TMG
Pooled trials show betaine lowers homocysteine by about 1.2 to 1.3 μmol/L. At 4 g a day or more, it raised total cholesterol by about 14 mg/dL and LDL by about 10 mg/dL. Meta-analyses disagree on body fat. One found small gains in lower-body strength. No trial measured lifespan.
Add to Bio HackChecked 2026-11-09
- Status
- Dietary supplement in the US.
- Also called
- trimethylglycine, betaine, betaine anhydrous, glycine betaine, methyl donor
- Taken for
- slowing aging, longer life, methylation, homocysteine, heart health, strength, power, body fat, liver health
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help3
- StrongShown to lower homocysteine about 1.2 to 1.3 μmol/L at 4 g a day or more in healthy adults. Heart disease was not measured.
- ModerateShown to raise maximal strength modestly, mostly lower body, in healthy people. Upper-body strength, sprint power and muscular endurance did not change.
- LimitedSmall trials without placebo found liver enzymes fell at 2 to 8 g a day in adults with fatty liver disease, but not at 1 g.
Reported risks3
- LimitedLimited evidence: about 35% reported mild, brief stomach symptoms in small trials without placebo.Very common
- StrongShown to raise total cholesterol, about 14 mg/dL in one review, at 4 g a day or more. Reviews differ on whether LDL rises.How often is not known
- LimitedThe label for prescription betaine warns it can raise blood methionine, with severe brain swelling reported in people with an inherited enzyme deficiency.How often is not known
What people take it for, and what was found
Shown to help3
Homocysteine
Shown to lower homocysteine about 1.2 to 1.3 μmol/L at 4 g a day or more in healthy adults. Heart disease was not measured.
The numbers and sources
- Effect
- Across 5 RCTs of at least 4 g a day for 6 to 24 weeks, betaine lowered plasma homocysteine by 1.23 μmol/L (95% CI -1.61 to -0.85) [1]. A later meta-analysis found a fall of 1.30 μmol/L (95% CI -1.61 to -0.98) [2].
- Population
- Healthy adults in 5 RCTs [1]; RCTs pooled up to February 2021 [2].
- Sources
- [1], [2]
- Caveats
- The two reviews overlap in trials. Neither measured heart disease or death.
Muscle strength and power
Shown to raise maximal strength modestly, mostly lower body, in healthy people. Upper-body strength, sprint power and muscular endurance did not change.
The numbers and sources
- Effect
- Across 17 studies, betaine raised maximal strength (SMD 0.47, 95% CI 0.04 to 0.89), mostly in the lower body (SMD 0.49, 95% CI 0.01 to 0.98). Upper-body strength, cycling sprint power, bench throw power and muscular endurance did not change. Vertical jump improved (SMD 0.36, 95% CI 0.03 to 0.69) after one low-quality study was excluded [3].
- Population
- 317 healthy people aged 15 to 60, 21% female, supplementing for at least 7 days [3].
- Sources
- [3]
- Caveats
- Small trials. The lower bounds of the intervals sit close to zero.
Liver health
Small trials without placebo found liver enzymes fell at 2 to 8 g a day in adults with fatty liver disease, but not at 1 g.
The numbers and sources
- Effect
- In three pilot trials, ALT, AST, cytokeratin 18, pro-C3 and a combined liver injury score fell from baseline at 8, 4 and 2 g a day over 12 to 24 weeks, but not at 1 g a day [6].
- Population
- 70 adults with metabolic dysfunction-associated steatotic liver disease and ALT of 50 U/L or more: 44 randomized to 4 or 8 g a day for 12 weeks, 10 on 1 g and 16 on 2 g a day for 24 weeks [6].
- Sources
- [6]
- Caveats
- No placebo group. Results compare each person's levels before and after treatment, and the outcomes are blood markers rather than liver biopsy [6].
Mixed results1
Body fat
Limited evidence: two reviews disagree. One found about 2.5 kg less fat mass, and a later one found no change in body fat.
The numbers and sources
- Effect
- One meta-analysis found lower fat mass (-2.53 kg, 95% CI -3.93 to -0.54) and body fat percentage (-2.44%, 95% CI -4.20 to -0.68), with no change in weight or BMI [4]. A later meta-analysis found no change in body mass, BMI, body fat percentage (WMD 0.26%, 95% CI -0.82 to 1.36), fat mass (WMD -0.57 kg, 95% CI -2.14 to 0.99) or fat-free mass [5].
- Population
- 195 participants in 6 RCTs [4]; studies published up to August 2021 [5].
- Sources
- [4], [5]
- Caveats
- The two reviews disagree. One funder of [4] was a research fund supported by DSM, a nutrition ingredient company.
Claimed, not studied in people1
Longer life
Not studied in people. Betaine supplements extended lifespan in roundworms, and a review describes effects on methylation and inflammation linked to aging.
No study in people. This rests on animal studies, how it acts in the body.
The numbers and sources
- Effect
- In C. elegans worms, betaine supplementation extended lifespan through FoxO, MAPK, autophagy and mTOR pathways, and three anti-aging drugs raised betaine levels [8]. A 2025 review reports that betaine may counter aging-related changes in methylation by raising S-adenosylmethionine, lowers homocysteine, and reduced oxidative stress and inflammation in studies, and found no clear link between dietary betaine and heart disease or type 2 diabetes [9].
- Population
- C. elegans roundworms [8]. Human and animal studies, reviewed [9].
- Sources
- [8], [9]
- Caveats
- A worm lifespan study and a narrative review. The review states that efficacy and safety of betaine in older people need further research [9]. No study of betaine and human lifespan was located.
Doses studied
Homocysteine trials used at least 4 g a day for 6 to 24 weeks [1]. Lipid trials used at least 4 g a day for 6 to 24 weeks [7]. One review found homocysteine fell at under 4 g a day without the rise in cholesterol seen at 4 g a day or more [2]. Exercise trials supplemented for at least 7 days [3]. Liver pilot trials used 1 to 8 g a day for 12 to 24 weeks [6].
Risks
Reported risks3
Gastrointestinal symptoms
Limited evidence: about 35% reported mild, brief stomach symptoms in small trials without placebo.
The numbers and sources
Higher cholesterol
Shown to raise total cholesterol, about 14 mg/dL in one review, at 4 g a day or more. Reviews differ on whether LDL rises.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- At 4 g a day or more, betaine raised total cholesterol by 0.34 mmol/L (95% CI 0.02 to 0.65). LDL, HDL and triglycerides did not change significantly [7]. A second meta-analysis found total cholesterol 14.12 mg/dL higher (95% CI 9.23 to 19.02) and LDL 10.26 mg/dL higher (95% CI 6.14 to 14.38). Triglycerides, HDL, glucose, CRP, liver enzymes and blood pressure did not change [2].
- Population
- Adults in 6 RCTs from 2002 to 2018 [7]; RCTs pooled up to February 2021 [2].
- Sources
- [7], [2]
- Caveats
- The reviews differ on LDL. Subgroup analysis suggested the rise appears at 4 g a day or more [2]. In uncontrolled liver pilot trials at 2 to 8 g a day, LDL did not change and HDL rose at 2 and 4 g [6].
Long-term use
The label for prescription betaine warns it can raise blood methionine, with severe brain swelling reported in people with an inherited enzyme deficiency.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Betaine anhydrous is an FDA-approved prescription drug (Cystadane) for homocystinuria. Its label warns that it may worsen high plasma methionine in people with CBS deficiency, and that severe cerebral edema with high methionine was reported 2 weeks to 6 months after starting, with complete recovery after stopping. In a physician survey covering 111 treated patients, reported reactions included nausea and gastrointestinal distress in 2 each [10].
- Population
- People with homocystinuria taking prescription betaine, from postmarketing reports and a survey of 41 physicians [10].
- Sources
- [10]
- Caveats
- Reports come from people with a rare inherited disorder, and postmarketing reports give no rate [10]. No long-term study in people without homocystinuria was located.
Claims tested and not found
Sources
- McRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. Journal of Chiropractic Medicine. 2013. https://doi.org/10.1016/j.jcm.2012.11.001
- Ashtary-Larky D, Bagheri R, Ghanavati M, et al. Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis. Critical Reviews in Food Science and Nutrition. 2021. https://doi.org/10.1080/10408398.2021.1902938
- Zawieja E, Machek S, Zanchi NE, et al. Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis. Journal of Sports Sciences. 2024. https://doi.org/10.1080/02640414.2024.2423578
- Gao X, Zhang H, Guo XF, et al. Effect of Betaine on Reducing Body Fat. A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2019. https://doi.org/10.3390/nu11102480
- Ashtary-Larky D, Bagheri R, Tinsley GM, et al. Betaine supplementation fails to improve body composition: a systematic review and meta-analysis. British Journal of Nutrition. 2021. https://doi.org/10.1017/s0007114521004062
- Lim AS, Cruz SN, Uddin AA, et al. Pilot trials of oral betaine in participants with metabolic dysfunction-associated steatotic liver disease and elevated alanine aminotransferase. Hepatology. 2026. https://doi.org/10.1097/hep.0000000000001477
- Zawieja EE, Zawieja B, Chmurzynska A. Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis. Journal of Dietary Supplements. 2019. https://doi.org/10.1080/19390211.2019.1699223
- Lan W, Xiao X, Nian J, et al. Senolytics Enhance the Longevity of Caenorhabditis elegans by Altering Betaine Metabolism. The Journals of Gerontology: Series A. 2024. https://doi.org/10.1093/gerona/glae221
- Zawieja E, Chmurzynska A. Betaine and aging: A narrative review of findings, possible mechanisms, research perspectives, and practical recommendations. Ageing Research Reviews. 2025. https://doi.org/10.1016/j.arr.2024.102634
- U.S. Food and Drug Administration. CYSTADANE (betaine anhydrous for oral solution), prescribing information. Revised 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31a684d0-cd98-4e46-b43a-ccbd17c41559