Ketone Bodies and Exercise

Much of what we know about the relationship between ketone bodies and exercise comes from pioneering work that occurred in the 60's, 70's and 80's. These works involved infusion of labelled ketone bodies (BHB/AcAc) or fasting in humans to elevate plasma levels of ketone bodies. Mentioned work is relevant to when exercise begins during hyperketonemia. 

Ketone body disposal into skeletal muscle is elevated up to five-fold during exercise, this is seen as a sharp decrease in plasma concentrations of beta-hydroxybutyrate and an increase in the metabolic clearance rate of ketone bodies. This shows exercise increases the body's ability to extract and use ketones as a fuel for muscular work alongside intramuscular carbohydrate and fat liberated from adipose tissue. 

Under prolonged fasting as the degree of ketonemia increases, so does the reduction in plasma levels at the onset of exercise (Fig), reflecting a higher reliance as a fuel source. However, we also see a reduction in the rate of appearance (Ra), rate of disappearance (Rd) and metabolic clearance rate (MCR), suggesting that ketone body production, extraction and clearance is self limiting in skeletal muscle to preserve their use as a fuel source for the brain during times of energy crisis. This threshold is likely around 2.5mM. 

Although the inhibition of oxidation is also present under exogenous ketosis, the initial rise in MCR causes a decrease in ketone body levels, which again stimulates the MCR etc. creating a loop, which is not evident during fasting ketosis, a key difference between the two conditions. As a result of exogenous ketosis in the form of infusions, levels reached approx. 6.0mM and the contribution of ketone bodies to overall fuel provision in these studies has been estimated at 2% over a 2 hour exercise bout at 52% VO2max), an intensity where you would expect a high(er) reliance on fat based metabolism. 

Post Exercise Ketosis (PEK)

At the onset of exercise in the post prandial state, ketone body levels are very low. Under these conditions, the pattern is for levels to slowly rise during the exercise period and continue to do so during the post exercise period, where they can reach 2.0mM and be maintained several hours into recovery. This can be explained by an increase in the Ra and a decrease in MCR at cessation of exercise. However, this effect can be abolished through nutritional manipulation such as glucose or alanine feedings. 

The general findings are that untrained individuals experience a higher degree of PEK than endurance trained individuals. The reason for this may lie in adaptations that take involving the ketogenic and ketolytic pathways during athletic training. However, there are divergent findings due to research methodology.

The role of PEK is likely to favour the replenishment of muscle glycogen, which goes along with the classical role of ketone bodies to preserve carbohydrate stores during times of energy crisis. This may be advantageous to athletes who place a high importance on repletion of muscle glycogen during the recovery period. Ketone bodies also spare protein, reducing alanine release during starvation and leucine oxidation. This suggests hyperketonemia during the post exercise recovery period may play a role in promoting a 'holistic' recovery model by promoting a positive protein balance and prioritising glycogen re-synthesis. 

Next: Training Adaptations and Ketone Pathways

References:

Beattie MA & Winder WW (1984). Mechanism of training-induced attenuation of postexercise ketosis. Am J Physiol Regul Integr Comp Physiol 247, R780–R785.

Balasse EO & Fery F (1989). Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev 5, 247–270.

Fery F & Balasse EO (1983). Ketone body turnover during and after exercise in overnight-fasted and starved humans. Am J Physiol Endocrinol Metab 245, E318–E325.

Fery F & Balasse EO (1986). Response of ketone body metabolism to exercise during transition from postabsorptive to fasted state. Am J Physiol Endocrinol Metab 250, E495–E501. 

Johnson RH & Walton JL (1972). The effect of exercise upon acetoacetate metabolism in athletes and non-athletes. Q J Exp Physiol Cogn Med Sci 57, 73–79. 

Koeslag JH (1982). Post-exercise ketosis and the hormone response to exercise: a review. Med Sci Sports Exerc 14, 327–334.

Nair KS, Welle SL, Halliday D & Campbell RG (1988). Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest 82, 198–205. 

Sherwin RS, Hendler RG & Felig P (1975). Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest 55, 1382–1390.