WHMC311. Session 4. Gastrointestinal & Alimentary Disease Part IV. Naturopathic Medicine Department

Transcription

1 WHMC311 Session 4 Gastrointestinal & Alimentary Disease Part IV Naturopathic Medicine Department 1 Endeavour College of Natural Health endeavour.edu.au 1

2 Topic Overview o Management of complex and multi-system conditions through the use of specific herbal medicines and their specific biochemical and physiological applications in the management of complex GIT complaints; irritable bowel syndrome, inflammatory bowel disease and coeliac disease. o Focus on the herbal support and modulation of these conditions drawing on relevant literature. o Discuss relevant drug interactions and potentiations. 2 Endeavour College of Natural Health endeavour.edu.au 2

3 Irritable Bowel Syndrome 3 Endeavour College of Natural Health endeavour.edu.au 3

4 Irritable Bowel Syndrome o Irritable bowel syndrome is a functional gastrointestinal disorder characterised by altered bowel habit and abdominal pain (Hawrelak 2014, p.73) o It is a chronic disorder of unclear aetiology (Hawrelak 2014, p.73) o IBS is not related to inflammatory bowel diseases, such as Crohn s disease or ulcerative colitis (Kumar & Clark, 2005) o Possible aetiological factors: enhanced visceral perception, low grade inflammation, altered GIT motility, and microflora (Hawrelak 2014, p.73) 4 Endeavour College of Natural Health endeavour.edu.au 4

5 Diagnostic Criteria o Diagnostic Criteria (Rome IV) o Recurrent abdominal pain at least 1 day/week, on average in the past 3 months associated with two or more of the following: on defecation with change in frequency of stool associated with a change in form of stool. o Symptom onset should occur at least 6 months prior to diagnosis and symptoms should be present during past 3 months (Rome Foundation, 2016) Endeavour College of Natural Health endeavour.edu.au 5

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7 Diagnostic Criteria Sub-classification of IBS Symptoms can be classified into: abnormal frequency = >3/day and <3/week abnormal form lumpy/hard of loose/watery abnormal stool passage (straining, urgency, tenesmus) Mucous Bloating or distension. This highlights the type of IBS i.e. Diarrhoea or constipation predominant IBS. (Kumar & Clark, 2005) 7 Endeavour College of Natural Health endeavour.edu.au 7

8 Clinical Presentation o Symptoms include: Frequent swings in bowel function Nausea Bloating Intermittent abdominal pain. (Kumar & Clark, 2005) o People with IBS are more likely than others to have backache, fatigue, and several other seemingly unrelated problems. 8 Endeavour College of Natural Health endeavour.edu.au 8

9 Pharmaceutical Management o Though no prescription medications specifically treat irritable bowel syndrome, antidepressant and antianxiety drugs may be used for people with mental depression or chronic pain, or for people who have symptoms that worsen during periods of stress. o Symptomatic treatment (antispasmodics, laxatives for constipation, antidiarrhoeal products etc.) (Health Notes 2009) 9 Endeavour College of Natural Health endeavour.edu.au 9

10 Pharmaceutical Management Anti-spasmodics Mebeverine o Is a local anaesthetic and has an anti-muscarinic effect on the smooth muscle of the GIT. Side Effects o GIT upsets, dizziness, insomnia, anorexia and headache (Bullock et al, 2010, Kumar & Clark, 2005) 10 Endeavour College of Natural Health endeavour.edu.au 10

11 Pharmaceutical Management Opioid Anti-diarrhoeal Loperamide o Stimulate opioid receptors on the wall of the GIT to reduce peristalsis. This allows greater time for reabsorption of water and electrolytes. Side Effects o Well tolerated but can only be used for short term. o Potential to exacerbate constipation (Bryant & Knights, 2011; Kumar & Clark, 2005) 11 Endeavour College of Natural Health endeavour.edu.au 11

12 Pharmaceutical Management Anti-emetic Dopamine Antagonists Domperidone, Droperidol, Haloperidol, Metoclopramide, Prochlorperazine o D2 receptor antagonist and have an affinity for serotonin receptors in the pharynx and upper gut allowing increased gastric emptying Side effects o Potential for increased prolactin levels due to dopamine antagonism & anti-muscarinic effects such as dry mouth, constipation, blurred vision. (Bryant & Knights, 2011; Bullock et al, 2010) 12 Endeavour College of Natural Health endeavour.edu.au 12

13 Pharmaceutical Management Stimulant Laxatives Bisacodyl, sodium picosulfate, senna o Block waster absorption to increase faecal mass & increase electrolyte concentration to increase peristalsis. Side Effects o Cramping, imbalances in fluid & electrolytes o Bisacodyl stimulates peristalsis on contact with mucous membranes so should always be administered in an enteric coated preparation o All take 6-12hrs for onset of action & are only recommended for short term use (Bryant & Knights, 2011; Kumar & Clark, 2005) 13 Endeavour College of Natural Health endeavour.edu.au 13

14 Pharmaceutical Management Anti-depressants Clomipramine (TCA) - Specific affinity for diarrhoea-predominant IBS (Kumar & Clark, 2005, p.339) Side Effects Anticholinergic effects, sedating, orthostatic hypotension & weight gain Paroxitine (SSRI) - Specific affinity for constipation-predominant IBS (Kumar & Clark, 2005, p.339) Side Effects Insomnia / agitation, gastro-intestinal distress & mild weight gain (Bryant & Knights, 2011) 14 Endeavour College of Natural Health endeavour.edu.au 14

15 Serotonin: A Mediator of the Brain Gut Connection? o SSRI s are frequently used in the treatment of irritable bowel syndrome (IBS), although evidence of their efficacy is scarce. o If it is accepted that Hypericum has a serotonin elevating action then is there a potential for incorporating Hypericum into the herbal treatment regime for IBS 15 Endeavour College of Natural Health endeavour.edu.au 15

16 Information Gathering o Confirm diagnosis Rome 3 criteria, determine subtype (diarrhoea or Constipation predominant, mixed bowel or unsubtyped) investigations o Determine contributing factors Dysbiosis, low grade GIT inflammation, stress, depression/anxiety, liver sluggishness, adverse food reactions o Treatment plan Manage GI symptoms, optimise GIT flora, reduce inflammation, support NS, Improve liver function, manage food reactions (Hawrelak, 2014, p.90) Endeavour College of Natural Health endeavour.edu.au 16

17 Treatment Aims o Treat the individual as symptoms vary considerably o Optimise GIT microflora o Support the nervous system o Promote normalisation of bowel patterns o Manage GIT symptoms o Decease guy inflammation and diminish visceral hypersensitivity o Support liver function o Manage adverse food reactions (Hawrelak, 2014, p.76) Endeavour College of Natural Health endeavour.edu.au 17

18 Treatment Considerations o Spasmolytic herbs Viburnum opulus Dioscorea villosa Matricaria chamomilla (also mild sedative) Mentha piperita o Sedative and nervine tonics Hypericum perforatum Scutellaria lateriflora Valeriana officinalis (Mills & Bone, 2013, p ) 18 Endeavour College of Natural Health endeavour.edu.au 18

19 Treatment Considerations o Pain Management Corydalis ambigua and Zingiber off. may have a role in some patients through a modification of the perception of visceral organ pain. o Hepatorestoratives & choleretics to improve liver function Silybum marianum (St Mary s) Chionanthus virginicus (Fringe tree) Schisandra chinensis (Schisandra) o Mucilage-containing herbs Ulmus fulva (Slippery elm), especially if there is constipation. (Mills & Bone, 2013, p ) 19 Endeavour College of Natural Health endeavour.edu.au 19

20 Treatment Considerations o GIT antiseptics to restore normal bowel flora Hydrastis canadensis (Golden seal) Citrus paradisi (Citrus seed extract) Allium sativum (Garlic) (IBS patients may be intolerant of Garlic) (Mills & Bone, 2013, p ) o Consider herbs high in FOS Ulmus fulva (Slippery Elm) (BHP specific (BHMP, 1983) Cynara scolymus (Globe artichoke) 20 Endeavour College of Natural Health endeavour.edu.au 20

21 Treatment Considerations o The presence of mucus implies irritation therefore consider GIT anti-inflammatories Filipendula ulmaria (Meadowsweet) Matricaria chamomilla (German chamomile) o Constipation should be treated with gentle herbs Rumex crispus (Yellowdock) Juglans nigra (Black walnut) Taraxacum officinale (Dandelion) (Bone & Mills 2013, p ) 21 Endeavour College of Natural Health endeavour.edu.au 21

22 Iberogast o Contains: Iberis amara (bitter candytuff), Angelica archangelica, Silybum marianum, Carum carvi, Chelidonium majus, Glycyrrhiza glabra, Matricaria recutita, Melissa officinalis, Mentha x piperita o Systematic review showed significant reduction in GI symptom scores without significant CNS effects (Saller et al, 2002) Endeavour College of Natural Health endeavour.edu.au 22

23 Iberogast o Double-blind, placebo-controlled, multi-centre trial, 203 patients. o STW 5 and STW 5-II were significantly better than placebo in reducing the total abdominal pain score (intention-to-treat: STW 5, P = ; STW 5-II, P = ) and the irritable bowel syndrome symptom score (intention-to-treat: STW 5, P = 0.001; STW 5-II, P = ) at 4 weeks o The commercially available herbal preparation STW 5 and its research preparation STW 5-II are both effective in alleviating irritable bowel syndrome symptoms. (Madisch et al, 2004) 23 Endeavour College of Natural Health endeavour.edu.au 23

24 Drug-Herb Interactions Loperamide Hypericum perforatum, Valerian off o Potential MAO-inhibitor reaction theorized, possibly in conjunction with loperamide-induced delirum as reason for hospitalisation of a woman (Brinker 2010, p.329) 24 Endeavour College of Natural Health endeavour.edu.au 24

25 Drug-Herb Interactions Anti-emetic Dopamine Antagonists o Haloperidol Ginkgo biloba (reduce drug side effects with an increase in drug efficacy) o Anti-emetics Piper methysticum (Kava) (reports of decreases and increases in side effects, co-administration is not advised) (Stargrove et al. 2008) o Any dopamine antagonists may be weakened by Vitex agnus castus (chaste tree) due to dopaminergic effects (Brinker 2010, p.97) 25 Endeavour College of Natural Health endeavour.edu.au 25

26 Anti-depressants Drug-Herb Interactions o Clomipramine (TCA) Andrographis paniculata (may reduce side effects, beneficial) Hypericum perforatum (additive effect, avoid unless under medical supervision) Silybum marianum (reduce side effects, beneficial) o Paroxitine (SSRI) Albizia lebbek (additive effect, observe) Ginkgo biloba (reduce side effects, beneficial) Lavender off. (additive effect, observe, beneficial possible) Hypericum perforatum (additive effect, avoid unless under medical supervision) (Braun & Cohen, 2010, p ) 26 Endeavour College of Natural Health endeavour.edu.au 26

27 Inflammatory Bowel Disease 27 Endeavour College of Natural Health endeavour.edu.au 27

28 Inflammatory Bowel Disease o Inflammatory bowel disease (IBD) refers to chronic disorders of the small and/or large intestine characterised by inflammatory changes in the intestinal tissue. o Instigating agent is linked to an immune inflammatory response due to microbial invasion, trauma, toxic agents or an auto immune response. This sets up a highly inflammatory response that is sustained that leads to strong tissue destruction (Coulson et.al. 2001) o The two major types of inflammatory bowel disease Crohn s disease Ulcerative colitis 28 Endeavour College of Natural Health endeavour.edu.au 28

29 Clinical Presentation o Pain o Nutrient deficiencies o Weight loss & failure to thrive o GI upset o Diarrhoea o Potential for joint & skin problems o Potential for colon cancer (Coulson et.al. 2001) 29 Endeavour College of Natural Health endeavour.edu.au 29

30 Crohn s Crohn s disease is a poorly understood inflammatory condition that usually affects the final part of the small intestine and the beginning section of the colon. Signs & symptoms o Malabsorption issues are magnified in Crohn s. o Abdominal pain. o Bloody stools may present. o Scarring & thickening of the mucosa this can lead to strictures, obstruction, abscesses and fistula formation. (Coulson et.al. 2001) 30 Endeavour College of Natural Health endeavour.edu.au 30

31 Ulcerative Colitis Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, which is relatively common but remains poorly understood. Signs & Symptoms characteristic to UC include: o Only present in the colon & affecting the mucosa. o Surgical resection of the large intestine can remove the disease. o Gastrointestinal bleeding (Coulson et.al. 2001) 31 Endeavour College of Natural Health endeavour.edu.au 31

32 Crohn s v s Ulcerative Colitis Pathophysiology in Crohn's disease vs. ulcerative colitis Autoimmune disease Crohn's Disease Widely regarded as an autoimmune disease Ulcerative Colitis No consensus Cytokine response Associated with Th17[5] Vaguely associated with Th2 Symptoms Crohn's Disease Ulcerative Colitis Defaecation Often porridge-like, sometimes steatorrhoea Often mucus-like and with blood Tenesmus Less common More common Fever Common Indicates severe disease Fistulae Common Seldom Weight loss Often More seldom (Halfvarsson, 2010) Endeavour College of Natural Health endeavour.edu.au 32

33 Crohn s v s Ulcerative Colitis Sign Crohn's Disease Ulcerative Colitis Terminal ileum involvement Commonly Seldom Colon involvement Usually Always Rectum involvement Seldom Usually Involvement around the anus Bile duct involvement Distribution of Disease Endoscopy Commonly No increase in rate of primary sclerosing cholangitis Patchy areas of inflammation (Skip lesions) Deep geographic and serpiginous (snake-like) ulcers Seldom Higher rate Continuous area of inflammation Continuous ulcer (Halfvarsson, 2010) Endeavour College of Natural Health endeavour.edu.au 33

34 Pharmaceutical Management 5-Aminosalicylic Acid - sulfazaline Mode of Action o Pro-drug that is retains a local prostaglandin inhibitor action in the colon. Side Effects o Nausea, abdominal pain, diarrhoea o Headache o Rash (Bullock, et.al, 2010; Bryant & Knights, 2011; Coulson et.al. 2001; Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 34

35 Pharmaceutical Management Corticosteroids Prednisolone, Budesonide Mode of Action o Anti-inflammatory agents that act similarly to endogenous cortisol. Side Effects o Sodium retention (potassium loss) with increases in blood pressure, fluid retention o Protein losses (thinning skin, hair, reduced wound healing, immune dysregulation) o Adrenal atrophy o Bone thinning (Bullock, et.al, 2010; Bryant & Knights, 2011; Coulson et.al. 2001; Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 35

36 Pharmaceutical Management Cyto-toxic Immuno-supressants azathioprine, methotrexate, cyclosporine Mode of Action o Inhibits cell replication & is utilized in this instance to reduce immune system responsiveness Side Effects o Bone marrow suppression & immunosuppression o Hair loss o GIT complaints nausea, vomiting, ulcers, bleeding (Bullock, et.al, 2010;Bryant & Knights, 2007;Coulson et.al. 2001;Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 36

37 Pharmaceutical Management Other drug classes utilised include: Anti-diarrhoeals (diphenoxylate, loperamide) o Used to reduce diarrhoea to sustain hydration and nutrient losses. Broad spectrum antibiotics (metronidazole) o Used when infection of abscesses and fistulas present (Coulson et.al. 2001;Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 37

38 Treatment Aims o Appropriate symptom management o Reduce pain and inflammation o Regulate immune system and heal damaged tissue o Treat underlying factors such as nervous system stress Endeavour College of Natural Health endeavour.edu.au 38

39 Mucilages Treatment Considerations o Althaea officinalis (Marshmallow) o Ulmus fulva (Slippery Elm), Linum usitatissimum (Linseed), Plantago psyllium (Psyllium) Anti-Inflammatories for GIT o Filipendula ulmaria (Meadowsweet) o Glycyrrhiza glabra (Licorice) o Matricaria chamomilla (Chamomile) Mucous membrane trophorestorative o Hydrastis canadensis (Goldenseal) (Mills & Bone, 2013, p ) Endeavour College of Natural Health endeavour.edu.au 39

40 Boswellia serrata o Boswellia extract (350 mg three times daily) was compared to sulfasalazine (1 g three times daily) in ulcerative colitis patients. o Patients on the Boswellia extract showed better improvements than patients on sulfasalazine o 82 percent of Boswellia patients went into remission compared with 75 percent on sulfasalazine (Gupta et al 1997) Endeavour College of Natural Health endeavour.edu.au 40

41 Herb-Drug Interaction Corticosteroids o Herbs with may enhance effects: Aloe vera, Ribes nigrum, Borago officinalis, Ananus comosus, Capsium spp., Glycyrrhiza glabra, Tripterygium wilfordii, Curcuma longa, Artemisia absinthium, yucca spp. (Brinker 2010, p.493) Endeavour College of Natural Health endeavour.edu.au 41

42 Corticosteroids Herb-Drug Interaction Glycyrrhiza glabra (licorice) Beneficial interaction possible under medical supervision; glycyrrhizin potentiates corticosteroids (Braun & Cohen, 2010, p.657) Aloe vera Water extract reduce PGE2 synthesis and may have contributed to extensive bleeding in surgical removal of a large hemangioma in one case (Brinker 2010, pp.36-37) Tabebuia avellanedae (Pau D Arco) Due to use in immunodeficiences concern has been expressed about potential to offset or minimise effects of corticosteroids (Brinker 2010, p. 260) Endeavour College of Natural Health endeavour.edu.au 42

43 Corticosteroids Herb-Drug Interaction Astragalus membranaceus, Echinacea spp. May offset or minimise the immunosuppresive effects (Brinker 2010, pp.52, 131) Rhamnus catharticus, Frangula purshiana, Rheum off, Rhamnus frangula May cause potassium loss and hypokalemia when taken together (Brinker 2010, pp.79, 85, 100, 157) Cassia spp. Laxative activity can aggravate loss of potassium associated with corticosteroids (Brinker 2010, p.285) Nigella sativa May potentially be complemented (Brinker 2010, p.485) Endeavour College of Natural Health endeavour.edu.au 43

44 o Cyclosporin Herb-Drug Interaction Scutellaria baicalensis (Baical skullcap - reduced drug effect, avoid) Mentha piperita (Peppermint oil - additive effects, avoid use unless under medical supervision) Echinacea spp. (decreased drug effects, exercise caution) Hydrastis canadensis (Goldenseal - increase drug effects, exercise caution) Hypericum perforatum (St John s wort - reduced drug effects, avoid) Silybum marianum (St Mary s thistle - reduced drug side effects but possible increase of drug effects, exercise caution) (Braun & Cohen, 2010, p.657) Endeavour College of Natural Health endeavour.edu.au 44

45 Coeliac Disease Endeavour College of Natural Health endeavour.edu.au 45

46 Coeliac Disease o Hyperactive immune responses due to incompatibility with antigenic stimulus causing chronic intestinal malabsorption. o Alpha-gliadin polypeptide derivative of gluten present in: Wheat Rye (secalin) Barley (hordein) Oats (avenin) (Kumar & Clark, 2009;Mahan & Escott-Stump, 2008) Endeavour College of Natural Health endeavour.edu.au 46

47 Clinical Presentation o Diarrhoea o Fatigue o Weight loss (failure to thrive) o Malabsorption symptoms: undigested food in stools, pale stools, bulky floating stools, anaemia o Intestinal dysbiotic diseases o Autoimmune disorders o Dermatitis herpetiformis (intense itchiness), Eczema (Duggan, 2004;Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 47

48 Pharmaceutical Management Drugs classes utilised to stabilise Coeliac disease include: Corticosteroids Prednisolone, Budesonide o Work similarly to endogenous cortisol to reduce inflammation. Cytotoxic immunosupressants azathioprine, methotrexate, cyclosporine o Reduce immune system cell replication to reduce the production of pro-inflammatory cytokines linked to colon mucosa destruction. (Bullock, et.al, 2010; Bryant & Knights, 2011; Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 48

49 Treatment Considerations o Symptomatic relief, consider: Anti-inflammatory Immune modulation Mucous membrane trophorestorative Nervines, adaptogen, sedative/hypnotic Spasmolytic, carminatives o Consider: Spasmolytics: Matricaria chamomilla (Chamomile); Viburnum opulus (Cramp Bark); Mentha piperita (Peppermint) Sedatives/nervines: Scutellaria lateriflora (Skullcap) and Valeriana off. (Mills & Bone 2000 p ) Endeavour College of Natural Health endeavour.edu.au 49

50 Pre-reading for next session o Reading 1: St Mary s Thistle Braun, L Cohen, M Herbs and Natural Supplements: An evidence based guide. o Reading 2: Gao, J Sun, CR Yang, JH Shi, JM Du, YG Zhang, YY Li, JH & Wan, HT 2011, Evaluation of the hepatoprotective and antioxidant activities of Rubus parvifolius L. Journal of Zhejiang University of Science B, vol. 12, no. 2, pp d o Reading 3: Gutiérrez, R Alvarado, JL Presno, M Pérez-Veyna, O Serrano, CJ & Yahuaca, P 2009, Oxidative Stress Modulation by Rosmarinus officinalis in CCl4-induced Liver Cirrhosis Phytotherapy Research, vol. 24, no. 4, pp s_personales/17478gutierrez2009.pdf 50 Endeavour College of Natural Health endeavour.edu.au 50

51 References Alun Jones, V McLaughlan, P Shorthouse, M et al 1982, Food intolerance: A major factor in the pathogenesis of irritable bowel syndrome, Lancet, pp Bagchi, D Garg, A Krohn, R Bagchi, M Tran, M Stohs, S 1997, Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro, Research Communications in Molecular Pathology and Pharmacology, vol.95, no.2, pp Banerjee, B Bagchi, D 2001, Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis, Digestion, vol.63, no.3, pp Better Health Channel, 2009, Coeliac Disease viewed 1/12/10 Bharucha, A 2007, Irritable Bowel Syndrome, Merck manuals online, viewed 8/11/10 Blumenthal, M Goldberg, A Gruenwald, J Hall, T Klein, Riggins, C Rister, R 1998, The complete German Commission E Monographs, American Botanical Council, Austin, Texas Bone, K Mills, S 2013, Principle and Practice of Phytotherapy: A Modern Herbal Medicine, 2 nd Edn, Churchill Livingstone, Edinburgh Braun, L & Cohen, M 2010, Herbs and Natural Supplements: An evidence-based guide. 3rd edn, Churchill Livingstone Elsevier, Australia Braun, L Cohen, M 2005, Herbs and Natural Supplements: An evidence-based guide. 2nd edn, Churchill Livingstone Elsevier, Australia. British Herbal Medicine Association, 1983, British Herbal Pharmacopoeia, BHMA, UK Bryant, B & Knights, K 2011, Pharmacology for health professionals 3rd edn, Elsevier, NSW. Bullock, S Manias, E & Galbraith, A 2010, Fundamentals of pharmacology, 6th edn, Pearson, NSW. Endeavour College of Natural Health endeavour.edu.au 51

52 References Chainman-Wu, N 2003, Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). Journal of alternative complementary medicine. Vol. 9, No.1, p Chen, W Li, D Cannan, R Stubbs, R 2003, Common presence of Helicobacter DNA in the gallbladder of patients with gallstone diseases and controls, Digestive and Liver Disease, vol.35, no.4, pp Coulston, A Rock, C & Monsen, E 2001, Nutrition in the prevention and treatment of disease, Elsevier, San Diego, viewed 04/11/10: ebook ISBN: Drossman, D 2006, The Launching of Rome III, Rome Foundation Duggan, J 2004, Coeliac disease: the great imitator, Medical journal of Australia, Vol.180, No.10. pp Gardner, T & Berk, B 2010, Pancreatitis acute: treatments and medications, Emedicine, Viewed 20/09/2010: Groff, J Groppe,r S 2000, Advanced Nutrition and Human Nutrition 3rd edn, Wadsworth, Australia Gupta I, Parihar A, Malhotra P, et al Effects of Boswellia serrata gum resin in patients with ulcerative colitis. European Journal of Medical Research, Vol 2, pp Halfvarsson, J 2010, Inflammatory Bowel Disease, Chronic, Internet medicine Sweden, viewed 6/ &layout=2&eotf=1&sl=sv&tl=en&u=http%3A%2F%2Fwww.internetmedicin.se%2Fdyn_main.asp%3Fpag e%3d240&act=url Harkness, R & Bratman, S 2003, Mosby s handbook of drug-herb and drug-supplement interactions, Mosby, Missouri. Haslett, C Chilvers, E Boon, N Colledge N (eds) 2002, Davidson s Principles and Practice of Medicine, Churchill-Livingston, London. Hawrelak, J 2014 Irritable Bowel Syndrome, in J Sarris & J Wardle (eds), Clinical naturopathy: an evidence based guide to practice, Churchill Livingston Elsevier, Sydney pp Endeavour College of Natural Health endeavour.edu.au 52

53 References Health Notes, 2009, Irritable Bowel Syndrome, viewed Helmut, S Tankred, S Christian, H & Malte, K 2005, Cocoa polyphenols and inflammatory mediators. American Journal of Clinical Nutrition, Vol.81, No.1, pp.304s-312s. Hutchison, R Tyrrrel, P Kumar, D et al. Pathogenesis of gall stones in Crohn's disease: an alternative explanation. Gut 1994, vol.35, issue 1, pp Kaltwasser, J Werner, E Schalk, K Hansen, C Gottschalk, R Seidl, C 1998, Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut, vol.43, no.5, pp Khatoon, S Rai, V Rawat, S Mehrotra, S 2006, Comparative pharmacognostic studies of three Phyllanthus species, Journal of Ethnopharmacology, vol.104, no.1-2, pp Kumakara, S Yamashita, M & Tsurufuji, S Effect of bromelain on kaolin-induced inflammation in rats. European Journal of Pharmacology. Vol. 150, No. 3, pp Kumar, P and Clark, M 2009, Clinical medicine, 7th edn, Elsevier Saunders, Philadelphia. Kumar, P and Clark, M 2005, Clinical medicine, 5th edn, Elsevier Saunders, Philadelphia. Madisch A, Holtmann G, Plein K, Hotz J, 2004 Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial, Aliment Pharmacol Ther. Feb 1;19(3):271-9 Mahan, L Escott-Stump, S 2008, Krause s Food & Nutrition Therapy, 12th edn, Saunders Elsevier, Canada. Medical Futures Incorporated, 2010, Iberogast, viewed Endeavour College of Natural Health endeavour.edu.au 53

54 References Magliulo, E Gagliardi, B Fiori, G 1978, Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres, Medizinische Klinik, vol.73, no.28-29, pp Mills & Bone, 2000, Principles and Practice of Phytotherapy, Churchill Livingstone Mills & Bone, 2007, The Essential Guide to Herbal Safety, Elsevier, Churchill Livingstone, USA Osiecki, H 2008, The physician s handbook of clinical nutrition, 7th edn, Bio-concepts, QLD. Paganelli, R Fagiolo, U Cancian, M et al. 1990, Intestinal permeability in irritable bowel syndrome. Effect of diet and sodium cromoglycate administration, Ann Allergy, Vol.64, pp Pandey, M 2007, Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases, World Journal of Surgical Oncology, vol.5, no.1, p.94. Pizzorno, J Murray, M 2000, The Encyclopedia of Natural Medicine, Churchill Livingstone, United States. Porr, P Szantay, J Rusu, M 2004, Post-Cholecystectomy Syndrome and Magnesium Deficiency, Journal of the American College of Nutrition, vol.23 no.6, pp.745s-747s. Pramyothin, P Ngamtin, C Poungshompoo, S Chaichantipyuth, C 2007, Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: In vitro and in vivo studies, Journal of Ethnopharmacology, vol.113, no.3, pp Rana, S Bhardqwaj, S 2008, Small intestinal bacterial overgrowth, Scandinavian Journal of Gastroenterology, vol.43 no.9, pp Rome Foundation, 2016, Rome IV: The Functional Gastrointestinal Disorders Fourth Edition, viewed 06 March 2016 < Sanders, G Kingsnorth, A 2007, Gallstones, British Medical Journal, vol.335, no.7614, pp Endeavour College of Natural Health endeavour.edu.au 54

55 References Sarris, J & Wardle, J 2010, Clinical naturopathy, an evidenced-based guide to practice, Elsevier, NSW. Schlenker, E & Long, S 2007, William s essentials of nutrition & diet therapy, 9 th edn, Mosby Elsevier, Missouri. Schoenberg, M Birk, D Beger, H 1995, Oxidative stress in acute and chronis pancreatitis, American Journal of Clinical Nutrition, vol.62, suppl.6, pp Schulz, H Niederau, C Klonowski-Stumpe, H Halangk, W Luthen, R Lippert, H 1999, Oxidative stress in acute pancreatitis, Hepatogastroenterology, vol.46, no.29, pp Shaffer, E 2007, Cholelithiasis, Merck manuals online, healthcare professionals. viewed 8/11/10 Shils, M Shike, M Ross, C Caballero, B & Cousins, R 2006, Modern Nutrition in Health and Disease, 10 th edn, Lippincott Williams and Wilkins, United States of America. Stargrove, MB Treasure, J & McKee, DL 2008, Herb, nutrient and drug interactions: clinical implications and therapeutic strategies. Mosby Elsevier, Missouri, USA Sturniolo, G Di Leo, V Ferronato, A D Odorico, A & D Incà, R 2001, Zinc Supplementation Tightens Leaky Gut in Crohn s Disease, Journal of Inflammatory Bowel Diseases, Vol.7, No.2, pp Syamasundar, K Singh, B Thakur, R Husain, A Kiso, Y Hikino, H 1985, Antihepatotoxic principles of Phyllanthus niruri herbs, Journal of Ethnopharmacology, vol.14, no.1, pp Sun, W Wei, W Wu, L Gui, S Wang, H 2007, Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on liver fibrosis induced by carbon tetrachloride in rats, Journal of Ethnopharmacology, vol.112, no.3, pp Tănăsescu, C Petrea, S Băldescu, R Macarie, E Chiriloiu, C Purice, S 1988, Use of the Romanian product Silimarina in the treatment of chronic liver diseases, Médecine Interne, vol.26, no.4, pp Endeavour College of Natural Health endeavour.edu.au 55

56 References Tripathi, S Bruch, D & Kittur, D 2008, Ginger extract inhibits LPS induced macrophage activation and function, BMC Complementary & alternative medicine, Vol. 8, No.1. Trivedi, N Rawal, U Patel, B 2007, Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury, Integrative Cancer Therapies, vol.6, no.3, pp Tsokos, M Braun, C 2007, Acute Pancreatitis Presenting as Sudden, Unexpected Death: An Autopsybased Study of 27 Cases, The American Journal of Forensic Medicine and Pathology, vol.28, no.3, pp Tuntawiroon, M Sritongkul, N Brune, M Rossander-Hultén, L Pleehachinda, R Suwanik, R Hallberg, L 1991, Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron absorption in men, American Journal of Clinical Nutrition, vol.53, no.2, pp Van Gossum, A Closset, P Noel, E Cremer, M Neve, J 1996, Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis, Digestive diseases and sciences, vol.41, no.6, pp Uden, S Bilton, D Nathan, L Hunt, L Main, C Braganza, J 1990, Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial, Alimentary Pharmacology and Therapeutics, Vol.4, no.4, pp Endeavour College of Natural Health endeavour.edu.au 56