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 supplementation could impact methylation dependent reactions, including DNA methylation, because of increased production and methylation dependent breakdown 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 common pathogenic mutations in the MTHFR gene known to affect one-carbon metabolism. 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.

 

Comments：

It is interesting to know that the study found no negative impact of NR supplementation on DNA methylation homeostasis in both blood cells and muscle tissue.

As you mentioned, concerns have been raised about the potential impact of NR supplementation on methylation-dependent reactions, including DNA methylation, due to the increased production and breakdown of nicotinamide (NAM). The study's finding that NR supplementation did not affect DNA methylation homeostasis is reassuring, particularly for individuals with pathogenic mutations in the MTHFR gene known to affect one-carbon metabolism.

The results of the pathway and methylation variance analyses suggesting minor regulatory responses to NR are also intriguing and warrant further investigation. Overall, the study's conclusion that short-term therapy with high-dose NR for up to 30 days has no deleterious impact on methylation homeostasis provides valuable information for individuals considering NR supplementation for neuroprotective effects.

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S2935	Nicotinamide Riboside Chloride	Nicotinamide Riboside Chloride is the chloride salt form of nicotinamide riboside(NR).NR is a new form pyridine-nucleoside of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide(NAD) or NAD+ . Nicotinamide riboside chloride is a crystal form of Nicotinamide riboside (NR) chloride. Nicotinamide riboside chloride increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside chloride is used in dietary supplements.

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Sirtuin