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 a possible benefit for vertical jump (significant only after one low-quality study was excluded), with no significant effect on upper-body strength, cycling sprint power, bench-throw power, or muscular endurance.

Studied Dose 1.5 to 6 g/day; athletic performance: 2.5 g/day (most studied dose); homocysteine reduction: 1.5 to 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 a commonly studied performance dose

Benefits

Athletic performance: strength, mainly lower body

A pooled analysis of 17 placebo-controlled trials (317 participants) found that betaine taken for at least 7 days moderately improved maximal strength (effect size 0.47), mainly in the lower body, where it only narrowly reached significance. Vertical jump improved only after one low-quality study was excluded, a tentative finding. Upper-body strength, sprint or throw power, and muscular endurance did not improve.

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 creatine-synthesis mechanism is unconfirmed in humans.

Homocysteine reduction (a cardiovascular risk marker)

Betaine helps maintain healthy homocysteine levels by donating a methyl group that converts homocysteine to methionine via the enzyme BHMT, a pathway independent of B vitamins. In a 6-week placebo-controlled trial in healthy adults, 1.5, 3 and 6 g/day lowered fasting homocysteine by 12, 15 and 20 percent versus placebo. This is a blood-marker change: 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, this may help maintain cell hydration and protein stability during intense exercise, one proposed explanation for the modest strength effects seen in some trials.

3

Creatine synthesis substrate provision

Betaine indirectly supplies methyl groups (via methionine and SAMe) for guanidinoacetate methylation, the final step in creatine synthesis. This has been proposed as one route to its ergogenic effects, but in a 10-day randomized placebo-controlled trial in untrained people, betaine (2 g/day) did not raise muscle phosphocreatine while creatine did, so the mechanism is unconfirmed in humans.

Clinical trials

1
Betaine Supplementation on Strength and Power Performance (Crossover RCT)
PubMed

Randomized, double-blind, placebo-controlled 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.

Bench throw power and isometric bench press force rose versus both pre-supplementation and placebo values; vertical jump power and isometric squat force rose versus pre-supplementation values only. No change in jump squat power or rep counts. Effects were more apparent in upper-body movements. 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 (body fat %, lean body mass, fat mass), arm and thigh size, bench press and back squat 1RM, vertical jump, training volume, urinary homocysteine thiolactone (HCTL). (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; a fishy body odor has been reported rarely, in people taking prescription doses.
Mild GI discomfort at higher doses; split into two doses to improve tolerance.
At 4 g/day or more, total cholesterol rose in pooled trials (LDL in some); 6 g/day raised LDL and triglycerides. Consider lipid checks.

Important Drug interactions

Methotrexate: a theoretical concern, as betaine's methyl donor activity could interact with its antifolate mechanism; consult a physician if on methotrexate
No established pharmacokinetic drug interactions at standard supplemental doses (2.5 to 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 liver health, and as an osmolyte it supports cellular hydration.

What is TMG good for?

It supports healthy homocysteine levels (alongside B vitamins) and may modestly aid strength in athletes; its role in liver health is still being studied. It also works with the body's methylation processes, complementing folate and B12.

How much betaine (TMG) should I take?

Supplements commonly provide 500 mg to 3 grams per day, but in controlled trials fasting homocysteine fell from 1.5 grams a day upward, while 1 gram a day or less had minimal effect. 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. At 4 grams a day or more, betaine raised total cholesterol in pooled trials, and 6 g/day raised LDL cholesterol in placebo-controlled studies. Folate is the main driver of fasting homocysteine; betaine adds a smaller effect. People with homocystinuria are treated with prescription betaine under medical monitoring and should not self-dose. Those with other 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 pooled analysis of 17 placebo-controlled trials (317 participants) found that betaine taken for at least 7 days moderately improved maximal strength (effect size 0.

Does Betaine / TMG interact with any medications?

Possible interactions include: Methotrexate: a theoretical concern, as betaine's methyl donor activity could interact with its antifolate mechanism; consult a physician if on methotrexate No established pharmacokinetic drug interactions at standard supplemental doses (2.5 to 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 study summaries and 8 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(8 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, Woźniewicz 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 (SMD 0.49, 95% CI 0.01 to 0.98), and on vertical jump (SMD 0.36) only after excluding one low-quality study, 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 of betaine (1.25 g twice daily), bench-throw power and isometric bench force rose versus both baseline and placebo, while vertical jump power and isometric squat force rose versus baseline only; jump-squat power and repetition counts did not change. 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, Alonso C, Montilla A, Karsdal MA, Leeming DJ, Mayorca-Guiliani AE, Svejsø FH, McClain CJ, Morgan TR. 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.0000000000001477.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.
  6. Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr. 2003;133(12):4135-8..PubMedUsed to support: Placebo-controlled trial in which four groups of 19 healthy adults took 1.5, 3 or 6 g/day of betaine or placebo for 6 weeks. Fasting plasma homocysteine was 12%, 15% and 20% lower than placebo at the three doses, and the homocysteine rise after methionine loading was also smaller.
  7. del Favero S, Roschel H, Artioli G, Ugrinowitsch C, Tricoli V, Costa A, Barroso R, Negrelli AL, Otaduy MC, da Costa Leite C, Lancha-Junior AH, Gualano B. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids. 2012;42(6):2299-305..PubMedUsed to support: Double-blind randomized placebo-controlled trial in untrained subjects. Betaine (2 g/day for 10 days) did not raise muscle phosphocreatine or improve strength or power versus placebo, whereas creatine (20 g/day) raised phosphocreatine and power; adding betaine to creatine gave no extra effect.
  8. Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med. 2005;2(5):e135..PubMedUsed to support: Pooled blood-lipid data from three randomized placebo-controlled betaine studies in healthy adults (n=151). Betaine at 6 g/day for 6 weeks raised LDL cholesterol by 0.36 mmol/L and triglycerides by 0.14 mmol/L versus placebo, with HDL unaffected. Lower doses also raised LDL, but not significantly.