Betaine Anhydrous (TMG)
Also sold as: TMG Trimethylglycine, Trimethylglycine
Best-in-class: Betaine Anhydrous
A methyl donor (trimethylglycine) that acts as a cellular osmolyte for power/strength output and lowers homocysteine for cardiovascular support.
Betaine Anhydrous (TMG) quick facts
| Suggested dose | 2.5 g daily. |
| How often | Daily |
| Who it's for | Strength/power athletes and methylation/cardiovascular support. |
Multiple resistance-training trials show improved power output and body composition at around 2.5 g daily, which is more consistent than most performance supplements manage. It is also the cheapest way to support methylation alongside folate and B12, and the reason it appears in NAD+ precursor stacks — heavy NMN or NR dosing consumes methyl groups. Do not confuse it with betaine HCl, which is a stomach acid supplement and a completely different thing despite the shared name.
How Betaine Anhydrous (TMG) actually works
Trimethylglycine does two things. It donates a methyl group to betaine-homocysteine methyltransferase, converting homocysteine back to methionine — a folate-independent route through the methylation cycle. Separately it is an osmolyte, accumulating inside cells to protect them against dehydration and thermal stress, which is the proposed basis for its performance effect.
Where to get Betaine Anhydrous (TMG)
Find Betaine Anhydrous (TMG) on iHerb →The evidence for Betaine Anhydrous (TMG)
Graded by what exists behind each claim.
✅ Clinically validated
- RCTs show improved power, strength and body composition with ~2.5 g/day in trained lifters.
- Lowers homocysteine as a methyl donor.
📊 Correlative data
- Betaine status supports methylation and cellular hydration under training stress.
🧪 Theoretical / extrapolated benefits
- Performance benefits are reasonably supported; mechanisms (osmolyte + methylation) are well-characterized.
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What Betaine Anhydrous (TMG) actually does
Betaine has two unrelated jobs and the supplement industry sells it for a third. Chemically it is trimethylglycine: a glycine with three methyl groups on the nitrogen and a permanent positive charge. That charge, paired with the carboxylate, makes it a zwitterion that stabilizes protein hydration shells without disturbing enzyme function, which is the osmolyte job. The three methyl groups make it a methyl donor, which is the biochemical job. Neither of those is obviously an ergogenic mechanism.
The methyl donation runs through one enzyme with a very specific location. Betaine-homocysteine methyltransferase, expressed mainly in liver and kidney, transfers a methyl group from betaine to homocysteine to make methionine and dimethylglycine. That is the folate-independent route out of homocysteine, running in parallel with methionine synthase and available when folate or B12 is short Steenge 2003.
The osmolyte job is what the kidney medulla and the liver actually use it for. Cells in a hypertonic environment accumulate betaine through the BGT-1 transporter to balance osmotic pressure without raising intracellular ionic strength. In the liver, that same capacity is implicated in the gut-liver axis work on chronic liver disease Perumal 2025.
The proposed ergogenic mechanisms are all downstream inferences. More methionine means more S-adenosylmethionine, which means more creatine synthesis; osmolyte accumulation might swell the muscle cell and trigger anabolic signaling; reduced homocysteine might improve endothelial function. Each is plausible, each has a step nobody has measured in an exercising human, and none of them predicts the size of effect the products claim.
And there is a metabolic neighbor that complicates the whole picture. Betaine sits one enzymatic step from choline and shares a gut-microbial neighborhood with carnitine; anaerobic gut bacteria metabolize carnitine-derived gamma-butyrobetaine to trimethylamine Rajakovich 2021, which the liver oxidizes to trimethylamine N-oxide. Betaine's relationship with that pathway is the reason it appears in the TMAO literature at all Ilyas 2022.
Cell, rodent, human — and where it stops
This page has the cleanest example in the whole cohort of one intervention moving two surrogates in opposite prognostic directions.
In humans the homocysteine effect is direct and dose-dependent. Betaine supplementation lowered plasma homocysteine in healthy men and women, with the effect visible at doses in the range products actually supply Steenge 2003. It works, it works quickly, and it works independently of folate status.
And in the same literature the lipid panel moves the wrong way. A systematic review and meta-analysis found that betaine supplementation moderately increases total cholesterol Zawieja 2021. A person taking trimethylglycine to lower a marker associated with cardiovascular risk is simultaneously raising a different marker associated with cardiovascular risk.
Neither marker has an outcome behind it for this compound. No trial has followed betaine-supplemented people to a cardiovascular event, in either direction. The two surrogates simply point at each other, and the honest summary is that nobody knows which one, if either, matters.
In the liver the mechanism has more support and the trials are small. Betaine regulates the gut-liver axis and has been proposed as a therapeutic approach for chronic liver disease Perumal 2025, with human trials in fatty liver reporting enzyme and imaging changes in small samples. That is the most promising indication on the page and it is still at the surrogate stage.
The obstacle to transfer for the performance claim is a measurement nobody has taken. The 2.5 g dose comes from a handful of small resistance-training studies with mixed results and inconsistent endpoints, and no study has measured muscle betaine content, muscle phosphocreatine or S-adenosylmethionine in a supplemented athlete. The chain from methyl donor to bench press has an unmeasured link in the middle of it.
Betaine Anhydrous (TMG) — which form, and does it matter
Betaine anhydrous and betaine hydrochloride are sold side by side for opposite purposes and confusing them is a real error. Betaine anhydrous is the neutral zwitterion used as a methyl donor and osmolyte. Betaine hydrochloride is the same molecule with a stoichiometric hydrochloride, sold to acidify the stomach; it delivers roughly 23 percent of its weight as hydrochloric acid and has been shown to re-acidify the stomach in people with drug-induced hypochlorhydria. Taking the hydrochloride for methylation means swallowing acid you did not intend to.
The exposure profile is why the dose is grams and the timing is flexible. Betaine is absorbed rapidly and almost completely by the amino acid transporter system in the proximal small intestine, peaks in plasma at roughly 1 to 2 hours after a single dose, and accumulates with repeated dosing because tissue uptake through BGT-1 is slower than absorption. The plasma half-life after a single dose is on the order of 14 hours, and it lengthens with continued dosing as tissue pools fill.
Its disposal is enzymatic rather than renal, which is unusual for a small polar molecule. Betaine is consumed by betaine-homocysteine methyltransferase rather than excreted, so renal clearance carries only a small fraction at ordinary intakes. There is no cytochrome involvement and no first-pass metabolism in the drug sense — the liver is the target organ rather than an obstacle. Betainuria appears only when intake exceeds the enzyme's capacity or in renal tubular disorders.
Food gives more of it than most people expect. Wheat bran, wheat germ, spinach, beets and quinoa are rich sources, and habitual dietary intake runs from about 100 to 400 mg a day. A 2.5 g supplement is therefore roughly ten times a normal dietary intake, which is a pharmacological rather than a nutritional dose.
What the panel in front of this reader contains. The methylation formula filed in the NIH label database declares 1.8 g of betaine anhydrous per three-capsule serving alongside riboflavin 5'-phosphate, P5P, 5-MTHF and methylcobalamin Office of Dietary Supplements. Anyone taking that plus a standalone 2.5 g betaine is at more than 4 g a day, which is the range where the lipid signal was observed Zawieja 2021.
What would have to be true, and how you would know it was not
1. Homocysteine falls, reliably and fast. Predict homocysteine down within 4 to 6 weeks on 2.5 to 6 g a day, independently of folate status, because the enzyme that does it is folate-independent Steenge 2003. Retest at 6 weeks.
2. The prediction that cuts against the product, and it is on the same blood draw. Predict total cholesterol and LDL cholesterol rise modestly over the same period Zawieja 2021. Run a lipid panel and ApoB alongside the homocysteine, not instead of it. A well-powered trial showing no lipid rise at 4 g and above would falsify this page's central caution.
3. Predict TMAO is worth measuring and predict the direction is not obvious. Betaine sits in the trimethylamine neighborhood Ilyas 2022 Rajakovich 2021, and whether supplementation raises TMAO (trimethylamine N-oxide) in people has not been settled. Measure it at baseline and 12 weeks; either result is informative and neither is currently predictable.
4. Predict the liver enzymes are where a real effect would show first. In fatty liver, predict a modest fall in ALT and GGT (gamma-glutamyl transferase) over 12 weeks and no change in a fibrosis measure Perumal 2025. That is the indication with the best mechanism and the thinnest outcome data.
5. Predict the performance claim does not survive a blinded test. Predict no reliable change in a 1-repetition maximum or in repeated-sprint output at 2.5 g a day over 6 weeks, because the training literature is small and inconsistent and no mechanistic intermediate has been measured. A trial that measured muscle betaine content alongside performance would be the study that settles it.
What nobody has tested yet
The two surrogates have never been reconciled. One intervention lowers homocysteine Steenge 2003 and raises total cholesterol Zawieja 2021, and no trial has followed anyone to an event. Which marker wins is the single most consequential unanswered question about this compound and it would take an outcome trial to settle.
Nobody has measured muscle betaine in a supplemented athlete. Every ergogenic hypothesis for this compound requires that the muscle cell accumulates it, and no human biopsy study has shown that at supplemental doses. It is a straightforward measurement that would either ground the claim or end it.
The lipid mechanism is unexplained. Proposals include increased S-adenosylmethionine driving phosphatidylethanolamine N-methyltransferase and altering very low density lipoprotein assembly and export. Nobody has demonstrated it in a supplemented human, which means the direction and the reversibility of the lipid change are both assumptions Zawieja 2021.
And the TMAO relationship is genuinely open. Betaine is a trimethylamine-containing compound, gut bacteria can liberate trimethylamine from related substrates Rajakovich 2021, and the human data on whether betaine supplementation raises circulating TMAO are inconsistent Ilyas 2022. Given that TMAO is itself a contested marker, this is a surrogate about a surrogate.
Betaine Anhydrous (TMG) — its own safety story, not its category's
The characteristic adverse effect is social rather than medical. A fishy body odor at high doses, from trimethylamine generated when the methyl donor load exceeds hepatic flavin-containing monooxygenase 3 capacity, is well documented in the high-dose homocystinuria literature and is reversible on reducing the dose.
The lipid effect is the one that belongs on a label and is not. A moderate increase in total cholesterol at supplemental doses is a meta-analytic finding, not a case report Zawieja 2021. Anyone taking betaine for cardiovascular reasons is entitled to know that one of the standard cardiovascular markers moves in the unfavorable direction.
Gastrointestinal effects and the acid form. Nausea, diarrhea and bloating are dose-related for betaine anhydrous. Betaine hydrochloride is a different problem: it delivers acid, and it is inappropriate for anyone with reflux, peptic ulcer disease or on a proton pump inhibitor, where it directly opposes the treatment.
The stack arithmetic is the practical risk. Betaine appears in methylation formulas, in pre-workout products, and in nicotinamide riboside blends, frequently at 85 mg to 1.8 g per serving Office of Dietary Supplements. Reaching 4 to 6 g a day without noticing is easy, and that is the range where the odor and the lipid signal both live.
Who should be careful. Anyone with existing hypercholesterolemia. Anyone with renal impairment, since betainuria and altered osmolyte handling have not been studied at supplemental doses. Anyone with trimethylaminuria, for obvious reasons. And pregnancy and lactation, where supplemental doses have no safety data. Nothing here is medical advice or diagnosis, and these statements have not been evaluated by the Food and Drug Administration.
Sources read for this page
- Steenge GR, et al. Betaine supplementation lowers plasma homocysteine in healthy men and women. The Journal of Nutrition, 2003 · PMID 12730412
- Zawieja EE. Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis. J Diet Suppl 2021 · PMID 31809615
- Ilyas A. Implications of trimethylamine N-oxide (TMAO) and Betaine in Human Health: Beyond Being Osmoprotective Compounds. Front Mol Biosci 2022 · PMID 36310589
- Perumal SK. Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases. Front Nutr 2025 · PMID 40196019
- Rajakovich LJ, et al. Elucidation of an anaerobic pathway for metabolism of l-carnitine-derived gamma-butyrobetaine to trimethylamine in human gut bacteria. Proceedings of the National Academy of Sciences 2021 · PMID 34362844
- Office of Dietary Supplements, National Institutes of Health. Methyl-Guard Plus (Thorne) -- filed Supplement Facts panel, 1-3 capsules daily; per 3 capsules: riboflavin 90 mg as riboflavin 5'-phosphate sodium, vitamin B6 45 mg as pyridoxal 5'-phosphate, folate 5,000 mcg DFE as 3 mg L-5-methyltetrahydrofolate (Quatrefolic glucosamine salt), vitamin B12 3 mg as methylcobalamin, betaine anhydrous (trimethylglycine) 1.8 g; on market. NIH Dietary Supplement Label Database, DSLD ID 291788
How you would know if it worked
Two claims in one tub and only one of them has a number attached. The power and body-composition data is a rep count, not a lab result. The methylation half is measurable: betaine hands a methyl group straight to homocysteine through BHMT, the remethylation route that does not need B12 or folate to work — so if your homocysteine is raised and it comes down on 2.5 g a day, the dose is doing something systemic and you have found the place it shows. Vitamin B12 is the second marker for the uncomfortable case: betaine can pull homocysteine down while the B12 deficiency that was driving it goes unfixed, and a masked deficiency does its damage in nerves rather than in the number you were watching. Homocysteine sits on panels built for cardiovascular risk and for vegetarians rather than on anything labeled for lifters, which is a fact about lab menus rather than about you.
- Homocysteine Retest: 8–12 weeks after starting B vitamins.
- Vitamin B12 Retest: 8–12 weeks after starting supplementation.
The cheapest panel carrying Homocysteine and at least one other of these is On Metformin — the B12 Nobody Checks, at $170 — the panel is named for a different question, and the marker is the same marker. That is the whole cost of finding out.
Draw before you start, not after. A result with nothing to compare it to answers nothing.
Betaine Anhydrous (TMG) — safety & side effects
- GI upset and diarrhea at higher doses. A fishy body odor in some people, again via trimethylamine.
- Raises total cholesterol and LDL in several trials — a real and reproducible effect that is worth knowing if you are managing lipids.
- Lowers homocysteine effectively, which is its main use. No major drug interactions.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this against it with a pharmacist or doctor — pharmacists are underused and free.
- When to take it, and what to take it with
- Which form actually absorbs
- Who it's worth it for
- Best-in-class brand pick
- Coach Cam's stacks and notes
- Fasted or with food, and when in the day
- Morning or night, and why that window
- Around training, or deliberately away from it
- What it must not share a window with
Everything above is free and stays free. Skool is where it becomes a plan — Betaine Anhydrous (TMG) in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Betaine Anhydrous (TMG)
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| Homocysteine | TMG lowers it directly. This is the marker to prove it worked |
| Lipid Panel (Cholesterol, HDL, LDL, Triglycerides) | Trials show TMG can RAISE LDL — the part supplement pages leave out |
| ApoB (Apolipoprotein B) | The particle count, which matters more than the cholesterol number |
The Real Cardiovascular Risk panel covers these in one order — 9 markers, $187.60 with the discount applied.
Check results you already have → · All 103 markers A–Z
Betaine Anhydrous (TMG) — frequently asked questions
What is Betaine Anhydrous (TMG)?
A methyl donor (trimethylglycine) that acts as a cellular osmolyte for power/strength output and lowers homocysteine for cardiovascular support.
What is the suggested dose of Betaine Anhydrous (TMG)?
2.5 g daily. This is a general reference for education only — statements have not been evaluated by the FDA and this is not medical advice.
Where can I find Betaine Anhydrous (TMG) dosing and the full breakdown?
The suggested dose and the full evidence — clinical, correlative and theoretical — are on this page. What's inside Skool is when to take it, which form actually absorbs, the brand worth buying and Coach Cam's stacks.
Where can I buy Betaine Anhydrous (TMG)?
Coach Cam sources Betaine Anhydrous (TMG) from vetted, top-rated brands on iHerb — use the buy link on this page.
Betaine Anhydrous (TMG) inside a finished plan
One arm of 1 Protocol Blueprint, free to read in full.
What Betaine Anhydrous (TMG) is used for
Betaine Anhydrous (TMG) appears under 6 goals in the goal router.
Related Performance supplements
Where this goes next
Betaine Anhydrous (TMG) is the substrate arm of this plan. The page above is the free breakdown of one compound; the plan it belongs to — the dosing, the order to correct things in, the week-by-week schedule and what to retest — is a lesson inside Skool.