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Studies
Tmg5.8
TMG Research
Mostly mechanism / observational
15 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most TMG studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2017–2026 with a typical study size of 44 participants.
Based on 15 studies · 4 meta-analyses · 4 RCTs · 117 total participants
In plain English: A deeper understanding of betaine may help elucidate crucial molecular mechanisms underlying its effects and offer theoretical insights for developing exercise-mimicking foods, supplements, and drugs, which are expected to benefit the human health.
Xu Y, Gao J, Wang M, Zhang H. · Frontiers in nutrition (2025)
As the global population ages, chronic diseases are posing the primary threat to the health of the elderly, significantly increasing the medical pressure on families and society.
Although exercise is a primary intervention for preventing and treating chronic diseases, many elderly individuals have motor disabilities.
Therefore, researchers are exploring natural products that mimic the therapeutic effects of exercise in individuals who are unable to exercise.
In plain English: These pieces of evidence are of great importance for deepening our understanding of the antidepressant mechanism of betaine, so as to develop betaine supplements for the supplementary treatment of depression.
Zhang YY, Cheng YY, Guan W. · Current drug targets (2025)
Interestingly, accumulating evidence has shown that betaine exerts a significant role in alleviating depressive-like behavior in patients and animals resulting from chronic stress.
Although the antidepressant effects of betaine have not been compared with traditional antidepressants with insufficient verification, based on the neurobiological mechanisms of depression, it may be a potential alternative medicine for the treatment of depression.
This is the first review aiming to provide a comprehensive overview of the remarkable effects of betaine in the pathophysiology of depression.
Liu Y, Li Q, Liu R, Wang Z, Zhao S. · Foods (Basel, Switzerland) (2026)
Published in Foods (Basel, Switzerland) (2026)
5Meta-Analysis2024
In plain English: In conclusion, betaine supplementation for at least 7 days significantly enhances muscular strength, especially lower body strength, and shows potential in improving vertical jumping performance.
Zawieja E et al. · Journal of sports sciences (2024)
Significant effect on maximal strength (SMD 0.47, 95% CI 0.04-0.89), particularly lower body
No significant effects on upper body strength, sprint power, or muscular endurance
In plain English: Supplementation with at least 4 g/d of betaine for a minimum of six weeks may moderately increase plasma TC, which might be important in the context of cardiovascular health.
Zawieja EE et al. · Journal of dietary supplements (2021)
Moderately increased total cholesterol (pooled +0.34 mmol/L, p = 0.0352) at ≥4 g/d
No significant effect on LDL, HDL, or triglycerides in this analysis
A meaningful trade-off at higher doses; important caution for cardiovascular risk
In plain English: Betaine supplementation had a significant effect on concentrations of betaine ... total cholesterol (TC) (MD: 14.12 mg/dl, 95% CI%: 9.23 to 19.02), low-density lipoprotein (LDL) (MD: 10.26 mg/dl, 95% CI: 6.14 to 14.38)], homocysteine (WMD: -1.30 micromol/L, 95% CI: -1.61 to -0.98)
Ashtary-Larky D et al. · Critical reviews in food science and nutrition (2022)
In plain English: The present systematic review and meta-analysis does not show any beneficial effects of betaine supplementation on body composition indices (BM, BMI, FM and FFM).
Ashtary-Larky D et al. · The British journal of nutrition (2022)
No significant change in body fat or lean mass
Tempers fat-loss claims
Performance effects are separate from body composition
In plain English: Betaine 8, 4, and 2 g/day for 12-24 weeks significantly reduced ALT and other serologic markers of liver injury among participants with clinically defined MASLD and an elevated ALT.
Lim AS et al. · Hepatology (Baltimore, Md.) (2026)
The primary outcome was the percent decline in the abnormal component of ALT (ie, ALT >30 for males or >25 for females).
At baseline, more than 75% of participants had NASH when tested by the MASEF score.
Approximately 35% reported mild, transient gastrointestinal symptoms.
In plain English: This work provides a theoretical basis for nutritional intervention strategies for obesity and resulting metabolic diseases.
Zhang L et al. · Nutricion hospitalaria (2026)
However, the observation group exhibited superior reductions in BMI (t = 7.329, p < 0.001) and WHR (Z = 7.059, p < 0.001) compared to controls.
Additionally, 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).
Conclusion: betaine-containing nutrients applied in overweight and obese patients with HHcy are capable of effectively decreasing Hcy levels and improving constitution parameters plus glycolipid metabolism indicators in such patients.
In plain English: Collectively, betaine represents a promising therapeutic candidate with significant translational potential for the treatment of metabolic, cardiovascular/cardiometabolic, and renal diseases.
Singh SK, Yadav P, Bishnolia M, Manhar N, Kumar P, Navik U, Weiskirchen R. · Frontiers in pharmacology (2026)
Furthermore, betaine regulates epigenetic modulations of genes linked to inflammation, fibrosis, and metabolic pathways.
Betaine is generally regarded as non-toxic.
However, its dose-dependent effects and long-term safety require further analysis, along with detailed evaluations of its multifaceted protective mechanism against disease conditions.
In plain English: We recommend that when combined with preconception counselling, early standardized diagnosis, optimal monitoring and postnatal care, prenatal OHCbl therapy can improve pregnancy outcomes and mitigate neurodevelopmental and ophthalmic complications in cbl-RD.
Stepien KM et al. · Journal of inherited metabolic disease (2026)
Notably, three of five infants harbouring severe MMACHC variants, who received high-dose pre- and postnatal OHCbl, exhibited normal neurodevelopment and no maculopathy up to age 2-3 years, though variability in genotype, treatment regimens, and duration of follow-up limit generalizability.
A literature review identified nine additional pregnancies in women with cbl-RD and seven prenatally treated fetuses, with follow-up available for three.
Collectively, our main findings support the safety of maternal and fetal OHCbl treatment during pregnancy.
In plain English: Evidence suggests that betaine may counteract aging-related changes in methylation potential by increasing concentration of S-adenosylmethionine, a key methyl donor. Additionally, betaine reduces homocysteine concentrations, potentially mitigating vascular, neurodegenerative, and oxidative damage.
Zawieja E et al. · Ageing research reviews (2025)
Methyl-donor and osmolyte roles; raises S-adenosylmethionine
Reduces homocysteine; enhances mitochondrial function and reduces oxidative stress
No clear link established between dietary betaine and CVD or type-2 diabetes incidence