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- 02/16/2021

Ketones for Post-exercise Recovery: Potential Applications and Mechanisms

AgroFOOD Industry Hi Tech

Ketogenic diet has been introduced in therapeutic areas for more than a century, but the role of ketones in exercise performance has only been explored in the past decade. One of the main reasons that allows the investigation of the role of ketones in exercise performance is the emergence of exogenous ketones, allowing athletes to achieve the state of ketosis acutely, and independent of their metabolic states. While there are mixed results showing either exogenous ketones improve exercise performance or no effect, the mechanisms of action are still being heavily researched. Moreover, these early data from exercise physiology studies suggested that exogenous ketones may play a more prominent role in post-exercise recovery, leading to a more pronounced cumulative impact over subsequent exercise performance. This review will look at existing evidence on the role of ketones in recovery and attempt to identify the current best practices and potential mechanisms that drive improved recovery.

The impact of ketosis, induced endogenously via a ketogenic diet (Prado et al., 2011; Huang et al., 2018; Ma et al., 2018a,b) or exogenously through exogenous ketones (Cox et al., 2016; Evans and Egan, 2018; Evans et al., 2019; Poffe et al., 2020a,b) on physical performance is an active, quickly evolving area of inquiry. Most studies to date have focused on probing a potential ergogenic impact of acute exogenous ketone ingestion pre-exercise. The corpus is mixed to date and potential utility is dependent on context specificity, on form of exogenous ketone, dosing, co-supplementation, and protocol. However, recent work investigating the role of ketones for post-exercise recovery suggests another more durable and clear application for ketones in sport performance. We identified and screened all relevant studies using the key phrase “ketone and exercise recovery” on PubMed (Figure 1) to identify the current bodies of research in post-exercise recovery involving ketones. Although some early animal studies showed that endogenous ketones, achieved by feeding animals with ketogenic diet, may be protective against oxidative damage and improve recovery (Huang et al., 2018; Ma et al., 2018a), there are also concerns that the lack of carbohydrates in the body may hinder performance, especially in the higher intensity bouts of exercise (Cox et al., 2016). As per Randle cycle, the increase in fatty acid oxidation decreases the glucose metabolic pathway (Randle et al., 1965), and therefore, ketogenic diet upregulating fatty acid metabolism may inhibit glycolytic rates and, subsequently, the capacity to produce ATP independent of oxygen availability. This is especially crucial for explosive and high intensity anaerobic exercises. This has always been the concern of researchers about utilizing ketogenic diet for performance or recovery. However, with the emergence of exogenous ketones, athletes may be able to increase their blood β-hydroxybutyrate (BHB) concentrations and be in ketosis, regardless of the diet they are on as well as being able to stack different substrates with ketones to optimize its effects in performance and recovery.


This review aims to elucidate the findings in animal and clinical work on the impact of ketones for post-exercise recovery, the potential mechanisms of action, and the metabolic interplay with other recovery-relevant metabolic pathways. We also examine the strengths and limitations between endogenous and exogenous ketosis in a post-exercise recovery indication.

Ketogenic Diet and Post-Exercise Recovery
The goal of the ketogenic diet is to achieve optimal nutritional ketosis, which is defined within the range of 0.5 up to 3.0mM of blood BHB but could also potentially reach up to 5–8mM BHB, depending on the keto-adaptability of the individual (Volek and Phinney, 2011; Poff et al., 2020). The earliest studies on ketones were done on ketogenic diet, with investigating if endogenous ketones from ketogenesis have an ergogenic effect on exercise performance and subsequently during recovery post exercise. In animal studies, fat- and keto-adapted mice on ketogenic diet for 8weeks (Table 1) showed enhanced performance without aggravated muscle injury while exerting potential protective effect on organ injury caused by exercise (Ma et al., 2018b). The authors suggested that this may be attributed to the increased efficiency in fat and ketone metabolism in the ketogenic diet group of mice as Ma et al. showed decreased BHB, non-esterified fatty acids (NEFA) and triglycerides during exercise while lipase was unchanged, indicating a more proficient manner at which these metabolites were mobilized and utilized in the ketogenic diet group. The same group of researchers, in another study, showed that an 8-week ketogenic diet not only enhanced exercise performance, but also attenuated muscle damage caused by exhaustive exercise as well. On top of that, the group of mice on ketogenic diet had improved fatigue recovery following exhaustive exercise, which may have contributed to the overall enhanced performance (Huang et al., 2018). The authors also investigate further to determine the potential mechanisms and additional markers that may indicate how ketogenic diet may help with performance and recovery. Plasma interleukin (IL)-6 was previously reported to increase over 100-fold after strenuous exercise (Suzuki et al., 1999, 2000, 2003), and this excessive exercise-induced IL-6 secretion may induce muscle damage and be detrimental to athlete’s health and performance (Suzuki et al., 1999, 2003). Exercise-induced IL-6 was also shown to stimulate lipolysis both in the intramuscular triglycerides’ pool and adipocytes (Path et al., 2001; Carey et al., 2006; Ma et al., 2018a). However, direct mechanism of action connecting ketone to these biomarker changes has not yet been determined. Given the overarching function of IL-6 on lipid metabolism and strenuous exercise, it has become a relevant biomarker to illustrate the relationship between ketogenic diet and exercise. Animal models showed that ketogenic diet may prevent muscle damage in specific muscle fiber types by mitigating excessive IL-6 synthesis and secretion during exercise (Ma et al., 2018a). Another biomarker that is often associated with muscle damage and interference with muscle energy imbalance is creatine kinase (CK). Ketogenic diet may play an important role in decreasing oxidative damage markers such CK and lactate dehydrogenase (LDH) caused by exhaustive exercise (Ma et al., 2018b).



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