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Are ketone esters a super fuel?



Ketone esters achieved “super fuel” status after a study led by Dr. Pete Cox entitled “Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes” was published in 2016. [5]

Cox et al Cell Metabolism July 2016
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The research team concluded that the ingestion of ketone esters was associated with muscle-glycogen sparing during exercise and, as a result, improved endurance performance. The researchers also suggested that the advantage was primarily due to the fact that ketone body oxidation is thermodynamically advantageous to that of carbohydrate oxidation. In essence, ketones were shown to be more efficient in their energy production.


However, the study had shortcomings. First, the subjects were tested in a fasted state over a two-hour period under constant load at 70 percent of VO2max. This low carbohydrate state is not a realistic representation of the fuel state for an endurance event, and in a fasted state the body will naturally transition from carbohydrates to fats for its energy.


Furthermore, operating at 70 percent of VO2max is not representative of a mass start cycling competition—road, cyclocross, or cross-country mountain biking—where competitors are hitting a spectrum of intensity levels or operating entirely at above-threshold intensities.


More recent studies have also poked holes in the Cox study. It is important to remember that metabolic pathways work in combination with each other in varying ratios depending on the energy demand, and never work in isolation.


Dr. Petrick and his research team discovered that when pyruvate—a molecule derived from glucose metabolism—was readily available, the use of ketones for fuel decreased in muscles. [6] This suggests that when adequate carbohydrate stores are in place, ketones become irrelevant as a fuel source.


Furthermore, this team’s findings contradicted the conclusion of the Cox team that ketones provided a thermodynamic advantage. In fact, the data suggested that the thermodynamic efficiency between the two fuel sources (ketones and carbohydrates) was identical.


Finally, the authors also stated that pyruvate generated three times greater amounts of ATP than ketones.


Numerous other studies, including those by Dr. Poffé, dispute the conclusions made by Cox and his team in 2016. [7,8]


Following is a summary of this recent research:

  • There is no thermodynamic advantage of ketones.

  • Exogenous ketones do not positively impact endurance performance when evidence-based recommendations for carbohydrate consumption are followed.

  • Ketone ester supplementation alone decreases blood pH, ultimately mitigating potential ergogenic gains to improve endurance performance and likely producing a detrimental effect on performance.

Can ketones boost recovery?

In 2019, Poffé and his team tested the potential for ketone esters to improve recovery and mitigate the development of non-functional overreaching symptoms during blocks of heavy training loads.


In the study, elite athletes were tested over a three-week period of heavy training. Both study and control groups received standardised carbohydrate-rich dinners and breakfasts, as well as an optimal recovery carbohydrate plus protein mix within 30 minutes of completing their workouts. The ketone esters group was also provided 25 grams of esters post-workout to increase their plasma ketone concentrations.


The findings produced some positive results regarding supplementation. For background, autonomic neural imbalance plays a critical role in the development of non-functional overreach. This is why monitoring and measuring both HRV and resting heart rate have become popular. HRV tends to decline in times of imbalance, while resting heart rate will increase.


In the Poffé study, the control group suffered from sympathetic stress which, among other things, negatively impacted resting heart rate. In the test group, ketone ester supplementation mitigated this. [8]


Additionally, the control group experienced increased heart rates during workouts and decreased maximal heart rates by 10-28 beats over the three-week training period. For the test group, supplementation counteracted these effects of fatigue on the heart.

Another major issue with increasing training loads or stage racing is a gradual loss of appetite, with energy intake not matching energy output, resulting in an energy imbalance. In the 2019 Poffé study, the control groups’ energy intake remained constant while the training load increased. However, in the ketone ester group, the participants’ energy intake spontaneously (without guidance or direction) increased to meet the higher energy demands. This increase in energy intake was primarily due to increased carbohydrate intake, and resulted in an energy balance for the participants.


Energy balance is particularly critical in non-weight-bearing sports like swimming and cycling, since an imbalance between output and intake can contribute to bone demineralisation. This study revealed that the increasing training load triggered a stress-induced hormone, GDF15, which decreased appetite.


GDF15 also decreases osteocalcin, a crucial protein for strong bones. Based on the findings of Poffé, it appeared ketone ester supplementation, when used as a recovery protocol, could help mitigate the unfavourable effects of GDF15. (Interestingly, this study may have stumbled upon a more reliable marker of non-functional overreaching in the form of GDF15.)


Taken together, ketone ester supplementation used as a recovery protocol would allow the athlete to endure greater training loads to achieve the intended adaptations while avoiding the pitfalls of non-functional overreaching.


In this study, the ketone ester group tolerated a 15 percent increase in their training load, which then resulted in the improvement of their 120-minute endurance performance.

That said, questions abound. For one, were the ketone esters mitigating overreach or just masking the symptoms? And, if it was the latter, is it healthy and beneficial to mask symptoms of overreaching? Or are these valuable signs that should guide our decision-making?


Dr. Lis has used ketone ester supplementation for recovery with a few riders, with some success.


“But I am not sure if it’s the result of the placebo effect—and it is expensive. I think it only makes sense to use ketone esters as a recovery strategy when aggressive recovery is required— for example, during an arduous three-week stage race. For normal people, it’s likely more important to focus on the fundamentals of recovery: eating, hydrating, and sleeping well.”


It’s hard to improve on the fundamentals

Other than the Cox study, which produced positive results of ketone body intake on a 30-minute time trial performance, most studies have not produced positive results when testing acute ketogenic supplementation before and/or during exercise to boost performance.


In fact, subsequent studies indicated that ketone ester ingestion alone impaired performance by inhibiting glycolysis required for high intensity work and triggering metabolic acidosis (a drop in blood pH).


These studies also concluded that the body did not transition to ketones as the preferred fuel when appropriate carbohydrates were in place to fuel training and racing. In addition, these studies established that there is a hierarchy of fuel use, and when athletes were fuelled appropriately with carbohydrates, ketones did not replace glycogen oxidation and, therefore, did not spare glycogen. Muscles prefers glycogen, or its derivative pyruvate, over ketones.


The studies of Poffé and his colleagues suggest ketone ester supplementation may be used as a recovery protocol to facilitate greater tolerance of training loads.

All of this to say, for those athletes seeking improved performance , your time and focus are best invested in the fundamentals: consistently and purposely training and resting hard in a systematic fashion over time, as well as establishing healthy habits of nutrition, hydration, and sleep. There are no silver bullets or short cuts; fall in love with the process and performance will follow.


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References

  1. Elamin, M., Ruskin, D. N., Masino, S. A., & Sacchetti, P. (2017). Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism? Frontiers in Molecular Neuroscience, 10, 377. Retrieved from https://doi.org/10.3389/fnmol.2017.00377

  2. Hagihara, K., Kajimoto, K., Osaga, S., Nagai, N., Shimosegawa, E., Nakata, H., … Kijima, T. (2020). Promising Effect of a New Ketogenic Diet Regimen in Patients with Advanced Cancer. Nutrients, 12(5), 1473. Retrieved from https://doi.org/10.3390/nu12051473

  3. Dearlove, D., Faull, O., & Clarke, K. (2019). Context is key: exogenous ketosis and athletic performance. Current Opinion in Physiology, 10: 81-89. https://doi.org/10.1016/j.cophys.2019.04.010. https://www.sciencedirect.com/science/article/pii/S2468867319300586

  4. Burke, L. M., Ross, M. L., Garvican‐Lewis, L. A., Welvaert, M., Heikura, I. A., Forbes, S. G., … Hawley, J. A. (2017). Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers. The Journal of Physiology, 595(9), 2785–2807. Retrieved from https://doi.org/10.1113/jp273230

  5. Cox, P., Kirk T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, A., Stubbs, B., West, J., McLure, S., King, M., Dodd, M., Holloway, C., Neubauer, S., Drawer, S., Veech, R., Griffin, J., & Clarke K (2016). Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metabolism 24, 256–268. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30355-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413116303552%3Fshowall%3Dtrue

  6. Petrick, H.L., Brunetta, H.S., Pignanelli, C., Nunes, E.A., van Loon, L.J.C., Burr, J.F. and Holloway, G.P. (2020), In vitro ketone‐supported mitochondrial respiration is minimal when other substrates are readily available in cardiac and skeletal muscle. J Physiol, 598: 4869-4885. https://doi.org/10.1113/JP280032

  7. Pinckaers, P. J., Churchward-Venne, T. A., Bailey, D., & van Loon, L. J. (2017). Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?. Sports medicine (Auckland, N.Z.), 47(3), 383–391. https://doi.org/10.1007/s40279-016-0577-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309297/

  8. Poffé, C., Ramaekers, M., Van Thienen, R. and Hespel, P. (2019), Ketone ester supplementation blunts overreaching symptoms during endurance training overload. The Journal of Physiology, 597: 3009-3027. https://doi.org/10.1113/JP277831. https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277831

  9. PoffÉ, C., Ramaekers, M., Bogaerts, S., & Hespel, P. (2020). Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise. Medicine & Science in Sports & Exercise, 53(2), 431–441. https://doi.org/10.1249/MSS.0000000000002467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803447/

  10. Poffé, C. & Hespel, P. (2020), Ketone bodies: beyond their role as a potential energy substrate in exercise. The Journal of Physiology, 598: 4749-4750. https://doi.org/10.1113/JP280597. https://www.researchgate.net/publication/344381474_Ketone_bodies_beyond_their_role_as_a_potential_energy_substrate_in_exercise

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