Betaine (Trimethylglycine / TMG)New
Betaine (trimethylglycine, TMG) is a naturally occurring methyl donor found in beets and spinach, and its purified form is an FDA-approved prescription treatment for homocystinuria. Multiple human RCTs confirm that 3-6g/day reliably lowers elevated homocysteine, and separate trials in resistance-trained adults (e.g., Cholewa et al., 2013) have found modest improvements in body composition and power output, though results are mixed. One notable caveat from human trials (Olthof et al., 2005) is that betaine supplementation can transiently raise LDL cholesterol in some people, so lipid monitoring is reasonable for those already at cardiovascular risk.
Mechanism of Action
Betaine donates a methyl group to homocysteine, converting it back to methionine via the enzyme betaine-homocysteine methyltransferase (BHMT) — a folate-independent pathway concentrated in the liver and kidney. This supports downstream production of S-adenosylmethionine (SAMe), the body's primary methyl donor for DNA, protein, and neurotransmitter methylation. Betaine also functions as an organic osmolyte, helping cells retain water and maintain protein stability under osmotic stress, which is proposed to contribute to its exercise-performance effects.
Dosing Protocol
1.5-3g daily (general use); higher doses used clinicallymg
Standard starting dose based on research
Therapeutic Range
1500
Minimum
6000
Maximum
With meals, divided doses
Dosages are general guidelines. Individual requirements vary based on body weight, health status, and specific goals. Start with lower doses and adjust based on response.
Benefits
Primary Benefits
- Homocysteine reduction
- Methylation support
- Liver fat metabolism
- Exercise performance (modest)
Secondary Benefits
Safety Information
Contraindications
Do not use if any of the following apply:
- •Pre-existing dyslipidemia (monitor lipids)
- •Renal impairment (caution)
Drug/Supplement Interactions
May interact with the following. Consult a healthcare provider before combining:
Potential Side Effects
Some users may experience:
This is not a complete list of interactions or side effects. Individual responses vary. Always start with the lowest effective dose and monitor your response. Report any adverse effects to your healthcare provider.
Quality Markers
Look for these specific quality indicators when sourcing this compound:
- Pharmaceutical-grade anhydrous betaine
- Third-party tested for purity
Trusted Certifications
Note: Supplement quality varies dramatically between brands. Cheap supplements often contain fillers, incorrect doses, or contaminants. Investing in quality products from reputable manufacturers is essential for safety and efficacy.
Evidence Profile
Evidence Score
6/10
Moderate Evidence
Some clinical trials with positive results, emerging research
Evidence Scale
8-10
Strong
5-7
Moderate
1-4
Emerging
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