Abstract
Irritable bowel diseases (IBD) are chronic immune-mediated conditions of unknown etiology, characterized by debilitating acute exacerbations and remissions. Emergency treatment may include surgical interventions and pharmacological agents: cortisone, aminosalicylates, and antibiotics.
There is mounting evidence that diet type can play a significant role in improving outcomes in the management of IBD in adult patients.
This article is a review of literature analyzing the benefits that an anti-inflammatory dietary regimen may have as an adjunct to conventional medicine in the management of IBD.
Studies show that agents derived from natural food sources, including ‘prebiotics’, probiotics, and animal and plant extracts have significant anti-inflammatory properties. This critical review assesses current evidence on the anti-inflammatory effects of nutrition as a complementary therapy in IBD symptom management in adult patients.
Introduction
The normal functioning of the human GI tract depends on factors such as intestinal microflora, genetic predisposition, and the nutritional status of an individual.
Conditions such as IBD (CD and UC), microbial gastroenteritis, NSAIDs-related enteropathy, and colorectal cancers cause severe inflammation of the intestinal tract that result in impaired absorption. The treatment options available for IBD have variable effectiveness, which calls for novel therapeutic interventions.
Treatment options for IBD usually involve pharmacological agents such as cortisone, aminosalicylates, and antibiotics, and surgical intervention. However, the treatment options sometimes produce counteractive effects, which impede sustained remissions in patients.
Moreover, therapy responsiveness varies among patients, which underscores the need for adjunctive interventions to reduce inflammatory effects and induce mucosal restoration.
In recent years, researchers have investigated dietary products derived from natural sources as potential adjunctive anti-inflammatory agents in IBD management. This article reviews literature analyzing the benefits that an anti-inflammatory dietary regimen may have as an adjunct to conventional medicine in the management of adult IBD.
The studies reviewed concur on the use of enteral nutrition (EN) as an effective feeding modality for treatment of IBD, especially CD, in adults (Yamamoto, Nakahigashi & Saniabadi, 2009; Hartman, Eliakim & Shamir, 2009; Rajendran & Kumar, 2010).
A range of dietary interventions, including anti-inflammatory diet or IBD-AID (complex carbohydrates, pre- and probiotics, and unsaturated fatty acids) and conjugated linoleic acid also induce sustained remission (Bassaganya-Reira & Hontecillas, 2010; Olendzki et al., 2014).
The research methods show great variability among the studies reviewed. They include systematic reviews of meta-analyses and randomized control trials (RCTs), prospective and retrospective cohort studies, case series, and experimental designs.
Evidence from the articles reviewed in this paper indicates that nutrition-based interventions can ameliorate IBD management and facilitate sustained remission. The conclusions made in the articles show that EN is an effective dietary therapy for CD treatment due to its low drug-interaction risk.
However, the scientific evidence to support the use of nutrition-based therapies (IBD-AID) as adjuncts in IBD treatment is lacking.
Nevertheless, there is compelling evidence that dietary agents are effective against GI disorders, including IBD. This literature review aims to synthesize the current evidence for the use of nutrition-based therapy as an adjunct in treating IBD and improving outcomes over pharmacological and/or surgical intervention.
The inclusion criteria entailed a Medline search of full text, peer reviewed research articles published between September 2008 and September 2014 using two key words/phrases: IBD and anti-inflammatory diet as an adjunct in symptom management.
The search yielded 16 articles, which were organized in order of increasing strength of evidence for analysis.
Methods
The methodology used to collect and analyze date in each study falls into either qualitative or quantitative category. Olendziki et al.’s (2014) study involved a retrospective review (case series) of the medical records of patients under IBD-AID to assess their progress and symptom remission.
Quantitative data were collected from a sample size of 40 patients and included concentration levels of “albumin, hematocrit, C-reactive protein (CRP), and drugs” (Olendziki et al., 2009, p. 8). Two statistical tools, “Harvey Bradshaw Index (HBI) and Modified Truelove and Witts Severity Index (MTLWSI)”, were used to analyze the data.
On their part, Oikonomou et al. (2012) used a randomized controlled trial to investigate the role of neutrophil gelatinase-associated lipocalin (NGAL) in IBD pathophysiology.
The researchers used quantitative approaches to collect and analyze data (NGAL levels) collected from 181 IBD patients and 82 healthy individuals (controls) between 2008 and 2010. The assessment of disease activity (serum NGAL levels) involved Cockroft–Gault and CKD-EPI statistical tools.
Sandhu et al. (2010) conducted a systematic review of a variety of pediatric IBD interventions in studies published in major medical databases. The study involved a review of 161 qualitative and quantitative studies to support treatment guidelines for the management of pediatric IBD in the UK.
The thematic analysis method was used to synthesize the evidence in the studies reviewed. A descriptive study by Todorovic (2010) examined holistic adjunctive interventions (alternative medicine) that can complement conventional therapies in IBD management.
The study relied on qualitative data to develop a framework for assessing the quality of care offered to IBD patients. The sample size for this study was 27 sources.
In contrast, Grunbaum et al. (2013) used a randomized controlled trial to test the correlation between serum vitamin D levels and IBD development. In this quantitative study, the researchers measured serum levels of vitamin D in patients exhibiting mild or inactive IBD, healthy controls, and their families.
The sample size for this study was 103 subjects (patients and controls). Dietary assessment (vitamin D) involved the food frequency questionnaire (FFQ). Watanabe et al. (2010) study was quantitative one, as it involved retrospective data collection from 268 CD patients under an elemental diet.
The researchers used Cox regression analysis to define intergroup correlations, Kaplan-Meier approach to determine non-hospitalization rates, and log-rank test to delimit confidence intervals.
A comparable quantitative study by Yamamoto et al. (2013) investigated the “long-term efficacy of EN” offered post-operatively to IBD patients after surgery. The study involved a sample size of 40 post-operative CD patients (15-75 years) that was given EN for five years.
Recurrence rates were measured using the Kaplan-Meier and log-rank test methods while cross-comparisons involved chi-square and Student’s t test methods.
Rajendran and Kumar’s (2010) study is a systematic review of qualitative and quantitative evidence on the role of dietary therapy on IBD treatment. The search criteria involved specific terms (UC, CD, and IBD as well as dietary therapy) and studies published in English in three medical databases (Medline, Pubmed, and Cochrane).
Ten studies that met the inclusion criteria were included in the final analysis. A more comprehensive systematic review by Yamamoto, Nakahigashi and Saniabadi (2009) included 143 studies (meta-analyses and RCTs) examining the correlation of diet and IBD and published in the Cochrane and Medline databases.
The quantitative data support the use of EN in the treatment of IBD symptoms.
On their part, Bassaganya-Riera and Hontecillas (2010) reviewed current quantitative evidence on the use of conjugated linoleic acid (CLA) and n-3 PUFA as effective anti-inflammatory dietary interventions against IBD. This review analyzed 64 empirical studies that met the inclusion criteria.
Another review article by Hartman, Eliakim, and Shamir (2009) examined 100 studies to compare nutritional therapy modalities (EN and parenteral nutrition) in IBD management in adults and children. The authors used thematic analysis to categorize and synthesize the empirical evidence.
On their part, Mosli et al. (2014) reviewed recent medical advancements used in the management of UC and CD in patients. The authors extracted qualitative data from relevant articles published between 1990 and 2013 from two databases Pubmed and EMBASE.
Descriptive analysis of the data revealed the current IBD assessment tools and therapeutic advances. In contrast, Stulic et al.’s (2013) quantitative study employed a cross-sectional design and a sample size of 134 subjects (UC and CD patients).
The subjects were divided into two categories based on histopathological activity grading. The CD and UC activity evaluation involved the “CD activity index (CDAI) and Truelove and Witt’s scale” respectively (p. 949). Data analysis tools included the Mann-Whitney test and the Z2 test.
Sanchez-Fidalgo, Sanchez de Ibarguen, Cardeno, and Alarcon de la Lastra (2012) randomized 25 mice into two groups: treatment (17 subjects fed with DSS to induce UC) and control (eight healthy ones). The mice were then killed and clinical colitis determined using a disease activity index.
The quantitative data was analyzed using the one way ANOVA method to test for significance and Tukey-Kramer test for cross-comparisons. A nutritional review by Wall, Ross, Fitzgerald, and Stanton (2010) evaluated evidence on the use of dietary omega-3 fatty acids as anti-inflammatory agents.
The review included 117 quantitative studies on the anti-inflammatory potential of polyunsaturated fatty acids (PUFAs). The article uses descriptive statistics to analyze and present the data. In contrast, Sephton’s (2009) study involved a double-blind review approach to evaluate nursing interventions that can prevent flares in IBD.
The review draws qualitative data from a sample of 45 relevant studies, which are analyzed through thematic analysis to provide valuable evidence for innovative nursing interventions that can be applied in IBD management.
Results
The results from the studies reviewed indicate that anti-inflammatory diet can ameliorate IBD management in adults.
The studies report that anti-inflammatory diet has therapeutic benefits, though further testing is required. Wall et al. (2010) found that food supplements containing n-3 fatty acids cause “immunomodulation of the inflammatory profiles” by reducing the concentration of pro-inflammatory cytokines in cells (p. 284).
In contrast, supplements rich in 6-n fatty acids exacerbate IBD symptoms. Thus, a diet rich in n-3 relative to n-6 fatty acids can be a good adjunct in IBD management.
Comparable findings made by Sanchez-Fidalgo et al. (2012) reveal that diets containing extra virgin olive oil fortified with hydroxytyrosol significantly reduce colonic ulcerations in mice exposed to DSS (an inflammation-inducing agent) indicating that the supplement has anti-inflammatory benefits.
In Stulic et al.’s (2013) study, 29% and 64% of patients with a histopathological activity value of below and above five respectively developed CD (p = 0.005). The results of a systematic review give evidence for the use of EN as an adjunct to IBD drug-based treatments (Rajendran & Kumar, 2010).
On the other hand, Hartman, Eliakim, and Shamir (2009) review of relevant literature linked supplementary EN to maintain CD remission while Bassaganya-Riera and Hontecillas (2010) found that an n-3/n-6 fatty acid ratio of more than 0.6 facilitates sustained IBD remission.
Such biomolecules are abundant in conjugated linoleic acid and polyunsaturated fatty acids. Another review by Yamamoto, Nakahigashi, and Saniabadi (2009) found complete EN to be an effective strategy in active and inactive CD management.
In contrast, Yamamoto et al. (2012) found that CD recurred in 10% and 45% of EN and control group patients respectively (p = 0.03).
Moreover, the “cumulative recurrence rate was lower in the EN group compared to the control (p = 0.02)” indicating that the difference between two groups is significant (p. 338). Wanatabe et al. (2010) found that of the 237 patients, 135 (under elemental diet) had a relatively high “cumulative non-hospitalization rate” (p. 135).
Comparable results by Grunbaum et al. (2013) indicate a correlation between patient and family vitamin D levels (82.3 nmol/l) in summer (p = 0.032). By comparison, there was no significant correlation between the control patients and their families.
Two reviews find patient education along with pharmacological methods (Infliximab and Ciclosporin), surgery, and nursing interventions to be effective in self-management of UC (Sephton, 2009; Todorovic, 2012).
On their part, Olendziki et al. (2014) found that in all patients who were under IBD-AID regimen IBD symptoms declined by a mean of 11 HBI and 7 MTLSI values respectively.
Another empirical study by Oikonomou et al. (2012) found “elevated NGAL levels in IBD patients (88.19 ng/ml)” compared to healthy controls (60.06 ng/Mol) (p. 523) implying that the serum NGAL concentrations can predict UC and CD remissions in adults.
In contrast, a review by Sandhu et al. (2010) found evidence to inform guidelines for diagnosis and management of IBD in children.
Discussion
Recent studies suggest a strong association between diet and the modulation of intestinal inflammatory response in IBD. Anti-inflammatory diet (IBD-AID) plays a critical role in symptom remission, which results in reduced pharmaceutical use (Olendziki et al., 2014).
Active factors such as n-3 fatty acids confer IBD-AID with anti-inflammatory characteristics, and thus, the intake of such a diet helps ameliorate IBD symptoms (Wall et al. 2010). Increased intake of n-3 PUFAs increases the levels of two anti-inflammatory eicosanoids: eicosapentaenoic acid and decosahexaenoic acid in inflammatory cells.
The mechanism of action involves an inhibition of n-6 PUFAs (arachidonic acid), which stimulate an inflammatory response in cells (Wall et al., 2010). N-3 PUFAs also act directly by down-regulating eicosanoid processes that produce inflammatory prostaglandins and leukotrienes.
Therefore, a diet high in n-3 fatty acids relative to 6-n PUFAs can reduce inflammatory processes that cause IBD.
Although the etiology of IBD is unclear, the disease tends to have a genetic basis. Grunbaum et al.’s (2013) cross-sectional study found serum levels vitamin D in patients and their families to be higher than in healthy people after a dietary regimen.
However, the concentration of vitamin D in the serum of CD patients (without the regimen) relative to that of healthy individuals is low. They concluded that metabolites of vitamin D play a role in symptom remission for active CD (Grunbaum et al., 2013). Another biomarker of IBD is NGAL, which is released by neutrophils in the blood.
Serum NGAL is higher in patients with IBD than in those with inflammatory bowel syndrome implying that it is can predict the development of the disease (Oikonomou et al., 2012). Thus, serum vitamin D and NGAL levels can be used as biomarkers to monitor IBD progression or symptom remission.
Extraintestinal manifestations, such as pancolitis, are also common indicators of IBD histopathology. Stulic et al. (2013) found that 35.3% of patients diagnosed with pancolitis developed UC symptoms. This indicates that extraintestinal inflammatory conditions can lead to IBD.
With regard to nursing care, the nutritional status of a patient with IBD determines his or her improvement or deterioration. Sephton (2009) recommends that patients with regular ulcerative colitis flare-ups be put under nutritional therapy.
Moreover, a ‘low residue/high protein’ regimen reduces the frequency of bowel movements, which promotes healing in post-surgery patients (Sephton, 2009; Todorovic, 2012). Such a diet complements pharmacological therapy involving inflixmab or ciclosporin.
However, for patients with severe symptoms, immediate corticosteroid therapy or surgery is recommended (Sandhu et al., 2010). Dietary administration of virgin olive oil fortified with a polyphenol called hydroxytyrosol has also been found to stop the progression of experimental colitis in vivo in mice (Sanchez-Fidalgo et al., 2012).
Olive oil diets also prevent cancerous growth associated with inflammation in cells. Sanchez-Fidalgo et al. (2012) attribute the anti-inflammatory effects to the “anti-oxidant properties of the phenolic compounds” in olive oil (p. 502).
The phenolic compounds play a role in antioxidant detoxification of inflammatory agents (reactive oxygen species) that cause cell damage. Hydroxytyrosol prevents oxidation-related damage to cellular macromolecules, including proteins and lipids and thus, inhibit cell inflammation.
The dietary therapy modalities show significant differences in efficacy as adjuncts to pharmacological treatment of CD patients. Evidence from many studies underscores the importance of enteral nutrition (EN) as an effective adjunctive strategy in adult IBD management.
EN promotes the “nutritional status of the patient, reduces inflammatory cytokines in cells, and promotes mucosal healing”, which induce active IBD remission (Hartman, Eliakim & Shamir, 2009, p. 575). The efficacy of EN is attributed to its lack of long-term side effects compared to corticosteroid therapy.
EN is recommended when the adult patients is under prolonged corticosteroid therapy, the risk of developing inflammation-related conditions is high, or the patient needs a change in therapy.
The efficacy of EN versus corticosteroid therapy in IBD treatment is variable among different studies. Yamamoto, Nakahigashi, and Saniabadi’s (2009) review of recent meta-analyses and trials found steroid therapy to be more effective than EN in inducing remission.
However, they note that the studies lack sufficient data to analyze subgroup variables. In addition, the efficacy of EN depends on other extraneous factors such as the ingredients of the enteral formulae, physical assessment criteria, patients’ demographic characteristics, and mode of administration (Yamamoto, Nakahigashi & Saniabadi, 2009).
Nevertheless, in the long-term, EN is more effective than steroid therapy because it has less side effects.
Elemental formulae in EN therapy determine the efficacy of nutritional therapy in IBD management. A comparison of various elemental formulae containing variable levels of proteins established that amino acids do not affect the efficacy of enteral nutrition (Hartman, Eliakim & Shamir, 2009).
On the other hand, diets low in fat have a positive effect on IBD remission due to modulated amounts of linoleic acid.
Conjugated linoleic acid (CLA), an octadecadienoic acid isomer, prevents inflammatory responses through the activation of peroxisome proliferator-activated receptors (PPARs), and thus, reduces the release of “inflammatory lipid mediators” that cause CD (Bassaganya-Riera & Hontecillas, 2010, p. 3).
The effect of food formulae on the efficacy of EN diets has been documented in literature. Long chain triglycerides have less effect on the management of CD compared to fat/protein supplements.
However, the inclusion of bioactive molecules, including glutamine and omega-3 fatty acids, in an EN diet improves its efficacy due to the anti-inflammatory properties of these elements (Hartman, Eliakim & Shamir, 2009). The central aim of IBD-AID diet is to reduce exacerbations and promote symptom remission.
IBD is linked to the alteration of the intestinal microflora, which stimulates an inflammatory response in gut lumen cells (Olendziki et al., 2014). In this regard, EN diets are usually enriched with food components that facilitate the proliferation of normal gut lumen flora.
Olendziki et al. (2014) outline five major ingredients of an effective anti-inflammatory diet. The first component is modified carbohydrates, especially lactose while the second consists of probiotics such as fermented dairy products (yoghurt) and onions. Carbohydrates and probiotics help regenerate flora in the intestines to normal levels.
The third component is fats/lipids such as PUFAs (omega-3) and saturated fatty acids, which have anti-inflammatory properties.
The fourth component involves an appropriate dietary pattern that eliminates food types to which a patient may be intolerant while the fifth entails texture modification through grinding to facilitate absorption. In addition, patients should take vitamins and digestive enzyme supplements to boost their nutritional status.
Besides restoring intestinal flora, IBD-AID also facilitate mucosal regeneration in IBD patients. This dietary regimen provides all the required nutrients in the correct proportions and reduces irritants to obtain remission.
It excludes whole grains contained in the specific carbohydrate diets (SCD) and increases the amount of probiotics to yield a balanced intestinal flora (Hartman, Eliakim & Shamir, 2009).
The IBD-AID regimen reduces saturated fatty acid intake and increases the consumption of PUFAs like omega-3 fatty acids, which are known to possess anti-inflammatory properties (Sanchez-Fidalgo et al., 2012). It also contains fermentable oats, which are a good source of probiotics.
Oats also help regulate the frequency and consistency of the stool. Patients under an IBD-AID that gives 900 kcal per day have a lower rate of hospitalization than those receiving a diet with less caloric content (Watanabe et al., 2010).
This indicates that a diet that gives 900 kcal per day can facilitate healing for patients with ileal lesions. The evidence reviewed in this paper indicates that dietary therapy can serve as an adjunct to pharmacological interventions to promote healing.
Conclusion
As the regular treatments (drugs and surgery) for IBD show variable effectiveness, nutritional therapy provides a novel strategy for the management of the disease.
This literature review has underscored the role of nutrition-based diets, including IBD-AID and supplements such as 3-n PUFAs and NGAL, as adjuncts in the management of gastrointestinal diseases.
Diet composition, mode of administration, and disease assessment criteria are some of the factors that influence the efficacy of nutrition-based therapy.
In general, in compliant patients, an enteral nutrition that balances 3-n/6-n PUFAs intake and gives over 900 kcal per day can reduce exacerbations and promote remission. 3-n PUFAs have anti-oxidant and anti-inflammatory properties, hence useful in IBD management.
Thus, EN presents a safe adjunct to pharmaceutical options, though its clinical efficacy is not clear in the articles reviewed. In this regard, further studies (RCTs) should examine nutrient bioavalability across the intestinal barrier on a particular inflammation site.
The findings would help evaluate and validate the clinical efficacy of various EN formulae. To sum up, in compliant patients, a nutritional management approach involving the patient a primary care provider can extend remission and improve quality of life, reducing acute exacerbations requiring GI or surgical intervention.
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