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Open label randomised controlled trial PubMed records 13 January 2026 as the publication date. Volume 32, issue 3, pages 1023 to 1033.

Five fasting mimicking days a month beat carrying on as normal in Crohn's disease, and the stool marker moved with it

AI narration, generated on first listen
Journal
Nature Medicine 32(3):1023 to 1033
Authors
Kulkarni C, Fardeen T, Gubatan J, Ye J, Jarr K, Longo VD, Habtezion A, Sonnenburg JL, Gardner C, Sinha SR
Institution
the Division of Gastroenterology and Hepatology at Stanford University School of Medicine
Published
13 January 2026
Source
PMID 41530382 · DOI 10.1038/s41591-025-04173-w
Design
Open label randomised controlled trial of a fasting mimicking diet for five consecutive days per month for three consecutive months, against continuing the baseline diet, in adults with mild to moderate Crohn's disease. Registered as NCT04147585.
Sample
Ninety seven adults with mild to moderate Crohn's disease, sixty five in the diet group and thirty two in the control group.

What what is being measured here is

A fasting mimicking diet is not a fast. It is five consecutive days of a low calorie plant based menu designed to produce the metabolic signature of fasting while people keep eating. The Crohn's Disease Activity Index used as the primary outcome is built largely from symptoms the patient reports, which matters when nobody was blinded. Faecal calprotectin is different. It is a protein released by white cells into the gut, measured in stool, and it does not respond to what a patient believes.

Drawn from standard clinical definitions, not from this paper.

Why they ran it

Short cycles of a fasting mimicking diet lower systemic inflammatory markers in healthy people, and the authors note that the potential benefits had never been investigated in Crohn's disease. This is the one place in the current literature where a fasting protocol beats its control on a clinical outcome rather than on a surrogate.

Drawn from the paper's introduction.

Open label randomised controlled trial. Patients in the diet group followed the fasting mimicking diet for five consecutive days per month for three consecutive months, returning to their regular baseline diet on all other days. Control participants continued their baseline diet.

The primary outcome was clinical response, defined as a fall of at least seventy points in the Crohn's Disease Activity Index or an index of one hundred and fifty or below, measured after the third cycle.

Forty five of sixty five patients in the diet group met it, 69.2 percent, against fourteen of thirty two in the control group, 43.8 percent, at p equals 0.03.

Clinical remission, a secondary outcome: forty two patients, 64.6 percent, against twelve, 37.5 percent, at p equals 0.02.

Faecal calprotectin fell 22.0 percent from baseline in the diet group and rose 8.0 percent in the control group, p equals 0.03.

Exploratory analyses of plasma metabolites and gene expression in peripheral blood mononuclear cells showed decreases in key inflammatory lipid mediators and immune effector transcripts after the diet, which the authors describe as concordant with the reduction in disease activity.

The numbers

Clinical response, primary outcome45 of 65, 69.2 percent, against 14 of 32, 43.8 percent, p equals 0.03
Clinical remission, secondary outcome42 of 65, 64.6 percent, against 12 of 32, 37.5 percent, p equals 0.02
Faecal calprotectin change from baselineminus 22.0 percent against plus 8.0 percent, p equals 0.03
Protocolfive consecutive days per month for three consecutive months
Control armcontinued their baseline diet, with no diet intervention

Why this might happen

Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.

The authors point at inflammation resolution rather than at anything gut specific. Plasma metabolite profiling showed decreases in key inflammatory lipid mediators after the diet cycles, and gene expression in peripheral blood mononuclear cells showed reduced immune effector transcripts, both of which they describe as concordant with reduced disease activity. They present this as a reason to investigate the approach in chronic inflammatory disease generally, not as a demonstrated pathway.

Drawn from the paper's exploratory analyses.

What this does not show

  • It does not show that fasting treats Crohn's disease. It shows that three cycles of this specific diet beat continuing to eat normally, in mild to moderate disease, over three months, as an addition to whatever treatment people were already receiving.
  • The trial was open label and the control arm received no diet at all. Expectancy is uncontrolled and the primary outcome is a symptom score. The calprotectin result is the part that is hard to explain by expectancy, and it is a secondary outcome.
  • There is no endoscopic endpoint. Nothing here describes what the bowel lining did. Symptom scores and a stool marker are not the same as looking.
  • It says nothing about severe or active disease. Only mild to moderate Crohn's disease was studied, and the safety of a repeated low calorie diet in active severe disease is a separate question this trial does not touch.

Where this leaves us

Three monthly cycles of a five day diet produced clinical response in about seven in ten patients against about four in ten continuing as normal, and an objective stool marker moved in the same direction.

Adults with mild to moderate Crohn's disease, over three months, alongside their existing treatment.

A blinded trial with a sham diet arm and an endoscopic endpoint, which the calprotectin result is strong enough to justify.

Caveats worth holding

  • Open label, with no attention control and no isocaloric comparator.
  • The primary outcome is a symptom weighted index in an unblinded trial.
  • Two to one allocation, so the control arm is half the size of the diet arm.

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