Betaine History: Beets, Homocysteine and Trimethylglycine

Betaine is a methyl donor found in beets, and supplement labels can call it trimethylglycine (TMG). The human trials cited here are small, and none measured lifespan. The homocysteine, liver and sports studies each measured a specific marker or performance outcome.

The history of betaine and TMG is a story about a methyl donor that beets supply and that supplement labels can list as trimethylglycine (TMG). The human research on it is thinner than those labels suggest. The sources we could check do not say who first isolated betaine, so this page does not name a discoverer. **Jump to** - [A methyl donor that foods also supply](#a-methyl-donor-that-foods-also-supply) - [Homocysteine results at three doses](#homocysteine-results-at-three-doses) - [Rats showed protection; the human trial did not beat placebo](#rats-showed-protection-the-human-trial-did-not-beat-placebo) - [Sports research is mixed](#sports-research-is-mixed) - [The label dose against the trial doses](#the-label-dose-against-the-trial-doses) - [What the trials did not measure](#what-the-trials-did-not-measure) - [Frequently asked questions](#frequently-asked-questions) ## A methyl donor that foods also supply Betaine is a modified amino acid made of glycine with three methyl groups. LiverTox describes it as a methyl donor in several metabolic pathways, names beets as a food source, and says the body can also make it from choline ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). According to PubMed, a 2004 review by Craig describes betaine's principal physiologic role as an osmolyte and methyl donor, working in the methionine cycle, mainly in the human liver and kidneys ([DOI](https://doi.org/10.1093/ajcn/80.3.539)). Craig lists seafood, wheat germ or bran, and spinach among the rich dietary sources. The [trimethylglycine ingredient page](/ingredients/trimethylglycine) covers the compound's reference details. In rats, a 2016 study found that betaine in the drinking water prevented fat from building up in the liver of animals fed a diet deficient in methionine and choline. The authors wrote that betaine also reversed a rise in liver homocysteine, which could be attributable to induction of two enzymes, BHMT and MAT ([DOI](https://doi.org/10.1016/j.bbrc.2016.06.080)). Those are findings in animals and cells, not in people. ## Homocysteine results at three doses LiverTox says betaine is believed to act by increasing methylation, one step of which converts homocysteine to methionine ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). According to PubMed, a 2003 randomized trial by Olthof and colleagues gave four groups of 19 healthy adults either placebo or one of three daily betaine doses: 1.5, 3 or 6 grams, for six weeks. Fasting plasma homocysteine after six weeks was 12%, 15% and 20% lower than in the placebo group, respectively ([DOI](https://doi.org/10.1093/jn/133.12.4135)). The authors noted that typical dietary betaine intake is about 0.5 to 2 grams a day. They also described high plasma homocysteine as a risk for cardiovascular disease, but the trial measured the blood level, not heart outcomes. The 2004 review ties inadequate dietary methyl intake to higher plasma homocysteine and lower S-adenosylmethionine concentrations ([DOI](https://doi.org/10.1093/ajcn/80.3.539)). ## Rats showed protection; the human trial did not beat placebo According to PubMed, a 1997 study in rats found that betaine supplementation protected the liver from ethanol-induced fatty buildup. Once fatty liver had formed, betaine partly reversed it after ethanol feeding stopped ([PubMed](https://pubmed.ncbi.nlm.nih.gov/9309323/)). A 2001 study by Barak and colleagues measured homocysteine in isolated rat liver cells. Cells from ethanol-fed rats released twice as much homocysteine as control cells, and adding betaine to the culture medium prevented the increase in both groups ([DOI](https://doi.org/10.1016/s0741-8329%2801%2900168-9)). The 2009 trial by Abdelmalek and colleagues randomized 55 people with biopsy-proven NASH to 20 grams of betaine a day or placebo for 12 months. Steatosis grade fell in the betaine group. Compared with placebo, the authors concluded that betaine did not improve hepatic steatosis, though it may have protected against worsening. Neither the activity score nor fibrosis stage changed in either group, and betaine did not lower S-adenosylhomocysteine, which was about twice normal ([DOI](https://doi.org/10.1002/hep.23239)). LiverTox says betaine has not been linked to liver injury, even at high doses of 6 to 20 grams a day ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). ## Sports research is mixed According to PubMed, a 2024 systematic review and meta-analysis in the Journal of Sports Sciences pooled 17 studies with 317 participants. It found a significant effect on maximal strength, particularly in the lower body. It found no significant effect on upper-body strength, cycling sprint power or muscular endurance. Vertical jump improved significantly, but only after the authors excluded a low-quality study ([DOI](https://doi.org/10.1080/02640414.2024.2423578)). For another sports supplement, see [creatine, from meat extract to the sports shelf](/blog/history/history-of-creatine-from-meat-extract-to-sports-shelf). A 2025 systematic review of endurance trials in Physical Activity and Nutrition found five studies that compared betaine with placebo, and rated all five at high risk of bias. The authors called the evidence scarce ([DOI](https://doi.org/10.20463/pan.2025.0008)). ## The label dose against the trial doses The label of [NMN + NR with Resveratrol and TMG](https://mtangelvitamins.com/products/nmn-nr-cellular-wellness-supplement?utm_source=learn_hub&utm_medium=content&utm_campaign=blog_post&utm_content=history-of-betaine-from-sugar-beet-to-trimethylglycine) lists 50 mg of trimethylglycine per two-capsule serving, printed as "Trimethylglycine (TMG) (Betaine anhydrous)". Its directions say to take two capsules daily. That is about one-thirtieth of the lowest dose in the 2003 trial. The trial tested betaine alone, so the comparison says nothing about the other ingredients in the capsule. For the article on that combination, see [NMN, NR, TMG, resveratrol and zinc](/research/nmn-nr-tmg-resveratrol-zinc-synergistic-stack). ## What the trials did not measure None of the human trials cited here measured lifespan. The 2009 trial also measured adiponectin, which the abstract calls an anti-inflammatory agent. It fell significantly in both groups, and betaine did not change it. The abstract does not say why. ## Frequently asked questions ### Why is betaine named after beets? The sources we could check do not explain the name, so this page offers no naming story. They do support the beet connection. LiverTox lists beets among the foods that supply betaine ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)), and Craig's 2004 review names seafood, wheat germ or bran, and spinach as rich dietary sources ([DOI](https://doi.org/10.1093/ajcn/80.3.539)). Beets are one food source among several, and the sources do not say whether they gave the compound its name. ### Who first isolated betaine, and from which source? The sources we could check do not name a discoverer or a year of first isolation, so this page gives neither. A dated primary account would settle the question, and none turned up in PubMed or in the NIH sources we reached. Until one does, the sources support one beet fact: beets contain betaine. That is where the compound is found, not who found it. ### What does trimethylglycine do in the body? Some supplement labels print trimethylglycine (TMG) with betaine anhydrous in parentheses, which treats the two names as one compound. According to PubMed, Craig's 2004 review describes betaine's principal physiologic role as an osmolyte and methyl donor in the methionine cycle, mainly in the human liver and kidneys ([DOI](https://doi.org/10.1093/ajcn/80.3.539)). A 2016 rat study points to a related pathway, with the authors suggesting induction of the BHMT and MAT enzymes ([DOI](https://doi.org/10.1016/j.bbrc.2016.06.080)). Those are findings in animals and cells, not outcomes measured in people. ### How does betaine connect to homocysteine research? LiverTox says betaine is believed to increase methylation, one step of which converts homocysteine to methionine ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). In the 2003 trial, fasting homocysteine ended 12% to 20% lower than in the placebo group, depending on the dose ([DOI](https://doi.org/10.1093/jn/133.12.4135)). The authors note that high plasma homocysteine is a risk for cardiovascular disease. The trial measured the blood level only, so it does not show any effect on heart outcomes. ### Why does TMG appear in longevity and sports products? The sources support a methyl-donor role, and LiverTox says betaine is believed to lower homocysteine by increasing methylation. They do not show a longevity outcome, and none of the human trials cited here measured lifespan. In sports, a 2024 meta-analysis of 17 studies found a significant effect on maximal strength, mainly in the lower body, but no significant effect on cycling sprint power or muscular endurance ([DOI](https://doi.org/10.1080/02640414.2024.2423578)). A 2025 endurance review found five studies, all at high risk of bias ([DOI](https://doi.org/10.20463/pan.2025.0008)). ### Which doses did the human trials use? The 2003 homocysteine trial used 1.5, 3 and 6 grams of betaine a day for six weeks ([DOI](https://doi.org/10.1093/jn/133.12.4135)). The 2009 liver trial used 20 grams a day for 12 months ([DOI](https://doi.org/10.1002/hep.23239)). LiverTox gives 3 to 10 grams twice daily as the typical therapy dose for homocystinuria, a rare inherited condition, and says high doses of 6 to 20 grams a day have not been linked to liver injury ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). LiverTox's bibliography lists the 2009 trial at 10 grams twice daily, so this page follows the trial's own abstract. ### What do the early betaine studies show about the liver? The early work was done in rats and cells. A 1997 rat study found that betaine protected the liver from ethanol-induced fatty buildup and partly reversed established fatty liver after ethanol stopped ([PubMed](https://pubmed.ncbi.nlm.nih.gov/9309323/)). In the 2009 trial of 55 people with biopsy-proven NASH, steatosis grade fell in the betaine group. Compared with placebo, the authors concluded that betaine did not improve hepatic steatosis, though it may have protected against worsening ([DOI](https://doi.org/10.1002/hep.23239)). LiverTox says betaine has not been linked to liver injury, even at 6 to 20 grams a day ([LiverTox](https://www.ncbi.nlm.nih.gov/books/NBK548774/)). ## Next reads - [Trimethylglycine ingredient page](/ingredients/trimethylglycine): the reference profile for the compound this history covers. - [Creatine, from meat extract to the sports shelf](/blog/history/history-of-creatine-from-meat-extract-to-sports-shelf): a second supplement origin story, from sports nutrition. ### Related reading - [the betaine and TMG origins page](/blog/history/history-of-black-pepper-from-spice-trade-to-piperine) - [the betaine and TMG origins page](/blog/history/history-of-resveratrol-from-hellebore-to-french-paradox)