European Journal of Clinical Nutrition, 2026 (SCI-Expanded, Scopus)
Background: Caffeine, a performance-enhancing substance, affects haemostasis. However, the interplay between caffeine, exercise, and circadian rhythms on haemostatic responses remains unclear. This study aimed to investigate the effects of acute caffeine intake on exercise-induced haemostatic responses in sedentary young men at different times of day. Methods: Thirty caffeine-naïve sedentary men completed a randomized, double-blind, placebo-controlled crossover study. Each participant performed 4 combined exercise sessions—2 at 07:00 and 2 at 18:00—after ingestion of either caffeine or a placebo. Blood samples were collected pre-exercise, post-exercise, and after 60 minutes of recovery. Results: Across all conditions, exercise elicited increases in platelet aggregation, thrombin generation, tPA activity, and clot lysis time. PAI-1 activity was unchanged post-exercise but declined during recovery. Caffeine further augmented exercise-induced increase in platelet aggregation, thrombin generation, and clot lysis time—most notably in the morning—without significantly altering tPA or PAI-1 activity. There was lower platelet aggregation, thrombin generation, PAI-1 activity, and clot lysis time, alongside higher tPA activity in the evening compared to the morning. Conclusion: These findings indicate that morning exercise triggers a greater prothrombotic status than evening exercise, and that acute caffeine intake exacerbates this effect. The enhanced fibrinolytic capacity in the evening may create a more favourable haemostatic setting for exercise and cardiovascular safety, a hypothesis that warrants confirmation with denser sampling protocols.