Cytochrome P450 3A4 (CYP3A4) is a key enzyme involved in the metabolism of nearly half of all clinically used drugs, including widely prescribed statins and antidiabetic agents. Dietary constituents can modulate CYP3A4 expression and activity through various mechanisms, thereby altering drug pharmacokinetics and potentially leading to therapeutic failure or toxicity. This narrative review compiles current evidence on dietary modulation of CYP3A4, with a particular focus on pharmacological and clinical implications for lipid-lowering and glucose-lowering drugs. Literature was identified through a comprehensive search in PubMed, Scopus, and Web of Science, including preclinical and clinical studies addressing food–drug interactions involving CYP3A4 substrates. Numerous dietary compounds, such as citrus furanocoumarins, polyphenols, herbal extracts, and vitamins, act as CYP3A4 inhibitors or inducers through competitive, mechanism-based, or nuclear receptor-mediated pathways. Specific examples include simvastatin, atorvastatin, repaglinide, and saxagliptin, whose systemic exposure can be significantly altered by dietary factors. Moreover, interindividual variability in CYP3A4 activity may be shaped by genetic polymorphisms, microbiota-derived metabolites, and epigenetic regulation, further influencing drug response. Understanding these interactions is crucial, especially in polymedicated patients or those receiving drugs with a narrow therapeutic index. Clinicians should remain aware of potential CYP3A4-related food–drug interactions and consider dietary habits and supplement use in therapeutic decision-making. Future research should aim to integrate pharmacogenomics, gut microbiome profiling, and personalized nutrition in order to improve the prediction and prevention of clinically significant interactions.

Cardiovascular disease is a leading cause of global morbidity and mortality, and processed meat consumption has been consistently associated with adverse cardiometabolic outcomes in observational studies. However, processed meat products differ substantially in composition and processing methods, and traditional dry-cured ham presents distinct nutritional and biochemical characteristics. This systematic review and meta-analysis aimed to synthesize evidence from human intervention studies evaluating the effects of dry-cured ham consumption on cardiometabolic and vascular health in adults. A comprehensive search of major databases identified eligible randomized and non-randomized intervention studies. Five trials were included in the qualitative synthesis, and meta-analyses were performed for blood pressure, lipid profile, and fasting blood glucose outcomes when sufficient data were available. The pooled analyses indicated a small but statistically significant reduction in diastolic blood pressure and total cholesterol associated with dry-cured ham consumption, whereas no significant effects were observed for systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, or fasting blood glucose. Substantial heterogeneity was present across most outcomes. Overall, the available intervention evidence suggests that dry-cured ham consumption at doses ranging from 40 to 120 g/day does not appear to adversely affect conventional cardiometabolic risk markers in adults. Nevertheless, the limited number and short duration of trials warrant cautious interpretation.

We thank the authors of the Comment for their careful reading of our article and for raising important interpretative and methodological considerations