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

cell.com/iscience/fulltext/...

Highlights

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NR 1000mg/day for 30 days does not alter the global DNA methylation profile in blood

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NR does not impact DNA methylation in individuals carrying common MTHFR mutations

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Pathway and methylation variance analyses indicate minor regulatory responses to NR

Summary

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). While generally considered safe, concerns have been raised that NR supplementation could impact methylation dependent reactions, including DNA methylation, due to 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.

[rescuema]

Qualifiers -

"However, our findings cannot exclude the possibility that individuals with biallelic mutations may be susceptible to methyl group depletion upon exposure to NAD replenishment therapies...

A limitation of our study is the relatively short timeframe of exposure (30 days). Based on our data, we cannot exclude that a long-term exposure to NR may over time incrementally...

Given this, and the dynamic nature of DNA methylation, we deem it highly likely that a biologically significant NR-induced methyl group depletion would have manifested within the time frame of our study. Still, data from longer studies are needed to confidently exclude this possibility. It should also be stressed that our findings in PBMCs do not necessarily reflect the state of other tissues and organs. "

That's as to blood cells and muscle tissue in PD subjects.