Angelo D'Alessandro1,2,3, Xiaoyun Fu4, Julie A Reisz1, Tamir Kanias2,3, Grier P Page5, Mars Stone6, Steve Kleinman7, James C Zimring8, Michael Busch6. 1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado. 2. Vitalant Research Institute, Denver, Colorado. 3. Department of Pathology, University of Colorado Denver, Aurora, Colorado. 4. BloodWorks Northwest, Seattle, Washington. 5. RTI International, Atlanta, Georgia. 6. Vitalant Research Institute, San Francisco, California. 7. University of British Columbia, Victoria, British Columbia, Canada. 8. University of Virginia, Charlottesville, Virginia.
Abstract
BACKGROUND: Coffee consumption is extremely common in the United States. Coffee is rich with caffeine, a psychoactive, purinergic antagonist of adenosine receptors, which regulate red blood cell energy and redox metabolism. Since red blood cell (purine) metabolism is a critical component to the red cell storage lesion, here we set out to investigate whether caffeine levels correlated with alterations of energy and redox metabolism in stored red blood cells. STUDY DESIGN AND METHODS: We measured the levels of caffeine and its main metabolites in 599 samples from the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study via ultra-high-pressure-liquid chromatography coupled to high-resolution mass spectrometry and correlated them to global metabolomic and lipidomic analyses of RBCs stored for 10, 23, and 42 days. RESULTS: Caffeine levels positively correlated with increased levels of the main red cell antioxidant, glutathione, and its metabolic intermediates in glutathione-dependent detoxification pathways of oxidized lipids and sugar aldehydes. Caffeine levels were positively correlated with transamination products and substrates, tryptophan, and indole metabolites. Expectedly, since caffeine and its metabolites belong to the family of xanthine purines, all xanthine metabolites were significantly increased in the subjects with the highest levels of caffeine. However, high-energy phosphate compounds ATP and DPG were not affected by caffeine levels, despite decreases in glucose oxidation products-both via glycolysis and the pentose phosphate pathway. CONCLUSION: Though preliminary, this study is suggestive of a beneficial correlation between the caffeine levels and improved antioxidant capacity of stored red cells.
BACKGROUND: Coffee consumption is extremely common in the United States. Coffee is rich with caffeine, a psychoactive, purinergic antagonist of adenosine receptors, which regulate red blood cell energy and redox metabolism. Since red blood cell (purine) metabolism is a critical component to the red cell storage lesion, here we set out to investigate whether caffeine levels correlated with alterations of energy and redox metabolism in stored red blood cells. STUDY DESIGN AND METHODS: We measured the levels of caffeine and its main metabolites in 599 samples from the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study via ultra-high-pressure-liquid chromatography coupled to high-resolution mass spectrometry and correlated them to global metabolomic and lipidomic analyses of RBCs stored for 10, 23, and 42 days. RESULTS:Caffeine levels positively correlated with increased levels of the main red cell antioxidant, glutathione, and its metabolic intermediates in glutathione-dependent detoxification pathways of oxidized lipids and sugar aldehydes. Caffeine levels were positively correlated with transamination products and substrates, tryptophan, and indole metabolites. Expectedly, since caffeine and its metabolites belong to the family of xanthine purines, all xanthine metabolites were significantly increased in the subjects with the highest levels of caffeine. However, high-energy phosphate compounds ATP and DPG were not affected by caffeine levels, despite decreases in glucose oxidation products-both via glycolysis and the pentose phosphate pathway. CONCLUSION: Though preliminary, this study is suggestive of a beneficial correlation between the caffeine levels and improved antioxidant capacity of stored red cells.
Authors: Richard O Francis; Sonia Mahajan; Francesca Rapido; Francesca La Carpia; Mark Soffing; Chaitanya Divgi; Randy Yeh; Akiva Mintz; Lenhurst Leslie; Irina Agrest; Matthew S Karafin; Yelena Ginzburg; Beth H Shaz; Steven L Spitalnik; Joseph Schwartz; Tiffany Thomas; Xiaoyun Fu; Pascal Amireault; Pierre Buffet; James C Zimring; Angelo D'Alessandro; Eldad A Hod Journal: Transfusion Date: 2019-04-19 Impact factor: 3.157
Authors: Thomas J Van 't Erve; Brett A Wagner; Sean M Martin; C Michael Knudson; Robyn Blendowski; Mignon Keaton; Tracy Holt; John R Hess; Garry R Buettner; Kelli K Ryckman; Benjamin W Darbro; Jeffrey C Murray; Thomas J Raife Journal: Transfusion Date: 2015-02-02 Impact factor: 3.157
Authors: Esther Lopez-Garcia; Rob M van Dam; Tricia Y Li; Fernando Rodriguez-Artalejo; Frank B Hu Journal: Ann Intern Med Date: 2008-06-17 Impact factor: 25.391
Authors: Rani K Powers; Rachel Culp-Hill; Michael P Ludwig; Keith P Smith; Katherine A Waugh; Ross Minter; Kathryn D Tuttle; Hannah C Lewis; Angela L Rachubinski; Ross E Granrath; María Carmona-Iragui; Rebecca B Wilkerson; Darcy E Kahn; Molishree Joshi; Alberto Lleó; Rafael Blesa; Juan Fortea; Angelo D'Alessandro; James C Costello; Kelly D Sullivan; Joaquin M Espinosa Journal: Nat Commun Date: 2019-10-18 Impact factor: 14.919
Authors: Alkmini T Anastasiadi; Vassilis L Tzounakas; Monika Dzieciatkowska; Vasiliki-Zoi Arvaniti; Effie G Papageorgiou; Issidora S Papassideri; Konstantinos Stamoulis; Angelo D'Alessandro; Anastasios G Kriebardis; Marianna H Antonelou Journal: Front Physiol Date: 2022-06-08 Impact factor: 4.755
Authors: Tiffany Thomas; Francesca Cendali; Xiaoyun Fu; Fabia Gamboni; Evan J Morrison; Jonathan Beirne; Travis Nemkov; Marianna H Antonelou; Anastasios Kriebardis; Ian Welsby; Ariel Hay; Karolina H Dziewulska; Michael P Busch; Steven Kleinman; Paul W Buehler; Steven L Spitalnik; James C Zimring; Angelo D'Alessandro Journal: Transfusion Date: 2021-04-26 Impact factor: 3.337
Authors: Travis Nemkov; Davide Stefanoni; Aarash Bordbar; Aaron Issaian; Bernhard O Palsson; Larry J Dumont; Ariel Hay; Anren Song; Yang Xia; Jasmina S Redzic; Elan Z Eisenmesser; James C Zimring; Steve Kleinman; Kirk C Hansen; Michael P Busch; Angelo D'Alessandro Journal: JCI Insight Date: 2021-02-08
Authors: Tiffany Thomas; Davide Stefanoni; Monika Dzieciatkowska; Aaron Issaian; Travis Nemkov; Ryan C Hill; Richard O Francis; Krystalyn E Hudson; Paul W Buehler; James C Zimring; Eldad A Hod; Kirk C Hansen; Steven L Spitalnik; Angelo D'Alessandro Journal: J Proteome Res Date: 2020-10-26 Impact factor: 4.466