Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate

Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate

John Quindry Ph.D., FACSM | Sep 09, 2018

This is part two of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the debate, "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training?" between Ron Evans, Ph.D., and John Hawley, Ph.D.


The first debate of ACSM’s Conference on Integrative Physiology of Exercise, “Are exercise 'mimetics' a realistic substitute for exercise training?” is in the books, and it was a conversation starter to say the least. Pro-mimetic commentary was provided by Ronald Evans, PhD, of the Salk Institute, while John Hawley, PhD, of the Mary MacKillop Institute for Health Research gave counter arguments on behalf of exercise.

My humble opinion of the session is that both presenters approached the topic from opposite ends on a spectrum of the human condition, albeit providing variable interpretations of the same data. Imagine a Venn diagram where Evans’ mimetics and Hawley’s exercise intersect modestly, but with spirited debate over common ground. At the crux of this particular debate is PPARg, or peroxisome proliferator-active receptor gamma – a name only a scientist could love.

If you haven’t been keeping score at home, PPAR activation is central to many of the well described adaptive responses to aerobic exercise. Staying out of the molecular weeds, it is fair to summarize that PPAR activation results in dramatic alteration in metabolic function to the extent that human exercise capacity is improved in elite athletes, mall walkers and type 2 diabetics alike. Perhaps ten seconds after characterizing this cellular pathway, the search for a medicinal approach to PPAR activation (agonist) began. Think of the potential: countless lives saved or improved, Nobel prizes, swimming pools of cash! Proof of concept experiments were first conducted by Ron Evans’ research team in which “couch potato” mice receiving newly formulated PPAR activators were suddenly running literal circles around their untreated cage mates.

Remarkable as this landmark discovery was, it immediately raised the ire of some in the exercise field. Correction – media-generated overstatements that “exercise in a pill had been discovered” rightfully inflamed the those of us who promote physical activity and exercise a as means to improved health.

So what’s the wrinkle? In short, PPAR agonists (and presumably other exercise mimetics not discussed currently), amazing as they are, are not as robust a stimulus when compared to formal exercise. The metabolic and exercise performance responses to the current forms of these pills are many fold lower than good old fashioned exercise training (think ACSM prescriptive criteria for furry critters).

But you want to know who won the debate.

Sorry, but they both did. Evans very clearly defended the position that PPAR activation, should it be scalable to humans, would be revolutionary to those who can’t exercise due to disease, severe deconditioning or extreme risk for precipitating a medical event with exercise. More pragmatically, most people in the developed world won’t exercise, and there is a solid rationale to suspect that this pill is better than nothing.

On the other side of the argument, Hawley deftly defended the fact that there is no substitute for exercise. No single pill discovered to date can provide the robust multi-tissue, multi-system benefits of a brisk walk.

And by the nature of this meeting, Hawley came to the podium wearing the white hat, but that doesn’t mean Evans had a black hat. Indeed, journalistic irresponsibility in overstating the claims of exercise mimetics has nothing to do with Evans’ position. Evans’ intentions are as altruistic as Hawley’s and it’s worth noting that Evans promoted exercise alongside his mimetic discoveries. In the end Evans mostly spoke to diseased applications while Hawley addressed healthier populations. The Venn diagram overlap, still to be negotiated, pertains to those that won’t exercise—a debate for another day.

Read Part 1: "Can exercise fill the reductionist gap? Reflections on Dr. Michael Joyner's Keynote."

John Quindry, Ph.D., FACSM, is a member of the faculty at the University of Montana, Department of Health and Human Performance. He served as a co-planner of ACSM's Conference on Integrative Physiology of Exercise.