A supplement of ketones may be the magic bullet that allows patients using weight-loss drugs to avoid the potentially adverse side-effect of a shrinking heart and skeletal muscle, according to a University of Alberta study that "fine-tunes" the popular therapy to protect lean muscle while shedding the same amount of fat.
"Our original study was prompted by reports showing that people taking semaglutide — the active ingredient in weight-loss drugs such as Ozempic, Wegovy and Rybelsus — lost a significant amount of skeletal muscle mass," says Jason Dyck, a pediatrics professor in the Faculty of Medicine & Dentistry. "We wanted to reproduce that in animal models so that we could find ways to intervene and prevent this from happening."
In their initial studies, Dyck's team confirmed the expected loss of skeletal muscle, which studies show can account for nearly 40 per cent of the total weight loss. But they also found an unexpected and more concerning effect: the heart was losing muscle mass as well.
Although the heart naturally shrinks with weight loss — especially if it was enlarged due to obesity — Dyck says some of the heart muscle loss appeared to be independent of the overall weight reduction. "The question is, if you have a healthy heart, what are the long-term effects of it shrinking more than it should?"
It is already known that muscle decline can lead to a host of long-term health issues including decreased immunity, increased risk of infections and poor wound healing. To address the unknowns, the team looked at a natural energy source the body produces: ketones.
Ketones are produced by the liver when the body runs low on carbohydrates, typically during fasting or when following a low-carb, or ketogenic, diet. Recent work also showed that ketones are necessary to preserve skeletal muscle mass.
For the followup study, Dyck's team paired semaglutide with a ketone ester, a drinkable supplement that the body converts into ketones, mimicking the elevated levels of ketones in the blood.
The results in obese mice were dramatic.
"It turns out it does a fantastic job in protecting from muscle loss — skeletal muscle loss and loss of cardiac mass," says Dyck, who is Canada Research Chair in Molecular Medicine, director of the Cardiovascular Research Centre and a member of both the Women and Children's Health Research Institute and the Alberta Diabetes Institute.
Mice that received the semaglutide and ketone ester combination did not lose as much total body weight as the group receiving semaglutide alone. However, further analysis showed that this lower total weight loss was actually a positive sign.
"When we looked deeper into where that weight loss came from, the same amount of fat was lost, but the ketones prevented muscle loss," Dyck says. "It really just fine-tunes, potentially, this therapy."
