Time-restricted feeding (TRF) significantly reduces symptomatic disease activity and systemic inflammation in adults with Crohn’s disease and overweight or obesity, according to new research.

In a randomized controlled study, restricting eating to an 8-hour window was associated with a 40% reduction in stool frequency and a 50% reduction in abdominal discomfort over 12 weeks compared with the usual eating schedule.

“The biological improvements we observed suggest promise for long-term maintenance of remission,” lead author Maitreyi Raman, MD, associate professor of medicine at the University of Calgary, Calgary, told Medscape News Canada.

In addition, the study “is the first to demonstrate that TRF, one form of intermittent fasting, is effective to improve body weight and decrease BMI and visceral fat in overweight or obese patients with Crohn’s disease,” she said.

The data were published on February 9 in Gastroenterology.

Visceral Fat Loss

The researchers randomly assigned participants to a TRF group (n = 20; mean age, 49 years) or control group (n = 15; mean age, 47 years). At baseline, mean BMI ranged from 29 kg/m² to 30 kg/m², and mean weight ranged from 88 kg to 89 kg.

Roughly 76% of participants had the inflammatory phenotype of Crohn’s disease, with roughly one quarter taking no medication. About 60% of the TRF group and 47% of the control group were on biologic therapy.

Other medications for Crohn’s disease included immunomodulators (20% of the TRF group and 7% of the control group), 5-aminosalicylic acid (5% and 27%, respectively), and steroids (5% and 7%, respectively).

The TRF group consumed their habitual diet within an 8-hour window on 6 days per week for 12 weeks and fasted for the remaining 16 consecutive hours per day, whereas the control group continued their usual eating pattern.

After 12 weeks, participants in the TRF group lost about 5.5 pounds, but those in the control group gained approximately 3.7 pounds despite similar calorie intake and diet quality. BMI was significantly reduced in the TRF group compared with the control group (-0.9 kg/m² vs +0.6 kg/m², P < .001). Clinical disease activity, measured by the Harvey-Bradshaw Index, also improved significantly in the TRF group (-2.0 vs -0.5, P = .02).

Furthermore, compared with control group, the TRF group exhibited significant reductions in serum adipokines from baseline, including leptin, a marker of adiposity and inflammation (P < .001), and plasminogen activator inhibitor-1, and adipsin, which both are associated with adipose tissue remodeling and immune regulation (P < .05 for both).

In a subset of participants with DEXA data, visceral adipose tissue decreased in the TRF group but increased in control group, resulting in a significant between-group difference (P < .05).

“Together, these hormonal and body composition changes strengthen evidence that TRF improves adipose tissue distribution and metabolic health,” wrote the authors. 

An examination of the cytokine profiles of TRF group participants who achieved a BMI reduction of greater than 1 unit showed that greater BMI loss correlated positively with both anti-inflammatory and pro-inflammatory cytokines, which “may be compatible with an evolving process of immune recalibration,” suggested the authors. No between-group differences were seen in C-reactive protein (CRP) at week 12.

Stool samples collected at baseline and week 12 showed no changes in fecal calprotectin. Microbiota analyses within the TRF group, however, revealed a trend toward increased microbial diversity and enrichment of short-chain fatty acid-producing taxa, including Butyricimonas synergistica, Odoribacter splanchnicus, and Blautia schinkii. 

Bacteroides ovatus and Escherichia/Shigella species were inversely associated with BMI reduction, whereas Clostridium ramosum, Anaerococcus vaginalis, and Peptoniphilus coxii were positively associated with BMI reduction (P < .05).

“Although these associations did not remain significant after correction for multiple testing, these exploratory findings suggest that TRF-related shifts in the gut microbiota may accompany or facilitate improvements in adiposity and immune regulation,” the authors wrote.

“We were surprised about how people who fasted lost not just weight but also visceral fat despite consuming the same energy content as those that did not fast, suggesting that other factors outside of total calories/energy were responsible for driving these effects,” said Raman. 

“Obesity, especially visceral fat, decreases the chances of achieving successful remission or maintenance of remission, even when using usual medications like biologic therapies,” she added. “Diet and nutrition are emerging effective treatments that can be used on their own or in combination with other medical therapies.”

No Disease Control?

Commenting on the findings for Medscape News Canada, John Mark B. Gubatan, MD, assistant professor and senior associate consultant at the Inflammatory Bowel Disease Center at the Mayo Clinic in Jacksonville, Florida, said that the results are “quite promising and give hope to patients with Crohn’s disease to use diet as an adjunct therapy to traditional therapies.” Gubatan was not involved in the study.

“The study highlights that when food is consumed (ie, timing) and not necessarily what (ie, food quality) and how much (ie, number of calories) can confer health benefits,” he added. The results are comparable to those of similar fasting diet research in patients with mild-to-moderate Crohn’s disease that his group published recently.

“While larger studies are needed to validate the results and evaluate the durability of the findings, this emphasizes the need for stakeholders to invest in research efforts exploring the effects and mechanisms of diet on inflammatory bowel disease,” said Gubatan.

The findings “are of interest but should not be overinterpreted,” cautioned David T. Rubin, MD, professor of medicine at the University of Chicago, Chicago, and chair of the International Organization for the Study of IBD.

“It is important to recognize that absence of meaningful changes in CRP and fecal calprotectin, which are established biomarkers of inflammation, suggests that this 12-week intervention is not substantial enough to achieve biochemical remission alone, and by extension this means that it is not achieving disease control,” he told Medscape News Canada. Rubin was not involved in the research.

“This study implies that weight loss in general, and perhaps by this particular TRF approach, is an adjunctive management strategy for Crohn’s disease,” he continued. “We have accumulating evidence that visceral fat (and fat in general) and inflammation associated with fat contribute to ‘total body’ inflammation, so it is important to demonstrate the benefit of losing weight on Crohn’s disease.”

Future studies should expand on these findings and examine strategies of diet that include anti-inflammatory therapy, said Rubin. “These studies will further clarify the role of fat, eating, the gut microbiome, and inflammatory cytokines in the future management of Crohn’s disease.”

The study was funded by Crohn’s Colitis Foundation, Litwin IBD Pioneers Grant, and Imagine Network. Raman, Gubatan, and Rubin reported having no relevant financial relationships.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.