Diet is one of the most common and frustrating questions for people living with Crohn’s disease. Despite widespread interest, there has been limited high-quality evidence to guide dietary recommendations for patients with inflammatory bowel disease.
A new randomized clinical trial led by researchers at Stanford Medicine offers new data. The study, published in Nature Medicine, found that a short-term fasting-mimicking diet improved both symptoms and biological markers of inflammation in people with mild-to-moderate Crohn’s disease.
The trial enrolled 97 adults with mild-to-moderate Crohn’s disease from across the United States. Participants were randomly assigned to follow either their usual diet or a fasting-mimicking diet for three months, while continuing their standard medical care.
Those in the fasting-mimicking group followed a structured, calorie-restricted diet for five consecutive days each month, consuming roughly 700 to 1,100 calories per day from plant-based meals. For the remainder of each month, participants returned to their usual diet.
At the end of the study period, about two-thirds of participants in the fasting-mimicking group experienced an improvement in symptoms, compared with fewer than half of participants in the control group.
“We were very pleasantly surprised that the majority of patients seemed to benefit from this diet,” said Sidhartha R. Sinha, an assistant professor of gastroenterology and hepatology and senior author of the study. “We noticed that even after just one FMD (fast-mimicking diet) cycle, there were clinical benefits.”
Beyond symptom reports, the researchers also measured objective indicators of inflammation. Participants following the fasting-mimicking diet showed a significant decline in fecal calprotectin, a stool marker commonly used to assess intestinal inflammation. Blood samples revealed reductions in several inflammation-promoting lipid mediators, and immune cells from these participants produced fewer inflammatory molecules.
“Our goal in collecting these and other biospecimens was to dig deeper into why there’s this differential response,” Sinha said. “Can we find mechanisms to explain the findings and signatures that might help predict patients who will respond to the diet?”
Some participants reported fatigue and headaches during the calorie-restricted days, but no serious adverse events were observed.
Steroids are currently the only approved treatment for mild Crohn’s disease, but their long-term use can carry significant side effects. The researchers emphasized that dietary interventions remain difficult to study and should not replace medical care, but the results provide rare clinical trial evidence that diet may play a therapeutic role for some patients.
“There’s still a lot more to be done to understand the biology behind how this and other diets work in patients with Crohn’s disease,” Sinha said.
The authors caution that the findings apply only to people with mild-to-moderate Crohn’s disease and that fasting-mimicking diets should be undertaken only with medical supervision.
The study was supported by a combination of public and nonprofit funding focused on digestive health, chronic disease research and physician-scientist training. Major funders included the National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Kenneth Rainin Foundation, the Doris Duke Foundation and Stanford University’s Plant Based Diet Initiative. Additional support came from the Chan Zuckerberg Biohub and related investigator programs.
One study author disclosed an equity interest in the company that provided the fasting-mimicking meals.