The magic pill

Imagine what it would be like if we could prescribe ourselves a pill that would give the benefits of exercise for our cardiovascular and metabolic health without exercising? It sounds crazy, doesn’t it? If you think about it, it might not be such an outrageous idea. Alejandro Marmolejo, a physician and PhD student in mitochondrial biology, shares his thoughts about how “exercise in a pill” could become an important therapy in the future.

Exercise in a pill will not sound that crazy after this:

We live longer but not necessarily healthier

We, the human race, have substantially improved our quality of life over the last half-century. We went from living around 46 years in 1950 to living around 71 years in 2015 (world average). The longer we lived, the more chronic diseases started to appear and interfere with our quality of life. This means that we improved our life-span, but our health-span is lagging far behind. By 2050, the world’s population of people over the age of 60 will double. Based on this fact, the WHO has proposed the “healthy aging” paradigm, in which ageing adults do not lose their autonomy due to chronic disease and can still take part in society.

Chronic degenerative diseases are also called non-communicable (referring to their non-contagious nature). They are conditions of progressive deterioration of tissues or organs. Their incidence correlates with age. Some aged individuals do not develop chronic disease. However, aging is a significant risk factor for the appearance of these diseases.

Sedentarism is the opposite of exercise

The COVID-19 pandemic hit the world hard, introducing important changes in our lifestyle. In most countries, some of the measures involved staying at home as much as possible, social distancing and avoiding crowded places. Actually, I have many friends that already have pre- and post-lockdown photos where they showed considerable weight gain blaming the new “lock-down lifestyle” (staying at home without exercising + ordering food). This goes to show that staying at home is a dangerous brew for sedentarism, a reason why maintaining our fitness status is a constant concern. Given that sedentary lifestyle is the opposite of an active lifestyle (AL) and AL has been shown to decrease overall mortality, it would be revolutionary  if a medicine was engineered for us to experience the beneficial effects of exercise! 

Why is exercise/physical activity so important?

When we exercise, our mitochondria (a component of all of our living cells that is in charge of producing energy for us to survive) gets mildly stressed to meet the demands of our activity. Think of mild stress as something like pushing the system: you try to do more with what you already have. So mitochondria get stressed in the sense that now they have to increase their energy production while some minutes ago they were resting and producing the minimum. Mild stressors, such as exercise or caloric restriction (fasting), are known stimuli that improve metabolic fitness. Because of its overall beneficial effects, exercise has been widely prescribed against cardiovascular disease, cancer and dementia. Now, if you think about it, prescribing exercise could help an individual with obesity that has had heart attacks, a patient with cancer on strong chemotherapies and a person with Alzheimer’s disease. However, they may be physically or mentally incapable of performing adequate physical activity. These are the cases for whom the idea of exercise in a pill has been proposed. 

Another group of people for whom the exercise pill could be of benefit are the elderly. I worked as a physician (GP) in México before coming to the Netherlands to pursue a research career. In general, the role of the GP is to promote health more than “cure disease”. In my clinic, the regular 60-70 year old patients had at least one of the following illnesses:

• Diabetes Mellitus 
• High Blood Pressure
• Obesity
• Mild Cognitive Impairment
• Chronic Kidney Disease

On top of prescribing their monthly meds to control their blood pressure or blood sugar, I recommended exercise to them, for example, going out for walks. To promote this, we had an exercise program in the clinic, where they could join and we could help them to perform basic exercises. Still, their capability was significantly reduced. Imagine if these patients could lower their risk of dying by taking the “exercise pill” to help them a bit? 

How can we prescribe exercise in a pill?

Current research that is focusing on the so-called “exercise-mimetics” (mimetic refers to the verb “to imitate”) is in the field of mitochondria and metabolism. Some drugs that are known to mildly stress mitochondria, such as metformin (an antidiabetic drug), resveratrol (a natural compound found in the skin of grapes), and other compounds are being tested. Metformin, for example, has already been shown to improve the health span and life-span in animal experiments. The problem with current approved drugs, however, is that they are not specific enough to obtain only the exercise effect, and may activate or inhibit other processes in our cells. Recent studies have deciphered the key players that drive the beneficial effects inside mitochondria, and it is now just a matter of time before specifically-designed compounds can reach clinical trials. 

Nevertheless, there are still a lot of unanswered questions, like:

• What could be the side-effects of a medicine like this?
• What experiments or clinical trials have to be performed to demonstrate that such medicine works? Against a specific disease or just give it to people and let them age and follow them over time?
• What would the dosage and schedule of a medicine like this be? Once a day, like exercise? Every 8 hours? Continuous supply over the day? Once a week?
• Who would get this medicine? The rich and wealthy? Released worldwide? The healthy population, to increase health span? Or the aged population, to increase life-span?
• Would a medicine like this replace exercise in all populations?
• When will this pill even exist?

Exercise has beneficial effects that are not exclusively metabolic. Articular health, bone strength, pulmonary capacity, heart rate reserve, endorphin secretion are some of the secondary beneficial effects of exercise. Would a pill that replaces exercise neglect these mechanisms?

In my personal opinion, I think that whoever discovers/designs the medicine that is capable of inducing the beneficial effects of exercise will be regarded as a visionary. Who knows, maybe deserving a Nobel prize. What do you think of exercise in a pill? Do you really think it will improve our health, or do you think it will give people the excuse to not exercise?

In the meantime, I will be doing some push-ups in my apartment, going the gym every now and then and watch my eating habits. As a GP, I suggest you perform exercise and watch your diet to stay as healthy as possible! 🤓👨‍⚕️#HealthyAging here we go!!

Please leave a comment, they are always appreciated!

Till later,
Alejandro

The featured image was taken from (https://www.shape.com/lifestyle/mind-and-body/exercise-pill-may-soon-exist-gym-haters) Creator: Viaframe | Credit: © Viaframe/CorbisCopyright: © Corbis. All Rights Reserved.