Betaine Anhydrous (TMG) Supplements Uses, Benefits, Dosages & Side Effects

Betaine Anhydrous (BA) is a compound that is used as dietary supplement for its osmolyte (cellular fluid-balancing) and methyl donor activities.

It has various purported health benefits and is known to be safe for most people to supplement with.

BA is approved by the FDA as a treatment for high levels in the urine of the chemical homocysteine in people with certain inherited disorders.

BA is also commonly used as a supplement for improving exercise performance, cardiovascular health, liver health, and weight loss.

Betaine is an amino acid that is often called trimethylglycine or just TMG. These terms are used interchangeably.

Do not confuse betaine anhydrous with betaine hydrochloride. They are similar but different compounds that have different effects in the body and are used for different purposes.

This article will review how betaine anhydrous works in the body, how it is used for people with certain metabolic conditions, dosages that have been studied in human trials, and its safety profile.

Trimethylglycine

Amino Acid

Muscle Growth

Athletics

Inflamm-ation

How It Works:

• Breaks down homocysteine
• Protects cells from damage
• May promote endurance with creatine

Dosage:

3 grams, twice per day

Safety:

Rated Likely Safe

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What Is Betaine Anhydrous?

The Natural Medicines Comprehensive Database (NMCD) reports that betaine anhydrous is a chemical that occurs naturally in the body from the oxidation of choline in the liver and kidneys. [1]

It is also naturally occurring in some food sources including quinoa, spinach, wheat bran, and beets. BA supplements are typically sourced from sugar beets.

Trimethylglycine (betaine) is also found naturally in many species of microbes, marine creatures, and plants.

Betaine anhydrous is a water-soluble colorless crystalline alkaloid with the chemical formula C5H11NO2.

Alkaloids are nitrogen-rich organic compounds that have been studied for physiological effects in humans. Some alkaloids like morphine (C17H19NO3), quinine (C20H24N2O2), and atropine (C17H23NO3) have medicinal effects. Natural betaine is one of the medicinal alkaloids.

Uses for Betaine Anhydrous

Betaine anhydrous has been approved by the FDA to treat various genetic disorders that cause homocystinuria, a condition that causes the body to be unable to metabolize some amino acids.

People with homocystinuria cannot properly metabolize methionine, which results in high levels of homocysteine in the blood and urine. Elevated homocysteine levels are associated with cardiovascular disease, skeletal abnormalities, osteoporosis, and optic lens issues.

Research shows that betaine anhydrous can lower homocysteine levels which can support health and may have other benefits as well.

The NMCD reports that betaine anhydrous is also used orally (by mouth) for:

• 5,10-methylenetetrahydrofolate reductase deficiency
• Alcoholic and nonalcoholic steatohepatitis (fatty liver disease)
• CHF (congestive heart failure)
• Cobalamin cofactor metabolism defect
• Cystathionine beta-synthase deficiency
• Depression
• Fibrocystic breast disease
• GERD (gastroesophageal reflux disease)
• Hyperhomocysteinemia (high blood-homocysteine levels)

Trimethylglycine anhydrous is also used for supporting fat loss, athletic performance, and the immune system. It has also been used for osteoporosis (brittle and fragile bones) and cancer.

The FDA has not approved betaine anhydrous’ use as a drug to prevent or treat osteoporosis or cancer.

Betaine anhydrous is included in some mouthwash and toothpaste products and used to improve subjective symptoms of dry mouth and mouth ulcers.

How Betaine Anhydrous Works in the Body

While betaine anhydrous occurs naturally in various common foods, it can also be synthesized inside the human body. It is made when certain choline-based compounds are oxidized in the kidneys and liver.

Betaine helps to keep cells protected during stressful events via its actions as an osmolyte and methyl donor. It also has roles in numerous other body processes and functions.

Trimethylglycine is an osmolyte, meaning it increases cellular water retention. It transports water through the cell membrane and helps maintain proper cellular hydration.

As an osmolyte, BA helps protect cells, proteins, and enzymes from various environmental stresses including dehydration, high salt levels, and high temperature.

Betaine anhydrous has similar function to the amino acid Creatine. Higher levels of betaine in the cells helps to preserve their structure and add resistance to oxidative stress. Creatine is important for muscular contractions and recycling ATP (adenosine triphosphate).

Betaine anhydrous is also a methyl donor, meaning it is able to “donate” methyl groups to other compounds. A methyl group is a carbon atom with 3 hydrogen atoms attached to it (CH3). Methyl groups occur naturally in many organic compounds.

Methylation is a common process that involves the addition of a methyl group on a substrate. Methylation is involved in the regulation of gene expression, protein function, and RNA processing.

Dr. Ray Sahelian states, “Many important biochemical processes rely on methylation, including the metabolism of lipids and DNA. Scientists suspect that adequate methylation of DNA can prevent the expression of harmful genes, such as cancer genes.” [2]

Methionine is an essential sulfur-containing amino acid that is present in most proteins.Homocysteine is an amino acid that occurs as an intermediate in the metabolism of cysteine and methionine.

Betaine anhydrous donates methyl groups during creatine synthesis and during the metabolism of homocysteine into methionine.

High blood homocysteine is associated with increased risk for heart disease because it can cause inflammation in blood vessels.

BA is known to reduce homocysteine levels in people with homocystinuria due to genetic conditions. Some research suggests that betaine anhydrous is able to reduce blood homocysteine levels in people without these conditions as well.

TMG is also popular among athletes like bodybuilders because it has been shown in some human trials to improve some physical performance markers. [1]

Taking a trimethylglycine anhydrous supplement may support muscle strength, size, and stamina.

Betaine Anhydrous Health Benefits

Cystadane is a prescription medication that contains betaine anhydrous as its active ingredient. Cystadane is an FDA approved drug used for reducing homocysteine levels by 20-30% in patients with several types of homocystinuria including those caused by:

• 5,10-methylenetetrahydrofolate reductase deficiency
• Cobalamin cofactor metabolism defect
• Cystathione beta-synthase deficiency

At this time use of BA as a drug is only approved for homocystinuria. Other uses of betaine anhydrous have not been approved by the FDA to prevent or treat any conditions.

There is a lot of promising data from animal studies and preliminary clinical research in various areas. However, more scientific research is still needed to determine the therapeutic efficacy of anhydrous betaine for these uses.

Either alone or used with herbs or other substances, betaine has been studied for possible effects in halitosis (bad breath), dry mouth, birth control, dry mouth, hepatic inflammation, acid reflux disease, physical performance enhancement, skin damage, brain development disorders, and mood disorders.

According to NMCD TMG anhydrous supplements may benefit high homocysteine levels, non-alcoholic fatty liver disease, digestion, body composition, dry mouth symptoms, low-density lipoprotein cholesterol levels, and muscle performance.

Betaine Anhydrous and Exercise Performance

Betaine anhydrous is proposed to improve athletic performance because of its capacity as a methyl donor during creatine synthesis.

The supplement is also hypothesized to improve exercise tolerance by enhancing oxygen extraction or consumption in muscle tissue.

Betaine is a popular ingredient in various pre-workout formulas because of research showing positive effects on factors associated with resistance training and body composition.

Some research suggests that betaine anhydrous can increase muscle power, endurance, fat loss, and muscle growth.

One study looked at BA effects on resistance training. Participants were men with strength training experience given 2.5 g betaine anhydrous daily for six weeks or a placebo. The betaine group had improved body composition, arm size, bench press work capacity, and power (but not strength) compared to the placebo group.

In another study resistance trained men were given either 2.5 g betaine in Gatorade as a treatment, or Gatorade alone as a placebo and tested for muscular power and force. It was seen that men in the treatment group had a moderate increase over their pretreatment levels in total repetitions and volume load in bench press exercises compared to the placebo group.

There is some evidence that taking betaine does not improve strength or power performance in untrained men. This suggests that the effects of betaine anhydrous supplementation are more evident in trained men engaging in resistance training.

Effects in untrained men and are limited, and more research is required to determine betaine’s therapeutic efficacy for this purpose.

Betaine Anhydrous and Cardiovascular Health

Elevated homocysteine levels are linked not only to increased risk for cardiovascular disease but also to increased risks for osteoporosis, optic lens dislocation, and skeletal abnormalities.

Betaine anhydrous is known to lower levels of homocysteine by donating methyl groups in the Methionine/Homocysteine Cycle in people with homocystinuria caused by genetic metabolism conditions.

When betaine donates a methyl group to homocysteine, it changes into methionine.

In people with these genetic conditions, betaine has been seen in research to significantly reduce elevated homocysteine levels. Supplementation has been seen to reduce high plasma homocysteine levels within one week of use, and a steady state is reached within a month.

In people without a genetic condition who have normal or mildly elevated homocysteine levels, most clinical research has shown that betaine supplementation can modestly decrease homocysteine levels (between 5.5-15% reduction).

However, it is not clear at this time if any reduction in homocysteine levels in people with normal or slightly elevated levels results in any decreased risk of cardiovascular disease. More research is still needed in this area to determine betaine anhydrous’ therapeutic efficacy for this purpose.

Betaine anhydrous has not been approved by the FDA as a drug to prevent or treat any conditions.

Betaine Anhydrous and Hepatic (Liver) Function

Betaine anhydrous acts as a methyl donor in the production of both methionine and a related chemical called SAMe (S-adenosylmethionine).

Because of this, researchers believe that BA might be important for fat metabolism inside the liver.

The NMCD states, “S-adenosyl-methionine is involved in the methylation of phosphatidylethanolamine to form phosphatidylcholine, which enhances secretion of very low-density lipoprotein (VLDL) to transport fat out of the liver.” [3]

Trimethylglycine anhydrous is said to act like a lipotropic substance, meaning it can normalize lipid (fat) metabolism.

BA may support normal fat metabolism in the liver; excessive accumulation of fat in the liver is linked to a number of health issues.

Betaine might be helpful for alcoholic and nonalcoholic steatohepatitis (fatty liver disease), and other conditions marked by hepatic fat accumulation.

According to Natural Medicines Comprehensive Database, preliminary animal research has shown that betaine supplementation may prevent and reverse alcoholic and niacin induced steatohepatitis. Research in humans is lacking though, and clinical studies are necessary to determine betaine’s therapeutic efficacy for this use.

Betaine Anhydrous and Weight Loss

Because of its possible effects on liver fat accumulation in humans, and the fact that it has been shown to reduce fat tissue in pigs, researchers are interested in betaine as a weight loss agent.

There has been one study done examining this effect in human patients. This study did not show notable weight loss effects.

The study gave 42 obese patients a low calorie diet and either 6g/day betaine anhydrous or a placebo. At the end of 12 weeks it was seen that betaine supplementation decreased homocysteine levels in the treatment group, but did not affect body composition more than the placebo group.

Therefore, more research is still needed to determine if betaine anhydrous has effects on weight loss in humans.

Betaine Anhydrous and Cancer

Low levels of both folate (vitamin B9) and methionine are associated with increased risk of colorectal adenoma (benign colon or rectum tumor that is a precursor to colon cancer).

Both of these dietary nutrients are known to be involved in methylation pathways. Because of this, it has been hypothesized that betaine supplementation may help to reduce the risk for colon cancer.

A combination of choline and betaine supplementation has been studied in relation to colorectal adenoma. In some research betaine intake has been seen to have a weak inverse relationship with adenoma risk. However other studies have seen no statistically significant association between betaine intake and colorectal cancer risk.

Choline and betaine supplementation has also been studied in relation to breast and lung cancers in some studies. Results from a few case-control studies have shown that consumption of choline and betaine are inversely associated with the risk of breast and lung cancers.

However, more research is still needed in this area to fully understand the effects of betaine on different cancers and to determine what therapeutic efficacy betaine may have for cancer prevention.

Betaine Anhydrous Foods and Supplements

Betaine anhydrous can be found in a number of food sources. Some of the sources with the highest levels arequinoa, spinach, sugar beets, wheat germ, liver, eggs, and seafood.

Cooking foods, especially boiling them, significantly decreases their betaine content.

If you would want to increase your betaine levels you can increase levels of BA foods in your diet. Dietary sources can be used as a tool to have optimal levels.

If you do choose to use a betaine anhydrous supplement in addition to or instead of increasing your dietary intake of BA, then it is important to do your research and choose a supplement from a respected vendor.

NMCD reports that there are more than twelve-hundred (1200) different dietary supplements available that contain betaine.

Some dietary supplements are of lower quality. They may contain fillers, contaminants, heavy metals, or various toxins. If possible, look for organic and non-GMO betaine anhydrous supplements from trusted suppliers.

It is important to buy from suppliers whose manufacturers have GMP certification and who participate in third party testing.

Betaine comes in a few different formats, including bulk powder and premade capsules or tablets. Tablets typically come in 500 mg or 1000 mg formats. The powder can be easily dissolved in warm water and has a naturally tart taste.

The anhydrous in betaine anhydrous means that BA contains no water. [3] Like other anhydrous substances, BA can absorb atmospheric moisture, and therefore supplements, especially powder supplements, must be stored properly in an airtight container.

Betaine Anhydrous Dosages

NMCD reports the following adult oral betaine anhydrous dosages have been used in research studies: [1]

• 10 grams BA twice daily for 12 months for NASH (nonalcoholic steatohepatitis);
• 125 mg BA plus 250 mg SAMe, twice daily, for up to 12 months for depression;
• 2.5 grams BA daily for 2 weeks for improving exercise performance;
• 3-6 grams BA daily for 1-12 weeks for hyperhomocysteinemia;
• 3-20 grams BA twice daily for treating homocystinuria;

Legion Athletics states, “To boost exercise performance and muscle gain and fat loss, 1000 to 6000 mg per day was used in the studies that reported positive results.” [4]

Manufacturer recommendations for a popular powder supplement suggest taking 750 mg (1/4 tsp) to 1500 mg (1/2 tsp) daily, or as directed by your physician.

Talk with your doctor to help determine the best dosage for your needs.

Betaine Anhydrous Safety and Side Effects

The Natural Medicines Comprehensive Database has rated Betaine anhydrous as Likely Safe when used orally and appropriately.

Betaine anhydrous side effects are rare. The supplement is typically well tolerated by the majority of users.

In rare cases this supplement has reportedly caused diarrhea, nausea, and allergic skin reactions.

In higher doses, betaine anhydrous might cause a fish-like body odor or breath. Anecdotally taking 200 mg riboflavin (vitamin B2) daily is said to reduce this odor.

There is insufficient evidence about betaine’s safety during pregnancy or breastfeeding and use is typically to be avoided. If your doctor has prescribed BA for a medical condition then speak with them first about safety during pregnancy and breastfeeding.

Before taking any new supplements it is always recommended that you speak with your doctor to help determine if that supplement is right for your needs.

Taking a B-complex multivitamin might interfere with betaine activity in the body.

Be aware that BA may influence methionine metabolism in the body due to its role in reducing homocysteine levels.

There are no known interactions with any drugs, herbs, or supplements. It is still recommended to speak with your doctor before using betaine anhydrous if you are taking any prescription drugs, over-the-counter medications, or any herbs and supplements.

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