Trimethylglycine (TMG), also called betaine, is a substance manufactured by the body. It helps break down another naturally occurring substance called homocysteine.
In certain rare genetic conditions, the body cannot dispose of homocysteine, resulting in its accumulation to extremely high levels. This, in turn, leads to accelerated cardiovascular disease and other problems. Oral TMG is an FDA-approved treatment for this condition. It "methylates" homocysteine, removing it from circulation.
Meaningful, but not altogether consistent, evidence suggests that the relatively slight elevation of homocysteine that can occur in healthy people is also harmful.6 On this basis, it has been suggested that TMG might reduce heart disease risk in healthy people as well. However, this has not been proven, and TMG has shown the potential for having adverse effects on cholesterol profile, which could counter any possible benefit via homocysteine.
Note: TMG is similar chemically to betaine hydrochloride, but it has entirely different actions.
TMG is not required in the diet because the body can manufacture it from other nutrients. Grains, nuts, seeds, and meats contain small amounts of TMG. However, most TMG in food is destroyed during cooking or processing, so food isn't a reliable way to get a therapeutic dosage.
After TMG has done its work on homocysteine, it is turned into another substance, dimethylglycine (DMG). Some manufacturers will tell you that DMG is identical to TMG, but this isn't true. DMG is not a methylating agent, so it can't have any effect on homocysteine. (See also Therapeutic Uses below.)
Optimal therapeutic dosages of TMG are not known. Common recommendations range from 375 to 3,000 mg daily.
There is no doubt that TMG greatly reduces homocysteine levels and improves health among people with the rare disease cystathionine beta-synthase deficiency (as well as related conditions).1 TMG also appears to reduce relatively mild homocysteine elevations in people without genetic defects.10-11 However, as noted above, TMG also seems to worsen cholesterol profile, and this may counteract any possible benefits.12 For this reason, if you have elevated levels of homocysteine, it may make more sense to reduce it by taking supplemental folate, vitamin B6, and vitamin B12; these supplements are known to reduce homocysteine levels, and, unlike TMG, they provide nutritional benefit as well.
TMG may help protect the liver against the effects of alcohol, perhaps by stimulating the formation of SAMe.2,3,4,7 In addition, it may be helpful for non-alcoholic forms of fatty liver (non-alcoholic steatosis) as well.8,9
TMG has also been suggested as a less expensive substitute for SAMe in other condition for which SAMe is used (such as osteoarthritis and depression). However, there is no evidence to show that it is effective.
A substance labeled pangamic acid or vitamin B 15 has been extensively used as a performance enhancer by Russian athletes and has also become popular among American athletes. However, it is not clear there really is any such substance; or, to state it another way, various substances have at various times been given that name. Most recently, the term has been associated with a mixture of calcium gluconate and DMG; one small study failed to find this form of pangamic acid effective for enhancing sports performance.5
The only known safety issue with TMG is regarding cholesterol profile, as already mentioned. People with high or borderline-high cholesterol should use TMG only with caution.
Maximum safe dosages for young children, pregnant or nursing mothers, or those with severe liver or kidney disease have not been established.
1. Wilcken DEL, Dudman NPB, Tyrrell PA. Homocystinuria due to cystathionine beta-synthase deficiency—the effects of betaine treatment in pyridoxine-responsive patients. Metabolism. 1985;34:1115-1121.
2. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol and the liver: a review. Alcohol. 1996;13:395-398.
3. Barak AJ, Beckenhauer HC, Junnila M, et al. Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res. 1993;17:552-555.
4. Murakami T, Nagamura Y, Hirano K. The recovering effect of betaine on carbon tetrachloride-induced liver injury. J Nutr Sci Vitaminol. 1998;44:249-255.
5. Gray ME, Titlow LW. The effect of pangamic acid on maximal treadmill performance. Med Sci Sports Exerc. 1982;14:424-427.
6. Mangoni AA, Jackson SH. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med. 2002;112:556-565.
7. Kanbak G, Inal M, Baycu C. Ethanol-induced hepatotoxicity and protective effect of betaine. Cell Biochem Funct. 2001;19:281-285.
8. Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001;96:2711-2717.
9. Angulo P, Lindor KD. Treatment of nonalcoholic fatty liver: present and emerging therapies. Semin Liver Dis. 2001;21:81-188.
10. Schwab U, Torronen A, Meririnne E et al. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr. 2005;136:34-38.
11. Olthof MR, Van Vliet T, Boelsma E et al. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr. 2003;133:4135-4138.
12. Olthof MR, Vliet TV, Verhoef P et al. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med. 2005;2:e135.
Last reviewed September 2014 by EBSCO CAM Review Board
Last Updated: 9/18/2014