Genetics of caffeine consumption and responses to caffeine

Abstract

Rationale Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine. Objective This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers. Results Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of poly-substance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users. Conclusion Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.

Correction to: The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis

“…Thus, when conducting caffeine supplementation studies, factors such as sex, age and smoking status should be taken into consideration when designing the study and comparisons that will be made. Genetics has also been shown to contribute to the variability in responses to caffeine ingestion [85]. Specifically the CYP1A2 and ADORA2A genes have been identified as large contributors to caffeine metabolism and caffeine sensitivity, respectively [85].…”

“…Genetics has also been shown to contribute to the variability in responses to caffeine ingestion [85]. Specifically the CYP1A2 and ADORA2A genes have been identified as large contributors to caffeine metabolism and caffeine sensitivity, respectively [85]. CYP1A2 is part of the cytochrome P450 enzyme family which is responsible for approximately 75% of the metabolism of drugs and is responsible for the metabolising caffeine into paraxanthine, theobromine and theophylline [86].…”

The effects of different doses of caffeine on performance, rating of perceived exertion and pain perception in teenagers female karate athletes

“…Caffeine (1,3,7-trimethylxanthine) is a plant alkaloid that occurs naturally in the diet (Sökmen et al, 2008) and nearly 90% of US adults consume caffeine in forms of coffee, tea, or other caffeinated food products (8 cup of coffee may contain 50-200 mg caffeine) (Owens, 2015;Yang, Palmer, De Wit, 2010). In the U.S.A., adults ingest an average of 3 mg/kg of caffeine daily in coffee, tea, caffeinated sodas, and many other drinks and food (Sökmen et al, 2008).…”

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

“…Indeed, first molecular genetic studies investigating the impact of ADORA2A gene variation on anxiety after caffeine intervention demonstrated higher self-reported anxiety levels upon caffeine administration dependent on the ADORA2A 1976T risk allele (Alsene et al, 2003;Childs et al, 2008;Rogers et al, 2010). The ADORA2A 1976 genotype has furthermore been shown to drive subjective and objective responses to caffeine during sleep (Retey et al, 2007) as well as to amphetamines (Hohoff et al, 2005; for review see Yang et al, 2010).…”