Exercise & Sports Performance, Cancer

Targeting differential energy substrate metabolism on a therapeutic ketogenic diet: a case report

This case report examines the relationship between exercise intensity and blood ketone levels in a 44-year-old male patient with glioblastoma who followed a therapeutic ketogenic diet during chemoradiation. While ketogenic diets are increasingly explored as adjunct therapies in cancer treatment due to their potential anti-inflammatory and anti-tumor effects, achieving and maintaining high ketone levels can be challenging, particularly in adults.

The patient adhered to a modified ketogenic diet (60–70 g/day protein, <20 g/day net carbs, 2,200–2,500 kcal/day), achieving ketone levels ≥4 mmol/L and a glucose-ketone index (GKI) ≤1 early in treatment. Initial physical activity consisted of intense indoor climbing, which was later reduced due to seizure risk. This reduction in exercise intensity coincided with a decline in ketone levels, despite unchanged dietary intake and similar caloric deficits.

To test the hypothesis that exercise intensity, rather than duration or caloric expenditure, was associated with higher ketone levels, the patient experimented with alternative high-intensity regimens (e.g., sprint cycling, and high-intensity circuit training. Ketone levels rebounded following reintroduction of high-intensity activity, suggesting a dose-response relationship.

Key Findings:

Regression Analysis (Model 1: Max Heart Rate as Intensity Proxy):

• Previous day’s ketone level: strongest predictor (β = 0.68, p < 0.001)
• Max heart rate: significant predictor (β = 0.23, p = 0.009)
• Dietary fat ratio, calories ingested, and active calories expended: not significant
• Model R² = 0.70

Regression Analysis (Model 2: Estimated Muscle Glycogen Use):

• Previous day’s ketone level: β = 0.64, p < 0.001
• Estimated glycogen degradation: β = 0.32, p < 0.001
• Calories and fat ratio: not significant
• Model R² = 0.77

Exercise Interventions and Outcomes:

• Intense climbing → High ketones (≥4 mM)
• Moderate biking/walking → Lower ketones
• Interval sprints + HICT → Return to high ketones

This case report suggests that exercise intensity is a modifiable factor that can support or enhance ketone levels during therapeutic ketogenic diets, potentially allowing for more flexible dietary adherence. Controlled studies are needed to establish causality and develop exercise guidelines that optimize ketosis, particularly for cancer patients aiming to maintain therapeutic ketone levels.