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Do I Need To Combine an NMN Supplement With Methyl Donors?

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If you’re taking an NMN supplement, you may be asking whether to combine it with methyl donors. The answer is, it depends. Some theorize that taking extra methyl donors might be helpful, because NMN uses methyl groups during its breakdown and elimination. (Methyl groups are small molecules that are attached to other molecules to process them.) However, this theory has not really been born out in any studies yet.

Nonetheless, we believe it would be worth pairing your NMN supplement, like NOVOS Boost, with methyl donors and methylation mediators. These include B vitamins, trimethylglycine (betaine), choline, or pterostilbene (contained in NOVOS Core), 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). It also allows rogue elements in our DNA (called retrotransposons) to multiply themselves, causing mutations and inflammation. 

In short, we should indeed take more substances that improve DNA methylation, whether we take NMN or not. 

Substances like B vitamins, choline (abundant in egg yolks), trimethylglycine (betaine), and pterostilbene support the methylation process by donating methyl groups that attach to DNA.

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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

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 helps build DNA and components of the cell membrane. Deficiencies of B vitamins and choline can have serious long-term effects on our health. 

For example, choline deficiencies have been associated with increased DNA breaks (R,R,R), a dysregulated epigenome (R), and deteriorated mitochondrial functioning (R,R). NMN could improve all these things, 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, choline deficiency can lead to serious issues like DNA breaks, epigenetic dysregulation, and increased risks of cancer, fatty liver disease, and Alzheimer’s. These potential harms may substantially outweigh the possible negative effects of elevated 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.

Some people carry a mutation that reduces their ability to methylate (namely the MTHFR mutation). We wrote about this mutation and its relevance to NMN here.


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