Complementary, Integrative, and Holistic Medicine: Integrative Approaches to Pediatric Ulcerative Colitis

Twenty-five percent of inflammatory bowel disease (IBD) occurs in childhood, with 2 of 100,000 children age 1 to 17 years diagnosed as having ulcerative colitis (UC) in North America. (1) In a genetically predisposed individual, environmental factors lead to a dysregulated adaptive immune response to luminal commensal bacterial antigens, resulting in IBD. Although diet, infections, medications, and lack of breastfeeding have been implicated, further research is needed to elucidate the complex environmental and genetic interaction producing IBD. (2)(3)(4) Pediatric UC is often more extensive at initial presentation, with a 20% colectomy rate at 1 year in severe disease. (5) The risk of colorectal cancer, a potential long-term complication, is increased in those with a longer duration and earlier age of disease onset and greater extent of inflammation. (6)Conventional treatment of UC includes the use of corticosteroids to induce remission in moderate to severe disease and topical 5-aminosalicylate (5-ASA) as maintenance therapy. Recent prospective data confirmed the steroid-sparing effects of maintenance therapy with the immune-modulating thiopurine drugs 6-mercaptopurine and azathioprine in moderate to severe disease unresponsive to 5-ASA agents. (7) In children in whom conventional therapy fails, infliximab, a monoclonal antibody directed against tumor necrosis factor α, has been effective. (8) Despite evidence of benefit, the risk of infection and malignancy affect acceptance of administering these immune-modifying agents.The incidence of complementary and alternative medicine (CAM) use in pediatric IBD patients ranges from 40% to 70%. (9)(10)(11)(12) The common reason for using CAM is concern about adverse effects and the lack of efficacy of conventional therapies. Use of CAM was increased, particularly in patients with worse quality of life (QoL). (11)(13) This article reviews the evidence for CAM therapy in UC as drawn from adult and pediatric data available in the English language.Diets such as the specific carbohydrate diet, elimination diets, low-sulfur diets, and Ayurvedic diets (based on Ayurveda, a system of traditional Indian medicine) are anecdotally purported to be beneficial but lack evidence; therefore, further study is needed. Until then, it is important to enforce the basic principles of a healthy diet low in saturated fats and sugar for children with UC. In a stable patient, if the family wishes to try dietary manipulation, it can be allowed by the health care team if it is deemed to be nutritionally safe.The current Western diet contains a growing proportion of omega-6 fatty acids, which are metabolized into proinflammatory cytokines thought to increase the risk of developing IBD. (14) Fish oil and other sources of omega-3 fatty acids have been theorized to be effective in IBD therapy because of their inhibitory effect on the cyclooxygenase pathway. (15) However, 2 recent Cochrane reviews reported the lack of sufficient data to support the use of fish oil for the induction and maintenance of remission in UC. (16)(17) Interpretation of the currently available studies can be challenging because most are small; use different formulations, dosages, and routes of administration; and have varying designs and end points. Also, in some studies, the placebo oils used, such as sunflower and olive oil, may have active anti-inflammatory effects. (18) These limitations may account for lack of clinical efficacy in studies despite biological plausibility. The 2007 Cochrane review on fish oil for maintenance of remission included 3 studies in which patients were followed up for 1 to 2 years using non–enteric-coated preparations. (16) None of the studies were able to demonstrate a significant difference in time to relapse of disease. (19)(20)(21) Dietary manipulation of fatty acids may help to decrease inflammation and maintain remission in UC, but further investigation is needed to make specific type and dose recommendations.Probiotic use is popular, with a mean of 40% of pediatric patients with IBD having tried a probiotic preparation. (9)(10)(11)(12)(22) Although more promising than in Crohn disease, the evidence of clinical efficacy of probiotics for UC is modest, in part because of heterogeneity among trials. Since 1999, eight randomized controlled trials have been published on probiotic use for active disease using varying doses and strains, including Escherichia coli Nissle 1917 (ECN), VSL#3 (a highly concentrated blend of 8 strains, mostly lactobacilli and bifidobacteria), a symbiotic combination of Bifidobacterium longum, and a prebiotic combination of inulin and fructo-oligosaccarides. (23)(24)(25)(26)(27)(28)(29)(30) Most studies found decreased disease activity in the probiotic group but were unable to find differences in remission rates. (24)(26)(27)(29)(30) However, significantly higher remission rates (92.8% vs 36.4%, P<.001) were found in the pediatric study of 29 children with newly diagnosed UC that used VSL#3 (28) vs placebo, with both groups taking steroids and mesalamine as well. One open-label, pilot study of children with mild to moderate active UC concluded that adding VSL#3 to their current regimen resulted in a 56% remission rate. (31) A few studies are available using probiotics to maintain UC in remission, mostly ECN compared with 5-ASA, with the data indicating equivalent rates of relapse and safety. (24)(32)(33) A single, open-label, pediatric, pilot study of children 11 to 18 years old is available using 5 × 1010 CFU ECN vs 5-ASA, with no other agents, for remission of UC, also indicating equivalent relapse rates at 1 year. (34) In the pediatric VSL#3 trial, 3 of 14 patients (21.4%) maintained with probiotics and 5-ASA experienced a relapse at 1 year vs 11 of 15 patients (73.3%) maintained with 5-ASA alone (P=.01). (28)Probiotics have also been studied for use after colectomy and ileo-pouch anal anastomosis for the prevention and management of recurrent pouchitis. A randomized, double-blinded, placebo-controlled trial using VSL#3 found benefit in the prevention of the initial episode of pouchitis after surgery. (35)(36) The data also suggested a role for VSL#3 after antibiotic therapy in preventing future episodes of pouchitis in patients with recurrent disease. (37)(38)The available evidence supports the use of probiotics, particularly ECN and VSL#3, to maintain remission for mild to moderate UC and pouchitis management. Studies on the potential beneficial effects of prebiotics and synbiotics in UC are ongoing.Aloe vera is a succulent plant in the lily family used medicinally for more than 5,000 years. Aloe contains multiple biologically active substances that have been promoted to have anti-inflammatory, antioxidant, and immune stimulatory properties. (39) In 2004, Langmead et al (40) published an in vitro study and a randomized, double-blind, placebo-controlled, in vivo study on oral aloe vera gel for active UC. The in vitro study demonstrated antioxidant properties. Subsequently, 44 adult patients with mild to moderately active UC taking stable doses of their maintenance medications were randomized to oral aloe gel twice a day or placebo. After 4 weeks the aloe group experienced symptomatic clinical response with a significant decrease in histologic disease activity, more than the placebo group, but remission rates were not significantly different. A larger study of longer intervention might clarify whether there is a role for aloe vera gel use in UC.Ayurveda, a 5,000-year-old whole system of medicine with its roots in India, has advocated turmeric, frankincense, and fenugreek for UC. Curcumin, the active compound in turmeric (Curcuma longa), has anti-inflammatory properties. (41) In 2006, Hanai et al. (42) randomized 89 patients in remission to curcumin, 1 g twice daily, with 5-ASA or placebo and 5-ASA. At 6 months, the curcumin group had a lower but not significant recurrence rate (P=.40) and decreased clinical (P=.038) and endoscopic scores (P=.0001). However, the difference in recurrence rates was not maintained at 12-month follow-up (P=.433). Frankincense (Boswellia serrata) has antioxidant and anti-inflammatory properties, inhibiting nuclear factor–κβ and cytokines, including tumor necrosis factor α. (43) One open-label, nonrandomized, exploratory study of 42 patients, 11 to 70 years old, with active UC were given 350 mg of Boswellia 3 times a day or 3 g of 5-ASA, with preliminary data suggesting Boswellia was not inferior to sulfasalazine. (44) Fenugreek (Trigonellum foenum gracum) seeds, which are rich in galactomannan and antioxidants, are also popularly used in Ayurvedic medicine; however, there are no in vivo studies to date. (45)Tormentil (Potentilla tormentilla) is a member of the rose family native to Europe with a high tannin concentration and has been used as a complementary therapy for patients with IBD. In vitro data have found antioxidant properties, and a phase 1 open-label trial recently demonstrated safety up to doses of 3,000 mg/d. (45)(46) Preliminary studies of herbal medicine for UC suggest the potential for benefit, but randomized controlled trials are needed.Acupuncture is thought to act on many different mediators in the inflammatory cascade. (47) It also affects motility and secretion via opioid and neural pathways. There is one randomized, controlled, pilot study in adults in which acupuncture and moxibustion were used for the treatment of active mild to moderate UC in addition to stable standard therapy. (48) After the initial 5 sessions, the acupuncture group had a significant decrease in disease activity compared with the sham acupuncture group (P=0.048), although not at 16 weeks of follow-up (P=0.390). The QoL also increased in both groups, although there was no statistically notable difference between groups.Stress has been found to alter gut permeability and cause the release of neuropeptides that have immune modulatory effects. (49) Several prospective studies have revealed a positive association between stress and IBD flares, particularly the perception of stressful events, as opposed to discrete events. (49) Unpredictable and potentially embarrassing symptoms of IBD add to the stress and challenges of adolescence. The incidence of psychiatric disorders in children with IBD is increased compared with those in healthy children and is comparable to the incidence in children with other chronic diseases, such as cystic fibrosis. (50) Biobehavioral CAM techniques, such as relaxation, meditation, and prayer, are popular and are used by adolescents with IBD, especially those with more severe disease. (13) Various strategies have been tried to improve QoL and psychosocial functioning in pediatric patients with IBD, such as a prospective analysis of children attending a 1-week camp sponsored by the Crohn’s and Colitis Foundation of America, (51) cognitive behavioral therapy, (52) and a psychological program that included relaxation, imagery, and deep breathing as part of an overall cognitive behavioral therapy program. (53) In addition, there is a potential role for “gut-focused hypnotherapy.” The authors of a small study performed in the United Kingdom in 2008 demonstrated a reduction of corticosteroid requirements after 12 sessions of gut-focused hypnotherapy. (54) Significant adult and pediatric research has been performed in the therapeutic applications of yoga to prevent and treat medical conditions. (55)(56) Yoga has been found to decrease functional disability and anxiety in children with irritable bowel syndrome. (57) Yoga may be helpful for similar reasons as stated above for IBD, but further studies are needed.Although the use of CAM in pediatric UC is common, quality evidence-based research is lacking. There is clearly a need for further randomized controlled trials. The available evidence supports the use of probiotics to maintain remission for mild to moderate UC and recurrent pouchitis management. The role of psychosocial distress in children with UC should not be overlooked, and thus biobehavioral techniques should be considered and incorporated when possible. Although no CAM approach is effective as monotherapy, when caring for those afflicted with this chronic disease, all health care professionals should partner with their patients and ask about CAM use, as well as maintain an awareness of efficacy, safety, harm, drug-supplement interactions, and appropriate referral sources.Note: To view the references for this article, visit the September issue at http://pedsinreview.aappublications.org and click on the “Complementary, Integrative, and Holistic Medicine” article.