This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (333)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Nutritional and Metabolic Disorders  • Metabolic Diseases  • Cardiovascular System  • Randomized Controlled Trial  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Trial

Katherine Esposito, MD; Raffaele Marfella, MD, PhD; Miryam Ciotola, MD; Carmen Di Palo, MD; Francesco Giugliano, MD; Giovanni Giugliano, MD; Massimo D'Armiento, MD; Francesco D'Andrea, MD; Dario Giugliano, MD, PhD

JAMA. 2004;292:1440-1446.

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.

Author Affiliations: Chair and Division of Metabolic Diseases (Drs Esposito, Marfella, Ciotola, Di Palo, and D. Giugliano), Chair of Urology (Drs F. Giugliano and D'Armiento), and Chair of Plastic and Reconstructive Surgery (Drs G. Giugliano and D'Andrea), Second University of Naples, Naples, Italy.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLES

Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly European Men and Women: The HALE Project
Kim T. B. Knoops, Lisette C. P. G. M. de Groot, Daan Kromhout, Anne-Elisabeth Perrin, Olga Moreiras-Varela, Alessandro Menotti, and Wija A. van Staveren
JAMA. 2004;292(12):1433-1439.
ABSTRACT | FULL TEXT  

Diet, Lifestyle, and Longevity—The Next Steps?
Eric B. Rimm and Meir J. Stampfer
JAMA. 2004;292(12):1490-1492.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Issues in Complementary and Alternative Nutrition Treatments
Mullin
Nutr Clin Pract 2009;24:543-548.
FULL TEXT  

The Metabolic Syndrome: Definition, Global Impact, and Pathophysiology
Potenza and Mechanick
Nutr Clin Pract 2009;24:560-577.
ABSTRACT | FULL TEXT  

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet
Chauveau et al.
Am. J. Clin. Nutr. 2009;90:969-974.
ABSTRACT | FULL TEXT  

Association of the Mediterranean Dietary Pattern With the Incidence of Depression: The Seguimiento Universidad de Navarra/University of Navarra Follow-up (SUN) Cohort
Sanchez-Villegas et al.
Arch Gen Psychiatry 2009;66:1090-1098.
ABSTRACT | FULL TEXT  

Cytokine and Cytokine-Like Inflammation Markers, Endothelial Dysfunction, and Imbalanced Coagulation in Development of Diabetes and Its Complications
Goldberg
J. Clin. Endocrinol. Metab. 2009;94:3171-3182.
ABSTRACT | FULL TEXT  

Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes: A Randomized Trial
Esposito et al.
ANN INTERN MED 2009;151:306-314.
ABSTRACT | FULL TEXT  

Effects of a Diet Higher in Carbohydrate/Lower in Fat Versus Lower in Carbohydrate/Higher in Monounsaturated Fat on Postmeal Triglyceride Concentrations and Other Cardiovascular Risk Factors in Type 1 Diabetes
Strychar et al.
Diabetes Care 2009;32:1597-1599.
ABSTRACT | FULL TEXT  

Mediterranean Diet and Late-Life Cognitive Impairment: A Taste of Benefit
Knopman
JAMA 2009;302:686-687.
FULL TEXT  

Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults
Czernichow et al.
Am. J. Clin. Nutr. 2009;90:329-335.
ABSTRACT | FULL TEXT  

Close adherence to a Mediterranean diet improves endothelial function in subjects with abdominal obesity
Rallidis et al.
Am. J. Clin. Nutr. 2009;90:263-268.
ABSTRACT | FULL TEXT  

Metabolic syndrome, endothelial function and lifestyle modification
Aizawa et al.
Diabetes and Vascular Disease Research 2009;6:181-189.
ABSTRACT  

Functional Foods as Modifiers of Cardiovascular Disease
Johnston
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2009;3:39S-43S.
ABSTRACT  

Which Mediterranean Diet in the Management of Metabolic Syndrome?--Reply
Salas-Salvado et al.
Arch Intern Med 2009;169:1077-1077.
FULL TEXT  

Mediterranean diet and inflammatory response in myocardial infarction survivors
Panagiotakos et al.
Int J Epidemiol 2009;38:856-866.
ABSTRACT | FULL TEXT  

Mediterranean Diet and Incidence of and Mortality From Coronary Heart Disease and Stroke in Women
Fung et al.
Circulation 2009;119:1093-1100.
ABSTRACT | FULL TEXT  

Mediterranean Diet and Mild Cognitive Impairment
Scarmeas et al.
Arch Neurol 2009;66:216-225.
ABSTRACT | FULL TEXT  

One-Year Comparison of a High-Monounsaturated Fat Diet With a High-Carbohydrate Diet in Type 2 Diabetes
Brehm et al.
Diabetes Care 2009;32:215-220.
ABSTRACT | FULL TEXT  

Impact of Genetic and Environmental Factors on hsCRP Concentrations and Response to Therapeutic Agents
Shen and Ordovas
Clin. Chem. 2009;55:256-264.
ABSTRACT | FULL TEXT  

Omega-3 fatty acids: a comprehensive review of their role in health and disease
Yashodhara et al.
Postgrad. Med. J. 2009;85:84-90.
ABSTRACT | FULL TEXT  

The Mediterranean Diet and Your Health
Brill
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2009;3:44-56.
ABSTRACT  

Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet
Mena et al.
Am. J. Clin. Nutr. 2009;89:248-256.
ABSTRACT | FULL TEXT  

Polymorphisms Cyclooxygenase-2 -765G>C and Interleukin-6 -174G>C Are Associated with Serum Inflammation Markers in a High Cardiovascular Risk Population and Do Not Modify the Response to a Mediterranean Diet Supplemented with Virgin Olive Oil or Nuts
Corella et al.
J. Nutr. 2009;139:128-134.
ABSTRACT | FULL TEXT  

Effect of a Mediterranean Diet Supplemented With Nuts on Metabolic Syndrome Status: One-Year Results of the PREDIMED Randomized Trial
Salas-Salvado et al.
Arch Intern Med 2008;168:2449-2458.
ABSTRACT | FULL TEXT  

Diet or exercise: what is more effective in preventing or reducing metabolic alterations?
Bo et al.
Eur J Endocrinol 2008;159:685-691.
ABSTRACT | FULL TEXT  

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients
Fruchart et al.
Diabetes and Vascular Disease Research 2008;5:319-335.
ABSTRACT  

Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)
Nettleton et al.
Am. J. Clin. Nutr. 2008;88:1405-1412.
ABSTRACT | FULL TEXT  

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen and Febbraio
Physiol. Rev. 2008;88:1379-1406.
ABSTRACT | FULL TEXT  

Activation of NF-E2-Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease
Xue et al.
Diabetes 2008;57:2809-2817.
ABSTRACT | FULL TEXT  

An unsuitable and degraded diet? Part three: Victorian consumption patterns and their health benefits
Rowbotham and Clayton
JRSM 2008;101:454-462.
FULL TEXT  

Review: Prehypertension: should we be treating with pharmacologic therapy?
Egan et al.
Ther Adv Cardiovasc Dis 2008;2:305-314.
ABSTRACT  

Food Intake Patterns May Explain the High Prevalence of Cardiovascular Risk Factors among Iranian Women
Esmaillzadeh and Azadbakht
J. Nutr. 2008;138:1469-1475.
ABSTRACT | FULL TEXT  

A Practical 'ABCDE' Approach to the Metabolic Syndrome
Blaha et al.
Mayo Clin Proc. 2008;83:932-943.
ABSTRACT | FULL TEXT  

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet
Shai et al.
NEJM 2008;359:229-241.
ABSTRACT | FULL TEXT  

Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study
Martinez-Gonzalez et al.
BMJ 2008;336:1348-1351.
ABSTRACT | FULL TEXT  

Lifestyle and Risk of Cardiovascular Disease and Type 2 Diabetes in Women: A Review of the Epidemiologic Evidence
Bassuk and Manson
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2008;2:191-213.
ABSTRACT  

Mediterranean Diet Inversely Associated With the Incidence of Metabolic Syndrome: the SUN Prospective Cohort: Response to Tortosa et al.
Giugliano et al.
Diabetes Care 2008;31:e36-e36.
FULL TEXT  

Mediterranean Diet Inversely Associated With the Incidence of Metabolic Syndrome: the SUN Prospective Cohort: Response to Giugliano, Ceriello, and Esposito
Martinez-Gonzalez et al.
Diabetes Care 2008;31:e37-e37.
FULL TEXT  

Fine-Tuning of the Prediction of Mortality in Hemodialysis Patients by Use of Cytokine Proteomic Determination
Badiou et al.
CJASN 2008;3:423-430.
ABSTRACT | FULL TEXT  

Dietary Intake and the Development of the Metabolic Syndrome: The Atherosclerosis Risk in Communities Study
Lutsey et al.
Circulation 2008;117:754-761.
ABSTRACT | FULL TEXT  

Flaxseed and Cardiovascular Risk Factors: Results from a Double Blind, Randomized, Controlled Clinical Trial
Bloedon et al.
J. Am. Coll. Nutr. 2008;27:65-74.
ABSTRACT | FULL TEXT  

Serum Micronutrient Concentrations and Decline in Physical Function Among Older Persons
Bartali et al.
JAMA 2008;299:308-315.
ABSTRACT | FULL TEXT  

Adherence to the Mediterranean Diet Is Inversely Associated With Circulating Interleukin-6 Among Middle-Aged Men: A Twin Study
Dai et al.
Circulation 2008;117:169-175.
ABSTRACT | FULL TEXT  

Are there specific treatments for the metabolic syndrome?
Giugliano et al.
Am. J. Clin. Nutr. 2008;87:8-11.
ABSTRACT | FULL TEXT  

The effects of a whole grain enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome
Katcher et al.
Am. J. Clin. Nutr. 2008;87:79-90.
ABSTRACT | FULL TEXT  

Glucose metabolism and hyperglycemia
Giugliano et al.
Am. J. Clin. Nutr. 2008;87:217S-222S.
ABSTRACT | FULL TEXT  

Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease
Zivkovic et al.
Am. J. Clin. Nutr. 2007;86:285-300.
ABSTRACT | FULL TEXT  

Acute effects of various fast-food meals on vascular function and cardiovascular disease risk markers: the Hamburg Burger Trial
Rudolph et al.
Am. J. Clin. Nutr. 2007;86:334-340.
ABSTRACT | FULL TEXT  

Cardiovascular Actions of Insulin
Muniyappa et al.
Endocr. Rev. 2007;28:463-491.
ABSTRACT | FULL TEXT  

Effect of a Traditional Mediterranean Diet on Lipoprotein Oxidation: A Randomized Controlled Trial
Fito et al.
Arch Intern Med 2007;167:1195-1203.
ABSTRACT | FULL TEXT  

Snack chips fried in corn oil alleviate cardiovascular disease risk factors when substituted for low-fat or high-fat snacks
St-Onge et al.
Am. J. Clin. Nutr. 2007;85:1503-1510.
ABSTRACT | FULL TEXT  

Associations between markers of subclinical atherosclerosis and dietary patterns derived by principal components analysis and reduced rank regression in the Multi-Ethnic Study of Atherosclerosis (MESA)
Nettleton et al.
Am. J. Clin. Nutr. 2007;85:1615-1625.
ABSTRACT | FULL TEXT  

Commentary: Dietary patterns in transition can inform health risk, but detailed assessments are needed to guide recommendations
Tucker
Int J Epidemiol 2007;36:610-611.
FULL TEXT  

New risk factors of heart failure?
Singh et al.
Eur Heart J 2007;28:1038-1039.
FULL TEXT  

Diet, Exercise, and C-Reactive Protein Levels in People With Abdominal Obesity: The ATTICA Epidemiological Study
Pitsavos et al.
ANGIOLOGY 2007;58:225-233.
ABSTRACT  

Soy Consumption, Markers of Inflammation, and Endothelial Function: A cross-over study in postmenopausal women with the metabolic syndrome
Azadbakht et al.
Diabetes Care 2007;30:967-973.
ABSTRACT | FULL TEXT  

Low Carbohydrate, High Fat Diet Increases C-Reactive Protein during Weight Loss
Rankin and Turpyn
J. Am. Coll. Nutr. 2007;26:163-169.
ABSTRACT | FULL TEXT  

Dietary Patterns and Markers of Systemic Inflammation among Iranian Women
Esmaillzadeh et al.
J. Nutr. 2007;137:992-998.
ABSTRACT | FULL TEXT  

Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women
Azadbakht et al.
Am. J. Clin. Nutr. 2007;85:735-741.
ABSTRACT | FULL TEXT  

Prevalence and Treatment of Low HDL Cholesterol Among Primary Care Patients With Type 2 Diabetes: An unmet challenge for cardiovascular risk reduction
Grant and Meigs
Diabetes Care 2007;30:479-484.
ABSTRACT | FULL TEXT  

Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease
Tolman et al.
Diabetes Care 2007;30:734-743.
FULL TEXT  

Low-carbohydrate diet and coronary heart disease in women.
Esposito et al.
NEJM 2007;356:750-750.
FULL TEXT  

Roles of Rho-Associated Kinase and Oxidative Stress in the Pathogenesis of Aortic Stiffness
Noma et al.
J Am Coll Cardiol 2007;49:698-705.
ABSTRACT | FULL TEXT  

The Association between Adherence to the Mediterranean Diet and Fasting Indices of Glucose Homoeostasis: The ATTICA Study
Panagiotakos et al.
J. Am. Coll. Nutr. 2007;26:32-38.
ABSTRACT | FULL TEXT  

Childhood maltreatment predicts adult inflammation in a life-course study
Danese et al.
Proc. Natl. Acad. Sci. USA 2007;104:1319-1324.
ABSTRACT | FULL TEXT  

Metabolic Syndrome
Opie
Circulation 2007;115:e32-e35.
FULL TEXT  

Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy
Sharma et al.
Cardiovasc Res 2007;73:257-268.
ABSTRACT | FULL TEXT  

Nutrition, physical activity, and cardiovascular disease: An update
Ignarro et al.
Cardiovasc Res 2007;73:326-340.
ABSTRACT | FULL TEXT  

The Effect of Weight Loss on C-Reactive Protein: A Systematic Review
Selvin et al.
Arch Intern Med 2007;167:31-39.
ABSTRACT | FULL TEXT  

Low serum carotenoids and development of severe walking disability among older women living in the community: the Women's Health and Aging Study I
Semba et al.
Age Ageing 2007;36:62-67.
ABSTRACT | FULL TEXT  

Nutrient Intake and Risk of Non-Hodgkin's Lymphoma
Chang et al.
Am J Epidemiol 2006;164:1222-1232.
ABSTRACT | FULL TEXT  

Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome
Esmaillzadeh et al.
Am. J. Clin. Nutr. 2006;84:1489-1497.
ABSTRACT | FULL TEXT  

Mediterranean Diet, Alzheimer Disease, and Vascular Mediation
Scarmeas et al.
Arch Neurol 2006;63:1709-1717.
ABSTRACT | FULL TEXT  

Obesity and the role of gut and adipose hormones in female reproduction
Gosman et al.
Hum Reprod Update 2006;12:585-601.
ABSTRACT | FULL TEXT  

The Changing Roles of Dietary Carbohydrates: From Simple to Complex
Griel et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:1958-1965.
ABSTRACT | FULL TEXT  

Nutrition and Stroke Prevention
Fisher et al.
Stroke 2006;37:2430-2435.
ABSTRACT | FULL TEXT  

Impact of Dietary Patterns and Interventions on Cardiovascular Health
Zarraga and Schwarz
Circulation 2006;114:961-973.
FULL TEXT  

The Effects of Diet on Inflammation: Emphasis on the Metabolic Syndrome
Giugliano et al.
J Am Coll Cardiol 2006;48:677-685.
ABSTRACT | FULL TEXT  

Thematic review series: Patient-Oriented Research. Nutritional determinants of insulin resistance
McAuley and Mann
J. Lipid Res. 2006;47:1668-1676.
ABSTRACT | FULL TEXT  

Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors: A Randomized Trial
Estruch et al.
ANN INTERN MED 2006;145:1-11.
ABSTRACT | FULL TEXT  

What to 'eat and chew' in acute myocardial infarction?
Singh et al.
Eur Heart J 2006;27:1628-1629.
FULL TEXT  

What to 'eat and chew' in acute myocardial infarction?: reply
Giugliano and Esposito
Eur Heart J 2006;27:1629-1630.
FULL TEXT  

Statins, diet, and low cholesterol.
Giugliano and Esposito
JAMA 2006;295:2479-2479.
FULL TEXT  

Defining high-fat-diet rat models: metabolic and molecular effects of different fat types.
Buettner et al.
J Mol Endocrinol 2006;36:485-501.
ABSTRACT | FULL TEXT  

Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA)
Nettleton et al.
Am. J. Clin. Nutr. 2006;83:1369-1379.
ABSTRACT | FULL TEXT  

Whole-grain and fiber intakes and periodontitis risk in men
Merchant et al.
Am. J. Clin. Nutr. 2006;83:1395-1400.
ABSTRACT | FULL TEXT  

Interleukin-6 in aging and chronic disease: a magnificent pathway.
Maggio et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2006;61:575-584.
ABSTRACT | FULL TEXT  

Chapter 5.1: Major public health problems -- cardiovascular diseases
Rosen
Scand J Public Health 2006;34:51-58.
 

Insulin Resistance and Atherosclerosis
Nigro et al.
Endocr. Rev. 2006;27:242-259.
ABSTRACT | FULL TEXT  

Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome
Esposito et al.
Diabetes Care 2006;29:1071-1076.
ABSTRACT | FULL TEXT  

Dietary Factors That Promote or Retard Inflammation
Basu et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:995-1001.
ABSTRACT | FULL TEXT  

Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms
Kim et al.
Circulation 2006;113:1888-1904.
ABSTRACT | FULL TEXT  

Association between dietary fiber and serum C-reactive protein.
Ma et al.
Am. J. Clin. Nutr. 2006;83:760-766.
ABSTRACT | FULL TEXT  

Is the whole-diet approach better than a low-fat diet in cardiovascular risk reduction?
Giugliano and Esposito
Am. J. Clin. Nutr. 2006;83:921-921.
FULL TEXT