Caffeine, a potent psychostimulant widely consumed worldwide, has a controversial impact on cognition. Genetic factors related to caffeine metabolism and physiological effects may contribute to research variability. Therefore, this research explores the interactions between genetic variations implicated in caffeine pharmacokinetics and pharmacodynamics and habitual and acute caffeine intake on performance across all key domains of cognition.
The present research consists of three studies. The first study involved a systematic review of genetics studies on caffeine and brain-related outcomes. The second study was an online population-based study (n = 131) assessing a) habitual caffeine intake from all sources, b) cognitive performance in social cognition, memory, executive function and attention) and c) genes associated with caffeine, sleep quality and cognitive performance. The methodology from the second study was transferred to the final study, a double-blind cross-over randomised trial (n = 12), involving a 4-week protocol of long-term caffeine/placebo intake and four experimental sessions of 3 mg/kg body mass acute caffeine/placebo supplementation. The cognitive test battery was performed during each session at baseline and 1-, 3- and 6-h post-supplementation.
Significant gene x caffeine interactions were observed for the domains of social cognition, F (2, 123) = 5.848, p = 0.004 and executive function, F (2, 109) = 3.690, p = 0.028. ‘Fast’ metabolisers had a lower performance in social cognition compared with ‘slow’ metabolisers, among high caffeine consumers (p = 0.004), while ‘slow’ metabolisers had a lower performance in executive function compared with ‘fast’ metabolisers among moderate caffeine consumers (p = 0.002). No other gene x caffeine interactions were observed. The present research has introduced, for the first time in genetics studies, a previously used protocol designed to control for caffeine withdrawal, a major limitation in caffeine research. Future genetics studies are recommended to incorporate this protocol to delineate how genetics can influence the effects of caffeine on cognition and other aspects of human health.
