The Role of Xenobiotic Caffeine on Cardiovascular Health: Promises and Challenges.

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Cardiovascular diseases (CVDs) represent a leading cause of premature mortality and disability worldwide, with their incidence expected to rise, potentially reaching 24 million deaths per year by 2030. These multifactorial diseases, including hypertension, coronary artery disease, arrhythmia, and heart failure, are often linked to metabolic disturbances such as diabetes, oxidative stress, endothelial dysfunction, and inflammation. Natural compounds, such as caffeine, have been explored for their potential therapeutic effects on CVDs. Caffeine, found in coffee, tea, cocoa, and various energy drinks, is a widely consumed psychoactive compound with noted analgesic and anti-inflammatory properties. Despite its long history of use, caffeine's impact on cardiovascular health remains controversial, with both beneficial and harmful effects reported. This review examines the current literature on the effects of caffeine on cardiovascular diseases (CVDs), with an emphasis on preclinical and clinical studies, its pharmacokinetic properties, and the molecular mechanisms it modulates. There is evidence that moderate caffeine intake can be beneficial for some CVDs, such as hypertension, while for other CVDs, such as dyslipidemia, the evidence collected so far suggests that caffeine intake could be detrimental since it increases total cholesterol levels. But variability in dosage, intake patterns, and individual factors (such as genetics and diet) complicates the reliability of results. Additionally, challenges related to dose standardization and the absence of consistent clinical trial designs hinder the full utilization of caffeine in CVD treatment. Nonetheless, caffeine appears to be safe for individuals without significant cardiovascular conditions. Future research should aim for well-designed studies with precise patient cohorts and standardized methodologies to better assess caffeine's role in CVD management.