Abstract: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction that significantly impacts quality of life. Studies indicate that more than one-third of patients with IBS use nonpharmacologic therapies, which include natural products and mind-body therapies, with higher prevalence identified among women, younger individuals, and those with higher education levels. This article examines the efficacy and safety of various natural products for the treatment of IBS, including fiber supplements, probiotics, herbal remedies (including Aloe vera and peppermint oil), and dietary supplements. Although some therapies show promise in symptom management, the evidence remains mixed for many of these interventions. Further high-quality research is needed to establish the role of many of these therapies in IBS treatment.
Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction (DGBI) and is defined by the Rome IV criteria as recurrent abdominal pain associated with disordered defecation. IBS can present as diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), mixed (IBS-M), or unsubtyped (IBS-U). IBS has an estimated prevalence of 4.7% to 6% in the United States.1-3 This condition is more prevalent in women than in men and is more commonly seen in younger individuals.3,4 IBS has a significant negative impact on quality of life (QoL). One study found that patients with IBS would give up 25% of their remaining life (average, 15 years) to receive a treatment that would make them symptom free.1 There have been a number of advances in treatment options for IBS, with many patients seeking nonpharmacologic treatments as initial interventions (Table 1).
Nonpharmacologic therapies include both natural products (eg, fibers, probiotics, herbs, and dietary supplements) and mind-body therapies (eg, hypnosis, cognitive behavioral therapy, yoga, and acupuncture).2,3 These therapies can be used as adjuncts to or in lieu of conventional medicine and are sought out by patients for many reasons. Patients turn to nonpharmacologic therapies not only because of a preference for natural treatments, but also to improve general wellness, energy, or immunity.4,5 Some patients believe that nonpharmacologic therapies can be used independently, without assistance from a medical professional. Other patients already incorporate these therapies into their well-being as part of their upbringing or culture. Nonpharmacologic treatments may also be used when conventional medicine has not yielded desired results.6
The term complementary and alternative medicine (CAM) was renamed complementary and integrative health by the National Institutes of Health in 2014, but CAM is still considered and used as the common colloquialism. CAM has historically referred to many of these nonpharmacologic therapies but does not include fiber. Recent articles exploring nonpharmacologic treatments for IBS have focused on CAM therapies across different DGBIs or have examined both natural products and mind-body therapies for IBS.3,7 This article provides an updated and comprehensive review focusing specifically on natural products for IBS (including fiber) in order to offer clinicians nuanced and evidence-based guidance (Table 2).
Prevalence of CAM Usage in Irritable Bowel Syndrome
Multiple studies have shown that CAM use is prevalent in patients with IBS. In 2008, a 6-month study from a health maintenance organization (HMO) that included more than 1000 DGBI patients found that 38% of those with IBS used at least 1 CAM therapy to treat gastrointestinal (GI) symptoms.6 Of those patients with IBS, the most commonly used CAM therapies were ginger root/tea (14.8%), massage therapy (12.6%), and yoga (10.0%). The 2012 National Health Interview Survey (NHIS) evaluated use of CAM in patients with any GI conditions and found that 42% had used CAM therapy within the prior year; however, only 3% had specifically used CAM to address a GI condition, and of those, 45% had used CAM to address abdominal pain.4 Single-center studies have found similar rates of CAM use among patients with IBS. A 2015 study that included patients attending GI or hepatology clinics at a single academic center found that 44% of patients had used CAM therapy. The most common symptoms targeted were constipation (44%), diarrhea (47%), and bloating (59%).5 A single-center study from Italy found that 45% of patients with IBS who were surveyed reported CAM use.8 Certain demographics are associated with increased use of CAM therapy. Female sex, younger age, higher body mass index, and higher levels of education have been associated with expanded use in patients with IBS.6,8-10
Potential Drawbacks of Nonpharmacologic Therapies
Although generally considered safe, dietary and herbal supplements have been associated with adverse events, including headaches, GI symptoms, and elevated liver enzymes.11 These supplements may interact with medications. The financial burden of such therapies for IBS remains unclear. A 2008 HMO study found that the median out-of-pocket cost for CAM therapy was $200 per year, which was roughly one-third of the median pharmacy cost.6 Updated analyses are needed to determine the current cost in 2025.
Multiple studies show that patients are reluctant to share their CAM use with providers.5,12 A single-center study of 269 GI clinic patients found that only 70% discussed CAM use with physicians. Of those who did not discuss CAM therapy, 82% cited that their doctor did not ask them about it, and 68% said they did not know that it was something they should discuss.5 Similar results were identified in a study by Dossett and colleagues using NHIS data in which the most common reasons patients did not disclose CAM use were because the provider did not ask (51%) or because they did not think the provider needed to know (44%).4
Provider factors also impact how CAM therapy is discussed. A Canadian survey-based study of practicing gastroenterologists found that only 18% had discussed CAM therapy in the majority of their patient encounters.13 Only 51% said they felt comfortable discussing CAM with patients (mostly owing to lack of knowledge of CAM). This may be reflective of the fact that most medical schools do not include CAM education as part of their curricula. Gastroenterologists may underestimate how many of their patients use CAM therapy. A 2013 Italian study revealed that 44% of gastroenterologists thought that less than 10% of patients with IBS use CAM therapy, which was significantly different from reported CAM use by IBS patients (close to 40%).14 Thus, practitioners should consider addressing the use of natural interventions with their patients and develop better knowledge of the risks and benefits of these therapies.
Fiber
Dietary fibers refer to those that are neither digested nor absorbed in the small intestine. Fiber acts as an osmotic bulking agent and decreases bowel transit time. It is categorized as insoluble and soluble. Insoluble fiber is found in certain vegetables, whole grains, and wheat bran. Soluble fiber is found in products such as oat bran, beans, and psyllium.
Data support positive benefits for soluble, but not insoluble, fiber for IBS. A 2015 European meta-analysis that included 22 studies comparing fiber with placebo for IBS found improvements in global symptoms in patients receiving soluble fiber (risk ratio, 1.49; 95% CI, 1.09-2.03). However, there was no improvement in global symptoms for insoluble fiber (risk ratio, 1.08; 95% CI, 0.89-1.31). There was significant improvement in abdominal pain scores for patients receiving soluble fiber (mean difference, −1.84; 95% CI, −2.72 to −0.97) vs no improvement for insoluble fiber.15 A meta-analysis that included 14 randomized controlled trials (RCTs) evaluating the effect of fiber in 906 patients with IBS found there was a significant benefit for only soluble fiber (risk ratio, 0.83; 95% CI, 0.73-0.94; P=.005) with a number needed to treat of 7. No effect was seen with bran (insoluble) fiber (risk ratio, 0.90; 95% CI, 0.79-1.03; P=.14).16 The American College of Gastroenterology (ACG) 2021 guideline on IBS recommends the use of soluble fiber to treat global IBS symptoms, with recommended fiber intake of 20 to 35 g/day.17 However, typical dietary fiber intake in the United States is only 15 g/day.18
Psyllium
Psyllium husk (Plantago ispaghula) is a soluble fiber commonly recommended for IBS. Psyllium increases water content in the small bowel and ascending and descending colon via its polymers.19 One of the major drawbacks of fiber is its propensity to increase gas and bloating in a population already experiencing these symptoms. Psyllium may minimize this effect. In a study evaluating the effects of inulin (rapidly fermented in the colon causing an increase in colonic gas and breath hydrogen) alone vs inulin with psyllium in 19 patients with IBS-D or IBS-C, combining inulin with 20 g of psyllium reduced colonic gas as measured by breath hydrogen (P=.02 and P=.007, respectively). However, adding psyllium to inulin did not decrease gas production in this in-vitro study.20 Psyllium may reduce colonic gas symptoms by decreasing the rate of delivery of inulin (or other poorly absorbed dietary polysaccharides) to the colon. Psyllium is inexpensive, available in multiple over-the-counter formulations, and has been shown to be safe and well tolerated with minimal adverse effects.
Probiotics
Probiotics are live microorganisms that provide a health benefit when given in adequate amounts.21 Probiotics are increasingly used by patients despite limited evidence of their efficacy. The global probiotics market was projected to be worth more than $70 billion by 2024.22 A survey-based study from a center in the Northeast United States queried 479 general GI patients undergoing endoscopy about their probiotic use. Approximately 27% reported probiotic use, with most (18.2%) using probiotics sporadically and 9% using probiotics daily. The most common reasons listed for using probiotics were to improve health and longevity (54%) and to improve GI symptoms (45%).22
Given validation that the gut microbiome plays a role in the pathogenesis of IBS, probiotics have been repeatedly studied.23 However, inconsistencies in the organisms (types and concentrations) used, dosing, small sample sizes, and high placebo rates have resulted in ambiguous results. Meta-analyses evaluating the impact of probiotics on patients with IBS vs placebo have found potential benefit with probiotics for improvement of global symptoms, abdominal pain, bloating, and distension with certain strains of bacteria.24-27 However, certainty in the evidence remains low, and further studies are needed.
Inconsistent results of probiotic studies have also led to discordant guidelines. The 2021 British guideline recommends probiotics be used as effective treatments for both global symptoms and abdominal pain for IBS. A 12-week trial of therapy is recommended, but recommendations regarding specific species or strains are not provided.28 The 2020 American Gastroenterological Association (AGA) clinical practice guidelines for probiotics make no recommendations regarding the use of probiotics in patients with IBS, citing issues with heterogeneity in the strains of probiotics used and study design.29 Probiotics are recommended only under the auspices of a clinical trial. The 2021 ACG IBS guideline recommends against the use of probiotics for the treatment of IBS; however, this is a conditional recommendation based on very low levels of evidence.17
Herbal Supplements
Aloe vera
Aloe vera (AV; Aloe barbadensis Mill.) has been used for many therapeutic purposes, including as a topical salve, oral supplement, and even for cosmetics. AV is thought to have anti-inflammatory and immunomodulatory properties, as well as possible prebiotic effects (as it is used by microbiota in the GI tract to support the microbiome) owing to its beta polysaccharides and short-chain fatty acids.30-33 AV has been used as a laxative to improve GI motility and therefore has been postulated to have benefit for patients with IBS, particularly IBS-C.
Individual RCTs have not identified improvements in symptoms or QoL. A randomized crossover, placebo-controlled study of 47 IBS patients who received AV found no difference between cohorts in any QoL parameters.31 A 2015 study randomized 68 patients with IBS of any subtype to receive AV or placebo for 4 weeks. The patients were assessed using IBS symptom severity scales (IBS-SSS). Overall, 55% of patients receiving AV were responders (defined as reduction in IBS-SSS by ≥50 points) compared with 31% in the placebo group (P=.09). There was improvement in secondary endpoints of pain severity, pain frequency, and bloating in the AV group, but the study was not powered to measure these effects.34 A 2020 RCT assigned 160 IBS patients (all subtypes) to receive either AV or control (inulin) for 4 weeks. There was no difference in responders between groups (30% vs 38%, respectively; P=.26).32 A meta-analysis from 2018 that included 3 RCTs and 151 patients with IBS of all subtypes found greater improvement in symptom scores with AV vs placebo (standardized mean difference, 0.41; 95% CI, 0.07-0.75; P=.020). However, this meta-analysis could not evaluate efficacy of AV by IBS subtype and predated the more recent RCTs.35 A subsequent analysis that added data from the aforementioned 2020 RCT to the 2018 meta-analysis made the response to treatment outcome no longer significant (risk ratio, 1.12; 95% CI, 0.84-1.48; P=.45).33
Overall, there are inconsistent data to suggest whether AV is effective in improving IBS symptoms, and further high-quality studies are needed. AV is considered a safe supplement. Rare reported side effects include diarrhea, although there have been some case reports of acute hepatitis.3,36
Cannabis
Cannabis can originate from 3 major plants—Cannabis sativa, indica, and ruderalis—and has been used as a natural remedy for centuries. Multiple hydrocarbon compounds known as cannabinoids can be extracted. The 2 most well-known are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychotropic cannabinoid, whereas CBD is nonpsychogenic.37
Cannabinoids can be plant-derived (phytocannabinoids), endogenously generated (endocannabinoids), or synthetic. They bind 2 different types of G protein–coupled receptors: CB1, which is located in the enteric and central nervous systems, and CB2, which is found in the immune system.2,38 Cannabinoids are thought to reduce gastric, small intestinal, and colonic motility.38
Cannabis is increasingly used in the United States as a medicinal or recreational therapy, particularly in states where it has been decriminalized. However, there are limited studies evaluating its efficacy in IBS. Dronabinol is currently the only cannabinoid medication approved by the US Food and Drug Administration. Dronabinol is a nonselective synthetic cannabinoid receptor agonist, which slows both gastric emptying and colonic motility. In a 2011 study, 72 patients were randomized to receive 2.5 mg or 5 mg of dronabinol or placebo. Results showed that 5 mg of dronabinol decreased the fasting left colonic motility index compared with placebo (P=.46) and increased colonic compliance (P=.058). These effects were greatest in patients with IBS-D and IBS-U.39
A 2019 population-based study that included 31,272 patients hospitalized for IBS from the Nationwide Inpatient Survey found that cannabis use disorder was associated with increased odds of IBS (adjusted odds ratio, 2.03; 95% CI, 1.53-2.71). This was postulated to be a result of cannabis-induced stress and anxiety on the brain, as well as an increased arousal state in patients using cannabis in excess.40 A retrospective cohort study that included 7163 patients with IBS from the 2016 Nationwide Readmissions Database found that there was no significant difference in 30-day readmission rates for IBS-specific causes in patients who reported cannabis use vs those who did not (P=.53). However, cannabis use was associated with reduced 30-day all-cause hospital readmission rates.41 A 2023 RCT evaluating the cannabinoid 2 receptor agonist olorinab at 3 different doses in patients with IBS-D and IBS-C found reductions in abdominal pain scores at 12 weeks in all 3 of the olorinab cohorts. However, there were no differences in average abdominal pain scores at week 12 between the placebo and olorinab groups.42
Cannabis can be taken in multiple formulations. Side effects are dependent on the dose and ratio of CBD to THC and include anxiety, psychogenic symptoms, drowsiness, and dizziness.37,39 Cyclic vomiting syndrome and cannabis hyperemesis syndrome can also be triggered.
In summary, cannabinoids have been validated to play a role in gut motility. The sensitive nature of their use and lack of high-quality studies leave their therapeutic implications unclear. Further research is needed to determine whether cannabis should be used for IBS.
Ginger
Ginger root (Zingiber officinale roscoe) has historically been used for multiple symptoms, including nausea, pain, and inflammation. It is one of the most commonly used natural products for IBS, with up to 14% of IBS patients reporting use in a 2008 study of 1012 patients with DGBIs.6 The mechanism of action requires further elucidation, although there is some evidence that ginger may have prokinetic effects on gut motility.43 One study found that ginger could improve intestinal hypersensitivity in rats with IBS-D via modulation of proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6.44 However, a double-blind RCT that included 45 IBS-D patients receiving placebo or 1 or 2 g of ginger for 28 days showed that patients receiving ginger did not have better response (as measured via IBS severity scale) compared with placebo.45 The AGA does not include ginger in its guidelines for the management of IBS, and there is no standard recommended dosage. Ginger is generally thought to be well tolerated.46
Peppermint Oil
Peppermint oil (Mentha piperita) has been used for centuries as a remedy for GI symptoms.47 The active ingredient, L-menthol, causes smooth muscle relaxation by blocking calcium channels. It has been postulated that peppermint oil has anti-inflammatory effects and impacts kappa opioid receptors, serotonergic receptors, and the microbiome.48-50 Peppermint oil is marketed as a treatment for IBS and comes in multiple over-the-counter formulations, including a triple-coated microspherical intestinal-release formulation containing 90 mg of purified peppermint oil. In a 4-week study, 72 patients with IBS-D or IBS-M were randomized to receive either placebo or 2 caplets of this formulation 3 times daily. Peppermint oil was associated with a 40% decrease in total IBS symptom score compared with placebo (24.3%) (P=.02246).49
Subsequent data regarding peppermint oil’s efficacy in treating IBS symptoms have been mixed. A 2019 meta-analysis evaluating peppermint oil in 835 IBS patients (any subtype) found that, compared with placebo, peppermint oil resulted in significant improvement in symptoms (risk ratio, 2.39; 95% CI, 1.93-2.97; P<.00001) and abdominal pain (risk ratio, 1.78; 95% CI, 1.43-2.20; P<.00001).48 The number needed to treat was 3 for global symptom improvement and 4 for abdominal pain improvement. However, a subsequent 8-week trial from the Netherlands examining 2 formulations (182 mg small intestinal release and 182 mg ileocolonic release) vs placebo found no difference in worst abdominal pain response between the cohorts. The small-intestinal release formulation did have greater improvement in abdominal pain (P=.16) and IBS severity (P=.20) compared with placebo.51,52 A 2021 placebo-controlled trial from a center in the Northeast United States randomized 133 patients with IBS (any subtype) to receive placebo vs 180 mg of enteric-coated, small-intestinal release peppermint oil 3 times daily (part of a larger open-label placebo vs double-blind placebo study). Both groups showed improvements in symptoms; however, there were no significant differences between groups in IBS-SSS, global improvement in IBS symptoms, or adequate relief of symptom scores. It was noted that the lack of a more robust separation may have been owing to a high placebo response rate.53
The ACG IBS guidelines recommend using peppermint oil for relief of global IBS symptoms based on low-quality evidence.17 Peppermint oil has been well tolerated, but rare side effects have been reported, including reflux/heartburn, belching, and abdominal pain.53
STW-5 and STW-5II
STW-5 is made from 9 herbal extracts: candy tuft (Iberis amara), lemon balm leaf (Melissa officinalis), chamomile flower (Matricaria chamomilla), caraway fruit (Carum carvi), peppermint leaf (Mentha piperita), licorice root (Glycyrrhiza glabra), Angelica root (Angelica archangelica), milk thistle (Silybum marianum), and celandine herb (Chelidonium majus). Its mechanism of action results from the combined effects of the 9 compounds, which play a role in gut motility, inflammation, neuronal signaling, the gut microbiome, and intestinal permeability.54
STW-5 has been used for more than 20 years for functional dyspepsia and other DGBIs, although it has not been commercially available in the United States. A 2004 RCT that included 208 patients with IBS who were randomized to receive 1 of 3 herbal preparations (one of which was STW-5) vs placebo found that patients receiving STW-5 experienced a significant reduction in abdominal pain scores (P=.0009) and IBS symptom score (P=.001) at 4 weeks.55 A 2024 crossover RCT evaluated the impact of STW-5 on colonic gas in patients with IBS. After 2 weeks of STW-5 or placebo, 10 patients underwent gas challenge tests in which gas was continuously infused into the colon. Gas filling was associated with a rise in abdominal symptoms to a greater extent in patients receiving placebo (score increment, 4.0 ± 0.3) vs those receiving STW-5 (score increment, 3.2 ± 0.4; P=.035).56 This study suggested that STW-5 may improve colonic gas tolerance in patients with IBS who have bloating. STW-5 is well tolerated. However, there have been case reports of liver injury (in particular from celandine herbs), with 1 individual requiring liver transplantation.57
Recently, a 6-herb formulation (STW-5II) has been released that includes Iberis amara, Carum carvi, Glycyrrhiza glabra, Matricaria chamomilla, Melissa officinalis, and Mentha piperita. Limited data on this newer formulation have focused on functional dyspepsia, where it has been shown to improve symptoms compared with placebo.58,59 STW-5II is available as liquid drops and softgels and can be purchased in the United States.
Turmeric
Turmeric is a flowering plant in the ginger family that has been used as a dye and a spice and is used to treat many GI symptoms. Its active ingredient is curcumin. It is thought to increase motility, have anti-inflammatory properties, and play a role in molecular signaling.60 There is a paucity of data evaluating the impact of turmeric on IBS. A 2004 study from the United Kingdom that included 207 IBS patients who took turmeric daily for 8 weeks found improvement in abdominal pain/discomfort.61 A more recent meta-analysis evaluating use of curcumin for IBS included 326 patients from 3 studies and found that curcumin resulted in improved IBS symptoms, although this was not statistically significant (−0.466; 95% CI, −1.113 to 0.182; P=.158), and there was heterogeneity across the studies, including lack of consistent IBS definition and different curcumin formulations.62 Turmeric is considered safe with minimal side effects, although there have been case reports of liver injury from turmeric supplements that may be related to contaminants in the products.63
Dietary Supplements
L-Glutamine
Some patients with IBS-D show increased small bowel and colonic intestinal permeability related to reduced expression of tight junctions.64 L-glutamine, an essential amino acid, has been postulated to alter tight junction proteins, impact inflammatory signaling, and reduce intestinal permeability. A 2019 study randomized 115 patients with postinfectious IBS-D to receive L-glutamine 5 g 3 times daily or placebo for 8 weeks. A greater than 50-point reduction in IBS-SSS scores was experienced by 79.6% of glutamine recipients vs 5.8% of placebo recipients (P<.0001), correlating with reduced intestinal permeability (r=0.72).65 L-glutamine also reduced daily bowel movements and improved stool form.66 Another study randomized 50 IBS patients (any subtype) to receive a low–fermentable oligo-, di-, monosaccharide, and polyol diet either with L-glutamine 15 g/day or placebo for 6 weeks. The L-glutamine group showed significant reduction in total IBS-SSS compared with placebo (P<.0001).67 L-glutamine is well tolerated without significant adverse effects. Further studies should explore L-glutamine’s effects in different IBS populations.
Melatonin
Melatonin (5-methoxy-N-acetyltryptamine) is a hormone secreted by the pineal gland in the brain that is involved in regulation of the sleep-wake cycle. However, melatonin is also made by enterochromaffin cells in the GI tract and is thought to impact gut motility.68 Patients with IBS are prone to sleep disturbances, and it has been proposed that melatonin deficiency may be involved in the pathogenesis of IBS.69 Thus, melatonin has been postulated to improve IBS symptoms either via sleep regulation or by direct impact on the gut.70 A 2005 study randomized 17 female patients with IBS to receive either melatonin 3 mg or placebo nightly for 8 weeks followed by washout and crossover. Patients had improvements in their mean IBS scores, as measured by the IBS Symptoms Evaluation Score Questionnaire, after melatonin compared with placebo (3.9 +/- 2.6 and 1.3 +/-4.0, respectively; P=.037).71 In a recent RCT from Iran evaluating the impact of melatonin in patients with IBS (subtype agnostic) with or without sleep disorders, 136 patients were randomized to receive either melatonin 6 mg daily (3 mg fasting and 3 mg at bedtime) or placebo for 8 weeks. There was an improvement in IBS-SSS in patients receiving melatonin compared with placebo, both for those with sleep disorders (P=.022) and those without (P=.025). There were also improvements in abdominal pain.72 Earlier small studies evaluating melatonin similarly found improvement in bowel symptoms and abdominal pain scores.71,73 Melatonin is well tolerated with side effects including daytime sleepiness.
Conclusion
Nonpharmacologic therapies represent a developing class of treatment options that may have some benefit for patients with IBS. However, evidence for many of these interventions remains limited or mixed. There is a demonstrated need for more rigorous, multicenter RCTs to evaluate the efficacy, safety, and long-term outcomes of these natural products. The prevalence of nonpharmacologic treatment use by patients with IBS highlights the need for gastroenterologists to actively discuss both the potential benefits and risks. Integrating evidence-based treatments into conventional therapies may offer a more personalized and thorough approach to IBS management.
Disclosures
Dr Brigstocke has no relevant conflicts of interest to disclose. Dr Brenner serves as a consultant, advisor, and/or speaker for Anji, Ardelyx, AbbVie, Ironwood, Salix, Bayer, Gemelli, Laborie, Vibrant, Mahana, Owlstone, CinPhloro, Dr. Reddy, and Blueprint Pharmaceuticals. He owns stock in Owlstone and sits on the board of directors for the nonprofit International Foundation for Gastrointestinal Disorders.
References
1. Drossman DA, Morris CB, Schneck S, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. J Clin Gastroenterol. 2009;43(6):541-550.
2. Shapiro JM, Deutsch JK, Chey WD. An evidence-based narrative review of oral supplements for the treatment of patients with irritable bowel syndrome. NeuroGastroLatam Rev. 2020;4(1):33-46.
3. Shapiro JM, Deutsch JK. Complementary and alternative medicine therapies for irritable bowel syndrome. Gastroenterol Clin North Am. 2021;50(3):671-688.
4. Dossett ML, Davis RB, Lembo AJ, Yeh GY. Complementary and alternative medicine use by US adults with gastrointestinal conditions: results from the 2012 National Health Interview Survey. Am J Gastroenterol. 2014;109(11):1705-1711.
5. Hung A, Kang N, Bollom A, Wolf JL, Lembo A. Complementary and alternative medicine use is prevalent among patients with gastrointestinal diseases. Dig Dis Sci. 2015;60(7):1883-1888.
6. van Tilburg MAL, Palsson OS, Levy RL, et al. Complementary and alternative medicine use and cost in functional bowel disorders: a six month prospective study in a large HMO. BMC Complement Altern Med. 2008;8:46.
7. Deutsch JK, Levitt J, Hass DJ. Complementary and alternative medicine for functional gastrointestinal disorders. Am J Gastroenterol. 2020;115(3):350-364.
8. Larussa T, Rossi M, Suraci E, et al. Use of complementary and alternative medicine by patients with irritable bowel syndrome according to the Roma IV criteria: a single-center Italian survey. Medicina (Kaunas). 2019;55(2):46.
9. Song J, Gibbens Y, Philpot L, Fadadu P, Green I, Jing (Iris) Wang X. S546 Age and gender differences in the attitudes towards complementary and alternative medicine in gastroenterology. Am J Gastroenterol. 2022;117(10S):e386-e387.
10. Gan WC, Smith L, Luca EJ, Harnett JE. The prevalence and characteristics of complementary medicine use by Australian and American adults living with gastrointestinal disorders: a systematic review. Complement Ther Med. 2018;41:52-60.
11. Billings W, Mathur K, Craven HJ, Xu H, Shin A. Potential benefit with complementary and alternative medicine in irritable bowel syndrome: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2021;19(8):1538-1553.e14.
12. Mountifield R, Andrews JM, Mikocka-Walus A, Bampton P. Doctor communication quality and friends’ attitudes influence complementary medicine use in inflammatory bowel disease. World J Gastroenterol. 2015;21(12):3663-3670.
13. Gallinger Z, Bressler B, Devlin SM, Plamondon S, Nguyen GC. A survey of perceptions and practices of complementary alternative medicine among Canadian gastroenterologists. Can J Gastroenterol Hepatol. 2014;28(1):45-49.
14. Lahner E, Emerenziani S, Cicala M, Arullani P, Annibale B. Complementary and alternative medicine in irritable bowel syndrome: a survey amongst Italian gastroenterologists. J Gastroenterol Hepatol Res. 2013;2(4):526-530.
15. Nagarajan N, Morden A, Bischof D, et al. The role of fiber supplementation in the treatment of irritable bowel syndrome: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2015;27(9):1002-1010.
16. Moayyedi P, Quigley EMM, Lacy BE, et al. The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(9):1367-1374.
17. Lacy BE, Pimentel M, Brenner DM, et al. ACG Clinical Guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44.
18. Slavin JL. Position of the American Dietetic Association: health implications of dietary fiber. J Am Diet Assoc. 2008;108(10):1716-1731.
19. Major G, Murray K, Singh G, et al. Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging. Neurogastroenterol Motil. 2018;30(9):e13400.
20. Gunn D, Abbas Z, Harris HC, et al. Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies. Gut. 2022;71(5):919-927.
21. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514.
22. Lynch E, Troob J, Lebwohl B, Freedberg DE. Who uses probiotics and why? A survey study conducted among general gastroenterology patients. BMJ Open Gastroenterol. 2021;8(1):e000742.
23. Pimentel M, Lembo A. Microbiome and its role in irritable bowel syndrome. Dig Dis Sci. 2020;65(3):829-839.
24. Goodoory VC, Khasawneh M, Black CJ, Quigley EMM, Moayyedi P, Ford AC. Efficacy of probiotics in irritable bowel syndrome: systematic review and meta-analysis. Gastroenterology. 2023;165(5):1206-1218.
25. Ford AC, Quigley EMM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109(10):1547-1561.
26. Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment Pharmacol Ther. 2018;48(10):1044-1060.
27. Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009;104(4):1033-1049.
28. Vasant DH, Paine PA, Black CJ, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021;70(7):1214-1240.
29. Su GL, Ko CW, Bercik P, et al. AGA Clinical Practice Guidelines on the role of probiotics in the management of gastrointestinal disorders. Gastroenterology. 2020;159(2):697-705.
30. Deehan EC, Al Antwan S, Witwer RS, Guerra P, John T, Monheit L. Revisiting the concepts of prebiotic and prebiotic effect in light of scientific and regulatory progress—a consensus paper from the Global Prebiotic Association. Adv Nutr. 2024;15(12):100329.
31. Hutchings HA, Wareham K, Baxter JN, et al. A randomised, cross-over, placebo-controlled study of Aloe vera in patients with irritable bowel syndrome: effects on patient quality of life. ISRN Gastroenterol. 2011;2011:206103.
32. Ahluwalia B, Magnusson MK, Böhn L, et al. Randomized clinical trial: effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2020;32(8):e13860.
33. Dimidi E, Whelan K. Food supplements and diet as treatment options in irritable bowel syndrome. Neurogastroenterol Motil. 2020;32(8):e13951.
34. Størsrud S, Pontén I, Simrén M. A pilot study of the effect of Aloe barbadensis Mill. extract (AVH200®) in patients with irritable bowel syndrome: a randomized, double-blind, placebo-controlled study. J Gastrointestin Liver Dis. 2015;24(3):275-280.
35. Hong SW, Chun J, Park S, Lee HJ, Im JP, Kim JS. Aloe vera is effective and safe in short-term treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Neurogastroenterol Motil. 2018;24(4):528-535.
36. Yang HN, Kim DJ, Kim YM, et al. Aloe-induced toxic hepatitis. J Korean Med Sci. 2010;25(3):492-495.
37. Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. Eur J Gastroenterol Hepatol. 2017;29(2):135-143.
38. Camilleri M. Cannabinoids and gastrointestinal motility: pharmacology, clinical effects, and potential therapeutics in humans. Neurogastroenterol Motil. 2018;30(9):e13370.
39. Wong BS, Camilleri M, Busciglio I, et al. Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 2011;141(5):1638-1647.e1-e7.
40. Adejumo AC, Ajayi TO, Adegbala OM, Bukong TN. Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity-matched analysis. Eur J Gastroenterol Hepatol. 2019;31(7):756-765.
41. Choi C, Abougergi M, Peluso H, Weiss SH, Nasir U, Pyrsopoulos N. Cannabis use is associated with reduced 30-day all-cause readmission among hospitalized patients with irritable bowel syndrome: a nationwide analysis. J Clin Gastroenterol. 2022;56(3):257-265.
42. Chang L, Cash BD, Lembo A, et al. Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: results from a phase 2b randomized placebo-controlled trial (CAPTIVATE). Neurogastroenterol Motil. 2023;35(5):e14539.
43. Ghayur MN, Gilani AH. Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders. Dig Dis Sci. 2005;50(10):1889-1897.
44. Zhang C, Huang Y, Li P, Chen X, Liu F, Hou Q. Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction. BMC Complement Med Ther. 2020;20(1):279.
45. van Tilburg MA, Palsson OS, Ringel Y, Whitehead WE. Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial. Complement Ther Med. 2014;22(1):17-20.
46. Crichton M, Marshall S, Marx W, et al. Effect of ginger root powder on gastrointestinal bacteria composition, gastrointestinal symptoms, mental health, fatigue, and quality of life: a double-blind placebo-controlled trial. J Nutr. 2023;153(11):3193-3206.
47. Chumpitazi BP, Kearns GL, Shulman RJ. Review article: the physiological effects and safety of peppermint oil and its efficacy in irritable bowel syndrome and other functional disorders. Aliment Pharmacol Ther. 2018;47(6):738-752.
48. Alammar N, Wang L, Saberi B, et al. The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis of the pooled clinical data. BMC Complement Altern Med. 2019;19(1):21.
49. Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Dig Dis Sci. 2016;61(2):560-571.
50. Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. Gastroenterology. 1991;101(1):55-65.
51. Weerts ZZRM, Masclee AAM, Witteman BJM, et al. Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Gastroenterology. 2020;158(1):123-136.
52. Cash BD. A minty breath of fresh air for irritable bowel syndrome. Gastroenterology. 2020;158(1):36-37.e1.
53. Nee J, Ballou S, Kelley JM, et al. Peppermint oil treatment for irritable bowel syndrome: a randomized placebo-controlled trial. Am J Gastroenterol. 2021;116(11):2279-2285.
54. Allescher HD, Burgell R, Malfertheiner P, Mearin F. Multi-target treatment for irritable bowel syndrome with STW 5: pharmacological modes of action. J Gastrointestin Liver Dis. 2020;29(2):227-233.
55. Madisch A, Holtmann G, Plein K, Hotz J. Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment Pharmacol Ther. 2004;19(3):271-279.
56. Aguilar A, Benslaiman B, Serra J. Effect of Iberogast (STW5) on tolerance to colonic gas in patients with irritable bowel syndrome: a randomized, double-blind, placebo control clinical trial. Neurogastroenterol Motil. 2024;36(10):e14765.
57. Sáez-González E, Conde I, Díaz-Jaime FC, Benlloch S, Prieto M, Berenguer M. Iberogast-induced severe hepatotoxicity leading to liver transplantation. Am J Gastroenterol. 2016;111(9):1364-1365.
58. Vinson B, Fink C, Wargenau M, Talley NJ, Holtmann G. Double-blind, randomized, 8-week multicenter study of the efficacy and safety of STW 5-II versus placebo in functional dyspepsia. JGH Open. 2024;8(5):e13054.
59. Andresen V, Shah A, Fink C, Rabini S, Wargenau M, Holtmann G. Efficacy and safety of STW 5-II for functional dyspepsia treatment: a patient data-based meta-analysis. Digestion. 2024;105(3):166-174.
60. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195-218.
61. Bundy R, Walker AF, Middleton RW, Booth J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med. 2004;10(6):1015-1018.
62. Ng QX, Soh AYS, Loke W, Venkatanarayanan N, Lim DY, Yeo WS. A meta-analysis of the clinical use of curcumin for irritable bowel syndrome (IBS). J Clin Med. 2018;7(10):298.
63. Turmeric. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Accessed June 29, 2024. http://www.ncbi.nlm.nih.gov/books/NBK548561/.
64. Coëffier M, Déchelotte P, Ducrotté P. Intestinal permeability in patients with diarrhea-predominant irritable bowel syndrome: is there a place for glutamine supplementation? Gastroenterology. 2015;148(5):1079-1080.
65. Zhou Q, Verne ML, Fields JZ, et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut. 2019;68(6):996-1002.
66. Ford AC, Gibson PR. Efficacy of glutamine in postinfection IBS. Gut. 2019;68(10):1905-1906.
67. Rastgoo S, Ebrahimi-Daryani N, Agah S, et al. Glutamine supplementation enhances the effects of a low FODMAP diet in irritable bowel syndrome management. Front Nutr. 2021;8:746703.
68. Wong RK, Yang C, Song GH, Wong J, Ho KY. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Dig Dis Sci. 2015;60(1):186-194.
69. Tu Q, Heitkemper MM, Jarrett ME, Buchanan DT. Sleep disturbances in irritable bowel syndrome: a systematic review. Neurogastroenterol Motil. 2017;29(3).
70. Saha L, Malhotra S, Rana S, Bhasin D, Pandhi P. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol. 2007;41(1):29-32.
71. Lu WZ, Gwee KA, Moochhalla S, Ho KY. Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2005;22(10):927-934.
72. Faghih Dinevari M, Jafarzadeh F, Jabbaripour Sarmadian A, Abbasian S, Nikniaz Z, Riazi A. The effect of melatonin on irritable bowel syndrome patients with and without sleep disorders: a randomized double-blinded placebo-controlled trial study. BMC Gastroenterol. 2023;23(1):135.
73. Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005;54(10):1402-1407.