The ultimate anti-aging combination: TMG & NMN to live significantly longer?

The ultimate anti-aging combination: TMG & NMN to live significantly longer?

Nicotinamide mononucleotide (NMN) is currently one of the most exciting supplements in the anti-aging world.

Its main function is its ability to increase nicotinamide adenine dinucleotide (NAD+) in our bodies.

NAD+ is an extremely important coenzyme that is responsible for energy creation and cell functionality. It also facilitates a group of enzymes called sirtuins or “longevity genes”.

Sirtuins can help reverse DNA damage and also help fight inflammation. Both of which are major contributing factors to age-related illnesses.

Similarly our DNA repairing genes PARPS(poly ADP-ribose polymerases) also heavily rely on adequate NAD+ levels to work efficiently.

Without sirtuins and PARPS, our DNA and bodies gradually degrade leading to all kinds of age-related diseases.

We need NAD+ levels to remain optimal because without NAD+ our Longevity systems fail.

Sadly, NAD+ levels inevitably decrease over our lifetimes and the decrease is quite fast.

Table 1. NAD+ Decline as we age.




We know this NAD+ decline is inevitable but that is where NMN comes into play.

NMN Supplement – a Fountain of Youth?
NMN is known to boost NAD+ levels in the body by up to 240%. Studies have shown "NMN may improve adult human metabolism, rendering it more like that of someone ten or twenty years younger" Shade et al (2020)! Human studies of NMN are coming in strong of late and showing NMN to be beneficial in athletic performance, insulin resistance and cardiovascular health.

NMN has also been confirmed as safe by multiple human studies including Irie et al (2020).

The longevity community has however found that NMN could be complemented by combining it with methylation support.

NMN Methylation – What is it?

Methylation is a natural bodily process in which three hydrogen atoms and one carbon atom (CH3) are transferred from one molecule to another. This process is vital for many of our body’s most important functions, such as:

Creating neurotransmitters
Cell division (Mitosis)
Energy production
DNA expression (epigenetics)
Fighting free radicals

As you can see methylation is extremely important, but our bodies don’t have an unlimited fuel source for methylation. Our bodies have ‘storage centres’ of CH3 methyl groups that we can draw upon whenever transfers need to be made for methylation. When we have enough ‘fuel’, methylation runs smoothly but when the CH3 fuel runs low it can lead to serious health problems.

Why do we need to support our Methylation Systems?

There are many reasons for decreased methylation efficiency as we age.

Epigenetics & Aging

NMN,  TMG,  NAD,  Dr Elena Seranove
For a start, aging is a big factor in our ability to maintain efficient methylation. As we get older our methylation ability declines. This is bad news for our DNA expression as without adequate methylation our ability to read and activate the correct parts of our DNA blueprints are hampered.

NMN, TMG, NAD, Dr Elena Seranova
This problem is similar to a builder trying to fix an issue in an old building.
Imagine there’s a leak in the piping but the old blueprints of the property are no longer readable for that part of the building. The builder can no longer work efficiently without the correct information and so the issues are harder to fix.
When our DNA is not being expressed efficiently, the ability for our bodies’ repair and production systems are hampered as the required information just isn’t as easily accessible.

MTHFR Variants

Methylenetetrahydrofolate reductase (MTHFR) is a gene that is susceptible to mutating variants that can cause high levels of homocysteine in our bodies. There are two main variants of MTHFR variants - heterozygous and homozygous – and these are found in many cultures all over the world. Up to 40% of US residents have one of these variants. If you are unlucky enough to have one or both of these variants then it can lead to improper methylation. This can cause issues with:

Cardiovascular health
Mental health
Chronic pain and fatigue
Pregnancy complications
However, methylation issues can be tackled with a healthy diet & correct supplementation of B vitamins or methyl donors such as TMG (Trimethylglycine or Betaine).

TMG Health Benefits – A Methylation Donor

Trimethylglycine (TMG) also called Betaine - is a naturally occurring substance in the body. It's involved in liver function, cellular reproduction, and it helps make essential metabolic compounds.

It is an amino acid with three methyl groups attached to each molecule of glycine. As a methyl donor, it can replenish our ‘methyl pool’ and therefore support healthy methylation.

As we age our ‘methyl pool’ can deplete which makes TMG a very useful supplement for replenishing our bodies’ methyl groups.

TMG also helps the body metabolize an amino acid called homocysteine, a process that the FDA found to be efficacious enough to endorse and approve. High homocysteine levels are a risk factor for cardiovascular and Alzheimer’s disease. High levels of homocysteine can cause damage to the lining of arteries and create clots which can lead to strokes, heart attacks and pulmonary embolisms.

TMG, cadiovascular health, NMN, NAD, Dr Elena Seranova

TMG, cadiovascular health, NMN, NAD, Dr Elena Seranova

TMG (or Betaine) has been proven to “lower plasma homocysteine” McRae et al (2013), which will protect against these unwanted cardiovascular issues.

Lastly, anti-aging guru Dr. David Sinclair uses TMG for methyl donor support. He has experimented with multiple supplements and settled on TMG as a means of supporting his methylation systems. Dr. Sinclairs’ research into longevity supplementation is world-class so we take his anecdotal support of TMG seriously.

NMN & TMG Supplement Combo

The power of NMN to boost NAD+ and thereby increase our bodies’ antiaging potential is already well established. For NMN to do its job it has to perform some biochemical activity in the body.

NMN uses the bodies’ salvage pathway to help in the creation of nicotinamide (NAM). This process requires methylation so that the NAM is methylated into N-methyl nicotinamide. This metabolite can then be expelled in urine.

Ultimately, this process of converting NMN to NAM and then excreting the NAM does require methylation, which as previously discussed, requires the use of our bodies’ methyl groups. TMG supplementation with NMN can mitigate any decrease in methyl group levels following NMN supplementation.
It should be noted that NMN is still considered to be very safe but TMG supplementation may improve the bodies’ consumption of it.

TMG + NMN Overview

NMN has been proven to provide antiaging benefits by enhancing the function of our sirtuins and PARPS. From DNA repair to inflammation control these essential elements love NMN. We have also looked at the importance of methylation in DNA expression and bodily functions. TMG has been approved by the FDA to lower homocysteine in our blood plasma which can help fight off cardiovascular issues. TMG has also been shown to support our bodies’ methyl pool by donating methyl groups to it. NMN & TMG work well together because NMN-induced NAD+ production requires the use of the methylation process, a process that TMG can support. NMN and TMG together offer one of the best ways to activate and maintain the healthy function of our antiaging processes.

 TMG, NMN, healthy heart, liver health

TMG, NMN, healthy heart, liver health


The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule -Shade et al 2020

Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men- Irie et al 2020

Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis - McRae et al 2013