A fasting-mimicking diet in patients with mild-to-moderate Crohn's disease: a randomized controlled trial

In healthy individuals, short cycles of a fasting-mimicking diet (FMD) decrease systemic inflammatory markers and improve metabolic health. Potential benefits of FMD have not been investigated in Crohn's disease (CD). We conducted an open-label, randomized, controlled trial to assess the effects of FMD in adults with mild-to-moderate CD. Patients in the FMD group followed an FMD for five consecutive days per month for three consecutive months, returning to their regular baseline diet on non-FMD days. Control participants continued their baseline diet. The primary outcome of clinical response was a reduction in CD Activity Index (CDAI) of at least 70 points or CDAI of ≤150 after the third 5-day diet cycle. Forty-five patients in the FMD group (69.2%) and 14 patients in the control group (43.8%) met the primary outcome of clinical response (P = 0.03). Forty-two patients in the FMD group (64.6%) and 12 patients in the control group (37.5%) achieved the secondary outcome of clinical remission (P = 0.02). There was also a decline from baseline in fecal calprotectin (an inflammatory marker) in the FMD group compared with the control group (-22.0% versus 8.0%, P = 0.03). Exploratory analyses of plasma metabolites and peripheral blood mononuclear cell gene expression revealed post-FMD decreases in key inflammatory lipid mediators and immune-effector transcripts, concordant with reduced CD activity. Together, these findings demonstrate that FMD is superior to a baseline diet for inducing clinical response, clinical remission and biochemical improvement in mild-to-moderate CD, and support further investigation of FMD as an adjunctive therapy for chronic inflammatory diseases. ClinicalTrials.gov registration: NCT04147585 .