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I heard about athletes supplementing with ketones sometime in the mid-2010s. A company reached out, promising the next big breakthrough in endurance performance from this liquid supplement composed of a molecule naturally produced in the body from the breakdown of free fatty acids. They told me that the top cyclists in the world were already using ketones and that it was destined to take over running, too. They sent a few boxes…and they collected dust in the pantry. It felt like a biohack, and I wasn’t comfortable with it.
Over the years, more studies on ketone ingestion emerged, and I started to get more and more intrigued. Rumors came out that about 70 percent of the cycling peloton used the stuff. But they cost a ton, and it was hard to discern what was actual practice and what was just marketing.
Context for Ketones
To be 100 percent honest, I was sad when I saw this study. I love performance physiology, but I don’t want to think about a new biohack. Maybe it’s a sign that I’m getting old when a study on cutting-edge science just makes me tired. Get these research protocols off my lawn!
But I also couldn’t bury my head in the sand (though that would probably increase EPO concentrations via hypoxia). Instead of giving into my old-coach fatigue, maybe I can help publicize the emerging science so fewer athletes have an information disadvantage. My final push was last week when a fantastic review article was published in the American Journal of Physiology-Cell Physiology by Ruben Robberechts and Chiel Poffé. If ketone supplementation has the potential that some think it may, the article could be a key step in the future of exercise physiology.
Introduction to Ketones
As stated by the review study, ketone bodies “are molecules that are continuously produced from the breakdown of free fatty acids,” primarily in the liver. Ketone body production is upregulated during periods of low carbohydrate availability—that’s why you have heard “ketosis” thrown around for ultrarunners who practice low carbohydrate, high-fat nutrition, aiming to improve fat oxidation and avoid bonking. Ketosis via nutritional interventions comes with way too many downsides for endurance athletes, though, including everything from reduced bone density to diminished high-intensity performance.
That makes sense intuitively because low carbohydrate availability is extremely stressful on most body functions, especially the endocrine system.
Ketones have mostly been marketed as a before-and-during-exercise supplement, at least in the podcast ads I have heard. Take ketones, burn more fat at higher intensities, win the Tour de France, etc. However, a bunch of studies have shown limited to no acute benefit. For example, a 2017 study in Frontiers of Physiology found that pre-exercise ketone supplementation caused around a two percent performance decrease in 10 male professional cyclists doing a 50-minute time trial.
So perhaps it’s something else. Maybe all this ketone hype is because taking them improves recovery and hematological variables, confounding variables that are actually the driving force behind their use (maybe that even explains some of the success stories behind low carb, high fat nutrition approaches. I’d love to see the blood work!).
Mechanisms of Post-Exercise Ketones
I can’t emphasize enough how great this review article is, summarizing extremely uncertain science and studies. Before getting to the EPO mechanisms, let’s briefly touch on a bunch of other considerations. First, ketone bodies may cause epigenetic changes.
For example, histone lysine β-hydro butylation could increase with ketone body increases, which may “increase transcription of genes involved in the adaptive response to exercise.” Across several different epigenetic mechanisms, it’s possible that ketone bodies could be a signal to the body to adapt to stimuli (which makes sense given their evolutionary role in exercise in energy-limited environments).
Are Ketones the Future?
Do the processes change in female athletes? That’s one of my big concerns in making any recommendations since metabolic processes can vary based on gender. While more research is needed, Dr. Poffé indicates that past studies likely show that the results can be extrapolated to female athletes. “In a recent, unpublished study,” he says, “we observed that some effects are even more pronounced in females.