Are Ketones changing pro cycling?

The recent Science and Cycling Conference in Belgium included a 2021 research into the miracle (legal) performance aid that are ketones. Rouleur was there to absorb and assimilate the latest findings… 

“I wonder about the peloton, but I’m only saying what people are seeing. Not everyone has the same restrictions on certain products like ketones. I am part of a team that has made commitments, as have others. But the whole peloton is not like us.” Groupama-FDJ’s Arnaud Démare recent interview with French daily Le Parisien once again shone the spotlight on ketone use in professional cycling, a subject that seemingly pokes its head above the parapet every July at the Tour de France before retreating to the shadows for another 11 months and one week.

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Démare’s team are one of 10 signed up to the Movement for Credible Cycling (MPCC), the organisation set up in 2007 to promote the idea of clean cycling. The MPCC’s stance on the ‘legal’ wonder drug is ‘to commit to the idea of non-use’, the lack of research into its long-term effects one of the MPCC’s major concerns. (Arguably their cost is seen as divisive, too, but we’ll come on to that.) Sprinter Démare’s comments went live in November, the 30-year-old reflecting that, in his eyes, the general pace of the peloton has cranked up in 2021. How much of that’s down to perception, reality or ketones remains to be seen. Démare at the 2021 Vuelta, sprinting for the victory on stage 5. Photo: Getty Images

A recent presentation by Peter Hespel, professor and head of the athletic performance centre at Leuven University, Belgium, will only rile Démare further, creating further divisions in a peloton that his teammate Thibaut Pinot commented now “operates at two speeds”. Hespel’s engaging seminar took place at the Science and Cycling Conference, held in Leuven just prior to the World Road Championships in Flanders. An exclusive audience comprised WorldTour staff, academics and this sport-science writer, who listened attentively to Hespel’s latest findings. Faster, higher stronger, it seems, is no longer the sole domain of the Olympic motto…

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Acidity equals impairment

“At this conference two years ago, I reported that ketones didn’t improve cycling performance during a race. Why not?” asks Hespel, who regularly works at Leuven’s Bakala Academy, the same place that Deceuninck-Quick Step put their minions through physiological testing. “It’s because ketone-ester ingestion lowers the pH of your blood. Making your blood more acidic and decreasing the alkaline buffer isn’t a good situation to be in during the final stages of a race.”

That’s because when you crank up the power, you start to endure ‘the burn’. This accumulating pain derives from high-intensity bursts generating ever-higher levels of lactic acid. To a point, lactate can be recycled in the muscle cells and ultimately reused as energy. But once you tip over your threshold, lactate spills out into your blood, drops those pH levels and, ultimately, does the same to power output and performance. At the 2019 conference, Hespel instead focused on the recovery benefits of ketones – still a huge win, especially for GrandTour riders. We’ll delve beneath that physiological lid shortly. But let’s stay present. Back to Hespel…

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Riders' ability to recover is paramount to perform in the third week of a Grand Tour. Tadej Pogačar (here, to the left) is claimed to have a above-average ability to recover from hard efforts one day to the next. Photo: Alex Whitehead/SWpix.com

“Because of that acidity issue is why we recently undertook another study into ketones and cycling performance, where we added bicarbonate to the mix. The idea was that this would reduce the decrease in blood pH. It was quite successful.”

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BICARBONATE BONUS

Hespel and his team had nine well-trained cyclists ride for 3hrs at sub-maximal intermittent pace followed by a 15-minute time-trial, all finished off by a 1-min sprint at 175% of lactate threshold. It’s a pacing template often utilised by Hespel to reflect the demands of a professional day in the saddle. The nine cyclists undertook the lab-based ride four times under these four conditions: after receiving 65g ketone ester; consuming 300mg/kg bodyweight of sodium bicarbonate; the ketone and sodium bicarbonate dose combined; or a placebo drink. For each of the four rides, they took these supplements before and during the ride, plus they’d also consume 60g carbohydrates per hour.

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The results? “When it came to power output, bicarbonate alone and ketones alone did not improve things,” says Hespel. “But the combination of ketones and sodium bicarbonate resulted in power-output improvements of between 10 and 30 watts in the time-trial across the board. That’s significant; in fact, it was about a 5% increase.”


In a clinical trial, a research has showed that a mix of ketones and sodium carbonate has improved a TT performance by 5%. Photo: Alex Whitehead/SWpix.com

That 5% boost is huge at the ‘performance’ recreational level, of which the nine subjects nestled in. Even if that full 5% doesn’t carry over to the WorldTour, half of that – even less – could be the difference between victory and defeat. And, reassuringly, this performance improvement didn’t come at the expense of gastro problems, of which sodium-bicarbonate ingestion is often linked. “Just note that we also experimented with ketones and bicarbonate during the warm-up of a standalone 15-min time-trial and we actually saw a small drop in power output, so consuming ketones before a short, 15-min effort isn’t a good idea,” warns Hespel. Key, it seems, is that longer intermittent-intensity efforts see ketones spare precious muscle glycogen for the end-game 15-min time-trial while the bicarbonate buffers the blood and so widens the acidic bandwidth of digging deep and sustaining a higher power output.

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So, if timed correctly says Hespel, ketone ingestion plus sodium carbonate elevates in-race performance. But that’s not all from the Belgian’s most recent research. “We also found that ingestion of ketone esters has an anti-diuretic effect,” he says. “We examined urine volume produced during 3.5hr races and it dropped from 1,400ml to 1,200ml.”

During a one-day race, this would have little effect on performance. But taken over three weeks of a GrandTour, especially an often brutally hot one like the Vuelta a Espana, and you can see how the hydrating benefits of maintaining blood viscosity and the catalogue of performance benefits that brings, including sustaining a high power output and aerobic capacity, would create further disharmony between the haves (non-MPCC teams Jumbo-Visma and Deceuninck-Quick Step are reported users) and the have-nots (MPCC teams like Démare’s Groupama-FDJ plus AG2R Citroen,  Bora-Hansgrohe, Cofidis, EF Education-Nippo, Intermarché Wanty Gobert, Israel Start-Up Nation, Lotto-Soudal, Qhubeka NextHash and DSM).

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Another hot day at the 2021 Vuelta. Photo: Getty Images

It’s results like these that had the MPCC submitting a request to the World Anti-Doping Agency earlier this year to investigate what many call a ‘miracle drink’, to investigate their benefits and, more importantly, any long-term issues. Proponents of ketones would argue long-term issues is a non-issue as ketones are naturally produced in the body.

KETONES VS KETOGENIC DIET

Which brings us conveniently onto the difference between ketones in the body and those taken orally (or, in more scientific terms, exogenously). Ketone bodies are produced from fatty acids by the liver mitochondria during long periods of energy deficiency like fasting and starvation. They’re your final back-up energy system, if you will. “In my eyes, following a ketogenic diet is the ideal way to impair performance,” says Hespel. “Okay, it’s possibly fine for conditioning work in early winter to stimulate fat metabolism. But this really shouldn’t be for long.”

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Simply put, fasting and high-intensity cycling efforts aren’t happy bedfellows. You just don’t have the spare glycogen, or efficiency of glycolysis (glucose breakdown), to generate high levels of power. But, it’s argued, the picture changes when ketone bodies are taken by mouth. Ketone bodies seem to inhibit glycolytic flux (in essence, glycogen breakdown) and, as stated earlier, spare muscle-glycogen reserves, which commonly max out at around 500-600g, without harming hard efforts. You tap into this extra energy source without having to starve yourself  that, on the face of it, is an easy performance win.
A good fat metabolism is very important in endurance sports, but in cycling, to perform high-intensity efforts at the end of a Grand Tour still require a substantial glycolytic capacity (energy coming form carbohydrates). Photo: Getty Images 

The problem is that as researcher Pedro L Valenzuela and his team concluded in their paper ‘Perspective: ketone supplementation in sports – does it work?’, published in March in the journal Advances in Nutrition, “There is a biological rationale to support a potential ergogenic effect of oral ketone supplementation, especially in its acute form. However, evidence to date shows no clear physiological or performance effects with acute supplementation.” 

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In short, until Hespel’s recent bicarbonate work, there was little evidence of ketones improving performance. On the day, that is. You see, Hespel’s previous ground-breaking work into ketones, presented at that 2019 Science and Cycling Conference, revealed that ketones come into their own between stages not during. Hespel reflected on these previous findings in Leuven.

KEY IS RECOVERY

“We know that the Tour de France puts riders into a catabolic state (muscle breakdown). So we had trained subjects complete a three-week training programme. They trained twice a day. It was brutal and by the end of week three they were almost dead, physically and mentally!”

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“After every training session, they received a dose of ketones. One of the major findings was that if you looked at the placebo group, despite training load increasing by 30% over the three weeks, energy intake remained constant. They didn’t increase energy intake to compensate for the higher energy expenditure. However, the ketone group increased energy intake without giving them any recommendations for doing so.”
Grand Tour put riders into a catabolic states, where muscle are broke down. Consuming more calories can help reducing this trend, and ketones may help in getting more energy in. Photo: Getty Images.

This is important as insufficient calorie intake and catabolic exercise results in health issues like upper-respiratory infections during the third week of a GrandTour, plus performance decrements like reduced power output. Then there are the mood swings that can be off the scale. Key to this caloric chasm between the two groups (4,200cals daily versus 3,500cals) were respective hormonal profiles of the subjects, specifically the stress-induced hormone GDF-15, which is involved in appetite regulation. In a GrandTour, the general pattern is a gradual increase in GDF-15 concentration that blunts the desire to eat. With ketones, this increase was suppressed. Vis-a-vis, the greater calorie intake and the potential for improved performance.

“We also observed that the subjects slept better after taking ketones,” Hespel continues. “We think this was down to slightly lower night-time levels of epinephrine (adrenaline). We’re looking into this further at the moment and will have a paper out soon.”

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As recovery’s deemed a major factor in peaking at a GrandTour – not surprising over the course of 21 stages where you’re burning through up to 8,500cals a day – ketones’ potential as a sleep agent could be reason enough to use it. It certainly helped Hespel’s lab rats fend off the chances of falling ill, as ketone ingestion suppressed the heart-rate fall-off-the-cliff associated with overtraining. “In the control group, resting heart rate dropped by 7-8bpm over three weeks. At sub-maximal levels, this dropped by 15pm. At maximal intensity, we’re talking 20bpm. Everyone involved in a GrandTour knows this is a typical GrandTour situation. Surprisingly, in the ketone group there was no drop in resting heart rate, while the drop at sub-maximal and maximal levels was much smaller. Ketones affected the autonomic nervous system, which I believe is the most important effect of ketones on performance.”

This recalibration of the neural system, dampening down markers that impair performance, is attracting the attention of the WorldTour teams’ support staff and riders. As is angiogenesis. This is the formation of new blood vessels. During Hespel and his team’s exhaustive studies, they took muscle biopsies – yes, extracting muscle from the active thigh – that revealed a 14% increase in capillaries in the ketone group compared to the placebo group. “We hypothesise that ketones stimulate a protein called VEGF (vascular endothelial growth factor), which is an important factor in the proliferation of capillaries of muscle.” The greater potential to deliver oxygen to working muscles while taking oxygen-poor blood back to the heart is a clear win for the endurance cyclist.
One study suggests that ketones may stimulate the proliferation of capillaries of muscle. A good thing when you need more oxygen. Photo: Getty Images.

Apart from the occasional stomach complaint and despite the protestations of the MPCC, Hespel believes all of these benefits come without detriment to health. But, he continues, these benefits should predominantly be tapped into by the peak of the performance pyramid; for those whose bodies regular descend into a catabolic state and who’ve ticked off other performance pillars. We’re talking consistent training, healthy eating and premium gear.

ESTERS VERSUS SALTS

They should also be tapped into only if the right product is sourced. “We use ketone esters in our research as we’re looking to raise blood-ketone concentration to over 3mmol per litre of blood. Any less than that, which includes levels seen on a ketogenic diet, and any effect is much smaller.”

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Hespel rarely uses ketone salts as, unlike purer ketone esters, salts are ketone bodies bound to a mineral like calcium, sodium or magnesium. Naturally, this is a diluter version, again dampening the effect.

“There are many ketone supplements on the market where the concentrations aren’t enough to enjoy an ergogenic boost,” says Hespel. “Take the KE1 ester and salt from Ketone Aid. This has less than 5g of ketone ester in. I don’t think there’s any scientific evidence that this nominal amount improves performance. In our studies, we use the KE4 version. This contains at least 25g of D-Beta Hydroxybutyrate [type of ketone] per serving, so much more beneficial.”Team Jumbo-Visma is among the teams allegedly using ketones. But despite the gains and the investment, the yellow jersey seems to evade the dutch team. Photo: Getty Images. 

The reason for the ketone disparity boils down to cost. While a single serving of the KE1 costs $7.99 per serving, a 59ml single-serve bottle of G Ketone Performance, created by endogenous ketones founder Professor Kieran Clarke of Oxford University and containing 25g of active ingredient, costs $117 for a pack of three. As it’s recommended to take one bottle 30mins before exercise followed by a serving every 2hrs, you can see how its cost is prohibitive to the majority. “The cost will eventually come down but it’s expensive to produce legitimate ketone products,” says Hespel.

It’s certainly dropped from the original prototype cost of £2,000 per litre when Clarke first started making it in the lab, but a degree of basic mathematics leads to speculation that the MPCC’s complaints might not solely be health-based. At a conservative estimate, say a Tour rider consumes three bottles of G Ketone Performance a day. Ignoring bulk discount, that’s $117 per rider or $936 for the team of eight. Multiply that by 21 stages and you’re talking $19,656 to enjoy optimum fuelling to Paris. That’s a small fiscal hit for a team like Jumbo-Visma. Less so for a team like Qhubeka NextHash. And that’s just one GrandTour. Throw in training and  other events and arguably that’s a competitive advantage that’s against the spirit of fair play. Then again, whenever has professional cycling been about fair play.  

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So, what of the future? Further research into its performance benefits and side-effects is a good start, of course, and an area that the MPCC’s hoping WADA is fervently looking in to. It’ll be interesting to see how the situation unfolds and could be a watershed moment for the MPCC’s authority, if not future survival. Where does the movement go, for instance, if WADA continues to allow ketones? Will the MPCC be satisfied of the outcome? Will they continue to advise their members to endure what’s perceived as a competitive disadvantage, especially when further studies show ketones maintain mental alertness in an exhaustive state and so could be regarded as a safety supplement? Time will tell where this ‘miracle’ legal drug fits into the modern-day peloton. But one thing that must change to ensure ketone equanimity is its taste. “It’s disgusting,” says Hespel, “but if you can cope with that, you could enjoy the benefits.”

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