The History of Betaine: How the Supplement Became Popular

Betaine, or trimethylglycine (TMG), has traveled an unusual path: from a byproduct of sugar production to a feed additive for livestock, a prescription drug for a rare genetic disease, and, ultimately, a popular component of sports nutrition. Our editorial team traced how the reputation of this substance changed and what in it was based on science and what on fashion.

Discovery in the sugar beet

The name “betaine” comes from the Latin name of the beet — Beta vulgaris. It was from beet juice that this substance was isolated in the 19th century, when chemists were actively studying the composition of plant raw materials for the sugar industry. In scientific reviews the discovery is usually associated with the German chemist Carl Scheibler.

Chemically, betaine is glycine to whose nitrogen atom three methyl groups are attached. Hence the second name — trimethylglycine. Later the word “betaines” came to denote a whole class of compounds of similar structure, so in the literature it is important to distinguish glycine betaine from other betaines.

For plants, betaine turned out to be an important osmolyte: it helps cells retain water under conditions of drought and soil salinity. That is why there is a lot of it in beets, spinach, and wheat bran.

For a long time betaine was of interest mainly to agrochemists and sugar-production technologists, since it accumulates in molasses — the residue after sugar crystallization.

From feed to medicine

In the 20th century betaine found wide use in livestock farming. The review by Eklund and colleagues (2005) describes its use in feed for poultry and pigs as a donor of methyl groups and an osmolyte that helps animals tolerate heat stress and can affect the ratio of muscle to fat tissue.

It was precisely the results in livestock farming — in particular data on “leaner” carcasses — that later became one of the reasons for interest in betaine in sports nutrition. However, transferring results from pigs to humans always requires separate verification.

In parallel, betaine entered medicine. Betaine hydrochloride was long sold as an agent for acidifying the stomach, although the evidence base for such use is weak.

A more important milestone was the use of anhydrous betaine to treat homocystinuria — a rare hereditary metabolic disorder in which homocysteine sharply accumulates in the blood. In the United States the drug Cystadane was approved by the FDA for this indication in the 1990s.

The era of homocysteine

At the turn of the 20th and 21st centuries, elevated homocysteine was actively discussed as a possible factor in cardiovascular risk. Betaine, being a donor of methyl groups, is able to convert homocysteine into methionine via the enzyme betaine-homocysteine methyltransferase.

The review by Craig (2004) in the American Journal of Clinical Nutrition summarized knowledge about betaine in human nutrition and became one of the most cited works on this topic. Studies by Olthof and colleagues (2003) showed that even moderate doses of betaine lower homocysteine levels in healthy people.

However, it later turned out that lowering homocysteine with B vitamins did not reduce cardiovascular events in large studies, and betaine in high doses can raise LDL (Olthof et al., 2005). The enthusiasm for the “cardiac” role of betaine subsided.

At the same time, betaine was studied in non-alcoholic fatty liver disease. A randomized study by Abdelmalek and colleagues (2009) showed no convincing improvement in histology compared with placebo.

Arrival in sports nutrition

The sports industry turned its attention to betaine in the late 2000s. Studies by Hoffman and colleagues (2009) and Lee and colleagues (2010) in trained people with a dose of 2.5 g per day reported improvement in certain measures of power and endurance in strength exercises.

Later, works with longer-term use appeared. Cholewa and colleagues (2013) described improvements in body composition and work capacity in trained men, and a review by the same group (2014) summarized the possible mechanisms: osmoprotection, methylation, and an effect on the hormonal response.

On this wave, betaine began to be added to pre-workouts, and manufacturers actively sold it separately as “TMG.” At the same time, the results were not always reproduced: some studies, in particular Trepanowski and colleagues (2011), found no significant effect on performance.

The spread of betaine in sport is typical of many supplements: a few positive studies, low cost, and safety quickly turn a substance into a standard ingredient.

Current status and the lessons of history

Today betaine is sold in three main niches: sports nutrition, “methyl” complexes to support homocysteine metabolism, and biohacker stacks, where it is often combined with other substances.

The history of betaine well illustrates several patterns of the supplement market:

• results in animals are easily turned into advertising, although for humans they require separate verification;
• a change in a biomarker, such as homocysteine, does not guarantee clinical benefit;
• a few small positive studies do not yet mean a sustained effect;
• anhydrous betaine and betaine hydrochloride are different products with different purposes.

For the consumer the main takeaway is that betaine is not a “miracle supplement,” but a well-studied substance that is safe in moderate doses, with narrow but real areas of application.

Modern research continues, and over time the picture regarding sports effects may become clearer.

Editorial conclusions

Betaine traveled the path from a component of beet molasses to a prescription drug and a supplement for athletes.

Betaine’s strongest evidence-based positions are the treatment of homocystinuria and the lowering of homocysteine; the sports effects are described but heterogeneous.

Its popularity in sports nutrition is largely due to a few studies from the late 2000s and the market fashion for “TMG.”

For more on practical application, read our materials “Betaine: What It Is and How It Works,” “Betaine During Bulking: Does It Make Sense,” and “Myths About Betaine.”

References

1. Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539–549.
2. Eklund M, Bauer E, Wamatu J, Mosenthin R. Potential nutritional and physiological functions of betaine in livestock. Nutr Res Rev. 2005;18(1):31–48.
3. U.S. Food and Drug Administration. Cystadane (betaine anhydrous for oral solution): prescribing information. Silver Spring (MD): FDA.
4. Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr. 2003;133(12):4135–4138.
5. Olthof MR, van Vliet T, Verhoef P, et al. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med. 2005;2(5):e135.
6. Abdelmalek MF, Sanderson SO, Angulo P, et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology. 2009;50(6):1818–1826.
7. Hoffman JR, Ratamess NA, Kang J, et al. Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr. 2009;6:7.
8. Cholewa JM, Guimarães-Ferreira L, Zanchi NE. Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms. Amino Acids. 2014;46(8):1785–1793.