The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake

Abstract

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.

Effect of ADORA2A Gene Polymorphism and Acute Caffeine Supplementation on Hormonal Response to Resistance Exercise: A Double-Blind, Crossover, Placebo-Controlled Study

“…A specific genetic variant within this gene, the single nucleotide polymorphism rs5751876 (also known as 1976 T > C), distinguishes individuals as either "fast" or "slow" caffeine responders based on the carriage of TT or CC/CT genotypes, respectively. People with the TT genotype tend to consume more caffeine, and may exhibit enhanced performance when taking caffeine supplements compared to those with the C allele, as noted previously [30][31][32].…”

“…Prior research has illustrated that caffeine exhibits anti-inflammatory [ 30 , 39 ], metabolic [ 40 ], anti-apoptotic [ 41 ], lipolytic [ 26 ], and sports performance-enhancing properties [ 42 ]. Although few studies address the impact of caffeine supplementation on GH and TS levels, the existing results are conflicting [ 22 , 24 , 26 ].…”

Instituto de pesquisa café e saúde: Prevenção de doenças e melhora da qualidade de vida

“…Para contestar esta sugestão é importante realçar que nenhum estudo mostrou que o consumo do café impedia qualquer doença; ao invés, todos os estudos mostraram que o consumo de café atenua, numa certa percentagem (chamada de odds ratio em estudos epidemiológicos), o aparecimento de várias doenças. Visto que quase só foram efetuados estudos observacionais e poucos ensaios clínicos randomizados, ainda não é possível estabelecer uma relação causal entre o consumo de café e a melhoria da saúde, nem saber se há grupos de indivíduos que terão mais benefícios do que outros, o que é esperado, visto que vários polimorfismos formatam o consumo de café (Cornelis et al, 2007;Nikrandt et al, 2022;Rahimi et al, 2023) e o impacto do consumo de café na suscetibilidade a diferentes doenças (Huin et al, 2019;Ohta et al, 2006). Todavia, estudos observacionais, episodicamente já reforçados por estudos mais detalhados em modelos animais, permitem concluir que o consumo de café representa um estilo de vida com benefícios cardiovasculares, metabólicos, imuneinflamatórios e cerebrais.…”

Genes and Athletic Performance: The 2023 Update

“…For example, combat athletes are more likely than untrained subjects to have the warrior ( COMT rs4680 GG) genotype [ 85 ], whilst chess players demonstrate an increased frequency of an allele linked to improved memory and spatial ability ( KIBRA rs17070145 T) [ 86 ]. Such discoveries demonstrate the broadening nature of sports genomics in recent times, with focus expanding from the traditional domain of investigating what makes elite performers different from the general population into other domains, such as sports nutrigenetics [ 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] and areas of sports medicine, such as genomic variants associated with soft-tissue injuries and sports-related concussion [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ].…”