Caffeine increases tear volume depending on polymorphisms within the adenosine A2a receptor gene and cytochrome P450 1A2

Ophthalmology. 2012 May;119(5):972-8. doi: 10.1016/j.ophtha.2011.11.033. Epub 2012 Feb 14.


Purpose: The primary aim of the present study was to examine the effect of caffeine on tear volume. The secondary aim was to investigate the relation between caffeine-induced changes in tear volume and polymorphisms in ADORA2A and CYP1A2.

Design: Double-masked, placebo-controlled, crossover study.

Participants: Seventy-eight healthy volunteers were recruited for the study.

Methods: Subjects participated in 2 sessions in which they received capsules containing either placebo or caffeine. The caffeine capsules were given to the subjects to keep the caffeine volume per body weight within 5 to 7 mg/kg. After caffeine intake, tear meniscus height (TMH) was measured. Subjects provided a blood sample for genotyping.

Main outcome measures: Tear meniscus height, single nucleotide polymorphism.

Results: The tear volume increased after caffeine consumption. The net increase in TMH was 0.08 mm (95% confidence interval, 0.05-0.10) greater when participants were given caffeine than when given placebo (P<0.0001). In ADORA2A, the difference in the net increase in TMH for participants who were heterozygous at rs5751876 and rs2298383 was 0.07 mm (P = 0.001) and who were minor homozygous was 0.08 mm (P = 0.007). In CYP1A2, the net increase in TMH for participants who were minor homozygous at rs2472304 was lower than for those who were major homozygous; the difference was 0.06 mm (P = 0.039).

Conclusions: Caffeine intake increases tear volume and polymorphisms within ADORA2A, and CYP1A2 is associated with the tear increase after caffeine intake. Genetic polymorphisms had a significant effect on tear meniscus that was of limited clinical significance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Body Constitution
  • Caffeine / administration & dosage*
  • Capsules
  • Cross-Over Studies
  • Cytochrome P-450 CYP1A2 / genetics*
  • Double-Blind Method
  • Female
  • Genotyping Techniques
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Receptor, Adenosine A2A / genetics*
  • Tears / metabolism*
  • Young Adult


  • Capsules
  • Receptor, Adenosine A2A
  • Caffeine
  • Cytochrome P-450 CYP1A2