Scientists are making progress towards creating an ‘exercise pill’
• But the proof’s not quite in the pudding yet
It’s every couch potato’s dream: a pill to mimic beneficial effects of exercise on the body. It’s an even bigger dream for overweight or obese couch potatoes, or those with heart or other health issues that make physical activity difficult.
Whether the dream will come true any time soon is in the realm of scientific research & development.
In other words, it’s still the stuff of science fiction.
But US scientists may be coming closer to realising it after publication of their multicentre study in the Journal of Pharmacology and Experimental Therapeutics recently. Their findings are the fruits of years of research into a class of experimental drugs called mimetics.
And this could be good news for SA, where rates of obesity and metabolic diseases, such as type 2 diabetes and cardiovascular disease (heart attack and stroke) are in the stratosphere.
Mimetics derive from the Greek word “mimetikos”, meaning imitation or mimicry. Scientists use mimetics to describe compounds that mimic effects of other substances or lifestyle interventions — in this case, diet and exercise.
Human trials into calorierestriction mimetic compounds mimic the effects of substantial reduction in food intake. They are looking so good that scientists have dubbed them “have your cake and eat it, too” drugs, though they are not yet available on the market.
Exercise mimetics work differently and stimulate a range of physiological responses that exercise activates.
The US study moves exercise mimetics a step closer to “fitness in a pill”. It’s in a mouse model, so the researchers can’t generalise findings to humans. The mice lost body fat despite eating whatever they fancied. They exercised only if they felt like it. They emerged with beachready bodies without even building up a sweat, says study co-author Thomas Burris, professor of pharmacodynamics at the University of Florida’s College of Pharmacology.
The mice also improved their health markers without trying, Burris says. Their blood lipid (including cholesterol) profiles improved, along with heart function and muscle strength. They avoided blood sugar issues.
They achieved all that simply by popping the exercise mimetic pill that Burris and his team developed.
It’s a small molecule, known as a “pan-agonist estrogen receptor-related receptor”, that the team has called SLU-PP332. It targets a receptor that Burris has been working on since the 1980s.
AEROBIC EXERCISE
Estrogen is the American spelling of the female hormone oestrogen. Despite the name, Burris says that estrogen receptor-related receptors do not respond to oestrogen. Rather, they “regulate energy or gene pathways that are critical in tissues, such as the muscle, where energy use is important”.
Pan-agonist is pharmacology-speak for a molecule that activates multiple oestrogen-related receptors simultaneously in the body. This gives the ability “to target and stimulate different subtypes of these receptors, leading to different effects on cellular function”, says Burris.
Different types of exercise, such as resistance, aerobic or anaerobic exercise, cause muscle to respond by expressing specific genes that allow it to adapt to exercise, he says. This increases muscle strength and endurance levels.
A single bout of aerobic exercise for 30 to 60 minutes, for example, activates a gene pathway that makes muscle work more efficiently, he says. Changes include increasing the number of mitochondria, which he calls “the body’s cellular powerhouses”, that are in skeletal muscle and all other bodily cells.
Other beneficial changes include more efficient energy production, or “cellular respiration”. Benefits of improved cellular respiration are well-documented and include enhanced endurance, improved cardiovascular health, weight management and other metabolic advantages.
Crucially, treatment with SLU-PP-332 in this study shows benefit for muscles independent of exercise.
“It mimics the same effects of aerobic exercise on mitochondria and cellular respiration and the effects of repeated aerobic exercise training in that the mice displayed enhanced exercise endurance,” Burris says.
The rodents could run up to 50% further and for longer compared with placebo.
He and his team believe that exercise mimetics have strong “potential value in treatment of obesity, metabolic syndrome, heart failure, nonalcoholic liver disease and chronic kidney disease”. They are pursuing improved versions of SLU-PP332 to evaluate this potential in clinical trials.
There are always downsides to even the best of medico-scientific intentions. Predictable concerns, apart from side effects, include misuse of these drugs by healthy people or athletes seeking possible performance enhancers.
Dr Jeroen Swart, professor and head of Sports and Exercise Medicine at the University of Cape Town, says the “full benefit of exercise will likely still require actually doing exercise — at least for the foreseeable future”.
The effect of exercise on the human body is “complex and involves signalling pathways in multiple organs and systems”, Swart says. This complexity means that “we can only ever realistically mimic only some of these effects”.
Exercise alone has clear health benefits, says Swart. Regular exercise can reduce cardiovascular mortality and all-cause mortality by nearly half compared with sedentary individuals.
It can also offset, to some extent, the negative effects of unhealthy diet or conditions, such as obesity. However, exercise alone is “not the most beneficial weight-loss intervention”, he says.
Together with other lifestyle interventions, such as a healthy diet, adequate sleep and stress reduction, exercise provides a combined benefit and cumulatively lower health risk profile than any one intervention alone, Swart says.
The research is clear and there is no one-size-fits-all diet. “The diet that works for you is the one you can stick to.”
BRISK WALKING
Low-carbohydrate diets are “particularly useful for diabetics”, as they provide glycaemic control and weight loss, Swart says. For weight loss alone, any diet that facilitates reduced calorie consumption is beneficial.
“Losing weight is probably the most effective means to increase your health status.”
To gain the most benefit for the least effort, he recommends brisk walking for at least 30 minutes, three to four times a week, and a diet low in processed foods.
If all else fails, a Tibetan proverb reveals the secret to living well and longer: “Eat half, walk double, laugh triple and love without measure.”