Beyond adherence: refractory dyslipidaemia, the mediterranean diet, and the case for personalized diet-drug complementarity
Open accessAbstract
Cardiovascular disease (CVD) remains the leading cause of death worldwide, and atherogenic dyslipidaemia is one of its most modifiable drivers. The Mediterranean diet (MedDiet) is among the most extensively studied and best-supported dietary patterns for cardiovascular protection, yet meta-analyses show only modest and heterogeneous effects on the conventional lipid panel: typically 5%−15% reductions in LDL cholesterol, 10%−20% reductions in triglycerides and 3%−6% increases in HDL cholesterol, with very high between-study heterogeneity ( I 2 often >90%). Lipoprotein(a) [Lp(a)] is genetically determined and largely diet-resistant. Rather than re-asking whether the MedDiet “works”, this narrative review addresses a clinically more useful question: who are the lipid non-responders to a well-adhered MedDiet, and how should the diet be combined with contemporary lipid-lowering pharmacotherapy to close the residual-risk gap? Drawing on PubMed, Scopus and Web of Science (January 2015–April 2026) and seminal earlier trials, we synthesize five themes: genetic and metabolic non-responder phenotypes; the gut microbiota–metabolome axis; inflammaging; MedDiet on top of statin and non-statin therapy; and the obligatory partnership of physical activity, weight loss and smoking cessation. The MedDiet should be reframed not as an alternative to lipid-lowering drugs but as a foundational lifestyle component, personalized by genotype, inflammatory status, microbiota composition and treatment goals.
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Flagged first, then by citations
Cited by
Still being checked.
- Authors
- Skrabic, R., Kumric, M., Santic, R., Skrabic, I., Pavlovic, N., Rusic, D., & Bozic, J.
- Affiliations
- Department of Internal Medicine, Division of Nephrology and Dialysis, University Hospital of Split
- Department of Pathophysiology, University of Split School of Medicine
- Klinički Bolnički Centar Split (HR)
- Department of Pharmacy, University of Split School of Medicine
- Venue
- Frontiers in Nutrition
- Publisher
- Frontiers Media SA
- Published
- 2026-06-22
- Volume
- 13
- Pages
- 1875074-1875074
- ISSN
- 2296-861X (ISSN-L)
- PMC
- PMC13334983
- OpenAlex
- W7165572965
- Cited by
- 0
- References
- 101
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Nutrition (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- Mediterranean diet, atherogenic dyslipidemia, personalized nutrition, statins, lipoprotein(a), gut microbiota, metabolome, inflammaging, residual cardiovascular risk, physical activity, weight loss, smoking cessation, cardiovascular disease prevention
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