Metabolic Health
Here’s How TMG Supplementation Might Improve Four Health Conditions.
Trimethylglycine (TMG) looks promising for improving cardiovascular, metabolic, mitochondrial, and mental health while improving fitness performance.
My First Encounter with the use of TMG Supplement in a Nutrition Conference
Cardiovascular diseases kill millions of people globally. Two of the major culprits are elevated homocysteine levels and chronic inflammation.
Recent studies associate trimethylglycine (TMG) molecule with heart health as they believe supporting healthy homocysteine levels promotes healthy cardiovascular function. However, trimethylglycine has been known as a heart-health-promoting amino acid since the 1950s.
I met Steve at an expensive international conference bringing nutrition scientists, clinicians, private practitioners, and biohackers to one place. I usually get free tickets to these conferences as I serve on the editorial board as an academic reviewer.
Some presentations by scientists usually bore the audience. However, Steve’s presentation on trimethylglycine was highly inspiring and exciting. He hooked the audience with his compelling presentation.
While his presentation had robust scientific backing, Steve presented it as a passionate biohacker using his experience as a case study. He created a bridge between theoretical and practical aspects with data he collected from his biomarkers presented in attractive charts.
He highlighted the frequent causes of “hyperhomocysteinemia,” including genetic defects, deficiencies of 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 did not know Steve was also a bodybuilder at the age of 53 until I met him at lunch break. When I complimented his speech, he appreciated it and wanted to start a conversation.
Instagram was new in those days, so he showed some fascinating photos from bodybuilding competitions. Like mine, his lunch plate was mainly protein and healthy fat. He was very approachable.
Nevertheless, since I found such a knowledgeable person and the supplementation aspect of the topic was relatively new to me, my goal was to pick Steve’s brain on the promising benefits of TMG, which I hadn’t used before.
However, I read a lot about the effects of betaine on dementia and depression when studying cognitive science. He was willing to share his knowledge generously.
His research and personal experimentation inspired me to learn more about this interesting molecule that our body naturally produces. Due to its importance, scientists also managed to create supplements that are now sold over the counter with no prescription.
Trusting the rigorous research and investigation of Steve, I decided to purchase a TMG supplement from a reliable company in the US, as it is not sold in Australia.
The product claimed that it promotes healthy homocysteine levels, inhibits inflammatory factors to encourage cardiovascular health, supports healthy blood pressure levels, and maintains healthy mitochondrial function.
It also pointed out using it with co-factors B6, B12, and folic acid, which I used to supplement in low doses then. Interestingly, Steve was not surprised when my related blood markers improved after six months of using TMG with no noticeable side effects.
Based on Steve’s initial findings and my follow-up investigation, I’d like to highlight four use cases of TMG supplements for physical and mental health, referring to scientific studies and scholarly reviews.
My particular focus is elevated homocysteine levels as a known risk factor for various health conditions.
1 — Betaine promotes healthy homocysteine levels.
The most compelling part of Steve’s presentation was about TMG’s health-promoting effects on elevated homocysteine levels. He grabbed my attention when he said, “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.
Steve’s claims encouraged me to investigate the literature on homocysteine. Later 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 published between 2002 and 2010 identified using MEDLINE.
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 — Betaine might prevent insulin resistance.
As covered in many of my articles related to metabolic and cognitive health, I pay attention to studies related to insulin resistance as it affects our physical and mental health. Since I suffered from insulin resistance, I made a concerted effort to make my body insulin-sensitive via a healthy lifestyle habit.
Therefore, when Steve mentioned the effects of TMG supplementation in improving his insulin sensitivity, I decided to investigate the literature further.
In my earlier reviews, I read about animal studies that have shown that betaine effectively reduced ethanol-induced hepatotoxicity, indicating insulin resistance.
Interestingly, 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 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.”
In addition, researchers demonstrated in a mice study that “Oral betaine supplementation prevented hepatic betaine deficiency and reversed insulin resistance and fatty liver without significantly changing body weight.” I am still searching for how TMG might affect insulin sensitivity in humans.
3 — Betaine might improve fitness performance.
Like Steve, many bodybuilders and athletes in my circles use TMG supplements to improve their fitness and athletic performance. The anecdotal evidence on workout performance, increasing energy, and reducing fatigue was overwhelming. Therefore I wanted to investigate the literature to validate the 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 — Betaine might improve mild depression.
When Steve mentioned SAMe (S-adenosyl-methionine), a supplement and medication I investigated and gained interest in during my cognitive science studies, I wanted to know more about its relationship with betaine.
His key point was TMG supplementation with SAMe improved his mood and reduced his mild depression.
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.
As Steve touched on the effects of homocysteine on depression during his presentation, my goal was to understand the relationship.
Interestingly, 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
Even though the research on subjective claims by fitness communities is still nonconclusive, the effects of betaine in supplementation format in reducing homocysteine from various studies look promising.
Besides, since the 1950s, trimethylglycine has been understood as a heart-health-promoting compound.
Trimethylglycine (also known as betaine) is a metabolite (an amino acid) formed in the body from choline. I want to present my finding on choline in another article as it is of great interest to me as a brain-boosting compound.
I paid specific attention to homocysteine in this article, as elevated levels indicate a high risk for heart disease, stroke, depression, and dementia. In addition, research associates high homocysteine levels with a deficiency in critical vitamins such as B12, B6, and folate.
As elevated homocysteine causes known health disorders, the viable solution seems to be using trimethylglycine to reduce the risk.
However, as every molecule we ingest might have risks for our health, it is always wise to discuss its potential use with qualified healthcare professionals.
While supplements might help, some foods such as broccoli, beets, spinach, grains, marine algae, and shellfish might include this helpful molecule.
We can get homocysteine levels checked by blood tests. Doctors can advise when the homocysteine levels are high and prepare a treatment plan.
It is important to note that elevated homocysteine levels can affect blood vessels, increasing cardiovascular risk. Therefore, this blood test is vital for those experiencing symptoms of cardiovascular disorders.
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you enjoyed this story, you might also check my reviews of other supplements and molecules, such as:
Lutein/Zeaxanthin, Phosphatidylserine, Boron, Urolithin, taurine, citrulline malate, biotin, lithium orotate, alpha-lipoic acid, n-acetyl-cysteine, acetyl-l-carnitine, CoQ10, PQQ, NADH, TMG, creatine, choline, digestive enzymes, magnesium, zinc, hydrolyzed collagen, nootropics, pure nicotine, activated charcoal, Vitamin B12, Vitamin B1, Vitamin D, Vitamin K2, Omega-3 Fatty Acids, N-Acetyl L-Tyrosine, and other nutrients to improve metabolism and mental health.
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