TMG (Trimethylglycine)
TMG is a methyl donor that keeps your homocysteine in check — especially important if you take NMN or have methylation issues. Simple, affordable, and effective.
TMG (trimethylglycine, also called betaine) donates methyl groups to lower homocysteine via the BHMT pathway. It's especially important for anyone taking NMN (which increases methyl group demand) and for people with elevated homocysteine despite adequate B12 and folate.
Good for you if: You take NMN or NR, your homocysteine is elevated, you have MTHFR variants, or you want to support your methylation cycle.
Dive deeper into the researchCommon side effects
- Fishy body odour at very high doses (trimethylamine production)
- Mild GI upset (nausea, diarrhoea)
- May raise LDL cholesterol slightly in some people
What does TMG do?
Your body constantly runs a process called methylation — transferring methyl groups (-CH₃) to DNA, proteins, neurotransmitters, and other molecules. It's essential for everything from gene expression to detoxification. TMG donates three methyl groups, helping keep this cycle running smoothly.
The most measurable benefit: TMG converts homocysteine (a toxic amino acid) back into methionine via the BHMT enzyme. This is especially important if you take NMN, which increases methyl group consumption.
What can you expect?
- Lower homocysteine — 10–20% reduction at standard doses
- Better methylation support — maintains SAMe levels (the body's universal methyl donor)
- NMN stacking partner — replenishes methyl groups that NMN metabolism consumes
- Liver protection — helps prevent fatty liver by supporting phosphatidylcholine synthesis
How to take it
500–1,000 mg per day with food. If taking NMN, match your TMG dose roughly 1:1 (e.g., 500 mg TMG with 500 mg NMN). If your homocysteine is elevated, doses up to 2,000 mg/day are used in clinical practice.
TMG is also called "betaine anhydrous" — this is the same thing. Don't confuse it with betaine HCl, which is a completely different supplement used for stomach acid.
Track your homocysteine over time
eterni tracks homocysteine, B12, folate, and methylation markers — essential for anyone on an NMN protocol.
Get early accessFrequently Asked Questions
Why should I take TMG with NMN?
NMN metabolism increases demand on the methylation cycle. When NAD+ is recycled, nicotinamide is methylated by NNMT for excretion, consuming SAMe-derived methyl groups. Without adequate methyl donors, homocysteine can rise. TMG donates three methyl groups via the BHMT pathway, replenishing the methyl pool and keeping homocysteine in check.
Is TMG the same as betaine?
Yes. TMG (trimethylglycine) is the chemical name for betaine. Betaine anhydrous is the supplement form. Betaine HCl is a completely different product — it provides hydrochloric acid for stomach acid support and does not provide methylation benefits.
What's the right dose of TMG?
Most longevity protocols use 500–1,000 mg/day alongside NMN. Clinical trials for homocysteine reduction have used 1,500–6,000 mg/day. For NMN stacking, 500–1,000 mg is sufficient. Start at 500 mg and increase if homocysteine remains elevated.
Can TMG lower homocysteine without B12 and folate?
Yes. TMG lowers homocysteine via the BHMT pathway, which is independent of the folate/B12 pathway. It's particularly useful when homocysteine stays elevated despite adequate B12 and folate — TMG provides an alternative remethylation route. For best results, ensure you have adequate B12, folate, and TMG.
How TMG works
TMG donates one of its three methyl groups to homocysteine via betaine-homocysteine methyltransferase (BHMT), converting homocysteine to methionine. Methionine is then converted to SAMe (S-adenosylmethionine), the universal methyl donor that methylates DNA, histones, neurotransmitters, and phospholipids. After donating all three methyl groups, TMG becomes glycine. This pathway operates primarily in the liver and kidneys, independent of the folate/B12-dependent methionine synthase pathway.
What the studies show
- Homocysteine: Meta-analysis — TMG reduced homocysteine by 1.3 µmol/L at doses of 4 g/day; larger reductions in hyperhomocysteinemic individuals
- Liver fat: TMG supplementation prevented high-fat diet-induced fatty liver in animal models via improved phosphatidylcholine synthesis
- Athletic performance: Some studies show modest improvements in power output and body composition at 2.5 g/day
- NAFLD: Human studies show TMG (betaine) improves liver steatosis and aminotransferase levels in non-alcoholic fatty liver disease
Side effects & safety
- Fishy body odour — At doses above 3,000 mg/day, some people produce excess trimethylamine, which has a fishy smell. Rare at standard longevity doses (500–1,000 mg).
- GI upset — Mild nausea or diarrhoea, usually with higher doses. Take with food.
- Cholesterol effect — Some studies show TMG can modestly increase LDL cholesterol. Monitor your lipid panel, especially at doses above 1,000 mg/day.
Which labs to check
- Homocysteine — the primary marker TMG targets; check at baseline and 8 weeks
- Lipid panel — monitor LDL, especially at higher doses
- Liver enzymes — should improve if fatty liver is present
- B12 & folate — ensure the other methylation pathways are also supported
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