Protocol
Mediterranean diet + extra-virgin olive oil
Randomized primary-prevention trial with a hard clinical endpoint An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture..
A Mediterranean diet with extra-virgin olive oil is an eating pattern. A large study followed 7,447 adults at high risk of heart disease. Those given olive oil or nuts had about 30 percent fewer major heart and blood vessel events than those on a lower-fat diet. A second study by another team, in 1,002 people with heart disease, also found fewer events. The gain was clearer in men. The larger study was pulled and reissued after problems with how some sites put people into groups. It still showed the benefit.
Randomized primary-prevention trial with a hard clinical endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.. PREDIMED assigned 7,447 people at high cardiovascular risk to a Mediterranean diet supplemented with extra-virgin olive oil or nuts, or to a reduced-fat control, and found a lower incidence of major cardiovascular events. Randomized, hard endpoint, large. This is what Grade A is for.
Why this gradeThe reasoning, and what the grade does not cover.
Grade A by the hard-outcome route: two randomized trials run by independent groups found fewer major cardiovascular events on a Mediterranean diet rich in extra-virgin olive oil. PREDIMED (Estruch et al., New England Journal of Medicine, 2018; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 29897866) randomized 7,447 adults at high cardiovascular risk and found roughly 30 percent fewer events, as primary prevention. CORDIOPREV (Delgado-Lista et al., Lancet, 2022; PMID 35525255), run from a single center in Cordoba, randomized 1,002 people with coronary heart disease to the diet or a low-fat diet and found fewer events, as secondary prevention.
THE TWO TRIALS ARE NOT THE SAME EXPERIMENTdifferent populations, different comparators, and CORDIOPREV's benefit was clearer in men than in women. They agree on the outcome that matters, which is what an A requires, and they do not make one another redundant. An older secondary-prevention trial, Lyon Diet Heart (de Lorgeril et al., Circulation, 1999; PMID 9989963), also found fewer events, but its diet was built around a canola-based margarine rich in alpha-linolenic acid, not extra-virgin olive oil, so it supports the dietary pattern more than the olive-oil version graded here.
THE PUBLICATION HISTORY MATTERS AND IS NOT A FOOTNOTEthe larger of the two trials was withdrawn and republished after irregularities in how some sites randomized participants, and PubMed indexes it as a corrected and republished article. The republished analysis still reports the benefit, and the trial remains the strongest randomized dietary evidence there is, but a reader is entitled to know half of this letter rests on a paper that had to be reissued.
WHAT THIS GRADE DOES NOT COVERparticipants were adults already at high cardiovascular risk, not the general population, and they were supplied with extra-virgin olive oil or nuts rather than asked to buy them. The epigenetic-age evidence cited on this record is a one-year cohort, not randomized, and carries no part of this letter.
Shared endpoint: Major cardiovascular events, Mediterranean diet rich in extra-virgin olive oil versus a control diet
- PREDIMED, Spanish multicenter network (Estruch): About 30 percent fewer major cardiovascular events, 7,447 adults at high risk, primary prevention (withdrawn and republished 2018). PMID 29897866 · Funding: academic; olive oil and nuts donated by industry
- CORDIOPREV, Reina Sofia Hospital, Cordoba, Spain (Delgado-Lista): Fewer major cardiovascular events than a low-fat diet, hazard ratio How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. about 0.72 to 0.75, 1,002 patients with coronary heart disease, secondary prevention. PMID 35525255 · Funding: academic
What the replication does not cover: The two trials differ in population (primary versus secondary prevention) and comparator (a reduced-fat control diet versus a structured low-fat diet), and CORDIOPREV's benefit was clearer in men. PREDIMED was withdrawn and republished in 2018 after randomization irregularities at some sites. Lyon Diet Heart (PMID 9989963) also found fewer events, but its diet was built around a canola-based margarine rich in alpha-linolenic acid, not extra-virgin olive oil, so it is not counted as a replication of the olive-oil version.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
No prominent contraindication A condition or medication that makes a treatment unsafe or unsuitable for a particular person.. The intervention is a dietary pattern, and the usual considerations are allergy to a constituent food and the calorie load of added olive oil and nuts.
The evidence, in fullFive papers, each linked to its PubMed record.
Estruch et al. (New England Journal of Medicine, 2018; PMID 29897866): the reanalyzed PREDIMED randomized trial: 7,447 high-risk adults, ~30% reduction in major cardiovascular events with a Mediterranean diet plus extra-virgin olive oil (hard endpoint). Delgado-Lista et al. (Lancet, 2022; PMID 35525255): the CORDIOPREV randomized trial, 1,002 patients with coronary heart disease, fewer major cardiovascular events than a low-fat diet. de Lorgeril et al. (Circulation, 1999; PMID 9989963): the Lyon Diet Heart final report, a Mediterranean-type diet built around a canola-based margarine rich in alpha-linolenic acid, after myocardial infarction. Sebastian et al. (Current Problems in Cardiology, 2024; PMID 38431146): meta-analysis A study that pools the numbers from several trials into one combined estimate.. Grade A on two independent randomized trials with a hard cardiovascular endpoint. Epigenetic-age evidence: Gensous et al. (GeroScience 2020; PMID 31981007), the NU-AGE one-year Mediterranean diet cohort in adults aged 65 to 79.
Fasting lipids (LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries., HDL, triglycerides) and hsCRP High-sensitivity C-reactive protein, a blood marker of low-grade inflammation. at baseline and 3 months: the PREDIMED trial used cardiovascular events as the primary endpoint The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight., but these biomarkers A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. serve as proxies in a non-trial setting. A validated dietary adherence score (14-item MEDAS) should be completed monthly to confirm the protocol is actually being followed. Weight and waist circumference are secondary; the EVOO arm showed no weight gain.
Evidence notes: randomized trial
Endpoint graded: Major cardiovascular events (PREDIMED) (hard)
Last reviewed: July 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
As studiedDose, form, population and duration for every use.
Olive oil is marketed on its own. In both trials it was one part of a whole dietary pattern delivered with repeated dietitian sessions; neither trial tested adding olive oil to an otherwise unchanged diet.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
Educational use only · Not medical advice · © Evidence Based Longevity, Inc. All rights reserved · Privacy · Disclosure · Terms · Accessibility
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →