What is TMG? Mechanism, benefits, dosage, and research

Short answer: TMG (trimethylglycine), also called betaine or betaine anhydrous, is a natural methyl donor found in foods such as beets, spinach and whole grains. Via the enzyme BHMT it helps convert homocysteine into methionine. In human studies, betaine supplements of 1.5 to 6 g per day lowered fasting plasma homocysteine by about 12–20% versus placebo (Olthof et al., 2003), and a meta-analysis found an average reduction of 1.23 µmol/L at 4 g per day or more (McRae, 2013). In the EU, betaine may carry the health claim that it contributes to normal homocysteine metabolism, based on an intake of 1.5 g per day. TMG is not the same as betaine HCl, which is used as a digestive acid supplement.

Effects on concrete health outcomes beyond homocysteine are less well established and differ per application.

TMG in brief

Question	Short answer
What is TMG?	Trimethylglycine, also known as betaine.
How does TMG work?	TMG can donate methyl groups and is involved, among other things, in the conversion of homocysteine to methionine via the BHMT pathway.
What is methylation?	A collective term for biochemical reactions in which a methyl group is transferred.
Does TMG occur in food?	Yes. Betaine is found in beets, spinach, quinoa, and various grain products, among others.
What is the correct dosage?	That depends on the goal, product, and context. Research dosages and supplement dosages vary.
Is TMG the same as betaine?	Trimethylglycine is the compound also called betaine. Do not confuse this with betaine HCl, which has a different use.

Diagram: how TMG donates methyl groups and converts homocysteine to methionine via BHMT

TMG can donate a methyl group within the BHMT pathway, where homocysteine is converted to methionine.

What is TMG (trimethylglycine)?

TMG stands for trimethylglycine. The substance is usually called betaine in scientific literature.

The name trimethylglycine refers to the chemical structure: a glycine compound with three methyl groups. TMG can function as a methyl group donor in the body.

A well-known function of betaine is its involvement in the conversion of homocysteine to methionine. Additionally, betaine functions as an osmolyte: a substance that can help cells regulate their fluid and osmotic balance.

TMG occurs naturally in the body and in various foods. Additionally, trimethylglycine is available as a dietary supplement.

1. TMG donates a methyl group

TMG contains three methyl groups and can function as a methyl group donor within certain biochemical reactions.

2. BHMT uses TMG

The enzyme betaine-homocysteine methyltransferase (BHMT) uses a methyl group from betaine in the conversion of homocysteine to methionine.

3. Methionine back in the cycle

Methionine can then be used in the formation of S-adenosylmethionine (SAMe), an important methyl group donor in numerous reactions in the body.

How does TMG work in the body?

One of the best-known mechanisms of TMG occurs via the BHMT pathway. BHMT stands for betaine-homocysteine methyltransferase.

In this reaction, betaine transfers a methyl group to homocysteine. This allows homocysteine to be converted to methionine.

Simplified, this pathway looks like this:

TMG (betaine) + homocysteine
↓ BHMT
methionine

Methionine then becomes part of a larger network of reactions in which SAMe, among others, is formed and used.

This mechanism is biochemically well-described. However, this does not automatically mean that extra TMG leads to a noticeable health benefit for every healthy person.

How does TMG work? Infographic with 3 steps: methyl donation, homocysteine conversion and energy

What is methylation and what role does TMG play?

Methylation is the transfer of a methyl group from one compound to another. Such reactions take place constantly and are involved in diverse biological processes.

TMG plays a specific role in this as a methyl group donor within the BHMT pathway. This is not the only pathway by which homocysteine can be converted to methionine.

TMG versus folate and vitamin B12

Folate (vitamin B9) and vitamin B12 are also involved in the remethylation of homocysteine, but via a different biochemical pathway.

Simplified:

TMG/betaine → BHMT pathway
folate + vitamin B12 → methionine synthase pathway

The pathways are thus part of the same broader one-carbon metabolism but use different enzymes and methyl sources.

The fact that TMG works via a different pathway than folate and vitamin B12 does not automatically mean that everyone needs these substances combined as a supplement. The need depends, among other things, on diet, health situation, and individual context.

What does scientific research say about TMG?

Trimethylglycine is usually referred to as betaine in scientific research. Research focuses, among other things, on the function of betaine as a methyl group donor and osmolyte and on the relationship with homocysteine metabolism.

Studies on supplementation show that betaine can influence plasma homocysteine. The magnitude and practical significance of the effect depend, among other things, on dosage, study design, and the population studied. For example, 1.5, 3 and 6 g of betaine per day for six weeks lowered fasting homocysteine by 12%, 15% and 20% compared with placebo (Olthof et al., 2003). A meta-analysis of five randomised trials (at least 4 g per day for 6 to 24 weeks) found an average reduction of 1.23 µmol/L (McRae, 2013). Another meta-analysis found that betaine supplementation can moderately increase total cholesterol (Zawieja et al., 2021).

Research area	What do we know?	Important nuance
Methyl group donation	Betaine functions as a methyl group donor within the BHMT reaction.	An established mechanism is not the same as a proven benefit of extra supplementation.
Homocysteine	Betaine can contribute to the conversion of homocysteine to methionine via BHMT.	Effects depend on dosage, baseline value, and population, among other factors.
Osmotic balance	Betaine also functions as an osmolyte and is involved in the osmotic balance of cells.	This biological mechanism should not automatically be translated into general health claims.

Those looking for research on TMG will therefore often find more relevant scientific publications with the search term betaine than with TMG alone.

Also view our more extensive overview of scientific research on TMG.

What are the potential benefits of TMG?

The most clearly described biological functions of TMG/betaine are its role as a methyl group donor and as an osmolyte.

In research on TMG, the following topics are studied, among others:

homocysteine metabolism;
methionine metabolism;
methylation processes;
osmotic balance of cells;
various metabolic outcomes.

It is important to distinguish between a biochemical effect and a noticeable health benefit. The fact that TMG is involved in the conversion of homocysteine, for example, does not automatically mean that everyone benefits from extra TMG supplementation.

Claims about more energy, focus, vitality, recovery, or anti-aging go beyond what can be concluded from the methylation mechanism alone.

TMG dosage: how much per day?

There is no single universal TMG dosage that applies to everyone and every purpose. Furthermore, the amount of betaine used in scientific research may differ from the amount in a regular dietary supplement.

When determining intake, the following are relevant, among others:

the amount of TMG per capsule or measuring scoop;
the total daily intake;
the purpose of use;
other supplements you use;
medication and personal health situation.

In human studies, betaine doses typically ranged from 1.5 to 6 g per day (Olthof et al., 2003; McRae, 2013). The EU health claim on homocysteine metabolism is based on an intake of 1.5 g per day. A research dosage should not automatically be interpreted as a recommended daily dosage.

For a more extensive overview, view our guide on TMG dosage and use.

What is the best time to take TMG?

There is no generally proven time at which TMG works best for everyone.

In practice, TMG supplements are often taken at a fixed time of day, for example, with a meal. The exact use depends on the product and the dosage.

Therefore, initially follow the instructions for use of the supplement you are using.

Are you using medication, are you pregnant, breastfeeding, or do you have a medical condition? Then consult a doctor or pharmacist before using TMG as a supplement.

TMG side effects

As with other supplements, undesirable effects can occur when using TMG. Which complaints occur and at what amount depends, among other things, on the dosage and the person.

Therefore, do not automatically use high research dosages and follow the instructions of the product you are using.

Do you want to know more specifically about this? View our page on TMG side effects and safety.

For whom is extra caution wise?

Consult a doctor, pharmacist, or other qualified healthcare professional before use if you:

use medication;
are pregnant or breastfeeding;
have a medical condition;
are under treatment;
combine multiple supplements in higher dosages;
doubt whether TMG is suitable in your situation.

A dietary supplement is not a replacement for medical diagnosis or treatment.

TMG in food

Betaine occurs naturally in various foods. Sources include:

beets;
spinach;
quinoa;
wheat and other grain products.

The amount of betaine varies per food, product, and preparation method.

A supplement offers a standardized amount of TMG, but that does not automatically mean that supplementation is necessary when you consume betaine through food.

TMG versus betaine: is there a difference?

TMG (trimethylglycine) and betaine refer to the same compound. In scientific publications, the name betaine is usually used, while dietary supplements often state TMG or trimethylglycine.

Confusion can arise with betaine HCl. That is betaine combined with hydrochloric acid and is offered for a different purpose. TMG/betaine and betaine HCl should therefore not simply be considered the same supplement.

Important concepts around TMG and methylation

TMG
Trimethylglycine, also known as betaine.

Betaine
The name often used in scientific literature for trimethylglycine.

Methyl group
A chemical group consisting of one carbon atom and three hydrogen atoms.

Methylation
A biochemical process in which a methyl group is transferred.

BHMT
Betaine-homocysteine methyltransferase; the enzyme that uses a methyl group from betaine in the conversion of homocysteine to methionine.

Homocysteine
A sulfur-containing amino acid that is part of methionine metabolism.

Methionine
An essential amino acid that plays a role in the methionine cycle, among other things.

SAMe
S-adenosylmethionine; an important methyl group donor in the body.

Osmolyte
A substance that can be involved in the regulation of the osmotic balance of cells.

Folate
Vitamin B9; involved in an alternative pathway for remethylation of homocysteine.

Vitamin B12
A vitamin that, together with folate, is involved in the methionine synthase pathway.

Frequently asked questions about TMG

What is TMG?

TMG stands for trimethylglycine and is also called betaine. It is a natural compound that can function as a methyl group donor, among other things.

Is TMG the same as betaine?

Yes. Trimethylglycine is the compound also called betaine. TMG is often used on supplements, while scientific publications usually speak of betaine. Betaine HCl is a different product and must be distinguished from this.

How does TMG work?

An important pathway runs via the enzyme BHMT. In this process, betaine donates a methyl group, allowing homocysteine to be converted to methionine.

What does TMG do with homocysteine?

TMG is involved in the remethylation of homocysteine to methionine via the BHMT pathway. In studies, betaine supplements of 1.5 to 6 g per day lowered fasting plasma homocysteine by about 12–20% compared with placebo, and a meta-analysis found an average reduction of 1.23 µmol/L at 4 g per day or more.

What does TMG have to do with methylation?

TMG can donate a methyl group within the BHMT pathway. As such, TMG is part of the broader one-carbon and methionine metabolism.

Why is TMG combined with vitamin B12 and folate?

TMG and folate/vitamin B12 are involved in different pathways by which homocysteine can be converted to methionine. However, that does not mean that everyone needs these supplements combined.

What is a good TMG dosage?

There is no universal dosage that applies to everyone and every purpose. In human studies, betaine doses typically ranged from 1.5 to 6 g per day; the EU health claim on homocysteine metabolism is based on 1.5 g per day. View our extensive explanation of TMG dosage.

When is the best time to take TMG?

There is no generally proven optimal time. Follow the instructions for use of the supplement and, for daily use, preferably choose a practical, consistent moment.

Does TMG have side effects?

Undesirable effects can occur with supplement use, and the reaction can depend on the person and dosage. Read our separate explanation of TMG side effects and safety.

What contains TMG?

Betaine occurs naturally in various foods, including beets, spinach, quinoa, and grain products.

Where can you buy TMG?

TMG is available as a dietary supplement. At Every Day Better, you will find TMG capsules 500 mg. Always check the composition, dosage, and instructions for use before use.

Scientific sources on TMG

In scientific literature, trimethylglycine is usually referred to as betaine. The sources below provide background on the biochemical functions and researched applications of betaine.

Beneficial Effects of Betaine: A Comprehensive Review.
A scientific overview of betaine, focusing on its function as a methyl group donor, methionine metabolism, and other researched biological effects.
View the publication.
Betaine in Inflammation: Mechanistic Aspects and Applications.
A review discussing the physiological functions of betaine as an osmolyte and methyl group donor, among other things.
View the publication.
NIH Office of Dietary Supplements – Choline: Health Professional Fact Sheet.
Background information on choline, betaine, and the relationship with one-carbon metabolism and methylation.
View the NIH factsheet.
Olthof et al. (2003). Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr.
View on PubMed.
McRae (2013). Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. J Chiropr Med.
View on PubMed.
Atkinson et al. (2009). Dietary and supplementary betaine: effects on betaine and homocysteine concentrations in males. Nutr Metab Cardiovasc Dis.
View on PubMed.
Zawieja et al. (2021). Betaine supplementation moderately increases total cholesterol levels: a systematic review and meta-analysis. J Diet Suppl.
View on PubMed.
Ashtary-Larky et al. (2022). Effects of betaine supplementation on cardiovascular markers: a systematic review and meta-analysis. Crit Rev Food Sci Nutr.
View on PubMed.
Commission Regulation (EU) No 432/2012 – list of permitted health claims (including betaine and normal homocysteine metabolism).
View on EUR-Lex.

Please note: a review describes existing research and possible mechanisms, but does not in itself constitute proof that TMG supplementation provides a clinically relevant benefit for every healthy person.