Ketogenic Diet May Restore Exercise Benefits in Individuals with Hyperglycemia

Conventional wisdom emphasizes regular exercise and limiting dietary fat for optimal health. However, a recent study suggests that dietary composition, specifically a ketogenic diet, may play a crucial role in how effectively muscle responds to exercise, particularly in individuals with chronically elevated blood glucose levels.

The Challenge of Hyperglycemia and Exercise

Regular exercise supports weight control, muscle development, and cardiovascular health, improving the body’s ability to absorb and use oxygen. Maximal oxygen uptake (VO2peak), a key indicator of aerobic capacity, is a robust predictor of cardiovascular health and longevity. However, individuals with persistent high blood sugar, or hyperglycemia, often fail to experience these expected physiological gains from exercise. Hyperglycemia increases the risk of cardiovascular and renal disease and appears to blunt the normal adaptive response of skeletal muscle to exercise, limiting improvements in aerobic fitness.

Ketogenic Diet Restores Aerobic Capacity in Mice

Research led by Dr. Sarah Lessard at the Fralin Biomedical Research Institute at Virginia Tech Carilion examined the effects of a high-fat, low-carbohydrate ketogenic diet in a mouse model of hyperglycemia. The study found that after just one week on the ketogenic diet, blood glucose concentrations in the animals returned to normal ranges.

“After one week on the ketogenic diet, their blood sugar was completely normal, as though they did not have diabetes at all,” said Lessard.

Prolonged adherence to the diet led to substantial changes in skeletal muscle structure and metabolism. The diet caused remodeling of the mice’s muscles, making them more oxidative and improving their response to aerobic exercise. Improvements in VO2peak were blunted in mice fed a standard high-carbohydrate diet but were restored with the ketogenic diet.

How Ketogenic Diets Perform

The ketogenic diet induces ketosis, a metabolic state where the body shifts from using glucose to fat as its primary fuel source. This transition leads to the production of ketone bodies, which serve as alternative energy substrates. The approach has been associated with clinical benefits in specific contexts, including epilepsy and Parkinson’s disease. Historically, carbohydrate restriction was also used to manage diabetes before the discovery of insulin due to its ability to reduce blood glucose concentrations.

Muscle Remodeling and Enhanced Oxygen Utilization

Mice consuming the high-fat, low-carbohydrate diet and having access to running wheels showed an increase in leisurely-twitch muscle fibers (type I fibers). These fibers contain higher mitochondrial density and rely predominantly on oxidative metabolism, supporting sustained endurance activity and correlating with greater aerobic capacity.

“Their bodies were more efficiently using oxygen, which is a sign of higher aerobic capacity,” said Lessard. Enhanced oxygen utilization reflects improved mitochondrial function and a greater capacity to oxidize fatty acids, processes that underpin endurance performance and metabolic health.

Diet and Exercise: A Combined Approach

Lessard’s previous research demonstrated that individuals with high blood sugar display lower exercise capacity. This study sought to determine whether dietary intervention could restore the physiological response to training. The findings suggest that hyperglycemia may directly interfere with the molecular pathways that enable muscle to adapt, reinforcing the view that diet and physical activity do not operate independently.

“What we are really finding from this study and from our other studies is that diet and exercise are not simply working in isolation,” said Lessard. “There are a lot of combined effects, and we can obtain the greatest benefit from exercise if we consume a healthy diet at the same time.”

Future Research and Considerations

Researchers emphasize the need for translation to human populations. Future research will investigate whether individuals with hyperglycemia or type 2 diabetes experience comparable improvements in aerobic capacity and metabolic flexibility when adopting a ketogenic dietary pattern. Lessard acknowledged the practical challenges of long-term adherence to strict carbohydrate restriction and suggested that less restrictive approaches, such as the Mediterranean diet, may be more feasible for many individuals. The Mediterranean diet includes carbohydrates from minimally processed sources while limiting refined sugars and saturated fats and has been associated with improved glycemic control.

Nuance in the Debate on Dietary Fat

The findings add nuance to the longstanding debate on dietary fat and metabolic health. The research underscores the importance of metabolic context, suggesting that for individuals with hyperglycemia, targeted dietary composition may determine whether exercise delivers its full physiological benefit.