Trimethylglycine (TMG) is a natural polysaccharide usually derived from betaine in beets (beetroot); it has three methyl groups and can convert dangerous oxidant and free-radical producer homocysteine into the safe amino acid methionine.
Because betaine is the natural compound from beets, and is the precursor to TMG, betaine is often the compound actually used in research. TMG itself may be referred to as betaine anhydrous.
Homocysteine blood levels linked to chronic illness
Homocysteine is known to build up in the microenvironment of cells, if we have a poor diet and also as we age. Research from Oxford University (1) has shown it builds up prior to Alzheimer’s, and that taking fish oils and B vitamins in combination can neutralise it. 2021 research (2) has shown that turmeric can neutralise the build-up of homocysteine (hyperhomocysteinemia) in cardiovascular risk cases. Homocysteine can cause artery damage. Plasma homocysteine can build up prior to cancer and cause problems with methylation of the DNA in breast cancer. Turmeric can inhibit this (3).
Homocysteine is a powerful oxidant and free radical generator, just what you do not want in the microenvironment of your cells. Increased levels in the blood have been linked with cardiovascular disease, Alzheimer’s, cancer, diabetes, lupus and a fatty liver.
The action of TMG
TMG is a methyl donor - Methyl group donation is believed to be able to prevent many illnesses. In one study, treatment of 19 patients with a combination of TMG, choline and folic acid normalised homocysteine levels in 17 of them. The researchers were again studying the link of high plasma homocysteine levels with heart disease and peripheral artery disease (4).
TMG thus protects the body from the oxidative stress and the build-up of free radicals caused by homocysteine.
TMG increases glutathione and may help with a fatty liver - Homocysteine can also cause liver damage. TMG production involves a multistep process - choline producing betaine, producing trimethylglycine, each step involving methyl transfer.
Trimethylglycine is methyl-rich having three methyl groups. TMG primarily works in the liver where it converts dangerous homocysteine immediately to the safe amino acid methionine.
The methionine itself is converted in the liver to SAMe (S-adenosyl methionine) which increases the production of glutathione (5) and cleans and protects the liver.
TMG may help with depression - SAMe is also an antidepressant, helping to produce norepinephrine, dopamine and serotonin. In one study of 45 people using standard treatments plus supplements of SAMe and TMG, the group taking the supplements had less anxiety, and feelings of helplessness (6).
More research is needed but TMG seems capable of protecting against an alcoholic or non-alcoholic fatty liver. Betaine itself can protect and even reverse a fatty liver (7). In another study (8) betaine reduced a fatty liver and increased blood HDL (good cholesterol) levels.
TMG is more effective in the presence of good levels of B vitamins (B-12, B-6, folic acid) and zinc.
Fatty livers are common in cancer patients. In a 2008 study, the production of TMG from raised choline and betaine consumption was linked with a greater breast cancer survival and less mortality (9).
Sources of TMG include choline, beetroot, avocado, asparagus, quinoa, seafood, wheat bran.
Supplements of TMG are in research are usually 2.5 gm to 6 gm.
Warnings
There are two older studies from 2002 and 2005 that suggest betaine supplementation might increase LDL cholesterol; quite how is rather baffling. Perhaps by defatting the liver it temporarily increases blood fasts (10, 11).
Chris Woollams, former Oxford University Biochemist and a founder of CANCERactive said, “When researching TMG after a patient with a fatty liver was prescribed it, I found a chronic lack of understanding of methylation, homocysteine and what was even going on in the microenvironments of cells. Some of the research commentary in the actual research article was just plain wrong. I would be very wary of taking TMG - certainly for longer than, say, 4-6 weeks. It may be advisable, until there is some quality research, to stick to eating beetroot.”
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References
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https://chriswoollamshealthwatch.com/your-illness/alzheimers-and-dementia/2307-pgsapr22/
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Effects of Turmeric on Cardiovascular Risk Factors, Mental Health, and Serum Homocysteine in Overweight, Obese Females - https://pubmed.ncbi.nlm.nih.gov/32088675/
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Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition; Nutrients, 2021 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910847/
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Prevalence of familial hyperhomocyst(e)inemia in men with premature coronary artery disease - https://www.ahajournals.org/doi/10.1161/01.ATV.11.5.1129
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Hanje AJ et al. The use of selected nutrition supplements and complementary and alternative medicine in liver disease. Nutr Clin Pract. 2006 Jun; 21(3):255-72
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Role of betaine in improving the antidepressant effect of S-adenosyl-methionine in patients with mild-to-moderate depression - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303396/
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Wenjuan Yang et al. Betaine attenuates chronic alcoholinduced fatty liver by broadly regulating hepatic lipid metabolism. Mol Med Rep. 2017 Oct;16(4):5225-5234
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Kirsti Tiihonen et al. Effect of Dietary Betaine on Metabolic Syndrome Risk Factors in Asian Males with Mild Fatty Liver. J Diabetes Metab 2016, 7:7
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High intakes of choline and betaine reduce breast cancer mortality in a population-based study; 2009; FASEB - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775010/
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Effect of Homocysteine-Lowering Nutrients on Blood Lipids: Results from Four Randomised, Placebo-Controlled Studies in Healthy Humans; 2005 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140947/
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Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects; 2002; - https://pubmed.ncbi.nlm.nih.gov/12399266/