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Sports 2019, 7(2), 40; https://doi.org/10.3390/sports7020040

Review
Keto-Adaptation and Endurance Exercise Capacity, Fatigue Recovery, and Exercise-Induced Muscle and Organ Damage Prevention: A Narrative Review
1
Graduate School of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, Japan
2
Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, Japan
*
Author to whom correspondence should be addressed.
Received: 5 January 2019 / Accepted: 10 February 2019 / Published: 13 February 2019

Abstract

:
A ketogenic diet (KD) could induce nutritional ketosis. Over time, the body will acclimate to use ketone bodies as a primary fuel to achieve keto-adaptation. Keto-adaptation may provide a consistent and fast energy supply, thus improving exercise performance and capacity. With its anti-inflammatory and anti-oxidative properties, a KD may contribute to muscle health, thus preventing exercise-induced fatigue and damage. Given the solid basis of its potential to improve exercise capacity, numerous investigations into KD and exercise have been carried out in recent years. This narrative review aims to summarize recent research about the potential of a KD as a nutritional approach during endurance exercise, focusing on endurance capacity, recovery from fatigue, and the prevention of exhaustive exercise-induced muscle and organ damage.
Keywords:
ketogenic diet; keto-adaptation; fatigue; muscle damage; organ damage

1. Introduction

Our metabolic system is remarkably flexible in its ability to use a variety of dietary macronutrients as fuels. Traditionally, carbohydrate-centered diets have been recommended for sports [1,2,3,4,5]. Carbohydrate-loading is one of the main nutritional strategies to improve exercise performance before crucial events [6,7,8,9,10]. However, for excellent athletes competing in endurance sports, this strategy may lead to an awkward dilemma. The capacity for the human body to store carbohydrates is limited, which is 5 g glucose in blood circulation and ~100 g or ~500 g glycogen in skeletal muscle or liver. A person of average weight may store 10 kg fat in the body, which makes the person capable of completing >30 marathon races if the stored fat is effectively utilized [11,12,13,14]. However, the abundant carbohydrates in traditional high-fat diets may restrict us from utilizing fat [15,16,17,18,19,20]. Therefore, whether we can find an effective way to enhance fat utilization is an important question.
A ketogenic diet (KD) involves using fat, a high-density substrate, as the main source in daily calorie intake while restricting carbohydrate intake [21,22]. In this way, the liver is forced to produce and release ketone bodies into the circulation [23,24,25,26]. This phenomenon is called nutritional ketosis [27,28,29]. Over time, the body will acclimate to using ketone bodies as a primary fuel, which is called keto-adaptation, an element of fat-adaptation [30,31,32]. Glucose oxidation requires 11 steps to produce energy, whereas fat and ketone bodies can quickly provide energy in only three steps [33,34]. In any case, the capacity for the body to reserve ketone bodies and fat is much stronger. Compared to glucose, ketone bodies are more energy-intensive, while a ketone body-centered metabolism has the potential to provide a consistent, fast energy supply [35]. Despite the potential to increase exercise performance and capacity, a KD may also contribute to muscle health by anti-inflammatory and anti-oxidative properties, thus preventing exercise-induced fatigue and muscle and organ damage [35,36,37,38,39,40,41,42,43,44]. Compared to glucose oxidation, fat-centered oxidation involves producing less reactive oxygen species during the process. Excessive free radicals and chronic inflammation are harmful to mitochondria, muscular cells, and whole-body health [45]. Long-term KD administration is linked with reduced inflammatory mediators by down-regulating NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome expression and reducing the generation of isoprostanes [46,47]. It is also reported that a high-fat diet could contribute to mitochondrial biogenesis and reduce mitochondrial autophagy, thus contributing to a rich mitochondrial reservoir in the muscle, boosting exercise performance, and contributing to athletes’ wellbeing [48,49].
Given the solid basis of its potential to improve exercise capacity, numerous investigations on KD and exercise have been carried out in recent years. This review aims to summarize the recent literature (mainly articles published in the past three years) about the potential of KDs as a nutritional approach during endurance exercise, in a narrative way. We searched MedLine extensively with the Medical Subject Headings (MeSH term) diet, ketogenic, ketone body, ketosis, and related keywords to access related articles. The main focus of this article is on endurance capacity, fatigue recovery, and the multi-faceted approach to prevent exhaustive exercise-induced muscle and organ damage.

2. KD, Keto-Adaptation, and Endurance Exercise Capacity

In interesting research conducted in keto-adapted ultra-endurance runners, keto-adaptation promoted higher peak fat oxidation (2.3-fold higher compared to un-adapted athletes, n = 10) [50]. This result has been attributed to increased fat oxidation capacity. In 2016, an article from Cell Metabolism reported that exhaustive cycling performance was improved by nutritional ketosis [51]. In 2019, McKay and colleagues reported that in keto-adapted elite race walkers, after a standardized 19–25 km race walk, IL-6, which is the myokine that may induce intense lipolysis, was measured. Subjects that adhered to a low-carbohydrate high-fat diet were significantly higher, exhibiting a potential performance enhancement in endurance capacity. However, as the authors concluded in this paper, the circulating IL-6 might be harmful inflammatory cytokines and may cause side effects [52]. This might be a limitation of the human study, and a well-designed in vivo or in vitro experiment may validate this result. Parry and colleagues reported that in an experiment that lasted for 762 days, muscle mitochondrial volume was increased by a KD (citrate synthase in gastrocnemius, p < 0.05 compared with the control, n = 8) [53,54]. Shimizu et al. reported that a 12-week KD combined with daily treadmill exercise induced higher gene expression in markers of fatty acid oxidation, as compared with the control diet combined with exercise (n = 6) [55]. We also reported that ketolytic metabolism and lipolytic metabolism were re-modeled by an eight-week KD in mice, therefore enhancing their endurance [35,36,37,38]. These results explain the partial mechanisms by which keto-adaption showed great potential in improving endurance exercise capacity.
However, on the contrary, Zinn et al. reported in a pilot study that in New Zealand endurance athletes, KD increased benefit in body composition and wellbeing, but failed to enhance endurance capacity [56]. The mean age of those subjects was 51.2 years old; thus, the generality of this study to younger athletes should be considered. Meanwhile, a low-carbohydrate, high-fat diet impaired exercise economy and performance after intensified training in a group of elite race walkers [57]. In an animal model, however, eight weeks of KD significantly enhanced the endurance capacity of C57/BL6 mice (n = 8) [35,36,37]. In this study, a correlation existed between body weight and running time until exhaustion, with mice on heavier a KD running longer. This was attributed to keto-adaptation [35]. Since there was an inter-individual difference, the subjects possessing higher metabolic flexibility may prefer KD and reflect the weight change. After a two-month KD, the average weight of KD mice decreased by 30% compared with normal diet-fed mice [36].

3. Keto-Adaptation, Fatigue Prevention, and Recovery

Glycogen depletion, lactate accumulation, and oxidative stress are considered the main factors promoting exercise-induced fatigue. While lactate may not be a reason causing fatigue, a higher removal rate of lactic acid is usually employed as a post-exercise fatigue indicator. In 2014, Zajac and colleagues reported that a one-month KD improved the lactate threshold in off-road cyclists [50]. In the article published in Cell Metabolism, nutritional ketosis was induced. Lactate concentrations were significantly lower with KD administration, resulting in a 50% reduction in lactate concentrations 30 min after exercise commencement compared to the non-KD group [51]. Carr et al. reported that compared to high-carbohydrate groups, low-carbohydrate KD ingestion contributed to a lower lactate accumulation post-endurance exercise (n = 8) [58]. In an animal study, after exhaustive exercise, muscle lactate was much lower in keto-adapted mice. After 24 h of rest, plasma lactate dropped more quickly in the keto-adapted subjects, showing that keto-adaptation has the potential to prevent fatigue or boost recovery after subjects reach fatigue [37].
In the study conducted in keto-adapted ultra-endurance athletes, after a 3-h submaximal exercise, muscle glycogen decreased in both KD-adapted athletes and un-adapted athletes, with no difference between them [59]. In another study, keto-adaptation contributed to a slower glycogen drop during 1 h of submaximal exercise [51]. These results imply the metabolic flexibility of muscle glycogen regulation via gluconeogenesis and the conservation of glycogen, thus potentially contributing to the prevention of fatigue.
In a 762-day experiment conducted in sedentary rats, either muscle, liver, or brain superoxide dismutase (SOD) 1 and 2, catalase, glutathione peroxidase (GPX), and 4-hydroxynonenal (4-HNE) conjugated protein were measured at the end, though no significance was observed [53]. In a mouse model involving exhaustive exercise, the hepatic protein carbonyl level was lower in the keto-adapted mice, whereas the same marker was significantly higher in the muscle tissue [37]. However, oxidative stress plays a subtle role in muscle hypertrophy; thus, reservations should be held on this issue. Evidence surrounding keto-adaptation and oxidative stress are limited; thus, future studies in this field are required.
On the other hand, it is also reported that a KD may induce fatigue perception, as a direct correlation between blood ketone bodies and fatigue was reported [60]. However, this study was conducted in overweight subjects, and the results may not relate to athletic groups. To summarize, though some negative results of keto-adaptation are reported, a solid basis and abundant evidence about the potential of KD on fatigue prevention and recovery makes it necessary to validate the efficacy of KD in future studies.

4. Keto-Adaption and Exercise-Induced Muscle/Organ Damage

Some scholars and researchers question whether a KD may contribute to weight loss, which may induce decreased muscle volume. However, in a randomized control trial, gymnasts consuming a one-month KD while receiving the same training did not lose muscle; instead, they experienced a non-significant increase of muscle mass (pre, 37.6 kg ± 3.9 vs. post, 37.9 kg ± 4.5, n = 4). Meanwhile, their average weight and fat mass significantly decreased. Furthermore, exercise performance was not influenced. In comparison, a typical western diet did not cause any significant difference in the experimental period [61]. Animal experiments have also provided evidence. An eight-week KD enhanced endurance exercise capacity in mice, while the percentage of muscle mass was not altered [37]. Kephart et al. conducted a three-month KD-intervention experiment in CrossFit trainees [62]. The authors warned that though no significance was observed in the present study, KD may reduce leg muscle mass; that is to say, prolonged KD may negatively influence muscle mass. However, combining long-term KD with other supplementation or periodic nutritional strategies may be a solution to counteract any loss of mass.
Blood levels of creatine kinase (CK) and lactate dehydrogenase (LDH) are usually used as muscle-damage markers. In Zajac’s research, a four-week KD significantly decreased CK and LDH activities, both at rest and after a 105-min cycling exercise [50]. Similar results were also found in animal studies. After a 24-h rest post-exhaustive exercise, plasma CK was reduced in KD-fed subjects, while in the normal-fed subjects, plasma CK was still significantly elevated due to the influence of acute exercise [37]. Organ damage-preventive effects were also reported. Blood urea nitrogen (BUN) and alanine transaminase (ALT) were usually employed as markers of exercise-induced acute renal damage and acute hepatic damage. In the previously narrated experiments, both markers were significantly decreased by a KD following an exhaustive exercise, both immediately after exercise and 24 h post-exercise [35,36].

5. Prospect: Combination of a KD with Other Supplementations, Exogenous Ketone Bodies, and Their Limitations

Though solid evidence has been collected about the potential of KD as a nutritional approach, based on recent studies, it is also worth addressing that a traditional KD may have limits and flaws. In a recent study, following a 12-week KD, corpuscular hemoglobin and mean corpuscular hemoglobin concentration decreased within endurance athletes (n = 9) [63]. Iron inefficiency and other pathological conditions may contribute to the above results, thus impairing endurance exercise capacity. Red blood cell status may need to be occasionally measured for athlete wellbeing. Vitamin E and iron supplementation or a high-altitude training plan that could promote erythropoietin production may help to resolve this problem [64,65,66].
As we discussed above, a KD may induce muscle loss and excess oxidative stress. To prevent oxidative damage, oxidative state and muscle mass may need to be occasionally monitored; antioxidant consumption is also recommended [37]. Green tea extract, curcumin, and some polyphenols have been extensively reported for their anti-oxidative properties together with endurance-enhancing properties; thus, the combination of KD and such antioxidants may be preferred [67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84]. Branched-chain amino acids (BCAA) are widely reported for their protective effects on muscle atrophy and muscle damage, and the combined use of BCAA or BCAA-like supplements and KD may be preferred to sustain muscle mass [85,86,87,88,89,90,91].
Another supplement that should be addressed is ketone supplements. These supplements usually constitute β-Hydroxybutyrate [92,93,94]. Exogenous ketone body ingestion could elevate blood ketones in a short time and induce acute ketosis [93,94,95,96,97]. It is reported that one-week or eight-month administration of ketone salt supplementation may be beneficial for multi-organ markers of oxidative stress and mitochondrial function [98]. However, there is insufficient data to prove whether exogenous ketone ingestion could successfully induce keto-adaptation, and the presumption itself may be speculative [99].
In a recent review about nutritional supplements that could induce ketosis, a negative conclusion was also reported; exogenous ketones may inhibit endogenous ketone production, and this application is more of mimicking effects [100].
KD was reported to cause hepatic insulin resistance in several studies, which could be attributed to increased hepatic diacylglycerol content that may lead to impaired insulin signaling. Hepatic steatosis and inflammation, as well as increased endoplasmic reticulum (ER) stress, were found in mice fed by a 12-week KD. Increased accumulation and size of macrophages were found in 12-week KD-fed mice, indicating that long-term KD application may aggravate exercise-induced inflammation. Apoptosis-related gene X-box binding protein 1 (Xbp1) was found to increase in the liver, indicating ER stress and hepatocyte apoptosis. A histological study showed that KD induced obvious fat vacuoles [101]. As the primary site for lipid metabolism, patients with impaired hepatic function, such as nonalcoholic fatty liver, should be cautious. Pancreas α-cell and β-cell masses were both reduced following a 22-week KD administration, thus leading to glucose intolerance [102]. Restricted intake of carbohydrate-enriched fruits or cereals may induce a headache, according to several KD studies [103,104]. A multi-task test that requires higher mental processing may be adversely affected by the KD according to a study [105]. These are potential symptoms that might happen during keto-adaptation and continual ketosis. A KD has potential and limitations, and further studies are warranted to investigate the combination of KD and other supplementations, or how to apply KD as a periodic nutritional approach, in order to discover a strategy for KD application.

Author Contributions

K.S. was the principal investigator and had primary responsibility for the final content. S.M. and K.S. read, critically revised, and approved the final manuscript.

Funding

S.M. received a fellowship from the China Scholarship Council. This study was part of the research activities of the Human Performance Laboratory, Organization for University Research Initiatives, Waseda University.

Acknowledgments

We want to thank Llion Roberts, School of Allied Health Sciences and Menzies Health Institute Queensland, Griffith University for valuable opinions and English editing.

Conflicts of Interest

The authors have no conflicts to declare.

References

  1. Hargreaves, M.; Costill, D.L.; Coggan, A.; Fink, W.J.; Nishibata, I. Effect of carbohydrate feedings on muscle glycogen utilization and exercise performance. Med. Sci. Sports Exerc. 1996, 16, 219–222. [Google Scholar] [CrossRef]
  2. Neufer, P.D.; Costill, D.L.; Flynn, M.G.; Kirwan, J.P.; Mitchell, J.B.; Houmard, J. Improvements in exercise performance: Effects of carbohydrate feedings and diet. J. Appl. Physiol. 1987, 62, 983–988. [Google Scholar] [CrossRef] [PubMed]
  3. Jeukendrup, A.E.; Brouns, F.J.P.H.; Wagenmakers, A.J.M.; Saris, W.H.M. Carbohydrate-electrolyte feedings improve 1 h time trial cycling performance. Int. J. Sports Med. 1997, 18, 125–129. [Google Scholar] [CrossRef] [PubMed]
  4. Jeukendrup, A.E. Carbohydrate intake during exercise and performance. Nutrition 2004, 20, 669–677. [Google Scholar] [CrossRef] [PubMed]
  5. Pomportes, L.; Brisswalter, J.; Hays, A.; Davranche, K. Effect of carbohydrate intake on maximal power output and cognitive performances. Sports 2016, 4, 49. [Google Scholar] [CrossRef] [PubMed]
  6. Rountree, J.A.; Krings, B.M.; Peterson, T.J.; Thigpen, A.G.; McAllister, M.J.; Holmes, M.E.; Smith, J.W. Efficacy of Carbohydrate Ingestion on CrossFit Exercise Performance. Sports 2017, 5, 61. [Google Scholar] [CrossRef]
  7. Newell, M.L.; Wallis, G.A.; Hunter, A.M.; Tipton, K.D.; Galloway, S.D. Metabolic responses to carbohydrate ingestion during exercise: Associations between carbohydrate dose and endurance performance. Nutrients 2018, 10, 37. [Google Scholar] [CrossRef]
  8. Febbraio, M.A.; Chiu, A.; Angus, D.J.; Arkinstall, M.J.; Hawley, J.A. Effects of carbohydrate ingestion before and during exercise on glucose kinetics and performance. J. Appl. Physiol. 2000, 89, 2220–2226. [Google Scholar] [CrossRef][Green Version]
  9. Chinevere, T.D.; Sawyer, R.D.; Creer, A.R.; Conlee, R.K.; Parcell, A.C. Effects of L-tyrosine and carbohydrate ingestion on endurance exercise performance. J. Appl. Physiol. 2002, 93, 1590–1597. [Google Scholar] [CrossRef]
  10. Jeukendrup, A.E. Carbohydrate and exercise performance: The role of multiple transportable carbohydrates. Curr. Opin. Clin. Nutr. Metab. Care 2010, 13, 452–457. [Google Scholar] [CrossRef]
  11. Jensen, J.; Rustad, P.I.; Kolnes, A.J.; Lai, Y.C. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise. Front. Physiol. 2011, 2, 112. [Google Scholar] [CrossRef] [PubMed]
  12. Horowitz, J.F. Fatty acid mobilization from adipose tissue during exercise. Trends Endocrinol. Metabol. 2003, 14, 386–392. [Google Scholar] [CrossRef]
  13. Fleck, S.J. Body composition of elite American athletes. Am. J. Sports Med. 1983, 11, 398–403. [Google Scholar] [CrossRef] [PubMed]
  14. Schutz, Y.; Flatt, J.P.; Jéquier, E. Failure of dietary fat intake to promote fat oxidation: A factor favoring the development of obesity. Am. J. Clin. Nutr. 1989, 50, 307–314. [Google Scholar] [CrossRef] [PubMed]
  15. Achten, J.; Jeukendrup, A.E. Optimizing fat oxidation through exercise and diet. Nutrition 2004, 20, 716–727. [Google Scholar] [CrossRef] [PubMed]
  16. Coggan, A.R.; Raguso, C.A.; Gastaldelli, A.; Sidossis, L.S.; Yeckel, C.W. Fat metabolism during high-intensity exercise in endurance-trained and untrained men. Metabolism 2000, 49, 122–128. [Google Scholar] [CrossRef]
  17. Watt, M.J.; Heigenhauser, G.J.F.; Dyck, D.J.; Spriet, L.L. Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man. J. Physiol. 2002, 541, 969–978. [Google Scholar] [CrossRef] [PubMed][Green Version]
  18. Volek, J.S.; Noakes, T.; Phinney, S.D. Rethinking fat as a fuel for endurance exercise. Eur. J. Sport Sci. 2015, 15, 13–20. [Google Scholar] [CrossRef] [PubMed]
  19. Lambert, E.V.; Speechly, D.P.; Dennis, S.C.; Noakes, T.D. Enhanced endurance in trained cyclists during moderate intensity exercise following 2 weeks adaptation to a high fat diet. Eur. J. Appl. Physiol. 1994, 69, 287–293. [Google Scholar] [CrossRef]
  20. Hancock, C.R.; Han, D.-H.; Chen, M.; Terada, S.; Yasuda, T.; Wright, D.C.; Holloszy, J.O. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc. Natl. Acad. Sci. USA 2008, 105, 7815–7820. [Google Scholar] [CrossRef][Green Version]
  21. Freeman, J.M.; Kelly, M.T.; Freeman, J.B. The Epilepsy Diet Treatment: An Introduction to the Ketogenic Diet (No. Ed. 2); Demos Vermande: New York, NY, USA, 1996. [Google Scholar]
  22. Hartman, A.L.; Vining, E.P. Clinical aspects of the ketogenic diet. Epilepsia 2007, 48, 31–42. [Google Scholar] [CrossRef] [PubMed]
  23. Astrup, A.; Larsen, T.M.; Harper, A. Atkins and other low-carbohydrate diets: Hoax or an effective tool for weight loss? Lancet 2004, 364, 897–899. [Google Scholar] [CrossRef]
  24. Ballaban-Gil, K.; Callahan, C.; O’dell, C.; Pappo, M.; Moshé, S.; Shinnar, S. Complications of the ketogenic diet. Epilepsia 1998, 39, 744–748. [Google Scholar] [CrossRef] [PubMed]
  25. Kennedy, A.R.; Pissios, P.; Otu, H.; Xue, B.; Asakura, K.; Furukawa, N.; Marino, F.E.; Liu, F.F.; Kahn, B.B.; Libermann, T.A.; et al. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am. J. Physiol. Endocrinol. Metab. 2007, 292, E1724–E1739. [Google Scholar] [CrossRef] [PubMed]
  26. Badman, M.K.; Kennedy, A.R.; Adams, A.C.; Pissios, P.; Maratos-Flier, E. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss. Am. J. Physiol. Endocrinol. Metab. 2009, 297, E1197–E1204. [Google Scholar] [CrossRef] [PubMed][Green Version]
  27. Jornayvaz, F.R.; Jurczak, M.J.; Lee, H.Y.; Birkenfeld, A.L.; Frederick, D.W.; Zhang, D.; Zhang, X.M.; Samuel, V.T.; Shulman, G.I. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E808–E815. [Google Scholar] [CrossRef] [PubMed][Green Version]
  28. McGrice, M.; Porter, J. The effect of low carbohydrate diets on fertility hormones and outcomes in overweight and obese women: A systematic review. Nutrients 2017, 9, 204. [Google Scholar] [CrossRef] [PubMed]
  29. McSwiney, F.T.; Wardrop, B.; Hyde, P.N.; Lafountain, R.A.; Volek, J.S.; Doyle, L. Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes. Metabolism 2018, 81, 25–34. [Google Scholar] [CrossRef] [PubMed]
  30. Hyde, P.N.; Lustberg, M.B.; Miller, V.J.; LaFountain, R.A.; Volek, J.S. Pleiotropic effects of nutritional ketosis: Conceptual framework for keto-adaptation as a breast cancer therapy. Cancer Treat. Res. Commun. 2017, 12, 32–39. [Google Scholar] [CrossRef]
  31. Hyde, P.N.; Cissn, V.J.M. Keto-Adaptation in Health and fitness. In Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease; Oxford University Press: Oxford, UK, 2016; p. 376. [Google Scholar]
  32. Campbell, I. Starvation, exercise, injury and obesity. Anaesth. Intensiv. Care Med. 2007, 8, 299–303. [Google Scholar] [CrossRef]
  33. Krebs, H.A. The regulation of the release of ketone bodies by the liver. Adv. Enzym. Regul. 1966, 4, 339–353. [Google Scholar] [CrossRef]
  34. Burstal, R.J.; Reilly, J.R.; Burstal, B. Fasting or starving? Measurement of blood ketone levels in 100 fasted elective and emergency adult surgical patients at an Australian tertiary hospital. Anaesth. Intensiv. Care 2018, 46, 463–467. [Google Scholar] [CrossRef]
  35. Ma, S.; Huang, Q.; Yada, K.; Liu, C.; Suzuki, K. An 8-week ketogenic low carbohydrate, high fat diet enhanced exhaustive exercise capacity in mice. Nutrients 2018, 10, 673. [Google Scholar] [CrossRef]
  36. Huang, Q.; Ma, S.; Tominaga, T.; Suzuki, K.; Liu, C. An 8-Week, Low carbohydrate, high fat, ketogenic diet enhanced exhaustive exercise capacity in mice Part 2: Effect on fatigue recovery, post-exercise biomarkers and anti-oxidation capacity. Nutrients 2018, 10, 1339. [Google Scholar] [CrossRef]
  37. Ma, S.; Huang, Q.; Tominaga, T.; Liu, C.; Suzuki, K. An 8-Week Ketogenic Diet Alternated Interleukin-6, Ketolytic and Lipolytic Gene Expression, and Enhanced Exercise Capacity in Mice. Nutrients 2018, 10, 1696. [Google Scholar] [CrossRef] [PubMed]
  38. Ma, S.; Suzuki, K. Potential application of ketogenic diet to metabolic status and exercise performance: A review. EC Nutr. 2018, 13, 496–499. [Google Scholar]
  39. Jarrett, S.G.; Milder, J.B.; Liang, L.P.; Patel, M. The ketogenic diet increases mitochondrial glutathione levels. J. Neurochem. 2008, 106, 1044–1051. [Google Scholar] [CrossRef] [PubMed][Green Version]
  40. Milder, J.; Patel, M. Modulation of oxidative stress and mitochondrial function by the ketogenic diet. Epilepsy Res. 2012, 100, 295–303. [Google Scholar] [CrossRef][Green Version]
  41. Maalouf, M.; Rho, J.M.; Mattson, M.P. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 2009, 59, 293–315. [Google Scholar] [CrossRef] [PubMed][Green Version]
  42. Yang, X.; Cheng, B. Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. J. Mol. Neurosci. 2010, 42, 145–153. [Google Scholar] [CrossRef]
  43. Sears, B. Anti-inflammatory diets. J. Am. Coll. Nutr. 2015, 34 (Suppl. 1), 14–21. [Google Scholar] [CrossRef] [PubMed]
  44. Ruskin, D.N.; Kawamura, M., Jr.; Masino, S.A. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet. PLoS ONE 2009, 4, e8349. [Google Scholar] [CrossRef] [PubMed]
  45. Radak, Z.; Torma, F.; Berkes, I.; Goto, S.; Mimura, T.; Posa, A.; Balogh, L.; Boldogh, I.; Suzuki, K.; Higuchi, M.; et al. Exercise effects on physiological function during aging. Free Radic. Biol. Med. 2019, in press. [Google Scholar] [CrossRef] [PubMed]
  46. Youm, Y.H.; Nguyen, K.Y.; Grant, R.W.; Goldberg, E.L.; Bodogai, M.; Kim, D.; D’Agostino, D.; Planavsky, N.; Lupfer, C.; Kanneganti, T.D.; et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nat. Med. 2015, 21, 263. [Google Scholar] [CrossRef] [PubMed]
  47. Kim, K.; Pyo, S.; Um, S.H. S6 kinase 2 deficiency enhances ketone body production and increases peroxisome proliferator-activated receptor alpha activity in the liver. Hepatology 2012, 55, 1727–1737. [Google Scholar] [CrossRef][Green Version]
  48. Bough, K.J.; Wetherington, J.; Hassel, B.; Pare, J.F.; Gawryluk, J.W.; Greene, J.G.; Shaw, R.; Smith, Y.; Geiger, J.D.; Dingledine, R.J. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann. Neurol. 2006, 60, 223–235. [Google Scholar] [CrossRef]
  49. Ahola-Erkkilä, S.; Carroll, C.J.; Peltola-Mjösund, K.; Tulkki, V.; Mattila, I.; Seppänen-Laakso, T.; Orešič, M.; Tyynismaa, H.; Suomalainen, A. Ketogenic diet slows down mitochondrial myopathy progression in mice. Hum. Mol. Genet. 2010, 19, 1974–1984. [Google Scholar] [CrossRef]
  50. Zajac, A.; Poprzecki, S.; Maszczyk, A.; Czuba, M.; Michalczyk, M.; Zydek, G. The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists. Nutrients 2014, 6, 2493–2508. [Google Scholar] [CrossRef]
  51. Cox, P.J.; Kirk, T.; Ashmore, T.; Willerton, K.; Evans, R.; Smith, A.; Murray, A.J.; Stubbs, B.; West, J.; McLure, S.W.; et al. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 2016, 24, 256–268. [Google Scholar] [CrossRef]
  52. McKay, A.K.; Peeling, P.; Pyne, D.B.; Welvaert, M.; Tee, N.; Leckey, J.J.; Sharma, A.P.; Ross, M.L.R.; Garvican-Lewis, L.A.; Swelm, R.P.L.; et al. Acute carbohydrate ingestion does not influence the post-exercise iron-regulatory response in elite keto-adapted race walkers. J. Sci. Med. Sport. 2019, in press. [Google Scholar] [CrossRef]
  53. Parry, H.A.; Kephart, W.C.; Mumford, P.W.; Romero, M.A.; Mobley, C.B.; Zhang, Y.; Robers, M.D.; Kavazis, A.N. Ketogenic diet increases mitochondria volume in the liver and skeletal muscle without altering oxidative stress markers in rats. Heliyon 2018, 4, e00975. [Google Scholar] [CrossRef] [PubMed]
  54. Parry, H.A.; Kephart, W.C.; Mumford, P.; Romero, M.; Hann, C.; Mobley, C.B.; Zhang, Y.; Robers, M.D.; Kavazis, A.N. Lifelong Ketogenic Diet Feeding Increases Longevity, But Does Not Alter Oxidative Stress Markers in Rats. Med. Sci. Sports Exerc. 2018, 50, 82. [Google Scholar] [CrossRef]
  55. Shimizu, K.; Saito, H.; Sumi, K.; Sakamoto, Y.; Tachi, Y.; Iida, K. Short-term and long-term ketogenic diet therapy and the addition of exercise have differential impacts on metabolic gene expression in the mouse energy-consuming organs heart and skeletal muscle. Nutr. Res. 2018, 60, 77–86. [Google Scholar] [CrossRef] [PubMed]
  56. Zinn, C.; Wood, M.; Williden, M.; Chatterton, S.; Maunder, E. Ketogenic diet benefits body composition and well-being but not performance in a pilot case study of New Zealand endurance athletes. J. Int. Soc. Sports Nutr. 2017, 14. [Google Scholar] [CrossRef] [PubMed][Green Version]
  57. Burke, L.M.; Ross, M.L.; Garvican-Lewis, L.A.; Welvaert, M.; Heikura, I.A.; Forbes, S.G.; Mirtschin, J.G.; Cato, L.E.; Strobel, N.; Sharma, A.P.; et al. Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers. J. Physiol. 2017, 595, 2785–2807. [Google Scholar] [CrossRef] [PubMed]
  58. Carr, A.J.; Sharma, A.P.; Ross, M.L.; Welvaert, M.; Slater, G.J.; Burke, L.M. Chronic ketogenic low carbohydrate high fat diet has minimal effects on acid–base status in elite athletes. Nutrients 2018, 10, 236. [Google Scholar] [CrossRef]
  59. Volek, J.S.; Freidenreich, D.J.; Saenz, C.; Kunces, L.J.; Creighton, B.C.; Bartley, J.M.; Davitt, P.M.; Munoz, C.X.; Anderson, J.M.; Maresh, C.M.; et al. Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism 2016, 65, 100–110. [Google Scholar] [CrossRef]
  60. White, A.M.; Johnston, C.S.; Swan, P.D.; Tjonn, S.L.; Sears, B. Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: A pilot study. J. Am. Diet. Assoc. 2007, 107, 1792–1796. [Google Scholar] [CrossRef]
  61. Paoli, A.; Grimaldi, K.; D’Agostino, D.; Cenci, L.; Moro, T.; Bianco, A.; Palma, A. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J. Int. Soc. Sports Nutr. 2012, 9, 34. [Google Scholar] [CrossRef][Green Version]
  62. Kephart, W.C.; Pledge, C.D.; Roberson, P.A.; Mumford, P.W.; Romero, M.A.; Mobley, C.B.; Martin, J.S.; Young, K.C.; Lowery, R.P.; Wilson, J.M.; et al. The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study. Sports 2018, 6, 1. [Google Scholar] [CrossRef]
  63. McSwiney, F.; Wardrop, B.; Volek, J.; Doyle, L. Effect of a 12 week low carbohydrate ketogenic diet versus a high carbohydrate diet on blood count indicators of iron status in male endurance athletes. Proc. Nutr. Soc. 2017, 76, E72. [Google Scholar] [CrossRef]
  64. Leon-Velarde, F.; Monge, C.C.; Vidal, A.; Carcagno, M.; Criscuolo, M.; Bozzini, C.E. Serum immunoreactive erythropoietin in high altitude natives with and without excessive erythrocytosis. Exp. Hematol. 1991, 19, 257–260. [Google Scholar] [PubMed]
  65. Cristol, J.P.; Bosc, J.Y.; Badiou, S.; Leblanc, M.; Lorrho, R.; Descomps, B.; Canaud, B. Erythropoietin and oxidative stress in haemodialysis: Beneficial effects of vitamin E supplementation. Nephrol. Dial. Transplant. 1997, 12, 2312–2317. [Google Scholar] [CrossRef] [PubMed]
  66. Macdougall, I.C.; Tucker, B.; Thompson, J.; Tomson, C.R.; Baker, L.R.; Raine, A.E. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int. 1996, 50, 1694–1699. [Google Scholar] [CrossRef] [PubMed][Green Version]
  67. Morgan, P.T.; Wollman, P.M.; Jackman, S.R.; Bowtell, J.L. Flavanol-Rich Cacao Mucilage Juice Enhances Recovery of Power but Not Strength from Intensive Exercise in Healthy, Young Men. Sports 2018, 6, 159. [Google Scholar] [CrossRef]
  68. Van Hoorebeke, J.S.; Trias, C.O.; Davis, B.A.; Lozada, C.F.; Casazza, G.A. Betalain-Rich Concentrate Supplementation Improves Exercise Performance in Competitive Runners. Sports 2016, 4, 40. [Google Scholar] [CrossRef] [PubMed]
  69. Sharp, M.H.; Shields, K.A.; Rauch, J.T.; Lowery, R.P.; Durkee, S.E.; Wilson, G.J.; De Souza, E.O. The Effects of a Multi-Ingredient Performance Supplement on Hormonal Profiles and Body Composition in Male College Athletes. Sports 2016, 4, 26. [Google Scholar] [CrossRef]
  70. Carbuhn, A.F.; Reynolds, S.M.; Campbell, C.W.; Bradford, L.A.; Deckert, J.A.; Kreutzer, A.; Fry, A.C. Effects of Probiotic (Bifidobacterium longum 35624) Supplementation on Exercise Performance, Immune Modulation, and Cognitive Outlook in Division I Female Swimmers. Sports 2018, 6, 116. [Google Scholar] [CrossRef]
  71. Barker, R.G.; van der Poel, C.; Horvath, D.; Murphy, R.M. Taurine and Methylprednisolone Administration at Close Proximity to the Onset of Muscle Degeneration Is Ineffective at Attenuating Force Loss in the Hind-Limb of 28 Days Mdx Mice. Sports 2018, 6, 109. [Google Scholar] [CrossRef]
  72. Townsend, J.R.; Bender, D.; Vantrease, W.C.; Sapp, P.A.; Toy, A.M.; Woods, C.A.; Johnson, K.D. Effects of Probiotic (Bacillus subtilis DE111) Supplementation on Immune Function, Hormonal Status, and Physical Performance in Division I Baseball Players. Sports 2018, 6, 70. [Google Scholar] [CrossRef]
  73. Taber, C.; Carroll, K.; DeWeese, B.; Sato, K.; Stuart, C.; Howell, M.; Hall, K.; Bazyler, C.; Stone, M. Neuromuscular Adaptations Following Training and Protein Supplementation in a Group of Trained Weightlifters. Sports 2018, 6, 37. [Google Scholar] [CrossRef] [PubMed]
  74. Oliveira, C.C.; Ferreira, D.; Caetano, C.; Granja, D.; Pinto, R.; Mendes, B.; Sousa, M. Nutrition and Supplementation in Soccer. Sports 2017, 5, 28. [Google Scholar] [CrossRef] [PubMed]
  75. Chen, Y.-M.; Lin, C.-L.; Wei, L.; Hsu, Y.-J.; Chen, K.-N.; Huang, C.-C.; Kao, C.-H. Sake Protein Supplementation Affects Exercise Performance and Biochemical Profiles in Power-Exercise-Trained Mice. Nutrients 2016, 8, 106. [Google Scholar] [CrossRef] [PubMed]
  76. Köhne, J.L.; Ormsbee, M.J.; McKune, A.J. Supplementation Strategies to Reduce Muscle Damage and Improve Recovery Following Exercise in Females: A Systematic Review. Sports 2016, 4, 51. [Google Scholar] [CrossRef] [PubMed]
  77. Guy, J.H.; Vincent, G.E. Nutrition and Supplementation Considerations to Limit Endotoxemia When Exercising in the Heat. Sports 2018, 6, 12. [Google Scholar] [CrossRef] [PubMed]
  78. Smith, J.W.; Krings, B.M.; Peterson, T.J.; Rountree, J.A.; Zak, R.B.; McAllister, M.J. Ingestion of an Amino Acid Electrolyte Beverage during Resistance Exercise Does Not Impact Fluid Shifts into Muscle or Performance. Sports 2017, 5, 36. [Google Scholar] [CrossRef] [PubMed]
  79. Zhou, J.; Mao, L.; Xu, P.; Wang, Y. Effects of (−)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet. Nutrients 2018, 10, 1681. [Google Scholar] [CrossRef]
  80. Clemens, D.L.; Duryee, M.J.; Sarmiento, C.; Chiou, A.; McGowan, J.D.; Hunter, C.D.; Schlichte, S.L.; Tian, J.; Klassen, L.W.; O’Dell, J.R.; et al. Novel Antioxidant Properties of Doxycycline. Int. J. Mol. Sci. 2018, 19, 4078. [Google Scholar] [CrossRef]
  81. Li, X.-W.; Chen, H.-P.; He, Y.-Y.; Chen, W.-L.; Chen, J.-W.; Gao, L.; Hu, H.-Y.; Wang, J. Effects of Rich-Polyphenols Extract of Dendrobium loddigesii on Anti-Diabetic, Anti-Inflammatory, Anti-Oxidant, and Gut Microbiota Modulation in db/db Mice. Molecules 2018, 23, 3245. [Google Scholar] [CrossRef]
  82. Lin, C.-L.; Lee, M.-C.; Hsu, Y.-J.; Huang, W.-C.; Huang, C.-C.; Huang, S.-W. Isolated Soy Protein Supplementation and Exercise Improve Fatigue-Related Biomarker Levels and Bone Strength in Ovariectomized Mice. Nutrients 2018, 10, 1792. [Google Scholar] [CrossRef]
  83. Chilelli, N.C.; Ragazzi, E.; Valentini, R.; Cosma, C.; Ferraresso, S.; Lapolla, A.; Sartore, G. Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo-Oxidation in Master Athletes. Nutrients 2016, 8, 745. [Google Scholar] [CrossRef] [PubMed]
  84. Manders, R.J.; Little, J.P.; Forbes, S.C.; Candow, D.G. Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia. Nutrients 2012, 4, 1664–1678. [Google Scholar] [CrossRef][Green Version]
  85. Falavigna, G.; Junior, J.A.A.; Rogero, M.M.; Pires, I.S.O.; Pedrosa, R.G.; Junior, E.M.; Castro, I.A.; Tirapegui, J. Effects of Diets Supplemented with Branched-Chain Amino Acids on the Performance and Fatigue Mechanisms of Rats Submitted to Prolonged Physical Exercise. Nutrients 2012, 4, 1767–1780. [Google Scholar] [CrossRef][Green Version]
  86. Zheng, L.; Wei, H.; He, P.; Zhao, S.; Xiang, Q.; Pang, J.; Peng, J. Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model. Nutrients 2017, 9, 17. [Google Scholar] [CrossRef] [PubMed]
  87. Asadi, A.; Arazi, H.; Suzuki, K. Effects of β-Hydroxy-β-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training. Nutrients 2017, 9, 1316. [Google Scholar] [CrossRef] [PubMed]
  88. Mu, W.-C.; VanHoosier, E.; Elks, C.M.; Grant, R.W. Long-Term Effects of Dietary Protein and Branched-Chain Amino Acids on Metabolism and Inflammation in Mice. Nutrients 2018, 10, 918. [Google Scholar] [CrossRef]
  89. VanDusseldorp, T.A.; Escobar, K.A.; Johnson, K.E.; Stratton, M.T.; Moriarty, T.; Cole, N.; McCormick, J.J.; Kerksick, C.M.; Vaughan, R.A.; Dokladny, K.; et al. Effect of Branched-Chain Amino Acid Supplementation on Recovery Following Acute Eccentric Exercise. Nutrients 2018, 10, 1389. [Google Scholar] [CrossRef]
  90. Hsueh, C.-F.; Wu, H.-J.; Tsai, T.-S.; Wu, C.-L.; Chang, C.-K. The Effect of Branched-Chain Amino Acids, Citrulline, and Arginine on High-Intensity Interval Performance in Young Swimmers. Nutrients 2018, 10, 1979. [Google Scholar] [CrossRef]
  91. Ari, C.; Kovács, Z.; Juhasz, G.; Murdun, C.; Goldhagen, C.R.; Koutnik, A.P.; Poff, A.M.; Kesl, S.L.; D’Agostino, D.P. Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats. Front. Mol. Neurosci. 2017, 9, 137. [Google Scholar] [CrossRef]
  92. Pilla, R. Clinical Applications of Ketogenic Diet-Induced Ketosis in Neurodegenerative and Metabolism-Related Pathologies. Cancer 2018, 15, 16. [Google Scholar]
  93. Yada, K.; Suzuki, K.; Oginome, N.; Ma, S.; Fukuda, Y.; Iida, A.; Radak, Z. Single Dose administration oftaheebo polyphenol enhances endurance capacity in mice. Sci. Rep. 2018, 8, 14625. [Google Scholar] [CrossRef] [PubMed]
  94. Kesl, S.L.; Poff, A.M.; Ward, N.P.; Fiorelli, T.N.; Ari, C.; Van Putten, A.J.; Sherwood, J.W.; Arnold, P.A.; D’Agostino, D.P. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutr. Metab. 2016, 13, 9. [Google Scholar] [CrossRef] [PubMed]
  95. Poff, A.; Kesl, S.; Koutnik, A.; Ward, N.; Ari, C.; Deblasi, J.; D’Agostino, D. Characterizing the metabolic effects of exogenous ketone supplementation—An alternative or adjuvant to the ketogenic diet. FASEB J. 2017, 31 (Suppl. 1), 970–977. [Google Scholar]
  96. Poff, A.; Kesl, S.; Ward, N.; D’Agostino, D. Metabolic effects of exogenous ketone supplementation—An alternative or adjuvant to the ketogenic diet as a cancer therapy? FASEB J. 2016, 30 (Suppl. 1), 1167-2. [Google Scholar]
  97. O’Malley, T.; Myette-Cote, E.; Durrer, C.; Little, J.P. Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Appl. Physiol. Nutr. Metab. 2017, 42, 1031–1035. [Google Scholar] [CrossRef]
  98. Kephart, W.C.; Mumford, P.W.; Mao, X.; Romero, M.A.; Hyatt, H.W.; Zhang, Y.; Mobley, C.B.; Quindry, J.C.; Young, K.C.; Beck, D.T.; et al. The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats. Nutrients 2017, 9, 1019. [Google Scholar] [CrossRef]
  99. Stubbs, B.J.; Koutnik, A.P.; Poff, A.M.; Ford, K.M.; D’Agostino, D.P. Commentary: Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Front. Physiol. 2018, 9, 279. [Google Scholar] [CrossRef]
  100. Harvey, C.J.D.C.; Schofield, G.M.; Williden, M. The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: A narrative review. Peer J. 2018, 6, e4488. [Google Scholar] [CrossRef]
  101. Garbow, J.R.; Doherty, J.M.; Schugar, R.C.; Travers, S.; Weber, M.L.; Wentz, A.E.; Ezenwajiaku, N.; Ctter, D.G.; Brunt, E.M.; Crawford, P.A. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 6, 956–967. [Google Scholar] [CrossRef]
  102. Ellenbroek, J.H.; van Dijck, L.; Töns, H.A.; Rabelink, T.J.; Carlotti, F.; Ballieux, B.E.; de Koning, E.J. Long-term ketogenic diet causes glucose intolerance and reduced β-and α-cell mass but no weight loss in mice. Am. J. Physiol. Endocrinol. Metab. 2014, 5, 552–558. [Google Scholar] [CrossRef]
  103. Yancy, W.S.; Olsen, M.K.; Guyton, J.R.; Bakst, R.P.; Westman, E.C. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: A randomized, controlled trial. Ann. Int. Med. 2004, 10, 769–777. [Google Scholar] [CrossRef]
  104. Westman, E.C.; Yancy, W.S.; Edman, J.S.; Tomlin, K.F.; Perkins, C.E. Effect of 6-month adherence to a very low carbohydrate diet program. Am. J. Med. 2002, 1, 30–36. [Google Scholar] [CrossRef]
  105. Wing, R.R.; Vazquez, J.A.; Ryan, C.M. Cognitive effects of ketogenic weight-reducing diets. Int. J. Obes. Relat. Metab. Disord. 1995, 11, 811–816. [Google Scholar]

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