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A new review study points toward post-exercise ketone supplementation as a way to improve adaptation and performance. What does the uncertain science mean for endurance athletes?

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.

It wasn’t until 2023, though, that I embraced that ketones were here to stay, whether I liked it or not. A 2023 study in the American Journal of Physiology-Endocrine and Metabolism had nine men complete two cycling trials, both with one hour consisting of two minutes at 90 percent of aerobic capacity (moderately hard), followed by two minutes at 50 percent of aerobic capacity (very easy). In both trials, the cyclists consumed a carb-protein drink immediately after exercise and at one, two, and three hours later. Here’s the study intervention: in just one trial, participants ingested 0.29 g/kg ketone monoester immediately after exercise and at one and two hours later.

The ketone trial led to 20 percent higher levels of natural erythropoietin (EPO) in the bloodstream.

For comparison, a 2005 study in the British Journal of Sports Medicine found that the initial exposure to altitude training increased EPO by an average of around 50 percent in swimmers, with large individual variability (returning to baseline after a couple of weeks of altitude training), with lots of variation across studies. Given that our bodies produce EPO to increase red blood cell production, and red blood cells transport oxygen that power endurance performance, the ketone study indicated that we could be seeing a supplement that supercharges adaptation and performance.

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.

Before getting to the science, I think it’s important to lay out the stakes. Based on the articles (mixed with a heaping dose of gossip), I can see three different scenarios unfolding over the next 10 years.

One, post-exercise ketones don’t live up to their promise, and this is all a nothingburger. That outcome would please me the most, and we all know that what’s most important in science is my pleasure. If researchers did this type of theoretical analysis on other interventions (i.e. heat training, Vitamin D, lifting, ashwagandha, strides, beta-alanine, doubles, creatine), they could come back with similar findings. We are only talking about a few intervention studies and lots of theory, and future research could have different results. Plus, some critics would already be confident making their judgments as the Supreme Court of Nothingburgerland.

Two, ketones could become a more commonly used supplement with benefits for performance and health (like iron). They are expensive, which isn’t great, but maybe they will help athletes be healthier and faster, with limited side effects. On the flip side, maybe more research indicates tradeoffs that lead to benefit:risk calculations with performance or health. Over email, Dr. Poffé–an author of the review study and a key researcher in this field–says that “studies have shown divergent effects on performance depending on the exercise context and whether you take them before, during or after exercise.” Even if they are beneficial in some contexts, it’s not a simple equation of take ketones = get faster.

The third possibility is that they are banned as an illegal performance enhancer. I have no inside info on whether that’s a possibility, and at first blush, it doesn’t seem likely without some health risks. Dr. Poffé says “I honestly don’t see much of a reason to ban ketones while allowing other ergogenic supplements.”

So, yeah, we’re talking about a wide range of possibilities, which makes sense given the uncertain mechanisms and effects at play. Let’s dig in. (We got even deeper into the nuance on our podcast this week, which you can listen to here.)

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.

Ketone esters, enter stage left. Researchers figured out how to create an ester bond between a ketone body precursor and a ketone body (first in 1978 in rats, but not undergoing human testing until 2012). These ketone esters cause a “rapid and transient increase in ketone bodies,” possibly inducing ketosis. It was as if this evolutionary mechanism honed over millions of years now had a dimmer switch. For the chemistry nerds out there, you can probably guess what oral ingestion of an ester is like—not fun. Companies like HVMN honed the taste over time, and now I’d say that ketone esters taste like a robot’s ass. We can only imagine what they tasted like before.

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.

Perhaps there’s some protocol being used in the cycling peloton that improves acute performance, as the marketing claims indicate. Heck, Tom Evans reportedly took ketone esters on his way to winning Western States, so there must be some benefit for some athletes (or at least neutral impacts), possibly related to perceived effort. Anecdotally, when I tried ketones on a fatigued long run, the lights went out. Thankfully, I had my phone to call the Wuber (when my wife Megan drives to pick me up).

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!).

According to the review, after exercise, circulating ketone bodies are increased. However, any benefits athletes may see from a sustained increase are blunted in advanced athletes practicing good recovery nutrition. Ketone esters “may induce a unique physiological milieu to enhance post-exercise recovery and exercise adaptation as it allows to benefit from the potential beneficial effect of post-exercise ketosis in combination with other nutritional exercise recovery strategies (e.g., carbohydrate-protein recovery drink).” They had me at physiological milieu. Dr. Poffé says that his lab started ketone work in 2016 when “there was already some preliminary data showing that it could help riders during the Tour de France as a recovery aid.”

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-hydroxybutylation 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).

Second, ketones could “enhance the restoration of cellular energy status after exercise” while also blunting AMPK phosphorylation, which could enhance recovery due to its role in cellular stress or decrease adaptation due to its role in mitochondrial biogenesis. I love this one because that maybe-good, maybe-bad uncertainty regarding downregulation of AMPK points out just how little is known about the long-term consequences of post-exercise ketones, particularly in conjunction with other impacts.

Third, ketones alter g-receptor signaling, which “mediate cellular responses to a wide variety of external agents.” Fourth, ketones show anti-inflammation and anti-oxidation properties, which seems good at first glance but could theoretically cause long-term reductions in training adaptations since the inflammation response can spur adaptation. Fifth, ketones may influence neurotransmitter concentrations in the brain, which could profoundly impact perceived exertion (and possibly even mental health, though that’s a topic for another day).

The next cohort of potential adaptations are at the cutting edge of science but still theoretical. Ketones could increase muscle glycogen resynthesis, reduce protein degradation and enhance protein synthesis, spur angiogenesis that leads to more capillaries to supply blood to working muscles, induce favorable changes in muscle mitochondria, and improve sleep quality in athletes who are training hard. You can put those variables together with a 2019 study in the Journal of Physiology, where male athletes completed a three-week overload training block with six days a week of two-a-day training sessions, with one group having post-exercise ketones. That study found higher tolerated training load in the ketone group and improved performance. (The study was the subject of a Letter to the Editor disputing some of the conclusions.)

A 2023 study looked at a similar three-week overload block, validating the findings. They had 18 male athletes complete 10 training sessions per week, with one group taking post-exercise and pre-sleep ketones and the other taking a placebo. The ketone group “increased the number of capillary contacts and the capillary-to-fibre perimeter exchange index by 44 percent and 42 percent,” plus “substantially increased vascular endothelial growth factor and endothelial nitric oxide synthase expression both at the protein and at the mRNA level.” And the money finding: EPO concentrations in the ketone group increased by 26 percent. That study was eye-opening for the possible recovery and adaptation benefits of ketones, and it brings us back to the elephant in the room: potential hematological changes from increased EPO production.

Hematological Changes

In 2018, a study in the Diabetes Care journal found increasing levels of EPO after a ketone body infusion. The authors of the 2023 study that started this article cited this study as part of the impetus for their investigation (read their amazing summary here). We’re seeing similar findings in athletes in the 2023 studies, which found 20 percent and 26 percent increases in EPO production in the ketone groups relative to controls. But the science is not there to make a definitive conclusion.

In the title of this article, I promised uncertain science, and now we are deep in it. First, we don’t know how much this EPO change may impact performance. “Currently,” the review says, “it has not been identified if the observed changes in EPO post-exercise are indeed sufficient to induce an improvement in hemoglobin mass and oxygen transport capacity in humans, and whether these effects are additive to stimuli that are frequently used by athletes to increases EPO such as hypoxia.” It’s possible that these changes don’t correspond to performance benefits.

And get a load of this: “The precise physiological mechanism underlying ketone body-induced upregulation of EPO is currently unknown.” However, based on mouse models, the researchers theorize that it relates to H39K acetylation in kidney cells.

Are Ketones the Future?

There are tons of unanswered questions. How do these types of adaptations change over time? The longest study right now is a few weeks.

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.”

How about aging athletes? Athletes of different levels, with different goals and backgrounds? What’s the right dosage and timing? Would the same responses happen at altitude? Should consumption be periodized? With similar studies, would other interventions lead to similar findings? Should ketones be banned altogether?

I don’t know the answers to those questions, and a lot more studies are needed before I make coaching recommendations other than “be careful” and “keep it simple.”

“Similar to most nutritional supplements,” Dr. Poffé says, “the long term effects (e.g. what occurs if you supplement for multiple years) are not known.” When athletes take ketones, he says instead of taking them chronically, to supplement “during periods of limited recovery opportunities,” like training camps. From a performance perspective, he advises to consider ketones when everything else is sorted out around training, nutrition, and recovery. They are “the final step,” not the first one.

In September, after reading the research, I dusted off that old package of ketones and opened up a serving for myself. Then I threw it in the trash because it seemed like a health hazard after all those years. I ordered a new package and started experimenting with them a couple days a week post-exercise. In October, at the Blue Sky Marathon, I closed the final four miles two minutes faster than last year to set a course record.

That probably had nothing to do with ketones, right? I’m no Olympian, but I train hard. And when looking back on the race and why I could finish so fast while feeling so good, I would be burying my head in the sand not to consider one of the only variables that changed.

I’m not sure what the future holds with post-exercise ketone supplementation. Maybe it’s all snake oil and placebo, with some studies that find physiological anomalies without a demonstration that it fundamentally alters performance trajectories, destined to be covering dust in the pantry of exercise physiology history.

Or maybe we’re seeing the dawn of a revolution in endurance training and performance.

 

Melissa Jefferson-Wooden delivered a sensational performance in Budapest, storming to victory in the women’s 100m at the inaugural World Athletics Ultimate Championship in a breathtaking 10.62 seconds.

The American produced a superb display of acceleration and composure to claim the World Ultimate Championship title while recording the fastest women’s 100m time in the world this year. Her 10.62 mark underlined her exceptional form and placed her firmly at the top of the global sprinting hierarchy.

Jefferson-Wooden controlled the race through the decisive stages and maintained her form all the way to the finish to secure a statement victory against a field packed with championship pedigree. She crossed the line ahead of Olympic champion Julien Alfred, who clocked 10.74 seconds with a -0.2 m/s wind, while Sha’Carri Richardson took third in 10.76.

Women’s 100m Final

1. Melissa Jefferson-Wooden — 10.62

2. Julien Alfred — 10.74 (-0.2 m/s)

3. Sha’Carri Richardson — 10.76

The victory was especially significant given the quality of the opposition. Jefferson-Wooden held her nerve against Alfred and Richardson, two of the most accomplished sprinters of the current generation, to produce the fastest performance in the world this year when it mattered most.

Alfred once again demonstrated her consistency at the highest level by taking silver, while Richardson completed an all-star podium in a race that brought together three of the biggest names in women’s sprinting.

But beyond the time, the title and the celebration, one of the most touching moments came after the race when Jefferson-Wooden embraced her father, Melvin, in an emotional celebration.

Their moment carried a deeply personal meaning. When Melissa was just 17 years old, she donated her stem cells to help her father undergo a bone marrow transplant after he was diagnosed with myelodysplastic syndrome. Years later, the two shared an unforgettable embrace in Budapest after she had become the World Ultimate Champion.

For Jefferson-Wooden, however, the evening was about far more than a medal. It was the culmination of an extraordinary journey, now highlighted by a world-leading 10.62 seconds on one of the biggest stages in athletics.

With the Ultimate Championship title secured and her father by her side, Jefferson-Wooden leaves Budapest with more than being an ultimate champion. She leaves with momentum, confidence and a powerful statement of intent — turning a high-profile showdown into one of the defining sprint performances of her season.

Audrey Werro has added another major title to her extraordinary season, storming to victory in the women’s 800m at the inaugural World Athletics Ultimate Championships in Budapest.

The Swiss star delivered a commanding performance, taking control from the opening gun and refusing to surrender the lead as she powered through an absorbing battle against two of the biggest names in the event.

Werro stopped the clock at 1:55.88 to become the Ultimate Championships 800m champion, producing another statement performance on one of the sport’s newest and most prestigious stages.

Behind her, Great Britain’s Keely Hodgkinson fought her way to second in 1:56.26, while the Netherlands’ Femke Broeders-Bol completed the podium in 1:56.74.

The result once again brought together the same formidable trio that featured on the podium at the European Championships, but Werro again proved to be the athlete who could rise above the challenge when it mattered most.

Her Budapest triumph is the latest chapter in a season that has already included records, a successful Diamond League Trophy defence and European Championship gold. Now, she can add the Ultimate Championships crown to a growing list of accomplishments.

Werro’s consistency has been particularly impressive in an 800m event packed with elite talent. Rather than simply relying on a fast finish, the Swiss athlete showed her authority by taking the initiative from the beginning and maintaining enough strength and composure to hold off Hodgkinson and Broeders-Bol all the way to the line.

The victory also underlined the remarkable depth of the women’s 800m, with three athletes separated by less than a second at the finish. Hodgkinson’s 1:56.26 and Broeders-Bol’s 1:56.74 showed just how fiercely contested the race was, but Werro’s decision to dictate the pace ultimately gave her the decisive advantage.

For Werro, this was more than another medal. It was another opportunity to demonstrate that her rise is no passing moment. On a stage featuring established champions and elite rivals, she once again produced the performance required to claim the biggest prize.

For Hodgkinson, the silver medal adds another major podium finish, while Broeders-Bol once again demonstrated her ability to compete with the very best over two laps.

But the spotlight in Budapest belonged unmistakably to Werro.

With another championship crown secured, the Swiss star has strengthened her claim as the athlete setting the standard in women’s 800m running. This is Audrey Werro’s era — and the rest of the field is chasing.

Busang Collen Kebinatshipi has delivered another sensational performance, storming to victory in the men’s 400m at the inaugural World Athletics Ultimate Championship in Budapest.

The reigning world champion stopped the clock at an astonishing 43.39 seconds, smashing his own Botswana national record and moving to fifth on the world all-time list.

Kebinatshipi produced a commanding finish to pull away from his rivals and secure the Ultimate Championship title. American star Rai Benjamin finished second in 44.15, while Jereem Richards of Trinidad and Tobago completed the podium in 44.23.

 Men’s 400m

1. Busang Collen Kebinatshipi — 43.39 NR

2. Rai Benjamin — 44.15

3. Jereem Richards — 44.23

The performance is even more remarkable considering that Kebinatshipi had already rewritten the Botswana record just one week ago in Brussels, where he ran 43.40. In Budapest, he lowered that mark by another 0.01 seconds to establish a new national record of 43.39.

That improvement has also propelled the 22-year-old into rare territory. His latest time now ranks him fifth fastest in history over 400m, placing him among an extraordinary group of athletes who have broken the 43.40 barrier.

Kebinatshipi's victory also caps an extraordinary season for the Botswana star. After establishing himself as a global champion, he has continued to demonstrate that he belongs among the very best one-lap runners in the world.

And there is a major reward for his historic night in Budapest: Kebinatshipi walks away as the Ultimate Champion and $150,000 richer.

From another national record to a place among the five fastest 400m runners ever, Kebinatshipi has turned an already remarkable season into something truly special.

Botswana has its latest sprinting superstar — and Kebinatshipi is showing that his ceiling may be even higher than anyone imagined. 

Marileidy Paulino once again proved why she is the undisputed queen of the one-lap event, powering to victory in the women’s 400m at the inaugural World Athletics Ultimate Championship in Budapest.

The Dominican Republic superstar produced a sensational 49.07 seconds to claim gold, pulling decisively away in the final straight and holding off a fiercely competitive field to extend her remarkable unbeaten run.

Paulino delivered her trademark combination of controlled speed and devastating finishing strength. She remained firmly in contention through the opening stages before unleashing her decisive move down the home straight, where she quickly opened a gap on her closest challengers.

Norway’s Henriette Jæger mounted a strong challenge but could not match Paulino’s finishing speed, crossing the line second in an impressive 49.28. Jamaica’s Nickisha Pryce completed the podium after clocking 49.56, ensuring that three of the world’s leading 400m talents occupied the medals.

The result once again underlined Paulino’s extraordinary consistency at the highest level. She entered Budapest as the world leader after running 48.48 in Paris in June, a performance that also set a Diamond League record. She subsequently remained unbeaten throughout her Diamond League campaign, closing the circuit with a meeting-record 48.64 in Brussels.

Budapest has also become a special venue in Paulino’s career. Three years ago, at the same National Athletics Centre, she captured her first individual world title, marking the beginning of another dominant chapter in her career. She later added Olympic gold in Paris in 2024, further establishing herself among the defining 400m athletes of her generation.

The inaugural World Athletics Ultimate Championship has brought together the sport’s biggest stars in a new winner-takes-the-spotlight format, with Olympic and world champions, Diamond League winners and leading performers competing for ultimate honours.

For Paulino, the occasion once again ended with Ultimate Crown on her arms.

With 49.07 seconds, she did more than win another major 400m title. She delivered another statement of authority, powering through the final straight with the confidence and speed that have made her one of the most dominant figures in modern women’s athletics.

Marileidy Paulino remains unbeaten, remains relentless and, once again, remains the queen of the one lap.

Jakob Ingebrigtsen has made a major decision regarding the remainder of his World Athletics Ultimate Championship campaign, confirming that he will withdraw from the men’s 1500m in Budapest despite producing a sensational performance to win the 5,000m title.

The Norwegian superstar stormed to victory in the inaugural Ultimate Championship 5,000m on Friday night, clocking a season-best 12:59.24 and delivering a devastating finishing kick to defeat Olympic 5,000m champion Cole Hocker and American Parker Wolfe.

Ingebrigtsen’s final 100 metres was arguably the defining moment of the race. The Olympic champion produced a remarkable 12.60-second closing 100m, powering away from the field to secure the $150,000 winner’s prize and underline just how far his fitness has progressed since returning from Achilles surgery.

The victory was particularly significant after what has been an extremely difficult period for the 25-year-old. Earlier in the season, Ingebrigtsen faced serious uncertainty over whether he would even be able to compete at the highest level again. His return has gradually gathered momentum, and his performance in Budapest offered perhaps the clearest indication yet that the Norwegian is rediscovering his formidable racing ability.

But rather than risk pushing his recovering body further, Ingebrigtsen has now opted to step away from the 1500m.

The decision means the highly anticipated showdown with British rival Josh Kerr will not take place in Budapest after all. The two stars had been expected to renew one of the biggest rivalries in modern middle-distance running in the 1500m final.

Instead, Ingebrigtsen is looking beyond the immediate opportunity and towards the bigger picture.

“I’m thinking about 2027… Fitness cannot be faked,” the Norwegian said, signalling that protecting his long-term condition has become more important than chasing another major victory only days after his return to peak-level competition.

The decision comes just one week after an emotionally charged Diamond League Final in Brussels, where Ingebrigtsen finished fourth in the 1500m behind Australia’s Cameron Myers, Kenya’s Phanuel Kipkosgei Koech and American Ethan Strand.

After that race, Ingebrigtsen delivered a fiery assessment of his rivals and questioned the tactics surrounding the pacemaking, particularly involving Hocker. He later acknowledged that there had been “a little too much adrenaline and emotion” when microphones were placed in front of him immediately after the race.

Yet his latest decision shows that beneath the emotion and competitive intensity lies a longer-term strategy.

Ingebrigtsen has already demonstrated that he can compete at an elite level again. His 12:59.24 in Budapest was not simply a victory — it was a statement that the Norwegian remains capable of producing a world-class finish even after months of injury rehabilitation.

Now, however, he is choosing not to gamble with that progress.

For a runner who has spent much of the year fighting his way back from injury, another 1500m race could have offered enormous rewards but also carried unnecessary risk. By withdrawing, Ingebrigtsen is effectively prioritising longevity over one more opportunity for immediate glory.

His message is clear: the comeback is underway, but it will not be rushed.

The 5,000m victory has given Ingebrigtsen confidence, momentum and perhaps, most importantly, proof that his body can once again handle elite competition.

Now comes the harder part — knowing when to stop.

With 2027 already firmly in his sights, the Norwegian has chosen recovery over risk. And after everything he has endured, that could ultimately prove to be one of the most important decisions of his comeback.

Jakob Ingebrigtsen is not walking away from the sport. He is protecting his future in it.