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The Effect of Creatine Supplementation on Markers of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Human Intervention Trials

Bethany Northeast and Tom Clifford

This systematic review and meta-analysis examined the effects of creatine supplementation on recovery from exercise-induced muscle damage, and is reported according to the PRISMA guidelines. MEDLINE and SPORTDiscus were searched for articles from inception until April 2020. Inclusion criteria were adult participants (≥18 years); creatine provided before and/or after exercise versus a noncreatine comparator; measurement of muscle function recovery, muscle soreness, inflammation, myocellular protein efflux, oxidative stress; range of motion; randomized controlled trials in humans. Thirteen studies (totaling 278 participants; 235 males and 43 females; age range 20–60 years) were deemed eligible for analysis. Data extraction was performed independently by both authors. The Cochrane Collaboration Risk of Bias Tool was used to critically appraise the studies; forest plots were generated with random-effects model and standardized mean differences. Creatine supplementation did not alter muscle strength, muscle soreness, range of motion, or inflammation at each of the five follow-up times after exercise (<30 min, 24, 48, 72, and 96 hr; p > .05). Creatine attenuated creatine kinase activity at 48-hr postexercise (standardized mean difference: −1.06; 95% confidence interval [−1.97, −0.14]; p = .02) but at no other time points. High (I2; >75%) and significant (Chi2; p < .01) heterogeneity was identified for all outcome measures at various follow-up times. In conclusion, creatine supplementation does not accelerate recovery following exercise-induced muscle damage; however, well-controlled studies with higher sample sizes are warranted to verify these conclusions. Systematic review registration (PROSPERO CRD42020178735).

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Rapid Weight Gain Following Weight Cutting in Male and Female Professional Mixed Martial Artists

Kadhiresan R. Murugappan, Ariel Mueller, Daniel P. Walsh, Shahzad Shaefi, Akiva Leibowitz, and Todd Sarge

Rapid weight loss or “weight cutting” is a common but potentially harmful practice used in mixed martial arts competition. Following the official weigh-in, competitors refeed and rehydrate themselves in a process known as rapid weight gain (RWG) to realize a potential competitive advantage. While data from surveys and small series have indicated the majority of mixed martial arts athletes engage in rapid weight loss, there is a lack of officially collected data from sanctioning organizations describing its prevalence. The present investigation represents a summary of the data collected between December 2015 and January 2018 by the California State Athletic Commission. In total, 512 professional mixed martial artists (455 males and 57 females) were included. Of these, 503 (98%) athletes gained body mass between weigh-in and their bouts. Total RWG between weigh-in and competition was 5.5 ± 2.5 kg, corresponding to an 8.1% ± 3.6% body mass increase. Total RWG was 5.6 ± 2.5 kg (8.1% ± 3.6%) for males and 4.5 ± 2.3 kg (8.0% ± 3.8%) for females. More than one quarter of men and one third of women gained >10% body mass between weigh-in and competition. Athletes from leading international promotions gained more absolute, but not relative, body mass than those from regional promotions. Our findings indicate RWG is nearly ubiquitous in professional , with a similar prevalence in male and female athletes. Trends based on promotion suggest a larger magnitude of RWG in presumably more experienced and/or successful mixed martial artists from leading international promotions.

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Cannabidiol Does Not Impair Anabolic Signaling Following Eccentric Contractions in Rats

Henning T. Langer, Agata A. Mossakowski, Suraj Pathak, Mark Mascal, and Keith Baar

Cannabidiol (CBD) has proven clinical benefits in the treatment of seizures, inflammation, and pain. The recent legalization of CBD in many countries has caused increased interest in the drug as an over-the-counter treatment for athletes looking to improve recovery. However, no data on the effects of CBD on the adaptive response to exercise in muscle are available. To address this gap, we eccentrically loaded the tibialis anterior muscle of 14 rats, injected them with a vehicle (n = 7) or 100 mg/kg CBD (n = 7), and measured markers of injury, inflammation, anabolic signaling, and autophagy 18 hr later. Pro-inflammatory signaling through nuclear factor kappa B (NF-kB) (Ser536) increased with loading in both groups; however, the effect was significantly greater (36%) in the vehicle group (p < .05). Simultaneously, anabolic signaling through ribosomal protein S6 kinase beta-1 (S6K1) (Thr389) increased after eccentric contractions in both groups with no difference between vehicle and CBD (p = .66). The ribosomal protein S6 phosphorylation (240/244) increased with stimulation (p < .001) and tended to be higher in the CBD group (p = .09). The ubiquitin-binding protein p62 levels were not modulated by stimulation (p = .6), but they were 46% greater in the CBD compared with the vehicle group (p = .01). Although liver weight did not differ between the groups (p = .99) and levels of proteins associated with stress were similar, we did observe serious side effects in one animal. In conclusion, an acute dose of CBD decreased pro-inflammatory signaling in the tibialis anterior without blunting the anabolic response to exercise in rats. Future research should determine whether these effects translate to improved recovery without altering adaptation in humans.

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Abstracts From the December 2020 Virtual International Sport + Exercise Nutrition Conference

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Daily Myofibrillar Protein Synthesis Rates in Response to Low- and High-Frequency Resistance Exercise Training in Healthy, Young Men

Brandon J. Shad, Janice L. Thompson, James Mckendry, Andrew M. Holwerda, Yasir S. Elhassan, Leigh Breen, Luc J.C. van Loon, and Gareth A. Wallis

The impact of resistance exercise frequency on muscle protein synthesis rates remains unknown. The aim of this study was to compare daily myofibrillar protein synthesis rates over a 7-day period of low-frequency (LF) versus high-frequency (HF) resistance exercise training. Nine young men (21 ± 2 years) completed a 7-day period of habitual physical activity (BASAL). This was followed by a 7-day exercise period of volume-matched, LF (10 × 10 repetitions at 70% one-repetition maximum, once per week) or HF (2 × 10 repetitions at ∼70% one-repetition maximum, five times per week) resistance exercise training. The participants had one leg randomly allocated to LF and the other to HF. Skeletal muscle biopsies and daily saliva samples were collected to determine myofibrillar protein synthesis rates using 2H2O, with intracellular signaling determined using Western blotting. The myofibrillar protein synthesis rates did not differ between the LF (1.46 ± 0.26%/day) and HF (1.48 ± 0.33%/day) conditions over the 7-day exercise training period (p > .05). There were no significant differences between the LF and HF conditions over the first 2 days (1.45 ± 0.41%/day vs. 1.25 ± 0.46%/day) or last 5 days (1.47 ± 0.30%/day vs. 1.50 ± 0.41%/day) of the exercise training period (p > .05). Daily myofibrillar protein synthesis rates were not different from BASAL at any time point during LF or HF (p > .05). The phosphorylation status and total protein content of selected proteins implicated in skeletal muscle ribosomal biogenesis were not different between conditions (p > .05). Under the conditions of the present study, resistance exercise training frequency did not modulate daily myofibrillar protein synthesis rates in young men.

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Cold-Water Effects on Energy Balance in Healthy Women During Aqua-Cycling

Lore Metz, Laurie Isacco, Kristine Beaulieu, S. Nicole Fearnbach, Bruno Pereira, David Thivel, and Martine Duclos

Background: While the popularity of aquatic physical activities continues to grow among women, the effects on energy expenditure (EE) and appetite control remain unknown. The objective of this study was to examine the effect of water temperature during aqua-cycling session on EE, rate of perceived exertion, energy intake, appetite sensations, and food reward in healthy premenopausal women. Methods: Participants completed three experimental sessions, in the postprandial condition, in a randomized order: a land control session (CON), an aqua-cycling session in 18 °C (EXO18), and an aqua-cycling session in 27 °C (EXO27). The EE, food intake, appetite sensations, and food reward were investigated for each condition. Results: EXO18 induced a significant increase in EE (p < .001) and oxygen consumption (p < .01) compared with EXO27. The carbohydrate oxidation was higher in EXO18 session compared with EXO27 and CON (p < .05 and p < .001, respectively). While fat oxidation was higher in exercise sessions compared with CONT (p < .01), no difference was observed between EXO18 and EXO27. Exercise sessions did not alter absolute energy intake session but induced a decrease in relative energy intake (p < .001) and in hunger, desire to eat, and prospective food consumption compared with CON (p < .001). The authors also show here that cold-water exposure can increase EE while rate of perceived exertion is lower at the end of exercise session compared with same exercise at 27 °C (p < .05). Conclusion: An exposure to a moderately cold-water during aqua-cycling is an efficient strategy to promote increased EE and decreased hunger, which may be effective for energy balance management in healthy premenopausal women.

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Determinants of Peak Fat Oxidation Rates During Cycling in Healthy Men and Women

Oliver J. Chrzanowski-Smith, Robert M. Edinburgh, Mark P. Thomas, Aaron Hengist, Sean Williams, James A. Betts, and Javier T. Gonzalez

This study explored lifestyle and biological determinants of peak fat oxidation (PFO) during cycle ergometry, using duplicate measures to account for day-to-day variation. Seventy-three healthy adults (age range: 19–63 years; peak oxygen consumption [ V ˙ O 2 peak ] : 42.4 [ 10.1 ] ml · kg BM 1 · min 1 ; n = 32 women]) completed trials 7–28 days apart that assessed resting metabolic rate, a resting venous blood sample, and PFO by indirect calorimetry during an incremental cycling test. Habitual physical activity (combined heart rate accelerometer) and dietary intake (weighed record) were assessed before the first trial. Body composition was assessed 2–7 days after the second identical trial by dual-energy X-ray absorptiometry scan. Multiple linear regressions were performed to identify determinants of PFO (mean of two cycle tests). A total variance of 79% in absolute PFO (g·min−1) was explained with positive coefficients for V ˙ O 2 peak (strongest predictor), FATmax (i.e the % of V ˙ O 2 peak that PFO occurred at), and resting fat oxidation rate (g·min−1), and negative coefficients for body fat mass (kg) and habitual physical activity level. When expressed relative to fat-free mass, 64% of variance in PFO was explained: positive coefficients for FATmax (strongest predictor), V ˙ O 2 peak , and resting fat oxidation rate, and negative coefficients for male sex and fat mass. This duplicate design revealed that biological and lifestyle factors explain a large proportion of variance in PFO during incremental cycling. After accounting for day-to-day variation in PFO, V ˙ O 2 peak and FATmax were strong and consistent predictors of PFO.

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Exercise Plus Presleep Protein Ingestion Increases Overnight Muscle Connective Tissue Protein Synthesis Rates in Healthy Older Men

Andrew M. Holwerda, Jorn Trommelen, Imre W.K. Kouw, Joan M. Senden, Joy P.B. Goessens, Janneau van Kranenburg, Annemie P. Gijsen, Lex B. Verdijk, and Luc J.C. van Loon

Protein ingestion and exercise stimulate myofibrillar protein synthesis rates. When combined, exercise further increases the postprandial rise in myofibrillar protein synthesis rates. It remains unclear whether protein ingestion with or without exercise also stimulates muscle connective tissue protein synthesis rates. The authors assessed the impact of presleep protein ingestion on overnight muscle connective tissue protein synthesis rates at rest and during recovery from resistance-type exercise in older men. Thirty-six healthy, older men were randomly assigned to ingest 40 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine-labeled casein protein (PRO, n = 12) or a nonprotein placebo (PLA, n = 12) before going to sleep. A third group performed a single bout of resistance-type exercise in the evening before ingesting 40 g intrinsically-labeled casein protein prior to sleep (EX+PRO, n = 12). Continuous intravenous infusions of L-[ring- 2H5]-phenylalanine and L-[1-13C]-leucine were applied with blood and muscle tissue samples collected throughout overnight sleep. Presleep protein ingestion did not increase muscle connective tissue protein synthesis rates (0.049 ± 0.013 vs. 0.060 ± 0.024%/hr in PLA and PRO, respectively; p = .73). Exercise plus protein ingestion resulted in greater overnight muscle connective tissue protein synthesis rates (0.095 ± 0.022%/hr) when compared with PLA and PRO (p < .01). Exercise increased the incorporation of dietary protein-derived amino acids into muscle connective tissue protein (0.036 ± 0.013 vs. 0.054 ± 0.009 mole percent excess in PRO vs. EX+PRO, respectively; p < .01). In conclusion, resistance-type exercise plus presleep protein ingestion increases overnight muscle connective tissue protein synthesis rates in older men. Exercise enhances the utilization of dietary protein-derived amino acids as precursors for de novo muscle connective tissue protein synthesis during overnight sleep.

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A Systematic Review of CrossFit® Workouts and Dietary and Supplementation Interventions to Guide Nutritional Strategies and Future Research in CrossFit®

Ricardo Augusto Silva de Souza, André Guedes da Silva, Magda Ferreira de Souza, Liliana Kataryne Ferreira Souza, Hamilton Roschel, Sandro Fernandes da Silva, and Bryan Saunders

CrossFit® is a high-intensity functional training method consisting of daily workouts called “workouts of the day.” No nutritional recommendations exist for CrossFit® that are supported by scientific evidence regarding the energetic demands of this type of activity or dietary and supplement interventions. This systematic review performed in accordance with PRISMA guidelines aimed to identify studies that determined (a) the physiological and metabolic demands of CrossFit® and (b) the effects of nutritional strategies on CrossFit® performance to guide nutritional recommendations for optimal recovery, adaptations, and performance for CrossFit® athletes and direct future research in this emerging area. Three databases were searched for studies that investigated physiological responses to CrossFit® and dietary or supplementation interventions on CrossFit® performance. Various physiological measures revealed the intense nature of all CrossFit® workouts of the day, reflected in substantial muscle fatigue and damage. Dietary and supplementation studies provided an unclear insight into effective strategies to improve performance and enhance adaptations and recovery due to methodological shortcomings across studies. This systematic review showed that CrossFit® is a high-intensity sport with fairly homogenous anaerobic and aerobic characteristics, resulting in substantial metabolic stress, leading to metabolite accumulation (e.g., lactate and hydrogen ions) and increased markers of muscle damage and muscle fatigue. Limited interventional data exist on dietary and supplementation strategies to optimize CrossFit® performance, and most are moderate to very low quality with some critical methodological limitations, precluding solid conclusions on their efficacy. High-quality work is needed to confirm the ideal dietary and supplemental strategies for optimal performance and recovery for CrossFit® athletes and is an exciting avenue for further research.

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Ultrasound Measurements of Subcutaneous Fat Thickness Are Robust Against Hydration Changes

Dale R. Wagner and James D. Cotter

Ultrasound is an appealing tool to assess body composition, combining the portability of a field method with the accuracy of a laboratory method. However, unlike other body composition methods, the effect of hydration status on validity is unknown. This study evaluated the impact of acute hydration changes on ultrasound measurements of subcutaneous fat thickness and estimates of body fat percentage. In a crossover design, 11 adults (27.1 ± 10.5 years) completed dehydration and hyperhydration trials to alter body mass by approximately ±2%. Dehydration was achieved via humid heat (40 °C, 60% relative humidity) with exercise, whereas hyperhydration was via ingestion of lightly salted water. Ultrasound measurements were taken at 11 body sites before and after each treatment. Participants lost 1.56 ± 0.58 kg (−2.0 ± 0.6%) during the dehydration trial and gained 0.90 ± 0.21 kg (1.2 ± 0.2%) during the hyperhydration trial even after urination. The sum of fat thicknesses as measured by ultrasound differed by <0.90 mm across trials (p = .588), and ultrasound estimates of body fat percentage differed by <0.5% body fat. Ultrasound measures of subcutaneous adipose tissue were unaffected by acute changes in hydration status by extents beyond which are rare and overtly self-correcting, suggesting that this method provides reliable and robust body composition results even when subjects are not euhydrated.