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.

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

Anhydrous betaine, betaine monohydrate

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

Betaine supplements are a byproduct of sugar beet processing.

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

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.

• 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

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

None

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

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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. 12^th ed. Whitehouse Station: Merck & Co., Inc.; 1996: 198.

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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. 8^th ed. Media: Williams & Wilkins; 1994: 452.

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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.

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