TMG (Trimethylglycine)
Also known as betaine anhydrous, TMG is a naturally occurring methyl donor with solid clinical research behind homocysteine management and an emerging case for exercise performance.
FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Always consult your physician before starting any supplement.
TMG (trimethylglycine), also called betaine or betaine anhydrous, is a naturally occurring compound derived from the amino acid glycine, with three methyl groups attached. It's found in significant amounts in beets (where it gets its name — "beta" is Latin for beet), spinach, and whole grains, and is also produced naturally in the body from choline.
TMG's primary biological role is as a methyl donor — it provides methyl groups for a critical reaction that converts homocysteine, a potentially harmful amino acid byproduct, back into methionine. This methylation pathway is the basis for most of TMG's established clinical uses, particularly in people with impaired homocysteine metabolism. In recent years, TMG has also gained attention in sports nutrition for a smaller but growing body of research on exercise performance and body composition.
It's worth distinguishing TMG/betaine anhydrous from betaine HCl, a different supplement used to support stomach acid for digestion — they share a name but serve entirely different purposes.
Donates Methyl Groups
TMG provides a methyl group in the enzymatic conversion of homocysteine back to methionine, an alternate pathway to the folate/B12-dependent route, which is particularly relevant for people with genetic variants affecting methylation.
Supports Liver Fat Metabolism
TMG plays a role in the synthesis of phosphatidylcholine and supports normal liver lipid export, which is the basis for its traditional clinical use in supporting fatty liver conditions under medical supervision.
Acts as a Cellular Osmolyte
TMG helps cells regulate water balance under stress, including during intense exercise — a proposed mechanism for its studied effects on power output and training volume in resistance training research.
Homocysteine Management
This is TMG's most clinically established use. Multiple trials have shown TMG supplementation significantly reduces elevated homocysteine levels, an effect particularly relevant for people with genetic variants (such as MTHFR mutations) that impair normal methylation.
Strongest evidence among TMG's studied benefits
Exercise Performance & Body Composition
Several trials have examined TMG supplementation in resistance-trained individuals, finding modest improvements in power output, training volume, and body composition compared to placebo over several weeks of training.
Effects are smaller and less consistent than established ergogenics like creatine
Liver Support (Clinical Use)
Betaine has an established clinical history of use in supporting fatty liver conditions, including a prescription form used for a rare genetic methylation disorder (homocystinuria), under direct medical supervision.
This use is clinical, not a general wellness recommendation
Cardiovascular Support
Since elevated homocysteine is associated with cardiovascular risk, TMG's homocysteine-lowering effect gives it a plausible, indirect role in cardiovascular health support, particularly for those with elevated baseline levels.
Indirect benefit through homocysteine management
| Form | Typical Dose | Notes |
|---|---|---|
| Betaine anhydrous powder/capsules | 1,500–3,000mg/day | Standard supplemental form for methylation and performance use. |
| Homocysteine management dose | 500–1,000mg, 2x daily | Lower end of the range used in clinical research for homocysteine reduction. |
Timing
Take with meals to reduce the chance of GI upset, divided into 2 doses for higher amounts. Exercise performance studies typically dosed TMG daily for several weeks of consistent training, not as a single pre-workout dose.
⚠️ Important Interactions & Cautions
- Cholesterol levels: Some research has noted modest increases in LDL and total cholesterol at higher doses; those with elevated cholesterol should monitor levels and discuss with their doctor.
- Pre-existing kidney conditions: Use caution and consult a physician, since TMG affects amino acid metabolism processed partly by the kidneys.
- Methylation-related medications: Those on methotrexate or other folate-pathway medications should consult a physician before supplementing.
- Pregnancy & breastfeeding: Limited safety data; consult a healthcare provider before use.
✅ Generally Safe
- Naturally occurring in many foods (beets, spinach)
- Well-tolerated at standard doses in clinical trials
- Long history of use in clinical settings for homocystinuria
Mild Side Effects
- GI upset, nausea — take with food
- Diarrhea at higher doses
- Body odor changes (rare, related to choline/TMAO metabolism)
🫀 Homocysteine Support Stack
- TMG (1,000–2,000mg/day)
- Folate — complementary methylation pathway
- Vitamin B12 — complementary methylation pathway
A common combination for people specifically targeting elevated homocysteine
💪 Performance Stack
- TMG (2,000–3,000mg/day)
- Creatine Monohydrate — established performance support
For those exploring TMG's exercise performance angle
- Olthof MR, Verhoef P. Effects of Betaine Intake on Plasma Homocysteine Concentrations and Consequences for Health. Curr Drug Metab. 2005;6(1):15–22.
- Cholewa JM, et al. Effects of Betaine on Body Composition, Performance, and Homocysteine Thiolactone. J Int Soc Sports Nutr. 2013;10:39.
- Craig SA. Betaine in Human Nutrition. Am J Clin Nutr. 2004;80(3):539–549.
Evidence-based supplement recommendations from a former physical store owner. No hype. No BS. Just facts.
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