Betaine, also called trimethylglycine (TMG) or betaine anhydrous, is a small molecule found in foods such as wheat bran, spinach, beets and seafood. The body also makes it from choline. It has two main jobs: it is an osmolyte (a compound that helps cells hold water and keep their proteins stable under stress), and it is a methyl donor that recycles homocysteine back into the amino acid methionine.
Betaine leads a double life. As a prescription drug (Cystadane and generics) it is FDA-approved to lower very high homocysteine in homocystinuria, a rare inherited disorder. As a dietary supplement it is marketed for strength, power and body composition. The sports evidence is modest: a 2024 meta-analysis found a small-to-moderate gain in maximal strength, but a 2022 meta-analysis found no effect on body composition. At 4 g/day or more, betaine also raises total and LDL cholesterol.
This page summarizes what the FDA label, randomized trials and meta-analyses report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Methyl donor; osmolyte; dietary supplement and prescription drug |
| Chemistry | C₅H₁₁NO₂, molecular weight 117.15 g/mol (N,N,N-trimethylglycine) |
| Prescription brand | Cystadane (betaine anhydrous for oral solution), US approval 1996; generics available |
| Labeled dose (homocystinuria) | 6 g/day as 3 g twice daily (ages 3 and up) |
| Doses in sports trials | Mostly 2.5 g/day, sometimes 5 g/day, for 1–8 weeks |
| Half-life | ≈14 h after one dose; ≈41 h after 5 days of twice-daily dosing (healthy men) |
| Main lab effects | Lowers homocysteine; raises total and LDL cholesterol at 4 g/day or more |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Betaine is glycine with three methyl groups attached to its nitrogen atom (PubChem). The Cystadane label describes the drug as pure betaine anhydrous, a white, water-absorbing powder (Cystadane label).
A 2004 review described two physiologic roles (Craig, Am J Clin Nutr 2004):
- Osmolyte. Betaine protects cells, proteins and enzymes from stresses such as dehydration, high salt and extreme temperature.
- Methyl donor. In the liver and kidneys, betaine gives one methyl group to homocysteine, converting it to methionine. Betaine itself becomes dimethylglycine (DMG). This route runs alongside the folate- and vitamin B12-dependent pathway (see vitamin B12).
Rich food sources contain about 1% betaine (marine invertebrates, wheat germ or bran) or about 0.7% (spinach) (Craig 2004). Intakes vary widely. One analysis of 28 observational studies found a mean intake of 182 mg/day (Nikrandt and Chmurzynska, J Nutr 2024). Supplement and drug doses are therefore often more than ten times usual dietary intake.
Betaine is not betaine HCl. Betaine hydrochloride is a different salt, sold as a “stomach acid” digestive aid. FDA has ruled that no OTC stomach-acidifier ingredient, betaine hydrochloride included, has been shown effective for that use (21 CFR 310.540). The trials on this page used betaine anhydrous.
Pharmacokinetics
The Cystadane label states that pharmacokinetic studies of the product are not available. The main human data come from 12 healthy men given 50 mg/kg as a single dose and then twice daily for 5 days (Schwahn et al., Br J Clin Pharmacol 2003):
| Parameter | Single dose | After 5 days of twice-daily dosing |
|---|---|---|
| Time to peak | 0.9 h | Absorption unchanged |
| Peak plasma level | 0.94 mmol/L | — |
| Elimination half-life | 14.4 h | 41.2 h |
Betaine is absorbed fast and is cleared mainly by metabolism, not by the kidneys: only about 4% of a dose appeared in urine. Its metabolite DMG accumulated with repeated dosing to the same extent as betaine. In three patients with homocystinuria, distribution and elimination appeared faster than in healthy men.
Approved medical use
Cystadane is FDA-approved for homocystinuria in children and adults, to lower elevated blood homocysteine (Cystadane label). The label covers three inherited causes:
- cystathionine beta-synthase (CBS) deficiency;
- 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency;
- cobalamin cofactor metabolism (cbl) defects.
| Population | Labeled dose |
|---|---|
| Adults and children 3 years and older | 6 g/day, as 3 g twice daily |
| Children under 3 years | Start 100 mg/kg/day in two doses; increase weekly by 50 mg/kg |
| Titration | Increase until total homocysteine is undetectable or present only in small amounts |
| Maximum | Up to 20 g/day has been needed in some patients; a simulation study suggested little benefit above 150 mg/kg/day |
In the label’s controlled trial, 6 patients with CBS deficiency took 3 g twice daily for 12 months in a double-blind crossover; plasma homocystine fell significantly compared with placebo (p under 0.01). In a review of 78 patients from case studies and that trial, homocysteine fell by 71–83% and homocystine by 83–88%. Treating physicians reported clinical improvement, such as fewer seizures or better behavior and cognition, in about three-quarters of patients.
In the EU, Cystadane was designated an orphan medicine in 2001 and authorized in February 2007 (EMA).
What the research shows
Homocysteine in healthy adults
Homocysteine lowering is the most consistent effect of betaine in people without homocystinuria.
| Study | Design | Dose and duration | Result |
|---|---|---|---|
| Olthof et al., J Nutr 2003 | RCT, 4 groups of 19 healthy adults | 1.5, 3 or 6 g/day for 6 weeks | Fasting homocysteine 12%, 15% and 20% lower than placebo |
| McRae, J Chiropr Med 2013 | Meta-analysis of 5 RCTs | At least 4 g/day for 6–24 weeks | −1.23 µmol/L (95% CI −1.61 to −0.85) |
| Ashtary-Larky et al., Crit Rev Food Sci Nutr 2022 | Meta-analysis | Various | −1.30 µmol/L (95% CI −1.61 to −0.98) |
Lower homocysteine has not been shown to prevent heart disease with betaine. No trial cited here measured cardiovascular events.
Strength and power
The largest pooled analysis is a 2024 meta-analysis of 17 placebo-controlled studies with 317 healthy people aged 15–60, of whom 21% were women (Zawieja et al., J Sports Sci 2024). All studies used betaine for at least 7 days.
| Outcome | Effect size (SMD, 95% CI) |
|---|---|
| Maximal strength (1RM, 3RM, isokinetic or isometric force) | 0.47 (0.04 to 0.89) |
| Lower-body strength | 0.49 (0.01 to 0.98) |
| Vertical jump (after excluding one low-quality study) | 0.36 (0.03 to 0.69) |
| Upper-body strength, cycling sprint power, bench throw power, muscular endurance | No significant effect |
An SMD (standardized mean difference) near 0.5 is usually read as a moderate effect. The confidence intervals are wide, and the lower bounds sit close to zero. A 2026 network meta-analysis of supplements for jump performance found a countermovement-jump gain of 3.72 cm with betaine (95% credible interval 1.24 to 6.18), but rated the certainty of most comparisons as very low (Sun et al., J Int Soc Sports Nutr 2026).
Individual trials are small and mixed:
| Trial | Participants | Dose and duration | Main findings |
|---|---|---|---|
| Lee et al., 2010 | 12 trained men, crossover | 1.25 g twice daily, 14 days | Higher bench throw power and isometric force; no change in jump squat power or reps |
| Trepanowski et al., 2011 | Trained men, crossover | 2.5 g/day, 14 days | No significant differences on the main analysis; ≈6.5% more bench reps on a secondary test |
| Cholewa et al., 2013 | 23 trained men | 2.5 g/day, 6 weeks | Body composition and bench work capacity improved in the betaine group only; no difference in 1RM bench, squat or jump |
| Cholewa et al., 2018 | 23 untrained women | 2.5 g/day, 8 weeks | Greater fat loss (−2.0 vs −0.8 kg); no difference in strength or lean mass |
| Moro et al., 2020 | 29 CrossFit trainees | 6 weeks | No between-group difference in strength, body composition or conditioning tests |
| Zawieja et al., 2023 | 43 CrossFit trainees, crossover | 2.5 or 5 g/day, 3 weeks | 8.7% better workout score; no change in Wingate power or body composition; no difference between doses |
Two of the earlier positive trials were funded by betaine suppliers (Danisco; DuPont Nutrition & Health), and an employee of the supplier was a co-author. This is stated in the competing-interest sections of Lee et al. and Cholewa et al. 2013.
In the 2023 crossover trial, testosterone rose by 7.0% with betaine (p = 0.046). This is a single small finding, and no change was seen in IGF-1 or cortisol. It does not make betaine an anabolic agent.
For comparison, creatine monohydrate has a much larger trial base for strength and lean mass. Other supplements studied for training performance include beta-alanine, HMB and citrulline malate.
Body composition
The two meta-analyses on body fat disagree:
| Meta-analysis | Studies | Fat mass | Lean mass | Body weight |
|---|---|---|---|---|
| Gao et al., Nutrients 2019 | 6 RCTs, 195 people | −2.53 kg (95% CI −3.93 to −0.54) | Not pooled | No change |
| Ashtary-Larky et al., Br J Nutr 2022 | RCTs published to August 2021 | −0.57 kg (95% CI −2.14 to 0.99), not significant | +0.61 kg (95% CI −1.27 to 2.49), not significant | No change |
The newer and larger analysis found no effect on body weight, body fat percentage, fat mass or fat-free mass. Results were the same across subgroups by age, sex, BMI, trial length, dose (under vs at least 4 g/day) and health status. In a 12-week trial in 42 obese adults on a calorie-restricted diet, 6 g/day did not improve weight loss or body composition more than placebo (Schwab et al., Am J Clin Nutr 2002). A 2024 narrative review took a more favorable view, reading the trials as showing improved body composition when betaine is combined with physical activity (Nikrandt and Chmurzynska 2024).
Side effects and risks
Cholesterol
Betaine raises blood cholesterol at higher doses.
| Source | Finding |
|---|---|
| Schwab et al. 2002 | 6 g/day for 12 weeks: total and LDL cholesterol higher than placebo (p under 0.05) |
| Zawieja et al., J Diet Suppl 2021 | 6 RCTs, at least 4 g/day for 6–24 weeks: total cholesterol +0.34 mmol/L (95% CI 0.02 to 0.65), ≈13 mg/dL; LDL, HDL and triglycerides not significant |
| Ashtary-Larky et al. 2022 | Total cholesterol +14.12 mg/dL (95% CI 9.23 to 19.02); LDL +10.26 mg/dL (95% CI 6.14 to 14.38); no change in triglycerides, HDL, glucose, CRP, liver enzymes or blood pressure |
In the 2022 meta-analysis, the lipid rise was seen at doses of 4 g/day or more. Doses below 4 g/day lowered homocysteine without raising lipids. The typical 2.5 g/day sports dose falls in that lower range, though that is a subgroup finding.
Cerebral edema in CBS deficiency
The Cystadane label’s only warning concerns patients with CBS deficiency (Cystadane label). Betaine turns homocysteine into methionine, so it can push already high methionine higher. Severe cerebral edema (brain swelling) has been reported within 2 weeks to 6 months of starting treatment. All affected patients had CBS deficiency and plasma methionine of 1,000–3,000 µmol/L, and all recovered fully after stopping betaine. The label says to keep methionine below 1,000 µmol/L.
Other side effects
- Gastrointestinal effects. Nausea and stomach upset were the most common reactions (over 2%) in a physician survey of 111 patients with homocystinuria. Postmarketing reports also list diarrhea, vomiting and glossitis (tongue inflammation).
- Body odor. “Skin odor abnormalities” appear among postmarketing reports.
- Other reports. Anorexia, agitation, depression, irritability, sleep disturbance, hair loss, hives and urinary incontinence. Causation was not established.
- Contraindications. The label lists none.
- Pregnancy. Limited case reports have not identified drug-related risks; animal reproduction studies have not been done.
Most sports and homocysteine trials cited here were small and lasted 8 weeks or less, so they say little about long-term safety in healthy people.
Regulatory status
- US. Betaine anhydrous is an FDA-approved prescription drug (Cystadane, approved 1996, and generics) for homocystinuria. Betaine is also sold as a dietary supplement. It is not a controlled substance.
- EU. Cystadane has been authorized since 2007 as an orphan medicine for homocystinuria.
- Sport. Betaine is not named on the WADA 2026 Prohibited List.
Key takeaways
- A methyl donor and osmolyte. Betaine recycles homocysteine to methionine and helps cells handle osmotic stress; foods supply far less than supplement doses.
- Proven medical use is narrow. In inherited homocystinuria, Cystadane lowered homocysteine by about 71–83%; the labeled dose for patients 3 and older is 6 g/day.
- Small strength effect, uncertain. A 2024 meta-analysis found a moderate effect on maximal strength (SMD 0.47), with wide confidence intervals and many small, partly industry-funded trials.
- No clear body-composition benefit. The larger 2022 meta-analysis found no change in fat mass or lean mass.
- Watch cholesterol at higher doses. At 4 g/day or more, LDL rose by about 10 mg/dL in pooled trials.
- Specific risk in CBS deficiency. Betaine can raise methionine to levels linked with brain swelling, so methionine is monitored in these patients.
Sources
- Recordati Rare Diseases. Cystadane (betaine anhydrous for oral solution) prescribing information. DailyMed version April 2026. DailyMed.
- European Medicines Agency. Cystadane (betaine anhydrous): EPAR. EMA.
- National Center for Biotechnology Information. Betaine, CID 247. PubChem.
- Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539–549. PubMed.
- Nikrandt G, Chmurzynska A. Decoding betaine: a critical analysis of therapeutic potential compared with marketing hype—a narrative review. J Nutr. 2024;154(11):3167–3176. PubMed.
- Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach acidifiers. 21 CFR 310.540. eCFR.
- Schwahn BC, Hafner D, Hohlfeld T, et al. Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria. Br J Clin Pharmacol. 2003;55(1):6–13. PubMed.
- 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):4135–4138. PubMed.
- McRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. J Chiropr Med. 2013;12(1):20–25. PubMed.
- Ashtary-Larky D, Bagheri R, Ghanavati M, et al. Effects of betaine supplementation on cardiovascular markers: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022;62(23):6516–6533. PubMed.
- Zawieja EE, Zawieja B, Chmurzynska A. Betaine supplementation moderately increases total cholesterol levels: a systematic review and meta-analysis. J Diet Suppl. 2021;18(1):105–117. PubMed.
- Zawieja E, Machek S, Zanchi NE, et al. Effects of chronic betaine supplementation on exercise performance: systematic review and meta-analysis. J Sports Sci. 2024;42(22):2131–2144. PubMed.
- Sun R, Su M, Xu X, et al. Effects of dietary supplements on lower-limb power and jump performance in physically active individuals and athletes: a systematic review and Bayesian network meta-analysis. J Int Soc Sports Nutr. 2026;23(1):2740221. PubMed.
- Lee EC, Maresh CM, Kraemer WJ, et al. Ergogenic effects of betaine supplementation on strength and power performance. J Int Soc Sports Nutr. 2010;7:27. PubMed; PMC.
- Trepanowski JF, Farney TM, McCarthy CG, et al. The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. J Strength Cond Res. 2011;25(12):3461–3471. PubMed.
- Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013;10(1):39. PubMed; PMC.
- Cholewa JM, Hudson A, Cicholski T, et al. The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial. J Int Soc Sports Nutr. 2018;15(1):37. PubMed.
- Moro T, Badiali F, Fabbri I, Paoli A. Betaine supplementation does not improve muscle hypertrophy or strength following 6 weeks of Cross-Fit training. Nutrients. 2020;12(6):1688. PubMed.
- Zawieja E, Durkalec-Michalski K, Sadowski M, et al. Betaine supplementation improves CrossFit performance and increases testosterone levels, but has no influence on Wingate power: randomized crossover trial. J Int Soc Sports Nutr. 2023;20(1):2231411. PubMed.
- 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;11(10):2480. PubMed.
- Ashtary-Larky D, Bagheri R, Tinsley GM, et al. Betaine supplementation fails to improve body composition: a systematic review and meta-analysis. Br J Nutr. 2022;128(5):975–988. PubMed.
- Schwab U, Törrönen A, Toppinen L, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr. 2002;76(5):961–967. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.