NMN raises NAD+, supports mitochondrial function, promotes DNA repair. This is correct and worth understanding. But it is only half of the relevant biochemistry. The other half is what NMN does as a side effect of doing its job — and what you need to do about it.
The Methylation Problem
NMN raises NAD+ via a biochemical pathway called the salvage pathway. In this pathway, NMN is converted to NAD+ through a reaction that generates nicotinamide as a byproduct, which the body then methylates before excreting it. Each cycle of NAD+ synthesis and recycling draws on the body's methyl donor pool.
Methyl groups are essential. Methylation regulates gene expression, neurotransmitter metabolism, homocysteine clearance, liver function, and the production of compounds including creatine, carnitine, and phosphatidylcholine. The methyl donor pool is finite. When NMN supplementation increases NAD+ turnover, it increases the demand on this pool.
For most people, dietary intake of methyl donors is sufficient under normal conditions. Under sustained NMN supplementation — particularly at higher doses — the increased demand can deplete the pool over time. The consequence is subtle but real: slightly reduced mood, slightly impaired cognitive function, slightly elevated homocysteine. All consistent with methyl depletion. All addressed by TMG.
What TMG Does
TMG — Trimethylglycine, also known as Betaine Anhydrous — is one of the most efficient methyl donors available. Each molecule carries three methyl groups and donates them readily in the methylation cycle. Beyond its role as a methyl donor, TMG has an independent body of research in sports supplementation: multiple trials have demonstrated improvements in bench press repetitions and cycling performance. It also supports healthy homocysteine levels and liver function via its role in fat metabolism.
"This is not optional biochemistry. It is the part of the NMN protocol that most brands do not tell you because it means recommending a second product. We are telling you because it is true."
Alchemy Fit — The Science of ProtocolThe Practical Protocol
Take TMG on the same schedule as NMN. If you take NMN in the morning, take TMG in the morning. The methylation demand from NMN supplementation is ongoing — TMG should be present continuously, not intermittently.
600mg of TMG daily is the dose consistent with both the sports performance research and the methyl donor replenishment requirement for standard NMN protocols. If you are running NMN at higher doses — 1000mg or above — consider whether 600mg of TMG remains sufficient.
Editorial note: This article is for informational and educational purposes only and does not constitute medical advice. These statements have not been evaluated by the MHRA. Consult a qualified healthcare professional before beginning any supplementation.