Banner by Sumana Kethu

One Dose of Exercise, Please

By Krithika Khati

Imagine you’re on a treadmill, legs racing one after the other one, gasping for as much air as your lungs can take as a bead of sweat rolls into your mouth. Can you keep going for another 10 seconds? Is it worth it? Do you ever wish there was an alternative with the same health benefits?

There have been several types of fitness pills on the market in the past few decades, but they claimed to have effects such as temporarily suppressing appetite rather than induce the same effects exercise can have on the body. “Exercise pills,” whose earliest mentions in literature were in the late 20th century, propose something else; they are drugs that can induce the same, or similar, metabolic and physiological effects as exercise. They were first proposed as a solution for meeting fitness needs in the elderly population, but may be used more broadly.

In 1978, Robert Butler, a former director of the National Institute of Aging, said, “If exercise could be packed into a pill, it would be the single most widely prescribed and beneficial medicine in the nation.” Today, an exercise pill would be able to help the 75.8% of American adults who do not meet the guidelines for both aerobic and strengthening exercises gain the benefits of exercise, as well as those with metabolic disorders. Scientists worldwide have been researching drugs that may do this.

One such drug that has recently been studied is called SLU-PP-332. This drug works by acting as an agonist (a substance that mimics the behavior or shape of a receptor’s ligand and can activate the receptor in place of the real ligand) for the estrogen-related receptors (ERRs): alpha, beta, and gamma nuclear receptors. These receptors play important biological roles. ERRs alpha and gamma, in particular, have been found to be primarily expressed in metabolically active tissues, especially those that prefer to use fatty acids as energy sources. They regulate the transcription of metabolic genes, physiological and developmental functions in muscles, mitochondrial function, and lipid catabolism. A study by Cyrielle Billon et al. suggests that the synthetic agonist SLU-PP-332 is able to induce exercise response, as well as enhance exercise endurance. Some of the exercise responses included increased skeletal muscle oxidative fibers, which is associated with higher levels of glucose tolerance and insulin sensitivity, and increased fatty acid oxidation, which is a sign of the body using fat as energy. In another study conducted by the same team, injecting obese mice with SLU-PP-332 twice a day for a month led them to lose 12% of their body fat without changing how they exercised or ate compared to control mice.

Another intriguing approach, called ExPlas, is in Phase II of clinical testing, meaning it is being tested in about 100 volunteers. ExPlas, which is short for exercised plasma, is a trial in which exercised plasma from young, fit adults are transfused into older adults with early Alzheimer’s disease. The study’s objectives include determining the outcomes of exercised plasma on “cognitive function, fitness level, vascular risk profile, assessment of cerebral blood flow and hippocampal volume, quality of life, [and] functional connectivity.” Results of the study will be available in 2025!

A future with “exercise pills” could be close in sight, but more tests and trials are needed to assess its efficacy and safety in humans. Despite the challenges that these testing periods may hold, the prospect of a drug that induces the same effects as exercise is a thrilling one. If successful, it could transform the lives of those who may have barriers to traditional exercise and lead to an overall healthier society. “Exercise pills” could be key in preventing some of the most prevalent conditions today, like heart disease, dementia, certain types of cancer, depression and anxiety, and type 2 diabetes. Here’s to a healthier future!