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 et al] # backfilled 2026-08-17 from PubMed during sequential re-read 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 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 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 | 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.