The Use of Continuous Glucose Monitors in Sport: Possible Applications and Considerations.

This review discusses the potential value of tracking interstitial glucose with continuous glucose monitors (CGMs) in athletes, highlighting possible applications and important considerations in the collection and interpretation of interstitial glucose data. CGMs are sensors that provide real time, longitudinal tracking of interstitial glucose with a range of commercial monitors currently available. Recent advancements in CGM technology have led to the development of athlete-specific devices targeting glucose monitoring in sport. Although largely untested, the capacity of CGMs to capture the duration, magnitude, and frequency of interstitial glucose fluctuations every 1-15 min may present a unique opportunity to monitor fueling adequacy around competitive events and training sessions, with applications for applied research and sports nutrition practice. Indeed, manufacturers of athlete-specific devices market these products as a "fueling gauge," enabling athletes to "push their limits longer and get bigger gains." However, as glucose homeostasis is a complex phenomenon, extensive research is required to ascertain whether systemic glucose availability (estimated by CGM-derived interstitial glucose) has any meaning in relation to the intended purposes in sport. Whether CGMs will provide reliable and accurate information and enhance sports nutrition knowledge and practice is currently untested. Caveats around the use of CGMs include technical issues (dislodging of sensors during periods of surveillance, loss of data due to synchronization issues), practical issues (potential bans on their use in some sporting scenarios, expense), and challenges to the underpinning principles of data interpretation, which highlight the role of sports nutrition professionals to provide context and interpretation.

The Impact of a Short-Term Ketogenic Low-Carbohydrate High-Fat Diet on Biomarkers of Intestinal Epithelial Integrity and Gastrointestinal Symptoms.

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40 kcal·kg FFM-1·day-1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50 g/day CHO, energy availability = 40 kcal·kg FFM-1·day-1); and low energy availability (n = 10; 65% CHO, energy availability = 15 kcal·kg FFM-1·day-1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1 hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p = .001). Similar findings were observed for soluble CD14 (p < .001) and lipopolysaccharide-binding protein (p = .003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p > .05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed.

Adaptation to a low carbohydrate high fat diet is rapid but impairs endurance exercise metabolism and performance despite enhanced glycogen availability.

KEY POINTS: Brief (5-6 days) adaptation to a low carbohydrate high fat diet in elite athletes increased exercise fat oxidation to rates previously observed with medium (3-4 weeks) or chronic (>12 months) adherence to this diet, with metabolic changes being washed out in a similar time frame. Increased fat utilisation during exercise was associated with a 5-8% increase in oxygen cost at speeds related to Olympic Programme races. Acute restoration of endogenous carbohydrate (CHO) availability (24 h high CHO diet, pre-race CHO) only partially restored substrate utilisation during a race warm-up. Fat oxidation continued to be elevated above baseline values although it was lower than achieved by 5-6 days' keto adaptation; CHO oxidation only reached 61% and 78% of values previously seen at exercise intensities related to race events. Acute restoration of CHO availability failed to overturn the impairment of high-intensity endurance performance previously associated with low carbohydrate high fat adaptation, potentially due to the blunted capacity for CHO oxidation. ABSTRACT: We investigated substrate utilisation during exercise after brief (5-6 days) adaptation to a ketogenic low-carbohydrate (CHO), high-fat (LCHF) diet and similar washout period. Thirteen world-class male race walkers completed economy testing, 25 km training and a 10,000 m race (Baseline), with high CHO availability (HCHO), repeating this (Adaptation) after 5-6 days' LCHF (n = 7; CHO: <50 g day-1 , protein: 2.2 g kg-1 day-1 ; 80% fat) or HCHO (n = 6; CHO: 9.7 g kg-1 day-1 ; protein: 2.2 g kg-1 day-1 ) diet. An Adaptation race was undertaken after 24 h HCHO and pre-race CHO (2 g kg-1 ) diet, identical to the Baseline race. Substantial (>200%) increases in exercise fat oxidation occurred in the LCHF Adaptation economy and 25 km tests, reaching mean rates of ∼1.43 g min-1 . However, relative V̇O2 (ml min-1  kg-1 ) was higher (P < 0.0001), by ∼8% and 5% at speeds related to 50 km and 20 km events. During Adaptation race warm-up in the LCHF group, rates of fat and CHO oxidation at these speeds were decreased and increased, respectively (P < 0.001), compared with the previous day, but were not restored to Baseline values. Performance changes differed between groups (P = 0.009), with all HCHO athletes improving in the Adaptation race (5.7 (5.6)%), while 6/7 LCHF athletes were slower (2.2 (3.4)%). Substrate utilisation returned to Baseline values after 5-6 days of HCHO diet. In summary, robust changes in exercise substrate use occurred in 5-6 days of extreme changes in CHO intake. However, adaptation to a LCHF diet plus acute restoration of endogenous CHO availability failed to restore high-intensity endurance performance, with CHO oxidation rates remaining blunted.

Sustained Exposure to High Carbohydrate Availability Does Not Influence Iron-Regulatory Responses in Elite Endurance Athletes.

This study implemented a 2-week high carbohydrate (CHO) diet intended to maximize CHO oxidation rates and examined the iron-regulatory response to a 26-km race walking effort. Twenty international-level, male race walkers were assigned to either a novel high CHO diet (MAX = 10 g/kg body mass CHO daily) inclusive of gut-training strategies, or a moderate CHO control diet (CON = 6 g/kg body mass CHO daily) for a 2-week training period. The athletes completed a 26-km race walking test protocol before and after the dietary intervention. Venous blood samples were collected pre-, post-, and 3 hr postexercise and measured for serum ferritin, interleukin-6, and hepcidin-25 concentrations. Similar decreases in serum ferritin (17-23%) occurred postintervention in MAX and CON. At the baseline, CON had a greater postexercise increase in interleukin-6 levels after 26 km of walking (20.1-fold, 95% CI [9.2, 35.7]) compared with MAX (10.2-fold, 95% CI [3.7, 18.7]). A similar finding was evident for hepcidin levels 3 hr postexercise (CON = 10.8-fold, 95% CI [4.8, 21.2]; MAX = 8.8-fold, 95% CI [3.9, 16.4]). Postintervention, there were no substantial differences in the interleukin-6 response (CON = 13.6-fold, 95% CI [9.2, 20.5]; MAX = 11.2-fold, 95% CI [6.5, 21.3]) or hepcidin levels (CON = 7.1-fold, 95% CI [2.1, 15.4]; MAX = 6.3-fold, 95% CI [1.8, 14.6]) between the dietary groups. Higher resting serum ferritin (p = .004) and hotter trial ambient temperatures (p = .014) were associated with greater hepcidin levels 3 hr postexercise. Very high CHO diets employed by endurance athletes to increase CHO oxidation have little impact on iron regulation in elite athletes. It appears that variations in serum ferritin concentration and ambient temperature, rather than dietary CHO, are associated with increased hepcidin concentrations 3 hr postexercise.

Mice with Whole-Body Disruption of AMPK-Glycogen Binding Have Increased Adiposity, Reduced Fat Oxidation and Altered Tissue Glycogen Dynamics.

The AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and metabolism, binds glycogen via its ß subunit. However, the physiological effects of disrupting AMPK-glycogen interactions remain incompletely understood. To chronically disrupt AMPK-glycogen binding, AMPK ß double knock-in (DKI) mice were generated with mutations in residues critical for glycogen binding in both the ß1 (W100A) and ß2 (W98A) subunit isoforms. We examined the effects of this DKI mutation on whole-body substrate utilization, glucose homeostasis, and tissue glycogen dynamics. Body composition, metabolic caging, glucose and insulin tolerance, serum hormone and lipid profiles, and tissue glycogen and protein content were analyzed in chow-fed male DKI and age-matched wild-type (WT) mice. DKI mice displayed increased whole-body fat mass and glucose intolerance associated with reduced fat oxidation relative to WT. DKI mice had reduced liver glycogen content in the fed state concomitant with increased utilization and no repletion of skeletal muscle glycogen in response to fasting and refeeding, respectively, despite similar glycogen-associated protein content relative to WT. DKI liver and skeletal muscle displayed reductions in AMPK protein content versus WT. These findings identify phenotypic effects of the AMPK DKI mutation on whole-body metabolism and tissue AMPK content and glycogen dynamics.

Contemporary Nutrition Interventions to Optimize Performance in Middle-Distance Runners.

Middle-distance runners utilize the full continuum of energy systems throughout training, and given the infinite competition tactical scenarios, this event group is highly complex from a performance intervention point of view. However, this complexity results in numerous potential periodized nutrition interventions to optimize middle-distance training adaptation and competition performance. Middle-distance race intensity is extreme, with 800- to 5,000-m races being at ∼95% to 130% of VO2max. Accordingly, elite middle-distance runners have primarily Type IIa/IIx fiber morphology and rely almost exclusively on carbohydrate (primarily muscle glycogen) metabolic pathways for producing adenosine triphosphate. Consequently, the principle nutritional interventions that should be emphasized are those that optimize muscle glycogen contents to support high glycolytic flux (resulting in very high lactate values, of >20 mmol/L in some athletes) with appropriate buffering capabilities, while optimizing power to weight ratios, all in a macro- and microperiodized manner. From youth to elite level, middle-distance athletes have arduous racing schedules (10-25 races/year), coupled with excessive global travel, which can take a physical and emotional toll. Accordingly, proactive and integrated nutrition planning can have a profound recovery effect over a long race season, as well as optimizing recovery during rounds of championship racing. Finally, with evidence-based implementation and an appropriate risk/reward assessment, several ergogenic aids may have an adaptive and/or performance-enhancing effect in the middle-distance athlete. Given that elite middle-distance athletes undertake ∼400 to 800 training sessions with 10-25 races/year, there are countless opportunities to implement various periodized acute and chronic nutrition-based interventions to optimize performance.

Estimated Sweat Loss, Fluid and Carbohydrate Intake, and Sodium Balance of Male Major Junior, AHL, and NHL Players During On-Ice Practices.

Several previous studies have reported performance decrements in team sport athletes who dehydrated approximately 1.5-2% of their body mass (BM) through sweating. This study measured on-ice sweat loss, fluid intake, sodium balance, and carbohydrate (CHO) intake of 77 major junior (JR; 19 ± 1 years), 60 American Hockey League (AHL; 24 ± 4 years), and 77 National Hockey League (NHL; 27 ± 5 years) players. Sweat loss was calculated from pre- to post-exercise BM plus fluid intake minus urine loss. AHL (2.03 ± 0.62 L/hr) and NHL (2.02 ± 0.74 L/hr) players had higher sweat rates (p < .05) than JR players (1.63 ± 0.58 L/hr). AHL (1.23 ± 0.69%; p = .006) and NHL (1.29% ± 0.63%; p < .001) players had ∼30% greater BM losses than JR players (0.89% ± 0.57%). There was no difference in fluid intake between groups (p > .05). Sodium deficits (sodium loss - intake) were greater (p < .05) in AHL (1.68 ± 0.74 g/hr) and NHL (1.56 ± 0.84 g/hr) players compared with JR players (1.01 ± 0.50 g/hr). CHO intake was similar between groups (14-20 g CHO/hr), with 29%, 32%, and 40% of JR, AHL, and NHL players consuming no CHO, respectively. In summary, sweat rates were high in all players, but the majority of players (74/77, 54/60, and 68/77 of JR, AHL, and NHL, respectively) avoided mild dehydration (>2% BM) during 60 min of practice. However, ∼15%, 41%, and 48% of the JR, AHL, and NHL players, respectively, may have reached mild dehydration and increased risk of performance decrements in a 90-min practice.

Ablating the protein TBC1D1 impairs contraction-induced sarcolemmal glucose transporter 4 redistribution but not insulin-mediated responses in rats.

TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase-mediated glucose transporter type 4 (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1 KO model. Although insulin administration rapidly increased (p < 0.05) plasma membrane GLUT4 content in both red and white gastrocnemius muscles, the TBC1D1 ablation did not alter this response nor did it affect whole-body insulin tolerance, suggesting that TBC1D1 is not required for insulin-induced GLUT4 trafficking events. Consistent with findings in other models of altered TBC1D1 protein levels, whole-animal and ex vivo skeletal muscle fat oxidation was increased in the TBC1D1 KO rats. Although there was no change in mitochondrial content in the KO rats, maximal ADP-stimulated respiration was higher in permeabilized muscle fibers, which may contribute to the increased reliance on fatty acids in resting KO animals. Despite this increase in mitochondrial oxidative capacity, run time to exhaustion at various intensities was impaired in the KO rats. Moreover, contraction-induced increases in sarcolemmal GLUT4 content and glucose uptake were lower in the white gastrocnemius of the KO animals. Altogether, our results highlight a critical role for TBC1D1 in exercise tolerance and contraction-mediated translocation of GLUT4 to the plasma membrane in skeletal muscle.

Interactive Roles for AMPK and Glycogen from Cellular Energy Sensing to Exercise Metabolism.

The AMP-activated protein kinase (AMPK) is a heterotrimeric complex with central roles in cellular energy sensing and the regulation of metabolism and exercise adaptations. AMPK regulatory ß subunits contain a conserved carbohydrate-binding module (CBM) that binds glycogen, the major tissue storage form of glucose. Research over the past two decades has revealed that the regulation of AMPK is impacted by glycogen availability, and glycogen storage dynamics are concurrently regulated by AMPK activity. This growing body of research has uncovered new evidence of physical and functional interactive roles for AMPK and glycogen ranging from cellular energy sensing to the regulation of whole-body metabolism and exercise-induced adaptations. In this review, we discuss recent advancements in the understanding of molecular, cellular, and physiological processes impacted by AMPK-glycogen interactions. In addition, we appraise how novel research technologies and experimental models will continue to expand the repertoire of biological processes known to be regulated by AMPK and glycogen. These multidisciplinary research advances will aid the discovery of novel pathways and regulatory mechanisms that are central to the AMPK signaling network, beneficial effects of exercise and maintenance of metabolic homeostasis in health and disease.

α-Linolenic acid and exercise training independently, and additively, decrease blood pressure and prevent diastolic dysfunction in obese Zucker rats.

KEY POINTS: α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining to their mechanisms of action when combined. We investigated both the independent and combined effects of exercise training and ALA consumption in obese Zucker rats, aiming to determine the potential for additive improvements in cardiovascular function. ALA and exercise training independently improved cardiac output, end-diastolic volume, left ventricular fibrosis and mean blood pressure following a 4 week intervention. Combining ALA and endurance exercise yielded greater improvements in these parameters, independent of changes in markers of oxidative stress or endogenous anti-oxidants. We postulate that divergent mechanisms of action may explain these changes: ALA increases peripheral vasodilation, and exercise training stimulates angiogenesis. ABSTRACT: Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.

Taurine and skeletal muscle function.

PURPOSE OF REVIEW: To discuss the recent work examining the importance of taurine in skeletal muscle and outline the discrepancy that exists between research findings in rodent vs. human skeletal muscle. RECENT FINDINGS: There is clear evidence that a normal taurine level is important for the normal functioning of skeletal muscle. Taurine is believed to be involved in many cellular functions, but in skeletal muscle its main roles are to facilitate Ca2+ dependent excitation-contraction processes, contribute to the regulation of cellular volume, and aid in antioxidant defense from stress responses. Most research has studied the importance of taurine in rodent skeletal muscle by downregulating and upregulating the muscle taurine content and examining the effects on the functioning of skeletal muscle at rest and during the stress of contractions (exercise). One successful research approach is to supplement the diet with taurine, which leads to increases in muscle taurine content and contractile function in rodents. However, this approach does not work in human skeletal muscle as the processes involved in the transport of taurine into the muscle are resistant to large and prolonged increases in plasma taurine following oral taurine supplementation. At present, attempts to influence muscle function with taurine supplementation can only occur through interactions outside the muscle cell in humans. SUMMARY: Future research should target the mechanisms responsible for the transport of taurine into human skeletal muscle and determine why the muscle defends the normal taurine content in the face of elevated plasma taurine levels, as opposed to the results in rodent muscle. This may lead to more fruitful usage of taurine as a skeletal muscle enhancing nutrient in athletic and clinical populations.

Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing.

The age-related loss of skeletal muscle mass and physical function leads to a loss of independence and an increased reliance on health-care. Mitochondria are crucial in the aetiology of sarcopenia and have been identified as key targets for interventions that can attenuate declines in physical capacity. Exercise training is a primary intervention that reduces many of the deleterious effects of ageing in skeletal muscle quality and function. However, habitual levels of physical activity decline with age, making it necessary to implement adjunct treatments to maintain skeletal muscle mitochondrial health and physical function. This review provides an overview of the effects of ageing and exercise training on human skeletal muscle mitochondria and considers several supplements that have plausible mechanistic underpinning to improve physical function in ageing through their interactions with mitochondria. Several supplements, including MitoQ, urolithin A, omega-3 polyunsaturated fatty acids (n3-PUFAs), and a combination of glycine and N-acetylcysteine (GlyNAC) can improve physical function in older individuals through a variety of inter-dependent mechanisms including increases in mitochondrial biogenesis and energetics, decreases in mitochondrial reactive oxygen species emission and oxidative damage, and improvements in mitochondrial quality control. While there is evidence that some nicotinamide adenine dinucleotide precursors can improve physical function in older individuals, such an outcome seems unrelated to and independent of changes in skeletal muscle mitochondrial function. Future research should investigate the safety and efficacy of compounds that can improve skeletal muscle health in preclinical models through mechanisms involving mitochondria, such as mitochondrial-derived peptides and mitochondrial uncouplers, with a view to extending the human health-span.

Iron Absorption in Highly Trained Male Runners: Does it Matter When and Where You Eat Your Iron?

PURPOSE: We examined iron absorption and its regulation during two common scenarios experienced by endurance athletes. Our aims were to: (i) compare the effects of preexercise versus postexercise iron intake on iron absorption; and (ii) compare the impact of training at altitude (1800 m) on iron absorption preexercise. METHODS: Male runners (n = 18) completed three exercise trials over a 5-wk period, each preceded by 24 h of standardized low-iron diets. First, athletes completed two 60-min treadmill running trials at 65% V̇O2max at near sea-level (580 m). In a randomized order, preexercise and postexercise test meals labeled with 4 mg of 57Fe or 58Fe were consumed 30 min before or 30 min after exercise. Then, the same exercise trial was performed after living and training at altitude (~1800 m) for 7 d, with the labeled test meal consumed 30 min preexercise. We collected venous blood samples preexercise and postexercise for markers of iron status and regulation, and 14 d later to measure erythrocyte isotope incorporation. RESULTS: No differences in fractional iron absorption were evident when test meals were consumed preexercise (7.3% [4.4, 12.1]) or postexercise (6.2% [3.1, 12.5]) (n = 18; P = 0.058). Iron absorption preexercise was greater at altitude (18.4% [10.6, 32.0]) than at near sea-level (n = 17; P < 0.001) and hepcidin concentrations at altitude were lower at rest and 3 h postexercise compared with near sea level (P < 0.001). CONCLUSIONS: In an acute setting, preexercise and postexercise iron absorption is comparable if consumed within 30 min of exercise. Preexercise iron absorption increases 2.6-fold at altitude compared with near sea-level, likely due to the homeostatic response to provide iron for enhanced erythropoiesis and maintain iron stores.

Short Severe Energy Restriction with Refueling Reduces Body Mass without Altering Training-Associated Performance Improvement.

PURPOSE: We investigated short-term (9 d) exposure to low energy availability (LEA) in elite endurance athletes during a block of intensified training on self-reported well-being, body composition, and performance. METHODS: Twenty-three highly trained race walkers undertook an ~3-wk research-embedded training camp during which they undertook baseline testing and 6 d of high energy/carbohydrate (HCHO) availability (40 kcal·kg FFM -1 ·d -1 ) before being allocated to 9 d continuation of this diet ( n = 10 M, 2 F) or a significant decrease in energy availability to 15 kcal·kg FFM -1 ·d -1 (LEA: n = 10 M, 1 F). A real-world 10,000-m race walking event was undertaken before (baseline) and after (adaptation) these phases, with races being preceded by standardized carbohydrate fueling (8 g·kg body mass [BM] -1 for 24 h and 2 g·kg BM -1 prerace meal). RESULTS: Dual-energy x-ray absorptiometry-assessed body composition showed BM loss (2.0 kg, P < 0.001), primarily due to a 1.6-kg fat mass reduction ( P < 0.001) in LEA, with smaller losses (BM = 0.9 kg, P = 0.008; fat mass = 0.9 kg, P < 0.001) in HCHO. The 76-item Recovery-Stress Questionnaire for Athletes, undertaken at the end of each dietary phase, showed significant diet-trial effects for overall stress ( P = 0.021), overall recovery ( P = 0.024), sport-specific stress ( P = 0.003), and sport-specific recovery ( P = 0.012). However, improvements in race performance were similar: 4.5% ± 4.1% and 3.5% ± 1.8% for HCHO and LEA, respectively ( P < 0.001). The relationship between changes in performance and prerace BM was not significant ( r = -0.08 [-0.49 to 0.35], P = 0.717). CONCLUSIONS: A series of strategically timed but brief phases of substantially restricted energy availability might achieve ideal race weight as part of a long-term periodization of physique by high-performance athletes, but the relationship between BM, training quality, and performance in weight-dependent endurance sports is complicated.

Disrupting AMPK-Glycogen Binding in Mice Increases Carbohydrate Utilization and Reduces Exercise Capacity.

The AMP-activated protein kinase (AMPK) is a central regulator of cellular energy balance and metabolism and binds glycogen, the primary storage form of glucose in liver and skeletal muscle. The effects of disrupting whole-body AMPK-glycogen interactions on exercise capacity and substrate utilization during exercise in vivo remain unknown. We used male whole-body AMPK double knock-in (DKI) mice with chronic disruption of AMPK-glycogen binding to determine the effects of DKI mutation on exercise capacity, patterns of whole-body substrate utilization, and tissue metabolism during exercise. Maximal treadmill running speed and whole-body energy utilization during submaximal running were determined in wild type (WT) and DKI mice. Liver and skeletal muscle glycogen and skeletal muscle AMPK α and ß2 subunit content and signaling were assessed in rested and maximally exercised WT and DKI mice. Despite a reduced maximal running speed and exercise time, DKI mice utilized similar absolute amounts of liver and skeletal muscle glycogen compared to WT. DKI skeletal muscle displayed reduced AMPK α and ß2 content versus WT, but intact relative AMPK phosphorylation and downstream signaling at rest and following exercise. During submaximal running, DKI mice displayed an increased respiratory exchange ratio, indicative of greater reliance on carbohydrate-based fuels. In summary, whole-body disruption of AMPK-glycogen interactions reduces maximal running capacity and skeletal muscle AMPK α and ß2 content and is associated with increased skeletal muscle glycogen utilization. These findings highlight potential unappreciated roles for AMPK in regulating tissue glycogen dynamics and expand AMPK's known roles in exercise and metabolism.

Six Days of Low Carbohydrate, Not Energy Availability, Alters the Iron and Immune Response to Exercise in Elite Athletes.

PURPOSE: To quantify the effects of a short-term (6-d) low carbohydrate (CHO) high fat (LCHF), and low energy availability (LEA) diet on immune, inflammatory, and iron-regulatory responses to exercise in endurance athletes. METHODS: Twenty-eight elite male race walkers completed two 6-d diet/training phases. During phase 1 (Baseline), all athletes consumed a high CHO/energy availability (CON) diet (65% CHO and ~40 kcal·kg-1 fat-free mass (FFM)·d-1). In phase 2 (Adaptation), athletes were allocated to either a CON (n = 10), LCHF (n = 8; <50 g·d-1 CHO and ~40 kcal·kg-1·FFM-1·d-1), or LEA diet (n = 10; 60% CHO and 15 kcal·kg-1·FFM-1·d-1). At the end of each phase, athletes completed a 25-km race walk protocol at ~75% V˙O2max. On each occasion, venous blood was collected before and after exercise for interleukin-6, hepcidin, cortisol, and glucose concentrations, as well as white blood cell counts. RESULTS: The LCHF athletes displayed a greater IL-6 (P = 0.019) and hepcidin (P = 0.011) response to exercise after Adaptation, compared with Baseline. Similarly, postexercise increases in total white blood cell counts (P = 0.026) and cortisol levels (P < 0.001) were larger compared with Baseline after LCHF Adaptation. Decreases in blood glucose concentrations were evident postexercise during Adaptation in LCHF (P = 0.049), whereas no change occurred in CON or LEA (P > 0.05). No differences between CON and LEA were evident for any of the measured biological markers (all P > 0.05). CONCLUSIONS: Short-term adherence to a LCHF diet elicited small yet unfavorable iron, immune, and stress responses to exercise. In contrast, no substantial alterations to athlete health were observed when athletes restricted energy availability compared with athletes with adequate energy availability. Therefore, short-term restriction of CHO, rather than energy, may have greater negative impacts on athlete health.

Myofibre Hypertrophy in the Absence of Changes to Satellite Cell Content Following Concurrent Exercise Training in Young Healthy Men.

Concurrent exercise training has been suggested to create an 'interference effect,' attenuating resistance training-based skeletal muscle adaptations, including myofibre hypertrophy. Satellite cells support myofibre hypertrophy and are influenced by exercise mode. To determine whether satellite cells contribute to the 'interference effect' changes in satellite cell and myonuclear content were assessed following a period of training in 32 recreationally active males (age: 25 ± 5 year; body mass index: 24 ± 3 kg⋅m-2; mean ± SD) who undertook 12-week of either isolated (3 d⋅w-1) resistance (RES; n = 10), endurance (END; n = 10), or alternate day (6 d⋅w-1) concurrent (CET, n = 12) training. Skeletal muscle biopsies were obtained pre-intervention and after 2, 8, and 12 weeks of training to determine fibre type-specific cross-sectional area (CSA), satellite cell content (Pax7+DAPI+), and myonuclei (DAPI+) using immunofluorescence microscopy. After 12 weeks, myofibre CSA increased in all training conditions in type II (P = 0.0149) and mixed fibres (P = 0.0102), with no difference between conditions. Satellite cell content remained unchanged after training in both type I and type II fibres. Significant correlations were observed between increases in fibre type-specific myonuclear content and CSA of Type I (r = 0.63, P < 0.0001), Type II (r = 0.69, P < 0.0001), and mixed fibres (r = 0.72, P < 0.0001). Resistance, endurance, and concurrent training induce similar myofibre hypertrophy in the absence of satellite cell and myonuclear pool expansion. These findings suggest that myonuclear accretion via satellite cell fusion is positively correlated with hypertrophy after 12 weeks of concurrent training, and that individuals with more myonuclear content displayed greater myofibre hypertrophy.

Corrigendum: Myofibre Hypertrophy in the Absence of Changes to Satellite Cell Content Following Concurrent Exercise Training in Young Healthy Men.

[This corrects the article DOI: 10.3389/fphys.2021.625044.].

Acute Ketogenic Diet and Ketone Ester Supplementation Impairs Race Walk Performance.

PURPOSE: This study aimed to determine if LCHF and ketone ester (KE) supplementation can synergistically alter exercise metabolism and improve performance. METHODS: Elite race walkers (n = 18, 15 males and 3 females; V˙O2peak, 62 ± 6 mL·min-1·kg-1) undertook a four-stage exercise economy test and real-life 10,000-m race before and after a 5-d isoenergetic high-CHO (HCHO, ~60%-65% fat; CHO, 20% fat; n = 9) or LCHF (75%-80% fat, <50 g·d-1 CHO, n = 9) diet. The LCHF group performed additional economy tests before and after diet after supplementation with 573 mg·kg-1 body mass KE (HVMN; HVMN Inc., San Francisco, CA), which was also consumed for race 2. RESULTS: The oxygen cost of exercise (relative V˙O2, mL·min-1·kg-1) increased across all four stages after LCHF (P < 0.005). This occurred in association with increased fat oxidation rates, with a reciprocal decrease in CHO oxidation (P < 0.001). Substrate utilization in the HCHO group remained unaltered. The consumption of KE before the LCHF diet increased circulating KB (P < 0.05), peaking at 3.2 ± 0.6 mM, but did not alter V˙O2 or RER. LCHF diet elevated resting circulating KB (0.3 ± 0.1 vs 0.1 ± 0.1 mM), but concentrations after supplementation did not differ from the earlier ketone trial. Critically, race performance was impaired by ~6% (P < 0.0001) relative to baseline in the LCHF group but was unaltered in HCHO. CONCLUSION: Despite elevating endogenous KB production, an LCHF diet does not augment the metabolic responses to KE supplementation and negatively affects race performance.