Mediterranean Diet as a Therapeutic Strategy for Hypertension and Cardiovascular Health

Abstract

Background: The Mediterranean diet (MedDiet) is a well-established cardioprotective dietary pattern with demonstrated efficacy in managing hypertension (HTN) and cardiovascular disease (CVD). Its rich array of bioactive compounds, including omega-3 polyunsaturated fatty acids, polyphenols and organosulfur compounds, targets multiple molecular pathways implicated in endothelial dysfunction, oxidative stress, inflammation and metabolic dysregulation. Methods: This review employed a structured, integrative methodology following preferred reporting items for systematic reviews and meta-analyses, guidelines to analyze literature from PubMed, Scopus, Web of Science and Google Scholar (2000-2025). The population, intervention, comparator and outcomes (PICO) framework guided the research question, focusing on mechanistic, physiological and clinical evidence linking MedDiet components to HTN and vascular health. Inclusion criteria prioritized studies on the MedDiet -specific pathways, such as short-chain fatty acid (SCFA)-G-protein-coupled receptors 41/43 signaling, endothelial nitric oxide synthase (eNOS) activation, nuclear factor erythroid 2-related factor 2-antioxidant response element modulation and renin-angiotensin-aldosterone system regulation. Data were qualitatively synthesized to rank mechanisms by translational relevance and clinical tractability. Mechanisms: The MedDiet exerts its antihypertensive effects through synergistic pathways: endothelial function enhancement via eNOS activation and nitric oxide bioavailability, oxidative stress reduction through nuclear factor erythroid 2-related factor 2-antioxidant response element pathway upregulation and nicotinamide adenine dinucleotide phosphate oxidase 4 inhibition. The third mechanism is anti-inflammatory actions via nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome suppression and cytokine modulation. The fourth is the renin-angiotensin-aldosterone system regulation through angiotensin-converting enzyme inhibition and angiotensin-converting enzyme 2 upregulation. Gut microbiota-derived SCFAs further amplify these effects by activating G-protein coupled 41/43 receptors, improving vasodilation and attenuating systemic inflammation. Conclusion: Compelling evidence supports the MedDiet as a first-line strategy for HTN and CVD, but research must address adherence, implementation and precision-nutrition gaps to translate proven cardioprotection into personalized, scalable therapies across diverse and resource-limited populations.