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   Oct 29

Complementary and Alternative Medicine in Irritable Bowel Syndrome

Physicians are seeing an increasing number of patients with irritable bowel syndrome seeking relief of symptoms, or even cures, through complementary and alternative medicine (CAM). Many patients learn about an expanding menu of options on blogs or from wellness-oriented Facebook groups. In a national health interview survey of 23,000 patients, approximately 40% reported having used a CAM therapy within the past year.1 CAM is now a $27 billion industry, with estimated annual expenditures equivalent to out-of-pocket expenditures for all U.S. physician-based services.2

IBS is a functional bowel disorder that affects 11% of adults worldwide. The typical patient is a woman under 50 years old, although men and children often are affected.3 Many patients express frustration that their workup fails to reveal an organic source of discomfort. Some turn to CAM as a perceived safer alternative to prescription medication and one that gives them more control over their condition. Most medical doctors are not trained in CAM therapy and many feel unprepared to discuss it with their patients. This article will review popular CAM therapies, including yoga, acupuncture, hypnotherapy, and herbal medications, and their role in IBS.

Treatment Approaches

Treatment of IBS depends on subcategorization and patient comorbidities. In 2009, the American College of Gastroenterology Task Force on IBS published a detailed systematic review regarding the management of IBS.4 The task force provided recommendations regarding modifications to diet or lifestyle; pharmacotherapy; or CAM therapies, such as hypnotherapy, cognitive-behavioral therapy, acupuncture, and herbal treatments.

Confounding the data of many well-designed IBS studies is the consistently strong placebo effect.4,5 In fact, the placebo effect has been found to rely on complex neurobiological mechanisms involving neurotransmitters (eg, dopamine) and activation of specific, measurable, and relevant areas of the brain. The strong placebo effect seen in IBS studies may reflect the importance of the role of the brain–gut axis or enteric nervous system (ENS), and the contribution that underlying neurotransmitter dysfunction from emotions, stress, and mood disorders have on IBS.

The most common treatment approach is pharmacotherapy. Medications are directed at symptom management but often fail because the exact mechanism of developing IBS is unknown and untargeted.6 Many patients experience an inadequate response or unacceptable adverse events, or prefer alternative therapies because of accessibility or safety concerns, enhanced benefits, and lower cost.7 Regardless of the reason, up to 50% of all IBS patients turn to CAM as a sole approach or in combination with pharmacotherapy to manage their life-altering symptoms.8

CAM

CAM offers a wide variety of therapeutic modalities: diet and lifestyle changes, herbal medications, mechanical interventions (acupuncture or massage), or behavioral therapy (cognitive-behavioral therapy, relaxation techniques, and hypnotherapy). The 2009 ACG Task Force on IBS and other organizations have been unable to provide strong recommendations on CAM because of a lack of evidence-based clinical trials.4 However, several recent studies and systematic reviews have found that some CAMs can improve symptoms and quality of life for patients with IBS.

The National Center for Complementary and Integrative Health defines mind–body therapies as those that “focus on interactions among the brain, mind, body, and behavior with the intent to use the mind to affect physical functioning and promote health.”9 Yoga, acupuncture, and hypnotherapy all fall under this definition and will be discussed in further detail.

Yoga

Yoga is a mind–body therapy that combines various poses with breathing techniques to enable focused practice on muscle contraction, relaxation and meditation. Its origins date back to 3000 bc and Patajali, a Sanskrit scholar and Indian physician.10 Yoga has been studied for various chronic conditions, including chronic low back pain, osteoarthritis, and fibromyalgia, with each form being individually tailored to the disease being treated.11-13 Similarly, certain poses can focus on GI motility and abdominal pain in IBS.

Researchers have proposed numerous hypotheses for how yoga may alter the perception of pain. These include the gate control theory that a faster pressure signal from yoga or massage reaches the brain before a sensation of pain and therefore “closes the gate” to the pain stimulus10; that yoga corrects the underactivity of the parasympathetic nervous system induced by stress14; or that yoga causes an increase in the release of serotonin, which results in decreased cortisol and substance P, a common pain-causing chemical.10 The gate control theory is most frequently used to explain the effect of massage therapy on pain syndromes and through the various poses, yoga acts as a form of self-massage.

Although pain normally stimulates nerve fibers with less myelination, which delays signaling to the brain, pressure signals are carried by nerve fibers that are better myelinated and therefore able to more rapidly transmit the stimulus and block the sensation of pain on the refractory sensory receptor.10

Schumann et al published the first and only systematic review on yoga in IBS in December 2016.15 After an extensive screening process, six international randomized controlled trials (RCTs) met their eligibility criteria. These trials compared yoga with usual care and nonpharmacologic or pharmacologic interventions in patients with IBS.16-21 This review was unable to promote yoga for the relief of IBS symptoms because of the heterogeneous methods of each study and unclear risk for bias. However, beneficial effects of yoga were seen on quality of life and anxiety when compared to no treatment.16-18

When comparing the yoga arm with a control group, individual studies reported considerable effects of yoga on symptoms related to IBS, measured by the IBS Severity Scoring System.16-21 No serious adverse events occurred during any of the yoga sessions in the six studies, indicating it is a safe CAM alternative for patients.

Each study had several limitations, such as in methodology, unknown risk for bias, and external validity that prevent authors and associations like the American College of Gastroenterology from strongly promoting yoga for IBS. Despite these limitations, yoga should not be discouraged in this patient population. Studies on yoga as CAM therapy for IBS may be inconclusive, but the data do suggest that yoga is associated with an improved quality of life. If patients report reduction of symptoms with yoga, they should not be deterred from continued practice. If they ask for advice on whether to try yoga as therapy, clinicians should feel comfortable stating that the activity is promising and safe, although well-designed and properly controlled studies are lacking.

Hypnotherapy

Another CAM mind–body therapy commonly practiced and studied in IBS is hypnotherapy. The first application of hypnosis for IBS treatment was described by Whorwell and colleagues at the University Hospital of South Manchester, England, in the 1980s.22 Unlike yoga, there is no mechanical component; instead, the treatment goal is to change physiologic function through psychological reprogramming.8

The process of hypnotherapy is as follows: Suggestive imaginative experiences are presented, followed by a hypnotic induction during which the subject enters an altered consciousness. Once the patient reaches this state, the inducer makes repetitive suggestions for normalization and control of GI function and improvement of symptoms.23

The mechanism of action of hypnotherapy is not fully understood. The treatment may affect gut function, visceral sensitivity, psychological outcomes including depression and anxiety, and normalize pain processing and perception via the brain–gut axis.24 Gut-directed hypnotherapy in IBS has 2 standard protocols: the Manchester Approach22 and the North Carolina Protocol.25 Both approaches attempt to increase control of GI function through the use of gut-directed imagery based on mental and muscular relaxation and hypnotic suggestions that focus and distract from symptoms. Each treatment involves 7 to 10 sessions within an 8- to 12-week period.

Whorwell et al conducted the first RCT of hypnotherapy for the improvement of IBS symptoms in 1984.26 Since then, there have been several RCTs with a recent systematic review and meta-analysis published in 2014 that compared 5 separate trials in 4 articles.27-31 These 5 studies compared hypnotherapy with control therapy in a total of 278 patients. Improvement in GI symptoms ranged from 24% to 73% in patients who received gut-directed hypnotherapy, where 3 of the 5 studies achieved better than 50% improvement.28,29,31 The number needed to treat was calculated as 4 (95% CI, 3-8).27 Long-term maintenance of symptom relief after cessation of hypnotherapy also was seen in 4 of the trials, and ranged from 2 months to one year.28,30,31 No adverse events were reported.

There are several limitations to each study and some of them may be difficult to overcome because of the nature of hypnotherapy. Conducting a well-designed RCT of hypnotherapy is difficult because participants and researchers cannot be easily blinded to treatment arms. Furthermore, all of these studies had small sample sizes, with fewer than 100 subjects. Despite these points, the systematic review and meta-analysis by Ford et al, in 2014, found that hypnotherapy is an effective treatment modality for IBS.27 Similarly, the 2009 Task Force on IBS also made a Grade 1C recommendation that hypnotherapy is more effective than usual care in alleviating global symptoms of IBS.4 Although larger RCTs are still required, publications support the use of hypnotherapy as a primary or adjunctive therapy, and it can be discussed with patients based on access to trained professionals in this field.

Acupuncture

Both gut-directed and general acupuncture have been studied as CAM therapy for IBS. Acupuncture has been a part of traditional Chinese medicine (TCM) for thousands of years, but entered the mainstream Western vernacular relatively recently. In TCM acupuncture, needles are inserted at particular meridian points to promote the flow of energy. The therapy targets serotonergic, cholinergic, and glutamatergic pathways, resulting in lower levels of cortisol in blood, and reducing the visceral and global perception of pain by increasing the release of endogenous opioids.32,33

A 2012 systematic review and meta-analysis by Manheimer et al estimated the effects of acupuncture for treating IBS. The review included 17 eligible RCTs that compared acupuncture with sham acupuncture, other active treatments, no treatment, or as an adjuvant to another treatment.34-35 Five of the RCTs compared the effects of acupuncture with sham acupuncture, and each individual study, as well as the pooled analysis, showed no differences between the two treatments on symptom severity and quality of life.36-40 Five of the RCTs compared acupuncture with pharmacologic therapies and found that subjects who received acupuncture reported a greater improvement in symptom severity.41-45 Five trials compared the combination of adjuvant acupuncture with an additional IBS treatment and another arm receiving the other IBS treatment alone. Pooled analysis showed an improvement in patients who received acupuncture as an adjunctive therapy.46-50 Furthermore, two RCTs compared the effects of acupuncture and no specific treatment and continued standard care for IBS.38,51 Both studies showed a statistically significant improvement in IBS symptom severity and benefit from acupuncture. Only one adverse event, syncope was reported in any of the trials; the subject withdrew from the study.42

The 2009 task force was unable to make any recommendations about the effect of acupuncture on IBS symptoms. At that time, the only available systematic review was a 2006 Cochrane Review, which has since been updated.35 Similar to previously discussed study limitations in hypnotherapy and yoga, the RCTs investigating acupuncture also have the following limitations: bias from unblinded design, questionable external validity of results, and study power reduced by small sample sizes. Overall, studies have found acupuncture to be beneficial and to result in improvement of symptoms, whether as a single or adjunct treatment. Although no statistically significant benefit was found for acupuncture over sham acupuncture, it is important to note that both interventions appear to result in improvement of IBS symptoms, indicating that the ritual of acupuncture may be at the root of its effectiveness.

Dietary Supplements

Herbal supplements, individually or in combination, are commonly self-administered as monotherapy or an adjunct therapy for IBS. Herbal medicine is the most common CAM used in patients with IBS, with an estimated 43% of patients resorting to such therapies at some point during the course of their illness.52 These medicines often have a traditional background as digestive aids.

Multiple trials of various herbal remedies have failed to demonstrate that herbal remedies as a whole are effective for treating the symptoms of IBS. However, a few products do appear to provide some benefit.

Peppermint oil, or mentha piperita, has been used for thousands of years in Persian traditional medicine.52 The naturally occurring plant acts as a antispasmodic by causing a blockade of calcium channels, resulting in relaxation of the smooth muscles in the GI tract.53,54 The 2009 task force gave a Grade 2B recommendation for the superiority of peppermint oil over placebo, but noted that the recommendation was based on a small number of studies with small sample sizes.4 The most recent systematic review and meta-analysis in 2014 by Khanna et al included 9 RCTs, with a total of 726 patients who took peppermint oil for 2 weeks or more.55 The authors found a statistically significant benefit for peppermint oil compared with placebo for global improvement of IBS symptoms and abdominal pain. Five studies found that 69% of patients who received peppermint oil had global improvement of IBS symptoms compared with 31% of placebo patients (relative risk [RR], 2.23; 95% CI, 1.78-2.21).55-60 Five studies reported treatment outcomes in terms of improvement in abdominal pain, and found that 57% of patients who took peppermint oil reported an improvement in abdominal pain, compared with 27% of placebo patients (RR, 2.14; 95% CI, 1.64-2.79).55,59-63 Few adverse events were reported, and all were mild and transient. The most common was heartburn caused by subjects chewing the capsules or taking the capsule with meals, which resulted in lower esophageal sphincter relaxation and acid reflux.58,59,62,63 Additional studies are needed involving larger sample sizes over a longer study duration, but the available data show that peppermint oil is a safe and effective short-term treatment with significant symptom improvement. Peppermint oil is available over the counter as the medical food IBgard (IM HealthScience), which contains enteric-coated, sustained-release microspheres that deliver peppermint oil to the small intestine.

Turmeric (curcuma longa) is a common spice in Asian cuisine and traditionally has been used in Iranian and Chinese traditional medicine for digestion, abdominal pain, bloating, and distention.52 Two trials have compared turmeric and placebo. One, a partially blinded RCT with 270 subjects, evaluated 72 or 144 mg per day of turmeric. The study found a decrease in IBS symptoms and an increase in quality of life.64 A double-blind, placebo-controlled RCT involved 106 subjects who received turmeric, the herbal supplement Fumaria officinalis, or placebo 3 times per day for 18 weeks. This study found no significant improvement in abdominal pain or IBS symptoms for either supplement over placebo.65 The contradictory results of these two trials indicate a need for larger studies to detect a true clinical difference or benefit, if any, of turmeric for IBS.

Iberogast (Bayer), also known as STW 5, is a proprietary combination of 9 herbal extracts. Initially intended for the treatment of functional dyspepsia, Iberogast consists of bitter candytuft, chamomile flower, peppermint leaves, caraway fruit, licorice root, lemon balm leaves, celandine herbs, angelica root, and milk thistle fruit. The extracts are thought to act on serotonin, acetylcholine, and opioid receptors in the GI tract.66 Three double-blind RCTs found that use of Iberogast was associated with a statistically significant global decrease in GI symptom scores.67-69 The 2006 Cochrane Database used the Madisch et al study when determining that STW 5 is effective in alleviating IBS symptoms.70

Conclusion

The popularity of CAM for treatment of IBS is growing and providers must stay current on treatments—whether bona fide or baseless—to have knowledgeable discussions with patients. Many of these treatments suffer from poorly designed studies with inherent biases unique to the particular therapy. For example, it is impossible to create a blind study or administer a placebo with treatments such as hypnotherapy or yoga without the subject being aware of the treatment arm. Despite these shortcomings, gastroenterologists should not let their practices be limited by the absence of high-quality data. Many CAM therapies are safe, if not particularly effective, and patients will be exploring their options with or without the support of their care providers.

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