Methyl donor; agent for the alternative homocysteine remethylation pathway
ATC code: A16AA06 (Betaine (Cystadane))
Brand names
Betaine anhydrous (various), Trimethylglycine TMG, Cystadane
Betaine (trimethylglycine) donates a methyl group to homocysteine via betaine-homocysteine methyltransferase (BHMT), converting it to methionine. This is the alternative remethylation pathway; the main one uses methionine synthase with vitamin B12 and methylfolate. In classical homocystinuria and B12 deficiency betaine lowers homocysteine and prevents vascular, skeletal and lens damage. approved Cystadane in 1996 for this indication. As an iHerb supplement it is marketed as a «methylation booster», but in people without BHMT/CBS defects this use has no clinical meaning.
First line
Betaine (Cystadane) is first-line treatment for classical homocystinuria and for methyltetrahydrofolate reductase deficiency or B12-dependent remethylation defects in children and adults. approved the drug in 1996; AEMPS confirms the indication. Dose: 100 mg/kg/day split into two intakes, titrated to plasma homocysteine below 15 µmol/L. Therapy is lifelong under a metabolic paediatrician and regular plasma amino-acid panels. There is no alternative regimen.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Sports marketing positions betaine as a «legal anabolic equivalent»: doses of 2.5 g/day allegedly improve strength and endurance. A 2017 Cholewa meta-analysis showed statistically significant but clinically modest strength improvement (about 2%) in untrained men; in trained athletes the effect is not reproducible. International sports federations do not recognise the drug as ergogenic. AEMPS and AESAN consider performance-enhancement claims unsubstantiated.
Not recommended
TMG is sold in sports nutrition shops as a «muscle mass» supplement. Most studies show lean mass gain comparable to placebo. NIH ODS states explicitly: data are conflicting, insufficient for recommendation. AEMPS has not approved the drug for this use. Evidence-based muscle gain rests on progressive overload, 1.6–2.2 g/kg protein and adequate sleep, not a TMG sachet in water.
Not recommended
High-dose betaine (10–20 g/day) was studied in non-alcoholic fatty liver disease. Several small studies reported reduced ALT and improved histology, but larger randomised trials did not confirm the effect. 2024 and 2023 do not recommend it for MASLD/NAFLD. High doses raise plasma methionine, which may worsen the lipid profile and cause unpleasant body odour. Evidence-based treatment of fatty liver targets weight, diet, glucose and lipid control.
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FDA Category C. Patients with homocystinuria continue Cystadane on vital indications – thrombotic and vascular risks without betaine outweigh potential toxicity. TMG supplements are not taken during pregnancy.
Use with caution. Hale L3. Limited data. In maternal homocystinuria Cystadane therapy continues; supplemental TMG doses during lactation are avoided.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Betaine (trimethylglycine, TMG) is evaluated for the following indications with varying evidence strength: Homocystinuria (evidence tier A), Muscle mass gain (bodybuilding self-use) (evidence tier D), Non-alcoholic fatty liver disease (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Betaine (trimethylglycine, TMG) (≥ 1 in 100): Nausea, vomiting, Abdominal pain, diarrhoea, Fishy body odour at high doses (trimethylaminuria), Rise in LDL cholesterol and total methionine. See the Safety section for uncommon and serious reactions.
FDA category C. FDA Category C. Patients with homocystinuria continue Cystadane on vital indications – thrombotic and vascular risks without betaine outweigh potential toxicity. TMG supplements are not taken during pregnancy.
Use with caution. Hale L3. Limited data. In maternal homocystinuria Cystadane therapy continues; supplemental TMG doses during lactation are avoided.
Betaine (trimethylglycine, TMG) is contraindicated in: Hypersensitivity to betaine; Severe dyslipidaemia and ischaemic heart disease (with high doses). Full list in the Safety section.