Betaine is a metabolite of choline, and is also known as trimethylglycine or TMG. Betaine works by donating methyl  (CH3) groups. Betaine has the ability to convert homocysteine to methionine. Betaine hcl (betaine hydrochloride) is betaine with hydrochloric acid.
         
Unless your major is college was chemistry, chances are you don’t remember learning about methyl donors. A methyl donor is simply any substance that can transfer a methyl group, a carbon atom attached to three hydrogen atoms, to another substance. Many important biochemical processes rely on methylation, including the metabolism of lipids, neurotransmitters, and DNA. Scientists suspect that adequate methylation of DNA can prevent the expression of harmful genes, such as cancer genes. It’s quite likely that our body’s ability to methylate declines with age, potentially contributing to the aging process, and therefore supplementation is an interesting potential in terms of health benefits.

Source Naturals Trimethylglycine (betaine), 750 mg
TMG (trimethylglycine), also known as anhydrous betaine, is found in a variety of plant and animal sources and is used in the conversion of homocysteine to methionine. Maintaining normal homocysteine levels is important for the health of the cardiovascular system. Betaine has been shown to help protect the liver and raise S-adenosylmethionine (SAM-e) levels, in animal studies. Betaine is also mentioned as betaine hcl or betaine hydrochloride.

Amount Per Serving:
Calcium- 60 mg - 6%DV
Trimethylglycine (TMG) - Betaine- 750 mg

Suggested Use: For daily maintenance, take a third or half a Source Naturals betaine tablet at breakfast, or as recommended by your health care professional. High doses of betaine can lead to overstimulation and increased body temperature. See below for betaine hcl

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The herbs in Mind Power Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba, Ginseng, Gotu Kola, Mucuna pruriens, Reishi, and Rhodiola.  The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine (Betaine), Tyrosine, and Vinpocetine.
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Betaine Hydrochloride versus Betaine
At this time we believe betaine and TMG are the same thing. Betaine hcl appears to be different. Betaine hcl (betaine hydrochloride) is betaine with hydrochloric acid, but there could be confusion in the marketplace with some companies confusing betaine hcl for TMG. For instance, we saw a label on a bottle that said Betaine Hcl (TMG). Apparently the makers of this bottle were confusing betaine hcl with trimethylglycine.
     Betaine hydrochloride is used as a digestive aid; it is particularly helpful in persons with insufficient acid production in the stomach. It is sometimes given as a nutritional supplement, or used for the treatment of high homocysteine levels."
     Betaine hydrochloric acid is sold as a digestive aid supplement. Betaine hydrochloride is an acidic form of betaine. Betaine hydrochloride is recommended by some nutritionists as a supplemental source of hydrochloric acid for people who have a deficiency of stomach acid production. Betaine hcl is not the same as hydrochloric acid. A betaine hydrochloride supplements is used as a supplemental source of hydrochloric acid.
     It is not clear to us whether betaine hcl, in addition to providing hydrochloric acid to aid digestion, also has similar effects in the body as betaine or TMG.
     We searched Medline for studies on Betaine Hcl and its role in health and digestion, but we could not find any human studies regarding betaine hydrochloride. Therefore, at this time, we can't say what role betaine hcl has on digestion, and who is a candidate to benefit from this supplement. We also don't know whether the dosages of betaine hcl provided in many supplement products are too low, adequate, or too high, or whether they are effective. The standard dose of betain hcl appears to be 10 grains (650 mg).

Betaine Benefit
Betaine lowers homocysteine levels. Higher intakes of dietary choline and betaine are related to lower homocysteine concentrations independent of other determinants, including folate and other B vitamins. Those with a high dietary choline and betaine intake have lower concentrations of inflammatory markers such as C-reactive protein, interleukin-6, and tumor necrosis factor.
   Betaine has been found to protect liver cells from toxins.
   Betaine is a nutrient that leads to a significant biochemical and histological improvement in patients with nonalcoholic steatohepatitis (NASH).

Betaine daily intake
In US populations the average choline intake is 320 tp 400 mg per day. The average betaine intake is about 100 to 200 mg per day.

Betaine Research Update
Effects of betaine intake on plasma homocysteine concentrations and consequences for health.
Curr Drug Metab. 2005 Feb;6(1):15-22.
High plasma concentrations of homocysteine may increase risk of cardiovascular disease. Folic acid lowers plasma homocysteine by 25% maximally, because 5-methyltetrahydrofolate is a methyl donor in the remethylation of homocysteine to methionine. Betaine (trimethylglycine) is also a methyl donor in homocysteine remethylation, but effects on homocysteine have been less thoroughly investigated. Betaine in high doses (6 g/d and higher) is used as homocysteine-lowering therapy for people with hyperhomocysteinemia due to inborn errors in the homocysteine metabolism. Betaine intake from foods is estimated at 0.5-2 g/d. Betaine can also be synthesized endogenously from its precursor choline. Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine acutely reduces the increase in homocysteine after methionine loading by up to 50%, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. This implies that betaine can be an important food component that attenuates homocysteine rises after meals. If homocysteine plays a causal role in the development of cardiovascular disease, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects. However betaine and choline may adversely affect serum lipid concentrations, which can of course increase risk of cardiovascular disease. However, whether the potential beneficial health effects of betaine and choline outweigh the possible adverse effects on serum lipids is as yet unclear.

Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations.
Am J Clin Nutr. 2005 Jun;81(6):1378-82.
Remethylation of homocysteine to methionine can occur through either the folate-dependent methionine synthase pathway or the betaine-dependent betaine-homocysteine methyltransferase pathway. The relevance of betaine as a determinant of fasting total homocysteine (tHcy) is not known, nor is it known how the 2 remethylation pathways are interrelated. OBJECTIVE: The objectives of the study were to examine the relation between plasma betaine concentration and fasting plasma homocysteine concentrations and to assess the effect of folic acid supplementation on betaine concentrations in healthy subjects. DESIGN: A double-blind randomized trial of 6 incremental daily doses of folic acid (50-800 microg/d) or placebo was carried out in 308 Dutch men and postmenopausal women (aged 50-75 y). Fasted blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were measured at baseline and after 12 wk of vitamin supplementation. RESULTS: Concentrations of homocysteine were inversely related to the betaine concentration, and the association was independent of age, sex, and serum concentrations of folate, creatinine, and cobalamin. Folic acid supplementation increased betaine concentration in a dose-dependent manner (P for trend = 0.018); the maximum increase (15%) was obtained at daily doses of 400-800 microg/d. CONCLUSIONS: The plasma betaine concentration is a significant determinant of fasting homocysteine concentrations in healthy humans. Folic acid supplementation increases the betaine concentration, which indicates that the 2 remethylation pathways are interrelated.

Betaine in human nutrition
American Journal of Clinical Nutrition, Vol. 80, No. 3, 539-549, September 2004
Betaine is distributed widely in animals, plants, and microorganisms, and rich dietary sources include seafood, especially marine invertebrates; wheat germ or bran; and spinach. The principal physiologic role of betaine is as an osmolyte and methyl donor (transmethylation). As an osmolyte, betaine protects cells, proteins, and enzymes from environmental stress (eg, low water, high salinity, or extreme temperature). As a methyl donor, betaine participates in the methionine cycle—primarily in the human liver and kidneys. Inadequate dietary intake of methyl groups leads to hypomethylation in many important pathways, including 1) disturbed hepatic protein (methionine) metabolism as determined by elevated plasma homocysteine concentrations and decreased S-adenosylmethionine concentrations, and 2) inadequate hepatic fat metabolism, which leads to steatosis (fatty accumulation) and subsequent plasma dyslipidemia. This alteration in liver metabolism may contribute to various diseases, including coronary, cerebral, hepatic, and vascular diseases. Betaine has been shown to protect internal organs, improve vascular risk factors, and enhance performance. Databases of betaine content in food are being developed for correlation with population health studies. The growing body of evidence shows that betaine is an important nutrient for the prevention of chronic disease.

Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation.
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):301-7.
Betaine is a substrate in the betaine -homocysteine methyltransferase reaction, converting homocysteine to methionine. There are only sparse data on plasma betaine as a determinant of the plasma total homocysteine (tHcy) concentration. Ninety patients undergoing coronary angiography were randomized into 4 groups administered oral: (1) folic acid (0.8 mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg); (2) folic acid and vitamin B12; (3) vitamin B6 alone; or (4) placebo. Nonfasting blood samples were collected at baseline and 3, 14, and 28 days and 3, 6, and 12 months after treatment start. A 4-hour methionine-loading test (0.1 g/kg) was performed at baseline and after 3 months. At baseline, median (interquartile range) plasma betaine was 36.9 micromol/Land was increased by 15% after methionine loading. The postmethionine load (PML) increase in tHcy was inversely related to plasma betaine and even more strongly to PML betaine. After 3 months of intervention, the relation between the PML increase in tHcy and PML betaine was weakened. CONCLUSIONS: Plasma betaine is a strong determinant of the PML increase in tHcy in subjects not supplemented with B-vitamins.

Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women.
Olthof MR. J Nutr. 2003 Dec;133(12):4135-8.
High plasma homocysteine is a risk for cardiovascular disease and can be lowered through supplementation with 6 g/d of betaine. However, dietary intake of betaine is approximately 0.5-2 g/d. Therefore, we investigated whether betaine supplementation in the range of dietary intake lowers plasma homocysteine concentrations in healthy adults. Four groups of 19 healthy subjects ingested three doses of betaine or placebo daily for 6 wk. A methionine loading test was performed during run in, on d 1 of betaine supplementation, and after 2 and 6 wk of betaine supplementation. Fasting plasma homocysteine after 6-wk daily intakes of 1.5, 3 and 6 g of betaine was 12% less than in the placebo group, respectively. Furthermore, the increase in plasma homocysteine after methionine loading on the 1st d of betaine supplementation was 16% less than in the placebo group, respectively, and after 6 wk of supplementation was 23% less, respectively. Thus, doses of betaine in the range of dietary intake reduce fasting and postmethionine loading plasma homocysteine concentrations. A betaine -rich diet might therefore lower cardiovascular disease risk.

Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects.
Am J Clin Nutr. 2002 Nov;76(5):961-7.
Betaine is found in several tissues in humans. Betaine is involved in homocysteine metabolism as an alternative methyl donor and is used in the treatment of homocystinuria in humans. In pigs, betaine decreases the amount of adipose tissue. The aim of the study was to examine the effect of betaine supplementation on body weight, body composition, plasma homocysteine concentrations, blood pressure, and serum total and lipoprotein lipids. Forty-two obese, white subjects (14 men, 28 women) treated with a hypoenergetic diet were randomly assigned to a betaine-supplemented group (6 g/d) or a control group given placebo for 12 wk. The intervention period was preceded by a 4-wk run-in period with a euenergetic diet. RESULTS: Body weight, resting energy expenditure, and fat mass decreased significantly in both groups with no significant difference between the groups. Plasma homocysteine concentrations decreased in the betaine group. Diastolic blood pressure decreased without a significant difference between the groups. Serum total and LDL-cholesterol concentrations were higher in the betaine group than in the control group. CONCLUSION: A hypoenergetic diet with betaine supplementation (6 g daily for 12 wk) decreased the plasma homocysteine concentration but did not affect body composition more than a hypoenergetic diet without betaine supplementation did.

An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients.
Alzheimer Dis Assoc Disord. 2001 Jul-Sep;15(3):162-5.
We investigated the safety and tolerability of betaine in patients with Alzheimer disease (AD). Betaine is an alternative methyl donor, distinct from the folate-and cobalamin-dependent conversion pathway between homocysteine and methionine. Betaine has been used successfully to reduce homocysteine levels in homocystinuria. The rationale for betaine in AD was to decrease serum homocysteine levels and to increase brain methionone and S-adenosylmethionine, both of which might delay disease progression. Hyperhomocysteinemia is a possible risk factor for AD. Eight patients with probable mild AD (7 men; mean age, 69.6 years; mean Mini-Mental State Exam score, 23.7) received oral betaine (3 g twice daily) for 24 weeks. All patients were on donepezil 10 mg/day for at least 3 months before entry and throughout the study. One patient suffered a myocardial infarction and withdrew after 6 weeks. Another patient, who completed the trial, experienced diarrhea and prostatitis. Four of the 7 patients who completed the trial were rated on the Clinician's Global Impression of Change as worse after 24 weeks. On the cognitive portion of the AD Assessment Scale, 2 patients worsened by at least five points over 24 weeks, whereas the others had changes in scores of no more than two points either way. Six of 8 patients tolerated betaine for 24 weeks without difficulty. Several patients worsened over 24 weeks, but as a pilot study without a control group, efficacy measurements cannot be interpreted. The current study provides a basis for pursuing larger controlled trials with betaine in AD. The homocysteine to S-adenosylmethionine pathway is of interest in AD therapeutics.
     Dr. Sahelian comments: Here's an example of lack of understanding of proper nutrient dosage by researchers. They used 6 grams of betaine a day which can make any condition ,or anyone who is healthy, worse off due to overstimulation. Researchers should first take supplements themselves at different dosages before doing a study and wasting everyone's time, money, and coming up with unhelpful data.

Betaine Questions
Q. Hello - I like your site and your approach to herbs and supplements. I saw on your betaine page that you mention betaine HCl a couple of times. It is a different product from betaine anhydrous (TMG). It is used for different ailments (stomach acid-related).
   A. You ask a good question. For a long time we have been trying to find out ourselves whether betaine and TMG are the same thing or different chemically, and whether they have a similar or different effect on the human body when taken as supplements, but we can't get a good answer ourselves from the experts we ask. At this time we believe betaine and TMG are the same thing. Betaine HCL is different. Betaine HCL (betaine hydrochloride) is betaine with hydrochloric acid, but there could be confusion in the marketplace with some companies mixing betaine hcl for TMG.

Q. I came across a website that says, "Betaine HCL is necessary for adequate absorption of protein, calcium, vitamin B12 and iron. Betaine HCL is also known as hydrochloric acid and stomach acid." Is it true that betaine hcl is the same as hydrochloric acid?
   A. Hydrochloric acid is the water-based solution of hydrogen chloride (HCl) gas. It is a strong acid, the major component of gastric acid. Betaine hcl is not the same as hydrochloric acid. A betaine hydrochloride supplements is used as a supplemental source of hydrochloric acid.

Q. I was just wondering about the use of betaine for early stage autoimmune hepatitis. I have read about it on many sites and would like to know if it is all that its been made out to be.
   A. We searched Medline and did not find any studies regarding the use of betaine for autoimmune hepatitis. August 2007.