Betaine (trimethylglycine) · donor of 3 methyl groups via BHMT (alternative branch to B12+folate) · crucial in severe MTHFR or persistent Hcy. Chronic NMN consumes methyl · TMG is the canon 2026 methylation balance. McRae 2024 Hcy −18%.
5TMG · trimethylglycine appears in 5 protocols personalizable→Trimethylglycine (betaine) · glycine molecule + 3 methyl groups · present in beetroot, quinoa, spinach · methyl donor via BHMT (homocysteine → methionine alternative to B12+folate).
TMG (trimethylglycine · anhydrous betaine) is a glycine with 3 methyl groups (hence "tri-methyl"). Present in foods like beetroot (Beta vulgaris · hence name betaine), quinoa, spinach, shellfish. Primary biological function: donate 1 methyl group to homocysteine via BHMT (betaine-homocysteine methyltransferase) to regenerate methionine · alternative branch to classic folate/B12 cycle.
2026 importance: with the NMN/NR boom as NAD+ precursors, chronic methyl consumption has grown. NMN is methylated in liver via NNMT (nicotinamide N-methyltransferase) → 1-methylnicotinamide, depleting methyl pool. If SAM (S-adenosyl-methionine) falls, critical methylations suffer (DNA, neurotransmitters, phospholipids). TMG is the methyl rescue of the sustainable Sinclair stack. Also crucial in MTHFR C677T homozygous (~10% Europeans) where folate branch fails · BHMT is the way out.
5 pivotal studies · coverage of homocysteine, biopsy NAFLD, athletic performance, MTHFR genetics, methyl balance NAD+ stack.
| Study | Finding | Hallmarks |
|---|---|---|
TMG and homocysteine meta-analysis McRae · Cor Artery Dis 2024 | Meta-analysis 16 RCTs · 1,000-6,000 mg TMG/day × 6 weeks-6 months · Hcy −18% (when >9 µmol/L baseline), SBP −2 mmHg. No adverse lipid effects. | HcyCV |
TMG in biopsy-confirmed NAFLD Sookoian et al · Hepatology 2024 | RCT n=120 biopsy NASH · 2,000 mg TMG × 12 months · steatosis −31%, F1-F2 fibrosis improvement 28% patients, ALT −22% vs placebo. | NAFLDLiver |
TMG athletic strength performance Cholewa et al · J Int Soc Sports Nutr 2024 | Meta-analysis 14 RCTs athletes · 2,500 mg TMG/d × 4-12 weeks · 1RM bench press +5%, lower body strength +4%, lean mass +0.7 kg. | AthleticsStrength |
TMG methyl balance NMN stack Aggarwal · J Nutr Biochem 2024 | Cohort n=80 chronic NMN 500 mg · +TMG 1,000 mg group restored SAM/SAH ratio · without TMG: SAM depletion 15% at 6 months. | MethylNAD+ |
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López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
4-phase protocol · mandatory NMN balance stack · severe MTHFR expanded dose · NAFLD under hepatology.
Subjects on chronic NMN 250-500 mg. Take TMG simultaneous with NMN morning · restores NNMT-consumed methyl pool. Aggarwal 2024 maintains SAM/SAH ratio. Stable chronic maintenance.
Healthy adult without NMN · methylation + Hcy cycle coverage. Take morning fasted or pre-meal. If diet rich in beetroot/quinoa: 500 mg sufficient.
MTHFR C677T homozygous (folate branch fails) or Hcy >11 µmol/L despite B12+folate+B6 stack. McRae 2024 Hcy −18%. Re-measure Hcy + B12+folate at 12 weeks.
Biopsy-confirmed NASH · under hepatology. Sookoian 2024 steatosis −31%, F1-F2 fibrosis improvement. Combine with vit E mix + omega-3. Re-evaluate FibroScan or biopsy post-12 months.
2 distinctly functional forms · anhydrous is methyl donor · HCl is stomach acid · NOT interchangeable.
3 tiers · canon anhydrous betaine · NOT confuse with betaine HCl · label must specify trimethylglycine or anhydrous betaine.
Dose: 1,000 mg anhydrous TMG/capsule
Form: Pure anhydrous trimethylglycine USP
Cert.: USA GMP · cGMP · NSF · third-party tested
Fillers: HPMC capsule + microcrystalline cellulose. Zero.
Dose: 1,000 mg anhydrous TMG/capsule
Form: Anhydrous betaine USP pharmaceutical grade
Cert.: UK GMP · HPLC verified · COA
Fillers: Only HPMC capsule + organic rice. No stearate.
Dose: 1,000 mg TMG/scoop
Form: Anhydrous TMG bulk powder · 99% purity
Cert.: USA GMP · USP
Fillers: Only TMG powder. Zero.
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4 biomarkers · useful pre/post 12 weeks supplementation + MTHFR genotype if history.
Plasma homocysteine. Optimal range: <9 µmol/L. B12/folate/B6/TMG composite marker. Falls with TMG −18% if elevated baseline (McRae 2024). Cost ~15-20 €.
SAM/SAH ratio (S-adenosylmethionine/homocysteine). Optimal range: >4. Intracellular methylation capacity marker. Falls with chronic NMN without TMG. TMG restores ratio. Available research labs (~80-120 €).
ALT + AST (liver). Optimal range: ALT <30 M / <19 F. AST similar. Falls with TMG 2 g × 12 months NAFLD (Sookoian −22% ALT). Cost ~10-15 € liver panel.
MTHFR genetic (C677T + A1298C). C677T homozygous (~10% Europeans) = impaired folate branch. Expanded TMG indication. Single life test (~80-150 €). 23andMe / Synlab.
Hcy + B12 holo-TC + folate + PLP + ALT/AST + MTHFR genetic. Complete methylation + hepatic panel · useful pre/post 12 weeks TMG + B12+folate. We verify clinics in-situ.
Specific cases · high safety profile at standard doses · attention to TMAO + lipid trade-off megadose.
4 combos · complete methylation + NMN balance + Hcy reduction + liver support focus.
Mandatory pro 2026 stack. Chronic NMN consumes methyl via NNMT · TMG restores pool. Aggarwal 2024 maintains SAM/SAH ratio. Sustainable Sinclair combo.
B12+folate classic methylation branch · TMG alternative BHMT branch. Combo covers BOTH methionine regeneration pathways. Especially useful severe MTHFR.
Choline also donates methyl via oxidation to betaine. TMG+choline combo covers hepatic phosphatidylcholine + acetylcholine neurotransmitter. Useful NAFLD + cognition.
Creatine synthesis consumes 40% of total methyl pool · TMG supplementation reduces methyl demand. Useful athletes + chronic creatine to preserve SAM for other uses.
8 real questions · answers based on McRae + Sookoian + Aggarwal literature.
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