Betaine supplement health benefit, side effects daily intake, the role of this nutrient in lowering homocysteine levels, relationship to choline, TMG
October 22 2016 by Ray Sahelian, M.D.

Betaine is a metabolite of choline, and is also known as trimethylglycine or TMG. Betaine hcl works by donating methyl  (CH3) groups. This nutrient has the ability to convert homocysteine to methionine. Betaine hydrochloride means it is in combination with hydrochloric acid. Intake from foods is estimated at 0.5 to 2 grams a day.
    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. Perhaps supplementation is an potential approach to provide anti-aging health benefits. Much more research is needed before we can come to any conclusions.

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Betaine Hydrochloride versus TMG
I am not sure but I think betaine and TMG are the same thing. Betaine hcl may be different. The HCl form has an extremely sour taste while the anhydrous has a mild, pleasant taste. Besides the taste, HCl may be used as a digestive aid for people with low stomach acid because of its high acidity while the anhydrous form does not include this benefit. 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, I saw a label on a bottle that said Betaine Hcl (TMG). Perhaps the makers of this product were confusing the two.
   Betaine hydrochloric acid is sold as a digestive aid supplement and is recommended by some nutritionists as a supplemental source of hydrochloric acid for people who have a deficiency of stomach acid production.
   It is not clear to me whether betaine hcl, in addition to providing hydrochloric acid to aid digestion, also has similar effects in the body as betaine or TMG.
   I searched Medline for studies on betaine hcl and its role in health and digestion, but we could not find any human studies. 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 betaine hcl appears to be 10 grains (650 mg).

Benefit research study, reduced inflammation
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.
The bran and particularly the aleurone fraction of wheat are high in betaine and other physiological methyl donors, which may exert beneficial physiological effects.

Betaine in human nutrition
American Journal of Clinical Nutrition, September 2004
Betaine protects cells, proteins, and enzymes from environmental stress (eg, low water, high salinity, or extreme temperature). As a methyl donor, it 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.

Br J Nutr. 2015. Postprandial plasma betaine and other methyl donor-related responses after consumption of minimally processed wheat bran or wheat aleurone, or wheat aleurone incorporated into bread. The bran and particularly the aleurone fraction of wheat are high in betaine and other physiological methyl donors, which may exert beneficial physiological effects. The consumption of minimally processed wheat bran, and particularly the aleurone fraction, yielded substantial postprandial increases in plasma betaine concentrations. Furthermore, these effects appear to be maintained when aleurone was incorporated into bread.

Alzheimer's disease, brain protection
An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients.
Alzheimer Dis Assoc Disord. 2001.
Eight patients with probable mild Alzheimer disease received oral betaine (3 grams 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.
     Dr. Sahelian comments: Here's an example of lack of understanding of proper nutrient dosage by researchers. They used 6 grams 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. I would like to see a study using 250 to 1000 mg rather than 6000 mg a day.

Iran J Basic Med Sci. 2015. Betaine protects cerebellum from oxidative stress following levodopa and benserazide administration in rats.

Depression, mood
Int J Gen Med. 2015. Preliminary results of a randomized controlled trial carried out with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression. S-adenosyl-L-methionine (SAMe), a safe, endogenous, pleiotropic methyl donor well known for its antidepressant role, has been assumed to have a possible role in increasing plasma levels of compounds known to be able to raise cardiovascular risk. Although the issue is still being debated, betaine (trimethylglycine), a specific methyl donor involved in the homocysteine circuit, may be able to reduce such a risk and/or, by determining a sparing effect on endogenous SAMe, may be able to improve the clinical efficiency of SAMe itself. Indeed, preliminary results have shown clinical improvement determined by an add-on therapy with betaine administered along with SAMe, versus SAMe alone, to patients affected by mild/moderate depression. This small, open-label, randomized, observational study enrolled 64 individuals with a diagnosis of mild depression according to the Zung Self-Rating Depression Scale. After randomization, they were treated with either Laroxyl (amitriptyline, 75 mg/day) or DDM Metile (enteric-coated SAMe, 500 mg/day, plus betaine, 250 mg/day) for 12 months. After 3 months, both treatments showed a small and not statistically significant improvement. After 6 and 12 months, both treated groups demonstrated a more noticeable improved response, although the group treated with SAMe plus betaine showed better results in terms of score, number of individuals in remission, and side effects. Compliance was overlapping in both treatments. The association of SAMe plus betaine seems to be a safe and effective tool to counteract mild depression and also when used as monotherapy in subjects with a recent diagnosis.

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.
    We searched Medline and did not find any studies regarding its use for autoimmune hepatitis.

Homocysteine reduction
Higher intakes of dietary choline and betaine are related to lower homocysteine concentrations independent of other determinants, including folate and other B vitamins.

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.
Forty-two obese, white subjects (14 men, 28 women) treated with a hypoenergetic diet were randomly assigned to a betaine supplemented group 6 grams per day or a control group given placebo for 12 wk. A low energy diet with betaine supplementation decreased the plasma homocysteine concentration but did not affect body composition more than a hypoenergetic diet without betaine supplementation did.

Effects of betaine intake on plasma homocysteine concentrations and consequences for health.
Current Drug Metabolism. 2005.
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. Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently. Moreover, it acutely reduces the increase in homocysteine after methionine loading, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. 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.

Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects.
American J Clinical Nutrition. 2008.
In a randomized crossover study, 8 healthy men consumed a betaine supplement (approximately 500 mg), high-betaine meal (approximately 517 mg), choline supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and -choline meal (approximately 517 mg betaine, approximately 622 mg choline). Dietary and supplementary betaine raised plasma concentrations relative to control under standard conditions. This was not associated with raised plasma dimethylglycine concentration, and no significant betaine appeared in the urine. A small increase in dimethylglycine excretion was observed when either was supplied. Small decreases in plasma homocysteine 6 h after ingestion under standard conditions were detected after a high-betaine meal and after a high-betaine and high-choline meal. Dietary betaine and choline and betaine supplementation attenuated the increase in plasma homocysteine at both 4 and 6 h after a methionine load.

Liver health
Betaine has been found to protect liver cells from toxins. It is a nutrient that leads to a significant biochemical and histological improvement in patients with nonalcoholic steatohepatitis (NASH).

J Nutritional Biochem. December 2013. Betaine attenuates hepatic steatosis by reducing methylation of the MTTP promoter and elevating genomic methylation in mice fed a high-fat diet.

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.

Food sources
Betaine is distributed widely in animals, plants, and microorganisms, and rich dietary sources include seafood, especially marine invertebrates; wheat germ or bran; and spinach.

Interactions with other dietary supplements
Just received my stomach enzymes, betaine hydrochloride, probiotics and glutathione that was shipped to Cambodia by Physician Formula website. Is there any potential conflict between them, Just wondered if I needed to take them at different times (apart from what the directions already advise).
  I am not aware of such conflicts but such studies are not available to know for sure.


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Doctor's Best, Betaine HCl, Pepsin & Gentian Bitters, 360 Capsules

Source Naturals - buy Betaine HCl 650 mg each pill, 180 Tablets

According to the manufacturer: In the stomach, hydrochloric acid converts pepsinogen to pepsin, an enzyme that breaks down protein. Pepsin breaks down proteins into smaller, more easily absorbed substances. As people age, hydrochloric acid secretion may be reduced, which can result in decreased levels of pepsin. Without proper pepsin levels, the body has a difficult time digesting food. Betaine hydrochloride is used as a supplemental source of hydrochloric acid, which can be utilized by the stomach to produce pepsin. The combination with pepsin provide an excellent stomach tonic.

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Supplement Facts
Serving Size: 1 Tablet
  Amount Per Serving % Daily Value
Betaine Hydrochloride 650 mg
Pepsin 1:3000 165 mg
†Daily Value not established.

Supplement Facts: Betaine Hydrochloride 650 mg
Pepsin 1: 3000 - 165 mg

Source Naturals Trimethylglycine 750 mg
TMG, 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.

Amount Per Serving:
Calcium 60 mg
Trimethylglycine 750 mg