Efficacy of Diet Based Interventions for Crohn’s Disease

Introduction

Crohn’s Disease is an Inflammatory Bowel Disease (IBD) that has increased in incidence worldwide in the last decade [2]. The disease results in the inflammation of the GI tract and can cause diarrhea, nausea, vomiting, and fatigue, among other symptoms. Crohn’s Disease is of unknown origin but is largely attributed to genetic, immunological, and environmental factors [5]. The two primary forms of treatment previously utilized were medications and surgical intervention. While the current leading forms of treatment for Crohn’s Disease have been immunosuppressive and biologic medications, more focus needs to be placed on alternative therapies for those who cannot tolerate the drugs that are frequently prescribed. One alternative therapy that is being researched is the implementation of a solely diet-based approach for the purpose of limiting disease activity. Diet has been shown to have a major impact on the progression of IBDs through the maintenance of homeostasis within the gut [1]. Furthermore, nutritional therapies have gained attention due to the current advancements in clinical nutrition, and the variety of diet options allowing for more flexibility with treatment [5]. In particular, diet can be utilized as a stand alone treatment, or in addition to the use of medications. The nutritional status of Crohn’s Disease patients is often suboptimal as a result of the decreased nutrient absorption caused by the disease, furthering the need for nutritional support even if medications are being utilized [5]. The purpose of this literature review is to evaluate the efficacy of the three main diet-based interventions as monotherapy: Exclusive Enteral Nutrition (EEN), Partial Enteral Nutrition (PEN), and the Crohn’s Disease Exclusion Diet (CDED). The focus of this review will be placed on the assessment of inflammatory markers and patient reported outcomes. This article will compare and contrast the three diets to first examine their effects on rates of remission, and then assess the quality of life of patients who have utilized the intervention as a primary form of treatment. 

Overview of Diet Interventions

The three diets being discussed in this review are the Exclusive Enteral Nutrition (EEN), Partial Enteral Nutrition (PEN), and Crohn’s Disease Exclusion Diet (CDED). To understand the efficacy of the diets, the methods in which they are utilized must first be discussed. Exclusive Enteral Nutrition (EEN), consisting of an entirely liquid diet, has been utilized primarily in children as a first line of treatment, due to their ability to better tolerate a lack of solid foods. In contrast, Partial Enteral Nutrition (PEN) involves the combination of both liquid nutrition and a free diet in which patients are able to consume a certain amount of solid foods per day [1]. A more recent creation, the Crohn’s Disease Exclusion Diet (CDED) is an entirely solid food diet that was formed as an alternative to the prior two diets, and utilizes a two-part approach in which several foods are excluded, then slowly reintroduced [5]. One of the primary reasons for the implementation of these diets is to retain the body’s gut microbiome [5]. Dietary components play a role in the maintenance of gut bacteria through the supply of essential macronutrients. The microbes in the microbiome play a crucial role in the metabolism and regulation of the immune and nervous systems [7]. Crohn’s Disease can cause damage to the intestinal mucosa, resulting in reduced diversity and imbalance of gut microbiota [7]. The inability to maintain intestinal homeostasis can result in negative effects to the intestinal lining and intestinal immunity, which can further lead to the aggravation of disease activity and trigger an inflammatory response [5]. If homeostasis is ignored, possible complications such as fistulas, obstructions, or strictures may arise. Careful implementation of targeted diets can result in the alleviation of many symptoms associated with Crohn’s Disease. Multiple studies have been conducted in which patients are placed under one of the three restrictive diets and evaluated at various points throughout the respective study, which will be further explored in this review.

Rates of Remission

With the lack of a definitive cure for Crohn’s Disease, achieving remission is the goal that all patients strive for. The induction of remission is quantified by the decrease in certain inflammatory markers that indicate the presence of active inflammation in patients with Crohn’s Disease. If a treatment has the ability to induce remission, it can therefore be concluded that the treatment is effective.

Evaluation of Inflammatory Markers

Several studies have assessed the efficacy of the diets by comparing the levels of inflammatory markers that are present before and after the implementation of the respective diets. The main inflammatory markers being evaluated were calprotectin, Crohn’s Disease Activity Index (CDAI), and Pediatric Crohn’s Disease Activity Index (PCDAI). Calprotectin is a protein indicator of inflammation within the intestine, while the CDAI and PCDAI are clinical scores that are utilized to quantify inflammatory levels. 

A decrease in the levels of inflammatory markers indicates a significant reduction in active inflammation. Szczubelek et al. found that 82.1% of participants in a study had experienced a decrease in CDAI levels to a score of 150 points or less while on the Crohn’s Disease Exclusion Diet [1]. The reduction of inflammation in these participants indicates that remission had been achieved, which suggests that participants are responding to the diet in a beneficial way. Furthermore, Levine et al. observed a significant drop in PCDAI levels from 25 to 2.5 by Week 6 in patients who were also placed on the CDED [3]. The consensus between the two studies is that the CDED presents as a viable option as a primary diet-based treatment based on the indication of symptom improvement due to the observed reduction of active inflammation.

Crohn’s Disease can present differently in children compared to adults, necessitating the use of two different markers in the two studies– CDAI vs PCDAI– to assess the efficacy of the diet on the two age groups involved. The study by Szczubełek et al. was one of the first to test the efficacy of the CDED alone, with no other diet used as a point of comparison [1]. The lack of a control variable results in the inability to utilize the outcomes of this study to conclude one diet is more effective than another. In contrast, the study by Levine et al. incorporated the use of PEN with the CDED, since it was an early study directly testing the potential of the CDED against

Exclusive Enteral Nutrition (EEN) [3]. Researchers previously lacked confidence in the ability of PEN alone or the CDED alone to provide a holistic calorie intake, and therefore combined the two together as they believed it would be more effective. Though it does not discuss PEN alone, the results of the study by Levine et al. bring light to the option of combining it with CDED as a viable option. As a result, the study can be utilized to better form a conclusion on which diet should be utilized by patients with Crohn’s Disease based on the use of two different groups for comparison.

Exclusive Enteral Nutrition (EEN) varies from the other two diets in that it fully restricts the patients from consuming solid foods and instead involves the exclusive consumption of a polymeric, casein-based formula either orally or through nasogastric tube feeding [4]. In a study testing the ability of the EEN to decrease inflammation, it was found that median calprotectin levels decreased from 1433 mg/kg to 453 mg/kg after the study [4]. Though remission had been achieved, it was not sustained. After reverting to a free food diet, the majority of the patients experienced a significant rise in calprotectin to pre-treatment levels within 52 days of completing EEN [4]. In contrast, patients on the combined CDED + PEN diet were able to sustain remission through the 24 weeks they were on the diet [2]. As a result, the short-term use of EEN has proven to be effective in inducing remission, but there is further research to be done to determine its efficacy in the long term.

Effect on Quality of Life

The improvement of a patient’s quality of life is a significant factor in determining the efficacy of a treatment. The use and validity of a treatment is heavily dependent on how patients react to it. In multiple studies, a diet’s effect on a patient’s life was determined by the patient’s ability to tolerate the diet [3], along with the reports they provided through question forms that focused on the patient’s perception of the efficacy of their treatment [1, 2].

Diet Tolerance

The ability of a participant to tolerate a treatment is directly related to the effect it has on the quality of their life. Tolerance in this context refers to the total adherence to the given diet for the allotted time. A tolerable treatment gives patients the opportunity to manage their symptoms and improve their overall well-being. It is also a significant factor that is considered when determining a treatment’s efficacy. One particular study performed by Levine et al. placed a heavy emphasis on whether participants were able to tolerate the CDED + PEN (Partial Enteral Nutrition) more or less than EEN [3]. A statistical difference was found as 97.5% of the CDED + PEN group tolerated their diet, while 73.3% of the EEN group were able to tolerate it for the full length of the study [3]. Noncompliance for the studies was identified  as the consumption of foods that were not allowed based on the diet’s instructions [6]. The lack of compliance with EEN compared to CDED + PEN can be attributed to the fact that EEN lacks the solid food component that the other diet has. Furthermore, one of the routes for the diet is a feeding tube, which requires the food to be liquified. Patients may be discouraged from utilizing the EEN via the feeding tube, which presents considerable limitations for patients in terms of social eating and drinking. Withstanding a solely liquid diet over a long period of time can negatively impact a patient’s mental health and willingness to comply, and can further lead to participants abandoning treatment altogether.

Questionnaire Based Outcomes

The type of assessment used to measure changes in quality of life was different in the two relevant studies [1, 2], but served the same purpose in obtaining patient reported feelings on the treatment. Szczubełek et al. utilized the Inflammatory Bowel Disease Questionnaire (IBDQ) in their study where participants were placed on the CDED. The IBDQ is commonly utilized by researchers as a method for assessing quality of life [1]. Through the questionnaire, patients answered a series of questions related to the symptoms they experience with their Inflammatory Bowel Disease (IBD), and how it affected their mental health and social life. Participants were given a numerical score based on the answers they provided at the start and end of the diet. After comparing the results of the IBDQ, there was a statistically significant increase in the numerical values determined by the questionnaire [1]. This increase in levels indicates that the CDED was effective in significantly improving the participants’ quality of life.

Yanai et al. utilized the Harvey-Bradshaw Index (HBI) as a method of comparing the effects of the CDED + PEN on a patient’s standard of living [2]. The HBI has historically been utilized as a simplified way for physicians to categorize patients based on the severity of their condition, and analyze the data they receive. Prior to diet implementation, participants answered a series of questions relating to their well-being and were assigned a score that measured the severity of their disease [2]. After the study, reanalysis showed that 63% of the participants had achieved clinical remission based on the significant decrease in their HBI scores [2]. The reported improvement in this index indicates that the patients themselves felt that the severity of their disease had improved, therefore allowing them to lead a better quality life.

The direct comparison of the two questionnaires is ineffective in qualitatively analyzing the effectiveness of the diets, based on the discrepancies in questioning and analysis of values. The IBDQ was used solely as a qualitative way to determine how the participants felt about their life prior to and after the diet, while the Harvey-Bradshaw Index was used to numerically quantify their disease activity. The questionnaires effectively determined that the lives of the participants had significantly improved in some capacity. However, the variance in the design of these questionnaires yields results that cannot be utilized to determine whether one diet is better at improving one’s quality of life than another.

Conclusion

Based on the aforementioned studies, there is statistical evidence to support the idea that diet-based treatments are effective in inducing remission and improving the quality of life in patients with Crohn’s Disease. There is significant data to determine that the Crohn’s Disease Exclusion Diet (CDED) is effective in reducing levels of inflammatory markers [1, 3], while also notably improving the participants’ standard of living [1, 2]. There is further research to be done in order to determine whether CDED alone is a better treatment compared to the combination of CDED + PEN, as the study directly comparing the two yielded statistically insignificant results [2]. Though Exclusive Enteral Nutrition (EEN) has also proven to be effective in lowering disease activity, the low tolerance levels and the high probability of relapse furthers the question of whether it is viable as a treatment over a greater period of time (several years). Across all diets, determining how long they should be applied ultimately depends on whether it is being used as a monotherapy, or in combination with a medication [6]. Patients may utilize diet therapy as a last resort due to the inability to achieve remission with medication. Furthermore, diets may be modified to adapt to the additional use of drug therapy to better suit the patient’s needs. Applications of diet as a primary treatment are becoming increasingly observed, and furthers the need for healthcare providers to consider the therapy as an alternative or an addition to medications.

About the Author: Subha Alluri

Subha Alluri is a 4th year Biological Sciences major, and is also minoring in Nutrition and Food Science. She is a pre-med student that wants to bring awareness to the importance of understanding the impact of nutrition and diet on GI related diseases. Her experience with having Crohn’s Disease led her to write this review that highlights the value in considering alternative means of treatment, beyond pharmaceutical drugs. She hopes to inform people on the prevalence of GI diseases, and how they can best manage their symptoms. There is no cure for Crohn’s Disease, so she hopes to further her interest in research that seeks to find better therapies not only for herself, but for everyone that struggles with Crohn’s. 

Author's Note

I originally wrote this Literature Review as part of my UWP104FY class with Professor Sperber, which led to me earning an A+ in the class. However, I put a lot of effort into the review because of my personal connection with the topic. I was diagnosed with Crohn’s Disease 5 years ago and will continue to live with it for the rest of my life. Writing this paper became emotional for me at times because of the recognition that my audience is people who suffer from the same condition that I do. I know the pain that they feel every day, and how it can feel as though there is no cure in sight. After my initial diagnosis, I was placed on several pharmaceutical drugs that caused intense side effects, including hair loss, nausea, stomach pain, etc. Being on intense drugs can affect a person’s physical, mental, and emotional state and left me wondering if there were alternative ways to treat my condition. One year, I decided to stop taking all medications and decided to focus strictly on diet. I was able to manage the symptoms of my condition but was unable to sustain it for the long term. I decided to do more research through this Literature Review, to find out what diet interventions are sustainable, and if people can rely on it as their sole method of treatment. Nutrition in particular is often overlooked in medicine but can be more effective than one might think. It is important for people to know that drugs are not the only way to treat GI disorders and that there are other options available to them. I hope that this Review can bring awareness to the complexity of Crohn’s Disease, and emphasize the need for more research to be done.

References

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