Effects of Mediterranean diet on the primary prevention of cardiovascular disease

ISRCTN	ISRCTN35739639
DOI	https://doi.org/10.1186/ISRCTN35739639
Protocol serial number	Red G03/140
Sponsor	Institute of Health Carlos III (Instituto de Salud Carlos III) (Spain)
Funders	Instituto de Salud Carlos III (ref: G03/140), Communal Patrimony Olivarero Foundation (Fundación Patrimonio Comunal Olivarero) (Spain), Hojiblanca SA (Spain), Borges SA (Spain), Morella Nuts SA (Spain), California Walnut Commission (USA)

Submission date: 02/09/2005
Registration date: 05/10/2005
Last edited: 17/11/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Ramon Estruch
Scientific

Servicio de Medicina Interna
Hospital Clinic
Villarroel, 170
Barcelona
08036
Spain

Phone	+34 (0)93 227 93 65
Email	restruch@clinic.ub.es

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	Effects of a Mediterranean diet enriched with virgin olive oil or mixed nuts versus a low fat diet on the primary prevention of cardiovascular disease: a randomised controlled trial
Study acronym	PREDIMED
Study objectives	A Mediterranean-style diet enriched with virgin olive oil or mixed nuts prevents cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke).
Ethics approval(s)	Institutional Review Board of the Hospital Clinic at Barcelona, Spain, 16/07/2002
Health condition(s) or problem(s) studied	Cardiovascular disease
Intervention	Participants are randomly assigned into three equal groups: 1. Mediterranean-style diet with added virgin olive oil 2. Mediterranean-style diet with added nuts 3. Low-fat diet according to American Heart Association guidelines Added 07/05/2009: All participants in the three arms will be treated and followed-up yearly from their inclusion to the second semester of 2011.
Intervention type	Other
Primary outcome measure(s)	A composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Added 07/05/2009: All participants are evaluated yearly for primary and secondary endpoints.
Key secondary outcome measure(s)	Death of any cause and incidence of angina leading to a revascularisation procedure, heart failure, diabetes mellitus, dementia, and cancer. Other outcomes: 1. Changes in blood pressure 2. Body weight 3. Adiposity measures 4. Blood sugar 5. Lipid profile 6. Markers of inflammation 7. Other intermediate markers of cardiovascular risk Added 07/05/2009: All participants are evaluated yearly for primary and secondary endpoints.
Completion date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	55 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	7500
Total final enrolment	7447
Key inclusion criteria	Participants are community-dwelling high-risk persons aged 55 to 80 for men and aged 60 to 80 for women, without a history of cardiovascular disease (CHD), who fulfill at least one of the two following criteria: 1. Type 2 diabetes 2. Three or more of the risk factors: 2.1. Current smoker 2.2. Hypertension 2.3. Hypercholesterolemia (low density lipoprotein cholesterol [LDL-cholesterol] more than 160 mg/dl or treatment with hypolipidemic drugs) 2.4. High density lipoprotein cholesterol (HDL-cholesterol) less than 40 mg/dl 2.5. Overweight or obesity (body mass index more than 25 kg/m^2) 2.6. Family history of premature CHD
Key exclusion criteria	1. Previous history of cardiovascular disease 2. Any severe chronic illness 3. Immunodeficiency or human immunodeficiency virus (HIV) positive status 4. Illegal drug use or chronic alcoholism 5. History of allergy to olive oil or nuts 6. Low predicted likelihood of changing dietary habits according to the Prochaska and DiClemente stages of change model
Date of first enrolment	01/10/2003
Date of final enrolment	31/12/2011

Locations

Countries of recruitment

Spain

Study participating centre

Servicio de Medicina Interna

Barcelona
08036
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	04/07/2006		Yes	No
Results article	results	11/06/2007		Yes	No
Results article	results	08/12/2008		Yes	No
Results article	results	01/06/2011		Yes	No
Results article	results	01/09/2011		Yes	No
Results article	results	01/11/2011		Yes	No
Results article	results	01/01/2012		Yes	No
Results article	results	01/03/2012		Yes	No
Results article	sub-study results	01/05/2012		Yes	No
Results article	results	01/06/2012		Yes	No
Results article	kidney function results	01/09/2012		Yes	No
Results article	phylloquinone intake results	01/11/2012		Yes	No
Results article	sub-study results	06/11/2012		Yes	No
Results article	primary results	04/04/2013		Yes	No
Results article	lifestyle and risk factor results	29/04/2013		Yes	No
Results article	white blood cell results	01/07/2013		Yes	No
Results article	mortality risk results	16/07/2013		Yes	No
Results article	sTWEAK concentration results	01/08/2013		Yes	No
Results article	transcriptomic results	01/09/2013		Yes	No
Results article	blood pressure results	19/09/2013		Yes	No
Results article	depression results	20/09/2013		Yes	No
Results article	gazpacho consumption results	01/10/2013		Yes	No
Results article	polyphenols results	01/10/2013		Yes	No
Results article	iron-induced insulin resistance results	22/10/2013		Yes	No
Results article	polymorphism results	01/11/2013		Yes	No
Results article	heme iron intake results	04/11/2013		Yes	No
Results article	cognition sub-study results	01/12/2013		Yes	No
Results article	magnesium intake results	01/01/2014		Yes	No
Results article	polymorphism results	06/01/2014		Yes	No
Results article	prevention of diabetes results	07/01/2014		Yes	No
Results article	carbohydrate response element binding protein results	01/02/2014		Yes	No
Results article	carotid intima-media thickness results	01/02/2014		Yes	No
Results article	plasma fatty acid composition results	20/03/2014		Yes	No
Results article	beer consumption results	01/04/2014		Yes	No
Results article	heart failure biomarkers results	01/05/2014		Yes	No
Results article	vitamin K intake results	01/05/2014		Yes	No
Results article	olive oil intake results	13/05/2014		Yes	No
Results article	polyphenol intake results	13/05/2014		Yes	No
Results article	re-analysis results	13/05/2014		Yes	No
Results article	habitual polyphenol intake results	01/06/2014		Yes	No
Results article	vascular wall inflammation and plaque vulnerability results	12/06/2014		Yes	No
Results article	atrial fibrillation results	01/07/2014		Yes	No
Results article	results	01/07/2014		Yes	No
Results article	results	29/07/2014		Yes	No
Results article	microRNA-410 regulated lipoprotein lipase variant rs13702 results	01/08/2014		Yes	No
Results article	blood pressure and depression results	26/08/2014		Yes	No
Results article	results	03/10/2014		Yes	No
Results article	fiber intake results	01/12/2014		Yes	No
Results article	plasma nitric oxide and blood pressure results	01/01/2015		Yes	No
Results article	telomere shortening results	01/02/2015		Yes	No
Results article	results	01/03/2015		Yes	No
Results article	results	01/07/2015		Yes	No
Results article	results	01/10/2015		Yes	No
Results article	results	01/10/2015		Yes	No
Results article	results	01/11/2015		Yes	No
Results article	results	01/12/2015		Yes	No
Results article	results	01/12/2018		Yes	No
Results article	results	01/05/2019	23/04/2019	Yes	No
Results article	results	01/06/2019		Yes	No
Results article	results	01/02/2018	25/07/2019	Yes	No
Results article	results	01/07/2018	05/08/2019	Yes	No
Results article	results	01/06/2018	13/09/2019	Yes	No
Results article	results	01/04/2018	27/09/2019	Yes	No
Results article	lysine pathway biomarker results	13/11/2019	15/11/2019	Yes	No
Results article	longitudinal association results	27/12/2019	31/12/2019	Yes	No
Results article	6 year follow up results	01/02/2019	26/03/2020	Yes	No
Results article	results	01/04/2020	26/05/2020	Yes	No
Results article	results	11/02/2020	13/08/2020	Yes	No
Results article	results	04/01/2021	10/12/2020	Yes	No
Results article	results	04/01/2021	10/12/2020	Yes	No
Results article	Sub-analysis in participants aged over 70 years	28/11/2021	29/11/2021	Yes	No
Results article	Arginine catabolism metabolites and atrial fibrillation or heart failure risk	16/05/2022	18/05/2022	Yes	No
Results article	Circulating citric acid cycle metabolites and risk of cardiovascular disease	12/01/2023	06/02/2023	Yes	No
Results article	AHA proposed 7 ideal cardiovascular health metrics and risk of atrial fibrillation	16/02/2023	24/03/2023	Yes	No
Results article	Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial	01/04/2023	03/04/2023	Yes	No
Results article		16/09/2023	18/09/2023	Yes	No
Results article	Association of diabetes with adherence to Mediterranean diet	29/09/2023	02/10/2023	Yes	No
Results article	Association between nuclear magnetic resonance spectroscopy markers and adherence to Mediterranean diet	08/11/2023	13/11/2023	Yes	No
Results article	Association between serum B12 levels and adherence to Mediterranean diet	04/11/2023	13/11/2023	Yes	No
Results article	Olive oil consumption and T2D and CVD risk	13/12/2023	20/12/2023	Yes	No
Results article	Extra-Virgin Olive Oil and Additional Cardiovascular Outcomes in the PREDIMED Trial: An Outcome-Wide Perspective	02/09/2025	05/09/2025	Yes	No
Other publications	metabolic syndrome status	18/11/2014		Yes	No
Other publications		10/11/2025	17/11/2025	Yes	No
Study website		11/11/2025	11/11/2025	No	Yes

Editorial Notes

17/11/2025: Publication reference added.
05/09/2025: Publication reference added.
20/12/2023: Publication reference added.
13/11/2023: Publication references added.
02/10/2023: Publication reference added.
18/09/2023: Publication reference added.
03/04/2023: Publication reference added.
24/03/2023: Publication reference added.
06/02/2023: Publication reference added.
18/05/2022: Publication reference added.
29/11/2021: Publication reference added.
10/12/2020: Publication references added.
13/08/2020: Publication reference added.
26/05/2020: Publication reference added.
26/03/2020: Publication reference added.
31/12/2019: Publication reference added.
15/11/2019: Publication reference added.
27/09/2019: Publication reference added.
13/09/2019: Publication reference added.
05/08/2019: Publication reference added.
25/07/2019: Publication reference added.
23/04/2019: The following changes have been made:
1. Publication reference added.
2. The total final enrolment has been added from the results publication.
21/02/2019: Publication reference added.
18/01/2019: Publication reference added.
04/06/2018: Trial website address updated.
14/01/2016: Publication reference added.
05/05/2009: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/12/2010 to 31/12/2011.
2. The target number of participants was changed from 9000 to 7500 high-risk participants.