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TMG (betaine)

Trimethylglycine / betaine anhydrous · Performance

ModerateSeveral human trials, smaller or less consistent.

A methyl donor with one well-established effect and one popular claim that keeps not replicating.

≥4 g/day
Where the LDL-raising trade-off appears in the trials, lower amounts lowered homocysteine without it

What it is

Trimethylglycine (betaine), a compound from beets that donates methyl groups. It has two almost unrelated selling points: a genuinely well-evidenced effect on homocysteine, and a much shakier reputation as a strength supplement.

How it works

TMG donates a methyl group to convert homocysteine back into methionine. That reaction is well characterized, which is why the homocysteine effect is one of the more reproducible findings on this shelf. The performance rationale (cellular osmolyte effects and creatine support) is far more speculative.

Which form to buy

TMG / betaine anhydrous powderBoth use cases

The form in essentially all trials; cheap by the kilogram and slightly sweet.

The default.

Betaine HClA DIFFERENT purpose

Sold for stomach acid, not methylation, commonly confused with TMG on labels.

Not the same product; check which you are buying.

Food (beets, spinach, wheat bran)Baseline intake

Beets are the namesake source.

Real dietary sources, below trial amounts.

What it actually does, graded

Lowers homocysteineStrong

Reliably demonstrated. Note prescription betaine anhydrous (Cystadane) is FDA-approved for homocystinuria, that is a DRUG approval and does not make OTC TMG an approved treatment.

Improves cardiovascular outcomes by lowering homocysteineNone shown

No clinical-outcome trial has established that betaine-induced homocysteine lowering prevents cardiovascular events, the negative outcome evidence comes mainly from the B-vitamin homocysteine trials.

Strength and power performanceLimited

A 2024 meta-analysis (17 studies, 317 people) found a modest significant effect on maximal and especially lower-body strength, but no benefit for upper-body strength, sprint power or endurance, on a small sample with confidence intervals near zero.

Body compositionLimited

A few trials suggest small changes; inconsistent.

Liver fat (fatty liver disease)Limited

Early research; not established.

Pros and cons

Pros
  • Very cheap
  • A rock-solid, reproducible biochemical effect
  • Stacks logically with creatine, with which it shares a metabolic relationship
Cons
  • No outcome trial has tested whether its homocysteine lowering prevents anything, the marker is not the disease
  • Higher doses (around 4 g/day and above) can raise LDL and total cholesterol, a genuine, under-mentioned trade-off
  • The performance signal is modest and rests on a small pooled sample
  • Fishy body odour at higher amounts

What to expect

  • Homocysteine falls within weeks, measurable on a blood test, not felt.
  • Performance: the trials disagree, so treat your own result as the data.

Interactions

CautionCholesterol managementDose-dependent: meta-analysis found roughly +10 mg/dL LDL overall, with the lipid rise concentrated at 4 g/day and above, under 4 g/day lowered homocysteine without it.
CautionHomocystinuriaPrescription betaine anhydrous is approved here, but strictly specialist-directed: in CBS deficiency it can markedly raise methionine, and cerebral edema has been reported. Not a self-managed use.
CompatibleMethylation-related supplements (folate, B12)They work in the same cycle and are commonly combined.

Is it for you?

Probably worth it if
  • Elevated homocysteine your clinician is tracking
  • You already take creatine and want a cheap, low-risk experiment with realistic expectations
Probably skip it if
  • You are managing LDL cholesterol and considering higher amounts, that is where the lipid rise shows up
  • You expect reliable strength gains, the trials do not agree

Who should avoid it

  • People actively managing high LDL, without clinician awareness

Research on this supplement

Papers about this supplement, not proof of the claims above. A title says what was studied, which is sometimes a negative result or a different question entirely.

  • Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis
    J Sports Sci, 2024
  • Betaine supplementation fails to improve body composition: a systematic review and meta-analysis
    Br J Nutr, 2022
  • Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis
    Crit Rev Food Sci Nutr, 2022

What the evidence says

Betaine lowers homocysteine reliably, that is established enough that it is an approved treatment for inherited homocystinuria. Whether lowering homocysteine improves cardiovascular outcomes is a separate and largely negative literature. The strength and power-output claims come from a handful of small trials with inconsistent results. It also appears in NAD+ stacks as a methylation buffer, which is mechanistic reasoning rather than trial evidence.

What studies used

Homocysteine studies used around 3-6 g/day; performance trials commonly used 2.5 g. Published studies had not established a preferred timing.

Reported from published studies and product labelling — a record of what was used in research, not a recommendation. What is right for you is a conversation with a clinician.

Watch out for

  • High doses can raise LDL cholesterol in some studies, worth knowing if lipids are already a concern

Evidence base

A3,408 research papers
established literature

Strong human evidence: either a phase 3 or 4 trial report alongside review-level evidence, or ten or more randomised controlled trial reports.

This letter measures how much human research exists, not whether it works for you — the tier above (Moderate) is the read on quality.

Research (12)

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Where next

Every supplement in the catalogThe full shelf, grouped and evidence-tiered.→The compound indexSteroids, nootropics and research chemicals.→The peptide indexInjectable peptides and what trials used.→