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An N of 1: When science meets sports


An N of 1: When science meets sports


Matthew J Laye, Department of Health and Human Performance, The College of Idaho, Idaho, USA

As an undergraduate biochemistry major and cross-country runner I wanted to get faster. I had heard about altitude training as something that professional runners did and wondered if a summer at altitude would speed my improvement. Luckily, at the University of California, Davis (UC Davis) we had William Adams, an expert on the effects of altitude training on performance. I asked Adams: “Should I go to altitude for the summer to get better?” His response? “You should take my class on environmental effects on human performance and figure it out for yourself!” So, like any easily persuaded undergrad I did and it changed my academic and athletic trajectory.

Scientific beginnings

At UC Davis I majored in exercise biology, studying exercise physiology alongside biochemistry, molecular biology, genetics, and organic chemistry. I thought of it as sports science with rigor. My roommate, Steve Laurie (who now works at NASA as a PhD physiologist) and I eventually did go to altitude to train, and with the help of one of our Professors we performed “case studies” on ourselves to look at how we adapted to altitude training over the summer. Turns out that dedicating yourself to training all summer is great for improvement, with or without the altitude. After that summer, my interest in sports science was piqued. Back at school, I worked in a lab studying skeletal muscle physiology, but using molecular biology techniques. Funding to do straight sports science was relatively scarce compared to funding for health sciences and basic biology, so I applied to a graduate school where researchers study how exercise improves health. I ended up in the lab of Frank Booth at the University of Missouri where we studied the molecular and physiological changes that occur in response to short periods of physical inactivity. Our goal was to determine the initial physiological changes in response to physical inactivity in order to identify the underlying mechanisms which link physical inactivity to 30 plus different chronic diseases (Booth et al., 2012).

After graduating, I continued studying exercise as it pertains to health during my first post-doctoral position at the Centre for Inflammation and Metabolism in the laboratory of Bente Klarlund Pedersen in Copenhagen, Denmark. We published several papers on the role of microRNAs in health and disease, and I developed a muscle cell culture model of exercise. On the side we had several studies more related to sports science for fun. In the first we conducted pre- and post-testing on a small cohort of runners who ran a marathon a day for seven consecutive days. One hypothesis 
we had was that excessive exercise might accelerate ageing. So we looked at markers of ageing such as telomere length, telomerase activity and different components of the shelterin complex, the protein cap that protects telomeres from damage. The runners had seemingly no detrimental effects on telomere length or telomerase activity, and actually increased the amount of some proteins associated with and a part of the shelterin complex in either skeletal muscle or peripheral blood mononuclear cells (Laye et al., 2012).

A second research question we attempted to untangle was the relationship between VO2 max and health. If you look at a large population, higher VO2 max is associated with a lower risk for many chronic diseases and even mortality. However, VO2 max is also subject to genetic influences, with some people born with a high VO2 max, others not, and some born with the ability to dramatically improve their VO2 max, others not so much. We wanted to know whether VO2 max and health could be uncoupled from each other. The experiment we did was a case-controlled experimental design which matched long-term marathon runners (5+ years, 10 marathons) with healthy, sedentary, non-runners of similar age, BMI and gender. Because of the intrinsic variation in VO2 max, a third of the runner–non-runner pairs actually had similar VO2 max values despite one of them running multiple marathons a year. When we looked at health and metabolic parameters we nevertheless found that the runners were more healthy with better blood lipids, body composition, and oxidative capacity in their muscles (Laye et al., 2015). Essentially, your VO2 max is not your health destiny, but how much physical activity you do might be.

My second postdoctoral position took me further away from the sports science area, as I worked at The Buck Center for Research on Aging (Novato, CA). There we tried to understand how dietary restriction and specific metabolites increased longevity in Drosophila Melanogaster. The science was interesting and challenging but as I continued to compete in endurance events and ventured into ultramarathons (any distance over 26.2 miles) it felt less connected to my own interests and was certainly more difficult to apply.

Putting the science to practice as an N = 1

Each athlete is their own experiment. You can’t control for all the variables nor definitively prove that any specific training is “best”. Instead, as an athlete, coach and scientist I try to weigh the scientific evidence and current coaching best practices against time constraints, potential benefits, and risks for a specific athlete. My goal is always to apply the most effective training stimulus given the situation. One example is how I used the existing science to support my own training for my first mountain ultra-race, 100 kilometres long with 6,000 metres of climbing and descent at altitude. While many athletes may look at those details and worry about the climbing, I was worried about all the descending and muscle damaging eccentric muscle contractions (i.e. muscle lengthening as it contracts) that occur when running downhill, especially since I was living in Copenhagen, a flat city, at the time. The science on eccentric exercise says that after each bout of muscle-damaging eccentric work it will take 2–3 weeks to adapt, but that the same amount of eccentric work the next time will elicit far less damage and lead to significant increases in muscle strength (Vogt and Hoppeler, 2014). Several months prior to the race I used the treadmill in the lab and set it to a -5% grade rather than up; 40 km later my quadriceps were destroyed (I wish I had an electron micrograph of the sarcomeres!) and I was sore for 2 weeks. A similar workout after a few weeks of normal running left me sore for 4–5 days, and then a third eccentric workout for only about 2 days. From 2 weeks to 2 days my quadriceps had adapted. Weeks later I completed the race and finished a respectable 25th given I lived at sea level in a very flat city.

When I prepared for my first 100 mile race I used a similar approach to training. This race was relatively flat, but I knew (and was told by other runners) that there was no way to mimic the eccentric demands of that distance by training on flat terrain alone. So I would climb our local mountain in the Bay Area and then bomb the downhills on the road to damage and then allow compensatory adaptations which hopefully would allow the muscles to complete 100 miles of running. I also used a periodised nutrition approach to maximise both fat and carbohydrate use. Some runs would have the goal of increasing my ability to use fat as energy and I’d take in no calories, while others I would practise taking in carbohydrates in the form of gels and food at 60–90 grams an hour. I managed to eat consistently throughout the race with good energy and strong legs the entire distance. My old roommate Steve paced me the last 20 miles as I ended up winning the race in 13 hours and 17 minutes, just under 8 minutes per mile for the 100-mile distance.

As a coach I’ve worked to apply and adapt the existing and new science. The simple principles of specificity, overload, and individuality guide my approach. For instance, many of these ultra-races can take place in hot conditions, with huge amounts of vertical gains, at significant altitude. I regularly prescribe 20–30 minutes of sauna time immediately after working out for my athletes to ensure they are heat adapted. The use of the sauna to transiently raise core temperature improves the body’s ability to deal with running in hot conditions. My runners have not had significant problems with the heat while racing even when they train in the typically mild climate of San Francisco. Another challenge is for athletes who train at sea level and want to compete at altitude, but are unable to spend the time at altitude needed for proper adaptation. Sometimes you can’t outperform the physiological challenges. I advise them to arrive as close to the race day as possible, and set lower goals than typical given the detrimental effects on performance. My athletes are not professional runners, and so training plans need to be individualised around their lives. When possible, I will “stack” workouts back to back to really stress the athlete when they have time to train, but then follow that up with a period of rest to coincide with the times when life is too busy for training. Sometimes this is two big runs on the weekend or a hard workout in the evening followed by a mellow, easier run first thing in the morning. Overload training stimulus when you can and build in rest around their day-to-day life.

From time to time I ignore the science to my own peril. For instance, a few years ago I fell and ended up damaging some knee cartilage and developing bone on bone pain that prevented me from training fully. I could still run, but instead of running 70 plus miles a week, I was reduced to under 30 miles a week. Nothing I tried could to get me back to normal training, so I looked to the science for some guidance on whether surgery might be an effective option for me. After reading the literature, I learned that most of the knee surgery techniques to restore or replace cartilage have very low long-term success rates and my particular surgery was inferior compared to others (Campbell et al., 2016). Still, I justified surgery because my lesion was small and I was certain I could improve my outcome with added passive knee movement and supplements which had marginal efficacy. Over a year later I’ve worked back to running about 30 miles a week and I still have occasional knee pain along the same magnitude as prior to the surgery. Unfortunately, I was not special and I did not seem to beat the odds and existing science.

From scientist runner to teacher coach

Eventually, I decided to trade in the laboratory for the classroom and trade my own running pursuits for those of others. In autumn 2015, I started as an Assistant Professor in the Department of Health and Human Performance at The College of Idaho, a small liberal arts school (enrollment of approximately 1,000) in Caldwell, Idaho. While my primary job is to teach, I still have research goals. With limited time and resources, the type of research is different and I’m given lots of autonomy to seek out my own interests. Naturally, this freedom takes me back to running-related topics. For instance, I’m interested in whether I can reduce the high prevalence of gastrointestinal issues of ultra-runners during exercise. My current study is characterising the microbiome of ultra-runners prior to and after 100-mile races to try and identify microbial compositions that are associated with gastrointestinal issues. However, what’s more important, is what my students want to research. These students are excited to do small research projects related to their own lives, and I get excited guiding them through the research project. The primary goal is not getting published or receiving grants but to show them how much fun, rewarding and sometimes hard research really is. Hopefully I provide my students with the same experience I had as an undergraduate.

I also volunteer coach and run with a local running group, The Boise Billies. Each week I write a short newsletter which includes a scientific study related to running or health. I also write a monthly column for UltraRunning magazine on the science of running. My goal is always to provide easy recommendations or takeaways on how to apply (or not apply) the research of the week. Writing about research to the general public helps me stay connected to the world of research and improve my ability to communicate how research might be applied.

Evidence-based performance science

Using scientific literature for sports science is a little like evidence-based medicine. In theory, these are concepts in which there is very little to disagree with. Base training or medical decisions on peer-reviewed science. It’s a very simple concept and yet incredibly complex when you consider the details. Age, gender, genetics and countless confounding variables and conditions all make it extremely unlikely to find peer-reviewed science that applies to a specific athletes’ or patients’ unique situation. Coaches and practitioners have to use evidence combined with experience and sound judgement.

An added difficulty is that many training studies are done on sedentary subjects. For a group with low physiological functioning, almost any intervention improves performance. Conversely, highly trained elite athletes are near the top of physiological functioning and already do the most effective training protocols. For elite athletes, it is far more difficult to find an intervention to improve performance, even when just fractions of a percentage improvement may separate the podium at the elite level. Just as it’s difficult for evidence-based medicine to tell us much about rare diseases of outlier patients, it’s difficult for sports science to tell us much about improving the already stellar performance of elite athletes. Those that coach or compete at the elite level must be even more skeptical than most, not ruling out all data in elite athletes while not believing everything that improves performance of previously sedentary individuals. It’s where the art meets the science at times.

For 10 years as an active researcher I spent a majority of my time doing things that were at best peripherally related to running and coaching. However, the skills I developed as a researcher – reading carefully, thoughtfully, skeptically, considering all of the confounding factors, isolating variables, and interpreting results in the appropriate context – were applied to every aspect of my training and coaching. Those are truly transferable skills, to whatever decisions and passions you have in life. I’m certainly grateful to all my fellow scientists, runners, and coaches who have taught me and continue to teach me how to create the best evidence-based training programs for an N of one.


Booth FW et al (2012). Lack of exercise Is a major cause of chronic diseases. Compr Physiol 2(2), 1143–1211.

Campbell AB et al. (2016). Return to Sport After Articular Cartilage Repair in Athletes’ Knees: A Systematic Review. Arthroscopy: The Journal of Arthroscopic & Related Surgery 32(4), 651–668.

Laye MJ et al. (2015). Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners. Disease markers 2015, 806418.

Laye MJ et al. (2012). ‘Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event. Journal of Applied Physiology 112(5), 773–781.

Vogt M, Hoppeler HH (2014). Eccentric exercise: mechanisms and effects when used as training regime or training adjunct. Journal of Applied Physiology (Bethesda, Md.: 1985) 116(11), 1446-1454.

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