Impact of Genetic Variability on Physiological Responses to Caffeine in Humans: A Systematic Review

Nutrients. 2018 Sep 25;10(10):1373. doi: 10.3390/nu10101373.


Emerging research has demonstrated that genetic variation may impact physiological responses to caffeine consumption. The purpose of the present review was to systematically recognize how select single nucleotide polymorphisms (SNPs) impact habitual use of caffeine as well as the ergogenic and anxiogenic consequences of caffeine. Two databases (PubMed and EBSCO) were independently searched using the same algorithm. Selected studies involved human participants and met at least one of the following inclusion criteria: (a) genetic analysis of individuals who habitually consume caffeine; (b) genetic analysis of individuals who underwent measurements of physical performance with the consumption of caffeine; (c) genetic analysis of individuals who underwent measurements of mood with the consumption of caffeine. We included 26 studies (10 randomized controlled trials, five controlled trials, seven cross-sectional studies, three single-group interventional studies and one case-control study). Single nucleotide polymorphisms in or near the cytochrome P450 (CYP1A2) and aryl hydrocarbon receptor (AHR) genes were consistently associated with caffeine consumption. Several studies demonstrated that the anxiogenic consequences of caffeine differed across adenosine 2a receptor (ADORA2A) genotypes, and the studies that investigated the effects of genetic variation on the ergogenic benefit of caffeine reported equivocal findings (CYP1A2) or warrant replication (ADORA2A).

Keywords: adenosine receptor; anxiety; caffeine; cytochrome P450; ergogenic; pharmacogenomics; polymorphism.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Anxiety / chemically induced*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Caffeine / pharmacology*
  • Cytochrome P-450 CYP1A2 / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Performance-Enhancing Substances
  • Pharmacogenomic Variants / genetics*
  • Polymorphism, Single Nucleotide
  • Receptor, Adenosine A2A / genetics*
  • Receptors, Aryl Hydrocarbon / genetics*


  • ADORA2A protein, human
  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Performance-Enhancing Substances
  • Receptor, Adenosine A2A
  • Receptors, Aryl Hydrocarbon
  • Caffeine
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2