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. NMN and TMG supplements are considered safe and do not significantly impact blood pressure levels.
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”. Just to put into perspective how important NAD+ is, if your levels of NAD+ would drop to zero, you would be dead in 30 seconds! As NAD+ sits at the Krebs cycle, without it, our cells cannot product ATP, or energy.
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.
Source: nmn.com/precursors/what-is-nad
We know this NAD+ decline is inevitable but that is where NAD+ boosters such as NMN come into play. There is a plethora of studies showing NMN and other NAD+ Boosters such as NR (although NR admittedly needs to convert itself into NMN first), help boost NAD+ levels in various peripheral tissues in the body while being well-tolerated with no major side effects. From overall body function, muscle support and heart health, to longevity specific applications such as boosting the collagen production pathway and offsetting physical & cognitive decline, NMN and NAD+ boosters are the daily supplement of choice for hundreds of thousands of people across the globe.
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, endurance, Vo2Max, insulin resistance and cardiovascular health. TMG supplements also offer various health benefits, including liver and mental health, insulin regulation, and athletic performance. Popular Key Opinion Leaders in the health and wellness space such as Dr Andrew Huberman also take NMN and publicly disclose the benefits they are seeing with this Vitamin B3 derivative. 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, and consumers experience enhanced benefits from this supplement combination.
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:
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Creating neurotransmitters
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Cell division (Mitosis)
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Energy production
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Metabolism
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DNA expression (epigenetics)
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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. Processed foods, seed oils and other environmental factors might be contributing to "methylation drainage" just to name a few. But as we age, not only methylation, but many other vital cellular systems and processes are in decline after the age of 25. This is our when our hormonal peak is happening, and the aging process basically starts.
Epigenetics & Aging
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.
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 of our bodies to 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:
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Cardiovascular health
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Mental health
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Cancer
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Chronic pain and fatigue
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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, and 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 (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. Sinclair’s research into longevity supplementation is world-class so we take his anecdotal support of TMG seriously.
NMN & TMG Supplement Combination
The power of NMN to boost NAD+ and thereby increase our bodies’ anti-aging potential is already well established. The first N in NMN stands for Nicotinamide, and when we take NMN and our body metabolises it, it's secreted via urine. In order for this process to take place though, Nicotinamide needs to have a methyl group attached to it. This is where TMG comes in. TMG (trimethylglycine - a glycine molecule with 3 methyl groups attached to it), is what we call a rich methyl donor. So it donates it's methyl groups to NMN, in order to optimise it's metabolism and maximise it's efficiency. Interestingly, consumers report a further increase in endurance and stamina at the gym, when adding TMG to their NMN supplementation.
TMG and NMN Summary
NMN has been proven to provide anti-aging benefits by enhancing the function of our Sirtuins and PARPS. From DNA repair to inflammation control these essential proteins 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 anti-aging processes.
References
The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule -Shade et al 2020
Researched and reviewed by Dr Elena Seranova, Ph.D.
Dr Seranova holds a master's degree in Translational Neuroscience from the University of Sheffield, UK, and a Ph.D in Stem Cell Biology and Autophagy from the University of Birmingham, UK. She is a published author in multiple peer-reviewed journals, including Cell Reports and Developmental Cell.
