11.4 Magen-Darmerkrankungen

Bei chronisch entzündlichen Darmerkrankungen findet man in der Lavage des Darmes erhebliche Mengen an Leukotrien. Mehrere Studien und Hunderte von Einzelbeobachtungen konnten inzwischen eine Verbesserung (keine Heilung) der Situation bei einschlägigen Patienten erzielen.

Colitis ulcerosa

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Publikationen

1. Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract.
Pellegrini L, Milano E, Franceschi F, Belcaro G, Gizzi G, Feragalli B, Dugall M, Luzzi R, Togni S, Eggenhoffner R, Giacomelli L

OBJECTIVE: Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome®) in Ulcerative Colitis (UC) during minimally symptomatic remission phase.

PATIENTS AND METHODS: In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome® supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study.

RESULTS: A significant beneficial effect of Casperome® was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome® supplemented patients.

CONCLUSIONS: Our study showed that Casperome® supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome® supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase.

Eur Rev Med Pharmacol Sci. 2016 Jun;20(12):2695-700.
PMID: 27383325 [PubMed - as supplied by publisher]

2. Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn's Disease and Ulcerative Colitis.
Parian A, Limketkai BN

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.

Curr Pharm Des. 2016;22(2):180-8.
PMID: 26561079 [PubMed - as supplied by publisher]

3. Medical Plant Extracts for Treating Knee Osteoarthritis: a Snapshot of Recent Clinical Trials and Their Biological Background.
Walzer SM, Weinmann D, Toegel S

In light of the growing global health problem associated with osteoarthritis, herbal remedies have become an important research focus in the scientific and medical community, and numerous studies have been published to identify their biological effects and mechanisms in vitro and in vivo. This review is a snapshot of the most recent clinical trials on the efficacy of medical plant extracts in knee osteoarthritis patients, and provides relevant background information on the biological mechanisms that may underlie the clinical observations. Therefore, we performed a PubMed literature survey and discussed a selection of clinical trials in the field, with special attention being drawn to the design and outcome measures of the studies. We further spotlighted on issues relating to the efficacy and safety of the plant extracts and discussed major challenges for upcoming studies in the field, which include the need for rigorously designed in vivo and in vitro studies, as well as the elucidation of potential additive effects and structure-modifying activities beyond symptom relief.

Curr Rheumatol Rep. 2015 Aug;17(8):54.
PMID: 26163305 [PubMed - indexed for MEDLINE]

4. Nutraceutical Supplements for Inflammatory Bowel Disease.
Parian AM, Limketkai BN, Shah ND, Mullin GE

Nutr Clin Pract. 2015 Aug;30(4):551-8.
PMID: 26024677 [PubMed - indexed for MEDLINE]

5. Herbal and plant therapy in patients with inflammatory bowel disease.
Triantafyllidi A, Xanthos T, Papalois A, Triantafillidis JK

Ann Gastroenterol. 2015 Apr-Jun;28(2):210-220.
PMID: 25830661 [PubMed - as supplied by publisher]

6. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases.
Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, Korzenik J

OBJECTIVE: We performed a systematic review for Complementary and Alternative Medicine [CAM] as defined by the National Institute of Health in Inflammatory Bowel Disease [IBD], ie Crohn's disease [CD] and ulcerative colitis [UC], with the exception of dietary and nutritional supplements, and manipulative therapies.

METHODS: A computerized search of databases [Cochrane Library, Pubmed/Medline, PsychINFO, and Scopus] through March 2014 was performed. We screened the reference sections of original studies and systematic reviews in English language for CAM in IBD, CD and UC. Randomized controlled trials [RCT] and controlled trials [CT] were referred and assessed using the Cochrane risk of bias tool.

RESULTS: A total of: 26 RCT and 3 CT for herbal medicine, eg aloe-vera gel, andrographis paniculata, artemisia absinthium, barley foodstuff, boswellia serrata, cannabis, curcumin, evening primrose oil, Myrrhinil intest®, plantago ovata, silymarin, sophora, tormentil, wheatgrass-juice and wormwood; 1 RCT for trichuris suis ovata; 7 RCT for mind/body interventions such as lifestyle modification, hypnotherapy, relaxation training and mindfulness; and 2 RCT in acupuncture; were found. Risk of bias was quite heterogeneous. Best evidence was found for herbal therapy, ie plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD.

CONCLUSIONS: Complementary and alternative therapies might be effective for the treatment of inflammatory bowel diseases; however, given the low number of trials and the heterogeneous methodological quality of trials, further in-depth research is necessary.

J Crohns Colitis. 2015 Jan;9(1):86-106.
PMID: 25518050 [PubMed - indexed for MEDLINE]

7. Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine?
Gilardi D, Fiorino G, Genua M, Allocca M, Danese S

The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.

Expert Rev Gastroenterol Hepatol. 2014 Sep;8(7):835-46.
PMID: 24813226 [PubMed - indexed for MEDLINE]

8. Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: a meta-analysis.
Rahimi R, Nikfar S, Abdollahi M

AIM: To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease (IBD) by conducting a meta-analysis.

METHODS: Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD. The search terms were: "herb" or "plant" or "herbal" and "inflammatory bowel disease". Data were collected from 1966 to 2013 (up to Feb). The "clinical response", "clinical remission", "endoscopic response", "endoscopic remission", "histological response", "histological remission", "relapse", "any adverse events", and "serious adverse events" were the key outcomes of interest. We used the Mantel-Haenszel, Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects. For subgroup analyses, we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.

RESULTS: Seven placebo controlled clinical trials met our criteria and were included (474 patients). Comparison of herbal medicine with placebo yielded a significant RR of 2.07 (95%CI: 1.41-3.03, P = 0.0002) for clinical remission; a significant RR of 2.59 (95%CI: 1.24-5.42, P = 0.01) for clinical response; a non-significant RR of 1.33 (95%CI: 0.93-1.9, P = 0.12) for endoscopic remission; a non-significant RR of 1.69 (95%CI: 0.69-5.04) for endoscopic response; a non-significant RR of 0.64 (95%CI: 0.25-1.81) for histological remission; a non-significant RR of 0.86 (95%CI: 0.55-1.55) for histological response; a non-significant RR of 0.95 (95%CI: 0.52-1.73) for relapse; a non-significant RR of 0.89 (95%CI: 0.75-1.06, P = 0.2) for any adverse events; and a non-significant RR of 0.97 (95%CI: 0.37-2.56, P = 0.96) for serious adverse events.

CONCLUSION: The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes, but the number of studies is limited to make a strong conclusion.

World J Gastroenterol. 2013 Sep;19(34):5738-49.
PMID: 24039370 [PubMed - indexed for MEDLINE]

9. Systematic review: the efficacy of herbal therapy in inflammatory bowel disease.
Ng SC, Lam YT, Tsoi KK, Chan FK, Sung JJ, Wu JC

BACKGROUND: Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited.

AIM: To systematically review the literature on the efficacy of herbal therapy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD).

METHODS: Publications in English and non-English literatures (MEDLINE, EMBASE, EBM Reviews, AMED, Global Health) were searched from 1947 to 2013 for controlled clinical studies of herbal therapy in IBD. Outcome measures included response and remission rates.

RESULTS: Twenty-one randomised controlled trials (14 UC; 7 CD) including a total of 1484 subjects (mean age 41, 50% female) were analysed. In UC, aloe vera gel, Triticum aestivum (wheat grass juice), Andrographis paniculata extract (HMPL-004) and topical Xilei-san were superior to placebo in inducing remission or response, and curcumin was superior to placebo in maintaining remission; Boswellia serrata gum resin and Plantago ovata seeds were as effective as mesalazine, whereas Oenothera biennis (evening primrose oil) had similar relapse rates as omega-3 fatty acids in the treatment of UC. In CD, Artemisia absinthium (wormwood) and Tripterygium wilfordii were superior to placebo in inducing remission, and preventing clinical recurrence of post-operative CD respectively.

CONCLUSIONS: Randomised controlled trials of herbal therapy for the treatment of IBD show encouraging results but studies remain limited and heterogenous. Larger controlled studies with stricter endpoints and better-defined patient groups are required to obtain more conclusive results on the use of CAM therapies in IBD.

Aliment Pharmacol Ther. 2013 Oct;38(8):854-63.
PMID: 23981095 [PubMed - indexed for MEDLINE]

10. Randomized, placebo-controlled, double-blind trial of Boswellia serrata in maintaining remission of Crohn's disease: good safety profile but lack of efficacy.
Holtmeier W, Zeuzem S, Preiss J, Kruis W, Böhm S, Maaser C, Raedler A, Schmidt C, Schnitker J, Schwarz J, Zeitz M, Caspary W

BACKGROUND: Complementary therapies are frequently used by patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the efficacy and safety of long-term therapy with a new Boswellia serrata extract (Boswelan, PS0201Bo) in maintaining remission in patients with Crohn's disease (CD).

METHODS: In 22 German centers a double-blind, placebo-controlled, randomized, parallel study was performed. In all, 108 outpatients with CD in clinical remission were included. Patients were randomized to Boswelan (3×2 capsules/day; 400 mg each) or placebo for 52 weeks. The primary endpoint was the proportion of patients in whom remission was maintained throughout the 52 weeks. Secondary endpoints were time to relapse, changes of Crohn's Disease Activity Index (CDAI), and IBD Questionnaire (IBDQ) scores.

RESULTS: The trial was prematurely terminated due to insufficient discrimination of drug and placebo with regard to the primary efficacy endpoint. A total of 82 patients were randomized to Boswelan (n=42) or placebo (n=40). Sixty-six patients could be analyzed for efficacy. 59.9% of the actively treated patients and 55.3% of the placebo group stayed in remission (P=0.85). The mean time to diagnosis of relapse was 171 days for the active group and 185 days for the placebo group (P=0.69). With respect to CDAI, IBDQ, and laboratory measurements of inflammation, no advantages in favor of active treatment were detected. Regarding safety concerns, no disadvantages of taking the drug compared to placebo were observed.

CONCLUSIONS: The trial confirmed good tolerability of a new Boswellia serrata extract, Boswelan, in long-term treatment of CD. However, superiority versus placebo in maintenance therapy of remission could not be demonstrated.

Inflamm Bowel Dis. 2011 Feb;17(2):573-82.
PMID: 20848527 [PubMed - indexed for MEDLINE]

11. Effect of exclusion diet with nutraceutical therapy in juvenile Crohn's disease.
Slonim AE, Grovit M, Bulone L

BACKGROUND: Most moderate-severe juvenile Crohn's disease (CD) patients are in a constant catabolic state resulting in poor weight gain and growth failure. Anti-inflammatory, immunomodulatory, and monoclonal antibody drugs, as well as growth hormone (GH), frequently fail to achieve sustained remission or reverse growth failure.

OBJECTIVE: To test whether an exclusion diet with nutraceutical therapy (DNT) could induce sustained clinical remission and weight gain, and if so does this enhance the ability for GH to reverse growth failure.

METHODS: An uncontrolled prospective case study was undertaken in six moderate- severe CD patients, two of whom had completed growth. All were treated with DNT. Adequate caloric and protein ( >or= 3g/kg/d) intake for catch up weight was prescribed. Dairy products, certain grains and carrageenan containing foods were eliminated. Nutraceuticals, consisting of fish peptides, bovine colostrum, boswellia serrata, curcumin and a multivitamin were administered daily. Lactobacillus GG, a probiotic, was administered twice weekly. Recombinant human GH (rhGH) was administered daily.

RESULTS: Within 2 months of starting DNT all six patients went into remission, with discontinuation of all pharmacological drugs. Three patients have remained in sustained remission for 4 to 8 years. One patient with very severe CD had recurrence of CD symptoms after being in complete remission for 18 months, one patient was in remission for 3 years but symptoms recurred when she became less compliant to DNT and one recently treated patient remains in remission after 6 months. With the addition of rhGH, the 4 growing patients had good-excellent growth response

CONCLUSION: DNT engendered prolonged remission and restoration of normal weight in moderate-severe juvenile CD patients, providing conditions that enabled rhGH to stimulate growth. These findings justify larger controlled trials to evaluate the long-term benefit of compliance to DNT in both juvenile and adult CD patients.

J Am Coll Nutr. 2009 Jun;28(3):277-85.
PMID: 20150601 [PubMed - indexed for MEDLINE]

12. Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial.
Madisch A, Miehlke S, Eichele O, Mrwa J, Bethke B, Kuhlisch E, Bästlein E, Wilhelms G, Morgner A, Wigginghaus B, Stolte M

BACKGROUND AND AIMS: The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis.

MATERIALS AND METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency
RESULTS: Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8-89.1 vs 26.7%, 95%CI, 7.7-55.1; p=0.04; intention-to-treat 43.8% vs 26.7%, p=0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n=1), unwillingness to continue (n=3), or loss to follow-up for unknown reasons (n=1). Seven patients received open-label BSE therapy, five of whom achieved complete remission.

CONCLUSIONS: Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.

Int J Colorectal Dis. 2007 Dec;22(12):1445-51.
PMID: 17764013 [PubMed - indexed for MEDLINE]

13. Use of complementary and alternative medicine in Germany - a survey of patients with inflammatory bowel disease.
Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B

BACKGROUND: Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). The aim of our study was to evaluate the use of CAM in German patients with IBD.

METHODS: A questionnaire was offered to IBD patients participating in patient workshops which were organized by a self-help association, the German Crohn's and Colitis Association. The self-administered questionnaire included demographic and disease-related data as well as items analysing the extent of CAM use and satisfaction with CAM treatment. Seven commonly used CAM methods were predetermined on the questionnaire.

RESULTS: 413 questionnaires were completed and included in the analysis (n = 153 male, n = 260 female; n = 246 Crohn's disease, n = 164 ulcerative colitis). 52 % of the patients reported CAM use in the present or past. In detail, homeopathy (55%), probiotics (43%), classical naturopathy (38%), Boswellia serrata extracts (36%) and acupuncture/Traditional Chinese Medicine (TCM) (33%) were the most frequently used CAM methods. Patients using probiotics, acupuncture and Boswellia serrata extracts (incense) reported more positive therapeutic effects than others. Within the statistical analysis no significant predictors for CAM use were found. 77% of the patients felt insufficiently informed about CAM.

CONCLUSION: The use of CAM in IBD patients is very common in Germany, although a large proportion of patients felt that information about CAM is not sufficient. However, to provide an evidence-based approach more research in this field is desperately needed. Therefore, physicians should increasingly inform IBD patients about benefits and limitations of CAM treatment.

BMC Complement Altern Med. 2006;6(0):19.
PMID: 16716218 [PubMed - indexed for MEDLINE]

14. Effects of gum resin of Boswellia serrata in patients with chronic colitis.
Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, Ammon HP

Patients studied here suffered from chronic colitis characterized by vague lower abdominal pain, bleeding per rectum with diarrhoea and palpable tender descending and sigmoid colon. The inflammatory process in colitis is associated with increased formation of leukotrienes causing chemotaxis, chemokinesis, synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes. The key enzyme for leukotriene biosynthesis is 5-lipoxygenase. Boswellic acids were found to be non-redox, non-competitive specific inhibitors of the enzyme 5-lipoxygenase. We studied the gum resin of Boswellia serrata for the treatment of this disease. Thirty patients, 17 males and 13 females in the age range of 18 to 48 years with chronic colitis were included in this study. Twenty patients were given a preparation of the gum resin of Boswellia serrata (900 mg daily divided in three doses for 6 weeks) and ten patients were given sulfasalazine (3 gm daily divided in three doses for 6 weeks) and served as controls. Out of 20 patients treated with Boswellia gum resin 18 patients showed an improvement in one or more of the parameters: including stool properties, histopathology as well as scanning electron microscopy, besides haemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils. In the control group 6 out of 10 patients showed similar results with the same parameters. Out of 20 patients treated with Boswellia gum resin 14 went into remission while in case of sulfasalazine remission rate was 4 out of 10. In conclusion, this study shows that a gum resin preparation from Boswellia serrata could be effective in the treatment of chronic colitis with minimal side effects.

Planta Med. 2001 Jul;67(5):391-5.
PMID: 11488449 [PubMed - indexed for MEDLINE]

15. [Therapy of active Crohn disease with Boswellia serrata extract H 15].
Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R

BACKGROUND: The purpose of this clinical trial was to compare efficacy and safety of the Boswellia serrata extract H15 with mesalazine for the treatment of active Crohn's disease.

PATIENTS AND METHODS: Randomised, double-blind, verum-controlled, parallel group comparison for which 102 Patients were randomised. The per protocol population included 44 patients treated with H15 and 39 patients treated with mesalazine. As primary outcome measure the change of the Crohn Disease Activity Index (CDAI) between the status of enrolment and end of therapy was chosen. H 15 was tested on non-inferiority compared to standard treatment with mesalazine.

RESULTS: The CDAI between the status of enrolment and end of therapy after treatment with H15 was reduced by 90 and after therapy with mesalazine by 53 scores in the mean. In this non-inferiority-trial the test hypothesis was confirmed by the statistical analysis. The difference between both treatments could not be proven to be statistically significant in favor to H15 for the primary outcome measure. The secondary efficacy endpoints confirm the assessment of the comparison of H15 and mesalazine. The proven tolerability of H15 completes the results of the shown clinical efficacy.

CONCLUSIONS: The study confirms that therapy with H15 is not inferior to mesalazine. This can be interpreted as evidence for the efficacy of H15 according to the state of art in the treatment of active Crohn's disease with Boswellia serrata extract, since the efficacy of mesalazine for this indication has been approved by the health authorities. Considering both safety and efficacy of Boswellia serrata extract H15 it appears to be superior over mesalazine in terms of a benefit-risk-evaluation.

Z Gastroenterol. 2001 Jan;39(1):11-7.
PMID: 11215357 [PubMed - indexed for MEDLINE]

16. Effects of Boswellia serrata gum resin in patients with ulcerative colitis.
Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP

Ulcerative colitis is a chronic inflammatory disease of the colon where leukotrienes are suggested to play an important role for keeping inflammation active. Boswellic acids, the biologically active ingredients of the gum resin of Boswellia serrata (Sallai guggal), have been shown to be specific, nonredox and noncompetitive inhibitors of 5-lipoxygenase, the key enzyme of leukotriene biosynthesis. In patients suffering from ulcerative colitis grade II and III the effect of Boswellia serrata gum resin preparation (350 mg thrice daily for 6 weeks) on stool properties, histolopathology and scan microscopy of rectal biopsies, blood parameters including Hb, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils was studied. Patients receiving sulfasalazine (1 g thrice daily) served as controls. All parameters tested improved after treatment with Boswellia serrata gum resin, the results being similar compared to controls: 82% out of treated patients went into remission; in case of sulfasalazine remission rate was 75%.

Eur J Med Res. 1997 Jan;2(1):37-43.
PMID: 9049593 [PubMed - indexed for MEDLINE]