CHAPTER 127 Complementary and Alternative Medicine
DEFINITION AND EPIDEMIOLOGY
Complementary and alternative medicine (CAM) is defined broadly as medical practices neither taught widely in medical schools nor generally available in U.S. hospitals.1 The prevalence of CAM therapies has increased at an exponential rate both in national and international medical communities. A study by Eisenberg and associates1 demonstrated that among the U.S. population, CAM use increased from 33.8% to 42.1% from 1990 to 1997. Estimated annual expenditures for CAM therapies are in excess of $27 billion, a sum that is equivalent to patients’ out-of-pocket expenditures for all U.S. physician-based services.1
In a study by Ganguli and colleagues, at least 50% of gastroenterology outpatients in a community setting were shown to have implemented CAM therapies to help ameliorate their symptoms.2 Given the widespread use of these modalities and the continuing trend of their increased use, an understanding of CAM therapies, including their potential risks and benefits, is necessary for the practicing gastroenterologist. A thorough knowledge of these practices allows physicians to provide comprehensive medical care and can help further a therapeutic rapport between physicians and their patients.
TYPES OF THERAPIES
There are a wide variety of CAM therapies, and those most commonly employed for gastrointestinal and hepatic disease are defined in Table 127-1. Regardless of the therapy employed, the overall philosophy of CAM takes a uniform holistic approach that all disease results from disturbances at a combination of physical, psychological, social, and spiritual levels. Thus, a CAM modality is used to restore balance and to facilitate the body’s own healing responses, thereby ameliorating troublesome symptoms.3
Table 127-1 Common Complementary and Alternative Therapies for Gastrointestinal and Hepatic Diseases
| Acupuncture |
| Based on the principles of Chinese medicine, qi is energy, which circulates among organs along channels called meridians. Through placement of needles at specifically defined locations (points), the flow of qi is restored to appropriate levels and the health of specific organs is improved. |
| Ayurveda |
| Holistic system of medicine from India that provides diet and lifestyle recommendations to improve overall health. |
| Colonic Irrigation Therapy |
| Cleansing of the colon through various oral and enema preparations to improve “digestive health.” |
| Herbal Medicine |
| Ingestion of various herbal therapies, supplements, or probiotics to improve physiologic function. |
| Homeopathy |
| Based on the principle “like should be cured with like.” Administration of a diluted solution that, when given to a healthy person in an undiluted form, causes symptoms identical to those experienced by the ill person. |
| Hypnosis |
| Induction of a deeply relaxed state during which therapeutic suggestions are made to alter behavior and enhance relief of symptoms. |
| Meditation, Relaxation |
| A process of reflection and contemplation allowing one to focus thoughts to help alleviate symptoms. |
| Reflexology |
| Areas on the feet correspond to organs of the body. Massage and pressure applied to these regions can improve symptoms throughout the body. |
DEMOGRAPHY OF CAM USERS
Certain patients are more likely to use CAM therapies than are others. Women and whites tend to use CAM more often than do men and African Americans, respectively. Patients with higher levels of education, higher annual incomes, and comorbid medical conditions also are more likely to use CAM therapies.1,2 Knowledge of these demographics assists the gastroenterologist in determining which patients are likely to be using these therapies, but it is also important to understand each patient’s rationale and motivation for choosing a particular therapeutic modality.
GASTROINTESTINAL DISORDERS ADDRESSED BY COMPLEMENTARY AND ALTERNATIVE THERAPIES
NAUSEA AND VOMITING
Nausea and vomiting have a wide array of causes ranging from viral gastroenteritis to pregnancy. These symptoms can be quite distressing, and patients often resort to CAM therapies to seek symptomatic improvement. In one study of pregnant women with nausea and vomiting, 61% reported using CAM therapies for relief.4 Several complementary modalities have been used to help ameliorate nausea and vomiting, ranging from herbal medicines to relaxation techniques (Table 127-2).
Ginger
Ginger (Zingiber officinale) is the herbal supplement most commonly employed to relieve nausea and vomiting and derives its name from the Sanskrit word for “horn,” which describes the twisted, gnarled shape of its roots. Several mechanisms have been postulated to explain the antiemetic effect of ginger. Animal studies have demonstrated that one component of the herb, 6-gingerol, improves gastrointestinal motility,5 and another component, galanolactone, is a 5-hydroxytryptamine (HT)3 antagonist,6 similar to ondansetron, an antiemetic agent used to treat chemotherapy-induced nausea and vomiting.
The antiemetic effect of ginger has been studied in various clinical conditions, including morning sickness, seasickness, chemotherapy-induced nausea, and postoperative nausea. Although no more effective than placebo for preventing experimentally induced motion sickness, ginger has been documented to reduce vertigo induced by caloric stimulation of the vestibular apparatus within the inner ear.7–9 In a systematic review of randomized clinical trials evaluating the efficacy of ginger for nausea and vomiting, Ernst and Pittler demonstrated that ginger is superior to placebo and equal in efficacy to metoclopramide for postoperative nausea and emesis. Furthermore, ginger relieved symptoms better than did placebo agents for the treatment of seasickness, morning sickness of pregnancy, and chemotherapy-induced nausea and vomiting.10 The dose of ginger prescribed in most of these studies ranged from 0.5 to 1 g/day.
Although ginger appears to be a natural supplement with therapeutic effect, its potential adverse reactions must be taken into consideration before advocating it for relief of symptoms. First, ginger has been shown to inhibit platelet aggregation by inhibiting thromboxane synthase. Therefore, if patients are taking warfarin, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or clopidogrel concurrently, the risk of bleeding is increased.11 Second, although not proved in animal studies, ginger has been documented to be potentially mutagenic in laboratory assays, thereby raising questions about the safety of the herbal supplement in pregnancy.12,13
Pyridoxine (Vitamin B6)
The water-soluble vitamin pyridoxine is another CAM therapy used to relieve the nausea and vomiting associated with pregnancy,14 and it was one of the most commonly employed CAM agents in a survey of pregnant Canadian women with nausea and vomiting, 29% of whom reported using it.4 Vutyavanich and colleagues reported a significant reduction in nausea, but no statistically significant reduction in vomiting, with pyridoxine, 30 mg daily, in a randomized controlled trial (RCT).15
Although the mechanism of action of pyridoxine is not established, certain drug interactions and adverse effects have been noted. Pyridoxine has been documented to decrease serum levels of levodopa, phenobarbital, and phenytoin when administered with these agents.16 Allergic reactions to pyridoxine also have been documented, and when taken in excess (more than 250 mg/day), pyridoxine has been reported to cause peripheral neuropathy, dermatoses, photosensitivity, and dizziness.17,18
Acupuncture and Acupressure
Acupuncture is another CAM modality commonly used to treat nausea and vomiting. In Chinese subjects, the P6 acupuncture point stimulated for relief of these symptoms is named neiguan, meaning “medial pass.” This acupuncture point is anatomically located three fingerbreadths above the proximal palmar crease on the volar aspect of the wrist in the midline. To date, more than 30 published trials have evaluated the role of stimulating the P6 acupuncture point for relief of nausea and vomiting.19 In a systematic review, acupuncture was demonstrated to be superior to placebo in ameliorating nausea and vomiting; the results were consistent despite numerous investigators, diverse patient populations, and various forms of acupuncture point stimulation.18 Trials have demonstrated that acupuncture effectively relieved nausea and emesis associated with chemotherapy,20 surgery,21,22 and pregnancy.23
Several adverse events have been noted with acupuncture, mainly from infection secondary to improper handling of needles or their reuse without sterilization.24 Such infections have included hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)25–27; bacterial endocarditis secondary to Propionibacterium acnes28; and bacteremia from Staphylococcus aureus and Pseudomonas aeruginosa with a consequent psoas abscess.29 Two fatalities have been documented in which acupuncture was thought to have led to sepsis with staphylococcal organisms.30 Although improperly sterilized needles seem to be the only risk factor for the aforementioned infections, it is difficult to prove such infections were a direct result of acupuncture, because patients might not have divulged other personal potential risk factors such as sexual preference or intravenous drug use.31 Other risks reported to be associated with acupuncture therapy include perforation of an organ during placement of the needles with resultant pneumothorax, hemopericardium with tamponade, and spinal cord injury.24,31,32
Relaxation Therapy
Relaxation therapies have been suggested as a CAM therapy for chemotherapy-induced nausea and vomiting. It has been reported that side effects related to chemotherapy are somewhat conditioned and are developed as a form of associative learning33; the anxiety experienced during chemotherapy sessions can serve as conditioning cues that lead to physiologic reactions. Through progressive muscle relaxation therapy, a patient’s anxiety can be alleviated and physical symptoms averted. Relaxation therapies often are used as an adjunct to standard antiemetic medications.31
FUNCTIONAL DYSPEPSIA
Functional dyspepsia is defined as pain or discomfort in the epigastric area in the absence of demonstrable structural or physiologic abnormalities. Because symptoms tend to be short in duration and relatively mild, dyspepsia often is self-managed34; therefore, CAM therapies clearly are appealing. Herbal therapy has been a mainstay of CAM treatments for functional dyspepsia. The most common supplement therapies for functional dyspepsia, including their active ingredients, proposed mechanisms of action, and adverse effects, are listed in Table 127-3.
Banana (Musa sapientum) has been evaluated for the treatment of functional dyspepsia in prospective open trials. This supplement is thought to promote gastric mucus secretion and has been documented to have antiulcerogenic properties in animals.35 In a study by Arora and Sharma,36 treatment with banana powder resulted in a reduction in symptoms in 75% of patients in the treatment group compared with 25% of those in the placebo group (P < 0.05). Causes of organic dyspepsia were excluded through various endoscopic and laboratory methods before subjects were included in the study. The only adverse effect reported was pruritus in the treatment group.36
Capsaicin, derived from the dried fruit of Capsicum annuum (red pepper), is an herbal supplement. Its mechanism of action is selective impairment of pain (C-type) fibers, which carry pain sensation from the abdominal viscera to the central nervous system.37 In one study, 2.5 mg of red pepper powder given daily improved epigastric pain, nausea, and bloating, whereas placebo did not.37 Although abdominal pain and diarrhea occurred initially in patients treated with capsaicin, these adverse effects were self-limited and of no serious clinical consequence.
Greater celandine (Chelidonium majus) was investigated in functional dyspepsia by Ritter and colleagues in a randomized, double-blind, placebo-controlled trial.38 Celandine accounted for a 34% greater reduction in symptoms compared with placebo (P = 0.003).38 This agent is thought to contain a variety of alkaloids that also have a spasmolytic effect on smooth muscle.39 Despite its apparent efficacy, celandine has many adverse effects, including xerostomia, insomnia, diarrhea, and fatigue. Idiosyncratic hepatotoxicity also has been described with celandine, but it resolved without complication in most cases when the supplement was discontinued.40
Liu-jun-zi-tang, also known as TJ-43, is a Chinese herbal medicine that has been used for relief of functional dyspepsia. The agent is a combination of several extracts including Actractylodis laneae rhizoma, Ginseng radix, Pinelliae tuber, Hoelen, Zizyphi fructus, Aurantii nobilis pericarpium, Glycyrrhizae radix, and Zingiberis rhizoma.34 Multiple mechanisms of action have been proposed, including increased gastric emptying, increased serum levels of gastrin and somatostatin,41 and relaxation of gastric smooth muscle.42 An RCT compared TJ-43, 2.5 g three times per day, with placebo for seven days in patients with functional dyspepsia. The treatment group displayed greater reductions in epigastric fullness, reflux, and nausea compared with the group treated with placebo (P < 0.05).41 The only adverse event noted with TJ-43 was one case of drug-induced interstitial pneumonitis, which resolved after therapy was discontinued.34
Peppermint (Mentha piperita) and caraway (Carum carvi) are the supplements that have been investigated most thoroughly for treating functional dyspepsia. Their proposed mechanism of action is thought to be inhibition of smooth muscle contractions by direct blockade of smooth muscle calcium channels.43,44 Several placebo-controlled trials have compared variable, fixed doses of these agents ranging from 180 to 270 mg for peppermint and 100 to 150 mg daily for caraway. A statistically significant improvement in symptoms such as bloating and epigastric pain was demonstrated when treatment groups were compared with placebo groups in several trials.34,45 Adverse effects seen with these supplements include diarrhea, nausea, vomiting, allergic contact dermatitis, contact urticaria,46 asthma exacerbations, and atrial fibrillation.47,48
Shenxiahewining is a mixture of Chinese herbs, specifically Ginseng radix, Pinelliae tuber, Coptidis rhizoma, Zingiberis rhizoma exsiccatum, and Glycyrrhizae radix, in a 3 : 9 : 3 : 3 : 3 ratio.34 In an RCT performed in China, 92% of patients treated with shenxiahewining reported improvement in symptoms compared with 20% of a control group. No important adverse events were noted.34
Turmeric (Curcuma longa) is an agent that also has been documented to have therapeutic efficacy in alleviating functional dyspepsia. This agent is thought to increase biliary secretion, promote contraction of the gallbladder, and act as an antispasmodic.49 In a placebo-controlled trial performed in Thailand, turmeric (2 g/day) was found to significantly improve dyspeptic symptoms (P = 0.003).34
Another agent that has been studied for the treatment of functional dyspepsia is STW 5, also known as Iberogast. This agent is an herbal preparation composed of bitter candytuft (Iberis umbellata), chamomile (Matricaria chamomilla), peppermint, caraway fruit, licorice root (Glycyrrhiza glabra), lemon balm leaves (Melissa officinalis), celandine (Chelidonium majus), angelica root (Angelica archangelica), and milk thistle (Silybum marianum). In a meta-analysis performed by Melzer and colleagues,50 evaluating three randomized, double-blind, placebo-controlled trials, STW 5 in a dosage of 1 mL three times daily for four weeks was noted to be more effective than placebo with regard to improving the study patients’ most bothersome dyspeptic symptoms. Twenty-six percent of patients in the placebo group compared with 7% in the STW 5 group reported that their symptom remained “severe” or “very severe” after treatment. Specifically, STW 5 appeared more effective in providing symptomatic relief to patients with predominant epigastric pain and gastroesophageal reflux symptoms.50
von Armin and colleagues51 also have demonstrated in the largest randomized, double-blind, placebo-controlled trial evaluating STW 5 that a significantly higher percentage of patients with functional dyspepsia who are prescribed STW 5 are free from their symptoms when compared with a placebo group.51 Pilichiewicz and coworkers showed that STW 5 affects gastric motility in a region-dependent manner, inducing gastric fundic relaxation and antral contraction.52 Although no adverse events have been reported for STW 5, individual components of the preparation are known to have potential toxicities, details of which are addressed in the next section.
The data on these supplement therapies suggest that some of those studied could be useful for patients with functional dyspepsia. Peppermint, caraway, and STW 5 are the most extensively evaluated to date and, given their encouraging safety profiles, warrant further study.34
IRRITABLE BOWEL SYNDROME
IBS is defined as abdominal discomfort and altered bowel function in the absence of structural and biochemical abnormalities (see Chapter 118).53 Symptoms include pain, bloating, cramping, constipation, and diarrhea. Gastroenterologists encounter this disease entity quite commonly. In a systematic review citing only studies that used Rome criteria for diagnosis, IBS prevalence was found to vary between 5% and 10%, with a pooled prevalence of 7%.53 Patients with IBS often are frustrated that laboratory, radiologic, and endoscopic examinations fail to reveal an “organic” source of their discomfort, and they therefore often employ CAM therapies to help ameliorate their symptoms.
Many CAM therapies have been investigated for the treatment of IBS (Table 127-4). Herbal supplement therapy and the use of probiotics have been evaluated most extensively. Psyllium (Plantago isphagula) is the most commonly prescribed dietary supplement for patients with IBS. This fiber product acts as an osmotic bulking agent and decreases bowel transit time. There have been three placebo-controlled trials of psyllium use in IBS,54–56 but only one fulfilled the five Rome criteria for appropriate study methodology (randomization, concealed allocation, placebo control, double blinding, and appropriate follow-up of study patients). Two additional trials compared psyllium with “active” agents, but neither trial was of high quality.57,58 In general, the evidence that stool frequency, consistency, and ease of passage were better with psyllium than with placebo was modest. There were no statistically significant differences in side effects among psyllium, lactulose, and placebo.
Although psyllium appears to be fairly harmless, allergic hypersensitivity reactions have been documented.59 Impaired absorption of certain medications taken concomitantly, such as lithium and carbamazepine, also has been reported.60,61 Cases of acute esophageal obstruction also have occurred with psyllium-based agents, suggesting that, in certain cases, dysphagia might preclude its use.62
Other supplemental therapies have been used for IBS. Peppermint oil, as previously discussed, is prescribed for its smooth muscle relaxant capabilities. In a meta-analysis by Pittler and Ernst,63 peppermint oil improved symptoms of IBS compared with placebo treatment. Although statistical significance was demonstrated in this study, flaws in the methodology of the trials studied preclude evidence-based acceptance of the efficacy of peppermint oil in the treatment of IBS.
STW 5 also has been used to treat patients with IBS. Placebo-controlled trials have demonstrated that STW 5 improves symptoms of IBS and reduces the severity of abdominal pain.64 Multiple mechanisms of action of STW 5 are postulated; certain components are thought to alter gastrointestinal motility, and others are thought to act as smooth muscle relaxants.60 Although no adverse events have been reported for STW 5, individual components of the preparation are known to have potential toxicities. Specifically, celandine is known to be hepatotoxic at certain doses (greater than 10 mg/day).40 Chamomile is known to contain a coumarin derivative, which increases the risk of bleeding if prescribed concurrently with warfarin, aspirin, or NSAIDs. Chamomile also has been noted to potentiate the central nervous system depressant effects of benzodiazepines and barbiturates,65,66 which often are prescribed to patients with IBS. Milk thistle is known to inhibit cytochrome P-450 3A4 (CYP3A4) and uridine diphosphoglucuronosyl transferase and thus could alter the metabolism of many pharmacologic agents.67
Chinese herbal medicine has been used for IBS symptoms, and RCTs have demonstrated a statistically significant benefit of its use over placebo. Patients treated with Chinese herbal medicine reported improvement in their symptoms and less interference in their daily lives from IBS, with an overall improvement in their quality of life.68
Probiotics are microorganisms that promote health effects through alterations of intestinal microflora.69 Patients with infectious and inflammatory disease states such as pseudomembranous colitis and IBD as well as patients with IBS also have had benefit from these agents. Evidence from RCTs has demonstrated that ingestion of Lactobacillus plantarum resulted in significant reductions in abdominal pain and flatulence in patients with IBS.70,71
A report of fermented milk containing Bifidobacterium animalis demonstrated that this probiotic improves abdominal distention and associated symptoms in patients with constipation-predominant IBS.72 In addition, a systematic review of probiotics demonstrated that Bifidobacterium infantis 35624 (Align) significantly improves abdominal pain, bloating, distention, and the sensation of incomplete evacuation.73
Hypnosis has been documented to have a significant therapeutic effect on symptoms of IBS. Through the use of gut-directed imagery, whereby patients imagine they are inhibiting gastric secretion, an overall symptom improvement rate of 80% has been reported.74 Clinical remission for up to three months has been documented in patients with IBS treated with hypnotherapy. Women and those younger than 50 years seem to respond well to this modality. Hypnotherapy has proved effective in the pediatric IBS population as well, one study having documented that successful treatment of functional abdominal pain or IBS was accomplished in 85% of children treated with hypnotherapy compared with 25% of patients treated with placebo.75
Acupuncture has been shown to be superior to sham therapy and fiber supplementation in patients with IBS.76,77 Homeopathy has demonstrated a trend toward efficacy in IBS.7 Lastly, Ayurvedic medicine (see Table 127-1) also has demonstrated efficacy in relief of symptoms from IBS. The trial of Ayurvedic medicine, however, had a large dropout rate and therefore should be interpreted with caution.78
INFLAMMATORY BOWEL DISEASE
The pathophysiology of Crohn’s disease is not completely understood despite decades of research (see Chapter 111). An overactive intestinal mucosal immune system driven at least in part by a reaction to normal luminal flora is thought to be involved in the pathogenesis,79 facilitated by failure of the mucosal epithelium to serve as an effective barrier to potential dietary and environmental toxins. Given the chronic and persistent nature of Crohn’s disease, many patients turn to CAM therapies when conventional therapies fail.
Probiotics are often employed by certain subgroups of patients with Crohn’s disease, those having had total proctocolectomy and creation of an ileal pouch-anal anastomosis (IPAA) claiming the greatest benefit from these agents. Pouchitis in these patients occurs with a frequency of approximately 50% after 10 years.80 Although the cause of pouchitis remains unknown, alteration in enteric bacterial flora appears to play an important role.80
