TMG (betaine) shows great promise in enhancing cardiovascular, metabolic, and mental health, potentially boosting fitness performance based on scientific reviews.

This story does not include health advice. It is for information, inspiration, and awareness purposes.

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Cardiometabolic diseases claim millions of lives worldwide, with elevated homocysteine levels and chronic inflammation being significant contributors. Numerous studies link the trimethylglycine (TMG) molecule to heart health, suggesting that maintaining healthy homocysteine levels supports optimal cardiovascular function.

Interestingly, like CoQ10, trimethylglycine has been recognized as a heart-health-promoting amino acid since the 1950s, but it is still not well-known compared to hyped supplements on the market.

Recently, I wrote a story related to the vitamin B12 deficiency epidemic titled MTHFR Polymorphisms or Mutations: Getting Checked to Prevent Cardiovascular Issues. Discerning readers, seeing one of the methylation donors as TMG, asked me to introduce this vital molecule and how they can benefit from it safely through food or supplementation.

Respecting their request, I crafted this concise article using straightforward language to inform and empower them to explore this molecule further through the credible sources I reference, enabling them to discuss the potential use of this nutrient with their healthcare advisors.

My First Encounter with TMG Supplementation in 2005

I was introduced to the remarkable effects of TMG during a scientific conference by an experimental scientist in 2005. Steve, a lifelong friend now, combined rigorous scientific evidence with his personal experience as a biohacker, effectively bridging the gap between theory and practice. His use of compelling charts displaying data from his biomarkers made the complex subject more accessible and engaging.

He highlighted the major causes of “hyperhomocysteinemia,” including genetic defects, deficiencies of B vitamins (folic acid, vitamin B6, B12), renal failure, and interference in homocysteine metabolism by drugs or metabolic alterations, as mentioned in this 2005 paper.

I wasn’t aware that Steve, as a scientist, was also a bodybuilder at 53 until we met during the lunch break. When I complimented his speech, he graciously engaged in a meaningful conversation. He shared captivating photos from his bodybuilding competitions, and we bonded over our similar choices of bioavailable protein and healthy fats for lunch. Steve was incredibly approachable and down-to-earth, walking his talk.

However, upon discovering Steve’s expertise and considering my limited familiarity with the supplementation aspect of the topic, I aimed to glean his insights regarding the promising benefits of TMG, a supplement I hadn’t previously explored. Having studied cognitive science, I had encountered extensive literature on the effects of betaine on dementia and depression. Steve graciously shared his knowledge with generosity.

His research and personal experimentation sparked my curiosity to delve deeper into this fascinating molecule naturally produced by our bodies. Given its significance, scientists have developed supplements available over the counter without a prescription. Impressed by Steve’s thorough research and investigation, I opted to procure a TMG supplement from a reputable company based in the US.

The product claimed to promote healthy homocysteine levels, inhibit inflammatory factors for cardiovascular health, support healthy blood pressure, and maintain healthy mitochondrial function. It also recommended using co-factors B6, B12, and folic acid, which I supplemented in low doses (1 gram daily) with a break once a week, every month, with no side effects but with noticeable benefits.

Interestingly, Steve wasn’t surprised when my relevant blood markers improved after six months of using TMG, with no noticeable side effects.

Then, I learned from a 2021 review that “betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.”

The keyword is homocysteine, which I covered in a previous article titled Why High Homocysteine Levels Matter and How to Optimize Them. Unfortunately, this health condition is often overlooked, leading to unnecessary confusion among the public by those who fail to grasp its significance. Let me highlight it with a scientific review:

As documented in this 2008 paper,

“Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer’s disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects.”

Building on Steve’s initial findings and my further investigation, I’d like to highlight four use cases and benefits of TMG supplements for physical and mental health, citing scientific studies and scholarly reviews. My particular focus is elevated homocysteine levels, a known risk factor for cardiometabolic health conditions.

What is trimethylglycine?

Tri-Methyl-Glycine, shortened as TMG, also known as betaine, is an important human nutrient obtained from foods and can also be synthesized from choline in the body through a biochemical reaction known as the betaine-homocysteine methyltransferase (BHMT)pathway.

Choline is converted into betaine through a series of enzymatic reactions, and betaine is essentially trimethylglycine. Its chemical structure includes a glycine molecule with three methyl groups attached, making it a vital methyl donor in the body’s biochemical processes.

TMG is a key player in methylation, a process critical for gene expression, protein function, and neurotransmitter synthesis. This function underscores its importance in various physiological functions.

As documented in this paper on Karger,

Betaine is much more abundant in the kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla, and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress.

This process has been thoroughly studied. In the liver, betaine primarily serves as a supplier of methyl groups in a cycle called the methionine cycle. While liver cells have a lot of a protein called BGT1 that helps transport betaine, its role in the liver hasn’t been widely explored.

Betaine needs to get inside liver cells to work effectively. Recently, there has been more interest in betaine because it’s being considered for various treatments, such as nonalcoholic fatty liver disease and hyperhomocysteinemia, which increases the risk of heart disease.

4 Potential Health Benefits of Trimethylglycine

1 —Promoting healthy homocysteine levels and lowering cardiovascular disease risks

This 2003 study in the Journal of Nutrition concluded that

“Doses of betaine in the range of dietary intake reduce fasting and post methionine loading plasma homocysteine concentrations. A betaine-rich diet might, therefore, lower cardiovascular disease risk.”

This 2021 review in the journal Biology focused on the biological and beneficial effects of dietary betaine (trimethylglycine), a naturally occurring and crucial methyl donor, that restores cell methionine homeostasis.

Some studies indicate that by promoting healthy homocysteine levels, TMG can inhibit inflammatory factors from contributing to improved cardiovascular health. I knew that elevated homocysteine might increase heart disease, stroke, and dementia risks from my prior research.

In 2013, when I read this meta-analysis in the Journal of Chiropractic Medicine, I learned that:

“Supplementation with at least 4g/d of betaine for a minimum of 6 weeks can lower plasma homocysteine.” It included five randomized controlled trials identified using MEDLINE published between 2002 and 2010. However, as pointed out in this review, “controversy regarding the effects of betaine supplementation on cardiovascular markers has persisted for decades.”

This 2021 systematic review and meta-analysis published in the Critical Reviews in Food Science and Nutrition journal supported “the advantage of a lower dose of betaine supplementation (<4 g/d) on homocysteine concentrations without the lipid-augmenting effect observed with a higher dosage.”

2 — Preventing Insulin Resistance, Lowering Obesity Risk, and Improving Liver Function

In my earlier reviews, I read about animal studies that have shown that betaine effectively reduced ethanol-induced hepatotoxicity, indicating insulin resistance.

This 2017 review published in Applied Nutritional Investigation demonstrated that “higher intake of dietary choline and betaine is associated with lower insulin resistance in the general population.” Furthermore, researchers found the association was more pronounced in women than men.

I have been investigating nonalcoholic fatty liver disease affecting the lives of 2 billion people for a long time. During that period, I came across a study published in the American Journal of Physiology titled “Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine.”

The paper published in the American Physiological Society states that “Betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL in mice. Betaine also reverses hepatic insulin resistance in part by increasing the activation of IRS1, with resultant improvement in downstream signaling pathways.

This 2018 Frontiers paper states,

“Accumulating evidence has shown that betaine has anti-inflammatory functions in numerous diseases. Mechanistically, betaine ameliorates sulfur amino acid metabolism against oxidative stress, inhibits nuclear factor-κB activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. Consequently, betaine has beneficial actions in several human diseases, such as obesity, diabetes, cancer, and Alzheimer’s disease.”

3 — Improving Fitness Performance

Since 2005, I have observed many bodybuilders and athletes in my circles using TMG supplements to enhance fitness and athletic performance. The anecdotal evidence regarding workout performance, increased energy, and reduced fatigue was overwhelming. Consequently, I sought to investigate the literature to validate these claims.

This 2014 review described “evidence for the use of betaine as an ergogenic and esthetic aid and discussed the potential mechanisms underlying these effects.”

Researchers pointed out that previous investigations convey the positive effects of betaine on sports performance in endurance and resistance-type exercises despite conflicting results.

They hypothesized that supplementation might involve stimulating lipolysis, inhibiting lipogenesis via gene expression, stimulating growth hormone secretion, and increasing creatine synthesis. However, they struggled to find the exact mechanisms behind betaine action and the long-term effects of supplementation on humans.

This systematic review published in the Journal of Strength and Conditioning Research investigated the effects of betaine supplementation on muscle strength and power.

The reviewer highlighted

“The lack of evidence for a clear ergogenic effect of betaine supplementation on strength and power performance. However, as two studies identified increases of up to 24.61% in strength and power due to betaine supplementation, the investigator proposed additional studies to evaluate its effectiveness.”

4 —Improving Mood Disorders, Particularly Addressing Mild Depression When Used with SAMe

As another methyl donor, SAMe (S-adenosyl-methionine), a supplement and medication I explored and became interested in during my cognitive science studies, I wanted to delve deeper into its relationship with betaine. I learned that TMG supplementation with SAMe improved mood and reduced mild depression for some people.

This 2015 paper provided preliminary results of a randomized controlled trial with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression.

Researchers concluded that

“The administration of SAMe plus betaine is a valid and safe nanotherapeutic option to treat individuals with a recent diagnosis of mild depression.”

A 2017 study in Nature suggests that

“Increased depression and anxiety may be positively associated with higher serum homocysteine levels in older boys.” Their results from Taiwan provided data on the biological aspects underlying anxiety and depression in the studied population.

A study examined the association of the severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents.

The study indicated that vitamin B12 deficiency and elevated homocysteine may contribute to the etiopathogenesis of depression.”

Interestingly, the researchers pointed out that lower vitamin D levels might be associated with depression. I documented my research on Vitamin B12 and vitamin D in previous articles.

Conclusions and Takeaways

While research on subjective claims from fitness communities remains inconclusive, the efficacy of betaine in supplementation, particularly in reducing homocysteine levels, is well-established through numerous studies and holds promise. So, I take 1 gram daily, with a break once a week, every month, with no side effects, gaining apparent benefits.

Since the 1950s, trimethylglycine, which was discovered from sugar beets, has been recognized as a heart-health-promoting compound. TMG is a metabolite derived from choline within the body, functioning as an amino acid.

I am intrigued by choline and its potential as a brain-boosting compound. I wrote about it in a story titled Here’s Why and How to Address Choline Deficiency.

In this article, I focused on homocysteine because elevated levels are linked to increased risks of heart disease, stroke, depression, and dementia. Moreover, research indicates that high homocysteine levels are associated with deficiencies in essential vitamins like B12, B6, and folate, as I covered in previous articles.

Given that elevated homocysteine is linked to known health disorders, using trimethylglycine appears to be a potential solution for reducing the risk. However, since every ingested molecule may have health risks, it is advisable to discuss the potential use of trimethylglycine with qualified healthcare professionals.

For instance, as highlighted in a 2019 review paper, betaine supplementation might slightly increase total cholesterol levels.

Therefore, it is crucial to consult qualified healthcare professionals, especially for individuals with underlying cardiovascular issues, as elevated cholesterol levels could exacerbate atherosclerosis. I wrote about the cholesterol paradox in a previous article.

While supplements may provide support, eating foods like broccoli, beets, spinach, grains, marine algae, and shellfish, as well as wheat bran, quinoa, sweet potatoes, turkey breast, beef, wheat germ, barley, shrimp, and crab, can naturally increase your intake of this beneficial molecule.

Blood tests can determine homocysteine levels, and family doctors or specialists like cardiologists can recommend a treatment plan if levels are elevated, which is crucial as high homocysteine levels can impact blood vessels, heightening cardiovascular risk. Therefore, this test is essential for individuals experiencing symptoms of cardiovascular disorders.

As mentioned in a previous article, genetic defects such as MTHFR polymorphisms or mutations can cause B vitamin deficiencies and elevated homocysteine levels, making screening for this genetic issue valuable.

Thank you for reading my perspectives. I wish you a healthy and happy life.

One of my writing goals is to raise awareness about the causes and risk factors of prevalent diseases that can lead to suffering and death for a large portion of the population. I aim to educate, create awareness, and empower my readers to take control of their health and well-being.

To raise awareness about health issues, I have written several articles that present my holistic health findings from research, personal observations, and unique experiences.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.

To inform my new readers, I wrote multiple articles that might inform and inspire you. My topics include brain and cognitive function, significant health conditions, longevity, nutrition/food, valuable nutrients, ketogenic lifestyle, self-healing, weight management, science, technology, business, and humor.