A new study shows that a high-fat ketogenic diet can normalize blood sugar levels in mice with hyperglycemia and enhance their muscles' response to exercise. Led by researcher Sarah Lessard, the research indicates that combining the diet with physical activity leads to better oxygen use and endurance. The findings suggest potential benefits for metabolic health when diet and exercise are paired.
Exercise typically enhances the body's ability to use oxygen, a vital indicator of health and longevity, but high blood sugar often hinders this benefit, increasing risks for heart and kidney disease. In a study published on February 25 in Nature Communications, researchers at Virginia Tech explored how diet influences exercise adaptation in mice with elevated blood sugar.
The team, led by Sarah Lessard, an associate professor at the Fralin Biomedical Research Institute at VTC Center for Exercise Medicine Research, fed mice a high-fat, low-carbohydrate ketogenic diet while allowing them to run on exercise wheels. After one week, the mice's blood sugar normalized. "After one week on the ketogenic diet, their blood sugar was completely normal, as though they didn't have diabetes at all," Lessard said.
Over time, the diet prompted muscle remodeling, increasing oxidative capacity and slow-twitch fibers for greater endurance. "Their bodies were more efficiently using oxygen, which is a sign of higher aerobic capacity," Lessard noted. The ketogenic diet induces ketosis, shifting the body from sugar to fat as fuel, contrasting with traditional low-fat recommendations.
Historically used for conditions like epilepsy, Parkinson's disease, and pre-insulin diabetes management, the diet showed combined effects with exercise. "What we're really finding from this study and from our other studies is that diet and exercise aren't simply working in isolation," Lessard explained. "There are a lot of combined effects, and so we can get the most benefits from exercise if we eat a healthy diet at the same time."
Lessard plans human trials and suggests alternatives like the Mediterranean diet for easier blood sugar control. "Our previous studies have shown that any strategy you and your doctor have arrived at to reduce your blood sugar could work," she said.
The study, titled 'A ketogenic diet enhances aerobic exercise adaptation and promotes muscle mitochondrial remodeling in hyperglycemic male mice,' appears in Nature Communications (2026; 17(1), DOI: 10.1038/s41467-026-69349-5).
