Eight weeks on a fully provided Mediterranean diet improved blood lipids but did not reduce inflammation in adults with metabolic risk factors; C-reactive protein fell only after participants added two fasting days a week and began losing weight, according to a randomized controlled-feeding trial published online October 21 in Cell Metabolism. The authors conclude that negative energy balance and weight loss, rather than diet quality alone, appear to be the stronger drivers of the diet’s anti-inflammatory effect, at least over this time frame.
The 16-week trial enrolled 53 adults, 77% of them women, with a mean age of 54.7 years. Each was assigned at random to receive a Mediterranean diet, with all meals supplied by the research team, or to continue their habitual Western diet for eight weeks. In the second eight weeks both groups added twice-weekly fasting days. The primary outcome was high-sensitivity C-reactive protein (hs-CRP), a blood marker of inflammation, measured at baseline, eight and 16 weeks.
During the diet-only phase, hs-CRP did not change in either group despite what the authors describe as clear dietary separation between them. Once fasting began, CRP fell in the Mediterranean-diet group relative to controls, alongside greater weight loss, improved insulin sensitivity and lower blood pressure. Lipid improvements had already appeared during the diet-only phase. Multi-omic analyses showed parallel reductions in inflammatory signaling, while the composition of the gut microbiome stayed largely stable throughout, the abstract reports.
The trial was registered on ClinicalTrials.gov as NCT02148458 and sponsored by Washington University School of Medicine, where it ran from June 2014 to June 2017. The registry entry sought men and women aged 30 to 65 with a body mass index of 22 to 28, described as the high-normal to moderately overweight range, who were sedentary to moderately active and had at least one metabolic abnormality such as elevated blood pressure, suboptimal cholesterol, impaired fasting glucose or a high-risk waist circumference. Smokers and people with chronic disease were excluded. The corresponding author is Luigi Fontana, now at the University of Sydney’s Charles Perkins Centre, with co-authors at Washington University, Amsterdam University Medical Centers, the US National Cancer Institute and other institutions.
A 2014 Washington University recruitment notice for the study described the Mediterranean arm as built around vegetables, beans, grains and whole-wheat bread and pasta, with meat limited to fish or poultry, and said participants collected prepared meals from the medical center two to three times a week. On fasting days, participants could eat a large salad or green vegetables with a small amount of olive oil at dinner but no protein, starchy vegetables or bread. “We know there are benefits from calorie restriction, but most people don’t want to do it. It’s too tough,” Fontana said at the time.
Why it matters
The Mediterranean diet is widely credited with anti-inflammatory effects, but observational studies and many trials cannot separate the diet’s composition from the weight loss that often accompanies it. By supplying every meal for eight weeks before introducing fasting, this trial was designed to isolate the two. The result suggests that, over two months, eating well without eating less did not move CRP, whereas creating an energy deficit did, even as lipids responded to the diet itself.
For clinicians, the finding does not diminish the diet’s effect on cholesterol, which emerged in the first phase, but it does suggest that patients expecting a reduction in inflammatory markers from diet quality alone may need a calorie deficit as well. The authors also report that the gut microbiome barely changed, which argues against microbiome shifts as the main route to the inflammation effect in this setting.
The caveats
This is a small trial, with 53 participants and a predominantly female sample, and it measured an eight-week diet-only window; longer exposure to a Mediterranean diet might behave differently. Because both groups added fasting in the second phase, the reduction in CRP is reported relative to the Western-diet controls rather than against a no-fasting comparison. The registry lists no masking, and participants had a BMI of 22 to 28 at entry, so results may not apply to people with obesity. The study is peer reviewed and published ahead of print; the authors declare no competing interests, and the funding source is not stated in the abstract available on PubMed. The trial was completed in 2017, nine years before publication.
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