Trimethylglycine (TMG), or betaine, lowers homocysteine levels, reduces heart disease risk, and improves exercise performance. However, it can also increase cholesterol levels. Read more to learn about all of its health benefits and possible side effects.

What is TMG?

Trimethylglycine (TMG) is a compound found in beetroot and other plants and animal foods. It was originally known as betaine because it was first discovered in sugar beets. However, TMG is one of the many betaines that have since been identified [1].

The main functions of TMG are to protect cells from stress and act as a source of methyl groups [1].

People can consume TMG normally in their diet or as a supplement. TMG is also produced by the body from choline [2].

TMG has many health benefits – it protects the liver, heart, and kidneys, and can enhance physical performance [1].

TMG is also known as betaine, glycine betaine, lycine, and oxyneurine.

TMG supplements are commonly referred to as betaine anhydrous.

Betaine hydrochloride (Betaine HCl) is made out of betaine (TMG) and hydrochloric acid. It is a supplement that increases stomach acid [3].

Mechanisms of Action

Donates Methyl Groups

In the body, TMG can donate one of its methyl groups to homocysteine. Methyl groups are three hydrogen atoms bonded to carbon. This turns homocysteine back into methionine and prevents homocysteine levels from getting too high [4].

High homocysteine levels in the blood is a risk factor for heart disease. Both TMG supplementation and dietary intake lower homocysteine levels, which can potentially protect the heart [4, 5].

Additionally, by donating a methyl group, it helps produce S-adenosylmethionine and can help protect against oxidative stress with its antioxidant effects [6, 7].

Is an Osmoprotectant

TMG is an osmolyte/osmoprotectant, which means that it keeps cells hydrated and increases stress resilience. It can stabilize proteins and membranes when environmental conditions are bad, such as drought, low temperatures, and high salt levels [8].

TMG helps cells adapt to stress. It protects against premature programmed cell death (apoptosis) [8, 1].

When TMG protects cell hydration, it can increase energy production. The protection improves glucose breakdown and lactate productivity, which results in greater energy production during exercise [9].

Increases Nitric Oxide

TMG supplementation can substantially increase blood levels of nitric oxide. Nitric oxide widens blood vessels and increases muscle blood flow during short-term exercise [9].

An increase in muscle blood flow can improve exercise performance by increasing nutrient delivery and waste excretion [9].

Health Benefits

1) Improves Exercise Performance

TMG is a common ingredient in workout supplements.

In a meta-analysis (of 7 RCTs), two studies reported increases in power and strength [10].

In two studies (DB-RCT) of active men, TMG supplementation increased total repetitions during exercise. Besides increasing strength, TMG can improve endurance and reduce fatigue [9].

TMG supplementation to improve physique is most effective when accompanied by exercise [11].

2) Improves Body Composition

In a study (DB-RCT) of 23 experienced strength-trained men, long-term TMG supplementation during an exercising training program (6 weeks) improved body composition. The men had significant increases in lean mass and decreases in body fat [11].

In a study (RCT) of 12 trained men, TMG supplementation alongside exercise sessions decreased cortisol levels. It also increased blood growth hormone, which helps with muscle protein synthesis. This caused their lean mass to increase [12, 11].

3) Protects the Heart

A high blood homocysteine level is a risk factor for heart disease. TMG supplementation lowers homocysteine levels in the blood, which can potentially protect the heart [4, 5].

In a review of 74 clinical trials, high choline and TMG intake were associated with lower blood inflammatory markers [13].

Because choline is a precursor to TMG, increased choline intake can lead to higher TMG blood levels. TMG then lowers homocysteine, which improves the mitochondrial membrane and protects cells from oxidative stress and inflammation [13].

Although TMG intake is not associated with heart attack incidence, long-term consumption can prevent heart disease-related deaths [13].

Additionally, TMG treatment protected against blood clots in mice by preventing clots in blood vessels and the circulatory system, it can prevent heart disease [14].

4) Helps Treat and Prevent Diabetes

TMG blood levels are associated with insulin sensitivity. Individuals with lower TMG levels are more likely to have insulin resistance [15].

In a study (RCT) of 3,000 individuals, those with lower TMG levels were more likely to have diabetes. After 2 years of lifestyle changes, higher TMG levels were associated with lower diabetes rates [16].

In mice, TMG supplementation:

  • Improves glucose tolerance [17]
  • Maintains glucose balance [18]
  • Improves insulin sensitivity [15]

5) Has Antioxidant Effects

When TMG donates a methyl group, it helps produce S-adenosylmethionine, an antioxidant [6, 7].

TMG also increases glutathione, another powerful antioxidant [7].

In rats, TMG pre-treatment reduced oxidative damage due to stress [19].

6) May Help with Cancer

In a meta-analysis of 14 trials, high TMG and choline consumption contributed to cancer prevention and significantly lowered the risk of developing cancer [20].

In a study of 1,500 breast cancer patients, a higher dietary intake of TMG was associated with fewer deaths from cancer. However, it did not affect the risk of developing breast cancer [21].

7) Helps Treat Depression

TMG increases S-adenosyl-methionine (SAMe), which helps produce serotonin, dopamine, and norepinephrine and can help treat depression [22].

TMG administration in depressed rats changed their behavior. It helped increase serotonin and norepinephrine levels in the rats’ brains, having an antidepressant effect [23].

In 45 depression patients, the treatment with SAMe and TMG for 90 days improved symptoms such as anxiety and feelings of helplessness and worthlessness. The combination also helped people who responded poorly to conventional antidepressants [22].

8) Improves Brain Function

In a study (DB-RCT) of 193 seniors, cobalamin supplementation increased TMG blood levels. This increase in TMG was associated with better reaction time, memory, and brain function [24].

Additionally, the participants with the largest increase in TMG levels had the greatest memory improvement [24].

9) May Treat Autism Symptoms

Children with Autism Spectrum Disorder have abnormal methionine cycles. The methionine cycle helps with blood vessel formation and other biological pathways. Abnormal methionine cycles can cause cognitive disorders [25].

Autistic children do not have enough levels of the by-products that are needed for the cycle and are also vulnerable to oxidative stress [25].

In autistic children, TMG and choline deficiency contribute to low methionine and SAMe levels, which can cause abnormal gene expression [26].

Although scientists are unsure if TMG supplementation affects SAMe levels in autistic children, studies of healthy participants showed that TMG can increase SAMe [26].

Oral supplementation with folinic acid and TMG normalized the methionine cycle in autistic children. TMG also increased antioxidant levels, which protects against oxidative damage [25].

10) May Protect the Liver

TMG can help treat both non-alcoholic and alcoholic liver injuries [18].

In the liver, TMG helps process methionine to produce S-adenosylmethionine, which helps lower inflammation. It can also help decrease liver cell death [18, 27].

TMG can help treat common characteristics of liver diseases. In mice, it:

  • Decreases insulin resistance in the liver [18]
  • Reduces fat buildup in the liver [18]
  • Increases activation of liver AMPK to help with glucose and fat (lipid) balance [18]
  • Prevents alcohol-induced inflammation and stress [18]
  • Protects the liver from toxins (like chloroform, methotrexate, LPS, etc) [1]
  • Protects liver cells from bile-induced apoptosis [1]

However, human trials have not supported this research.

In a study (RCT) of 55 non-alcoholic fatty liver disease patients, TMG did not reduce fat buildup in their livers. Even though the dosage was very high (at 20 g daily), it could only stop fat buildup from worsening and could not treat the disease [28].

TMG Increases Hepatitis C Treatment Response

The addition of SAMe and TMG during hepatitis C treatment can enhance drug effectiveness, especially in nonresponders. Thus, by treating hepatitis C infection, TMG can prevent chronic liver disease [29].

In a study of 29 nonresponders, more than half the patients responded to the addition of SAMe and TMG to their hepatitis C treatment [30].

Additionally, SAMe and TMG increased the antiviral efficiency of hepatitis drugs in liver cells. They stopped the virus from multiplying, better than the drug alone [29].

11) May Help Protect the Kidneys

In the kidneys, TMG’s main role is making sure the cells stay hydrated. During cellular stress, it preserves cell volume without changing cell functions [31].

In mice, TMG supplementation lowered high uric acid levels, protecting the kidney from injury [32].

Additionally, TMG treatment protected rat kidneys from CCL4-induced toxicity. CCL4 can cause kidney cell death and cirrhosis (liver disease) [33].

12) Relieves Skin Irritation

In 21 healthy subjects, TMG relieved the skin irritating effects caused by detergents and decreased allergic responses [34].

TMG’s osmolyte properties increased skin hydration and improved skin barrier. Also, by acting as a methyl donor, it protected the cells from detergent attacks [34].

13) Protects the Hair from Damage

Shampoos and other hair products can harm cells through osmotic stress. Since TMG is an osmolyte, it can keep hair cells hydrated and protect against environmental damage [35].

Shampoo with TMG protected hair protein structure [35].

14) Relieves Dry Mouth

TMG’s osmolyte properties can protect the mouth from chemicals and other mouth irritants [36, 37].

Toothpaste that contains TMG reduced dry mouth symptoms in a study (DB-RCT) of 45 individuals. The patients reported less lip dryness and difficulty eating [38].

15) May Help Protect Bone

In human bone cells, TMG treatment activated pathways that increased osteoblast cell formation. Osteoblasts are cells that increase new bone formation [39].

Additionally, TMG helped maintain bone health and bone tissue reshaping and replacement after injuries [39].

Side Effects/Negatives

1) Common Side Effects of TMG Supplements

Common side effects include [40]:

  • Agitation
  • Irritability
  • Sleep Disturbances
  • Diarrhea
  • Vomiting
  • Nausea
  • Hair Loss

2) Increases Cholesterol Levels

TMG increases cholesterol levels. This potentially cancels out TMG’s benefits on heart health [41].

In a review of 4 studies (RCTs), TMG supplementation increased LDL (bad) cholesterol in healthy individuals. These effects were present after 2 weeks of 6 gram/day of TMG supplementation [41].

Although not statistically significant, TMG doses under 6 grams can also increase LDL cholesterol. It can also increase triglyceride blood levels (the main component of body fat) in obese individuals [41].

In another study (RCT) of 42 obese subjects, daily supplementation of 6 grams of TMG increased LDL (bad) and total cholesterol [42].

3) Other

The breakdown of TMG in the body can make trimethylamine. TMG supplementation can cause a person’s urine and sweat to smell fishy [40].


Although TMG shows promising health benefits, few human trials have been performed. Additionally, like any other supplement, TMG may have different effects depending on the individual.

Natural Sources


  • Bread
  • Wheat germ
  • Cereal
  • Pasta
  • Biscuits [1, 2]


  • Beef
  • Chicken
  • Mutton
  • Fish
  • Shrimp
  • Other shellfish [1, 2]

Fruits and Vegetables

  • Spinach
  • Beets
  • Avocados
  • Asparagus
  • Potatoes [1, 2]

Supplementing with TMG


A normal dietary intake of TMG from food is .5-2 grams/day [5].

A normal daily dose for TMG supplements is around 6 grams. It is effective at 2.5-gram doses, and it is safe at an intake of 9-12 grams/day [5, 11].

Most human trials use 2.5-gram doses of TMG supplements because it is most likely the minimum dose needed to increase blood TMG levels. Splitting this dose into 1.25 grams twice a day might not yield the desired results [10].

Genes Interactions

TMG increases the expression (production) of genes that help with bone formation.

In human bone cells, TMG increased RUNX2, OSX, and SOD2 gene expression. This increases the production of proteins that increase bone formation and protects against bone cell stress [39].

User Reviews

  • “I have suffered from horrible anxiety/panic attacks and depression for 12 years. I read a review that this product helped someone suffering from depression and so decided to give it a shot. To my astonishment and delight, this product worked immediately!”
  • “When added to folate, TMG makes a first arsenal defense against the damaging effects of high homocysteine levels. Recommended!”
  • “A necessary supplement for virtually all adults nowadays, primarily as it helps the liver eliminate toxins like heavy metals.”
  • “This gave me a pressure headache within minutes of ingestion.”
  • “Added to my sleeping issues, unfortunately.”


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