“What should I eat?” is one of the most common questions people with inflammatory bowel disease ask their doctors.
It’s also the most difficult question to answer. Inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, are less well studied when it comes to diet. Large, well-controlled studies of dietary modification are limited.
Now, researchers at Stanford Medicine and Collaborative Research may be looking to fill that gap. A national randomized controlled trial found that a short-term calorie-restricted diet plan produced meaningful improvements in both symptoms and biological markers in patients with mild to moderate Crohn’s disease. The results were recently natural medicine.
Learning about diet is difficult. Participants do not always accurately report what they eat. Also, participants know what diet they are following, so it is difficult to avoid a placebo effect. Still, the results were outstanding. Not only did patients report feeling better, but biological samples also showed a measurable reduction in inflammation. The findings could help doctors provide clearer dietary guidance to patients.
“The type of dietary information we were able to provide to patients was very limited,” said Siddhartha R. Sinha, MD, assistant professor of gastroenterology and hepatology and senior author of the paper. “This study will provide physicians with evidence to support recommendations in an area of great interest to patients.”
Crohn’s disease and limited treatment options
Crohn’s disease is a long-term disease that affects approximately 1 million Americans. It can cause inflammation in the gastrointestinal tract, causing symptoms such as diarrhea, cramps, abdominal pain, and weight loss.
For mild cases, steroids are the only currently approved treatment. However, it can cause serious side effects, especially if used for a long period of time.
How have fasting-mimicking diets been tested?
The clinical trial followed 97 patients with mild to moderate Crohn’s disease from across the United States. Of these, 65 participants followed a fasting-mimicking diet, while 32 continued their normal eating habits as a control group. The study lasted for 3 months.
People in the fasting mimic group reduced their calorie intake for five consecutive days each month, consuming about 700 to 1,100 calories per day. During this period, they were fed a plant-based diet. For the rest of the month they returned to their normal diet.
Significant improvement in symptoms
By the end of the study, about two-thirds of participants who followed the fasting-mimicking diet reported improvement in symptoms.
“We were very pleasantly surprised that the majority of patients seemed to benefit from this diet,” Sinha said. “We realized that even just one FMD cycle can have clinical benefits.”
In contrast, less than half of the control group experienced improvement in symptoms. The researchers noted that these changes were likely due to natural fluctuations in the disease and continued standard treatments, such as medications.
No serious side effects were observed, although some people in the fasting mimic group reported fatigue and headaches.
visible reduction in inflammation
Researchers also looked beyond symptoms to understand what’s happening inside the body.
Sinha’s interest in fasting-mimicking diets stems from previous research showing that they can reduce levels of C-reactive protein, an inflammatory marker, in people with high baseline levels. “Many patients with Crohn’s disease also have elevated inflammatory markers, so the effects seen on inflammatory markers made this diet attractive for studying Crohn’s disease,” he said.
To investigate this further, the team collected and analyzed biological samples such as blood and stool to track changes in inflammation.
“Our goal in collecting these and other biospecimens was to dig deeper into why such different responses exist,” Sinha said. “Can we find mechanisms that explain the findings and signs that may help predict which patients will respond to dietary therapy?”
They found that levels of fecal calprotectin, a protein that signals inflammation in the intestines, were significantly reduced in the fasting mimic group compared to the control group. Other inflammation-related molecules, such as certain lipid mediators derived from fatty acids, were also reduced. Furthermore, these participants’ immune cells produced fewer inflammatory signals.
Researchers are currently investigating whether changes in the gut microbiome may help explain these benefits.
Future developments in diet and Crohn’s disease research
“There is still much work to be done to understand the biology behind how this and other diets work in people with Crohn’s disease,” Professor Sinha said.
The study’s first authors are Chiraag Kulkarni, MD, lecturer in gastroenterology and hepatology at Stanford University, and Touran Fardeen, clinical research assistant coordinator. Researchers from the University of Southern California and the University of California, San Francisco also contributed.
Author Dr. Valter Longo owns stock in L-Nutra, the company from which he purchased the fasting-mimicking diet, and has applied for patents related to the diet.
This 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 Stanford University Plant-Based Diet Initiative, and Kenneth Rainin Foundation, Doris Duke Foundation Physician-Scientist Fellowship Award, CZ Biohub Physician-Scientist Scholar Award, Colleen and Robert D. Hass Foundation, and Chan Zuckerberg Biohub Investigator Program.
