Google “what are the health benefits of ketones” and you’ll get dozens of hits promising everything from epilepsy control to improved heart health to more effective muscle-building at the gym. Researchers at the University of Alberta are examining the evidence to understand how ketone biology—including ketone-based therapies—may shape the management of cardiometabolic diseases including Type 2 diabetes, high blood pressure and coronary artery disease.
The good news is that there’s a lot of research underway, but much of it is still inconclusive.
A part of normal biology
Most people learn about ketones through the ketogenic diet, says Amir Tabatabaei Dakhili, assistant professor in the Faculty of Pharmacy and Pharmaceutical Sciences. It’s a high-fat, low-carbohydrate diet that forces the body to burn fat for energy, producing ketones in the process.
“What people don’t know is that ketones are part of normal biology,” explains Tabatabaei Dakhili. “When food intake drops during fasting, exercise and some illnesses, the body shifts and starts producing ketones in the liver, mostly to keep the brain active, but also to fuel other organs.”
Ketones are also now understood to be involved in the signaling pathway that can influence inflammation and regulate genes, but most of this research is still not definitive, says Tabatabaei Dakhili, who is a member of the Alberta Diabetes Institute and the Cardiovascular Research Institute.
Ketones were first discovered in people with uncontrolled Type 1 diabetes, so they were associated with poor health.
“Insulin not only regulates glucose but also keeps ketone production in check, so without insulin there is nothing to regulate them,” Tabatabaei Dakhili explains. “Ketones make the blood acidic, which is life-threatening.”
Promising studies
More recently, ketone supplements have been used effectively for reducing seizures in people with drug-resistant epilepsy.
Manipulating ketone levels also shows promise in protecting the heart and improving blood sugar for people with Type 2 diabetes. Tabatabaei Dakhili was a Canadian Institutes of Health Research graduate student under John Ussher, Canada Research Chair in Pharmacotherapy of Energy Metabolism in Obesity, when the team identified a drug that lowered blood sugar in mice by changing the way their muscles burn fuel. By making the muscles rely less on ketones and more on glucose, the treatment helped reduce blood sugar levels.
That was back in 2020. Since then, the group has refined the original compound and developed a next-generation version that reduces ketone use in peripheral organs while limiting effects on the brain.
The group has since optimized the drug and created a new one that decreases ketone oxidation in peripheral organs rather than in the brain. They are currently looking for industry partners to take the drug development to the next step.
Another U of A team under Jason Dyck, a pediatrics professor in the Faculty of Medicine & Dentistry, is working towards a clinical trial using ketone supplements to protect heart muscle for people who take semaglutide in weight-loss products such as Ozempic, Wegovy and Rybelsus.
Yet another field where ketones show clinical promise is heart failure. Tabatabaei Dakhili notes that a growing body of preclinical and early human studies suggests that ketones may help support heart function in some forms of heart failure, although the mechanisms and long-term clinical benefits are still under study.
A note of caution
As for improving exercise performance, boosting brain health or reducing inflammation using ketones, Tabatabaei Dakhili says the clinical evidence is still limited or mixed.
He points out that ketones are widely available, but they are generally sold as supplements or natural health products rather than as approved drugs for improving exercise performance in the general public. The supplements are expensive and short-acting, Tabatabaei Dakhili says, and they may cause side effects in the stomach that can actually interfere with exercise. Some trials on exercise performance showed promise, but later studies had only mixed results.
“Most of the trials were done with trained athletes, so the impact for the average person is unproven,” Tabatabaei Dakhili concludes. “A lot more trials need to be done to piece together the efficacy at this point.”
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