On January 29, the Dutch Anti-Doping Authority declared that the use of ketone supplements was a “grey area.” They said that they didn’t feel “comfortable” with the professional cycling team Jumbo-Visma using them.
But in the last couple of years, ketone supplements have been on the rise. They’re popular not only among professionals but also among recreational athletes although not everyone is keen to admit to using them. The main purported benefits are gains in performance and faster recovery rates. Is that true? What are ketones exactly? And is it safe to use them?
The first distinction that needs to be made is between endogenous (produced by the body) and exogenous (that have an external origin) ketones. A second distinction is within the endogenous ketones themselves, differentiating a ketone (or a ketone group) from a ketone body.
Endogenous Ketone Bodies
“A ketone is something that has a carbonyl group [a carbon atom double-bonded to an oxygen atom C=O] with two hydrogen-carbon atoms,” said Asker Jeukendrup, sports nutrition scientist and head of nutrition for the team Jumbo-Visma (he is also a six–time Kona finisher). “But when people talk about ketones, they usually mean ketone bodies, which are the water-soluble molecules containing the ketone group.”
Ketone bodies are a by-product of fat metabolism and are produced mostly in the liver from fatty acids. The production of ketone bodies can happen in several ways: through exercise, after a period of low food intake, carbohydrate-restrictive diets, or starvation, among others. In these situations, your body tries to get energy through lipolysis, which is the breakdown of triglycerides and adipose tissue (the primary fuel store of the body) into glycerol and fatty acids. And when lipolysis is high, some ketone bodies will be produced as well.
“It is something that your body automatically produces when fatty acid levels go up, and you can’t prevent it, it just happens, and it happens mostly in the liver,” Jeukendrup said.
The body produces three types of ketone bodies: acetoacetate (produced in the liver), beta-hydroxybutyrate (converted from acetoacetate), and acetone. Beta-hydroxybutyrate is the most common one, and the most important for fuel delivery into the muscles.
“The most important role of ketone bodies is during starvation when there is a shortage of glucose,” Jeukendrup said. “In that situation, your ketone bodies go up because glucose, which is normally the most important fuel for the brain, is not available anymore, so your brain needs a different fuel.”
That is why the endogenous ketone bodies are often referred to as ”starvation fuel.”
Although the science behind endogenous ketone groups and ketone bodies is well established, to recreate them artificially took time and money—including even an investment from the U.S. Army.
“We started to work on ketones in the early 1990s in Oxford,” says Kieran Clark, Professor of Physiological Biochemistry at the University of Oxford and one of the inventors of the technology behind ketone supplements. “We showed that ketones increase cardiac efficiency, meaning you get more work done per unit of oxygen. Then, in 2003, during the war in Iraq, the U.S. Army found that people were losing physical performance and cognitive functioning in the battlefield.”
What the Army was looking for was a more efficient food to give to the soldiers and improve their performance. And that’s when DARPA (Defense Advanced Research Projects Agency), responsible for the development of emerging technologies for military use, got in touch with Clark and her team.
“DARPA awarded 10 million dollars to see if we could invent a new food group based on ketone metabolism,” Clark said. “And so we spent from 2003 until now working on this, and working out whether it would work. It took us three years to figure out what we needed, and that was ketone ester. We went for one particular one that we call DeltaG, and it works.”
Ketone esters are one of the two types of ketone body supplements you can find on the market. The other type of ketone body supplements are called ketone salts, and they’re ketone bodies (usually beta-hydroxybutyrate) combined with sodium, magnesium, or potassium. Although more affordable than the esters, ketone salts are more difficult to tolerate for the stomach. The ketone esters, on the other hand, combine a ketone body with another ketone body, and they’re manufactured to give fewer stomach problems. Their downside is their price: a bottle of 25mL (less than an ounce) can cost around $40.
One of the companies producing the esters in a liquid form (HVMN) contacted Clark in 2016. “We had published a study paper in cell metabolism,” she said. “HVMN had been going for about a year selling supplements online. They contacted us and asked for the license to sell. But what we did was a collaborative effort [Clark is still an advisor for the brand], because it was the first time on the market.”
The question remains: Do ketones improve performances and help athletes to recover faster? And are they safe?
“They are acid, so when you take ketones, you make your blood more acid,” said Dan Lorang, coach of IM World Champions Jan Frodeno and Anne Haug, and Head of Performance for the pro cycling team BORA-Hansgrohe. “And that is something that generally you’d never do (to drink a composition that makes your body acid).”
That’s only the first problem, believes Lorang. The other, more cogent issue is the lack of strong evidence showing that ketones could actually benefit performance and recovery. “If we are honest, there are some studies,” he says, “but studies about performance, and especially for long-time performances, there is not so much at the moment. We did some internal studies, and we were not so convinced that using ketones for cycling would be a good option.”
Lorang and team BORA-Hansgrohe have looked mostly into the benefits for recovery of ketones, while Jeukendrup and Jumbo—who are using them—are taking the opportunity to test them in both areas. But that there is a lack of evidence for both is indisputable.
“We need to talk about potential benefits because at this point, we don’t know if they do anything for performance or recovery,” Jeukendrup said. “The research on both performance gains and recovery is far from conclusive. On the performance side, there are two studies: one shows positive effects, one shows negative effects (decreased performance). It’s still early days, and I think in some of those studies, the dosing was not optimal, and in other studies, they didn’t look at the right type of exercise.”
Nevertheless, Jeukendrup is convinced that, at least, they are safe. “For some reason, the discussion seems to focus on ketones and potential negative effects, where I find it very difficult to see how ketones could have negative effects long term, especially being mainly a derivative of fatty acids and being used completely as a fuel during exercise.”
While the world’s health concerns have changed over the last months, ketones are still dividing those in the endurance world. Team Jumbo-Visma’s rider Tom Dumoulin (winner of the 2017 Giro d’Italia) has recently quit the group “Mouvement Pour un Cyclisme Crédible” because of their stance against ketones. The purpose of the MPCC is “to defend the idea of clean cycling based on notions of transparency, responsibility, and mobilization of its members”—according to their website—and they recommend not to use ketones “given the side effects and the uncertainty of the long term effects.”
Dumoulin, who left the MPCC also because they allowed the Paris-Nice cycling race to go ahead in the midst of the Covid-19 outbreak in France, said that “they came up with the story that the use of ketones is very dangerous. I thought that was a very hypocritical attitude of the MPCC. Our team uses ketones, so it’s a bit hypocritical for me to be a member of the MPCC. Those two things together moved me to unsubscribe.”