Do I need to take methyl donors with my NMN?

It depends.

There is a theoretical assumption that one would need to take extra methyl donors given NMN uses up methyl groups in order to be degraded and excreted (methyl groups are small molecules that are attached to other molecules to process them). However, this has not really been born out in any studies yet.

Nonetheless, we still believe it could be interesting to combine your NMN supplement with methyl donors and methylation mediators, like B vitamins, trimethylglycine (betaine) and choline, and to see how it impacts you.

The importance of proper methylation of our DNA

Methyl donors and methylation mediators are important for general health and to slow down aging.

These substances make sure our DNA is methylated. This is very important for proper functioning of our cells. By methylating DNA (or specific genes), these genes are switched off.

When we get older, many regions in the DNA become too little methylated. This allows genes to become active that should not be active (like cancer genes), and allows rogue elements in our DNA (called retrotransposons) to multiply themselves, causing mutations and inflammation.

To make a long but fascinating story short, we should indeed take more substances that improve DNA methylation, whether we take NMN or not.

These are substances like B vitamins, that help the methylation process, choline (found in abundance in egg yolks) and trimethylglycine (betaine) that provide the methyl groups (which are then put on the DNA).

B vitamins

Ideally, one would take a B vitamin complex, containing all B vitamins, such as vitamin B12, vitamin B9 (folate) and vitamin B6, given many B vitamins work in a synergistic way.

Learn more about B vitamins and other important supplements everyone should take, even if you eat healthy.


Choline is an important methyl donor. Unfortunately, many people have a deficiency, especially people who eat a more plant-based diet.

Choline is necessary to methylate DNA (and thus plays an important role in the epigenome).

Choline is also needed to build DNA and to build components of the cell membrane. Deficiencies of B vitamins and choline can have serious long-term effects on our health.

For example, deficiencies of choline have been associated with increased DNA breaks (R,R,R), a dysregulated epigenome (R), and deteriorated mitochondrial functioning (R,R), which are all things that NMN could improve, but giving it a hand via choline is likely prudent.

Some studies show that choline can be converted by specific gut bacteria into TMAO, which could increase the risk of atherosclerosis. However, to make a long story short, not all studies have yet shown a convincing correlation with (only) choline intake and an increased risk of heart disease.

More importantly, the detrimental effects of not taking adequate choline (such as DNA breaks, epigenetic dysregulation, an increased risk of cancer, fatty liver disease and Alzheimer’s) could substantially outweigh the potential negative effect of TMAO.

Nonetheless, some people aim to reduce the risk of choline forming too much TMAO by taking half of the amount of choline and combining it with trimethylglycine (TMG or betaine). However, in some people, too much TMG can cause side effects, like sleep problems or digestive issues. Others combine choline with phosphatidylcholine (PC). PC is an important fatty acid that contains choline, and that also improves brain function.

To learn more about B vitamin and choline, we wrote a blog post about the most important supplements to take.