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Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome: A Randomized Trial
Abstract
CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). MAIN OUTCOME MEASURES: Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to l-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). RESULTS: After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P =.22). Mean (SD) body weight decreased more in patients in the intervention group (-4.0 [1.1] kg) than in those in the control group (-1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P =.01), IL-6 (P =.04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P =.33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome, compared with 78 patients in the control group (P<.001). CONCLUSION: A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.
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“On the basis of evidence linking Mediterranean-style diet with a reduced risk of inflammation (42), we divided study members according to their daily intake of fruit and vegetables.”
From Childhood maltreatment predicts adult inflammation in a life-course study (2007) · cites this paper as [42]
In the citing paper
“An important difference between the Mediterranean and ADA diets is likely to be the content of MUFAs, which has been shown to have an impact on the lipd profile (54,55), insulin sensitivity (56-58), and postprandial glucose concentrations (59).”
From Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes (2013) · cites this paper as [56]
In the citing paper
“Studies in experimental animals fed or injected with radiolabelled protein-bound AGE and human volunteers receiving diets enriched with MRP or specific AGE have shown that absorption of ingested MRP is variable and dependent on the MRP (464,465,527 -529) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [527]
In the citing paper
“In RCTs, diets that emphasize consumption of fruits and vegetables produce substantial improvements in several risk factors, including blood pressure (BP), lipid levels, insulin resistance, inflammatory biomarker levels, endothelial function, and weight control.19–25”
From Components of a Cardioprotective Diet: New Insights (2011) · cites this paper as [19]
In the citing paper
“However, diets high in polyunsaturated fatty acids such as the Mediterranean diet have been linked to beneficial outcomes, such as improved cardiovascular health [14,15].”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [15]
In the citing paper
“Similarly, reduced triglyceride levels were reported in the Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) Study.401”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [401]
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Metadata
- Authors
- Esposito, K., Marfella, R., Ciotola, M., Di Palo, C., Giugliano, F., Giugliano, G., D'Armiento, M., D'Andrea, F., & Giugliano, D.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2004-09-22
- Volume
- 292
- Issue
- 12
- Pages
- 1440
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2058699849
- Cited by
- 2,126
- References
- 30
- Citations by year
- 2026: 32 · 2025: 58 · 2024: 79 · 2023: 63 · 2022: 76 · 2021: 87 · 2020: 141 · 2019: 79 · 2018: 101 · 2017: 92 · 2016: 96 · 2015: 111 · 2014: 125 · 2013: 99 · 2012: 111
- FWCI
- 106.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- Mediterranean diet, metabolic syndrome, endothelial dysfunction, vascular inflammation, C-reactive protein, interleukin-6, IL-7, IL-18, n-6/n-3 ratio, olive oil, whole grains, fruit and vegetable intake, nuts, dietary intervention, weight loss, insulin sensitivity, cardiovascular risk reduction, physical activity
- MeSH terms
- Adult, Blood Glucose, Blood Pressure, C-Reactive Protein, Endothelium, Vascular, Female, Humans, Inflammation, Insulin, Interleukins, Lipids, Male, Middle Aged, Platelet Aggregation, Single-Blind Method, Metabolic Syndrome, Diet, Mediterranean
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