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Updated: May 24, 2026

Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions
Published on: October 2, 2018
Caffeine increases tear volume depending on polymorphisms within the adenosine A2a receptor gene and cytochrome P450
Reiko Arita1, Yasuo Yanagi, Norihiko Honda
1Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan. ritoh@za2.so-net.ne.jp
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.
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