Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.

INTRODUCTION: Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown. Cilastatin treatment was recently identified as an experimental treatment to prevent RIAKI at injury. To determine potential interacting factors in RIAKI treatment, we test the hypothesis that caffeine and ibuprofen worsen RIAKI and interfere with treatment. MATERIALS AND METHODS: In mice, RIAKI was induced by glycerol intramuscular injection. Simultaneously, mice received caffeine (3 mg/kg), ibuprofen (10 mg/kg), or vehicle. A second cohort received volume resuscitation (PlasmaLyte, 20 mL/kg) in addition to caffeine or ibuprofen. In a third cohort, cilastatin (200 mg/kg) was administered concurrently with drug and glycerol administration. Glomerular filtration rate (GFR), blood urea nitrogen (BUN), urine output (UOP), renal pathology, and renal immunofluorescence for kidney injury molecule 1 were quantified after 24 hours. RESULTS: Caffeine did not worsen RIAKI; although BUN was modestly increased by caffeine administration, 24-hour GFR, UOP, and renal histopathology were similar between vehicle-treated, caffeine-treated, and caffeine + PlasmaLyte-treated mice. Ibuprofen administration greatly worsened RIAKI (GFR 14.3 ± 19.5 vs. 577.4 ± 454.6 µL/min/100 g in control, UOP 0.5 ± 0.4 in ibuprofen-treated mice vs. 2.7 ± 1.7 mL/24 h in control, and BUN 264 ± 201 in ibuprofen-treated mice vs. 66 ± 21 mg/dL in control, P < .05 for all); PlasmaLyte treatment did not reverse this effect. Cilastatin with or without PlasmaLyte did not reverse the deleterious effect of ibuprofen in RIAKI. CONCLUSIONS: Caffeine does not worsen RIAKI. The widely used performance-enhancing drug ibuprofen greatly worsens RIAKI in mice. Standard or experimental treatment of RIAKI including the addition of cilastatin to standard resuscitation is ineffective in mice with RIAKI exacerbated by ibuprofen. These findings may have clinical implications for the current therapy of RIAKI and for translational studies of novel treatment.

Sports Medicine: Ergogenic Aids.

Ergogenic aids include performance-enhancing substances, nutritional supplements, and a variety of techniques aimed to improve an athlete's exercise performance capacity. Dietary supplement consumption in athletes is common and is higher in those with desire to become Olympic or world champions. Supplements with performance benefits include caffeine, creatine, nitrate, and sodium bicarbonate. Anabolic-androgenic steroids; stimulants, such as ephedrine; and body mass builders, such as human growth hormone, are the most used performance-enhancing substances in competition. The World Anti-Doping Agency (WADA) is responsible for generating the list of banned performance-enhancing substances as well as establishing the testing standards for national and international events. Makers of dietary supplements are not required to prove the products are safe or test them for quality. Products with third-party testing certifications can help minimize the risk of ingesting contaminated or banned substances. Therapeutic use exemptions may be granted in Olympic, professional, or NCAA sports for athletes with a medical necessity for banned substances. The role of the physician or other medical professional is to guide informed decision-making.

Education Interventions to Improve Knowledge, Beliefs, Intentions and Practices with Respect to Dietary Supplements and Doping Substances: A Narrative Review.

The misuse of dietary supplements and doping substances is commonly associated with toxicity, nutritional imbalances, and health and psychological consequences. This is alarming especially in light of the increasing prevalence of the use of dietary supplements and doping, particularly among young adults including athletes. There is evidence that education interventions can lead to improved knowledge, intentions, and practices. However, no review has summarized and evaluated the effectiveness of such interventions. The aim of this article is to review the characteristics, contents and effects of education interventions that were designed and implemented to improve knowledge, attitudes, beliefs and intentions with respect to the use of dietary supplements and doping agents in different populations. PubMed, Scopus, CINAHL, PsycInfo and Google Scholar were searched for English-language education interventions targeting dietary supplements and doping substances. A total of 20 articles were identified and have generally provided consistent findings. Most interventions reported a significant improvement in knowledge on dietary supplements and doping agents. Unfortunately, the heavy reliance on self-reported assessment tools limits the validity of these interventions, with almost all articles targeting athletes and adolescents.

Supplement Intake in Recreational Vegan, Vegetarian, and Omnivorous Endurance Runners-Results from the NURMI Study (Step 2).

Nutrient deficiency is a common cause of underperformance in endurance athletes, and supplement intake is frequently considered compensatory for vegan and vegetarian athletes specifically. This study aimed to investigate the patterns of supplement intake among vegan, vegetarian, and omnivorous distance (>10 km) runners and its association with age, sex, and race distance. From a total of 317 runners who participated in an online survey, 220 distance runners (mean age: 38.5 years; mean BMI: 21.75 kg/m2) were selected for the final sample after data clearance and assigned to 100 omnivores, 40 vegetarians, or 80 vegans. Sociodemographic information, racing experience, and patterns of supplement intake, including type, frequency, dosage, etc., were collected using a questionnaire. Macronutrient intake was assessed using a food frequency questionnaire. ANOVA and logistic regression were used for data analysis. The prevalence of supplement intake was 51% for total runners and 72% among vegan runners. Age, sex, and race distance had no significant effect on the type of supplement intake (p > 0.05). Compared to omnivores and vegetarians, vegan runners reported consuming more vitamin (but not carbohydrate/protein or mineral) supplements (p < 0.05). Vitamin B12, magnesium, and multivitamin had the most prevalent use amongst micronutrient supplements. This study points to a central role for supplementary nutritional strategies in different groups of distance runners. The present findings may help future investigations by design to identify specific requirements of endurance runners when adhering to specific kinds of diet particularly plant-based diets.

United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA).

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

Caffeine improves performance but not duration of the countermovement jump phases.

BACKGROUND: The countermovement jump (CMJ) test is often employed to assess power generated in the lower limbs and has been related to performance in several sports modalities. The objective of this study was to assess the effects of caffeine supplementation on jump height, average power (AP), peak power (PP), maximum velocity (Vmax), force production and duration of the eccentric, isometric and concentric muscle contraction phases of a CMJ. METHODS: Sixteen resistance-trained men (age: 22.69±2.12 years; height: 1.78±0.06 m; weight: 78.09±10.27 kg) performed a CMJ 60 minutes after having taken an oral supplement containing 6 mg·kg-1 of caffeine or placebo (sucrose). The study design was randomized, double-blind crossover. RESULTS: Caffeine ingestion improved jump height (+3.86%, P=0.02), Vmax (+1.49%, P=0.023), AP (+4.83%, P=0.006), and PP (+3.49%, P=0.004). CONCLUSIONS: Acute caffeine supplementation leads to improved CMJ height, Vmax, AP and PP without significantly affecting the duration of the different test phases. Therefore, caffeine supplementation may be employed as ergogenic aid in sports where CMJ performance has been associated with sport-specific performance enhancements.

The role of sexual minority stress and community involvement on disordered eating, dysmorphic concerns and appearance- and performance-enhancing drug misuse.

Prior research has established that sexual minority (SM) individuals are more likely to experience disordered body image behaviors and concerns than heterosexual individuals. This increased risk may be explained by minority stress theory - that SM individuals are subject to SM-specific stressors, leading to health disparities - but this has not yet been fully examined. Furthermore, this theory states that SM community involvement may mitigate negative outcomes. The current study examines whether minority stress is associated with screening positive for an eating disorder, screening positive for body dysmorphic disorder, and appearance- and performance-enhancing drug misuse in a sample of SM individuals (483 women and 479 men) in the US. This study also examines whether the effect of minority stress is moderated by SM community involvement. Logistic regressions were conducted for each type of minority stress (internalized homophobia, sexual orientation concealment, and heterosexist discrimination) interacting with community involvement. After correction for multiple comparisons, all minority stressors and community involvement were positively associated with increased odds of disordered body image behaviors and concerns, with no evidence of a buffering effect for community involvement. The lack of a buffering effect is contrary to minority stress theory and may inform future prevention efforts.

Use of Sports Supplements in Competitive Handball Players: Sex and Competitive Level Differences.

Sports supplements are commonly used by elite athletes with the main goal of enhancing sport performance. Supplements use might be substantially different depending on the sport discipline, sex, and competitive level. To date, data about prevalence and the most-commonly used supplements in handball are scarce. Thus, the aim of this investigation was to determine the patterns of supplements use by handball players of both sexes and with different competitive levels: One hundred and eighty-seven handball players (112 men and 75 women) of different competitive levels (106 professional and 81 amateur) completed a validated self-administered questionnaire about supplements use. Supplements were classified according to the categorization of the Australian Institute of Sport (AIS). Overall, 59.9% of the handball players (n = 112) declared the use of at least one supplement and there were no significant differences between men and women (58.9% vs. 61.3%, p = 0.762) nor between professional vs. amateur handball players (67.1% vs. 53.8%, p = 0.074). The most prevalent supplements were sports drinks (42.2%), followed by energy bars (35.3%) and caffeine-containing products (31.6%). However, a greater consumption of group A supplements (those with strong scientific evidence; p = 0.029) and group B supplements (those with emerging scientific support, p = 0.012) was observed in male compared to female handball players. Supplements categorized as medical supplements were more commonly consumed in professional vs. amateur players (0.48 ± 0.80 vs. 0.21 ± 0.44, supplements p < 0.006). Additionally, a higher consumption of group B supplements was observed in professional compared to amateur players (0.58 ± 0.88 vs. 0.33 ± 0.72 supplements, p = 0.015). Handball players revealed a moderate use of supplements while sex and competitive level slighted changed the pattern of supplements use. A high portion of handball players use supplements as fuel during exercise and reported the use of caffeine-containing supplements to enhance performance.

Health Behaviors and Psychosocial Attributes of US Soldiers.

BACKGROUND: Health trends, which promote performance enhancement and maintaining or increasing muscle strength, may appeal to soldiers looking to maintain health standards set by the US Army, but often these trends require further investigation to assess safety and efficacy. High-intensity interval training (HIIT) and use of weight loss and/or performance-enhancing/body-building dietary supplements (WL/PES DS) are two such trends that, if implemented inappropriately, can negatively impact soldier health and readiness. OBJECTIVE: Our aim was to establish health/psychosocial profiles of US Army soldiers who participate in HIIT and/or use WL/PES DS. DESIGN: This cross-sectional observational study used data from the 2016 US Army Global Assessment Tool. PARTICIPANTS: Data were analyzed from respondents to the 2016 US Army Global Assessment Tool (n=299,996) who consented to have their data used for research purposes. RESULTS: Soldiers were classified into four groups based on HIIT and/or WL/PES DS use. Thirty-five percent of soldiers participated in HIIT and 10% took WL/PES DS at least once per month in the last year. HIIT participation was associated with higher reported odds of healthy behaviors and higher emotional and social fitness. In contrast to HIIT, WL/PES DS use was associated with higher reported odds of risky behaviors (hazardous drinking and tobacco use) and lower psychosocial fitness. The group participating in HIIT but not using WL/PES DS reported fewer unhealthy behaviors compared to the HIIT+WL/PES DS and WL/PES DS-only groups. CONCLUSIONS: Engaging in HIIT is associated with higher reported odds of healthy behaviors and increased psychosocial fitness. However, soldiers who engaged in HIIT also have increased odds of WL/PES DS use, which is associated with greater reported risky behaviors and reduced fitness. Although HIIT and WL/PES DS use are related, they are associated with different reported health/risky behaviors and different psychosocial attributes.

Cannabidiol in sport: Ergogenic or else?

In the sports domain, cannabis is prohibited by the World Anti-Doping Agency (WADA) across all sports in competition since 2004. The few studies on physical exercise and cannabis focused on the main compound i.e. Δ9-tetrahydrocannabinol. Cannabidiol (CBD) is another well-known phytocannabinoid present in dried or heated preparations of cannabis. Unlike Δ9-tetrahydrocannabinol, CBD is non-intoxicating but exhibits pharmacological properties that are interesting for medical use. The worldwide regulatory status of CBD is complex and this compound is still a controlled substance in many countries. Interestingly, however, the World Anti-Doping Agency removed CBD from the list of prohibited substances - in or out of competition - since 2018. This recent decision by the WADA leaves the door open for CBD use by athletes. In the present opinion article we wish to expose the different CBD properties discovered in preclinical studies that could be further tested in the sport domain to ascertain its utility. Preclinical studies suggest that CBD could be useful to athletes due to its anti-inflammatory, analgesic, anxiolytic, neuroprotective properties and its influence on the sleep-wake cycle. Unfortunately, almost no clinical data are available on CBD in the context of exercise, which makes its use in this context still premature.

Health care engagement behaviors of men who use performance- and image-enhancing drugs in Australia.

Background: Although people who inject performance- and image-enhancing drugs (PIEDs) report fewer unsafe injecting practices, stigma and discrimination may negatively impact their access to help and information. Engagement with health care services, compared with social networks (friends, relatives, and gym associates) and the Internet and media (steroid user forums, information sites, and magazines), may be important for harm minimization. Methods: A cross-sectional Internet or in-person survey of men who use PIEDs in Australia in 2014-2015 examined differences in sources for PIEDs, injecting equipment, and anabolic-androgenic steroids (AAS) information and factors associated with having periodical medical checks related to PIEDs issues using multivariate logistic regression. Results: In total, 267 men (mean age: 25 years, SD: 8.7 years; 246 of 267 [92%] reported recent AAS injection) were recruited. Most participants sourced injecting equipment from health professionals, PIEDs from their social networks, and AAS information from the Internet and media. Self-reported AAS knowledge was high and frequent. Higher income (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.03, 4.00), ≥2 different PIEDs used in addition to AAS (AOR: 1.94, 95% CI: 1.08, 3.49), and sourcing AAS information from health care professionals (AOR: 3.14, 95% CI: 1.81, 5.46) were independently associated with periodical medical checks. Participants nominated preference for improved health services through needle-syringe programs, primary care services, and peer educator support groups. Conclusion: Men who use PIEDs in Australia consider themselves well informed but tend to use Internet and media sources, providing potentially misleading or inaccurate information. Increasing trust between men who use PIEDs and health care providers may enable delivery of PIEDs-specific information to those at greatest need.

Update on the Role of Actovegin in Musculoskeletal Medicine: A Review of the Past 10 Years.

BACKGROUND: Actovegin is a biological drug with a controversial history of use in the treatment of sports injuries during the past 60 years. Particular concerns have been raised about its ergogenic potential to enhance performance, but some of these have been based on little more than anecdote. OBJECTIVES: In this article, we review the most recent scientific evidence to determine the clinical efficacy, safety profile, and legal status of Actovegin. METHODS: We considered all studies directly commenting on experience with Actovegin use as the primary intervention within the past 10 years. Outcomes included mechanisms of action, clinical efficacy in enhancing muscle repair, any report of safety issues, and any evidence for ergogenic effect. RESULTS: Our database search returned 212 articles, abstracts were screened, and after inclusion/exclusion criteria were applied, 25 articles were considered: Publications included 11 primary research articles (7 in vitro studies and 4 clinical trials), 8 review articles, 5 editorials, and a single case report. CONCLUSIONS: Current literature is still yet to define the active compound(s) of Actovegin, but suggests that it shows antioxidant and antiapoptotic properties, and may also upregulate macrophage responses central to muscle repair. Clinical efficacy was supported by one new original research article, and the use of Actovegin to treat muscle injuries remains safe and supported. Two articles argued the ergogenic effect of Actovegin, but in vitro findings did not to translate to the outcomes of a clinical trial. An adequate and meaningful scientific approach remains difficult in a field where there is immense pressure to deliver cutting-edge therapies.

The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses.

Polyphenols are secondary metabolites involved in a myriad of critical processes in plants. Over recent decades, special attention has been paid to the anti-oxidative role of fruit-derived polyphenols in the human diet, with evidence supporting the contribution of polyphenols in the prevention of numerous non-communicable disease outcomes. However, due to the low concentration in biological fluids in vivo, the antioxidant properties of polyphenols seem to be related to an enhanced endogenous antioxidant capacity induced via signaling through the nuclear respiratory factor 2 pathway. Polyphenols also seem to possess anti-inflammatory and antioxidant properties and have been shown to enhance vascular function via nitric oxide mediated mechanisms. Consequently, there is rationale to support fruit-derived polyphenol supplementation to enhance exercise performance, possibly via improved muscle perfusion. Fruit-derived polyphenol supplementation in exercise studies have included a variety of fruits, e.g., New Zealand blackcurrant, pomegranate, and cherry, in the form of extracts (multicomponent or purified), juices and infusions to varying degrees of benefit. For example, research has yet to link the health-related benefits of black elderberry (Sambucus nigra L.) ingestion to exercise performance in spite of the purported health benefits associated with black elderberry provision in vitro and in vivo models, which has been attributed to their high antioxidant capacity and polyphenol content. This review summarizes the existing evidence supporting a beneficial effect of fruit-derived polyphenols on various biological processes and outlines the potential for black elderberry ingestion to improve nitric oxide production, exercise performance, and the associated physiological responses before-, during- and post-exercise.

Toxicity From Unintentional Pediatric Ingestion of a Performance-Enhancing Drug: A Case Report With Review of Clenbuterol Toxicity and Treatment.

BACKGROUND: Clenbuterol is a long-acting ß-adrenergic agonist that is not Food and Drug Administration-approved for use in the United States, but may be obtained without a prescription from various unregulated sellers. It has seen increasing use as a performance-enhancing drug for sports. Literature on pediatric toxicity and treatment is limited. CASE REPORT: We report a case of a 2-year-old female presenting after an exploratory ingestion of clenbuterol. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Use of performance-enhancing agents is increasing and physicians should be aware of the potential toxicity of intentional and unintentional ingestions of ß-adrenergic agonists. Patients may exhibit nausea, vomiting, tremor, tachycardia, and hypotension, along with laboratory abnormalities, including hyperglycemia, hypophosphatemia, hypokalemia, and hyperglycemia. Hypotension might not respond to adrenergic agents and may require administration of ß-adrenergic antagonists to maintain adequate perfusion.

Sex Differences in the Health Status of Endurance Runners: Results From the NURMI Study (Step 2).

Boldt, P, Knechtle, B, Nikolaidis, P, Lechleitner, C, Wirnitzer, G, Leitzmann, C, and Wirnitzer, K. Sex differences in the health status of endurance runners: results from the NURMI study (step 2). J Strength Cond Res 33(7): 1929-1940, 2019-Optimized endurance performance is closely linked to a good health status (HS), which is crucially affected by sex. Therefore, the purpose of this study was to investigate sex differences in the HS of endurance runners of different distances. A total of 281 female and male recreational runners completed an online survey. Health status included body mass, smoking habits, felt stress, chronic diseases, allergies, intolerances, medication intake, supplement intake, health-related food choice, enhancement substance use, and health care utilization. Data analysis was performed using the independent t-test and chi-squared test with Cohen's d and Cramer's phi (φ) to evaluate the magnitude of the differences and associations. There were 159 female and 122 male participants, with 173 runners meeting the inclusion criteria, among them 103 half-marathoners, and 70 marathoners and ultramarathoners, of which one hundred eight 10-km runners were defined as the control group. Statistical significance (p < 0.05) was determined for the following findings: there was a higher prevalence of hypothyroidism in women; the use of thyroid medication and the intake of hormones and supplements prescribed by a doctor were more common in women; men reported more often a decrease in body mass due to running training, and women reported more often choosing food to obtain phytochemicals. There was no statistically significant association (p > 0.05) between sex and body mass change because of a change in diet, smoking habits, felt stress, chronic diseases except hypothyroidism, allergies, food intolerances, intake of antihypertensives and cholesterol-lowering medication, intake of performance-enhancing substances, or health care utilization. Both female and male runners had a good HS with no difference between sexes. Based on the findings of this study, monitoring thyroid parameters and vitamin D levels is required in female athletes, whereas adequate body mass control strategies are needed for their male counterparts.

Pharmacologic Strategies for Exercise-Induced Bronchospasm with a Focus on Athletes.

Exercise-induced bronchoconstriction (EIB) is the transient narrowing of the airways during and after exercise that occurs in response to increased ventilation in susceptible individuals. It occurs across the age spectrum in patients with underlying asthma and can occur in athletes without baseline asthma. The inflammatory mechanisms underlying EIB in patients without asthma may be distinct from those underlying EIB in patients with asthma. This review summarizes mechanistic and clinical data that can guide the choice of chronic and acute pharmacologic therapies targeting control of EIB. Relevant regulations from the World Anti-Doping Agency are also discussed.

Exercise and Sinonasal Disease.

Physical exercise requires proper function of the upper and lower airways in order to meet exertional ventilatory requirements. Athletes performing frequent intensive exercise experience more sino-nasal symptoms and demonstrate objective decreases in sino-nasal function when compared with the general population. Sino-nasal dysfunction is known to interfere with sport performance. Nasal epithelial injury, neutrophilic influx, and decreased mucociliary clearance have been associated with intensive training. In this review, the authors provide a comprehensive overview of the prevalence of sino-nasal disease in athletes, the possible underlying pathophysiologic mechanisms, and a summary of diagnostic and treatment options.

l-Carnitine Supplementation in Recovery after Exercise.

Given its pivotal role in fatty acid oxidation and energy metabolism, l-carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l-carnitine on the recovery process after exercise. It is demonstrated that l-carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness. The supplementation-based increase in serum and muscle l-carnitine contents is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function thereby reducing hypoxia-induced cellular and biochemical disruptions. Studies in older adults further showed that l-carnitine intake can lead to increased muscle mass accompanied by a decrease in body weight and reduced physical and mental fatigue. Based on current animal studies, a role of l-carnitine in the prevention of age-associated muscle protein degradation and regulation of mitochondrial homeostasis is suggested.

Carbohydrate Mouth Rinse Fails to Improve Four-Kilometer Cycling Time Trial Performance.

We investigated if a carbohydrate (CHO) mouth rinse may attenuate global fatigue and improve 4-km cycling time trial (TT4km) performance. After a preliminary session, cyclists (n = 9) performed a TT4km after a CHO or placebo (PLA) mouth rinse. Mean power output, time, and ratings of perceived exertion (RPE) were recorded throughout the TT4km. Twitch interpolation responses (%VA; voluntary activation and ∆Tw; delta peak twitch torque) were compared pre and post TT4km with traditional statistics and effect size (ES) analysis. Time-to-complete the 4 km and mean power output were comparable between CHO (386.4 ± 28.0 s) and PLA (385.4 ± 22.4 s). A lower central (p = 0.054) and peripheral (p = 0.02) fatigue in CHO than in PLA were suggested by an extremely-large ES in %VA (manipulation main effect: p = 0.052, d = 1.18; manipulation-by-time interaction effect: p = 0.08, d = 1.00) and an extremely, very-large ES in ∆Tw (manipulation main effect: p = 0.07, d = 0.97; time-by-manipulation interaction effect: p = 0.09, d = 0.89). The RPE increased slower in CHO than in PLA (p = 0.051; d = 0.7). The apparent reduction in global fatigue (central and peripheral) and RPESLOPE with only one CHO mouth rinse were not translated into improved TT4km performance. Further tests may be required to verify if these likely differences in global fatigue might represent an edge in the short-lasting cycling time trial performance.

ß-2 Agonists as Misusing Drugs? Assessment of both Clenbuterol- and Salbutamol-related European Medicines Agency Pharmacovigilance Database Reports.

A recent years' increase in misusing levels of image- and performance- enhancing drugs (IPEDs) has been observed. Out of these drugs, beta-2 agonists have recently emerged for their potential of misuse, especially for slimming and bodybuilding purposes. To this perspective, clenbuterol ('the size zero pill') has been reported as being both popular and widely available from the illegal market. All clenbuterol and salbutamol misuse/abuse/dependence/withdrawal/overdose/off-label spontaneous reports (2006-2016) from the European Medicines Agency (EMA) EudraVigilance (EV) database were collected and analysed by age range, gender, concomitant therapies and source of information. From the EV database, 55 of a total number of 920 'suspect' misuse/abuse/dependence/withdrawal/overdose/off-label ADRs (e.g. 5.97%; corresponding to 25 of 138 individuals) and 1310 of 62,879 ADRs (e.g. 2.08%; corresponding to 474 of 6923 individuals) were, respectively, associated with clenbuterol (typically ingested in combination with a range of anabolic steroids) and salbutamol. Proportional reporting ratio (PRR) value for misuse/abuse ADRs was higher (PRR = 18.38) for clenbuterol in comparison with salbutamol. Clenbuterol misuse/abuse could be a cause for major concern, especially in vulnerable individuals.