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 .
TMG has many health benefits – it protects the liver, heart, and kidneys, and can enhance physical performance .
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 .
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 .
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 .
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 .
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 .
An increase in muscle blood flow can improve exercise performance by increasing nutrient delivery and waste excretion .
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 .
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 .
TMG supplementation to improve physique is most effective when accompanied by exercise .
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 .
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
In a review of 74 clinical trials, high choline and TMG intake were associated with lower blood inflammatory markers .
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 .
Although TMG intake is not associated with heart attack incidence, long-term consumption can prevent heart disease-related deaths .
Additionally, TMG treatment protected against blood clots in mice by preventing clots in blood vessels and the circulatory system, it can prevent heart disease .
4) Helps Treat and Prevent Diabetes
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 .
In mice, TMG supplementation:
5) Has Antioxidant Effects
In rats, TMG pre-treatment reduced oxidative damage due to stress .
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 .
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 .
7) Helps Treat Depression
TMG administration in depressed rats changed their behavior. It helped increase serotonin and norepinephrine levels in the rats’ brains, having an antidepressant effect .
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 .
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 .
Additionally, the participants with the largest increase in TMG levels had the greatest memory improvement .
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 .
Autistic children do not have enough levels of the by-products that are needed for the cycle and are also vulnerable to oxidative stress .
In autistic children, TMG and choline deficiency contribute to low methionine and SAMe levels, which can cause abnormal gene expression .
Although scientists are unsure if TMG supplementation affects SAMe levels in autistic children, studies of healthy participants showed that TMG can increase SAMe .
Oral supplementation with folinic acid and TMG normalized the methionine cycle in autistic children. TMG also increased antioxidant levels, which protects against oxidative damage .
10) May Protect the Liver
TMG can help treat both non-alcoholic and alcoholic liver injuries .
TMG can help treat common characteristics of liver diseases. In mice, it:
- Decreases insulin resistance in the liver 
- Reduces fat buildup in the liver 
- Increases activation of liver AMPK to help with glucose and fat (lipid) balance 
- Prevents alcohol-induced inflammation and stress 
- Protects the liver from toxins (like chloroform, methotrexate, LPS, etc) 
- Protects liver cells from bile-induced apoptosis 
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 .
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 .
In a study of 29 nonresponders, more than half the patients responded to the addition of SAMe and TMG to their hepatitis C treatment .
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 .
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 .
Additionally, TMG treatment protected rat kidneys from CCL4-induced toxicity. CCL4 can cause kidney cell death and cirrhosis (liver disease) .
12) Relieves Skin Irritation
In 21 healthy subjects, TMG relieved the skin irritating effects caused by detergents and decreased allergic responses .
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 .
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 .
Shampoo with TMG protected hair protein structure .
14) Relieves Dry Mouth
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 .
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 .
Additionally, TMG helped maintain bone health and bone tissue reshaping and replacement after injuries .
1) Common Side Effects of TMG Supplements
Common side effects include :
- Sleep Disturbances
- Hair Loss
2) Increases Cholesterol Levels
TMG increases cholesterol levels. This potentially cancels out TMG’s benefits on heart health .
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 .
In another study (RCT) of 42 obese subjects, daily supplementation of 6 grams of TMG increased LDL (bad) and total cholesterol .
The breakdown of TMG in the body can make trimethylamine. TMG supplementation can cause a person’s urine and sweat to smell fishy .
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.
Fruits and Vegetables
Supplementing with TMG
A normal dietary intake of TMG from food is .5-2 grams/day .
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 .
TMG increases the expression (production) of genes that help with bone formation.
- “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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