TMG (Trimethylglycine)

What it is

Betaine is a derivative of the amino acid glycine with three attached methyl groups, hence the name trimethylglycine. Your body makes it itself from choline and takes it in with food. Particularly high amounts are found in wheat bran with 1,339 mg and wheat germ with 1,241 mg per 100 g, as well as in spinach, shrimp and wheat bread.

As a supplement, anhydrous betaine is usually sold. The same substance has been approved in the EU since 2007 as the medicine Cystadane, for the adjunctive treatment of homocystinuria, a rare inherited metabolic disorder with extremely high homocysteine.

How it is supposed to work

Betaine donates one of its methyl groups to homocysteine via the enzyme betaine-homocysteine methyltransferase. This produces methionine, and betaine becomes dimethylglycine. This is a second recycling pathway alongside the one via folate and vitamin B12; the Cochrane analyses on B vitamins concern only that other pathway.

In humans, the chain is well traced: on betaine, betaine, dimethylglycine and methionine rise in the blood, and homocysteine falls. Further promises build on this. Because methyl groups are needed everywhere in metabolism, TMG is supposed to influence the liver, performance and aging. These steps are much less well supported than the first.

In the longevity scene, TMG is considered an obligatory companion to NMN or NR, because the breakdown of nicotinamide consumes methyl groups. The reasoning is biochemically understandable. We have not found a human study showing that NMN or NR relevantly deplete the methyl group pool or that the combination with TMG brings any benefit.

Betaine also arrives in appreciable amounts through the diet. Whole grains and spinach are the most important sources. Anyone who eats a lot of wheat bran or wholegrain bread already takes in betaine, though far less than the amounts used in the studies.

What the studies show

Homocysteine in five trials

A meta-analysis pooled 5 randomized trials from 2002 to 2010. All participants were healthy and took at least 4 g of betaine daily for 6 to 24 weeks. Homocysteine fell by an average of 1.23 µmol/l, clearly statistically significant.

Strength and jumping

In 17 studies with 317 mostly male participants aged 15 to 60, betaine slightly improved maximal strength, especially in leg exercises. Upper-body strength, cycling sprint and strength endurance remained unchanged. Individual studies found no difference from placebo, for example 6 weeks of CrossFit with 29 trainees.

Weight loss with betaine

Forty-two people with overweight followed a calorie-reduced diet for 12 weeks and took 6 g of betaine or placebo. Both groups lost weight and fat; betaine added nothing. Homocysteine fell, but total and LDL cholesterol were higher in the betaine group.

Betaine versus creatine

In a double-blind study in untrained people, participants received 2 g of betaine, creatine, both or placebo for 10 days. Creatine filled the energy stores in muscle and increased strength and power. Betaine alone did not, and on top of creatine it brought no further advantage. The strength finding of the meta-analysis therefore rests on longer intake and trained groups.

Fatty liver: twelve months

Fifty-five patients with biopsy-confirmed steatohepatitis received 20 g of betaine daily or placebo; 34 had a second biopsy after 12 months. Compared with placebo, neither fat accumulation nor inflammatory activity nor fibrosis improved. The authors see at most protection against further deterioration.

Where the data stop

Homocysteine is a lab value, not a disease. How much a reduction brings is shown by a Cochrane review on B vitamins: in 15 randomized trials with 71,422 participants, despite lower homocysteine there were no fewer heart attacks and no lower mortality, only a small advantage for strokes. For betaine itself, studies with such hard endpoints are missing entirely.

In sport, the strength advantage is small and statistically marginal; the confidence interval begins just above zero. For body composition, a separate meta-analysis shows no effect, neither on weight nor on fat or muscle mass. The hope for liver protection has not been confirmed by the largest randomized trial to date. Inflammatory markers barely moved in a meta-analysis of 6 studies. And the rationale as an NMN partner is so far a consideration, not a study result. Finally, most studies ran for 6 to 24 weeks, the longest for 12 months in patients. We have not found data on healthy people taking betaine for years.

Status, approval and legal

In Germany, betaine is freely available as a food supplement and at the same time approved as the medicine Cystadane for homocystinuria. The EU permits the health claim that betaine contributes to normal homocysteine metabolism, but only for products with at least 500 mg per serving and with the information that the effect occurs at 1.5 g daily. In addition, it must be stated that more than 4 g daily may significantly increase cholesterol levels. The meta-analyses on homocysteine reduction used at least 4 g per day. These are statements about studies and the legal situation, not an intake recommendation. Betaine is not on the WADA Prohibited List for 2026.

Safety

Betaine is well studied and was used in one study over 12 months at 20 g daily. The most important side effect concerns blood lipids: from 4 g per day, total cholesterol rose by 0.34 mmol/l in a meta-analysis of 6 studies, and a second meta-analysis found an increase of 10.26 mg/dl in LDL. Below 4 g, the homocysteine reduction was preserved without blood lipids rising. Anyone with elevated cholesterol or a high cardiovascular risk should weigh this with medical supervision. In patients with homocystinuria, betaine can raise methionine sharply; the EMA warns of possible cerebral edema and requires monitoring of methionine. We have not found an official maximum amount for food supplements.

Sources

• McRae, J Chiropr Med 2013 – meta-analysis on betaine and homocysteine
• Ashtary-Larky et al., Crit Rev Food Sci Nutr 2022 – betaine and cardiovascular markers
• Zawieja et al., J Diet Suppl 2021 – betaine and cholesterol
• Zawieja et al., J Sports Sci 2024 – meta-analysis on performance
• Ashtary-Larky et al., Br J Nutr 2022 – betaine and body composition
• Abdelmalek et al., Hepatology 2009 – betaine in steatohepatitis
• Martí-Carvajal et al., Cochrane 2017 – homocysteine lowering and cardiovascular events
• Regulation (EU) No 432/2012 – authorized health claims
• EMA – Cystadane (betaine anhydrous), EPAR
• Zeisel et al., J Nutr 2003 – betaine content of foods