The 111th edition of the world famous Tour de France begins on June 29 in Florence, Italy. This year, the grueling 21-stage cycling race takes place over 2,175 miles (3,500 kilometers) in Italy and France.
Slovenian rider Tadej Pogacar of UAE Team Emirates is considered the favorite to win after winning the yellow jersey in 2020 and 2021 and finishing second in the last two years. Part of Pogachar’s success comes down to Inigo San Milanwho coached the cycling champion for years as head of performance for the UAE Emirates team.
But besides being an expert in sports performance, San Milan has a second passion: he is looking for new ways to beat cancer.
As an assistant professor of medicine at the University of Colorado School of Medicine, San Milan studied the interactions between cancer and lactate, a byproduct released by cells during regular metabolism—and specifically by muscle cells during intense exercise such as cycling. While the bodies of elite athletes easily flush this lactate out of their systems, in people with cancer, tumors release massive amounts of lactate, which then sticks around, fueling the cancer. San Millán is researching how to break this vicious cycle.
Live Science spoke with San Millán about his dual life as a sports performance coach and cancer researcher, discussing his work in both realms.
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James Witts: What does the role of Head of Performance in Elite Sport involve?
Inigo San Milan: Years ago you had to do a little bit of everything. Now you have the resources to hire excellent trainers, nutritionists, biomechanics, psychologists… and then it’s a matter of coordinating and integrating them as seamlessly and productively as possible.
I have been very fortunate over the past 25 years to work in a variety of sports. … If you focus on one sport, you can be blinded by developments elsewhere. However, cycling is perhaps the most advanced sport when it comes to understanding an athlete.
JW: What does this understanding consist of?
ISMS: You need to understand the physiology and metabolism of the rider before moving into the fields of nutrition, biomechanics and training. You then establish goals for the season and monitor the riders during a race.
Everyone responds differently to training. Someone like Pogachar can take a heavy load. But if we give his training plan to someone else, it could kill them. You need to understand who you are working with.
JW: Why do you go to altitude to train?
ISMS: There are two key adaptations to training at altitude that then carry over to racing at both sea level and in the mountains. The first is around increasing your hematological values, especially your red blood cells. Red blood cells are the taxi of oxygen, while hemoglobin [acts as the] the seats where the oxygen is located. At altitude, the thinner air forces your body to produce more red blood cells.
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Because one gram of hemoglobin carries about 1.36 milliliters [0.05 fluid ounces] oxygen, then you can generate better results at the next race. You also have an angiogenic response, which is the formation of new blood vessels and again helps transport oxygen to the working muscles.
JW: What do you measure physiologically when it comes to riders like Pogačar?
ISMS: First, you establish the physiological and metabolic parameters of each athlete to prescribe the most accurate and progressive training program. You have to evaluate the athlete. Do we have a Ferrari or a Fiat? You identify their weaknesses and strengths. In my system factors such as lactate variation, lactate metabolism, fat metabolism and carbohydrate metabolism are very important. By evaluating these parameters, it is possible to create a suitable individual training program for an athlete. And all this is achieved thanks to metabolomics [the study of chemical processes involving metabolites, small molecules made during or used for cell metabolism].
JW: Tell us about your metabolomic work in cycling.
ISMS: With a few drops of blood we can analyze between 1000 and 2000 parameters of the body and thus understand how the body functions at a level never seen before in cycling. Mitochondrial function, cellular oxidation, glycolysis, anaerobic capacity, catabolic capacity… We can identify the differences between cyclists and see what makes a truly elite athlete.
We had Pogachar and 20 other UAE Team Emirates athletes undertake a 15-minute warm-up at a low intensity of 2 watts per kilogram [w/kg] of body weight. The intensity is increased by 0.5 w/kg every 10 minutes. Power output, heart rate and lactate were measured throughout the test, including at the end when the riders were exhausted. We found that [the] the lactate clearing capacity of the stronger riders was amazing.
JW: What does “lactate clearance capacity” mean?
ISMS: When a rider sprints or climbs, they generate a huge amount of lactate. We call this “high glycolytic”. The problem is, the more your muscles use glucose, the more lactate is produced because it’s a byproduct of glucose use. This lactate builds up and the hydrogen ions bound to the lactate increase the acidosis [a build-up of acid] of the muscle microenvironment, reducing contractile capacity and power output. Therefore, it is extremely important to clear this lactate.
One of the measurements I take is for lactate to see how quickly lactate levels recover after hard effort. With Pogachar, I noticed that his lactate recovery capacity was huge. Its levels return to normal after 2 minutes, while some riders need 20 minutes. This is a big advantage when attacking a climb as you can keep attacking. World-class athletes have been shown to produce more because they have a higher glycolytic capacity and can clear it more efficiently. Well, Pogačar has one of the greatest glycolytic capacities I have ever seen.
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JW: When did you start to see your metabolomics work pay off in competitions?
ISMS: I remember the 2019 Vuelta a España. Many thought we were crazy to have a 20-year-old [Pogačar] leads the team in its first three-week stage race. Many said he was there for an experiment and that in 10 or 12 days he would go home.
But we knew otherwise. We knew from his blood parameters that he could not only recover quickly between stage efforts, but also between stages. No one improves during a race of this length, but it’s about reducing performance degradation. And that’s what Pogachar managed, and why the three stage wins he won came in the second and third weeks.
JW: Your job in sports is just one hat you wear. You are also involved in cancer research. Tell us about it, please.
ISMS: We can see with riders like Pogachar how well they clear the elbow. Well, through my clinical work we know this crab burns glucose, creating huge amounts of lactate. But unlike exercise, this lactate is not cleared. This is bad for the cell and is a key driver of carcinogenesis [the formation of cancer].
Our work aims to reprogram the metabolism of cancer patients by, among many possibilities, blocking the enzyme that produces lactate. We have a new study under review where we have silenced the enzyme that produces lactate, LDHA, and we can see that after 6 hours EGFR is not expressed [made by the cells]. EGFR is a protein mutated in many types of cancer and also the “mother” of key signaling pathways that are mutated in most types of cancer that increase cell growth and proliferation of cancer cells. By inhibiting the production of lactate, we can inhibit the production of EGFR, and so we should be able to inhibit the signaling pathway cascade initiated by EGFR.
We are proving that this is a new door to better understanding cancer and to someday beating it.
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JW: Tell us about the importance of mitochondria in both athletic performance and general health.
ISMS: When training a rider, you are looking for both central and local adaptations. Central adaptations are cardiorespiratory adaptations, so things like increased blood volume, decreased heart rate, increased sweating response… It’s important, but at this level, the local adaptations at the cellular level are the game changers. Things like mitochondrial efficiency. [Mitochondria are small structures in cells that make chemical energy.]
It’s not about how much oxygen you can deliver to the cells, it’s about how well that oxygen is used by the cell and how different fuels and substrates are used by the mitochondria. Someone like Pogachar can burn fat at a high intensity in their Mitochondrial Furnace, which is a big advantage since you have huge fat stores. Really hard effort requires a greater use of carbohydrates, but their stores are frugal in the body – so if you can ride hard using fat stores, well, I think that’s where the great cyclists differ from the good ones.
When we talk about general health… Cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes, and even Alzheimer’s disease, which will soon be called “type 3 diabetes,” shows one thing in common: mitochondrial dysfunction. They can’t burn glucose efficiently, which means glucose builds up, leading to insulin resistance and eventually type 2 diabetes. The same things happen with fat. You can’t burn it properly, it accumulates, leads to inflammatory reactions and eventually cardiovascular disease, weight gain.
JW: Finally, apart from your desire to win the Tour de France in 2024, what does the future hold?
ISMS: Unfortunately, I recently closed my US lab. It was heartbreaking because I wasn’t able to finish all the experiments I had started, experiments where we had made important discoveries in the hope of opening new doors in terms of cancer treatment or at least a better understanding of its metabolism.
Fortunately, a renowned cancer researcher at the best research institute in the Basque Country has the technology and resources to help me complete my experiments. Now with time and without much haste I should be able to finalize my experiments and contribute to the opening of new doors.
Editor’s note: This interview has been shortened and edited for clarity.
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