Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run.

RATIONALE: Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function. METHODS: 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7-14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals. RESULTS: BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [-2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (-35.7 [-72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (-26.9 [-50.5, -3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (p = 0.049, ηp2 = 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (-23.2 [-43.4, -2.4] %, p = 0.029) and PX+CA (-29.6 [-50.3, -8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers. CONCLUSIONS: Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

Caffeine Improves Sprint Time in Simulated Freestyle Swimming Competition but Not the Vertical Jump in Female Swimmers.

Caffeine (CAF) has been shown to be an effective ergogenic aid in enhancing sports performance, including vertical jump (VJ), sprint, balance, agility, and freestyle swimming performance (FSP). However, whether acute CAF supplementation improves FSP in moderately trained female swimmers has not been well documented. Therefore, this study aimed to investigate the effects of CAF intake on vertical jump, balance, auditory reaction time (ART), and swimming performance in female swimmers. In a double-blind, cross-over design, eight moderately trained female swimmers (age: 21.3 ± 1.4 years, height: 161.2 ± 7.1 cm, body mass: 56.3 ± 6.7 kg, body mass index (BMI): 21.9 ± 1.3 kg/m2, and habitual CAF intake: 246.4 ± 111.4 mg/day) ingested caffeine (CAF) (6 mg/kg) or a placebo (PLA) 60 min before completing VJ, balance, ART, and 25/50 m FSP. CAF supplementation resulted in a significantly lower time both in 25m (p = 0.032) and 50m (p = 0.033) FSP. However, CAF resulted in no significant difference in VJ, ART, and RPE (p > 0.05). Balance test results showed a non-significant moderate main effect (d = 0.58). In conclusion, CAF seems to reduce time in short-distance swimming performances, which could be the determinant of success considering the total time of the race. Thus, we recommend coaches and practitioners incorporate CAF into swimmers' nutrition plans before competitions, which may meet the high performance demands.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Effects of Caffeinated Coffee on Cross-Country Cycling Performance in Recreational Cyclists.

The ergogenic effects of acute caffeine intake on endurance cycling performance lasting ~1 h have been well documented in controlled laboratory studies. However, the potential benefits of caffeine supplementation in cycling disciplines such as cross-country/mountain biking have been rarely studied. In cross-country cycling, performance is dependent on endurance capacity, which may be enhanced by caffeine, but also on the technical ability of the cyclist to overcome the obstacles of the course. So, it is possible that the potential benefits of caffeine are not translated to cross-country cycling. The main objective of this study was to investigate the effects of acute caffeine intake, in the form of coffee, on endurance performance during a cross-country cycling time trial. Eleven recreational cross-country cyclists (mean ± SD: age: 22 ± 3 years; nine males and two females) participated in a single-blinded, randomised, counterbalanced and crossover experiment. After familiarisation with the cross-country course, participants completed two identical experimental trials after the ingestion of: (a) 3.00 mg/kg of caffeine in the form of soluble coffee or (b) 0.04 mg/kg of caffeine in the form of decaffeinated soluble coffee as a placebo. Drinks were ingested 60 min before performing a 13.90 km cross-country time trial over a course with eight sectors of varying technical difficulty. The time to complete the trial and the mean and the maximum speed were measured through Global Positioning System (GPS) technology. Heart rate was obtained through a heart rate monitor. At the end of the time trial, participants indicated their perceived level of fatigue using the traditional Borg scale. In comparison to the placebo, caffeine intake in the form of coffee significantly reduced the time to complete the trial by 4.93 ± 4.39% (43.20 ± 7.35 vs. 41.17 ± 6.18 min; p = 0.011; effect size [ES] = 0.300). Caffeine intake reduced the time to complete four out of eight sectors with different categories of technical difficulty (p ≤ 0.010; ES = 0.386 to 0.701). Mean heart rate was higher with caffeine (169 ± 6 vs. 162 ± 13 bpm; p = 0.046; ES = 0.788) but the rating of perceived exertion at the end of the trial was similar with caffeinated coffee than with the placebo (16 ± 1 vs. 16 ± 2 a.u.; p = 0.676; ES = 0.061). In conclusion, the intake of 3 mg/kg of caffeine delivered via soluble coffee reduced the time to complete a cross-country cycling trial in recreational cyclists. These results suggest that caffeine ingested as coffee may be an ergogenic substance for cross-country cycling.

Common questions and misconceptions about caffeine supplementation: what does the scientific evidence really show?

Caffeine is a popular ergogenic aid that has a plethora of evidence highlighting its positive effects. A Google Scholar search using the keywords "caffeine" and "exercise" yields over 200,000 results, emphasizing the extensive research on this topic. However, despite the vast amount of available data, it is intriguing that uncertainties persist regarding the effectiveness and safety of caffeine. These include but are not limited to: 1. Does caffeine dehydrate you at rest? 2. Does caffeine dehydrate you during exercise? 3. Does caffeine promote the loss of body fat? 4. Does habitual caffeine consumption influence the performance response to acute caffeine supplementation? 5. Does caffeine affect upper vs. lower body performance/strength differently? 6. Is there a relationship between caffeine and depression? 7. Can too much caffeine kill you? 8. Are there sex differences regarding caffeine's effects? 9. Does caffeine work for everyone? 10. Does caffeine cause heart problems? 11. Does caffeine promote the loss of bone mineral? 12. Should pregnant women avoid caffeine? 13. Is caffeine addictive? 14. Does waiting 1.5-2.0 hours after waking to consume caffeine help you avoid the afternoon "crash?" To answer these questions, we performed an evidence-based scientific evaluation of the literature regarding caffeine supplementation.

Effect of Acute Sodium Bicarbonate and Caffeine Coingestion on Repeated-Sprint Performance in Recreationally Trained Individuals: A Randomized Controlled Trial.

INTRODUCTION: The acute and isolated ingestion of sodium bicarbonate (NaHCO3) and caffeine (CAF) improves performance and delays fatigue in high-intensity tasks. However, it remains to be elucidated if the coingestion of both dietary supplements stimulates a summative ergogenic effect. This study aimed to examine the effect of the acute coingestion of NaHCO3 and CAF on repeated-sprint performance. METHODS: Twenty-five trained participants (age: 23.3 [4.0] y; sex [female/male]: 12/13; body mass: 69.6 [12.5] kg) participated in a randomized, double-blind, placebo (PLA) -controlled, crossover study. Participants were assigned to 4 conditions: (1) NaHCO3 + CAF, (2) NaHCO3, (3) CAF, or (4) PLA. Thus, they ingested 0.3 g/kg of NaHCO3, 3 mg/kg of CAF, or PLA. Then, participants performed 4 Wingate tests (Wt), consisting of a 30-second all-out sprint against an individualized resisted load, interspersed by a 1.5-minute rest period between sprints. RESULTS: Peak (Wpeak) and mean (Wmean) power output revealed a supplement and sprint interaction effect (P = .009 and P = .049, respectively). Compared with PLA, NaHCO3 + CAF and NaHCO3 increased Wpeak performance in Wt 3 (3%, P = .021) and Wt 4 (4.5%, P = .047), while NaHCO3 supplementation increased mean power performance in Wt 3 (4.2%, P = .001). In Wt 1, CAF increased Wpeak (3.2%, P = .054) and reduced time to Wpeak (-8.5%; P = .008). Plasma lactate showed a supplement plus sprint interaction (P < .001) when NaHCO3 was compared with CAF (13%, P = .031) and PLA (23%, P = .021). CONCLUSION: To summarize, although the isolated ingestion of CAF and NaHCO3 improved repeated-sprint performance, the coingestion of both supplements did not stimulate a synergic ergogenic effect.

Multi-omics reveals changed energy metabolism of liver and muscle by caffeine after mice swimming.

In recent years, numerous studies have investigated the effects of caffeine on exercise, and provide convincing evidence for its ergogenic effects on exercise performance. However, the precise mechanisms underlying these ergogenic effects remain unclear. In this study, an exercise swimming model was conducted to investigate the effects of orally administered with caffeine before swimming on the alterations of proteome and energy metabolome of liver and muscle after swimming. We found proteins in liver, such as S100a8, S100a9, Gabpa, Igfbp1 and Sdc4, were significantly up-regulated, while Rbp4 and Tf decreased after swimming were further down-regulated in caffeine group. The glycolysis and pentose phosphate pathways in liver and muscle were both significantly down-regulated in caffeine group. The pyruvate carboxylase and amino acid levels in liver, including cysteine, serine and tyrosine, were markedly up-regulated in caffeine group, exhibiting a strong correlation with the increased pyruvic acid and oxaloacetate levels in muscle. Moreover, caffeine significantly decreased the lactate levels in both liver and muscle after swimming, potentially benefiting exercise performance.

Food for thought: Physiological considerations for nutritional ergogenic efficacy.

Top-class athletes have optimized their athletic performance largely through adequate training, nutrition, recovery, and sleep. A key component of sports nutrition is the utilization of nutritional ergogenic aids, which may provide a small but significant increase in athletic performance. Over the last decade, there has been an exponential increase in the consumption of nutritional ergogenic aids, where over 80% of young athletes report using at least one nutritional ergogenic aid for training and/or competition. Accordingly, due to their extensive use, there is a growing need for strong scientific investigations validating or invalidating the efficacy of novel nutritional ergogenic aids. Notably, an overview of the physiological considerations that play key roles in determining ergogenic efficacy is currently lacking. Therefore, in this brief review, we discuss important physiological considerations that contribute to ergogenic efficacy for nutritional ergogenic aids that are orally ingested including (1) the impact of first pass metabolism, (2) rises in systemic concentrations, and (3) interactions with the target tissue. In addition, we explore mouth rinsing as an alternate route of ergogenic efficacy that bypasses the physiological hurdles of first pass metabolism via direct stimulation of the central nervous system. Moreover, we provide real-world examples and discuss several practical factors that can alter the efficacy of nutritional ergogenic aids including human variability, dosing protocols, training status, sex differences, and the placebo effect. Taking these physiological considerations into account will strengthen the quality and impact of the literature regarding the efficacy of potential ergogenic aids for top-class athletes.

Topical application of L-Menthol - Physiological and genetic considerations to assist in developing female athlete research: A narrative review.

L-menthol is a cyclic monoterpene derived from aromatic plants, which gives a cooling sensation upon application. With this in mind, L-menthol is beginning to be considered as a potential ergogenic aid for exercise and sporting competitions, particularly in hot environments, however female-specific research is lacking. The aim of this narrative review is to summarize available literature relating to topical application of L-menthol and provide commentary on avenues of consideration relating to future research developments of topical L-menthol in female athletes. From available studies in male participants, L-menthol topical application results in no endurance exercise performance improvements, however decreases in thermal sensation are observed. Mixed results are observed within strength performance parameters. Several genetic variations and single nucleotide polymorphisms have been identified in relation to sweat production, fluid loss and body mass changes - factors which may influence topical application of L-menthol. More specifically to female athletes, genetic variations relating to sweat responses and skin thickness, phases of the menstrual cycle, and body composition indices may affect the ergogenic effects of L-menthol topical application, via alterations in thermogenic responses, along with differing tissue distribution compared to their male counterparts. This narrative review concludes that further development of female athlete research and protocols for topical application of L-menthol is warranted due to physiological and genetic variations. Such developments would benefit research and practitioners alike with further personalized sport science strategies around phases of the menstrual cycle and body composition indices, with a view to optimize ergogenic effects of L-menthol.

Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases.

PURPOSE: Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans. METHODS: PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review. RESULTS: Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements. CONCLUSION: Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.

Moderators of Caffeine's Effects on Jumping Performance in Females: A Systematic Review and Meta-Analysis.

We aimed to perform a systematic review and meta-analysis of caffeine's effects on vertical jumping performance in females, with subgroup analyses for potential moderators, including phase of the menstrual cycle, testing time of day, caffeine dose, and test type. Fifteen studies were included in the review (n = 197). Their data were pooled in a random-effects meta-analysis of effect sizes (Hedges' g). In the main meta-analysis, we found an ergogenic effect of caffeine on jumping performance (g: 0.28). An ergogenic effect of caffeine on jumping performance was found when the testing was carried out in the luteal phase (g: 0.24), follicular phase (g: 0.52), luteal or follicular phase (g: 0.31), and when the phase was not specified (g: 0.21). The test for subgroup differences indicated that the ergogenic effects of caffeine were significantly greater in the follicular phase compared to all other conditions. An ergogenic effect of caffeine on jumping performance was found when the testing was carried out in the morning (g: 0.38), evening (g: 0.19), mixed morning or evening (g: 0.38), and when time was not specified (g: 0.32), with no subgroup differences. An ergogenic effect of caffeine on jumping performance was found when the dose was ≤3 mg/kg (g: 0.21), or >3 mg/kg (g: 0.37), with no subgroup differences. An ergogenic effect of caffeine on jumping performance was found in the countermovement jump test (g: 0.26) and squat jump test (g: 0.35), with no subgroup differences. In summary, caffeine ingestion is ergogenic for vertical jumping performance in females, and it seems that the magnitude of these effects is the largest in the follicular phase of the menstrual cycle.

In the main meta-analysis, which included 15 studies and ∼200 participants, we found a small but very precise ergogenic effect of caffeine on vertical jumping performance in females.In a subgroup analysis for phase of the menstrual cycle, the ergogenic effects of caffeine on jumping performance were the largest in the follicular phase.An ergogenic effect of caffeine was consistently found in analyses for testing time of day (morning, evening, mixed morning or evening, or not specified), caffeine dose (≤3 mg/kg or >3 mg/kg) and test type (squat or countermovement jump).

A Double-Blind, Randomized, Placebo-Controlled Pilot Study examining an Oxygen Nanobubble Beverage for 16.1-km Time Trial and Repeated Sprint Cycling Performance.

There is growing interest of ergogenic aids that deliver supplemental oxygen during exercise and recovery, however, breathing supplemental oxygen via specialist facemasks is often not feasible. Therefore, this study investigated the effect of an oxygen-nanobubble beverage during submaximal and repeated sprint cycling. In a double-blind, randomized, placebo-controlled study, 10 male cyclists (peak aerobic capacity, 56.9 ± 6.1 mL·kg-1·min-1; maximal aerobic power, 385 ± 25 W) completed submaximal or maximal exercise after consuming an oxygen-nanobubble (O2) or placebo (PLA) beverage. Submaximal trials comprised 30-min of steady-state cycling at 60% peak aerobic capacity and 16.1-km time-trial (TT). Maximal trials involved 4 × 30 s Wingate tests interspersed by 4-min recovery. Time-to-completion during the 16.1-km TT was 2.4% faster after O2 compared with PLA (95% CI = 0.7-4.0%, p = 0.010, d = 0.41). Average power for the 16.1-km TT was 4.1% higher for O2 vs. PLA (95% CI = 2.1-7.3%, p = 0.006, d = 0.28). Average peak power during the repeated Wingate tests increased by 7.1% for O2 compared with PLA (p = 0.002, d = 0.58). An oxygen-nanobubble beverage improves performance during submaximal and repeated sprint cycling, therefore may provide a practical and effective ergogenic aid for competitive cyclists.

Investigating the methods and characteristics of the trafficking of performance and image enhancing drugs in Australia.

INTRODUCTION: Using case law, the aims of this study were to document the methods for trafficking of performance and image-enhancing drugs (PIED) into Australia, and the characteristics of individuals and groups involved. METHODS: Data was collected from judges' sentencing comments. Searches were conducted using the Australasian Legal Information Institute database across all states in Australia, for the period of January 2010 to December 2021. After removing duplicates and cases which did not meet the inclusion criteria, 31 cases were included in the analysis. RESULTS: Across the 31 cases, 37 individuals were named as being involved in the supply and/or trafficking of PIEDs, with three cases involving an unknown number of individuals. One case named four actors involved in the supply and/or trafficking of PIEDs, three cases involved three actors, four cases involved two actors and 17 cases involved one actor. In 20 of the 31 cases, individuals operated alone. Over half (19 of the 37) of the individuals were health professionals. The majority (n = 17) of cases involved prescription as the method of acquisition, while seven cases involved the importation of PIEDs. DISCUSSION AND CONCLUSION: The small number of cases identified, with the majority involving only a single actor, and half of the cases involving those in the medical profession. The findings suggest that discrete occurrences of trafficking involves individuals or small groups that do not appear to be linked to large-scale networks or networks involving the supply and trafficking of other illicit substances.

Rhodiola rosea as an adaptogen to enhance exercise performance: a review of the literature.

Rhodiola rosea (RR) is a plant whose bioactive components may function as adaptogens, thereby increasing resistance to stress and improving overall resilience. Some of these effects may influence exercise performance and adaptations. Based on studies of rodents, potential mechanisms for the ergogenic effects of RR include modulation of energy substrate stores and use, reductions in fatigue and muscle damage and altered antioxidant activity. At least sixteen investigations in humans have explored the potential ergogenicity of RR. These studies indicate acute RR supplementation (∼200 mg RR containing ∼1 % salidroside and ∼3 % rosavin, provided 60 min before exercise) may prolong time-to-exhaustion and improve time trial performance in recreationally active males and females, with limited documented benefits of chronic supplementation. Recent trials providing higher doses (∼1500 to 2400 mg RR/d for 4­30 d) have demonstrated ergogenic effects during sprints on bicycle ergometers and resistance training in trained and untrained adults. The effects of RR on muscle damage, inflammation, energy system modulation, antioxidant activity and perceived exertion are presently equivocal. Collectively, it appears that adequately dosed RR enhances dimensions of exercise performance and related outcomes for select tasks. However, the current literature does not unanimously show that RR is ergogenic. Variability in supplementation dose and duration, concentration of bioactive compounds, participant characteristics, exercise tests and statistical considerations may help explain these disparate findings. Future research should build on the longstanding use of RR and contemporary clinical trials to establish the conditions in which supplementation facilitates exercise performance and adaptations.

Is melatonin as an ergogenic hormone a myth? a systematic review and meta-analysis.

PURPOSE: Melatonin supplementation has been disclosed as an ergogenic substance. However, the effectiveness of melatonin supplementation in healthy subjects has not been systematically investigated. The present study analyzed the effects of melatonin supplementation on physical performance and recovery. In addition, it was investigated whether exercise bout or training alter melatonin secretion in athletes and exercise practitioners. METHODS: This systematic review and meta-analysis were conducted and reported according to the guidelines outlined in the PRISMA statement. Based on the search and inclusion criteria, 21 studies were included in the systematic review, and 19 were included in the meta-analysis. RESULTS: Melatonin supplementation did not affect aerobic performance relative to time trial (-0.04; 95% CI: -0.51 to 0.44) and relative to VO2 (0.00; 95% CI: -0.57 to 0.57). Also, melatonin supplementation did not affect strength performance (0.19; 95% CI: -0.28 to 0.65). Only Glutathione Peroxidase (GPx) secretion increased after melatonin supplementation (1.40; 95% CI: 0.29 to 2.51). Post-exercise melatonin secretion was not changed immediately after an exercise session (0.56; 95% CI: -0.29 to 1.41) and 60 min after exercise (0.56; 95% CI: -0.29 to 1.41). CONCLUSION: The data indicate that melatonin is not an ergogenic hormone. In contrast, melatonin supplementation improves post-exercise recovery, even without altering its secretion.

Caffeine, CYP1A2 Genotype, and Exercise Performance: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to summarize and meta-analyze existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance and to investigate the interaction between genotype, dosage, and timing of caffeine supplementation. METHODS: Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise performance between CYP1A2 genotypes. Three-level meta-analyses were performed using standardized mean differences (SMD; Hedge's g ) to determine the effect of caffeine on exercise outcomes within and between CYP1A2 genotypes (AA, AC, and CC). Meta-regressions were performed for dose, timing, and presence of reported conflict of interests (RCOI). A meta-analysis was also performed with placebo values to assess for imbalances between genotypes. RESULTS: Thirteen studies, totaling 119 outcomes and 440 participants, were included (233 AA, 175 AC, ad 34 CC). Caffeine improved performance for AA (SMD = 0.30, 95% confidence interval [CI] = 0.21-0.39, P < 0.0001) and AC (SMD = 0.16, 95% CI = 0.06-0.25, P = 0.022) but worsened performance for CC (SMD = -0.22, 95% CI = -0.44 to -0.01, P < 0.0001). Dose affected only CC, with greater doses generating more positive SMD (CC-dose estimate: +0.19/1 mg·kg -1 body mass, 95% CI = 0.04-0.33, P = 0.01). Timing influenced only CC, with better performance with later onset of exercise after supplementation (CC-timing estimate: +0.01/min, 95% CI = 0.00-0.02, P = 0.02). RCOI only affected SMD of CC (CC-RCOI estimate: -0.57, 95% CI = -1.02 to -0.12, P = 0.01). After excluding studies with RCOI, no influence of genotype was seen (all P ≥ 0.19). Small, nonsignificant differences were seen in placebo between genotypes (SMD AA vs CC: -0.13; AA vs AC: -0.12; AC vs CC: -0.05; all P ≥ 0.26). CONCLUSIONS: Caffeine improved performance for AA and AC but worsened performance for CC. Dose and timing moderated the efficacy of caffeine for CC only. Caution is advised because baseline differences and studies with RCOI could have influenced these results.

Across the spectrum of legality: The market activities of influencers specialized in steroids and other performance and image enhancing drugs.

BACKGROUND: Like many other goods and services, performance and image enhancing drugs (PIEDs), and particularly androgenic anabolic steroids (AAS), are increasingly discussed and promoted by social media influencers. Little, however, is known about the influencers specialized in PIEDs and which drugs and services they promote and sell. AIMS: Against this background, the study has been intended to identify prominent influencers specialized in PIEDs, examine the market activities they engage in, and assess the latter's legality. METHODS: We first searched the clean internet to identify prominent PIED influencers. Second, we conducted a six-month-long, non-reactive digital ethnography of the social media accounts of 20 influencers and, via a content analysis, identified the market activities they engage in. Third, we assessed the latter's legality, primarily using the EU legislation as a benchmark. FINDINGS: The selected influencers are all current or former bodybuilders, predominantly male and from the United States. Many of them have developed a considerable number of followers, in three cases exceeding one million. They engage in various market activities that span the whole spectrum of legality, from legal to illegal, with many activities having an uncertain, but often dubious, legal status. CONCLUSIONS: Though they may promote harm reduction for some users, PIED influencers also promote the public acceptance of PIED use beyond the bodybuilding community and enhance access to PIEDs for millions of people. Multifaceted policy interventions are required, aiming at preventing influencers from becoming a major source of information on, and route of access to, PIEDs.

Annual banned-substance review 16th edition-Analytical approaches in human sports drug testing 2022/2023.

In this 16th edition of the annual banned-substance review on analytical approaches in human sports drug testing, literature on recent developments in this particular section of global anti-doping efforts that was published between October 2022 and September 2023 is summarized and discussed. Most recent additions to the continuously growing portfolio of doping control analytical approaches and investigations into analytical challenges in the context of adverse analytical findings are presented, taking into account existing as well as emerging challenges in anti-doping, with specific focus on substances and methods of doping recognized in the World Anti-Doping Agency's 2023 Prohibited List. As in previous years, focus is put particularly on new or enhanced analytical options in human doping controls, appreciating the exigence and core mission of anti-doping and, equally, the conflict arising from the opposingly trending extent of the athlete's exposome and the sensitivity of instruments nowadays commonly available in anti-doping laboratories.

Big business: The private sector market for image and performance enhancing drug harm reduction in the UK.

This article draws on three mutually independent ethnographic studies to explore the private sector market for image and performance enhancing drug (IPED) harm reduction in the UK, specifically examining (1) steroid accessory supplements; (2) blood testing services; and (3) bloodletting services. After contextualising the work with a discussion of IPED use and harm reduction and the substantial growth of the global health and fitness industry, each private sector provision is critically interrogated with the following questions in mind: what is the role and utility of these services compared to public sector provision? Why has the private sector begun to deliver IPED harm reduction products and services in the UK? And how does this provision relate to the health and fitness industry more broadly? The paper concludes with some reflections about the future direction of IPED harm reduction, the importance of community-led services, and the need to think innovatively if we are to best protect users' health and wellbeing.

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.