NutriDex

The Supplement Research Compendium
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Betaine (TMG)

Trimethylglycine

Methyl donor that lowers homocysteine and may aid lower-body strength.

Moderate evidence ⚡Performance🫀Heart & Metabolic

✚ Updated · How we grade evidence

Evidence tier
Moderate
Research weight
Citations
8 verified / 8
Classification
Performance
❝
What the evidence says. Graded moderate: meta-analyses reliably show betaine lowers homocysteine (~12%) and a modest lower-body strength signal (ES ~0.49), but it has no proven effect on cardiovascular events, raises total/LDL cholesterol, and body-composition trials directly conflict. (Moderate evidence: Several controlled trials; effects real but modest or context-dependent.)

What is Betaine (TMG)?

Betaine (TMG) (Trimethylglycine) is a performance supplement used for lower plasma homocysteine. NutriDex grades the human evidence as Moderate. Betaine (trimethylglycine, TMG) is a methyl donor found in beets and whole grains. Its best-replicated effect is lowering plasma homocysteine: a meta-analysis of 5 RCTs found 4-6 g/day cut it by about 1.23 micromol/L (~12%). Whether this translates to fewer heart events is unproven, and the same and later meta-analyses show betaine moderately raises total and LDL cholesterol (~14 and ~10 mg/dL), which may offset any benefit. For exercise, a 2024 meta-analysis (17 trials) found a small significant gain in maximal strength, concentrated in the lower body (ES ~0.49), with no effect on upper-body or power measures. Body-composition results conflict outright: one meta-analysis found modest body-fat loss, another found none. A 12-month NASH trial improved liver steatosis on imaging but not fibrosis. Overall: a real but narrow biomarker and strength effect, no hard outcomes.

Purported Benefits

✓Lower plasma homocysteine
✓Lower-body strength & power
✓Support liver fat metabolism
✓Osmolyte / cell hydration

Evidence by outcome

The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.

OutcomeEvidenceEffectStudies
Lowers plasma homocysteineTwo meta-analyses consistently show ~12% / ~1.2-1.3 umol/L reduction at 4-6 g/day; surrogate marker, no hard outcomes. Strong ↑ benefit · moderate 2
Raises total/LDL cholesterolMeta-analysis and RCT show total/LDL rise (~14/~10 mg/dL), potentially offsetting any homocysteine benefit. Moderate ⚠ risk · small 2
Increases lower-body maximal strength17-trial meta-analysis found small strength gain (ES 0.47) confined to lower body; no effect on upper body or power. Moderate ↑ benefit · small 1
Reduces body fatOne meta-analysis found fat loss (-2.5 kg), another found no effect; results conflict outright. Mixed ↔ mixed · small 2
Improves hepatic steatosis in NASH12-month RCT improved steatosis on imaging but not inflammation or fibrosis. Preliminary ↑ benefit · small 1

Dosing & Compounds

Typical Dose
2.5 g/day (split) for performance; 4-6 g/day to lower homocysteine. Betaine HCl is a separate digestive product, not interchangeable.
Active Compounds
Trimethylglycine (anhydrous betaine)

Safety & Cautions

Generally well tolerated; at high doses (>4-6 g/day) it can cause nausea, diarrhea, GI upset and a fishy body odor (trimethylaminuria). Its main concern is raising total and LDL cholesterol, so people with dyslipidemia or cardiovascular risk should be cautious. No major drug interactions are established, but because it lowers homocysteine it may add to the effect of B-vitamins/folate; the high-dose prescription form (Cystadane, for inborn homocystinuria) has rarely caused cerebral edema. Discuss with a clinician if you have heart disease, kidney disease, or are pregnant. Educational only — always check with your doctor or pharmacist before combining Betaine (TMG) with any medicine.

Key Studies

Meta-analysis Zawieja 2024 ✓ PubMed
Meta-analysis of 17 trials (317 participants): chronic betaine raised maximal strength (ES 0.47), driven by lower body (ES 0.49); no effect on upper-body or power.
Meta-analysis Ashtary-Larky 2022 ✓ PubMed
Meta-analysis: betaine lowered homocysteine (-1.30 micromol/L) but raised total cholesterol (+14.1 mg/dL) and LDL (+10.3 mg/dL); no effect on BP, glucose, CRP.
Meta-analysis Gjorgjieva / Cholewa 2021 ✓ Full text
Conflicting meta-analysis: betaine failed to significantly affect body mass, BMI, body-fat %, fat mass or fat-free mass.
Meta-analysis Gao 2019 ✓ PubMed
Meta-analysis of 6 RCTs (195 participants): betaine reduced body-fat mass (-2.53 kg) and body-fat % (-2.44%), but no change in body weight or BMI.
Meta-analysis McRae 2013 ✓ PubMed
Meta-analysis of 5 RCTs: 4-6 g/day betaine for 6-24 wk lowered plasma homocysteine by 1.23 micromol/L (~11.8%) in healthy adults.
RCT Cholewa 2018 ✓ PubMed
9-week RCT in untrained collegiate females (n=23): 2.5 g/day betaine cut body-fat % and fat mass vs placebo, but did not improve absolute strength.
RCT Abdelmalek 2009 ✓ PubMed
12-month RCT (n=55 biopsy-proven NASH): 20 g/day betaine improved hepatic steatosis vs placebo but did not improve inflammation or fibrosis.
RCT Olthof 2005 ✓ PubMed
RCT: 6 g/day betaine for 6 wk raised LDL cholesterol by 0.36 mmol/L and triacylglycerol in healthy adults, potentially offsetting homocysteine benefit.
8 sources cited · 8 verified Search all studies on PubMed ↗

Common questions about Betaine (TMG)

What is Betaine (TMG) used for?

Betaine (TMG) is most often taken for Lower plasma homocysteine, Lower-body strength & power, Support liver fat metabolism, Osmolyte / cell hydration. Methyl donor that lowers homocysteine and may aid lower-body strength.

Does Betaine (TMG) work — what does the evidence say?

Moderate evidence. Several controlled trials; effects real but modest or context-dependent. Betaine (trimethylglycine, TMG) is a methyl donor found in beets and whole grains. Its best-replicated effect is lowering plasma homocysteine: a meta-analysis of 5 RCTs found 4-6 g/day cut it by about 1.23 micromol/L (~12%). Whether this translates to fewer heart events is unproven, and the same and later meta-analyses show betaine moderately raises total and LDL cholesterol (~14 and ~10 mg/dL), which may offset any benefit. For exercise, a 2024 meta-analysis (17 trials) found a small significant gain in maximal strength, concentrated in the lower body (ES ~0.49), with no effect on upper-body or power measures. Body-composition results conflict outright: one meta-analysis found modest body-fat loss, another found none. A 12-month NASH trial improved liver steatosis on imaging but not fibrosis. Overall: a real but narrow biomarker and strength effect, no hard outcomes.

What is the typical dose of Betaine (TMG)?

2.5 g/day (split) for performance; 4-6 g/day to lower homocysteine. Betaine HCl is a separate digestive product, not interchangeable.

Is Betaine (TMG) safe? Any cautions or side effects?

Generally well tolerated; at high doses (>4-6 g/day) it can cause nausea, diarrhea, GI upset and a fishy body odor (trimethylaminuria). Its main concern is raising total and LDL cholesterol, so people with dyslipidemia or cardiovascular risk should be cautious. No major drug interactions are established, but because it lowers homocysteine it may add to the effect of B-vitamins/folate; the high-dose prescription form (Cystadane, for inborn homocystinuria) has rarely caused cerebral edema. Discuss with a clinician if you have heart disease, kidney disease, or are pregnant.

How many studies support Betaine (TMG)?

NutriDex cites 8 sources for Betaine (TMG), graded "Moderate".

Cite this page
APA

Peh, D. (2026). Betaine (TMG) (Trimethylglycine): Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/betaine-tmg

BibTeX
@misc{nutridex_betaine_tmg,
  author       = {Peh, Daryl},
  title        = {Betaine (TMG) (Trimethylglycine): Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/betaine-tmg},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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