Caffeine is an adenosine A2A receptor (ADORA2A) antagonist with ergogenic and anti-inflammatory effects. Previous studies have reported that the ADORA2A gene regulates glutamate metabolism and immune responses, with the ADORA2A rs5751876 TT genotype (with high sensitivity to caffeine) showing larger ergogenic effect following caffeine ingestion. We therefore hypothesized that the TT genotype would be associated with greater anti-inflammatory effects of caffeine in response to exercise, and with higher coffee intake in physically active individuals. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A variant with the anti-inflammatory effects of caffeine in response to intense resistance exercise (RE), and (2) to analyze the association of the rs5751876 with coffee intake in physically active individuals (n = 134). Fifteen resistance-trained athletes participated in a randomized, double-blind, placebo-controlled cross-over study, where they consumed 6 mg/kg of caffeine or placebo one hour prior to performing an RE protocol. Blood samples were taken immediately from the arterial vein before, immediately after, and 15 min after RE for the analysis of inflammatory markers myeloperoxidase (MPO) and acetylcholinesterase (AChE). We found that the ADORA2A TT genotype carriers experienced lower exercise-induced inflammatory responses (p < 0.05 for AchE) when compared to the C allele carriers (i.e., CC/CT) one hour following the ingestion of caffeine. Furthermore, the ADORA2A TT genotype was positively associated with coffee intake (p = 0.0143; irrespective of CYP1A2 rs762551 polymorphism). In conclusion, we found that the ADORA2A gene polymorphism is associated with anti-inflammatory effects of caffeine in response to resistance exercise, as well as with habitual coffee intake in physically active individuals.

Background Growth/differentiation factor-15 (GDF-15) is a stress responsive cytokine linked to obesity, cardiovascular disease and inflammation. Exercise can be a transient physiological stress in whole-body energy metabolism. Objective The aim of this study was to evaluate the glucose, insulin and GDF-15 serum responses to acute effects of two intermittent and continuous exercises in sedentary obese males. Methods In this quasi-experimental study, eight inactive men (Mean±SD age, 25.75±2.37 years, body mass index: 31.96±3.03 kg/m 2) were asked to perform two types of high-intensity intermittent activity (HIIT, 6×1-min running with 85% VO 2 max intensity and 4-min rest with 60% VO 2 max intensity between sets) and moderate-intensity continuous exercise (MIT, 30-min running with 65% VO 2 max intensity) in a crossover and randomly designed protocol along with control session. Findings GDF-15 serum level exercise significantly increased after HIIT and MIT exercises compared to the control (P<0.001) and after 24 h, no significant difference was seen between the results of two groups (P>0.62). Serum glucose level significantly decreased after both HIIT and MIT protocols compared to the controls (P<0.001), but no significant differences were observed in insulin serum levels between protocols (P>0.13). Conclusion Exercise can increase plasma GDF-15 level and improve glucose metabolism in inactive obese males.