Caffeine Impairs Red Blood Cell Metabolism, Transfusion Efficacy
FRIDAY, Sept. 12, 2025 -- Caffeine may impair the quality of donated blood and reduce transfusion effectiveness, according to a study published online Sept. 4 in Haematologica.
Monika Dzieciatkowska, M.D., from the University of Colorado Denver in Aurora, and colleagues leveraged data from 13,091 blood donors to examine the peripheral physiological effects of caffeine.
The researchers found that caffeine was a significant modulator of red blood cell (RBC) storage quality and transfusion outcomes. Across multiple donations from 643 recalled donors, elevated caffeine levels were reproducible. In both the screening and recalled cohorts, there was an association for higher caffeine levels with disrupted RBC metabolism, which was characterized by reduced glycolysis, depletion of adenylate pools or 2,3-bisphosphoglycerate, and increased markers of oxidative stress and osmotic fragility, including accumulation of kynurenine. In eight volunteers, these observations were recapitulated in plasma and RBCs on consumption of a cup of coffee. Elevated caffeine correlated with increased hemolysis and lower posttransfusion hemoglobin increments, which was especially pronounced in recipients of RBCs from donors carrying common polymorphisms in the ADORA2b gene. Mechanistic validation of these findings occurred in a murine model deficient in ADORA2b, which had impaired glycolytic flux, compromised antioxidant defenses including caffeine-dependent direct inhibition of recombinantly expressed glucose 6-phosphate dehydrogenase, and decreased transfusion efficacy. These effects were exacerbated with exposure to caffeine during storage.
"Donor caffeine consumption, a common dietary exposure for up to 75 percent of Americans, emerges as a modifiable behavioral factor potentially influencing RBC storage quality and transfusion outcomes," senior author Angelo D'Alessandro, Ph.D., also from the University of Colorado Denver, said in a statement.
Several authors disclosed ties to the biotechnology industry.
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