Explore the vast range of titles available.

Background/ObjectivesEvidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity.Subjects/MethodsA cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the −163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers.ResultsCoffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = −5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week).ConclusionsCYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

Determining factors that contribute to interindividual and intra‐individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe‐drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7‐day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis.

Purpose The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise. Methods Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO 2 max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity). Results Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p  = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p  = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO 2 max in AA (all p  < 0.050) and 50–60% VO 2 max in CA and CC participants (all p  < 0.050). Conclusion Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism. Trial registration The study was registered on clinicaltrials.gov with ID: NCT05975489.

Caffeine’s metabolism is determined by CYP1A2 genotypes: AC/CC (SLOW) and AA (FAST). This trial evaluated CYP1A2 genotypes’ impact on exercise and cognitive effects in 36 resistance-trained females assessed under placebo (PL) and caffeine (6 mg/kg bw anhydrous caffeine-CAF) conditions, before ingestion and throughout the session. 23andMe® (San Francisco, CA, USA) determined genotypes using saliva. Data were analyzed using two-way RMANOVA and paired-samples t-tests (p < 0.05). A significant main effect for genotype existed for leg press repetitions to failure (RTF) for CAF (p = 0.038), with the FAST group performing more repetitions than the SLOW (p = 0.027). There was a significant condition x genotype interaction for the subjective outcome index score (p = 0.045), with significant differences for time (p < 0.01) and between genotype (p < 0.001). Follow-up analysis revealed a higher total score (p = 0.028) following CAF for the FAST group and a lower total score (p < 0.01) in the SLOW group. Dizziness was reported following CAF in the SLOW group (p = 0.014; Cohen’s d = 0.725). Aside from leg press RTF, subjective outcome index score, and dizziness, the genotype groups experienced similar responses to resistance exercise performance and subjective mood states following caffeine ingestion.

Previous investigations have determined that some individuals have minimal or even ergolytic performance effects after caffeine ingestion. The aim of this study was to analyze the influence of the genetic variations of the CYP1A2 gene on the performance enhancement effects of ingesting a moderate dose of caffeine. In a double-blind randomized experimental design, 21 healthy active participants (29.3 ± 7.7 years) ingested 3 mg of caffeine per kg of body mass or a placebo in testing sessions separated by one week. Performance in the 30 s Wingate test, visual attention, and side effects were evaluated. DNA was obtained from whole blood samples and the CYP1A2 polymorphism was analyzed (rs762551). We obtained two groups: AA homozygotes (n = 5) and C-allele carriers (n = 16). Caffeine ingestion increased peak power (682 ± 140 vs. 667 ± 137 W; p = 0.008) and mean power during the Wingate test (527 ± 111 vs. 518 ± 111 W; p < 0.001) with no differences between AA homozygotes and C-allele carriers (p > 0.05). Reaction times were similar between caffeine and placebo conditions (276 ± 31 vs. 269 ± 71 milliseconds; p = 0.681) with no differences between AA homozygotes and C-allele carriers. However, 31.3% of the C-allele carriers reported increased nervousness after caffeine ingestion, while none of the AA homozygotes perceived this side effect. Genetic variations of the CYP1A2 polymorphism did not affect the ergogenic effects and drawbacks derived from the ingestion of a moderate dose of caffeine.

PurposeThe 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.MethodsCompetitive 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 (%).ResultsThere 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.ConclusionCaffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine.Trial registrationThis study was registered with clinicaltrials.gov (NCT02109783).

Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (−163C  > A, rs762551; characterized such as “fast” (AA genotype) and “slow” caffeine metabolizers (C-carriers)) and ADORA2A (1976T  > C; rs5751876; characterized by “high” (TT genotype) or “low” sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d−1) ingested 3 mg·kg−1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the −163C  > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T  > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8–4.3%, p = 0.001–0.022, effect size = 0.17–0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg−1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.

There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have been few longer-term interventions, directly examining the effects of coffee intake on glucose and lipid metabolism. Previous studies may be confounded by inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a ‘slow’ metaboliser phenotype. This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals, with novel analysis by rs762551 genotype. Participants were randomised to either a coffee group (n 19) who consumed four cups/d instant coffee for 12 weeks or a control group (n 8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post-intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Before coffee intake, the AC genotype (‘slow’ caffeine metabolisers, n 9) displayed higher baseline glucose and NEFA than the AA genotype (‘fast’ caffeine metabolisers, n 10, P<0·05). Post-intervention, reduced postprandial glycaemia and reduced NEFA suppression were observed in the AC genotype, with the opposite result observed in the AA genotype (P<0·05). These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk.

The caffeine metabolic ratio is an established marker for cytochrome P450 (CYP) 1A2 activity. Optimal sample size calculation for clinical pharmacokinetic xenobiotic–caffeine interaction studies requires robust estimates of interindividual and intraindividual variation in this ratio. Compared with interindividual variation, factors contributing to intraindividual variation are less defined. An exploratory analysis involving healthy nonsmoking non‐naïve caffeine drinkers (1–3 cups/day; 12 men, 12 women) administered caffeine (160 mg) on five occasions evaluated the effects of CYP1A2 induction status (based on genotype) and other factors on intraindividual variation in CYP1A2 activity. Results were compared with those from previous studies. Regardless of whether a hyperinducer (CYP1A2*1A/*1F or CYP1A2*1F/*1F) or normal metabolizer (CYP1A2*1A/*1A, CYP1A2*1C/*1F, or CYP1A2*1C*1F/*1C*1F), sex, age, oral contraceptive use by women, and smoking status, intraindividual variation was ≤30%. A value of 30% is proposed for optimal design of pharmacokinetic xenobiotic–caffeine interaction studies. Prospective studies are needed for confirmation.

Background The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3 , is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease. Methods a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 ( ADORA2A ), rs2298383 ( ADORA2A ), rs762551 ( CYP1A2 ) and rs478597 ( NOS1 ) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats ( p  < 0.05). Results 171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years ( p  = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516). Discussion Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A , CYP1A2 and NOS1 .