Topics in Clinical Nutrition:
The Efficacy and Safety of 4 Natural Products for the Management of IBS
Hutcheon, Deborah A. MS, RD, LD
School of Health-Related Professions, Department of Nutritional Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey; and Division of Natural Science, Department of Biology, Bob Jones University, Greenville, South Carolina.
Correspondence: Deborah A. Hutcheon, MS, RD, LD, Division of Natural Science, Department of Biology, Bob Jones University, 1700 Wade Hampton Blvd, Greenville, SC 29614 ( email@example.com).
The author discloses that she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Traditional therapies are not always effective for the management of irritable bowel syndrome (IBS). Complementary and alternative medicine interventions are emerging in an attempt to find more effective means of IBS treatment. This article provides an overview of the literature for the integrative use of 2 probiotics, peppermint oil, and Aloe vera in the management of IBS in both adults and children. While there is scientific support for the efficacy and safety of specific probiotic strains and peppermint oil, the efficacy of Aloe vera gel is questionable due to the lack of scientific evidence and standardization of dosage.
IRRITABLE BOWEL SYNDROME (IBS) is a varied and multisymptom chronic functional bowel disorder evidenced by a combination of recurrent abdominal pain/discomfort and alterations in bowel habits. The 2 main criteria used for the diagnosis of IBS include the Manning Criteria1 and the Rome III Criteria.2 Irritable bowel syndrome manifests itself in 3 forms, which are constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed (IBS-M).3 The exact etiology of IBS is unknown but has been theorized to include genetics, altered bowel motility, imbalanced gastrointestinal (GI) microbiota, visceral hypersensitivity, impaired neurohormonal activity, and stress-response bowel inflammation.4
The treatment of IBS has focused on the management of symptoms through the use of medications and medical nutrition therapy (MNT), depending on the severity and form of IBS. Antidiarrheal, antibiotic, 5HT3- and 5HT4-receptor antagonists, selective C-2 chloride channel activators, and antidepressants are the most commonly prescribed medications for the management of IBS; however, many of these medications are not effective and may produce undesirable adverse effects.3 Medical nutrition therapy focuses on the management of symptoms through personalized dietary modification via the elimination of trigger foods, fermentable foods, gluten, high-fat foods, and alcohol5,6 and the increased consumption of fiber.6 Like medical management, the effectiveness of MNT varies by individual.
Complementary and alternative medicine (CAM) interventions for IBS are emerging in an attempt to find a more effective means of relief for the patient with IBS. These interventions include the use of natural products, defined as botanicals, vitamins, minerals, and probiotics; mind-body medicine, such as meditation, acupuncture, and hypnosis; and manipulative and body-based practices, such as spinal manipulation and massage, which are typically not considered part of conventional medicine, to promote health.7 When these therapies are found to be substantially safe and effective in the treatment of specific health conditions, they may be used in conjunction with conventional medicine to result in integrative medicine.7
A discussion of all CAM therapies for the management of IBS is beyond the scope of this article; therefore, the focus is on 4 natural product interventions. Two probiotics and the botanical peppermint oil will be discussed on the basis of their recognition as potential therapeutic agents by the American College of Gastroenterology Task Force on IBS3 and their commercial availability. A brief discussion of the botanical Aloe vera is included on the basis of anecdotal recommendation by natural product vendors. Thus, the purpose of this article is to provide an overview of the literature for the integrative use of 2 probiotics, peppermint oil, and Aloe vera in the management of IBS in adults and children.
Probiotics are living, nonpathogenic, metabolically active microorganisms found in some food substances which, when consumed, alter the GI microflora to provide a physiological and immunological benefit to the host.8 Many trials have been conducted on the safety and efficacy of probiotics for IBS. Because of the vastness of the literature and the strain variation among studies, this review will focus on 2 commercially available formulations, one being a composite multistrain probiotic and the other being a singular probiotic strain.
One composite probiotic medical food supplement (VSL 3, Sigma-Tau Pharmaceuticals, Inc, Gaithersburg, Maryland) that has been studied and is marketed for use in IBS contains 3 strains of Bifidobacterium (B longum, B infantis, and B breve), 4 strains of Lactobacillus (L acidophilus, L casei, L delbrueckii subspecies bulgaricus, and L plantarum), and 1 strain of Streptococcus (S salivarius subspecies thermophiles).9 This composite probiotic may be purchased as capsules, providing 250 billion live colony-forming units (CFU) per 2-capsule dose,9 or as powder packets, providing 450 billion CFU per packet dose.10
This composite probiotic appears to influence the physiological alterations common with IBS in 3 ways. First, it reduces the sensitivity of the intestinal lumen to environmental stimuli, which are responsible for triggering bowel motility and pain in patients with IBS.11 Second, it strengthens the structural arrangement of the intestinal cells, or enterocytes, making them less permeable to bacteria and dietary antigens, which also trigger bowel motility and pain.11 Third, it changes the composition of the GI microflora and the environment of the colon so that bacterial fermentation and fluid and electrolyte absorption do not over- or understimulate bowel motility.12 Thus, by these mechanisms of action, patients with IBS may experience less bloating, gas, pain, and fluctuation in bowel habits.
According to the Natural Medicines Comprehensive Database, this composite probiotic is likely safe for use in both adults and children when consumed according to product directions.13 A recent systematic review graded its safety as high when used under the supervision of a qualified health care provider to manage IBS in adults.14 The specified formulation of this composite probiotic is classified by the manufacturer as a generally recognized as safe medical food.9 However, it should be noted that this status is self-affirmed by the manufacturer and not independently confirmed. Adverse effects with oral administration appear limited to mild abdominal bloating with initial use.9,13
Three randomized controlled trials (RCTs),12,15,16 predominantly in adult patients with IBS-D, have been conducted using the specified composite probiotic at doses of 450 to 900 billion CFU daily in powder form for 8 weeks. Table 1 provides a summary of these studies. Kim et al15 demonstrated no improvement in colonic transit, individual symptoms, and overall symptoms compared with placebo but did demonstrate a significant improvement in bloating between pre- and posttreatment (P = .046) for those who consumed the composite probiotic. Michail and Kenche16 demonstrated a reduction in both individual and overall symptom measures in both the composite probiotic and placebo groups, but no statistically significant difference was seen between the groups except for the satiety score, which was improved in the composite probiotic group. In addition, both groups demonstrated an improvement in quality of life (QoL) scores without a statistically significant difference between the groups. No statistically significant change in fecal microbiota was observed in either group.16 A second study by Kim et al12 resulted in a decrease, though not statistically significant, in individual and overall symptom measures, including bloating, compared with placebo. A statistically significant reduction (P = .011) in flatulence and an increase (P = .05) in the 24-hour colonic transit time were observed in the composite probiotic group compared with the placebo group.12
Because the results of these studies are mixed, a recent systematic review by Hungin et al14 classified this specified composite probiotic as one that does not provide significant benefit for overall symptom relief in adult patients with IBS-D nor specific symptom (abdominal pain, bloating/distension, and frequency and/or consistency of bowel movements) relief in adult patients with IBS. However, it was classified as a probiotic that may or may not reduce flatulence in adult patients with IBS.
One randomized crossover trial17 of the specified composite probiotic has been performed in children between the ages of 4 and 18 with IBS. The study protocol indicates that patients were given either 1 packet or 2 packets of the composite probiotic daily, depending on patient age, but the protocol does not disclose the CFU count of these dosages. After 6 weeks of treatment, the probiotic improved overall symptom relief (P < .05), abdominal pain/discomfort (P < .05), abdominal bloating/gassiness (P < .05), and family assessment of life disruption (P < .01). The stool pattern was also improved, but it was not statistically significant. Thus, further research is required to determine an appropriate dosage and verifiable effectiveness for use in children with IBS.
Bifidobacterium infantis 35624
Bifidobacterium infantis 35624 (Align, Proctor & Gamble, Inc, Cincinnati, Ohio), a single-strain probiotic dietary supplement, can be purchased in the form of a capsule to provide 1 billion CFU per capsule.18 Although the commercial product has not been tested specifically for its effectiveness in IBS, Bifidobacterium infantis 35624 has demonstrated effectiveness and safety in IBS symptom reduction.19,20 Most of these studies investigate Bifidobacterium infantis 35624 at doses of either less than or greater than the 1 billion CFU per commercial capsule. Therefore, further research may be warranted to determine the effectiveness of 1 commercial capsule daily in IBS management.
Bifidobacterium infantis 35624 appears to be effective in the treatment of IBS by reducing proinflammatory and increasing anti-inflammatory cytokine production,19,21 by inducing a GI immune response to intestinal pathogens,21 and by reducing the sensitivity of the intestinal lumen to environmental stimuli to attenuate the pain22 and distension23 response. According to the Natural Medicines Comprehensive Database, Bifidobacterium is likely safe for use in both adults and children when consumed daily for up to 1 year.24 Like the composite probiotic, the systematic review by Hungin et al14 graded the safety of Bifidobacterium infantis 35624 as high when used under the supervision of a qualified health care provider to manage IBS in adults. The potential adverse effects are limited to mild abdominal bloating and gas.18
Two RCTs19,20 have been conducted using Bifidobacterium infantis 35624 at doses ranging from 1 million to 10 billion CFU daily for 4 to 8 weeks to modify the symptoms of IBS. Both trials produced positive results. An RCT by O'Mahony et al in which adult patients with IBS received 10 billion CFU Bifidobacterium infantis 35624, 10 billion CFU Lactobacillus salivarius UCC4331, or placebo daily for 8 weeks showed Bifidobacterium infantis 35624 to be superior to the other treatment regimens at reducing composite and individual symptom scores for pain/discomfort, bloating/distention, and bowel movement difficulty during most weeks of the treatment protocol. An improvement in the ratio between anti-inflammatory and proinflammatory cytokines, which returned to levels seen in healthy subjects, was observed in the Bifidobacterium group. Bowel movement frequency and consistency remained unchanged.19
An RCT by Whorwell et al,20 where adult female IBS patients received 1 million, 100 million, or 10 billion CFU Bifidobacterium infantis 35624 or placebo daily for 4 weeks, showed that Bifidobacterium infantis 35624 at 100 million CFU daily was significantly superior to the other treatments tested at improving composite and individual symptom scores in patients with either IBS-D or IBS-C. The 10 billion bacteria capsule appeared to have some formulation flaws, which may have limited its effectiveness in this study.20
Although these studies present limited and preliminary data, Bifidobacterium infantis 35624 at either 100 million or 10 billion CFU daily demonstrates the potential for improvement in overall and individual IBS symptoms. Hungin et al14 classified the evidence for this probiotic as high for improving overall symptoms in some adult patients with IBS and moderate for improving overall symptoms in some adult patients with IBS-D. Pertaining to individual symptoms, it was classified as high for reducing abdominal pain, moderate for reducing bloating/distension, low for reducing flatulence, and moderate for improving frequency and/or consistency of bowel movements. However, it was classified as a probiotic that may not reduce overall symptoms in adult patients with IBS-C or improve QoL in some adult patients with IBS. To date, no studies using Bifidobacterium infantis 35624 have been conducted in children with IBS. Further research is recommended in both adults and children to definitively determine specific and overall symptom relief, QoL improvement, and effective dosage for IBS, including the necessity of short-term versus long-term, or even life-long, and consistent versus inconsistent consumption.
Peppermint oil is a volatile oil extracted through distillation of the herbaceous plant Mentha piperita Labaiatae.25 Peppermint oil is composed of 35% to 60% menthol, 15% to 30% menthone, and 4% to 14% menthyl acetate in addition to smaller percentages of other compounds.25 For internal use, peppermint oil may be purchased and consumed as a liquid or a capsule.
Menthol, the active compound in peppermint oil, serves as a calcium-channel blocker to promote smooth muscle relaxation in GI tissue.26,27 Peppermint oil may also serve as a mild topical analgesic to reduce pain28 and as an antibacterial agent to reduce bacterial overgrowth.29 Through these mechanisms of action, the symptoms of IBS caused by stress-response inflammation, by the sensitivity of the intestinal lumen to environmental stimuli, and by alterations in the composition and activity of the GI microflora may be reduced.
In the United States, peppermint oil is considered a generally recognized as safe essential oil or natural extractive food additive by the Food and Drug Administration (FDA);30 however, because of insufficient data, the FDA does not recognize peppermint oil as a safe and effective ingredient in over-the-counter digestive aids.31 According to the Natural Medicines Comprehensive Database, oral administration of peppermint oil at doses up to 220 mg 3 to 4 times daily is likely safe for use in both adults and children.32 Consumers of peppermint oil should note the quality of the product, choosing a product containing an independent purity verification by either the United States Pharmacopeia or the NSF International to limit, or avoid, exposure to pulegone, a neuro- and hepatotoxin.25 Pulegone is present in immature peppermint leaves, from which low-quality peppermint oil may be derived.25 Pulegone is converted into methone during leaf maturation.25 Therefore, this toxin is typically not present in mature leaves from which high-quality, or pharmaceutical grade, peppermint oil would be made.25 Pulegone content, not disclosed on product labels, may range from less than 1%, a safe amount found in pharmaceutical products, to 4%, an unsafe amount found in products without purity verification.25
Peppermint oil is a carminative, or a substance that produces and expels gas. As such, it is known to reduce pressure of the lower esophageal sphincter, leading to an increased risk of gastric irritation and heartburn. To prevent irritation in the stomach and to promote action within the intestines, a pH-dependent, enteric-coated peppermint oil capsule is advised.32 Such capsules (Colpermin, Tillotts Pharma AG, Rheinfelden, Switzerland and Mintoil, Cadigroup, Rome, Italy) provide either 187 mg33 or 220 mg34 peppermint oil, respectively, per capsule.
No significant adverse effects have been seen in studies using enteric-coated peppermint oil for the treatment of IBS.28,29,35,36 Patients who chew the capsules rather than swallow them whole may experience heartburn.29,35 Because of the menthol content within the capsule, some patients may experience burning upon defecation.35
In adults, Liu et al35 found that more than 75% of patients who consumed peppermint oil exhibited a significant improvement (P < .05) in abdominal pain, abdominal distension, the movement of gas though the GI tract and resultant intestinal grumbling, stool frequency and consistency, and flatulence compared with placebo. These improvements were seen within 2 weeks of treatment. Likewise, Cappello et al29 found peppermint oil to be effective in improving the overall symptoms of IBS both at the end of treatment (75% treatment vs 38% placebo, P < .01) and at 4 weeks posttreatment (54% treatment vs 11% placebo, P < .05) compared with placebo. Merat et al found that peppermint oil significantly decreased (P < .001) abdominal pain/discomfort compared with placebo (42.5% vs 22.2%, respectively). In addition, a significant improvement (P = .016) in QoL was seen in the peppermint oil group.36 In children, Kline et al28 found that peppermint oil significantly improved the severity of symptoms (76% vs 19%), the change in symptoms (71% vs 43%), and the severity of pain compared with placebo. Similar to the Liu et al study,35 these improvements were seen within 2 weeks of treatment.28 Data from these 4 studies are summarized in Table 2.
In 1998, Pittler and Ernst published a critical review and meta-analysis of peppermint oil's effectiveness in IBS. The meta-analysis, which included 5 double-blind, placebo-controlled RCTs, showed a significant improvement (P < .001) in total IBS symptoms for those treated with peppermint oil at doses of 0.2 to 0.4 mL 3 times daily. However, the authors concluded that, due to conflicting results, a positive benefit could not be established.37 In contrast to the meta-analysis published by Pittler and Ernst,37 a meta-analysis published by Ford et al,38 including the aforementioned studies,28,29,35,36 concluded that peppermint oil is more effective than placebo in the treatment of IBS.38 While further research involving larger sample sizes and long-term duration (>8 weeks) is warranted to strengthen the scientific body of knowledge, present findings point to demonstrated short-term (2–8 weeks) effectiveness and safety for enteric-coated peppermint oil capsules in the treatment of IBS in both adults and children.
ALOE VERA GEL
Aloe vera is a tropical cactus in the Lily family whose leaves secrete a clear, gel-like substance commonly used in the topical treatment of skin ailments.39,40Aloe vera gel has been recommended anecdotally for IBS based on its potential antimicrobial,39 healing,39 and anti-inflammatory properties39,41 derived from its more than 70 biologically active compounds.39 Because it is composed of polysaccharides with many β 1–4 glycosidic bonds, Aloe vera gel is a nondigestible fiber fermented by intestinal bacteria to produce short-chain fatty acids, which provide an anti-inflammatory effect.42
According to the Natural Medicines Comprehensive Database, the oral ingestion of Aloe vera gel extracted from the inner leaf pulp is possibly safe in adults without any adverse effect.43 In gel form, the FDA permits the use of Aloe vera as a natural flavoring food additive.44Aloe vera latex extracted from the outer leaf pulp contains anthraquinones, mainly as aloins, which have been shown to produce a laxative effect,39 but are carcinogenic in animal models.45 Because of such safety concerns, since 2002, the FDA has banned the use of Aloe vera latex in over-the-counter laxative products.46 The Natural Medicines Comprehensive Database warns against the oral ingestion of Aloe vera latex because it is likely unsafe for use by adults and children.43
Despite anecdotal evidence for the use of Aloe vera gel in the treatment of IBS, only 2 RCTs involving adult patients have been published. In 2006, Davis et al found that the consumption of 50 mL of Aloe vera juice 4 times daily for 1 month improved symptoms in patients with either IBS-D or IBS-M, but not in all patients with IBS, compared with placebo. This improvement, though not statistically significant, continued for up to 2 months posttreatment.47 In 2011, Hutchings et al48 found that the consumption of 60 mL of Aloe vera juice twice daily for 5 months did not significantly improve QoL and general symptom scores compared with placebo. Both of these studies present multiple weaknesses including small sample sizes, large patient withdrawal because of increased symptoms with Aloe vera ingestion, loss at follow-up, and short duration. Further research is needed to determine whether or not Aloe vera is clinically effective and safe for the management of IBS in adults and children.
Probiotics, peppermint oil, and Aloe vera gel are natural products that have been studied for the management of IBS. Of the 2 probiotics discussed, Bifidobacterium infantis 35624 at doses up to 10 billion CFU daily demonstrates the stronger evidence for reducing overall and individual symptoms and for improving QoL in adults with IBS. Likewise, enteric-coated peppermint oil capsules at 187 to 220 mg peppermint oil prior to meals 3 to 4 times daily appear to provide similar benefits in both adults and children with IBS. While scientific support for the effectiveness and safety of these natural products is sound, the effectiveness of Aloe vera gel in adults with IBS is questionable due to the lack of scientific evidence and standardization in dosage. Therefore, peppermint oil and certain strains of probiotics seem safe and effective in the short-term management (up to 8 weeks) of IBS in adults (peppermint oil and Bifidobacterium infantis 35624) and children (peppermint oil), but Aloe vera should be avoided for use in all patients with IBS until evidence-based efficacy and safety are established.
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Aloe vera; complementary and alternative medicine; integrative medicine; irritable bowel syndrome; peppermint oil; probiotics
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