A large new study led by the University of Colorado Anschutz School of Medicine found that daily consumption of caffeinated drinks such as coffee may reduce the quality of donated red blood cells, thereby making blood transfusions less effective, especially for patients who need blood transfusions most.
Approximately 1 billion people around the world drink coffee, consuming up to 2.25 billion cups per day. Previous studies have generally believed that caffeine has many health benefits, but new analysis shows that caffeine may impair the quality of blood donations and its performance in patients.
“We have long understood the effects of caffeine on the brain and nervous system, but this study is the first to discover its effects on the physiology of red blood cells themselves on a large scale,” said Angelo D’Alessandro, PhD, professor of biochemistry at the Colorado School of Medicine and corresponding author of the study. “This finding suggests that a daily cup of coffee may have an important impact on the quality of stored blood and the effectiveness of blood transfusions.”
The research team analyzed red blood cell samples from 13,091 blood donors in the US "REDS RBC-Omics" project, measured the caffeine content in the stored blood, and studied its impact on red blood cell metabolism, hemolysis (cell destruction) and transfusion outcomes. For 643 blood donors whose red blood cells were detected to be extremely fragile or not fragile, the researchers arranged for them to donate blood again at different storage times (10, 23, and 42 days) for comparison.
In a short-term trial, eight healthy volunteers drank a cup of coffee, and researchers compared blood samples before and after drinking to track the immediate effects of caffeine on red blood cells. In addition, the laboratory also analyzed the effects of caffeine on key red blood cell signaling pathways such as the ADORA2b receptor (which helps resist stress and relieve hypoxia) and G6PD enzyme activity, and further verified its mechanism and post-transfusion recovery through ADORA2b-deficient mice.
The results showed that considerable levels of caffeine were detected in the red blood cells of many blood donors, with frequent coffee drinkers having the most stable levels. The higher the caffeine level, the lower the levels of the "fuel molecules" adenosine triphosphate (ATP) and 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells. Red blood cells do not have nuclei or mitochondria and normally rely on a few chemical "fuels" to maintain life and function, the most important of which are ATP and 2,3-BPG.
Studies have also found that caffeine makes red blood cells more fragile and more susceptible to stress rupture and more oxidative damage. Blood transfusion experiments have shown that donating blood containing high levels of caffeine leads to a smaller increase in the recipient's hemoglobin. In other words, caffeine seems to deplete the "battery" of red blood cells and reduces the oxygen-carrying function.
For blood donors who carry certain ADORA2b gene variants, the adverse effects of caffeine are even greater. This combination makes stored red blood cells extremely vulnerable. In animal experiments, the red blood cells of mice lacking ADORA2b are very fragile. Adding caffeine during blood storage will aggravate the damage, reflecting a "double hit" effect: on the one hand, caffeine blocks the ADORA2b signal, on the other hand, it directly inhibits G6PD, weakening antioxidant protection.
D’Alessandro said, “Our study has important implications for clinical practice. Caffeine consumption, as an extremely common dietary behavior, is likely to affect the storage quality of red blood cells and blood transfusion outcomes. Fortunately, the biological half-life of caffeine is very short, so it is possible to reduce its negative effects by simply adjusting the diet within a short period of time before blood donation. This is consistent with the practice of some European countries that recommend limiting caffeine intake before blood donation.”
However, the research team also pointed out that the number of coffee-drinking volunteers in the trial was limited, none of them had been teetotal for a long time (no caffeine intake at all), and the blood samples were donated for nearly ten years. In addition, the physiology of red blood cells in mice is also different from that in humans. Clinical data show that the overall effect of caffeine on blood transfusion is mild, and the risk to individual patients is not great, but it is worthy of attention in large-scale blood donation groups.
This study proposes new ideas for precise blood matching based on blood donors' lifestyle (such as caffeine intake habits) and genetic characteristics (such as ADORA2b variation). For high-risk patients such as neonates and critically ill patients, preferential transfusion of low-caffeine donated blood may lead to better outcomes.
The above-mentioned research was published in the medical journal "Haematologica".