Posted by Heather Kaplan on June 28, 2022
Study Authors
Kaplan HC, Opipari-Arrigan L, Yang J, Schmid CH, Schuler CL, Saeed SA, Braly KL, Chang F, Murphy L, Dodds CM, Nuding M, Liu H, Pilley S, Stone J, Woodward G, Yokois N, Goyal A, Lee D, Yeh AM, Lee P, Gold BD, Molle-Rios Z, Zwiener RJ, Ali S, Chavannes M, Linville T, Patel A, Ayers T, Bassett M, Boyle B, Palomo P, Verstraete S, Dorsey J, Kaplan JL, Steiner SJ, Nguyen K, Burgis J, Suskind DL; ImproveCareNow Pediatric IBD Learning Health System
Study Background
Many patients with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are interested in nutritional therapy. The role of diet in managing IBD was identified as an important research question by patients, parents, and providers in ImproveCareNow (ICN). The Personalized Research on Diet in Crohn’s Disease and Ulcerative Colitis (PRODUCE) study was designed to begin to look at this research question.
Study Overview
The PRODUCE study compared the specific carbohydrate diet (SCD) to a less restrictive version of the diet (modified specific carbohydrate diet; MSCD), and also compared both to patients’ usual diet. The SCD includes whole, unprocessed foods like: meat, fish, poultry, eggs, some legumes, 24-hour fermented yogurt, some aged cheese, non-starchy vegetables, ripe fruits, nuts, seeds, honey, and nut flours. The following foods were not permitted: grains, liquid milk products, starchy vegetables, processed foods, food additives, and sweeteners (aside from honey). The MSCD expands the foods allowed on the SCD to include pre-defined amounts of oats, organic rice, sweet potatoes, Grade A maple syrup, and 100% cocoa or 100% cacao powder, or nibs. More details about the SCD and MSCD are available on the NiMBAL website.
The study design that was used to compare the diets is called an N-of-1 trial. This type of design allowed each patient to test the different diets and to learn how each diet impacted their symptoms and disease activity. After all participants completed the N-of-1 trial in the same way, their information was collected and combined. Combing all participant’s data allowed us to learn about the effectiveness of the different diets for the overall group.
Each participant who finished the study completed two 8-week periods of each of the diets. When participants started the study, they ate their typical, unrestricted diet for 1-2 weeks. This allowed us to collect information about their symptoms and inflammation while eating their usual diet. Next, participants were randomly selected to begin following either the SCD or MSCD. They continued to follow one assigned diet for 8 weeks and then switched to the other diet. This pattern was repeated two times for a total of 32 weeks (total of four diet periods).
Participants kept track of their symptoms using the Eureka mobile app. Key symptom measures included:
- Number of stools per day
- Consistency of stool each day (Bristol Stool Scale)
- Pain Interference each week (PROMIS® Pain Interference scale).
- IBD symptoms (Pediatric IBD Symptom Scale).
At the beginning of the study and at the end of each of the four diet periods, participants collected a stool sample to measure fecal calprotectin, a medical test that is a marker of inflammation in the intestines.
After a patient completed the study, their clinical provider reviewed their individual results with them. The research team collected information about the treatment choices each patient made following the results review or when the participant stopped the study (if they ended their N-of-1 trial early or withdrew).
Study Results—What does it all mean?
This is the largest study of dietary therapy with the SCD and MSCD in pediatric IBD to date. We enrolled a total of 54 patients in the PRODUCE study between April 2018 and December 2019. Patients were enrolled across 19 participating ICN sites throughout the US. The median participant age was 12.5 years (range 7-18 years). A majority of enrolled patients (74%) had CD.
Of the 54 enrolled participants, 21 (39%) completed the entire N-of-1 trial (two periods on each diet). We refer to these individuals as full completers. Nine (17%) participants completed one period on each diet (about half of the study). We refer to these individuals as early completers. Twenty-four (44%) participants withdrew before completing one period on each diet.
The overall result was that when comparing the SCD and MSCD to each other, for most patients, neither diet was better than the other. Even though this was the largest study to date, more participants would have been needed to feel scientifically confident that there really is no difference between the diets.
Some participants health improved on these diets compared to their typical diet while others did not. Among full completers, >50% had improvement in symptoms and decreased inflammation on the SCD and/or MSCD compared to their usual diet. Most full completers continued either the SCD or MSCD after completing their N-of-1 trial. The high numbers of patients that withdrew or chose to stop early (early completers) indicates that, for many patients, the SCD and MSCD were ineffective or partially effective (meaning there was improvement in symptoms without reduction in inflammation).
The PRODUCE study does not support SCD and MSCD diets as effective treatments for all patients. However, the results do suggest that SCD and MSCD may be reasonable options for some patients to consider with their clinical provider. Providers should understand there are still many unanswered questions about dietary therapy and discuss this with patients and families.
Study status
The PRODUCE study was published in 2022. You can locate it:
- In the American Journal of Gastroenterology
- In the Completed Research and Publications listings on our website