Suplmnt

TMG (Trimethylglycine) vs Betaine HCl

Evidence Level: promising

Pick TMG if your goal is methylation/homocysteine support; pick Betaine HCl only for short-term gastric acid support (e.g., with pH-dependent drugs) and ideally under clinician guidance. [3][1][2][10][11]

For the most common consumer goal—lowering homocysteine or supporting methylation—TMG (betaine anhydrous) is the clearer choice with randomized evidence and defined dosing, though watch lipids at higher intakes. Betaine HCl is best reserved for brief, targeted re-acidification (minutes to ~1 hour) and lacks strong trials for chronic digestive complaints; it also carries more practical contraindications. [3][4][5][1][2][10][11]

TMG (betaine anhydrous; trimethylglycine) Products

Betaine HCl (betaine hydrochloride) Products

The Comparison

A TMG (betaine anhydrous; trimethylglycine)

Standardization: Betaine anhydrous (USP/EP grade); also Rx Cystadane (betaine anhydrous) 1 g scoop

Dosage: 1.5–6 g/day orally; homocystinuria Rx typical 6 g/day split BID

Benefits

  • •Lowers homocysteine dose-dependently
  • •Possible modest ergogenic effects in some studies

Drawbacks

  • •Can raise LDL and triglycerides at ≥6 g/day
  • •GI upset, body odor (rare)

Safety:Monitor lipids if using ≥3–6 g/day; in CBS deficiency, monitor methionine to avoid hypermethioninemia (Rx labeling).

B Betaine HCl (betaine hydrochloride)

Standardization: Typically 325–1,000 mg betaine HCl per capsule; often combined with pepsin

Dosage: ~650–1,500 mg with meals in studies; onset minutes; duration ≈1 hour

Benefits

  • •Rapid, temporary gastric re-acidification; can restore absorption of some pH-dependent drugs under hypochlorhydria

Drawbacks

  • •Evidence for symptom relief/digestion outcomes is limited; may cause heartburn

Safety:Avoid with active ulcers; caution with GERD; don't combine with PPIs/H2 blockers; safety for chronic multi-dose use is unclear.

Head-to-Head Analysis

Efficacy for primary outcomes Critical

Winner:TMG (betaine anhydrous; trimethylglycine)• Importance: high

TMG lowers homocysteine 10–20% across RCTs and meta-analyses; Betaine HCl lacks robust outcomes for dyspepsia but does acidify transiently. [3][4][1]

Onset and time‑to‑effect

Winner:Betaine HCl (betaine hydrochloride)• Importance: medium

Betaine HCl drops gastric pH to <3 within ~6 minutes, lasting ~1 hour; TMG needs days–weeks for homocysteine changes. [1][9]

Side effects/tolerability Critical

Winner:Tie• Importance: high

TMG can raise LDL/TG at 6 g/day and cause mild GI effects; Betaine HCl may cause heartburn and has more contraindications; overall tolerability acceptable with caution. [5][10]

Standardization/consistency

Winner:TMG (betaine anhydrous; trimethylglycine)• Importance: medium

TMG is available as prescription-grade betaine anhydrous (Cystadane) with defined dosing; Betaine HCl products vary in dose and often add pepsin. [9][16]

Bioavailability/formulation fit

Winner:Betaine HCl (betaine hydrochloride)• Importance: medium

For gastric acidification, HCl salt directly and rapidly re-acidifies the stomach; TMG provides systemic methyl groups rather than acute gastric effects. [1]

Cost/value per effective dose

Winner:TMG (betaine anhydrous; trimethylglycine)• Importance: medium

For methylation targets (grams/day), bulk TMG is practical; HCl capsules typically provide hundreds of mg, impractical for methylation doses. [1][9]

Real‑world adoption and availability

Winner:Tie• Importance: low

Both widely available; TMG also exists as an FDA-approved Rx for homocystinuria, while HCl remains a supplement (not an OTC drug). [9][11]

Which Should You Choose?

Lowering elevated homocysteine or supporting methylation

Choose: TMG (betaine anhydrous; trimethylglycine)

TMG consistently lowers homocysteine in RCTs; start ~1.5–3 g/day, reassess labs; monitor lipids at higher intakes. [3][4][5]

Temporarily counteracting PPI‑induced hypochlorhydria to aid a pH‑dependent drug

Choose: Betaine HCl (betaine hydrochloride)

Single 1.5 g betaine HCl rapidly re-acidifies and restored dasatinib exposure in volunteers; use only with clinician oversight. [1][2]

General digestive complaints (bloating/heartburn) without tested hypochlorhydria

Choose: Either option

Evidence for Betaine HCl symptom relief is weak; address underlying causes first; TMG is not for acute digestive symptoms. [12][11]

Strength/power performance experimentation

Choose: TMG (betaine anhydrous; trimethylglycine)

TMG 2–2.5 g/day shows mixed but occasionally positive results; overall effects modest/inconsistent; set expectations. [7][6][8]

Safety Considerations

TMG/betaine anhydrous: RCTs show LDL and triglyceride increases at 6 g/day—monitor lipids if using higher doses; GI upset possible. In CBS deficiency on Rx betaine, monitor methionine to avoid hypermethioninemia/cerebral edema. [5][9] Betaine HCl: May cause heartburn; avoid with active peptic ulcer disease; caution with GERD; do not co-use with PPIs/H2 blockers meant to raise gastric pH; chronic multi-dose safety data are limited; pregnancy/lactation safety unknown; powder from opened capsules may irritate oral mucosa. [10][11][16]

Common Questions

Can Betaine HCl replace TMG for lowering homocysteine?

Not practically. HCl capsules provide hundreds of mg per dose; homocysteine trials use grams/day of betaine anhydrous. [4][3]

How fast does Betaine HCl work and how long does it last?

pH typically falls within ~6 minutes and stays low ~1 hour in induced hypochlorhydria. [1]

Will TMG raise my LDL?

At 6 g/day, pooled RCT data show modest LDL and triglyceride increases; monitor lipids if using higher doses. [5]

Is Betaine HCl approved by FDA for digestion?

No. FDA deems OTC stomach acidifiers (incl. betaine HCl) not GRASE; products are sold as supplements, not OTC drugs. [11]

What’s a reasonable TMG trial?

Common practice is 1.5–3 g/day for 6–12 weeks with homocysteine (and lipids if higher dose) checked by your clinician. [4][5]

Sources

  1. 1.
    Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole‑induced hypochlorhydria (2013) [link]
  2. 2.
    Use of betaine HCl to enhance dasatinib absorption in hypochlorhydria (2014) [link]
  3. 3.
    Betaine supplementation decreases plasma homocysteine in healthy adults: meta‑analysis (2013) [link]
  4. 4.
    Low‑dose betaine supplementation lowers fasting and post‑load homocysteine in adults (2003) [link]
  5. 5.
    Effect of homocysteine‑lowering nutrients on blood lipids (pooled RCT analyses) (2005) [link]
  6. 6.
    NIH ODS Fact Sheet: Dietary Supplements for Exercise & Athletic Performance (Betaine) (2024) [link]
  7. 7.
    Systematic review: betaine supplementation and strength/power (2017) [link]
  8. 8.
    Double‑blind RCT: 2 g/day betaine in youth soccer players (2021) [link]
  9. 9.
    Cystadane (betaine anhydrous) FDA label (2024) [link]
  10. 10.
    WebMD: Betaine Hydrochloride overview, safety, and OTC status (2025) [link]
  11. 11.
    21 CFR 310.540: OTC stomach acidifiers not GRASE (incl. betaine HCl) (1993) [link]
  12. 12.
    EBSCO Research Starters: Betaine HCl’s therapeutic uses (review) (2024) [link]
  13. 13.
    NIH ODS: Consumer summary on betaine for performance (2024) [link]
  14. 14.
    Low folate status, betaine, and homocysteine during pregnancy (2013) [link]
  15. 15.
    Critical review: betaine supplementation (Strength & Conditioning Journal) (2021) [link]
  16. 16.
    Product label example: betaine HCl + pepsin (Thorne) (2025) [link]

TMG (betaine anhydrous; trimethylglycine) vs Betaine HCl (betaine hydrochloride) • 16 sources

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