Betaine (Trimethylglycine)

Also indexed as: TMG (Trimethylglycine)

What does it do? Betaine (trimethylglycine) functions very closely with choline, folic acid, vitamin B12, and a form of theamino acid methionine known as SAMe (S-adenosylmethionine).1 2 All of these compounds function as “methyl donors.” They carry and donate methyl molecules to facilitate necessary chemical processes. The donation of methyl groups by betaine is very important to proper liver function, cellular replication, and detoxification reactions. Betaine also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage.3

Betaine is closely related to choline. The difference is that choline (tetramethylglycine) has four methyl groups attached to it. When choline donates one of these groups to another molecule, it becomes betaine (trimethylglycine). If betaine donates one of its methyl groups, then it becomes dimethylglycine.

Betaine has been reported to play a role in reducing blood levels of homocysteine, a toxic breakdown product of amino-acid metabolism that is believed to promote atherosclerosis and osteoporosis. While the main nutrients involved in controlling homocysteine levels are folic acid, vitamin B6, and vitamin B12, betaine has been reported to be helpful in some people whose elevated homocysteine levels did not improve with these other nutrients. Betaine has also been shown to be helpful in certain rare genetic disorders involving cysteine metabolism.4 5 6 7 8 However, in normal situations or with supplementation of the other methyl donors, betaine is not likely to produce any lowering effect on homocysteine levels.9 10 Its primary use as a nutritional supplement is in supporting proper liver function.

Betaine is often referred to as a “lipotropic factor” because of its ability to help the liver process fats (lipids). In animal studies, betaine supplementation has been shown to protect against chemical damage to the liver.11 12 13 14 The first stage of liver damage that results from drinking alcohol is the accumulation of fat in the liver (alcohol-induced fatty liver disease). Betaine, because of its lipotropic effects, has been shown to produce significant improvements in this condition in several human clinical studies.15 16 Betaine has been studied in clinical trials conducted in Germany, Italy, and France in the treatment of alcohol-related liver disease.17 18 19 20 21 22 23 24 Some success was noted in these studies, but the popularity of betaine for alcohol-related liver disease has been supplanted by SAMe and milk thistle extract. However, it has recently been suggested that betaine may be a more cost-effective method as a first-step therapy for alcohol-induced fatty liver disease.25

Betaine is also showing promise as a toothpaste ingredient, as it has been shown to produce significant relief of dry mouth.26

Where is it found? Dietary sources of betaine include fish, beets, and legumes. Betaine is most widely available as betaine hydrochloride (betaine-HCl), but that form is used primarily as a source of hydrochloric acid for people with hypochlorhydria (low stomach acid). The forms used specifically to provide betaine are betaine citrate and betaine aspartate. These forms have also been used to improve liver function.

Betaine has been used in connection with the following conditions (refer to the individual health concern for complete information):

Rating Health Concerns
2Stars Alcohol-induced fatty liver
Hepatitis (nonalcoholic steatohepatitis)
Homocysteine (high)
1Star Atherosclerosis
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

Who is likely to be deficient? Betaine is not an essential nutrient, and thus no deficiency state exists.

How much is usually taken? For people with alcohol-induced fatty liver, the recommended amount for betaine citrate or betaine aspartate supplementation is 1,000 to 2,000 mg three times daily. Lower amounts are often used as nutritional support for general liver health, although use of betaine in this manner has not undergone clinical research.

Are there any side effects or interactions? No side effects with betaine at recommended levels have been noted.

At the time of writing, there were no well-known drug interactions with betaine.

References:

1. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217–46 [review].

2. Barak AJ, Tuma DJ. Betaine, metabolic by-product or vital methylating agent? Life Sci 1983;32:771–4 [review].

3. Chambers ST. Betaines: their significance for bacteria and the renal tract. Clin Sci 1995;88:25–7 [review].

4. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217–46 [review].

5. Wendel U, Bremer HJ. Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Eur J Pediatr 1984;142:147–50.

6. Wilcken DE, Wilcken B, Dudman NP, Tyrrell PA. Homocystinuria—the effects of betaine in the treatment of patients not responsive to pyridoxine. N Engl J Med 1983;309:448–53.

7. Gahl WA, Bernardini I, Chen S, et al. The effect of oral betaine on vertebral body bone density in pyridoxine-non-responsive homocystinuria. J Inherit Metab Dis 1988;11:291–8.

8. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol 1996;13:395–8 [review].

9. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217–46 [review].

10. van Guldener C, Janssen MJ, de Meer K, et al. Effect of folic acid and betaine on fasting and postmethionine-loading plasma homocysteine and methionine levels in chronic haemodialysis patients. J Intern Med 1999;245:175–83.

11. Junnila M, Barak AJ, Beckenhauer HC, Rahko T. Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats. Vet Hum Toxicol 1998;40:263–6.

12. Kim SK, Kim YC, Kim YC. Effects of singly administered betaine on hepatotoxicity of chloroform in mice. Food Chem Toxicol 1998;36:655–61.

13. Barak AJ, Beckenhauer HC, Matti J, Tuma DJ. Dietary betaine promotes generation of hepatic S-adenosylmethioine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res 1993;17:552–5.

14. Murakami T, Nagamura Y, Hirano K. The recovering effect of betaine on carbon tetrachloride-induced liver injury. J Nutr Sci Vitaminol 1998;44:249–55.

15. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol 1996;13:395–8 [review].

16. Barak AJ, Beckenhauer HC, Badakhsh S, Tuma DJ. The effect of betaine in reversing alcoholic steatosis. Alcohol Clin Exp Res 1997;21:1100–2.

17. Semmler F. Treatment of liver diseases, especially of fatty liver with betaine citrate. Ther Ggw 1977;116:2113–24 [in German].

18. Kandziora J. Therapeutic experience with the lipotropic hepatic drug Flacar in the internal medicine practice. ZFA 1976;52:1561–3 [in German].

19. Babucke G, Sarre B. Clinical experience with betain citrate. Med Klin 1973;68:1109–13 [in German].

20. Hilt G, Tuzin P. Clinical results using betaine citrate (Flacar) in fatty livers. Med Monatsschr 1973;27:322–5 [in German].

21. Hilt G, Tuzin P. Clinical results using betaine citrate (Flacar) in fatty livers. Med Monatsschr 1973;27:322–5 [in German].

22. Nicrosini F. Therapeutic activity of betaine aspartate. Clin Ter 1972;15;61:227–36 [in Italian].

23. Cairella M, Volpari B. Betaine aspartate in the therapy of liver diseases. Clin Ter 1972;60:513–34 [in Italian].

24. Cachin M, Pergola F. Betaine aspartate in the hepato-digestive domain. Sem Ther 1966;42:423–4 [in French].

25. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol 1996;13:395–8 [review].

26. Soderling E, Le Bell A, Kirstila V, Tenovuo J. Betaine-containing toothpaste relieves subjective symptoms of dry mouth. Acta Odontol Scand 1998;56:65–9.