Trimethylglycine (TMG) / Betain
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Overview
Betaine, also called betaine anhydrous or trimethylglycine (TMG), is a substance that' s made in the body, where it' s involved in liver function, cellular reproduction, and helping make carnitine. It also helps the body metabolize homocysteine, an amino acid. Betaine is approved by the US Food and Drug Administration (FDA) to treat a genetic condition where too much homocysteine builds up in the body.

Betaine has also been proposed as a way to lower homocysteine levels in people who don' t have the genetic disease. That' s because higher levels of homocysteine are associated with heart disease.


What is Trimethylglycine (TMG) ?
Trimethylglycine (TMG), also called betaine, is a substance manufactured by the body. It helps break down another naturally occurring substance called homocysteine.

In certain rare genetic conditions, the body cannot dispose of homocysteine, resulting in its accumulation to extremely high levels. This, in turn, leads to accelerated cardiovascular disease and other problems. Oral TMG is an FDA-approved treatment for this condition. It "methylates" homocysteine, removing it from circulation.

Meaningful, but not altogether consistent, evidence suggests that the relatively slight elevation of homocysteine that can occur in healthy people is also harmful. On this basis, it has been suggested that TMG might reduce heart disease risk in healthy people as well.


How it is made?
Trimethylglycine is a nutrient produced in the body that aids several chemical processes, such as decreasing homocysteine levels.

Where it is found?
TMG is not required in the diet because the body can manufacture it from other nutrients. Grains, nuts, seeds, and meats contain small amounts of TMG. However, most TMG in food is destroyed during cooking or processing, so food isn't a reliable way to get a therapeutic dosage.

After TMG has done its work on homocysteine, it is turned into another substance, dimethylglycine (DMG).


Benefits / uses
Heart Disease
Studies suggest that betaine, along with vitamins B6 and B12 and folic acid, helps reduce higher levels of homocysteine. Having high levels of homocysteine is related to a higher risk of heart disease and stroke. However, scientists don't yet know whether homocysteine itself is harmful, or whether it is just an indicator of increased risk for heart disease. Some studies show that high levels of homocysteine may encourage atherosclerosis (hardening of the arteries).

Betaine supplements may increase cholesterol levels, which could work against any treatment for heart disease. If you are at risk for heart disease, your doctor may test levels of homocysteine in your blood.


Homocystinuria
Some people have a genetic condition called homocystinuria, in which homocysteine levels build up in the body. They are at much higher risk of developing heart disease and osteoporosis as early as their 20s. Betaine supplements are used to lower levels of homocysteine in people with this inherited health condition.

Liver Disease
Studies in rats suggest that betaine may help protect against harmful fatty deposits in the liver. These deposits can be caused by alcohol abuse, obesity, diabetes, and other causes. A few studies on people have been positive, but the studies were not all of good quality. More research is needed.

Dry Mouth
One study found that a toothpaste containing betaine helped relieve dry mouth.Best Form For Human Consumption
Betaine supplements are manufactured as a byproduct of sugar beet processing. They are available in powder, tablet, and capsule forms.

Doses
Pediatric: Betaine is not recommended for children unless it is prescribed by your child's health care provider to treat homocystinuria, a genetic condition.

Adult: Recommended doses of betaine vary depending on the condition being treated. Ask your health care provider to help you determine the right dose for you.

Betaine is usually taken with folic acid, vitamin B6, and vitamin B12.

Possible Side effects / Precautions / Possible Interactions:
Most side effects from betaine are mild and include diarrhea, stomach upset, and nausea. Betaine can raise total cholesterol levels.

People who are overweight, have heart disease, or are at risk for heart disease should not take betaine without talking to their health care provider.
People with kidney disease should not take betaine.

Possible Interactions: In people with kidney disease, betaine may interfere with drugs taken to lower cholesterol levels in the blood.


Research studies / References
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Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217-46 [review].
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Barak AJ, Tuma DJ. Betaine, metabolic by-product or vital methylating agent? Life Sci 1983;32:771-4 [review].
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Chambers ST. Betaines: their significance for bacteria and the renal tract. Clin Sci 1995;88:25-7 [review].
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Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 2001;96:2711–17.
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Wilcken DEL, 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.
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Jancin B. Amino acid defect causes 20% of atherosclerosis in CHD. Fam Pract News 1994(Oct 15):7.
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Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr 2005;82:111–7.
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Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 2003;133:4135–8.
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Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877–81.
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Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiobascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077–80.
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Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204–10.
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Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196–9 [editorial/review].
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Stolzen berg-Solomon RZ, Miller ER III, Maguire MG, et al. Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am J Clin Nutr 1999;69:467–75.
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Selhub J, Jacques PF, Wilson PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693–8.
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Ubbink JB, Hayward WJ, van der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927–33.
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Manson JB, Miller JW. The effects of vitamin B12, B6, and folate on blood homocysteine levels. Ann NY Acad Sci 1992;669:197–204 [review].
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Franken DG, Boers GHJ, Blom HJ, et al. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler Thromb 1994;14:465–70.
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Ubbink JB, Vermaak WJH, van der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927–33.
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Ubbink JB, van der Merwe A, Vermaak WJH, Delport R. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig 1993;71:993–8.