Trimethylglycine as a therapeutic supplement
Trimethylglycine (TMG), also known as betaine, is a naturally occurring substance in the human body that plays a role in breaking down homocysteine, an amino acid linked to cardiovascular issues when elevated. TMG is primarily used as a therapeutic supplement for individuals with high homocysteine levels, such as those with the genetic disorder homocystinuria, where it helps detoxify excess homocysteine. The substance has also been explored for additional uses, including potential benefits for alcoholic liver disease and nonalcoholic fatty liver, as well as its role as a possible performance enhancer in sports.
While some studies suggest TMG may lower homocysteine levels and thus reduce heart disease risk, the evidence is mixed, and concerns have been raised about its effect on cholesterol levels, which might negate any cardiovascular benefits. TMG is synthesized by the body and can be found in foods like broccoli, spinach, and grains; however, cooking often diminishes its content. Common dosages for TMG range from 375 to 3,000 milligrams daily, though specific therapeutic dosages remain unclear, and safety profiles for certain populations, such as pregnant women, are not well established.
In summary, while TMG shows promise in certain therapeutic contexts, further research is needed to clarify its efficacy and safety, particularly regarding cardiovascular health and performance enhancement.
Trimethylglycine as a therapeutic supplement
DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
- PRINCIPAL PROPOSED USE: High homocysteine levels
- OTHER PROPOSED USES: Alcoholic liver disease, enhancing sports performance, nonalcoholic steatosis, substitute for S-adenosylmethionine (SAMe)
Overview
Trimethylglycine (TMG), also called betaine or betaine anhydrous, is a substance manufactured by the body. It helps break down another naturally occurring substance called homocysteine.
In certain rare genetic conditions, such as homocystinuria, the body cannot dispose of homocysteine, which results in its accumulation at extremely high levels. This, in turn, leads to accelerated cardiovascular disease and other problems. An oral TMG supplement called Cystadane is approved by the US Food and Drug Administration (FDA) 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. On this basis, it has been suggested that TMG may reduce heart disease risk in healthy people. 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 from removing homocysteine. TMG is chemically similar to betaine hydrochloride, but it has entirely different actions.
Requirements and Sources
TMG is not required in the diet because the body can manufacture it from other nutrients. Common food sources include broccoli, spinach, beets, shellfish, and grains. Nuts, seeds, and meats also contain small amounts of TMG. However, most TMG in food is destroyed during cooking or processing, so food is not 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 maintain that DMG is identical to TMG, but this is not true. DMG is not a methylating agent, so it cannot have any effect on homocysteine.
Therapeutic Dosages
The optimal therapeutic dosages of TMG are unknown. Common recommendations range from 375 to 3,000 milligrams daily. Maximum safe dosages for children, pregnant or nursing mothers, and those with severe liver or kidney disease have not been established.
Therapeutic Uses
Research indicates that TMG greatly reduces homocysteine levels and improves health among people with the rare disease cystathionine beta-synthase deficiency and related conditions. TMG also appears to reduce relatively mild homocysteine elevations in people without genetic abnormalities. However, TMG also worsens the cholesterol profile, which may counteract any possible benefits. For this reason, it may make more sense for people with elevated levels of homocysteine to reduce it by taking supplemental folate, vitamin B6, and vitamin B12; these supplements are known to reduce homocysteine levels, and unlike TMG, they also provide nutritional benefit.
TMG may help protect the liver against the effects of alcohol by stimulating the formation of S-adenosylmethionine (SAMe). In addition, it may be helpful for nonalcoholic forms of fatty liver (nonalcoholic steatosis). Promising studies have been performed in rats, but further human trials are needed. TMG has also been suggested as a less expensive substitute for SAMe in other conditions 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 B15 has been extensively used as a performance enhancer by Russian athletes and has become popular among American athletes. However, it is unclear if there really is any such substance because various substances have been given that name at various times. The term has also 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. Various studies on athletes in several sports found conflicting information regarding TMG and performance enhancement in the 2010s and 2020s. In these studies, the dosages used and the chosen measures of gauging improvement varied significantly between trials. Standardized research is needed to find reliable results.
Some research indicates that taking 4 milligrams of TMG daily may prevent heart disease by helping the body change the amino acid homocysteine into methionine. While this research is promising, other studies have found that TMG increases the risk of heart disease in certain groups of people.
Safety Issues
The only known safety issue with TMG is regarding cholesterol profile. People with high or borderline high cholesterol should use TMG only with caution. Individuals who are obese may experience a rise in cholesterol with this supplement.
Bibliography
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