TMG (Trimethylglycine / Betaine)
Research Reliability -
A methyl donor involved in homocysteine metabolism. Replenishes methyl groups consumed by NAD+ precursors, creatine, and other methylation-heavy stacks.
Appetite
Mood
Sleep
TMG (Trimethylglycine / Betaine)
Description
Trimethylglycine donates methyl groups directly to homocysteine, converting it back to methionine via the betaine-homocysteine methyltransferase pathway — an alternative route to the folate/B12-dependent methylation cycle. It is a quiet workhorse in biohacking stacks because high-dose NAD+ precursors, creatine, and phosphatidylcholine all consume methyl groups during their own metabolism, and TMG helps prevent the resulting depletion. Clinical use also includes supporting liver health in non-alcoholic fatty liver disease, where it reduces fat accumulation in hepatocytes.
Effects
First 2 weeks
subtle
Weeks 2–4
Ongoing
How It Feels
Mostly a methylation supporter measured by homocysteine on labs, though some people notice a mild boost in energy or gym performance. It is often stacked with NMN to offset methylation demand. Gentle and well tolerated.
Evidence
Evidence Strength
Moderate (some human RCTs)
Caveats
Homocysteine-lowering effect is well established; evidence for athletic performance benefits is more preliminary and mixed.
Usage
Commonly Referenced Starting Amount
500 mg/day
Commonly Referenced Amount
500 mg to 6 g/day covers the range used in homocysteine-lowering research
Referenced Upper Limit
No formal upper limit has been established, but higher doses have been associated with a rise in LDL and total cholesterol — worth tracking lipids if using it at the higher end long-term
Onset
2–4 weeks (homocysteine)
Biomarkers to Track
Subjective
(Daily)
Energy and mental clarity (1–10)
Liver and digestive comfort
Mood stability
Objective
(Quarterly)
Homocysteine level
Liver enzymes (ALT, AST)
Lipid panel
Generally safe. It lowers homocysteine and pairs well with methylation-demanding compounds.
People with kidney disease should check first.
Overlooking it as an NMN companion, and expecting a strong felt effect.
Disclaimer
This information is for educational purposes only and is not medical advice. It is not intended to diagnose, treat, cure, or prevent any disease. Consult a qualified healthcare provider before starting any new supplement, especially if you are pregnant, nursing, taking medication, or managing a health condition.
Olthof MR, Verhoef P (2005). Current Drug Metabolism. Review (betaine and homocysteine metabolism). PMID: 15975043.
MORE SUPPLEMENTS LIKE THIS
