Metabolomics: the science behind a Tour de France winner

A CU Anschutz research team, experts in athletes’ baseline metabolic profiles and how these physiologies change during competition, are helping guide some of the world’s elite athletes to their best performances, including the recent Tour de France winner. Their understanding of the metabolic underpinnings of top athletes has implications for improved treatments of disease, including cancer, diabetes and Alzheimer’s.

To say cycling enthusiasts were stunned by the Tour de France performance of rookie rider Tadej Pogačar might be an understatement. Jaws dropped as the 21-year-old Slovenian, the second-youngest rider to ever win the Tour, ascended the final 5.9-kilometer final climb of the time trial and secured the yellow jersey.

Pogačar’s victory, however, did not surprise Iñigo San Millán, PhD, an assistant professor in the Division of Endocrinology, Metabolism and Diabetes at the University of Colorado School of Medicine (SOM). His team at the SOM had already employed science – specifically the measurement of hundreds of thousands of metabolites in Pogačar’s – and knew the young cyclist was on another level.

“Last year he was third in the Tour of Spain and won three stages there,” said San Millán, who is Director of Performance for Team United Arab Emirates (UAE) and Pogačar’s coach. “He was the youngest guy ever doing that, and this year he was stronger. For sure, he was a contender for the Tour (de France), and that’s what we had in mind.”

Going into the stage-20 time trial, the penultimate day of the three-week Tour de France, Pogačar trailed his compatriot, Primoz Roglic, by 57 seconds. Pogačar’s time trial vaulted him past Roglic by 59 seconds.

In interviews following the time trial, which included grades of 8.5%, Pogačar told the media: “I guess my genetics are really good. I have to thank my parents, probably.”

San Millán may agree, but he also knows that being able to investigate Pogačar’s whole blood responses to elite-level exercise pays big dividends. San Millán, a former competitive cyclist, knew from Pogačar’s physiological measurements that the cyclist would benefit from staying off his bike for a week in May as he was already too fit and the Tour was still three months away.

Such insight is important because the Tour de France is considered the world’s most physically demanding race. “We’re talking about 5,000 to 9,000 calories of expenditure a day for 21 days,” San Millán said. “That’s like playing 10 football games each day for 21 days in a row. That’s why you need to have a very good recovery capacity.”

Metabolomics as difference-makers

A new study performed by San Millán’s team, including Angelo D’Alessandro, PhD, an associate professor and director of the Metabolomics Core of the SOM, Department of Biochemistry and Molecular Genetics, and CU Cancer Center member, and Travis Nemkov, PhD, a Postdoctoral Fellow in biochemistry and molecular genetics and senior author on the study, examined the metabolomics of endurance capacity in 20 elite professional cyclists.

The study offers insight into the exceptional ability of team UAE riders – the team of Pogačar, now age 22 – to efficiently burn fuel and recover. The team collected blood samples from the cyclists and measured their metabolic parameters relevant to mitochondrial function, as well as use of carbohydrates, fats and proteins.

While in the current study they established the athletes’ baseline metabolic profiles and measured how these physiologies changed during a short, intense cycling test, CU researchers are also wrapping up a similar study on these cyclists’ physiology during the course of a multi-stage world tour. “From this information, we try to define what the upper limits of human physiology are – what’s the gold standard?” Nemkov said.

When the team compared the metabolic measurements of the various cyclists, the signature of a champion in the making stood out. “As the stages (in a race) become harder and harder, racers accumulate a specific subset of metabolites,” D’Alessandro said. “Elite riders have a metabolic signature, a unique phenotype, that makes their recovery much faster.”

Through the methodologies created by D’Alessandro and Nemkov, the researchers also could assess athletes’ capacity to burn fat, which allows them to preserve an all-important fuel – glycogen.

“The goal of the study was trying to understand, with more resolution, what is specifically different about the metabolism as your lactate-clearance capacity improves,” Nemkov said.

Cycling toward better disease treatments

If researchers can better define the metabolic traits of fatigue, for example, they can more accurately measure athletes’ pre-race physiology as well as predict their susceptibility to injury.

The research is helping to inform personalised approaches to “exercise-as-medicine” interventions for other diseases and conditions, including cardiovascular and neurological disorders, and inflammation.

“Through the medication of exercise, we want to try to elicit changes at the metabolic and cellular level,” San Millán said. “Right now, there are very limited ways to quantify that. It’s why metabolomics has a tremendous future – it has a huge space. We should be able to see the metabolic signatures and what’s happening at the cellular level, and how a person with diabetes or cancer or a metabolic syndrome (eg. obesity) is responding to exercise. And we can see how changes and personalised intensities (of exercise) and durations could help them.”

Author credit: Chris Casey, CU Anschutz

Image credit: Arni Svanur Danielsson

 

 

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