Comprehensive Guide to Trimethylglycine (Betaine)

Trimethylglycine (Betaine)Dr. James Meschino DC, MS, ND
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General Features
Trimethylglycine functions in the body as a methyl donor (as do folic acid, vitamin B12, choline and S-adenosyl-methionine).1,2 As a methyl donor Trimethylglycine is particularly involved in liver function, including detoxification reactions. As well, it plays a role in carnitine synthesis, which also occurs in the liver.3
Trimethylglycine is closely related to choline (tetramethylglycine) in that as choline donates one of its four methyl groups to another molecule, it becomes Trimethylglycine (Betaine). If Trimethylglycine donates one of its methyl groups, then it becomes dimethylglycine.2
In animals Trimethylglycine has been shown to protect against chemical damage to the liver.4-7 In alcohol-induced liver damage, the first stage is accumulation of fat in the liver (fatty liver degeneration). Trimethylglycine has been shown to be of benefit in these cases due to its lipotropic properties (donating a methyl group to aid in the transport of fat out of the liver) in both animal and human studies.8,9 Betaine as a treatment for alcohol-related liver damage is very popular in Germany, Italy and France, as is the use of milk thistle and S-adenosylmethionine.8-16
Betaine should not be confused with Betaine hydrochloride, which is primarily a supplement to provide hydrochloric acid to patients with low stomach acidity, aiding digestion.
Betaine or Trimethylglycine supplementation is usually in the form of betaine citrate or betaine aspartate
Clinical Application and Mechanism of Action
1. Alcohol-Induced Fatty Liver Disease
The first step in liver damage that results from drinking alcohol is the accumulation of fat in the liver. Due to its lipotropic effects, betaine has been shown to produce significant improvement in this condition in several human studies.10-16
2. Hyperhomocysteinemia
Trimethylglycine may aid folic acid and vitamin B12 in helping to reduce elevated levels of homocysteine (1,000 mg, two or three times daily). Betaine has been reported to be helpful in some patients whose homocysteine levels did not improve with supplementation with folic acid, vitamin B6 and vitamin B12.17 High levels of homocysteine increases risk of heart disease, and therefore, betaine supplementation should be considered as an adjunctive treatment in patients whose elevated homocysteine levels do not respond adequately to supplementation with B-vitamins alone (see folic acid in this document for a detailed discussion regarding hyperhomocysteinemia).
Dosage and Standardized Grade
1. Liver Disease: 1,000 mg to 2,000 mg, three times per day.10,11,12,13,14,15,16
2. Hyperhomocysteinemia (unresponsive to folic acid, vitamin B6 and vitamin B12): 1,000 mg, two to three times per day.17
3. General Wellness Support: 500-1,000 mg per day.
Adverse Side Effects and Toxicity
No side effects have been reported at recommended levels of intake. Betaine is a very non-toxic compound

Drug-Nutrient Interactions
A Betaine-containing substance in the urine (glycine-betaine) has been shown to reduce the effectiveness of antibiotic therapy for urinary tract infections (UTI), and compounds similar to betaine are known to enhance the growth of bacteria that cause UTIs. Thus, betaine supplementation should not be used during active urinary tract infects or in concert with antibiotics intended to treat UTIs
References
1. Selhub J. Homocysteine metabolism. Ann Rev Nutr 1999;19:217-46.
2. Barak AJ, Tuma DJ. Betaine, metabolic by-product or vital methylating agent? Life Sci 1983;32:771-4.
3. Chambers ST. Betaines: their significance for bacteria and the renal tract. Clin Sci 1995;88(1):25-7.
4. Junnila M, Barak AJ, Beckenhauer HC, Rahko T. Betaine reduces hepatic lipidosis induced by carbon tetracholoride in Sprague-Dawley rats. Vet Hum Toxicol 1998;40:263-6.
5. Kim SK, Kim YC, Kim YC. Effects of singly administered betaine on hepatotoxicity of chloroform in mice. Food Chem Toxicol 1998;36:655-61.
6. Barak AJ, Beckenhauer HC, Matti J, Tuma DJ. Dietary betaine promotes generation of hepatic S-adenosylmethione and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res 1993;17:552-5.
7. 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.
8. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol 1996;13:395-8[review].
9. Barak AJ, Beckenhauer HC, Badakhsh S, Tuma DJ. The effect of betaine in reversing alcoholic steatosis. Alcohol Clin Exp Res 1997; 21:1100-2.
10. Semmler F. Treatment of liver diseases, especially of fatty liver with betaine citrate. Ther Ggw 1977;116:2113-24 [in German].
11. Kandziora J. Therapeutic experience with the lipotropic hepatic drug Flacar in the internal medicine practice. AFA 1976;5f2:1561-3 [in German].
12. Babucke G, Sarre B. Clinical experience with betain citrate. Med Klin 1973;68:1109-13 [in German].
13. Hilt G, Tuzin P. Clinical results using betaine citrate (Flacar) in fatty livers. Med Monatsschr 1973;27(7):322-5 [in German].
14. Nicrosini F. Therapeutic activity of betaine aspartate. Clin Ter 1972;15;61:227-36 [in Italian].
15. Cairella M, Volpari B. Betaine aspartate in the therapy of liver diseases. Clin Ter 1972;60:513-34 [in Italian].
16. Cachin M, Pergola F. Betaine aspartate in the hepato-digestive domain. Sem Ther 1972;60:513-34 [in Italian].
17. Healthnotes, Inc. 2001. www.healthnotes.com : Betaine.
18. Peddie BA, Chambers ST. Effects of betaines and urine on the antibacterial activity of aminoglycosides. J Antimicrob Chemother 1993;31:481-8.
19. Chambers ST, Peddie BA, Randall K, Lever M. Inhibitors of bacterial growth in urine: what is the role of betaines? Int J Antimicrob Agents 1999;11:293-6 [review].