|
|
|
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. | |