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    Caffeine Habituation, Not CYP1A2 Genotype, Modulates the Acute Effect of Caffeine on Exercise-Induced Hemostatic Responses in Adults with Obesity
    (Lippincott Williams & Wilkins, 2025) Sajedi, Heidar; Aydin, Elif; Keskin, Ozlem; Ercis, Sertac; Akpinar, Selahattin; Khodadadi, Davar
    Purpose: This study aimed to investigate how genotype and caffeine habituation influence the acute effects of caffeine ingestion on exercise-induced hemostatic responses in individuals with obesity. Methods: Using a randomized, double-blind, placebo-controlled crossover design, 40 physically inactive young men with obesity (age, 22.2 +/- 2.3 yr; body mass index, 34.1 +/- 2.7 kgm(-2)) completed two moderate-to-high-intensity concurrent exercise sessions following ingestion of caffeine (3 mgkg(-1)) or placebo. Blood samples were collected at baseline, after exercise, and after 60 min of recovery. Statistical analysis was performed by repeated-measures multivariate analysis of variance. Results: Acute exercise increased platelet count and aggregation, fibrinogen, F1 + 2, tPA antigen, D-dimer, and clot lysis time, regardless of genotype or caffeine habituation status (P < 0.05). PAI-1 antigen remained unchanged after exercise (P > 0.05) but decreased following recovery (P < 0.01). Caffeine resulted in a greater increase in platelet aggregation, fibrinogen, F1 + 2, and clot lysis time, alongside a blunted increase in tPA antigen levels post-exercise in na & iuml;ve consumers (P < 0.05). In contrast, habitual caffeine consumers exhibited a mitigated increase in clot lysis time and a greater post-recovery reduction in PAI-1 antigen following caffeine ingestion (P < 0.001). Caffeine's impact on hemostatic responses to exercise was unaffected by genotype (P > 0.05). Conclusions: Moderate-to-high-intensity concurrent exercise induces a transient prothrombotic state in physically inactive individuals with obesity. Acute caffeine supplementation at a moderate dose modulates the hemostatic responses depending on caffeine habituation status rather than CYP1A2 genotype: it exacerbates the prothrombotic response in na & iuml;ve consumers but attenuates it in habitual consumers.