A Virginia Tech study in mice suggests a high-fat ketogenic diet can normalize blood sugar and restore key exercise benefits in the context of diabetes. The work highlights how diet and exercise may need to work together to protect the heart, muscles and metabolism.
For people with high blood sugar, the usual advice to exercise more does not always deliver the expected health payoff. Now, new research from Virginia Tech suggests that changing what is on the plate — not just how often someone works out — could help restore some of exercise’s most important benefits.
In a study of mice with high blood sugar, or hyperglycemia, a high-fat ketogenic diet not only brought blood sugar levels back to normal but also made the animals’ muscles respond better to aerobic exercise. The findings, published in the journal Nature Communications, point to a potential way to help people with diabetes or prediabetes get more out of their workouts.
Lead researcher Sarah Lessard, an associate professor at the Fralin Biomedical Research Institute at VTC’s Center for Exercise Medicine Research, studies how diet and exercise interact to shape blood sugar control and muscle function. Her team has previously shown that people with high blood sugar often have lower exercise capacity and do not improve their ability to use oxygen as much as expected, even when they stick to an exercise program.
That is a serious problem, because the body’s ability to take in and use oxygen efficiently during exercise — known as aerobic capacity — is one of the strongest predictors of long-term health and lifespan. People with high blood sugar are already at greater risk for heart and kidney disease, and a blunted response to exercise can leave them doubly vulnerable.
In the new study, Lessard and colleagues asked whether a ketogenic diet could change that equation. A ketogenic, or keto, diet is very high in fat and very low in carbohydrates. It pushes the body into a metabolic state called ketosis, where fat rather than sugar becomes the main fuel.
The approach is controversial because it runs counter to decades of low-fat dietary advice. Yet keto has a long medical history. Before insulin was discovered in the 1920s, it was used to help manage diabetes by lowering blood sugar. Today, versions of the diet are used for conditions such as epilepsy and are being explored for other neurological diseases.
In this experiment, hyperglycemic male mice were fed a high-fat, low-carbohydrate ketogenic diet and given access to running wheels for exercise. Lessard noted the changes in blood sugar were rapid and dramatic.
“After one week on the ketogenic diet, their blood sugar was completely normal, as though they didn’t have diabetes at all,” Lessard said in a news release.
As the study went on, the researchers saw deeper changes inside the animals’ muscles.
“Over time, the diet caused remodeling of the mice’s muscles, making them more oxidative and making them react better to aerobic exercise,” Lessard added.
In practical terms, that meant the mice developed more slow-twitch muscle fibers — the type that supports endurance — and became better at using oxygen during activity.
“Their bodies were more efficiently using oxygen, which is a sign of higher aerobic capacity,” added Lessard.
Those shifts are important because they suggest that, at least in this animal model, a ketogenic diet can restore the muscle’s ability to adapt to exercise, even in the context of high blood sugar. Instead of exercise benefits being blocked by hyperglycemia, the diet appeared to reopen the door.
The work also reinforces a broader message emerging from Lessard’s lab and others: diet and exercise are deeply intertwined, and their effects on health cannot be fully separated.
“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 added. “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.”
The study was done in mice, so it does not prove that the same results will occur in people. Lessard emphasized that the next step is to test whether similar benefits appear in human volunteers with high blood sugar who adopt a ketogenic diet and exercise.
If the results translate, the work could eventually help doctors tailor diet-and-exercise prescriptions so that patients with diabetes or prediabetes gain more protection for their hearts, muscles and metabolism.
At the same time, Lessard noted that a strict ketogenic diet is difficult for many people to follow over the long term. It typically requires cutting out most carbohydrate-rich foods, including many fruits, whole grains and starchy vegetables, and carefully tracking fat intake.
Because of that, she is also interested in whether less restrictive eating patterns could deliver similar benefits when combined with exercise. One candidate is the Mediterranean diet, which emphasizes vegetables, fruits, whole grains, legumes, nuts, olive oil and fish. That style of eating can help keep blood sugar lower while still allowing unprocessed carbohydrate sources, rather than eliminating carbs altogether.
Lessard’s earlier work suggests that the exact diet may matter less than achieving good blood sugar control in a way that a person can sustain.
“Our previous studies have shown that any strategy you and your doctor have arrived at to reduce your blood sugar could work,” added Lessard.
For now, the new mouse data add to a growing body of evidence that the right combination of diet and exercise may unlock health gains that neither can fully provide alone. For people living with high blood sugar, the research offers a hopeful message: with the right metabolic support, their bodies may be able to reclaim more of the powerful benefits of moving more.