Betaine

non-nutrient/non-botanicalglycine betaine

What is it

Betaine, also called trimethylglycine (TMG), is a naturally occurring compound found in many plants and animals, particularly beets (from which it gets its name), spinach, wheat bran, and seafood. In the body, it functions as a methyl donor in one-carbon metabolism and as an osmolyte protecting cells from osmotic stress.

How it works

Betaine donates methyl groups to homocysteine, converting it to methionine via the enzyme betaine-homocysteine methyltransferase (BHMT). This pathway lowers blood homocysteine, an amino acid linked to cardiovascular disease risk when elevated. Folate, vitamin B12, and betaine all participate in homocysteine remethylation; betaine becomes more important when folate intake is inadequate. As an osmolyte, betaine helps cells maintain volume under stress, accumulating in tissues like the kidney and brain. This protective function may underlie some of its effects on cellular function and exercise performance, where it may improve muscle endurance and power output. Betaine is also a precursor to dimethylglycine (DMG), which then becomes sarcosine and finally glycine, contributing to broader methylation and one-carbon metabolism. The body produces some betaine from choline, but dietary intake supplements this internal production.

Evidence for 5 uses

AI-assisted evidence assessment — talk to your doctor before relying on any single supplement.

Homocysteine reduction

Grade A

Strong evidence

Strong evidence supports betaine for reducing elevated blood homocysteine. Effects are dose-dependent and complement folate and B12 supplementation. FDA-approved for homocystinuria (a rare genetic disorder).

Exercise performance (power/strength)

Grade B

Good evidence

Several clinical trials suggest 2,500 mg per day for 1 to 2 weeks may modestly improve muscular power, endurance, and certain measures of strength performance. Effects are subtle but reasonably consistent.

Body composition

Grade C

Moderate evidence

Some research suggests betaine may modestly support fat loss and muscle gain when combined with resistance training. Effects are small.

Liver health (NAFLD)

Grade C

Moderate evidence

Some small trials suggest betaine may improve markers of non-alcoholic fatty liver disease and modestly reduce liver fat. Evidence is moderate.

Cardiovascular outcomes

Grade D

Mixed evidence

Although betaine lowers homocysteine (a cardiovascular risk marker), large trials of homocysteine-lowering interventions have not consistently shown reduced cardiovascular events. Whether betaine specifically affects cardiovascular outcomes is unclear.

3 commercial forms

Betaine anhydrous (TMG)

Most common supplement form; well absorbed.

Standard form for general supplementation. Available as powder or capsules.

Betaine HCl (with hydrochloric acid)

Combined with HCl; used for digestive support, not methylation.

Different use case (gastric acid support), not interchangeable with betaine anhydrous for methylation.

Prescription betaine anhydrous (Cystadane)

FDA-approved for homocystinuria at very high doses.

Used in medical settings for genetic homocystinuria.

Dosage

For homocysteine reduction, doses of 1,500 to 6,000 mg per day are typical. The FDA-approved prescription betaine anhydrous for homocystinuria uses much higher doses (6 to 20 g per day). For exercise performance, 2,500 mg per day is the most studied dose. There is no established Tolerable Upper Intake Level.

When and how to take it

WHEN: Take betaine at any consistent time of day. With meals reduces GI upset. For exercise performance, taking before training (e.g., 30 to 60 minutes pre-workout) may align with timing in some studies. HOW: Take with food and water. Split larger daily doses (above 3 g) into multiple administrations. Powdered forms dissolve easily in water with a slightly salty taste.

Food sources

Food	Amount	%DV
Beets	1/2 cup cooked	—
Spinach	1 cup cooked	—
Wheat bran	1/4 cup	—
Quinoa	1 cup cooked	—
Shrimp	3 oz	—
Sweet potatoes	1 medium	—
Whole grain bread	1 slice	—
Lamb	3 oz	—

Safety

Betaine is generally well tolerated. Side effects at supplement doses are uncommon and include mild GI upset and nausea. High doses (especially the prescription doses for homocystinuria) can cause fishy body odor due to trimethylamine production. There is some evidence that supplementation may raise total cholesterol or LDL in some individuals; monitor lipids if using long-term at higher doses.

Who should be cautious

Pregnant and breastfeeding women should consult a clinician for supplement doses, though food sources are safe. People with elevated cholesterol should monitor lipids during supplementation. Those with kidney disease should consult a clinician given betaine's osmolyte role. People with trimethylaminuria should avoid high doses due to fishy odor production.

Interactions

Betaine may potentiate the homocysteine-lowering effects of folate and vitamin B12 supplements. Lipid-modifying medications should be used carefully with high-dose betaine due to the potential for cholesterol changes. People taking medications affected by liver methylation pathways should monitor for interactions.

Frequently asked questions

What's the difference between betaine and betaine HCl?⌄

Betaine anhydrous (TMG) is used for methylation and homocysteine reduction. Betaine HCl is combined with hydrochloric acid and used as a digestive aid for low stomach acid. They are not interchangeable for most purposes.

Does betaine help with workouts?⌄

Several clinical trials suggest 2,500 mg per day for 1 to 2 weeks may modestly improve muscular power and endurance. Effects are subtle but reasonably consistent. Common in pre-workout formulas.

Should I take betaine with B vitamins?⌄

Betaine, folate, and vitamin B12 all work in the same homocysteine remethylation pathway. Combining them can be more effective for homocysteine reduction than betaine alone.

Can betaine raise cholesterol?⌄

Some studies suggest betaine may raise total or LDL cholesterol in some individuals at higher doses (3 g or more daily). Monitor lipids if using long-term at higher doses.

Is betaine safe long-term?⌄

Short to medium-term safety is well established. Long-term safety at high doses has less data; monitor lipids and overall health markers if using chronically.

References

Wikidata: Betaine — Wikidata link
PubChem: Betaine (CID 247) — PubChem link

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Disclaimer: These statements have not been evaluated by the FDA. This page is educational, not a substitute for personalized medical advice. Evidence grades are AI-assisted assessments — talk to your doctor before starting any new supplement, especially if you're pregnant, breastfeeding, on medications, or managing a chronic condition.