It is also one of the hardest to answer. Inflammatory bowel disease, which includes ulcerative colitis and Crohn’s disease, has not been studied extensively when it comes to diet. Large, well-controlled studies on dietary changes have been limited.

Now, researchers from Stanford Medicine and collaborating institutions may be closing that gap. In a national randomized controlled trial, they found that a short-term, calorie-restricted eating plan led to meaningful improvements in both symptoms and biological markers in people with mild-to-moderate Crohn’s disease. The results were recently published in Nature Medicine.

Studying diet is challenging. Participants may not always accurately report what they eat, and placebo effects are difficult to avoid since people know which diet they are following. Even so, the results stood out. Patients not only reported feeling better, but also showed measurable reductions in inflammation in biological samples. The findings could help doctors give clearer dietary guidance to patients.

“We have been very limited in what kind of dietary information we can provide patients,” said Sidhartha R. Sinha, MD, an assistant professor of gastroenterology and hepatology and the senior author on the paper. “This study will give physicians evidence to support recommendations in an area that patients are very curious about.”

Crohn’s Disease and Limited Treatment Options

Crohn’s disease is a long-term condition that affects roughly one million Americans. It causes inflammation in the digestive tract and can lead to symptoms such as diarrhea, cramping, abdominal pain and weight loss.

For mild cases, steroids are currently the only approved treatment. However, they can cause serious side effects, especially when used over long periods.

How the Fasting Mimicking Diet Was Tested

The clinical trial followed 97 patients with mild-to-moderate Crohn’s disease across the United States. Of these, 65 participants followed a fasting mimicking diet, while 32 continued with their usual eating habits as a control group. The study lasted three months.

Those in the fasting mimicking group reduced their calorie intake for five consecutive days each month, consuming roughly 700 to 1,100 calories per day. During this period, they were given plant-based meals. For the rest of the month, they returned to their normal diet.

Significant Symptom Improvement

By the end of the study, about two-thirds of the participants following the fasting mimicking diet reported improvement in their symptoms.

“We were very pleasantly surprised that the majority of patients seemed to benefit from this diet,” Sinha said. “We noticed that even after just one FMD cycle, there were clinical benefits.”

In contrast, fewer than half of those in the control group experienced symptom improvement. Researchers noted that these changes were likely due to natural fluctuations in the disease and ongoing standard treatments, such as medications.

Some people in the fasting mimicking group reported fatigue and headaches, but no serious side effects were observed.

Measurable Reductions in Inflammation

The researchers also looked beyond symptoms to understand what was happening inside the body.

Sinha’s interest in the fasting mimicking diet came from earlier research showing it could lower levels of C-reactive protein, a marker of inflammation, in people with elevated baseline levels. “The effects seen on inflammatory markers made this an appealing diet to study in Crohn’s disease since many patients with this disease also have elevated inflammatory markers,” he said.

To explore this further, the team collected and analyzed biological samples, including blood and stool, to track changes in inflammation.

“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?”

They found that levels of fecal calprotectin, a protein that signals inflammation in the gut, dropped significantly in the fasting mimicking group compared with the control group. Other inflammation-related molecules, including certain lipid mediators derived from fatty acids, were also reduced. In addition, immune cells in these participants produced fewer inflammatory signals.

Researchers are now investigating whether shifts in the gut microbiome could help explain these benefits.

What Comes Next for Diet and Crohn’s Research

“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 study’s first authors are Stanford Medicine’s Chiraag Kulkarni, MD, an instructor in gastroenterology and hepatology, and assistant clinical research coordinator Touran Fardeen. Researchers from the University of Southern California and the University of California, San Francisco, also contributed.

Author Valter Longo, PhD, has equity interest in L-Nutra, the company from which the fasting mimicking meals were purchased and has filed patents related to the diet.

The research was supported by The Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health (grants UM1TR004921, 2L30 DK126220, T32DK007056, K08DK134856 and NIDDK R01DK085025), the Plant Based Diet Initiative at Stanford University, the Kenneth Rainin Foundation, the Doris Duke Foundation Physician Scientist Fellowship Award, a CZ Biohub Physician Scientist Scholar Award, the Colleen and Robert D. Hass fund, and the Chan-Zuckerberg Biohub Investigator Program.