Intake: Het mediterrane dieet

PREDIMED randomized 7,447 people aged 55 to 80 at high cardiovascular risk to a Mediterranean diet with extra-virgin olive oil, the same diet with mixed nuts, or a low-fat control. Over a median 4.8 years the primary composite endpoint occurred in 3.8%, 3.4% and 4.4% respectively, with adjusted hazard ratios of 0.69 (95% CI 0.53 to 0.91) for olive oil and 0.72 (95% CI 0.54 to 0.95) for nuts. These are the 2018 revised estimates after the original 2013 report was withdrawn for protocol deviations; results held after excluding 1,588 participants with known or suspected assignment problems.

In the PREDIMED pilot phase, 772 high-risk adults were randomized to a Mediterranean diet with virgin olive oil, the same with nuts, or a low-fat control for three months. Both Mediterranean arms lowered systolic and diastolic blood pressure, fasting glucose, the total-to-HDL cholesterol ratio and C-reactive protein relative to the low-fat arm. Changes appeared within weeks and preceded meaningful weight loss, pointing to the composition of the diet, not calorie restriction.

This two-year trial randomized 180 patients with metabolic syndrome to a Mediterranean-style diet or a prudent control diet. The Mediterranean group showed improved endothelium-dependent vasodilation, lower high-sensitivity C-reactive protein and interleukins (IL-6, IL-7, IL-18), and reduced insulin resistance, with the number still meeting metabolic-syndrome criteria falling markedly compared with controls. It measures vascular and inflammatory mechanisms, not clinical events, giving a plausible route for the event reductions seen in larger trials.

In 3,541 non-diabetic PREDIMED participants, new-onset type 2 diabetes rates were 16.0, 18.7 and 23.6 cases per 1,000 person-years in the olive-oil, nut and control arms over a median 4.1 years. Adjusted hazard ratios versus control were 0.60 (95% CI 0.43 to 0.85) for the olive-oil arm and 0.82 (95% CI 0.61 to 1.10) for nuts. No energy restriction was prescribed, so the effect came from diet composition. This was a prespecified secondary outcome and subgroup analysis, not the primary endpoint.

PREDIMED-Reus randomized 418 non-diabetic adults to a Mediterranean diet with olive oil, with nuts, or a low-fat control. After a median 4 years, diabetes incidence was 10.1% (95% CI 5.1 to 15.1) and 11.0% (5.9 to 16.1) in the Mediterranean arms versus 17.9% (11.4 to 24.4) in the control arm, with no change in body weight or physical activity between groups. As a single-center trial of modest size it carries wider uncertainty and is best read alongside the pooled PREDIMED diabetes analysis.

This random-effects meta-analysis of 50 studies (35 clinical trials, 2 prospective, 13 cross-sectional) and 534,906 participants found higher Mediterranean-diet adherence associated with reduced risk of metabolic syndrome. In the clinical-trial subset, the diet improved waist circumference, systolic and diastolic blood pressure, triglycerides, HDL cholesterol and fasting glucose. Because the pooled set includes cross-sectional and prospective studies alongside trials, the association carries some observational confounding, while the component effects rest more on the randomized data.

This meta-analysis pooled 12 prospective cohorts (1,574,299 people, followed 3 to 18 years). A two-point increase in adherence score was associated with a 9% reduction in overall mortality (pooled RR 0.91, 95% CI 0.89 to 0.94), a 9% reduction in cardiovascular mortality, a 6% reduction in cancer incidence and mortality, and reduced incidence of Parkinson's and Alzheimer's disease. As a pool of observational cohorts it carries the confounding of its inputs; the strength lies in the size and consistency, which agree with the PREDIMED randomized findings.

This umbrella review synthesized 13 meta-analyzes of observational studies and 16 meta-analyzes of randomized trials. It found robust evidence that higher Mediterranean-diet adherence reduces overall mortality, cardiovascular disease, coronary heart disease, myocardial infarction, overall cancer incidence, neurodegenerative disease and type 2 diabetes. For most site-specific cancers and for several inflammatory and metabolic markers the evidence was only suggestive or weak, and no association was found for bladder, endometrial or ovarian cancer or for LDL cholesterol. It grades existing evidence, not generating new data.

This population-based prospective study of 22,043 Greek adults used a 10-point Mediterranean-diet adherence scale. Over a median 44 months (275 deaths), a two-point increment in the score was associated with an adjusted hazard ratio for total mortality of 0.75 (95% CI 0.64 to 0.87), with similar reductions for coronary heart disease and cancer mortality, adjusted for age, sex, BMI, physical activity and other confounders. As an observational study it establishes association; residual confounding from lifestyle and socioeconomic differences cannot be excluded.

This meta-analysis pooled prospective studies that followed older adults living independently and recorded who went on to develop frailty, the loss of strength, weight, and stamina that raises the risk of falls and dependence. Higher Mediterranean diet adherence lined up with a large drop in frailty, in a step-wise way from moderate to high adherence. Because the underlying studies are observational, the diet travels together with an active, connected, better-resourced life, and the odds ratio reads larger than the true risk change since frailty is common. Still, the consistency across cohorts and the dose-response gradient make this a substantial signal for healthy aging.

Within PREDIMED, 447 cognitively healthy older adults were randomized and 334 had follow-up cognitive testing after a median 4.1 years. The Mediterranean-diet-plus-olive-oil group scored better than controls on the Rey Auditory Verbal Learning Test (P = 0.049) and Color Trail Test part 2 (P = 0.04), with the control group tending to decline. Other individual tests showed no significant between-group difference. This is a secondary outcome from one trial showing slower decline, not dementia prevention.

In a prospective cohort of 2,258 non-demented older adults in New York followed for a mean of 4 years, higher Mediterranean-diet adherence was associated with lower risk of incident Alzheimer's disease in models adjusted for age, sex, education, calorie intake, smoking, comorbidity and other factors. Each unit of the adherence score lowered risk, with a clear gradient across thirds of adherence. Because it is observational, unmeasured differences between high and low adherers could contribute to the association.

The DIRECT trial randomized 322 moderately obese adults (mean age 52, 86% male) to low-fat, Mediterranean, or low-carbohydrate diets for two years. Among the 272 who completed, mean weight loss was 7.3 lb (3.3 kg) (low-fat), 10.1 lb (4.6 kg) (Mediterranean) and 12.1 lb (5.5 kg) (low-carb). Among the 36 participants with diabetes, changes in fasting glucose and insulin were more favorable on the Mediterranean diet than the low-fat diet (P < 0.001 for the interaction). Adherence was high (84.6% at two years), unusual for a diet trial of this length.

This meta-analysis combined prospective studies that tracked initially depression-free adults and measured how closely their eating matched a Mediterranean pattern. Higher adherence lined up with meaningfully lower odds of later depression. Because this is observational, it cannot separate the food from the wider healthy lifestyle it usually travels with, and low mood that has not yet been diagnosed can drag diet quality down on its own. The finding is best read alongside the SMILES treatment trial, which tested cause directly in a randomized design.

The SMILES trial gave one group seven sessions with a dietitian to shift toward a Mediterranean pattern (vegetables, legumes, fruit, whole grains, fish, olive oil, nuts) while the comparison group received matched social contact. Both groups mostly stayed on their existing antidepressants or therapy, so the diet was tested as an add-on to usual care. Depression scores fell substantially further in the diet group, and remission was roughly four times as common. The sample was small and at a single center, so the size of the benefit carries uncertainty, but the direction was clear and clinically meaningful.

Each participant tried both a Mediterranean diet and a conventional low-fat, high-carbohydrate diet, separated by a washout, so each person served as their own comparison. Liver fat was measured directly by magnetic resonance spectroscopy. The Mediterranean pattern, rich in olive oil, oily fish, and plants, reduced liver fat and sharpened insulin sensitivity even though body weight did not change between diets, pointing to an effect from food quality, not calorie cutting. The trial was small, and head-to-head trials against low-fat diets are mixed on which wins, so the durable takeaway is the benefit without weight loss.

Within PREDIMED, 4,152 women aged 60 to 80 without prior breast cancer were followed a median 4.8 years, yielding 35 confirmed incident cases (rates per 1,000 person-years: 1.1 olive-oil, 1.8 nut, 2.9 control). The multivariable hazard ratio for the olive-oil arm versus control was 0.32 (95% CI 0.13 to 0.79); the nut arm was not significantly different. As a secondary outcome resting on 35 cases the confidence interval is wide and the estimate is fragile, so it is a hypothesis-generating signal awaiting confirmation.