Weight loss during intermittent fasting, not Mediterranean diet quality alone, is associated with lower inflammation: A randomized controlled trial.

Whether the anti-inflammatory effects of a Mediterranean diet reflect diet quality itself or accompanying weight loss is unclear. In a 16-week randomized controlled-feeding trial, 53 adults (77% female; mean age 54.7 years) with metabolic risk factors received a fully provided Mediterranean diet or their habitual western diet for 8 weeks, then added twice-weekly fasting days for a further 8 weeks. The primary outcome, high-sensitivity C-reactive protein, did not change during the diet-only phase despite clear dietary separation. After fasting began, C-reactive protein fell in the Mediterranean-diet group relative to controls, alongside greater weight loss, improved insulin sensitivity, and lower blood pressure; lipid improvements had already emerged during the diet-only phase. Multi-omic analyses showed parallel reductions in inflammatory signaling, with gut microbiome composition largely stable. Thus, diet quality alone does not lower inflammation over 8 weeks; negative energy balance and weight loss during fasting appear to be the stronger drivers. This study was registered at ClinicalTrials.gov (NCT02148458).