No active regulatory warningsFDA MedWatch, EMA EudraVigilance, WHO VigiBase, WADA Prohibited List · 2026-05-29
Updated: 2026-05-29 · v2.0 · Prof. G. Pkhakadze, MD, MPH, PhDCiteEditorial
📰Read the full Betaine (TMG) evidence review on GMJ News →Complete clinical article, references and updates on news.gmj.ge. This page is the structured safety summary.
1
Safe
Betaine (TMG)
Trimethylglycine
Generally SafeModerateOther
RDA
Typical 1.5–6 g
Target
<15 µmol/L
Upper limit
No UL
Products
Dosage by population group — reference
🔗 Best with: 5-MTHF, Vitamin B12, SAMe✅ USP Verified, NSF Contents Certified, ConsumerLab Approved
⚠ TMG ≠ betaine HCl — completely different products [1]
⚠ Alternative methylation pathway to folate/B12 — useful in MTHFR [1]
⚠ Sports: modest strength improvement (small effect size) [2]
ℹ️ Not obtained from food. Obtained from beets, spinach and whole grains; counted within normal diet rather than a set daily target.
🔬 Lab interpreter
Recommended test
Plasma homocysteine
Reference range / target
<15 µmol/L
When to test
8 weeks after starting [1].
Primary marker for betaine efficacy [1].
Full lab monitoring ↓
⚕ For professionals — confirm ranges against your local laboratory.
Clinical verdict
TMG is a methyl donor (homocysteine → methionine via BHMT) — alternative to the folate/B12 pathway. FDA-approved for homocystinuria. Sports: 2.5 g/day for modest strength gains. TMG (methyl donor) ≠ betaine HCl (stomach acid) — DIFFERENT products [1] [2].
1 How much do I need?
👤 Adults: Specific dosage data under clinical review
👴 Elderly: Specific dosage data under clinical review
🤰 Pregnancy: See guidance
Endogenous. No supplementation data [1].
👦 Pediatric: See guidance
Cystadane used in pediatric homocystinuria [1].
🏃 Athletes: Standard dose
⚖️ Obesity: Standard dose
Fat-soluble compounds may require dose adjustment in obesity.
🩺 Renal: Consult specialist
Dose adjustment may be needed in renal impairment.
🌱 Vegan: Standard dose

How to take

🍽 Timing: Divided BID or with meals [1].
💊 With food: With or without food [1].
🚫 Avoid: Confusing with betaine HCl [1].
2 Which form?
FormBioavailabilityVeganCost
['Betaine anhydrous (TMG)', 'preferred', 'Methyl donor. 2.5 g/day. Pure betaine [1].']StandardCheck label
['Cystadane (Rx)', '', 'FDA-approved for homocystinuria. 6 g/day [1].']StandardCheck label
['Betaine HCl (DIFFERENT PRODUCT)', '', 'Stomach acid supplement. NOT a methyl donor [1].']StandardCheck label
3 Common questions
TMG vs betaine HCl?
COMPLETELY DIFFERENT products. TMG (betaine anhydrous) = methyl donor for homocysteine. Betaine HCl = supplemental stomach acid for hypochlorhydria. Same word 'betaine,' different chemicals [1].
Does betaine lower homocysteine?
Yes — it provides a methyl group to convert homocysteine → methionine via BHMT. This is an alternative pathway to the folate/B12-dependent methionine synthase [1].
Does betaine build muscle?
Meta-analysis of 6 RCTs: modest strength and power improvements at 2.5 g/day. Effect size is small. Not a game-changer [2].
4 Clinical evidence

Strong

Homocysteine remethylation via BHMT: established biochemistry [1]. FDA-approved for homocystinuria (Cystadane) [1]. HIGH

Moderate

Homocysteine reduction: effective in supplementation studies [1]. Exercise: meta-analysis of 6 RCTs — betaine 2.5 g/day modestly improved strength and power output [2]. Body composition: some trials positive for lean mass [2]. MODERATE

Insufficient

Cardiovascular outcomes [1]. Cognitive function [1]. NAFLD (some positive data in animal models) [1]. Depression (methylation theory) [1]. LOW
5 Safety, toxicity & adverse events

Absolute contraindications

✕ Homozygous cystathionine-β-synthase deficiency context — use only under specialist guidance (can raise methionine dangerously)

Relative

⚠ May raise LDL cholesterol at high doses
⚠ Renal impairment
⚠ Pregnancy and lactation — limited supplemental data

🚩 Red flags

Patient confusing TMG with betaine HCl — different products [1]
6 Interactions

Supplement synergies

5-MTHF + B12 · 400–1,000 µg 5-MTHF + 500 µg B12
Complete methylation support: TMG (BHMT pathway) + 5-MTHF/B12 (methionine synthase pathway) [1].
7 Regulatory
United States (FDA): TMG: GRAS/dietary supplement. Cystadane: Rx for homocystinuria [1].
Betaine (TMG) vs 5-MTHFBetaine (TMG) vs Vitamin B12
8 Cite this page
Vancouver: Pkhakadze G. Betaine (TMG) — safety profile [Internet]. Tbilisi: PHIG; 2026 [cited 2026 Aug 15]. Available from: https://supplement.ge/ingredients/betaine-tmg/
APA 7th: Pkhakadze, G. (2026). Betaine (TMG) — Safety profile. Public Health Institute of Georgia. https://supplement.ge/ingredients/betaine-tmg/
📋 Editorial information
Author: Prof. G. Pkhakadze, MD, MPH, PhD
Affiliation: David Tvildiani Medical University (DTMU)
First published: January 2026
Last reviewed: 2026-05-29
Next review: February 2027
References: 2 cited sources
COI: SupplementIndex receives no funding from supplement manufacturers. All content independently authored by PHIG.
Process: Systematic literature review
📄 License & reuse
Published under Creative Commons Attribution 4.0 International (CC BY 4.0). You may share and adapt for any purpose with attribution.
Pkhakadze G. "Betaine (TMG) — Safety Profile." SupplementIndex, PHIG, 2026. https://supplement.ge/ingredients/betaine-tmg/ CC BY 4.0.
GP
Prof. G. Pkhakadze, MD, MPH, PhD
Professor of Public Health · Head of Department, DTMU
Editor-in-Chief, Georgian Medical Journal (ISSN 3088-4322)
Chair, Public Health Institute of Georgia · UEMS Public Health Section
Educational and public health purposes. CC BY 4.0. Consult your healthcare provider before starting any supplement. Corrections: info@accreditation.ge. Publisher: PHIG