What is betaine, trimethylglycine (TMG)?

Betaine, also known as Trimethylglycine (TMG), is a naturally occurring molecule found in foods such as spinach, beets, or quinoa. Your own body is also capable of producing TMG.

In recent years, the potential health benefits and performance-enhancing effects of betaine as a dietary supplement have been researched. Learn more here about how betaine, as a methyl group donor, can positively impact your longevity, why it is beneficial for athletes to supplement with TMG, and what the difference is between betaine and betaine HCL.

What is Betaine / Trimethylglycine (TMG)?

Betaine is a derivative of the amino acid glycine with vitamin-like effects and properties. Its name is derived from the beetroot or beet, which also contains a portion of the substance.Another name for betaine is trimethylglycine (TMG).

This also tells us that betaine contains three (tri-) methyl groups. A methyl group is the simplest organic arrangement of one carbon and three hydrogen atoms in chemistry. However, this compound does not represent an independent substance but merely forms part of a larger molecule, in our case, betaine. 

The main molecular mechanisms are its function as a Methyl group donor and osmolite. But what does that even mean?

Health-promoting effects of Betaine (TMG) – What is a methyl group donor?

To better understand the complex biochemistry behind TMG, let's imagine the methyl group as a cap. This cap can be passed on through a process called "methylation." A new molecule now "puts on" this cap and is thereby altered in its biochemical properties. This manifests in a changed activity up to a completely different function of the new cap wearer. This step thus forms a crucial part of many physiological processes in the human body.

Since Betaine has several such "caps" and can also put them on other molecules, Betaine is referred to as a donor (from Latin  donare "to give") of methyl groups.Additionally, betaine has a  strong anti-inflammatory effect, as it blocks pro-inflammatory transcription factors on one hand and extinguishes the cell's cauldron – the inflammasome – on the other. Well, that’s it for now with the theory – now comes the practice:

“Spinach makes you strong.” This sentence is probably something many of us heard in our childhood. But is there any truth to this statement? This thesis is based on the then-emerging view that spinach, due to its high iron content, was an ideal strengthening agent. This iron myth unfortunately turned out to be only half true, as only dried spinach contains a large amount of iron. In fresh spinach, however, the proportion is about one-tenth smaller due to the high water content.

Despite this misunderstanding, additional strengthening ingredients have been discovered over time. According to current studies, the nitrates and steroids present in spinach are responsible for increased muscle growth. In addition,  spinach forms the largest natural source of the multifunctional nutrient  Betaine with approximately 550  mg per 100  g. This corresponds to 0.55  % of the total amount. So, it is likely that it is less the iron and more the betaine in spinach that makes us strong.

Homocysteine and Betaine (Trimethylglycine)

Homocysteine is a physiological intermediate product that is formed in normal metabolism through demethylation (release of the methyl group) from the essential amino acid methionine. An elevated level of homocysteine in the blood plasma is considered an independent risk factor for diabetes mellitus, Alzheimer, and cardiovascular diseases, as it leads to a more pronounced development of arteriosclerosis due to damage to the vessel walls.

Just as homocysteine is formed in the cell from methionine, it can be converted back to methionine by adding the methyl cap. In this way betaine can lower the dangerously elevated homocysteine levels in the human body by donating a methyl group. Thus, the molecule acts protectively against arteriosclerotic diseases such as strokes or heart attacks.

In combination with its anti-inflammatory effects at the cellular level, betaine has also shown a reduction in the risk of degeneration and dementia, alongside positive metabolic outcomes for patients with type II diabetes or liver diseases.

NAD+ and TMG – better together?

In another clinical example, NAD+ precursor molecules play an important role. These increase the NAD+ levels in the human body and activate the production of nicotinamide. And now comes the catch: Nicotinamide requires a methylation step in order to be excreted with urine. Therefore, the increase in nicotinamide levels leads to increased methylation processes and depletes the methylation resources.A TMG supplement could counteract the overload of the methylation system while simultaneously boosting NAD.

Performance-enhancing effect of Betaine – What is an Osmolyte?

An osmolite is a substance that helps maintain the fluid balance inside and outside of cells. If the fluid ratio tips, an imbalance occurs, which in the worst case can even lead to cell death. This happens both through strong shrinking – similar to a balloon losing air – and through uncontrolled swelling of the cell – when too much air causes the balloon to burst.

Betaine, when not involved in the methylation metabolism, is absorbed by the tissue and acts there as an organic osmolite in regulating cell volume. TMG protects the cell by helping to maintain and stabilize the water and energy balance, as well as metabolic function. In skeletal muscle, it contributes to the swelling of muscle fibers, thereby stimulating protein synthesis and improving its stability.

Additionally trimethylglycine (betaine) promotes the biosynthesis and availability of creatine, another muscle-building substance that is quite popular among athletes. Creatine acts as an energy storage molecule and supports the cell's power capacity. On the other hand, it also stimulates protein synthesis and the formation of new muscle cells. It is suspected, that betaine promotes muscle growth through the combination of these anabolic, i.e., building, processes.

And what do current studies say about this? Results from a recent scientific analysis suggest that betaine as a supplement represents an effective approach to reducing body fat . A high-quality study also showed that regular supplementation of betaine improved body composition, arm circumference , and training capacity in bench pressing and even tended to increase strength. Overall, many studies support both the health-promoting and performance-enhancing effects of betaine and thus its use as a supplement.