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TMG (Trimethylglycine / Betaine Anhydrous)
A methyl donor (betaine) that reliably lowers homocysteine and modestly aids strength/power and endurance — but can raise LDL cholesterol, and doesn't improve body composition.
What the evidence says
Most TMG studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2017–2026 with a typical study size of 44 participants.
Based on 15 studies · 4 meta-analyses · 4 RCTs · 117 total participants
Confidence
High confidenceBy outcome
Meta-analyses reliably show TMG lowers homocysteine and modestly aids lower-body strength, but it does not improve body composition and can raise LDL/total cholesterol at higher doses.
17 trials ongoing or recruiting · 47 completed on ClinicalTrials.gov
9 of the completed trials have posted results
Registered trials show research momentum for TMG, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Sep 2026
TMG (trimethylglycine), also called betaine anhydrous, is a methyl donor and cellular osmolyte.
It reliably lowers homocysteine (by remethylating it to methionine) and is used as a performance aid: meta-analyses show modest improvements in strength/power and some endurance measures, likely via cellular hydration and methylation support.
Two honest caveats from the evidence: it does NOT improve body composition, and it can moderately raise total/LDL cholesterol — a real cardiovascular trade-off at higher doses. (Distinct from betaine HCl, which is used for stomach acid, not methylation.)
Donates methyl groups to remethylate homocysteine to methionine, supporting methylation and lowering homocysteine.
Acts as an osmolyte that supports cell hydration and may aid muscular performance.
Methylation support contributes to endogenous creatine production.
How TMG works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Monitor lipids — betaine can raise LDL.
Food amounts fine; supplemental doses not well studied.
Few documented drug interactions; monitor lipids if at cardiovascular risk. This possible interaction has not been individually evaluated for this supplement; its likelihood and severity are unknown. If you take an anticoagulant or antiplatelet medicine, ask a pharmacist or prescriber before using this product. Do not stop or change prescribed medicines based on this notice.
Tip: Monitor lipids; lower dose; pair with lipid-aware diet
Tip: Reduce dose
TMG has an evidence score of 5.8/10 — moderate evidence based on 12 indexed studies, including 4 meta-analyses. A methyl donor (betaine) that reliably lowers homocysteine and modestly aids strength/power and endurance — but can raise LDL cholesterol, and doesn't improve body composition. Representative study: PMID 39514262.
The commonly studied dose of TMG is 2.5-6g betaine/TMG daily (performance studies commonly use ~2.5g; methylation/homocysteine use up to 6g). Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take TMG is with meals. Taking it with food is preferred. Taken with meals; performance protocols often split or dose pre-workout.
TMG is generally safe at recommended doses, with a few precautions worth noting. Reported side effects are uncommon and include raised LDL/total cholesterol, GI upset/fishy body odor (high doses). Use caution if any of these apply to you: High cardiovascular risk / elevated LDL (may raise cholesterol); Kidney disease (use caution).
Caffeine
Likely helpsBlocks adenosine receptors to boost alertness, reaction time, and endurance — one of the most proven ergogenic aids.
CoQ10
Likely helpsA lipid-soluble antioxidant central to mitochondrial energy production, with the strongest trial support for fertility/IVF outcomes and heart failure.
Berberine
Likely helpsActivates AMPK to regulate blood sugar, improve insulin sensitivity, and support lipid metabolism — comparable to metformin in some trials.
Beta-Sitosterol
Likely helpsPlant sterol that reduces BPH urinary symptoms in clinical trials and blocks intestinal cholesterol absorption.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 15 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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