Betaine / TMG (Trimethylglycine)

Evidence Level
Moderate
2 Clinical Trials
4 Documented Benefits
3/5 Evidence Score

Betaine (trimethylglycine, TMG) is a naturally occurring compound found in beets, spinach, and whole grains that serves as a methyl donor in the homocysteine remethylation pathway — a critical step in one-carbon metabolism. Beyond its role in lowering homocysteine (a blood marker), betaine has been studied for athletic performance. A 2024 systematic review and meta-analysis of 17 trials (317 participants) found a significant but moderate benefit for maximal strength, mainly lower-body strength, and for vertical jump, with no significant effect on upper-body strength, cycling sprint power, bench-throw power, or muscular endurance.

Studied Dose 2–6 g/day; athletic performance: 2.5 g/day (most studied dose); homocysteine reduction: 1.5–6 g/day; split into 2 doses for best tolerance
Active Compound Betaine anhydrous (trimethylglycine, TMG) — naturally from beet root; synthetic betaine anhydrous is identical; 2.5 g/day is the performance-validated dose

Benefits

Athletic performance — power and strength

A 2024 systematic review and meta-analysis (17 trials, 317 participants) found betaine (typically 2.5 g/day for at least 7 days) produced a significant but moderate improvement in maximal strength (standardized mean difference 0.47), driven mainly by lower-body strength, and a significant improvement in vertical jump. The same meta-analysis found no significant effect on upper-body strength, cycling sprint power, bench-press-throw power, or muscular endurance. The effect is real but selective, and it is smaller and less consistent than creatine's.

Body composition improvement

In a 6-week randomized trial of 23 strength-trained men, body fat percent, fat mass, and lean body mass improved significantly within the betaine (2.5 g/day) group but not the placebo group. The trial did not report a significant between-group difference in these body-composition measures, so the result should be read cautiously. A proposed mechanism is betaine's role as a methyl donor for creatine synthesis.

Homocysteine reduction (a cardiovascular risk marker)

Betaine is one of the most effective natural agents for reducing elevated homocysteine — a cardiovascular risk factor. As the methyl donor for homocysteine remethylation to methionine via BHMT (betaine-homocysteine methyltransferase), betaine addresses homocysteine through a B-vitamin-independent pathway. Homocysteine reductions of roughly 10 to 20 percent are achieved with 1.5 to 6 g/day. Lowering homocysteine is a change in a blood marker: no trial has shown that betaine reduces heart attacks, strokes, or other cardiovascular events.

Methylation support and fatty-liver evidence (mixed)

Betaine is a methyl donor used in phosphatidylcholine synthesis and SAMe regeneration in the liver. Human evidence in fatty liver disease is mixed: a 12-month randomized placebo-controlled trial of high-dose betaine (20 g/day) in 55 NASH patients did not improve steatosis, fibrosis, or the NAFLD activity score versus placebo. More recent pilot trials at lower doses (2 to 8 g/day) reported reductions in ALT and other blood markers of liver injury, but these were small, mostly within-group comparisons rather than placebo-controlled results. Benefit on hepatic fat is not established.

Mechanism of action

1

BHMT-mediated homocysteine remethylation

Betaine donates a methyl group to homocysteine via betaine-homocysteine methyltransferase (BHMT) in the liver and kidneys, converting potentially harmful homocysteine back to methionine. This B-vitamin-independent remethylation pathway complements the folate/B12-dependent methionine synthase route, providing a backup mechanism particularly important when folate or B12 are insufficient.

2

Cellular osmolyte protection

Betaine accumulates intracellularly as an organic osmolyte, protecting cells from hypertonic stress by balancing water activity without disrupting protein structure. In muscle cells under the osmotic stress of intense exercise, betaine maintains cellular hydration, protein stability, and enzyme activity — improving muscle performance during high-intensity training.

3

Creatine synthesis substrate provision

Betaine provides methyl groups for guanidinoacetate methylation — the final step in creatine biosynthesis. By increasing the efficiency of the body's endogenous creatine production, betaine amplifies the cellular creatine pool and enhances the phosphocreatine energy system in muscle, contributing to the ergogenic effects observed in strength and power athletes.

Clinical trials

1
Betaine Supplementation on Strength and Power Performance — RCT
PubMed

Within-subject crossover study in 12 recreationally trained men examining 14 days of betaine supplementation (1.25 g twice daily, 2.5 g total) on strength and power outcomes including bench press throw power, isometric bench press force, vertical jump power, and isometric squat force. (Lee et al. 2010, J Int Soc Sports Nutr)

12 recreationally trained men (mean age 21). 14-day intervention, within-subject design.

Betaine increased bench throw power, isometric bench press force, vertical jump power, and isometric squat force vs pre-supplementation values. No improvement in jump squat power or rep counts. Effects more pronounced in upper-body movements. Note: this was a randomized, double-blind, placebo-controlled crossover, but the sample was small (n=12) and a later meta-analysis found betaine's strength benefit is mainly in lower-body movements.

2
Betaine and Body Composition in Resistance-Trained Men — 6-Week RCT
PubMed

Randomized, placebo-controlled trial in 23 resistance-trained men receiving betaine (2.5 g/day, n=11) or placebo (n=12) during a 6-week periodized training program. Outcomes: body composition (bench press work capacity, body fat %, lean body mass, fat mass), homocysteine thiolactone (HCTL), training volume. (Cholewa et al. 2013, J Int Soc Sports Nutr)

23 resistance-trained men. 6-week intervention.

Body composition (body fat percent, fat mass, lean body mass) and arm size improved significantly within the betaine group but not the placebo group, and bench press work capacity was greater in betaine at two of three microcycles. Vertical jump power showed only a trend (p=0.07). Betaine attenuated the rise in urinary homocysteine thiolactone. There were no significant between-group differences in maximal strength (1RM bench press or squat).

Side effects and drug interactions

Common Potential side effects

Generally very well tolerated at 2.5 g/day; slight fishy body odor possible at higher doses (>6 g/day)
Mild GI discomfort at higher doses — split into two doses to improve tolerance
May elevate LDL cholesterol in some individuals — monitor lipid panel with long-term use

Important Drug interactions

Methotrexate — betaine's methyl donor activity may interact with antifolate mechanism; consult physician if on methotrexate
No established pharmacokinetic drug interactions at standard supplemental doses (2.5–6 g/day)

Frequently asked questions about Betaine / TMG (Trimethylglycine)

What is betaine (TMG) used for?

Betaine, also called trimethylglycine (TMG), is a compound that donates methyl groups and helps lower homocysteine, a cardiovascular marker. It is also studied for exercise performance and supports liver and cellular hydration.

What is TMG good for?

It supports healthy homocysteine levels (alongside B vitamins), liver function, and may modestly aid strength and power in athletes. It also works with the body's methylation processes, complementing folate and B12.

How much betaine (TMG) should I take?

For homocysteine and general use, around 500 mg to 3 grams per day is common; exercise studies often use about 2.5 grams per day. Follow product labeling and split larger doses.

Is betaine (TMG) safe?

It is generally well tolerated; higher doses may cause digestive upset or, rarely, raise cholesterol slightly. It works best with adequate B vitamins. Those with medical conditions should check with a doctor.

What is Betaine / TMG?

Betaine (trimethylglycine, TMG) is a naturally occurring compound found in beets, spinach, and whole grains that serves as a methyl donor in the homocysteine remethylation pathway — a critical step in one-carbon metabolism.

What is Betaine / TMG used for?

Betaine / TMG is researched primarily for Athletic Performance, Cardiovascular, and Liver Health. A 2024 systematic review and meta-analysis (17 trials, 317 participants) found betaine (typically 2.5 g/day for at least 7 days) produced a significant but moderate improvement in maximal strength (standardized mean difference 0.

What is the recommended dosage of Betaine / TMG?

The clinically studied dose is 2–6 g/day; athletic performance: 2.5 g/day (most studied dose); homocysteine reduction: 1.5–6 g/day; split into 2 doses for best tolerance Always follow the product label and check with a healthcare provider for personal advice.

Is Betaine / TMG safe, and does it have side effects?

For most healthy adults, Betaine / TMG is well tolerated at studied doses. Reported effects can include: Generally very well tolerated at 2.5 g/day; slight fishy body odor possible at higher doses (>6 g/day) Mild GI discomfort at higher doses — split into two doses to improve tolerance It may also interact with some medications. Betaine / TMG is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Betaine / TMG interact with any medications?

Possible interactions include: Methotrexate — betaine's methyl donor activity may interact with antifolate mechanism; consult physician if on methotrexate No established pharmacokinetic drug interactions at standard supplemental doses (2.5–6 g/day) If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Betaine / TMG?

NutraSmarts rates the evidence for Betaine / TMG as Moderate (3 out of 5). It is backed by 2 clinical trials and 5 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(5 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Zawieja E, Machek S, Zanchi NE, Cholewa J, Wozniewicz M. Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis. J Sports Sci. 2024;42(22):2131-2144..PubMedUsed to support: Systematic review and meta-analysis of 17 trials (317 participants) of chronic betaine supplementation. Found a significant but moderate effect on maximal strength (standardized mean difference 0.47), mainly lower-body strength, and on vertical jump, with no significant effect on upper-body strength, cycling sprint power, bench-press-throw power, or muscular endurance.
  2. Lee EC, Maresh CM, Kraemer WJ, Yamamoto LM, Hatfield DL, Bailey BL, Armstrong LE, Volek JS, McDermott BP, Craig SA. Ergogenic effects of betaine supplementation on strength and power performance. J Int Soc Sports Nutr. 2010;7:27. doi: 10.1186/1550-2783-7-27.PubMedUsed to support: Randomized double-blind placebo-controlled crossover trial in 12 resistance-trained men. After 14 days, betaine (2.5 g/day) raised bench-throw power, isometric bench force, vertical jump power, and isometric squat force versus placebo and baseline, but did not change jump-squat power or repetition counts. Small sample.
  3. Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, Jakubowski H, Matthews T, Wood R, Craig SA, Paolone V. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013;10(1):39. doi: 10.1186/1550-2783-10-39.PubMedUsed to support: Randomized placebo-controlled trial in 23 strength-trained men. Over 6 weeks, betaine (2.5 g/day) improved body composition and arm size within the betaine group and increased bench-press work capacity, but produced no significant between-group difference in maximal strength (bench or squat 1RM).
  4. Abdelmalek MF, Sanderson SO, Angulo P, Soldevila-Pico C, Liu C, Peter J, Keach J, Cave M, Chen T, McClain CJ, Lindor KD. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology. 2009;50(6):1818-26. doi: 10.1002/hep.23239.PubMedUsed to support: Randomized placebo-controlled trial in 55 patients with biopsy-proven nonalcoholic steatohepatitis. High-dose betaine (20 g/day) for 12 months did not improve steatosis, fibrosis, or the NAFLD activity score compared with placebo, and did not improve insulin, glucose, or inflammatory markers.
  5. Lim AS, Cruz SN, Uddin AA, Malysheva O, Caudill MA, et al. Pilot trials of oral betaine in participants with metabolic dysfunction-associated steatotic liver disease and elevated alanine aminotransferase. Hepatology. 2026;83(6):1515-1528. doi: 10.1097/HEP.0000000000001063.PubMedUsed to support: Three small pilot trials in patients with metabolic-associated steatotic liver disease and elevated ALT. Betaine at 2 to 8 g/day (but not 1 g/day) for 12 to 24 weeks lowered ALT and several blood markers of liver injury, measured mainly as within-group change rather than against a placebo group.