Effect of Caffeine on Endurance Performance in Athletes May Depend on HTR2A and CYP1A2 Genotypes.

ABSTRACT: Guest, NS, Corey, P, Tyrrell, PN, and El-Sohemy, A. Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res 36(9): 2486-2492, 2022-This investigation determined whether variation in the HTR2A (serotonin receptor) gene modifies the ergogenic effects of caffeine on endurance and further modifies performance by the CYP1A2 genotype. Male athletes ( n = 100; 25 ± 4 years) completed 10-km cycling time trials under 3 conditions as follows: 0, 2, or 4 mg of caffeine per kg body mass. Using a randomized, double-blinded, placebo-controlled design, data were analyzed using analysis of covariance to compare changes in cycling time between placebo (0 mg·kg -1 ) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of ρ ≤ 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine- HTR2A interaction ( p = 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant ( p = 0.37). Because of the strong caffeine- CYP1A2 interaction ( p < 0.0001) previously reported in these subjects, where the 4-mg dose resulted in divergent effects (slower and faster) on the 10-km cycling time, we conducted a simplified model to examine these same factors by the HTR2A genotype. The post hoc analysis excluded HTR2A CT heterozygotes and 2-mg·kg -1 caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p = 0.006) was observed when comparing (4- vs. 0-mg·kg -1 caffeine trials) between the HTR2A CC ( n = 16; 2.4 minutes) and TT ( n = 7; 0.7 minutes) genotypes. Our results show that 4-mg·kg -1 caffeine improves performance in individuals with the HTR2A CC genotype but only in those who are also CYP1A2 AA fast metabolizers. This study was registered with clinicaltrials.gov (NCT02109783).

Caffeine, genetic variation and anaerobic performance in male athletes: a randomized controlled trial.

PURPOSE: The effect of caffeine on anaerobic performance is unclear and may differ depending on an individual's genetics. The goal of this study was to determine whether caffeine influences anaerobic performance in a 30 s Wingate test, and if 14 single nucleotide polymorphisms (SNPs) in nine genes, associated with caffeine metabolism or response, modify caffeine's effects. METHODS: Competitive male athletes (N = 100; 25 ± 4 years) completed the Wingate under three conditions: 0, 2, or 4 mg of caffeine per kg of body mass (mg kg-1), using a double-blinded, placebo-controlled design. Using saliva samples, participants were genotyped for the 14 SNPs. The outcomes were peak power (Watts [W]), average power (Watts [W]), and fatigue index (%). RESULTS: There was no main effect of caffeine on Wingate outcomes. One significant caffeine-gene interaction was observed for CYP1A2 (rs762551, p = 0.004) on average power. However, post hoc analysis showed no difference in caffeine's effects within CYP1A2 genotypes for average power performance. No significant caffeine-gene interactions were observed for the remaining SNPs on peak power, average power and fatigue index. CONCLUSION: Caffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (NCT02109783).

CYP1A2 Genotype Modifies the Effects of Caffeine Compared With Placebo on Muscle Strength in Competitive Male Athletes.

Caffeine is commonly used to improve athletic performance across a variety of sports. Previously, the CYP1A2 gene has been shown to modify the effects of caffeine on endurance performance. The effect of caffeine on strength and power activities is unclear and may differ depending on an individual's CYP1A2 genotype. A randomized controlled trial was used to determine whether caffeine impacts strength and power, determined by the handgrip and vertical jump tests, respectively, and whether CYP1A2 genotype modifies any effects. Competitive male athletes (age = 25 ± 4 years) completed vertical jump (n = 97), and handgrip tests (n = 102) under three conditions: 0 (placebo), 2, or 4 mg of caffeine per kilogram of body mass (in milligrams per kilogram). CYP1A2 (rs762551) genotype was determined from saliva samples. No differences between caffeine doses and placebo were observed for strength or power; however, significant Caffeine × Gene interactions were observed for all exercise tests. Individuals with the CC genotype experienced a 12.8% decrease in handgrip strength with 4 mg/kg of caffeine compared with placebo (53 ± 11 kg vs. 61 ± 17 kg, p = .02). No differences were observed in those with the AC or AA genotypes. Despite observing a significant Caffeine × Gene interaction for vertical jump performance, no differences were observed between caffeine doses and placebo for all genotypes. In summary, caffeine (4 mg/kg) worsened handgrip strength performance in those with the CC genotype, but no differences were observed in those with the AC or AA genotypes. Athletes may want to consider their CYP1A2 genotype prior to using caffeine to improve muscle strength.

HFE Genotype and Endurance Performance in Competitive Male Athletes.

INTRODUCTION: Hereditary hemochromatosis can cause individuals to absorb too much iron from their diet. Higher tissue iron content, below the threshold of toxicity, may enhance oxygen carrying capacity and offer a competitive advantage. Single nucleotide polymorphisms (SNP) in the homeostatic iron regulator (HFE) gene have been shown to modify iron metabolism and can be used to predict an individual's risk of hemochromatosis. Several studies have shown that HFE genotypes are associated with elite endurance athlete status; however, no studies have examined whether HFE genotypes are associated with endurance performance. PURPOSE: The objectives of this study were to determine whether there was an association between HFE risk genotypes (rs1800562 and rs1799945) and endurance performance in a 10-km cycling time trial as well as maximal oxygen uptake (V˙O2peak), an indicator of aerobic capacity. METHODS: Competitive male athletes (n = 100; age = 25 ± 4 yr) completed a 10-km cycling time trial. DNA was isolated from saliva and genotyped for the rs1800562 (C282Y) and rs1799945 (H63D) SNP in HFE. Athletes were classified as low risk (n = 88) or medium/high risk (n = 11) based on their HFE genotype for both SNP using an algorithm. ANCOVA was conducted to compare outcome variables between both groups. RESULTS: Individuals with the medium- or high-risk genotype were ~8% (1.3 min) faster than those with the low-risk genotype (17.0 ± 0.8 vs 18.3 ± 0.3 min, P = 0.05). V˙O2peak was ~17% (7.9 mL·kg-1⋅min-1) higher in individuals with the medium- or high-risk genotype compared with those with the low-risk genotype (54.6 ± 3.2 vs 46.7 ± 1.0 mL·kg-1⋅min-1, P = 0.003). CONCLUSION: Our findings show that HFE risk genotypes are associated with improved endurance performance and increased V˙O2peak in male athletes.

International society of sports nutrition position stand: caffeine and exercise performance.

Following critical evaluation of the available literature to date, The International Society of Sports Nutrition (ISSN) position regarding caffeine intake is as follows: 1. Supplementation with caffeine has been shown to acutely enhance various aspects of exercise performance in many but not all studies. Small to moderate benefits of caffeine use include, but are not limited to: muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions. 2. Aerobic endurance appears to be the form of exercise with the most consistent moderate-to-large benefits from caffeine use, although the magnitude of its effects differs between individuals. 3. Caffeine has consistently been shown to improve exercise performance when consumed in doses of 3-6 mg/kg body mass. Minimal effective doses of caffeine currently remain unclear but they may be as low as 2 mg/kg body mass. Very high doses of caffeine (e.g. 9 mg/kg) are associated with a high incidence of side-effects and do not seem to be required to elicit an ergogenic effect. 4. The most commonly used timing of caffeine supplementation is 60 min pre-exercise. Optimal timing of caffeine ingestion likely depends on the source of caffeine. For example, as compared to caffeine capsules, caffeine chewing gums may require a shorter waiting time from consumption to the start of the exercise session. 5. Caffeine appears to improve physical performance in both trained and untrained individuals. 6. Inter-individual differences in sport and exercise performance as well as adverse effects on sleep or feelings of anxiety following caffeine ingestion may be attributed to genetic variation associated with caffeine metabolism, and physical and psychological response. Other factors such as habitual caffeine intake also may play a role in between-individual response variation. 7. Caffeine has been shown to be ergogenic for cognitive function, including attention and vigilance, in most individuals. 8. Caffeine may improve cognitive and physical performance in some individuals under conditions of sleep deprivation. 9. The use of caffeine in conjunction with endurance exercise in the heat and at altitude is well supported when dosages range from 3 to 6 mg/kg and 4-6 mg/kg, respectively. 10. Alternative sources of caffeine such as caffeinated chewing gum, mouth rinses, energy gels and chews have been shown to improve performance, primarily in aerobic exercise. 11. Energy drinks and pre-workout supplements containing caffeine have been demonstrated to enhance both anaerobic and aerobic performance.

Sport Nutrigenomics: Personalized Nutrition for Athletic Performance.

An individual's dietary and supplement strategies can influence markedly their physical performance. Personalized nutrition in athletic populations aims to optimize health, body composition, and exercise performance by targeting dietary recommendations to an individual's genetic profile. Sport dietitians and nutritionists have long been adept at placing additional scrutiny on the one-size-fits-all general population dietary guidelines to accommodate various sporting populations. However, generic "one-size-fits-all" recommendations still remain. Genetic differences are known to impact absorption, metabolism, uptake, utilization and excretion of nutrients and food bioactives, which ultimately affects a number of metabolic pathways. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients and other food components. Although there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to an ergogenic aid, there is a growing foundation of research linking gene-diet interactions on biomarkers of nutritional status, which impact exercise and sport performance. This foundation forms the basis from which the field of sport nutrigenomics continues to develop. We review the science of genetic modifiers of various dietary factors that impact an athlete's nutritional status, body composition and, ultimately athletic performance.

Cognitive dietary restraint is associated with stress fractures in women runners.

High levels of cognitive dietary restraint (CDR) have been associated with subclinical menstrual cycle irregularities and increased cortisol levels, both of which can affect bone mineral density (BMD). Low BMD has been implicated in stress fracture risk. We assessed CDR in female runners (> or = 20 km/wk) with a recent stress fracture (SF) and with no stress fracture history (NSF). A sample of 79 runners (n = 38 SF, 29 +/- 5 y; n = 41 NSF, 29 +/- 6 y) completed a 3-d food record and questionnaire assessing physical activity, menstrual cycle history, and perceived stress. SF and NSF runners had similar body mass index (21.2 +/- 1.8 vs. 22.0 +/- 2.5 kg/m2), physical activity (35.7 +/- 13.5 vs. 33.4 +/- 1.34 km/wk), perceived stress, and dietary intakes. CDR, however, was higher in SF runners (11.0 +/- 5.4 vs. 8.4 +/- 4.3, P < 0.05). Subclinical menstrual cycle disturbances and increased cortisol levels that are associated with high CDR, might in turn contribute to lowered BMD and increased stress fracture risk.