The Ketogenic Diet Alters Endocrine Regulation of Energy Metabolism in Ultra-Endurance Athletes
Abstract
Purpose
The ketogenic diet induces a profound shift in energy metabolism from carbohydrate oxidation towards fat oxidation, both at rest and during exercise. We compared endocrine regulators of energy metabolism in keto-adapted and non-keto-adapted ultra-endurance athletes before, during, and after aerobic exercise to better understand the role of endocrine function in adaptation to a ketogenic diet (keto-adaptation).
Methods
Twenty elite ultra-endurance athletes (male, age 33.5 ± 6.4 yr, BMI 22.1 ± 1.5 kg/m2, VO2max 64.5 ± 4.9 mL/kg/min) who habitually consumed a high-carbohydrate (HC, 59:14:25 % carbohydrate:protein:fat) or very-low carbohydrate (LC, 10:19:70) diet for at least 6 months ran on a treadmill for 180 min at 64% of VO2max. Glucagon, cortisol, and leptin were measured from serum collected before exercise (BL); 60 and 120 min after initiation of exercise (RUN60, RUN120); and 0, 60, and 120 min after completion of exercise (IP, P60, P120). After BL and IP, participants consumed a shake with macronutrient ratios similar to their habitual diet (5 kcal/kg body mass, HC: 50:36:14, LC: 5:81:14 % carbohydrate:protein:fat). Glucagon, cortisol, and leptin were further analyzed for correlations with non-esterified fatty acids (NEFA), glycerol, β-hydroxybutyrate, total ketones, insulin, glucose, and muscle glycogen.
Results
Glucagon increased with exercise (p<0.0001) and was significantly higher in keto-adapted athletes at all time points except IP and P120 (p<0.05). Cortisol also increased with exercise (p<0.0001) and was significantly higher in keto-adapted athletes at RUN60 (p<0.05). Leptin decreased with exercise (p<0.0001), but without any significant effect of diet. Glucagon and, to a lesser extent, cortisol positively correlated with markers of increased fat oxidation (β-hydroxybutyrate, total ketones, NEFA, and glycerol, p<0.05) and negatively correlated with markers of increased carbohydrate metabolism (glucose, insulin, and lactate, p<0.05). Glucagon's correlations with β-hydroxybutyrate and total ketones were persistent, occurring at all time points except BL (p<0.01). Glucagon and cortisol also positively correlated with each other at P120 (p<0.005). Muscle glycogen content negatively correlated with glucagon at IP (p<0.05) and positively correlated with leptin at P120 (p<0.05).
Conclusion
In elite ultra-endurance athletes, a long-term ketogenic diet is associated with higher glucagon levels before, during, and after aerobic exercise. This is in conjunction with a more than two-fold higher rate of peak fat oxidation, indicating glucagon may have an important role in keto-adaptation. The similar but less persistent patterns of cortisol suggest these two hormones may contribute to keto-adaptation in a coordinated manner.
Support or Funding Information
Support for this work was provided by Quest Nutrition and The Robert C. and Veronica Atkins Foundation.
