Betaine: The Molecule Behind Exercise’s Anti-Aging Effects

Nothing matches the health benefits of exercise. It is the closest thing we have to a universal prescription for healthy aging. But have you ever wondered how? How does movement and exercise actually slow aging and extend healthspan? Exercise initiates a complex cascade of biochemical events that lead to adaptations in the body designed to improve whole body health. And by identifying what those adaptations are specifically, we can tap into some of the systems nature has evolved in order to optimize our health. Now that's the question, that's the query that the researchers behind the study we are going to review today together set out to explore. They weren't trying to replace exercise, but they were curious if they could bottle up part of its benefits. So in this study, 13 men were instructed to exercise by running 5 kilometers, first every other day and then every day for 25 days. The researchers then measured a broad suite of metabolites in their bodies before and after the exercise regimen. So what did they find? They found first that routine exercise decreased markers of inflammation, including C-reactive protein, hsCRP, TNF-alpha, and increased levels of the so-called geroprotective or anti-aging antioxidant proteins and pathways like the Nrf2 pathway, which we reviewed in prior videos on this channel, like this one, SOD1, and glutathione. These proteins and pathways help defend your body from oxidative stress, basically the wear and tear that contributes to aging. But then, the researchers dug a little deeper. They wanted to know which metabolites specifically were linked to these anti-inflammatory and geroprotective effects of exercise. And one molecule stood out. A molecule called betaine. Betaine was originally discovered in beets, hence the name, and is also known as trimethylglycine. Now, while betaine is easier to say, trimethylglycine tells you exactly what this molecule is: the amino acid glycine with 3 methyl groups attached to it. Fancy that, terminology that actually makes sense. Now, betaine can be consumed through the diet, as from beets or spinach, or it can be produced by the body.

And just fair warning, In case you haven't noticed this already, eating lots of beets can actually turn your urine bright pink or even red.

This is called beeturia, and it's caused by a natural dye found in beets called betanin, not to be confused with betaine.

By the way, it's totally harmless, so don't panic. It certainly freaked me out when I first saw it, so just a fair warning.

But tangent aside, betaine plays a key role in metabolic pathways by acting as what's called a methyl—

donor.

Remember, it's trimethylglycine, it has 3 methyl groups to give away. Basically, it serves as a reservoir for important molecular tags, these methyl groups, which are involved in gene expression, detoxification pathways, neurotransmitter synthesis, and so on. Methylation pathways are really critical in the basics of metabolism. And it's generally thought that trimethylglycine, betaine, supports cardiovascular health and physical performance, which we will touch on more later in this video. But back to this core study. By combining their human data with results they then collected from experiments on rodents and in cells, the researchers dissected a pathway, a fascinating pathway. They found that exercise, regular exercise, boosts the body's production of betaine, especially from the kidneys, by about 73%. And then betaine acts as an inhibitor of a protein called Ready for it? Tank Binding Kinase 1, or TBK1 for short, which helps regulate immune and inflammatory responses. Now, I'll be honest, you don't need to memorize Tank Binding Kinase 1, but consider it a little memory aid for the metabolic action of betaine. Just picture Tank Man. Have you seen this image before? It's the lone protester who stood in front of those tanks in Tiananmen Square in China. Like Tank Man, betaine steps in to block the inflammatory tanks that accelerate aging. So what are the consequences? What are the results? Well, in aged mice, betaine supplementation reduced several signs of aging. The mice showed lower levels of cellular senescence, a key marker of biological aging, as well as improved grip strength, increased muscle size, and better cognitive performance. So, while no supplement can truly replace exercise—I'm not claiming that—understanding the molecules that underlie the metabolic benefits of exercise, like betaine, brings us one step closer to decoding the biological magnificence of the effects of movement on metabolism. It's not about cheap shortcuts; it's about evolving our understanding and capitalizing on the system that nature has already evolved to potentially move us closer to our modern goals of extending healthspan and lifespan, well beyond just our reproductive years. But now, let's shift gears to discuss other benefits of betaine, trimethylglycine. First, betaine lowers something you might have heard of called homocysteine. High homocysteine, which is a byproduct of metabolism, is well known to be linked to poor cardiovascular health. Betaine acts, as we've mentioned, as a methyl donor, in a reaction in which an enzyme transfers a methyl group from betaine to homocysteine, converting homocysteine into methionine. Just think about it like biochemical recycling, turning harmful leftovers into something useful. Or if you're a baker, and I used to be, it's like turning cardiotoxic old bananas into healthy banana bread.

Did you like that analogy? Let me know.

Anyway, the warm embrace of nostalgic scents aside, the data show betaine can lower homocysteine. For example, in a meta-analysis of 5 randomized controlled trials, 4 grams per day or more of betaine supplementation effectively lowered homocysteine by 12%, which in this case was 1.23 micromolar. The authors of this analysis estimates this translates into about a 5-8% reduced risk of cardiovascular disease. And there also appears to be a dose-response effect. In another 6-week randomized controlled trial, supplementation with 1.5, 3, or 6 grams of betaine lowered homocysteine by 12, 15, and 20% respectively as compared to a placebo control. Now moving on, there are also data that betaine can improve athletic performance. In one double-blinded randomized controlled trial, professional soccer players were matched by position and then randomized to consume 2 grams per day of betaine, or a placebo control for 14 weeks. The results? Betaine supplementation in these professional athletes resulted in statistically significant improvements in a wide range of athletic tests, including VO2 max, 30-meter sprints, and muscle power and strength. These benefits may have been due, at least in part, to improved hormone balance, improved testosterone and cortisol ratio. The result of both an 84% increase in testosterone and a 22% decrease in cortisol. And other studies have found similar benefits on hormonal balance. It's pretty cool, right? Now, I'm sure you're curious about dosing betaine. Well, based on the available evidence, consuming a diet rich in betaine, including foods like beetroot, spinach, and to a lesser extent shellfish like shrimp, is likely to have betaine-dependent biological effects. That said, for those interested in supplementation, doses between 1.5 grams per day and 6 grams per day appear to be effective.

And the most common side effect, which is relevant to Raisin, is mild gastrointestinal upset. So if you're interested in that, I'm not pushing it, but there's an option for you. And if you want an option of a particular supplement, you can check the links below.

But wrapping up, at the end of the day, betaine is not going to turn you into a superhuman, no supplement will, but it's a great reminder that a small molecule can have a big impact. So while it's not a magic bullet, betaine is another tool to support your health, especially when combined with exercise and otherwise proper human nutrition.

Now, if you want more science that can't be beet, make sure to hit that subscribe button. Until next time, stay curious. And also a special thanks to my mother for requesting I do a video breakdown of this Cell paper. That's how loving and nerdy our relationship is. Paper comes out in Cell, 2 days later I have a newsletter on it and we're producing a video. So you can thank my mom for that. And by the way, doesn't she look good for 60? Peace. Stay curious. Have a good one.