Morning Brew, Hidden Risks Caffeine May Undermine Blood Transfusion Effectiveness

A large-scale study from the University of Colorado Anschutz Medical Campus reveals that caffeine consumption before blood donation may impair red blood cell quality and reduce transfusion effectiveness. The findings highlight the role of genetics and open the door to more personalized donor guidelines.

A new study from the University of Colorado Anschutz Medical Campus has found that caffeine, the world’s most consumed psychoactive substances, may impair the quality of donated blood and reduce the effectiveness of transfusions — especially in recipients whose red blood cell (RBC) metabolism is influenced by a common genetic variant.

“We’ve long understood caffeine’s effects on the brain and central nervous system, but this is the first large-scale study to demonstrate its impact on RBC biology,” said Angelo D’Alessandro, PhD, professor of biochemistry at the University of Colorado School of Medicine and study senior author. “These findings suggest that something as common as your morning cup of coffee could have important implications for the quality of stored blood and how well it works when transfused into patients.”

Published today in Haematologica by researchers involved in the REDS RBC-Omics study, which analyzed samples from over 13,000 blood donors, the study reveals that higher levels of caffeine in the blood are linked to RBCs that are more prone to damage during storage and less effective after transfusion. In a clinical setting, transfusions of RBCs with relatively high levels of caffeine resulted in lower increases in patients’ hemoglobin levels and greater signs of RBC breakdown (hemolysis).

These negative effects were especially pronounced in transfusion recipients and blood donors carrying common variants in the ADORA2b gene, which regulates how RBCs function under low-oxygen conditions. The findings open the door to a new, more individualized approach to blood transfusion that takes into account not just blood type, but lifestyle factors and genetic traits that influence red blood cell quality.

“The translational implications of our findings are significant,” said D’Alessandro.“First, donor caffeine consumption, a common dietary exposure for up to 75% of Americans, emerges as a modifiable behavioral factor potentially influencing RBC storage quality and transfusion outcomes.

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“Given caffeine's short biological half-life, transient dietary modifications around the time of blood donation might mitigate its negative impact, aligning with blood donation guidelines in several European countries where donors are advised to limit caffeine intake prior to donation. Conversely, in other regions, such as the United States or Italy, caffeine consumption before blood donation is not actively discouraged and may even be implicitly encouraged due to its known beneficial acute effects on blood pressure, potentially expediting the donation process and reducing vasovagal reactions.

“Indeed, moderate caffeine intake can transiently increase donor blood pressure and vascular tone, facilitating venous access and blood withdrawal efficiency. However, this advantage must be balanced against caffeine’s mild diuretic properties, which may predispose donors to dehydration — an established risk-factor for adverse donation-related events and poorer blood flow during collection.”

This study may also help explain the well-documented performance-enhancing effects of caffeine in exercise and sports. Caffeine increases oxidative stress in red blood cells by two distinct mechanisms: it blocks activation of the ADORA2B receptor and inhibits glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in the antioxidant pentose phosphate pathway. Both actions can elevate oxidative stress, which —paradoxically — may promote physiological adaptation. Exercise itself triggers the production of reactive oxygen species, and a controlled increase in oxidative stress is thought to drive beneficial training responses.

“Interestingly, we recently discovered that mice with G6PD deficiency showed improved exercise tolerance,” said Travis Nemkov, PhD, co-author and associate professor of biochemistry. “These findings illustrate how insights from transfusion medicine can inform our understanding of exercise physiology and broader aspects of human health.”

Original Article: Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity; Haematologica; DOI:10.3324/haematol.2025.288332

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