NMN and TMG: Why You Should Stack Them for Better Results
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If you take NMN, there is a strong scientific argument for adding TMG (trimethylglycine, also called betaine) to your stack. David Sinclair, the Harvard longevity researcher behind much of the NMN research boom, takes both. This guide explains why, and whether the evidence supports it.
What Is TMG and Why Does It Matter for NMN Users?
TMG is a methyl donor — a compound that donates methyl groups to biochemical reactions throughout the body. When NMN is converted to NAD+ in your cells, it generates a byproduct called nicotinamide, which your body processes via a pathway that consumes methyl groups. At higher NMN doses (500mg and above), this methyl consumption becomes meaningful.
Without adequate methyl donors, this process can theoretically deplete your body's methyl pool, affecting everything from DNA methylation to neurotransmitter synthesis. TMG replenishes that pool directly.
The NMN and TMG Stack: What the Evidence Shows
The case for combining NMN and TMG is both mechanistic and practical:
- Methyl balance: TMG provides the methyl groups that NAD+ metabolism consumes, maintaining healthy homocysteine levels and supporting methylation reactions
- Cardiovascular support: TMG independently reduces homocysteine — a known cardiovascular risk marker — making the combination beneficial for heart health beyond NMN's direct effects
- Liver health: TMG supports healthy liver fat metabolism and has been studied in the context of non-alcoholic fatty liver disease
- Synergistic methylation: TMG works alongside other methyl donors like vitamin B12 and folate to maintain optimal DNA methylation patterns
How Much TMG to Take with NMN
Most longevity-focused practitioners recommend a 1:1 or 2:1 ratio of TMG to NMN by weight. At 500mg NMN daily, a typical TMG dose would be 500mg to 1000mg per day. TMG is well-tolerated at these doses and widely available as a standalone supplement.
When to Take NMN and TMG Together
Both NMN and TMG are typically taken in the morning. NMN is best taken on an empty stomach or with a light meal to maximise absorption. TMG can be taken at the same time without any known interaction concerns.
Bottom Line
If you are taking NMN 500mg daily, adding TMG is a sensible precaution backed by sound biochemistry. It is low-cost, well-studied and may actively enhance the cardiovascular and methylation benefits of your NMN protocol.