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Betaine
Overview
Dietary Sources
Constituents/Composition
Commercial Preparations
Therapeutic Uses
Dosage Ranges and Duration of Administration
Side Effects/Toxicology
Warnings/Contraindications/Precautions
Interactions
References

Overview

Betaine, also known as trimethylglycine, or oxyneurine, is involved in methylation reactions that play a critical role in the health of the cardiovascular system. Homocysteine (Hcy) has been shown to be a major independent risk factor for coronary artery disease (CAD). Betaine is formed through oxidation of choline. Once formed, it can donate a methyl group to homocysteine, thereby producing dimethylglycine and methionine. The end result is a reduction in potentially toxic homocysteine levels. It is believed that accumulation of homocysteine, over time, can damage the endothelial cells and predispose individuals to premature atherosclerosis. Mild hyperhomocysteinemia is common in patients with premature vascular disease. Mild hyperhomocysteinemia, significant enough to cause vascular problems, is also relatively common in the general population, and may account for a substantial proportion of vascular disease in the United States. Some researchers estimate that 10% of the populations's CAD risk is attributable to Hcy.

S-adenosylmethionine (SAM) is synthesized from methionine, a by-product of homocysteine methylation. Oral administration of betaine to laboratory rats has been shown to cause an increase in S-adenosylmethionine levels. This has lead researchers to conclude that betaine may be a possible alternative to expensive SAM in the treatment of liver disease and other disorders.

Folic acid, vitamin B12 and vitamin B6 are also involved in methylation reactions that convert homocysteine to methionine. The Third National Health and Nutrition Examination Survey, conducted by the U.S. Department of Health & Human Services Center for Disease Control, found that Americans are consuming inadequate amounts of these three vitamins. Furthermore, Americans typically consume inadequate amounts of fruits and vegetables, which may limit their dietary intake of betaine. These statistics indicate that Americans may significantly benefit by increasing intake of these nutrients, either by diet or supplementation. Supplementation is necessary to achieve the high levels of betaine (6 grams per day) required to treat hypercysteinemia in premature vascular disease or genetic homocystinuria.


Dietary Sources

Betaine is widely distributed in plants and animals. Broccoli, spinach, and beets are rich sources of betaine.


Constituents/Composition

Anhydrous betaine, betaine monohydrate

Note: Betaine-HCL is a stomach acidifier that is not the same as trimethylglycine (betaine).


Commercial Preparations

Betaine supplements are a byproduct of sugar beet processing.

  • Powder
  • Tablets (500, 750, 1000 mg)
  • Capsules (500, 750, 1000 mg)

Therapeutic Uses

Cardiovascular disease: Betaine (0.84 g twice daily for one week) was shown to significantly reduce homocysteine levels in patients with premature vascular disease, comparable to choline, pyridoxine, or folic acid treatment. In a similar study, 6 g of betaine per day was shown to reduce homocysteine levels in the majority of patients tested.

Liver disease: It is hypothesized that betaine may be a promising therapeutic agent in the treatment of liver disease. Oral administration of betaine has been shown to increase SAM levels sufficiently enough to protect against the early stages of alcoholic liver injury in rats.

Homocystinuria: Homocystinuria is an inherited disease caused by a deficiency in 5-10-methylenetetrahydrofolate reductase or cystathionine beta-synthase activity, or a defect in cobalamin metabolism. Betaine treatment (6 g per day) has been shown to correct metabolic abnormalities in patients with homocystinuria caused by methylenetetrahydrofolate reductase, and cystathione beta-synthase, deficiency.

In some forms of homocystinuria, betaine may be more efficacious than vitamin B6, B12, or folate. In one study, treatment with betaine monohydrate caused a significant improvement in symptoms in an adolescent with 5-10-methylenetetrahydrofolate reductase defiency, while the B vitamins caused no response. SAM levels were significantly elevated in the cerebrospinal fluid after treatment with betaine.


Dosage Ranges and Duration of Administration
  • Most experts recommend that patients with homocystinuria or premature vascular disease be kept on a methylation regimen (folic, B6, B12, and/or betaine) indefinitely.
  • General cardiovascular health: 500 to 1000 mg/day 
  • Inherited homocystinuria: 6 g/day 
  • Premature vascular disease: 6 g/day

Side Effects/Toxicology

No side effects were observed at a dosage of 6 grams betaine, daily.


Warnings/Contraindications/Precautions

None


Interactions

No clinically significant interactions between betaine and conventional medications are known to have been reported in the literature to date.


References

Barak AJ, et al. S-adenosylmethionine generation and prevention of alcoholic fatty liver by betaine. Alcohol. Nov-Dec 1994; 11(6): 501-503.

Barak AJ, et al. Betaine, ethanol, and the liver: a review. Alcohol. Jul-Aug 1996; 13(4): 395-398.

Berkow R, et al, eds. The Merck Manual of Diagnosis and Therapy. 15 th ed. Rahway: Merck Sharp & Dohme Research Laboratories; 1987: 556.

Boushey CJ, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. Oct 4, 1995; 274(13): 1049-1057.

Budavari S, O'Neil MJ, Heckelman PE, Kinneary JF, eds. The Merck Index. 12th ed. Whitehouse Station: Merck & Co., Inc.; 1996: 198.

Dudman NPB, et al. Disorderd Methionine/Homocysteine Metabolism in Premature Vascular Disease. Arterioscl and Thromb. 1993; 13(9): 1253-1260.

Franken DG, et al. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler and Thromb. March 1994;14 (3): 465-470.

Holme E, et al. Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reducatase deficiency. Arch Dis Child. 1989; 64: 1061-1064.

Kishi T, et al. Effect of betaine on S-adenosylmethionine levels in the cerebrospinal fluid in a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy. J Inherit Metab Dis. 1994; 17(5): 560-565.

Shils M, Olson J, Shike M, eds. Modern Nutrition in Health and Disease Vol 1. 8th ed. Media: Williams & Wilkins; 1994: 452.

Shils M, Olson J, Shike M, eds. Modern Nutrition in Health and Disease. 7th ed. Media: Williams & Wilkins; 1988: 1363-1365.

Stampfer MJ, Malinow MR. Can lowering homocysteine levels reduce cardiovascular disease N Engl J Med. Feb. 2, 1995; 332: 328-329.

Steinmetz CA, et al. Vegetables, fruit, and cancer prevention: A review. Am Diet Assoc. 1996: 1027-1039.

The Third National Health and Nutrition Examination Survey. Phase 1, 1989-91. The National Center for Health Statistics. Accessed at: www.cdc.gov/nchs/faq/hanesii1.htm. on November 3, 1999.

Wilcken DE, et al. Homocystinuria due to cystathione beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients. Metab. Dec 1985; 34(12): 1115-1121.


Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.