As with many things NAD+ related, there’s confusion among consumers as to whether taking oral supplement Nicotinamide Riboside “NR” (FAQs) (Reviews) might cause methyl depletion. Not according to the following:

From NAD+ Expert Dr. Charles Brenner (FAQs):

From the FAQs of the Nicotinamide Riboside “NR” SubReddit:

Question: Should I be worried about methyl depletion?

“Probably not.

A research team looking at NR in Parkinson’s disease in 2023 noted that concerns had been raised that NR supplementation could impact methylation dependent reactions, including DNA methylation, because of increased production and methylation dependent breakdown of nicotinamide (NAM).

So they investigated the effect of NR supplementation on DNA methylation in a double blinded, placebo-controlled trial of 29 human subjects for 30 days.

Their results showed that NR had no impact on DNA methylation homeostasis, including individuals with the MTHFR gene, which is known to affect one-carbon metabolism.

They said, “We show that NAD-replenishment therapy by oral supplementation with 1,000 mg NR daily for 30 days has no influence on global levels or genome-wide distribution of DNA methylation…Currently, the only evidence that NAD replenishment could lead to methylation depletion derives from studies in which animals were given very high doses of NAD precursors commonly combined with stress conditions such as dietary deprivation of methyl-donors.”

The study was published in iScience.

A new human clinical trial in November 2023 found that “NR even at a dose of 3000 mg for 4 weeks does not cause depletion of the methyl-group pool.”

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