Trimethylglycine (Betaine): Mechanisms, effects, and potential benefits for health and body composition

Trimethylglycine, better known as betaine, is a molecule present in the body that plays a central role in one-carbon metabolism as a methyl donor. Although betaine is mainly associated by many people with sports performance or methylation, it affects multiple fundamental biological processes that are relevant to healthy aging and metabolic resilience.

Methylation and homocysteine regulation

Betaine functions as a methyl donor in the betaine-homocysteine methyltransferase (BHMT) pathway, converting homocysteine into methionine. Through this remethylation, betaine lowers homocysteine levels, which is important because elevated homocysteine is associated with cardiovascular risks and inflammatory stress. Meta-analyses show that betaine supplementation can significantly lower plasma homocysteine in healthy adults.¹

Epigenetic stability and DNA integrity

Betaine provides methyl groups that are crucial for one-carbon metabolism, which in turn is involved in DNA methylation, gene expression, and cellular signaling pathways. Properly functioning methylation supports the epigenetic infrastructure of cells, an important factor in genome stability and in limiting processes associated with aging. Ongoing methylation support may contribute to genomic stability and better regulation of cellular processes.¹

Metabolic health and liver function

Betaine also plays a role as an osmolyte, a substance that helps cells maintain their water balance during metabolic stress, and supports liver function and fat metabolism. Animal and human data show that betaine can modulate how fats are processed in the liver and may contribute to a more favorable fat metabolism.²

Effects on Body Composition: Fat Loss and Lean Mass

Research shows that betaine supplementation in combination with strength training can support significant improvements in body composition:

• In a double-blind RCT, young resistance-trained men who took betaine (± 2.5 g/d) for 6 weeks showed a significant decrease in fat mass and increase in lean body mass compared with placebo, alongside improved work capacity.³
• In a similar study in young women, betaine plus resistance training led to greater fat-loss outcomes than training alone, indicating a favorable effect on body composition when betaine is combined with physical training.⁴

Support from meta-analysis

Meta-analytic evidence supports these favorable shifts:

• A systematic review of RCT’s showed that betaine supplementation caused significant reductions in total body composition (fat mass and body fat percentage) in humans, suggesting that betaine may be important for promoting a favorable «lean vs. fat» balance.⁵

Observational research shows that higher dietary betaine intake is associated with more favorable body composition, including lower body fat percentage and higher lean mass in broad populations.⁶

💡 These positive findings indicate that betaine, especially in combination with resistance training and an active lifestyle, may contribute to fat loss and the maintenance or improvement of muscle mass, factors that are important for functional health and resilience during aging.

Mechanisms that can influence body composition

The exact mechanisms by which betaine affects body composition are the subject of ongoing research, but possible pathways include:

• Energy metabolism: betaine can improve fractions of fat metabolism and inhibit lipogenesis.
• Cellular osmolysis: better cellular hydration can increase anabolic response capacity.
• Training response: the combination of betaine with resistance training programs appears to have synergistic effects on fat loss and lean mass.⁷([turn0search23]

Summary of potential benefits

Betaine supports multiple biological systems:

• Methylation & homocysteine regulation — contributes to epigenetic stability and the reduction of a cardiovascular risk factor.¹
• Metabolic health & liver function — participates in one-carbon metabolism and can modulate fat metabolism and liver function.²
• Body composition — in combination with resistance training and an active lifestyle, betaine can help reduce fat mass and improve lean mass.³ ⁴ ⁵ ⁶

Sources:

1. Meta-analysis shows that betaine supplementation significantly lowers plasma homocysteine, a marker related to cardiovascular risks.
   https://pmc.ncbi.nlm.nih.gov/articles/PMC3610948/
2. Review: Betaine supports metabolic processes, oxidative stress, and liver health via methylation and other pathways.
   https://pmc.ncbi.nlm.nih.gov/articles/PMC8224793/
3. Randomized clinical trial: 6 weeks of betaine supplementation improved body composition (fat mass ↓, lean mass ↑) in resistance-trained men. https://pubmed.ncbi.nlm.nih.gov/23967897/
4. Betaine supplementation plus resistance training resulted in improved body composition in active women.
   Effect of betaine supplementation on body composition and performance in collegiate females (abstract summary). https://pmc.ncbi.nlm.nih.gov/articles/PMC6069865/
5. Meta-analysis: Betaine supplementation reduces total fat mass and body fat percentage in humans.
   https://pmc.ncbi.nlm.nih.gov/articles/PMC6835719/
6. Observational evidence that higher dietary betaine is associated with more favorable body composition.
   https://link.springer.com/article/10.1186/s12970-018-0243-x
7. Studies suggest that betaine together with training has a greater impact on body composition compared with training alone.
   https://pmc.ncbi.nlm.nih.gov/articles/PMC6069865/