (NR) has been shown to confer neuroprotective effects in models of aging and neurodegenerative diseases, including Parkinson's disease (PD). Although generally considered safe, concerns have been raised that NR sup-plementation could impact methylation dependent reactions, including DNA methylation, because of increased production and methylation dependent break-down of nicotinamide (NAM). We investigated the effect of NR supplementation on DNA methylation in a double blinded, placebo-controlled trial of 29 human subjects with PD, in blood cells and muscle tissue. Our results show that NR had no impact on DNA methylation homeostasis, including individuals with com-mon pathogenic mutations in the MTHFR gene known to affect one-carbon meta-bolism. Pathway and methylation variance analyses indicate that there might be minor regulatory responses to NR. We conclude that short-term therapy with high-dose NR for up to 30 days has no deleterious impact on methylation homeostasis.

Automated summary

Studies have shown that supplementing nicotinamide adenine dinucleotide (NAD) through nicotinamide riboside (NR) can provide neuroprotective effects in aging and neurodegenerative disease models, including Parkinson's disease (PD). This study investigated the impact of NR supplementation on DNA methylation in 29 human subjects with PD. The results indicate that short-term therapy with high-dose NR for up to 30 days does not negatively affect methylation homeostasis.