Short-term, calorie-restrictive diet improves Crohn’s disease symptoms

A Stanford Medicine-led study finds a short-term, calorie-restrictive diet significantly improved symptoms.

"What should I eat?" is perhaps the most common question patients with inflammatory bowel disease ask their doctors.

It's notoriously difficult to answer. There have been few large studies of dietary interventions for IBD, a group of disorders that includes ulcerative colitis and Crohn's disease.

Now, new research by Stanford Medicine investigators and their colleagues provides one potential answer. Their national, randomized controlled clinical trial found that a short-term, calorie-restrictive diet significantly improved both physical symptoms and biological indicators of mild-to-moderate Crohn's disease. The findings will be published Jan. 13 in Nature Medicine.

While dietary interventions are difficult to study - participants' reports of what they're eating aren't always accurate, and the placebo effect can't be avoided because participants know which diet they're on - the findings were notable, demonstrating significant declines in objective markers of inflammation in biologic samples alongside improvements in clinical symptoms. The study may help physicians guide patients in finding a diet that alleviates symptoms.

We have been very limited in what kind of dietary information we can provide patients. This study will give physicians evidence to support recommendations in an area that patients are very curious about."

Sidhartha R. Sinha, MD, assistant professor of gastroenterology and hepatology and senior author on the paper

A common condition, few treatments

A chronic condition affecting about a million Americans, Crohn's disease causes inflammation in the digestive tract, leading to symptoms of diarrhea, cramping, abdominal pain and weight loss. Steroids are the only approved therapeutic for mild Crohn's, but their use is limited due to significant side effects, particularly with long-term use.

The study compared the symptoms and biological indicators of patients with mild-to-moderate Crohn's disease as they either followed a fasting mimicking diet or ate their normal diet for three consecutive months. The study enrolled 97 patients across the country, with 65 in the fasting mimicking group and 32 in the control group.

Participants in the fasting mimicking group severely limited their calories for five consecutive days per month, eating between about 700 and 1,100 calories a day, Sinha said. Plant-based meals were provided during the fasting period. For the remainder of the month, the fasting mimicking group ate their normal diet.

At the end of the study, about two-thirds of the fasting mimicking group experienced 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 the control group, less than half experienced improvements in their symptoms. The improvement was likely a result of natural symptom fluctuations in Crohn's disease and because patients continued to follow their standard care regimens, such as taking medications.

Some participants in the fasting mimicking group experienced fatigue and headache, Sinha said, but no serious side effects were reported.

Biological indicators get a boost

Sinha was inspired to study the fasting mimicking diet in patients with Crohn's disease after earlier research indicated the diet could reduce levels of C-reactive protein, a common marker of systemic inflammation in patients who had high baseline C-reactive protein 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.

Along with tracking participants' clinical response and remission, the researchers also explored changes in biological specimens, such as shifts in common markers of inflammation in both stool and blood. "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?"

The researchers found a significant decline in fecal calprotectin, a protein in the stool that indicates gut inflammation, in the fasting mimicking group compared with the control group. Some inflammation-promoting lipid mediators derived from fatty acids also declined in fasting mimicking group participants. Similarly, the immune cells of fasting mimicking group participants produced fewer of several types of inflammatory molecules. The researchers are now exploring whether changes in the gut microbiome may also help explain some of the benefits of the fasting mimicking diet.

"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, contributed to the work.

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.

This work was supported by a grant from 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.