Supplements
betaine decreases homocysteine
Strong support Supplements 💰 Industry COI noted
RefutedContestedStrong support
consensus score 1.00
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: All trials, pooled (Meta-analysis)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
4 support 0 contradict 0 tested null 0 mixed · 4 sources, 4 independent groups
What the evidence shows
Betaine (TMG) lowers homocysteine via the BHMT pathway.
The evidence (6)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Gu X, Fu Y, Zhao Y, Liu Z, Yang Y, Xie Q, Ma P, Peng Z, Liu Z, Li J, Xie J 2026 · Antioxidants | animal | supports | moderate | Mouse model (high-methionine diet 8 wk -> hHcy, then betaine 14 d) + HT-22 cells: betaine attenuated cognitive impairment, suppressed ROS, neuronal apoptosis and Tau hyperphosphorylation (Ser396/Thr231) via PI3K/AKT/GSK-3b (blocked by LY294002; NAC phenocopies). Hcy-lowering by betaine is cited as background, not measured as an outcome. |
| McRae MP 2013 · J Chiropr Med | meta-analysis | supports | moderate | Random-effects MA of 5 placebo-controlled RCTs (2002-2010; healthy adults; >=4 g/d betaine for 6-24 wk): pooled reduction in plasma homocysteine of 1.23 umol/L (95% CI -1.61 to -0.85). Search was MEDLINE plus a manual search, single author; no sub-4 g/d arms pooled. The '5-20% at 6 g/d' figure previously recorded here is the paper's introductory premise, not its own result. |
| Zhang L, Zhang Y, Yang D, Yang C, Rong X, Li X, Zhang X, Zhang J, Zhang P 2026 · Nutr Hosp | RCT | supports | low | Single-centre unregistered RCT, 102 overweight/obese inpatients with hyperhomocysteinemia, 8 weeks: 'Finally, 102 included subjects were allocated to an observation group (n = 52, given betaine-containing nutrients) or a control group (n = 50, routinely administered with vitamin B6, vitamin B12 and folic acid) using a random number table.' The betaine arm fell further on Hcy than the active B-vitamin arm - 'the betaine group achieved greater improvements in FBG (t = 5.570), TG (Z = 3.988), low-density lipoprotein cholesterol (LDL-C) (Z = 6.929), Hcy (Z = 6.400), and AIP (t = 6.794) (p < 0.001)' - but the intervention is an unnamed multi-ingredient product with no stated betaine dose, no blinding or allocation concealment is reported, and BMI/WHR/body-fat fell in BOTH arms, so a weight-loss co-intervention is uncontrolled. Directionally supportive; attribution to betaine itself is not established. Abstract-only (publisher full text Cloudflare-blocked). |
| Lu XT, Wang YN, Mo QW, Huang BX, Wang YF, Huang ZH, Luo Y, Maierhaba W, He TT, Li SY, Huang RZ, Yang MT, Liu XZ, Liu ZY, Chen S, Fang AP, Zhang XG, Zhu HL 2023 · Eur J Nutr | RCT | supports | low | Combination product only: 400 ug folic acid + 8 mg B6 + 6.4 ug B12 + 1 g betaine + zinc vs placebo, 12 wk, n=92 Chinese adults with hyperhomocysteinemia. Plasma homocysteine fell 3.87 umol/L vs placebo (95% CI -6.90 to -0.84; P=0.012; -10.1%). Betaine is NOT isolated - the authors state 'our study precluded assessment of the separate effects of B vitamins and betaine. We could only discuss the integrated effects of the four nutrients'. The only betaine-specific signal is a non-randomized within-arm regression at n=35 (beta -1.421, P=0.020), alongside a stronger folate signal (beta -1.680, P=0.004). Product manufactured by By-Health with a corresponding author at the BYHEALTH Institute, yet no COI declared. |
| betaine-meta-2021 2021 · Journal of dietary supplements | meta-analysis | supports | moderate | SR+MA of 6 placebo-controlled RCTs (>=4 g/d betaine, 6-24 wk): pooled endpoints are blood LIPIDS only — total cholesterol +0.34 mmol/L (95% CI 0.02-0.65, p=0.035) vs placebo; no significant HDL/LDL/TG effect reported in abstract. Homocysteine is not a pooled outcome. |
| Çakır Gündoğdu A et al 2022 · J Invest Surg | animal | supports | moderate | Wistar rats given oral betaine 250 mg/kg for 21 days before ethanol-induced gastric ulcer showed significantly reduced homocysteine levels vs vehicle. Also improved oxidative-stress markers (TOS, MDA down; TAS, GSH, CAT up). |
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Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.