TMG (Trimethylglycine / Betaine)
Research Reliability -
A methyl donor that lowers homocysteine and replenishes methyl groups used up by NAD+ boosters and other 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
homocysteine drops on labs; some notice steadier energy or workout output
Ongoing
methylation support, pairs with B-vitamins
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.
Usage
Entry Dose
500mg
Standard Dose
1–3g
Max Dose
6g
Onset
2–4 weeks (homocysteine)
Combinations
Pairs well with
Synergistic
NMN or NR — replenishes methyl groups consumed during NAD+ synthesis
Creatine — addresses the methylation burden of endogenous creatine production
5-MTHF and B12 — covers both methylation pathways for comprehensive homocysteine support
Avoid combining
Contraindicated
Kidney disease — limited data on betaine handling in significant renal impairment
Existing elevated LDL cholesterol — some studies show modest LDL increases at high doses
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.