Irritable Bowel Syndrome: Treatment Options

Review

Irritable bowel syndrome: treatment options

Magdy El-Salhy*1,2, Doris Gundersen3, Jan Gunnar Hatlebakk2 & Trygve Hausken2

Practice Points Nonpharmacological approaches can be sufficient in patients with mild irritable bowel syndrome symptoms. Information and reassurance, dietary guidance, regular exercise and probiotic intake individually and in combination reduces symptoms and improves quality of life. The information and reassurance should be provided by the patient’s doctor. Intake of probiotics increases the patient’s tolerance to fermentable oligosaccharides, disaccharides, monosaccharides and polyols. In addition to nonpharmacological treatment, a drug directed to the main symptom that troubles patients can be used. Irritable bowel syndrome patients that do respond to nonpharmacological and pharmacological treatment are candidates for gut-directed hypnotherapy.

Summary Irritable bowel syndrome is a common gastrointestinal disorder that considerably reduces the patient’s quality of life and represents an economic burden to society due to the high consumption of healthcare resources and the nonproductivity of irritable bowel syndrome patients. The options for the treatment of irritable bowel syndrome are nonpharmacological and pharmacological. The nonpharmacological approach includes: information and reassurance, dietary guidance, regular exercise, probiotic intake, hypnotherapy and cognitive therapy, psychodynamic interpersonal therapies and relaxation training. There is still some uncertainty regarding the role of cognitive behavior, psychodynamic interpersonal therapies and relaxation training in managing irritable bowel syndrome. This is due to significant challenges in terms of study design, patient selection and the interpretation of results.

1Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, Box 4000, 54 09 Stord, Norway 2Section for Gastroenterology, Institute of Medicine, University of Bergen, Norway 3Department of Research, Helse-Fonna, Haugesund, Norway *Author for correspondence: Tel.: + 47 53491000; Fax: +47 53491001; [email protected] part of

Pharmacological treatment mainly includes laxatives, antidiarrheal drugs, antispasmodic drugs, antidepressants and antianxiety drugs. Patient confidence is higher for the nonpharmacological approach than medication. The nonpharmacological approach is also more effective than medication.

Irritable bowel syndrome (IBS) is a chronic func- constipation-predominant (IBS-C) or a mix- tional disorder of the gut. Patients with IBS suf- ture of both diarrhea and constipation (IBS-M), fer from abdominal pain/discomfort, bloating, and unsubtyped IBS in patients with insufficient abdominal distension and diarrhea alternating abnormality of stool consistency to meet criteria with constipation. The intensity of symptoms for IBS–C, D or a mixture of both diarrhea and varies in different patients from mild to severe. constipation. The division is useful for clinical Some patients complain of daily symptoms, practice and symptomatic treatment. In clinical while others report intermittent symptoms at practice, however, it is common for IBS patients intervals of weeks/months. The prevalence of to switch from one subtype to another over time. IBS is from 5 to 10% of the world’s popula- These patients are now called ‘alternators’. More tion and the annual incidence is approximately than 75% of IBS patients change to either of the 200 per 100,000 [1–3]. IBS is more common in other two subtypes at least once over a 1-year women than in men, and is more commonly period [10]. In clinical practice, few clinicians in diagnosed in patients younger than 50 years of primary and secondary care use the Rome cri- age [1]. IBS reduces quality of life with the same teria systematically, but instead rely more on a degree of impairment as major chronic diseases holistic approach [11–14]. such as diabetes, congestive heart failure, renal insufficiency, hepatic cirrhosis and inflammatory Treatment options bowel diseases [4–6]. IBS is not known, however, The treatment options for IBS include nonphar- to be associated with the development of serious macological and pharmacological options [1]. disease or with excess mortality. The nonpharmacological approach com- IBS patients visit physicians more often than prises: information, reassurance, dietary guid- other patients with common somatic diseases ance, regular exercise, probiotic intake, hypno- such as diabetes, hypertension or asthma, and therapy and cognitive therapy, amongst others they represent 12–14% of primary care patient [1]. Pharmacological treatment mainly includes visits and 28% of referrals to gastroenterologists laxatives, antidiarrheal drugs, antispasmodic [1]. IBS represents an economic burden to soci- drugs, antidepressants and antianxiety drugs [1]. ety in the form of direct and indirect costs. The The use of nonpharmacological treatments and direct costs are caused by overconsuming medi- pharmacological drugs in primary healthcare cations, diagnostic tests and being hospitalized and by gastroenterologists is almost the same frequently [1,7,8]. The indirect costs are brought [1]. Patient confidence is higher for the non about by the lower work productivity of IBS pharmacological approach than medication, and patients [1,7,8]. the nonpharmacological approach is also more There is no biochemical, histopathological or effective than medication [1]. radiological diagnostic test for IBS. Rather, the diagnosis of IBS is based on symptom assess- Nonpharmacological approaches ment. Thus, Rome III criteria have been estab- Information & reassurance lished (Box 1), where elaborated, detailed, accurate Approximately 52% of IBS patients believe that and clinically useful definitions of the syndrome IBS is caused by a lack of digestive enzymes, are used [9]. In addition to these criteria, warn- 42.8% believe that IBS is a form of colitis, 47.9% ings symptoms (red flags) such as age >50 years, believe it will worsen with age and 43% believe short history of symptoms, nocturnal symptoms, it can develop into colitis, 37.7% into malnutri- weight loss, rectal bleeding, anemia and the pres- tion and 21.4% into cancer [15]. The IBS patients ence of markers for inflammation or infections are interested in learning about which foods to should be excluded. IBS patients are subgrouped avoid (63.3%), the causes of IBS (62%), cop- on the basis of differences in predominant bowel ing strategies (59.4%) and medications (55.2%); pattern as diarrhea-predominant (IBS-D), they are also interested in finding out whether

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Box 1. Rome III criteria for the diagnosis of irritable bowel syndrome. Recurrent abdominal pain or discomfort with onset at least 6 months prior to diagnosis, associated with two or more of the following, at least 3 days/month in the last 3 months: Improvement with defecation Onset associated with change in frequency of stool Onset associated with change in form (appearance) of stool Symptoms that cumulatively support the diagnosis are: Abnormal stool frequency (greater than three bowel movements per day or less than three bowels movements per week) Abnormal stool form (lump/hard or loose/watery stool) Abnormal stool passage (straining, urgency or feeling of incomplete evacuation) Passage of mucus Bloating or feeling of abdominal distension Reproduced with permission from [1] © Nova Science Publisher, Inc. (2012). or not they would have to live with IBS for life see someone succeeding at something, their (51.6%) and in reading research studies (48.6%) self-efficacy is more likely to increase, whereas [16]. The qualities in healthcare providers desired when they see people failing, their self-efficacy by the IBS patients are the ability to provide is more likely to decrease. This process is more comprehensive information, the ability to lis- effective when a person sees him- or herself as ten and answer their questions, and to provide being similar to his or her own model. Regarding support and hope [1]. The majority of the IBS this matter, the IBS patients who attended the patients stated that they prefer to get informa- IBS school apparently failed to cope with IBS; tion from a doctor in person [1]. An effective according to the modeling, seeing failed people physician–patient relationship that provides is more likely to decrease self-efficacy. both reassurance and a thorough explanation Optimal consultation techniques designed to of the IBS disorder has been found to reduce elicit a therapeutic alliance between patients and the use of healthcare resources, the fear of can- physicians are especially important in consulta- cer and self-perceptions of impairment in daily tions with IBS patients. The patients should be functioning [1]. allowed to tell their story in their own words We believe that information and reassur- in order to feel that the doctor has understood ance should be provided by the patient’s doctor their concerns. This becomes even more impor- simply because this is what the patients prefer tant when previous consultations may have been (Box 2). Moreover, this is important in establish- unsatisfactory in this respect. Furthermore, the ing patient–doctor relationships. Consequently, first consultation should include a thorough these patients need longer consultations than physical examination and some blood tests to normal. Dedicated longer time slots may be exclude infection/inflammation, anemia, dia- an appropriate way to manage the disorder betes, or thyroidal, liver or kidney diseases. An rather than repeated brief consultations. The educational booklet containing the same infor- arguments that are given in favor of providing mation provided should be freely available at the information to a small group of patients (IBS end of the consultation, along with the opportu- school) instead of providing information indi- nity for patients to discuss their concerns again vidually are that it is less time-consuming and once they have read this material. that patient education in a group setting offers an opportunity to share experiences with oth- Dietary guidance & regular exercise ers in the same situation, which can contribute Diet seems to play an important role in the mani- to improvements in coping strategies. Actually festation of IBS symptoms. The mechanisms providing information for a group of patients thought to lie behind this have been discussed does not save a doctor time as 2 h of a gastro elsewhere [1]. Fermentable oligosaccharides, enterologist’s time are used to inform a group of disaccharides, monosaccharides and polyols five to ten patients [16,17]. Modeling, according (FODMAPs) are short-chain carbohydrates that to the self-efficacy theory, is a process of com- are poorly absorbed so that a significant portion of paring oneself with someone else. When people the ingested carbohydrates enters the distal small

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Box 2. The contents of the information provided to irritable bowel syndrome patients. IBS is recognized as a common illness in the population and there is some evidence to show that it could be hereditary IBS is not known to be associated with the development of serious disease, cancer or with excess mortality IBS is a chronic condition and the intensity of symptoms fluctuate, in that there will be good days and bad days A clear knowledgeable explanation of the known pathophysiology and the pathogenesis of IBS The possible coexistence of other gastrointestinal and extragastrointestinal symptoms in patients with IBS There is no miracle cure for IBS. An explanation of the treatment options and the fact that a nonpharmacological approach could be sufficient and could be combined with pharmacological treatment on bad days A thorough explanation regarding the fact that a physical examination, blood tests, gastroscopy and colonoscopy can exclude other diseases that the patients fear. In patients who have already undergone gastroscopy and colonoscopy, an explanation should be offered as to what these tests have excluded Intensive research is being carried out on IBS worldwide and our understanding of this disorder increases every day, which will hopefully offer new treatment possibilities. In other words, there will be light at the end of the tunnel IBS: Irritable bowel syndrome. Adapted with permission from [1] © Nova Science Publisher, Inc. (2012).

bowel and colon. There they increase the osmotic calcium, magnesium and phosphorus [23]. pressure and provide a substrate for bacterial fer- Furthermore, they reported a better quality of mentation with the production of gas, distension life and improved symptoms [23]. In addition of the large intestine and abdominal discomfort to general dietary advice, individual dietary or pain. A restricted intake of FODMAPs has guidance is also required. been shown to reduce symptoms of IBS [18,19]. An Regular exercise has been found to reduce increased consumption of dietary fiber is thought symptoms and improve the quality of life in to accelerate oro–anal transit time and decrease patients with IBS [1]. Based on clinical expe- intracolonic pressure, therefore playing a role in rience and circumstantial evidence physi- the management of IBS symptoms, particularly cians recommended exercise for IBS patients. regarding constipation [20]. However, more recent Physical activity effects on IBS patients have studies where dietary fiber was considered as a previously been attributed to promoting overall whole entity, yielded controversial results [1]. In well being. However, physical activity has been studies that distinguished between insoluble found to increase gastrointestinal transit [24,25]. and soluble fiber, soluble fiber tended to improve The increased gastrointestinal motility has been symptoms whereas insoluble fiber worsened them attributed to vagus stimulation and/or decreased [21]. Moreover, a recent, randomized, double- blood flow to the gut, which leads to an increase blind, placebo-controlled trial of soluble fibers in important gastrointestinal hormones [25,26]. showed a significant reduction in the intensity of abdominal pain, constipation and diarrhea, Probiotics as well as an improvement in the performance of Probiotics are live microorganisms that, when daily activities [22]. A lower intake of FODMAPs administered in adequate amounts, confer should be recommended to IBS patients, as well health benefits to the host. The most commonly as increasing their intake of foods rich in water used probiotics include bacteria or yeasts from soluble fibers(Box 3) . the genera Lactobacillus, Bidifobacteria and In the clinic, tolerance to FODMAPs and Saccharomyces. Commercially available probiot- insoluble fibers varies between different patients ics contain either single strains or a mixture of with IBS. This wide variation could be owing to strains and are available in capsules, powders, differences in intestinal flora between patients. yoghurts and fermented milks. Probiotics must Furthermore, consuming food supplemented be well tolerated for human consumption, they with probiotics increases a patient’s tolerance to must survive transit through the gastrointesti- FODMAPs and insoluble fibers. IBS patients nal tract and they must have some physiological received two sessions, 1 h each, of individual impact. Some of the beneficial effects attributed dietary guidance recommending that they to probiotics are enhancement of the host’s anti- increase their daily intake of dairy products inflammatory and immune response and the and food items supplemented with probiot- stimulation of anti-inflammatory cytokines, ics. They subsequently increased their intake improving the epithelial cell barrier, inhibiting of b-carotene, retinol equivalents, riboflavin, bacterial translocation and growth, inhibiting

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the adhesion of viruses and inactivating bile gut-directed hypnotherapy is to use hypnotic acids [27,28]. In animal models, probiotics have induction, progressive relaxation and imagery been found to reduce hypermotility and visceral directed to the control of gut function [36–39]. hypersensitivity [29,30]. Controlled clinical trials The dropout rates in patients with refractory of a single probiotic preparation and a probiotic IBS are relatively high [39]. This therapy has been mixture demonstrated that IBS symptoms are shown to be effective not only in improving IBS improved depending on the preparation used, symptoms but also in improving many of the and that some products appear to be more effec- features of the condition, including quality of tive than others [1,31–34]. The bacteria that have life and psychological status [38–41]. The benefi- been proven to be effective in this aspect are cial effects appear to be sustained over time [35]. Bifidobacterium infantis 35624, Bifidobacterium lactis DN–173–010, Lactobacillus plantrum, Box 3. General food advice to irritable bowel Lactobacillus GG, Lactobacillus acidophilus and syndrome patients. Saccbaromyces faecium. The mechanism by which Food allowed: these bacteria exert their effects is attributed to Meat the ability of these bacteria to reduce the num- Fish ber of sulphite-reducing Clostridia spp., which is Chicken known to produce gas upon the fermentation of Milk nutrients. This could contribute to improvements Fat and oils in flatulence, bloating and abdominal distension Rice in IBS patients [28]. Although probiotics have Potatoes beneficial effects in some patients with IBS, they Carrot are not potent enough to be used alone, especially Apple and pear (peeled) in patients with severe symptoms [28]. In clinical practice, a relapse of IBS symptoms was observed Citrus in some patients as soon as they stopped taking Banana Raspberry blueberry and strawberry the probiotics [1]. Honeydew melon Combined program Kiwifruit and passionfruit A health program combining of reassurance Tomato and information, dietary management, probi- Coffee and tea otic intake and regular exercise was followed Chocolate by 143 IBS patients, who were followed up Alcohol over 2 years [35]. The patients who followed Probiotic supplemented this program reported improved quality of Spelt and spelt products life and reduced symptoms throughout the Food advised to avoid: follow-up period [35]. These findings are in Onion favor of the additive effect of combining sev- Garlic eral nonpharmacological approaches in a short Light products (food containing artificial health program. sweeteners) Paprika Psychological treatment Beans There is still some uncertainty regarding the role Peas of cognitive behavior, psychodynamic interper- Cabbage and rutabaga sonal therapies and relaxation training in man- Carbonated beverages (soda) aging IBS [1]. This is due to significant chal- Avocado lenges in terms of study design, patient selection Artichokes and the interpretation of results. Broccoli Gut-directed hypnotherapy requires six to 12 Cabbage sessions, 30–60 min each, spread over several Watermelon months [36–39]. The goal of this therapy is to Flour and flour products make IBS patients independent of healthcare Adapted with permission from [1] © Nova Science Publisher, in managing their symptoms. The rationale of Inc. (2012).

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This form of treatment should be restricted to have the adverse effects of bloating and flatu- specialist centers caring for more severe forms of lence. Psyllium preparations have been proven IBS (refractory IBS) [34]. to be effective and free from the side effects of Gut-directed hypnotherapy normalizes vis- other bulking agents [50–53]. Osmotic laxatives, ceral sensation, reduces colonic phasic contrac- such as polyethylene glycol and lactulose, are tions and reverses the negative thoughts that used for constipation in IBS, although lactulose patients often have regarding their condition is associated with bloating and abdominal pain [42–44]. It has been proposed that the action of and is not suitable for chronic use [54]. Stimulant hypnotherapy is probably owing to the activation laxatives as bisacodyl and senna are effective but of certain areas of the brain, especially the ante- are associated with abdominal cramping, elec- rior cingulated, which is supported by the find- trolyte depletion and diarrhea, and consequently ing that the hypnotic reduction of somatic pain should not be used for long periods [1]. is associated with a reduction in the activation Diarrhea in IBS patients can be treated with of this brain region [44]. loperamide or diphenoxylate. Loperamide is an opiate µ-agonist that does not cross the Pharmacological approaches blood–brain barrier. It is widely used in clinical Symptomatic treatment practice because it is effective for urgent loose Pharmacological treatments for the relief of IBS stools and it is safe, well tolerated and inexpensive symptoms have been presented in detail in recent [55]. Loperamide stimulates absorption, inhibits comprehensive reviews [45–49]. Drug treatment is secretion and slows intestinal transit. However, chosen based on the main symptoms that trouble it is not effective in abdominal pain [56]. patients; thus, pharmacological drugs against Several tricyclic antidepressants are used abdominal pain and/or bloating, diarrhea and to treat IBS patients, especially those with constipation are most commonly used (Table 1). diarrhea as the predominant symptom. These Several treatment options are available for have anticholinergic and antiselective sero- the symptomatic relief of constipation in IBS tonin reuptake inhibitor effects. These drugs patients [1]. Soluble fibers and bulking agents are may alter pain perception independent of their most frequently used as the first-line treatment; antidepressant or anxiety effects. However, conventional bulking agents include psyllium, even treatment with low doses of these drugs methylcellulose and calcium polycarbophil. can cause side effects such as a dry mouth, Bulking agents containing insoluble fibers often constipation, fatigue and drowsiness in over a

Table 1. Pharmacological options for the treatment of irritable bowel syndrome patients. Target symptom Drug class Generic name Dose Diarrhea Opiate µ-agonist Loperamide 2 mg with each loose stool, up to a maximum of 16 mg daily Diarrhea, abdominal distension and pain Tricyclic antidepressants Desipramide 10–150 mg at night Amitrpyline 10–150 mg at night Nortripyline 10–150 mg at night Global benefit without benefit to bowel Selective serotonin Paroxetine 20–50 mg daily symptoms reuptake inhibitors Fluoxetine 10–40 mg daily Global improvement of symptoms and Antibiotics Rifaximin 400–550 mg three-times daily over improvement in bloating and distension 7–10 days Neomycin 1 g daily over 10 days Metronidazol 400 mg twice daily over 15 days Improve straining and hard stools Bulking agents Psyllium 2.5–30 g daily in divided doses Ispaghula 3.5 g one to three-times daily Osmotic laxative Polyethylene glycol 17 g in 237 ml solution daily Emollient laxative Mineral oil 5–10 cm3 daily Limited proven efficacy Antispasmodics Hysocamine sulfate 0.125 mg up to four-times daily Dicyclomine 10–20 mg two- to four-times daily Adapted with permission from [1] © Nova Science Publisher, Inc. (2012).

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third of patients. Selective serotonin reuptake Ondansetron, granisetron, alosetron and inhibitors inhibit the reuptake of serotonin by cilansetron are 5-HT3 receptor antagonists blocking the serotonin transporter protein at [1]. These antagonists have been found to presynaptic nerve endings and increasing syn- decrease small intestinal secretion, small and aptic exposure to a high concentration of sero- large intestinal motility and nausea, as well as tonin [57]. A standard dose of selective serotonin reducing colonic hypersensitivity [1]. Alosetron reuptake inhibitors has been shown to lead to a was approved for the treatment of IBS-D in significant improvement in the health-related female patients, but it was later withdrawn quality of life in patients with chronic or from the market because of its side effects [1,61]. treatment-resistant IBS [58]. These drugs con- Other 5-HT3 receptor antagonists, especially fer global benefits without significant changes cilansetron, have been investigated or are still in bowel symptoms or pain [1]. These drugs under development for the treatment of IBS-D are better tolerated by patients than tricyclic patients [1]. antidepressants. The 5-HT4 receptors are located on affer- The rationale for using antibiotics in the treat- ent neurones in the myenteric plexus, smooth ment of IBS is based on the assumption that IBS muscles and enterochromaffin cells[57,58] . These symptoms could be caused by small intestinal receptors mediate the release of the colonic bacterial overgrowth and the presence of inflam- neurotransmitters acetylcholine, substance P, matory mediators and/or inflammatory cells in vasoactive intestinal polypeptide and calcitonin the mucosa of some IBS patients. Clinical trials gene-related peptide, which stimulate the peri- with antibiotics have shown global relief of IBS staltic reflex [1]. Furthermore, 5-HT4 receptor symptoms and bloating [1]. activation induces small bowel and colonic fluid In randomized, double-blind, placebo-con- secretion [1]. Tegaserod, prucalopride, renza- trolled studies, administration of melatonin pride and cisapride are 5-HT4 receptor agonists. 3 mg at bedtime attenuated abdominal pain Tegasrode has been shown to promote small and reduced rectal pain sensitivity. This treat- intestinal transit time and to enhance proxi- ment had no effect on sleep disturbances or psy- mal colonic emptying in IBS-C patients [59]. In chological stress suggesting that the beneficial healthy humans, tegaserod stimulates intestinal effects of melatonin are independent of its action secretion and promotes the evacuation of jejunal on sleep disturbances or psychological profiles gas [1]. Tegaserod has been used to treat IBS-C, [59,60]. The rationale behind the use of an anti- but it was withdrawn from the market because spasmodic agent is to attenuate the heightened of its side effects. Prucalopride has also been baseline and postprandial contractility observed reported to decrease colonic transit time [1,62–64]. in IBS patients; however, the efficacy of these agents in the treatment of IBS is limited [1]. Other treatment options Acupuncture The use of gut neuroendocrine Acupuncture is an ancient traditional Chinese peptides/amines in the treatment of IBS medical practice based on the theory that energy The neuroendocrine peptides/amines of the gut or the life force ‘qi’ runs through the body in have the potential to be used in the treatment channels, or ‘meridians’. Qi is essential for health of IBS; this could be considered as the correc- and any disruption of its flow causes symptoms tion of a pre-existing abnormality in the neuro and disease. This disruption is believed to be endocrine system of the gut or through the use corrected by acupuncture at identifiable ana- of the pharmacological actions of gut hormones. tomical locations called ‘acupoints’. The effect The neuroendocrine peptides/amines of the of acupuncture on IBS is believed to be caused gut have broad physiological/pharmacological by altering visceral sensation and motility by effects: they can often bind to and activate sev- stimulating the somatic nervous system and eral receptors with independent actions. Thus, vagus nerve [1]. in order to be able to target these bioactive sub- Acupuncture intervention in a random- stances, receptor-specific agonists or antagonists ized controlled pilot study showed significant should be developed. Both serotonin agonists improvements in IBS symptoms. In another and antagonists have been proven to be useful two large, randomized controlled studies, no in clinical practice. difference was found in the global outcome

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measurements between patients who received real Conclusion & future perspective or sham acupuncture [65,66]. However, improve- The available options for the treatment of IBS ments were found in IBS symptoms and quality are nonpharmacological and pharmacological. of life in patients who received real and sham acu- The nonpharmacological approaches are suffi- puncture compared with baseline values and IBS cient in treatment of patients mild IBS, which patients on the waiting list [65,66]. These findings constitutes the majority of IBS patients. Gut- suggest that the observed effect of acupuncture directed hypnotherapy is effective in patients may have been due to the placebo effect. with refractory IBS. Pharmacological treatment is by far symptomatic. There is ongoing intensive Herbal therapy research on the role of intestinal flora in IBS, In traditional Chinese medical theory IBS is a which may result in expanding our knowledge in syndrome of stagnated liver energy and a dys- this area and might improve the use of probiotics function of the spleen. Thus, Chinese herbal in nonpharmacological treatment of IBS. Four treatments for IBS were developed to relieve sup- neuroendocrine peptides/amines are candidates pressed liver functioning and to replenish the for pharmacological treatment of IBS, namely energy of the spleen. There are several Chinese serotonin, ghrelin, peptide YY and cholecysto- herbal formulations for IBS, such as Tong Yao kinin. Receptor specific agonists and agonists Fang (the essential formula for abdominal pain for theses neuroendocrine peptides/amines are and diarrhea), which contains up to 20 herbal under development, and new serotonin agonists ingredients, and the Tibetan herbal formulation and antagonists are actually on their way to the Padma Lax. Studies on the beneficial effects of clinic. herbal treatments have shown conflicting results and the efficacy of this type of treatment remains Financial & competing interests disclosure controversial [1,67]. The authors have no relevant affiliations or financial Extracts from the peppermint plant (Mentha involvement with any organization or entity with a finan- piperita, Lamiaceae) are believed to have a spas- cial interest in or financial conflict with the subject matter molytic effect on the smooth muscles of the gut or materials discussed in the manuscript. This includes causing a relief in IBS symptoms. employment, consultancies, honoraria, stock ownership or Most trials support the effectiveness of pep- options, expert testimony, grants or patents received or permint oil in improving IBS symptoms; how- pending, or royalties. ever, further studies are needed to elucidate the No writing assistance was utilized in the production of beneficial effects of such a treatment [1]. this manuscript.

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