Can a pill really mimic all the beneficial effects of exercise? You’d think so from some of the stories about substances that “could make going to the gym unnecessary”. There was another rash of these a few weeks ago, when researchers from Aarhus University in Denmark announced that a drug called LaKe “brings the body into a metabolic state corresponding to running 10km at high speed on an empty stomach”. But what’s going on here? Even if a pill can replicate parts of what exercise does for us, how useful is that, really?
First things first: the most commonly accepted term for drugs like LaKe is “mimetics”, because what they do, as a rule, is mimic the biological effects of working out without the need to actually break a sweat. The idea has been around for a while: in 2008, San Diego’s Salk Institute introduced the world to a drug called GW501516 (516 for short), which signals key genes to burn fat instead of sugar, helping rodent test subjects run for longer without hitting the proverbial wall.
In later tests, a pair of rodents nicknamed Couch Potato Mouse and Lance Armstrong Mouse, both reared on the same diet of fatty, sugary pellets, did the same amount of daily physical activity, but Lance Armstrong Mouse was dosed with 516 – and markedly increased its endurance, while staying much leaner than its control counterpart. A variant of 516 quickly ended up on the black market as a banned doping agent known as Endurabol, and the World Anti-Doping Agency issued warnings to athletes that it was unsafe – but plenty more mimetics were already in development.
Compound 14, first announced in 2015, started development as a way to treat other diseases, before researchers discovered that it could reduce fasting blood glucose levels, improve glucose tolerance and promote weight loss in obese mice. Since then, we’ve also seen research on Lac-Phe, a chemical usually produced in the body through resistance training, and a new molecule known as SLU-PP-332, which boosts metabolism and endurance, helping rodents run 50% further than they previously could. The latter, its lead researcher says, tells skeletal muscle to make the changes typically provoked by endurance training. That has the potential to help dieters maintain muscle mass during weight loss, or older people avoid sarcopenia as their bodies respond less strongly to exercise.
LaKe is still in the rat-study stage of development, so it’s not certain that the results will transfer over to humans. But what it seems to do is first prompt a quick surge of lactate in the body – mimicking the sort of effect you’d typically see after a bout of high-intensity exercise – and then a more gradual increase of a chemical called beta-hydroxybutyrate (BHB). BHB is a ketone, or a chemical synthesised in the liver from fatty acids to provide the body with energy when it doesn’t have enough glucose – which is where the notion of “running on an empty stomach” comes from.
Between them, these two changes do seem to lower the level of free fatty acids in the bloodstream and also suppress appetite – which are effects you’d expect from fasted exercise (working out without eating beforehand), and could help to reduce the risk of conditions such as heart disease, stroke and type 2 diabetes over the long term. And (again, in rats) the pill seems to show no signs of toxicity – unlike early versions of 516, which promoted rapid cancer cell growth in their rodent test subjects. Promising stuff, then – but is it really that simple?
Well, it’s tough to say. Exercise affects almost all of the body’s systems, in often intricate ways that we’re a long way from understanding (the largest research programme dedicated to comprehending its impact at the molecular level, using almost 2,600 volunteers, is still ongoing). Together, many of the drugs mentioned above might be able to mimic any number of these – perhaps working in conjunction with already government-approved interventions like Ozempic to encourage a host of benefits. But any supplement has limitations: exercise is a full-body experience, with downstream effects that include everything from improved bone density to better sleep. It enhances mood and self-esteem while decreasing stress, and it seems to have qualities that protect against dementia. All of these impacts come from complex interactions between any number of biological effects – but even if science could mimic them all with pills, it would be much tougher to recreate the psychological advantages of running a 5k with friends, or hitting a new personal best in the squat.
We’re still a fairly long way from finding safe drugs that can replicate exercise’s most beneficial effects in humans, but when they exist, they’ll probably be most useful for people who are elderly, ill, infirm, or otherwise unable to do the real thing. They might help people recovering from surgery – or astronauts who, even if they work out while in orbit, suffer bone loss and muscle wastage because their bodies work less hard in microgravity. For the rest of us, the benefits of a gentle walk or a handful of squats are tough to mimic with pills, and (reasonably) easy to get without them. One day, perhaps we’ll be able to take our exercise in pill form – but right now, it’s much easier to hit the road.
