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Women's health update: irritable bowel syndrome in women.

Irritable bowel syndrome (IBS) is the most common reason for gastrointestinal abdominal pain seen in primary-care and gastroenterology practices, and is very prominent in gynecological practices. Up to 20% of adults in the US have IBS, which predominantly affects reproductive-aged women, and is most likely to occur in association with, or be similar to, gynecologic disorders. (1) In 50% of individuals, the age of onset is less than 35 years of age. (2), (3)

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IBS is a functional gastrointestinal (GI) tract disorder and is defined as chronic abdominal pain, usually in the lower abdomen, with disturbed bowel habits in the absence of structural or biochemical abnormalities. Bowel patterns can be diarrhea, constipation, or alternating between the two. It is now suggested that abnormal gut motility and bowel hypersensitivity are influenced by psychosocial factors and the result of dysregulation of brain-gut interactions. (4), (5) Interplay between the enteric nervous system and the central autonomic neural network through parasympathetic and sympathetic nerves regulates motor and sensory function in the intestines. (6) This dual directional interaction between brain and gut suggests that individuals with IBS have altered perception of pain. (7), (8) Hyperexcitability of the neurons in the dorsal horn are thought to contribute to the prolonged pain memory in IBS patients or in a disruption in the coordination of these centers. (9-11) Communication between the brain and gut is mediated by many biochemical factors with input from the neuroendocrine and neuroimmunologic body systems. Several mediators may be involved in the visceral hypersensitivity and motility, including 5-hydroxytryptamine (5-HT). 5-HT is both a neurotransmitter in bowel sensory fibers and paracrine signaling molecule in the bowel. (12), (13) The concentration of 5-HT is considerably greater in the gut than in the brain, and 95% of the body's 5-HT is synthesized and stored in the enterochromaffin cells of the gut. (14), (15)

Psychosocial factors such as early life experiences, physical stress, coping skills, psychological stressors and coexisting health problems are not thought to cause IBS, but rather influence the manifestation of symptoms and the ability to cope with the illness. Stress can affect gastrointestinal (GI) function and cause various symptoms in most people, but this happens to a greater extent in IBS individuals. (16-18) In women, there is a high prevalence of prior physical and sexual abuse in those with IBS. (19) One study reported that 53% of gastroenterology clinic patients with functional intestinal disorders had a history of sexual abuse.

Diagnosis

The characteristic description of IBS is abdominal pain or discomfort relieved by defecation. Onset associated with a change in the consistency or frequency of the stools. A diagnostic workup includes a complete history and physical exam. Laboratory and diagnostic tests might be considered. In women under 50 years old, these include a CBC, electrolytes, liver function tests (LFTs), occult blood, and optional sigmoidoscopy. In women over 50: CBC, electrolytes, LFTs, colonoscopy, or barium enema with sigmoidoscopy. Stool tests to rule out ova and parasites, bacteria or fungal overgrowth, and flora imbalance can be considered as well. Diagnostic criteria are at least 12 weeks (not necessarily consecutive) in the preceding 12 months of abdominal discomfort or pain that has at least two of the following:

* relieved with defecation

* onset associated with a change in stool frequency

* onset associated with a change in stool form/appearance

Abdominal pain or discomfort tends to be nonlocalized, migratory and variable. It is often worse after a meal, during times of stress, and before/during menses.

Other symptoms that increase the likelihood of the diagnosis of IBS but are not essential for the diagnosis include:

* more than three stools per day or fewer than three per week

* lumpy/hard or loose/watery stools in more than 25% of the defecations

* straining, urgency, or incomplete evacuation in more than 25% of stools

* passage of mucus in more than 25% of stools

* bloating or abdominal distention more than 25% of the time

It can be helpful in treatment strategies to categorize IBS patients as constipation-predominant, diarrhea-predominant, or a combination of both at variable times. Some patients alternate between the subgroups.

Atypical symptoms should cause the practitioner to consider a diagnosis other than IBS and possibly a referral to a gastroenterologist. These include: severe constipation, persistent diarrhea, anemia, fever, weight loss, rectal bleeding, nocturnal pain, nocturnal abnormal bowel function, family history of Gl cancer/inflammatory bowel disease or celiac disease, new onset of symptoms in those older than 50. A differential diagnosis of chronic or recurrent abdominal discomfort and bowel function includes: malabsorptive conditions (e.g., celiac), dietary factors (lactose intolerance, caffeine, chewing gum), infections (Giardia), inflammatory bowel disease, psychological disorders (depression), and miscellaneous conditions (e.g., endometriosis, carcinoid syndrome).

Treatments

This interplay of physiological factors, psychosocial influences, and trigger foods in IBS is best addressed with an integrated approach to treatment. Attending to several levels leads to the most optimal outcomes.

With high-sugar/low-fiber diets so common in the US, it is not surprising that an increase in dietary fiber from grain, fruits, and vegetables has been a cornerstone of IBS treatment in conventional and alternative medicine approaches. Constipation-dominant IBS patients appear to benefit more from using fiber/bulking agents than do those with diarrhea. Some individuals may improve by increasing dietary fiber from fruits and vegetables, and others from cereal sources, although in one uncontrolled clinical study, no significant difference was observed in those who had a diet composed of 30 g of fruit and vegetable fiber and 10 g of cereal fiber vs. those with 30 g of cereal fiber with 10 g of fruit/vegetable fiber. (20) For those with a diarrhea-dominant component, cooked vegetables may be the best choice to help reduce symptoms. Fiber choices in the diet and in supplement form must be individualized to see how each patient reacts. If the fiber aggravates her, then good clinical judgment with a change to another fiber intervention, or perhaps avoiding the increased fiber approach must be considered.

There are two forms of fiber, insoluble and soluble. Insoluble fiber does not readily dissolve in water and increases the bulk of the stool, softens the stools, and shortens the transit time. Soluble fiber dissolves in water and forms a soft gel substance and eases elimination of stool. Psyllium husks and flax seeds are bulk-forming agents that absorb water, soften stool, and increase stool weight and the number of bowel movements per day. Even fordiarrhea-dominant IBS, psyllium husks make the stools less watery. (21) However, sometimes they can increase flatulence and bloating. Citrus pectin serves as a soluble fiber in that it helps with intestinal flora stabilization and can ease both constipation and diarrhea associated IBS. (22) Guar gum is a soluble dietary fiber produced from the seed of the guar plant and is used as a bulk laxative for treating diarrhea, constipation, and IBS. (23) When taken orally, it expands and normalizes bowel function. All methods of increasing fiber are best used by starting with smaller doses and slowly increasing, while also taking it with at least 8 ounces of water.

If fiber sources are not beneficial, then osmotic laxatives such as magnesium can be utilized in those with constipation-dominant IBS. Magnesium citrate, sulfate, and hydroxide salts are the most common forms of magnesium indicated for constipation. The magnesium sulfate salt is the most potent.

Most alternative medicine practitioners consider the role of food allergies or food intolerances in the etiology or course of IBS. This is based on historical empirical observation, as well as several studies documenting the association between food allergy and IBS. (24-27) Identifying aggravating foods and improving the diet based on these findings along with general whole foods dietary guidelines puts the patient on a sound path towards wellness, not only with her IBS, but with her general health as well.

Recent research suggests that dysregulation in gut flora of the small bowel occurs in patients with IBS. (28) Two important clinical trials confirm this. In a randomized, placebo-controlled 5-month trial, 86 IBS patients were randomized to receive either a multispecies probiotic supplement daily or a placebo. (29) The IBS score at 5 months decreased 14 points from baseline with the probiotics vs. only 3 points with placebo. Abdominal distension and pain were especially affected. In the second clinical trial, 40 IBS patients were randomized into a placebo or probiotics treatment group. (30) After 4 weeks of treatment with Lactobacillus acidophilus, there was a 20% greater reduction in abdominal pain or discomfort in the treatment group vs. the placebo group.

Peppermint oil, specifically enteric-coated peppermint oil (ECPO), inhibits gastrointestinal smooth muscle spasms of the intestinal tract and improves the rhythmic contractions, presumably due to the menthol. Peppermint oil has been studied in children and adults with IBS, but the results have been conflicting. (31), (32) A meta-analysis of five studies in 1999 was not conclusive. (33) In one of those studies, ECPO or placebo was given to 110 patients with symptoms of IBS. (34) Patients took one capsule of either 0.2 ml ECPO or placebo three to four times daily 15 to 30 minutes before meals for one month. In all categories: abdominal pain/distension, stool frequency, gas, and borborygmi, there was double to almost triple the symptom relief in the ECPO group.

One problem with ECPO is that in some individuals with GERD it can increase the symptom of heartburn. Alternative formulas without ECPO are an important clinical option.

Artichoke leaf extract (ALE), (Cynara scolymus L), has been shown to reduce the severity of IBS in a subset of patients with dyspepsia. (35) A similar study was done in patients with dyspepsia and IBS. Patients were randomly assigned to either 320 or 640 mg capsules of a standardized (1:5) aqueous extract of artichoke leaves taken daily for 2 months. (36) IBS symptoms decreased significantly by 26.4%, total symptom scores decreased by 41 %, and 20% improvement was seen in the dyspepsia index total quality-of-life score after treatment with artichoke leaf extract.

Turmeric may also help with reducing IBS symptoms. A pilot study group of 207 patients were given one tablet with 72 mg or two tablets of a standardized turmeric extract for 8 weeks. (37) IBS prevalence decreased 53% in the one tablet per day group and 60% in the two tablets per day group with approximately two thirds of all individuals reporting an improvement in symptoms after treatment.

Historically, both Western herbal medicine traditions and Traditional Chinese Medicine (TCM) have included bitters in IBS formulas. The bitters are herbs that stimulate the function and motility of the Gl tract, increasing gastric secretions and having a tonic effect. This normalization of digestive function then is thought to balance the intestinal ecology, thereby reducing flatulence and distension. Common bitters used typically 10 to 30 minutes before a meal include ginger (Zingiber officinale) rhizome, dandelion (Taraxacum officinalis), fumitory (Fumaria officianlis) leaf, wormwood (Artemisia spp.), gentian (Gentiana spp.) root, candytuft (Iberis amara), and artichoke (Cynara scolymus) leaf. From a Western botanical traditional approach, combining these bitters with herbal cholagogues, carminatives, antispasmodics, antimicrobials, anti-inflammatories, astringents, nerviness, adaptogens, antidiarrheals, and aperients (mild laxatives) can possibly address the multiplicity of IBS symptoms more effectively.

One herbal combination formula that has been studied in IBS contains the bitter candytuft lberis amara); a cholagogue (celandine [Chelidonium majus] leaf and flower); carminatives (caraway [Carum carvi], peppermint [Mentha piperita], chamomile [Matricaria recutita]); an antiinflammatory (licorice [Glycyrrhiza spp. root]); nervines, (lemon balm [Melissa officinalis]) and angelica (Angelica archangelica); and milk thistle (silybum marianum). In a randomized, double-blind, multicenter study of 208 patients with IBS, patients received the alcohol extraction of the above herbal combination, or the above formula excluding the celandine, angelica, and milk thistle, or bitter candytuft only or placebo. (38) Twenty drops were given three times per day for four weeks. Both the full combination formula and the preparation excluding the celandine, angelica, and milk thistle demonstrated effectiveness. The preparation containing the single herb, bitter candytuft, did not.

Marshmallow root (Althaea officinalis) has a rich tradition for its use in constipation, diarrhea, gastric inflammation, and peptic ulcers. The leaves and root contain mucilage polysaccharides that can soothe and protect mucous membranes, and it is thought that this mucilaginous herb can provide a soothing effect on the intestinal wall and help stool more easily move through the bowel, thereby increasing comfort and elimination. (39)

One of my favorite herbs to use for abdominal cramping related to IBS is wild yam (Dioscorea villosa) in tincture form. The historical botanical use of wild yam includes its antispasmodic effects on smooth muscle. One teaspoon twice per day will likely yield positive results.

Two additional nutrients in supplement form are important to consider: tryptophan or 5-hydroxytryptophan. We mentioned the brain-gut connection in the early part of this article. L-tryptophan and 5-hydroxytryptophan (5-HTP) are produced in both the brain and digestive tract. Approximately 95% of the body's serotonin is found in the Gl tract. When the serotonin is released, it can interact with several different 5-HT (5-hydroxytryptamine) receptors. The receptor subtypes 5-HT.sub.1], [5-HT.sub.3], and [5-HT.sub.4] play major roles in Gl motor and secretory function as well as visceral sensation. (40) [5-HT.sub.3] receptor antagonists delay transit in the GI tract, reduce colonic tone, dampen the gastrocolic reflex, and decrease intestinal sensation. (41-43) [5-HT.sub.4] agonists improve abdominal discomfort, bloating, and bowel habits in most randomized clinical trials. (44) The critical role of 5-HT in IBS is to support alternative and conventional antidepressants binding to these receptors. Given the influence of psychological factors such as depression and stress on IBS, modulation of the serotonin pathway with the use of either L-tryptophan or 5-HTP, appears to be a logical approach in treating IBS. Common dosing for L-tryptophan is 500 mg up to 6000 mg per day, before bed. Common dosing for 5-HTP is 50-100 mg/day, before bed. Be aware that tryptophan can cause side effects such as heartburn, belching, flatulence, nausea, vomiting, diarrhea, drowsiness, and anorexia.

Melatonin has been studied in individuals with IBS. An 8-week placebo-controlled trial demonstrated that those taking melatonin experienced 3.5 times the improvement in their IBS score. (45) In addition, quality of life was nearly 3 times greater in the melatonin group (43.6% vs. 14.6% in the placebo group). Another placebo-controlled trial of 40 individuals found that supplementing with melatonin reduced abdominal pain and rectal pain. (46) Lastly, in a study of young women with IBS, those in the melatonin group reported less abdominal pain, diarrhea, and constipation after eight weeks. These IBS symptoms improved without any impact on improving sleep. (47) Typical dosing of melatonin is in the range of 0.3-5 mg nightly, before bed, although higher doses can be used.

With attention to this multifactorial, brain-gut interplay, a combination product of psyllium husk, guar gum seed extract, citrus pectin, marshmallow root, probiotics, and melatonin was tested in a randomized, single-blind, two-phase study in 20 volunteer subjects with IBS. Phase I of the study was done to determine the optimal dosage of melatonin. Results demonstrated that nearly complete relief (over 95%) of gas, bloating, constipation, and diarrhea was achieved. There was also an 81.7% improvement in abdominal discomfort, and 64% of the individuals had more comfortable bowel movements. (48)

Psychological/behavioral interventions are also options for IBS and can be included in a holistic approach as needed. Relaxation training, hypnosis, psychotherapy, cognitive-behavioral therapy, stress reduction, and perhaps a change of pace/change in one's approach to life can be suited to each individual situation.

Conclusion

IBS is one of the most frequently diagnosed problems. It is especially common in women, and is often confused with gynecologic disorders. Although a single cause of IBS is not identified, it is generally agreed that there is interplay between physiological and psychosocial causes. Symptoms range from mild to severe. And while most patients respond to the above natural treatments, more severe cases may require selected natural therapies in conjunction with conventional antispasmodics, tricyclic antidepressants, selective serotonin reuptake inhibitors, antidiarrheals, or osmotic laxatives. Alosetron, a selective [5-HT.sub.3] receptor antagonist, is the first FDA-approved drug for treating severe IBS in women whose predominant symptom is diarrhea. This drug was withdrawn within months of its introduction to the market, due to serious, life-threatening gastrointestinal side effects. It was reintroduced in June 2002 with restrictions on its use.

Fortunately, IBS is very well treated with a holistic approach and attention to avoiding food triggers, increasing dietary fiber, introducing probiotics, choosing from the herbal options, and considering the interplay of the gut-brain interaction in embracing melatonin/tryptophans and/or psychological/behavioral interventions.

Notes

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(7.) Wood J, Alpers D, Andrews P. Fundamentals of neurogastroenterology. Cut. 1999;45(suppl 2): ii6.

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(9.) Mayer E, Gebhart G. Basic and clinical aspects of visceral hyperalgesia. Gastroenterol. 1994;107:271.

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(14.) Everhart J, Renault P. Irritable bowel syndrome in office-based practice in the United States. Gastroenterol. 1991;100:998.

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(28.) Riordan S, Kim R. Bacterial overgrowth as a cause of irritable bowel syndrome. Curr Opin Gastroenterol. 2006;22:669-673.

(29.) Kajander K, Myllyluoma E, Rajilic-Stojanovics M, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther. 2008;27:48-57.

(30.) Sinn DH, Song JH, Kim HJ, et al. Therapeutic effect of Lactobacillus acidophilus-SDC 2012, 2013 in patients with irritable bowel syndrome. Dig Dis Sci. 2008;53:2714-2718.

(31.) Kline R, Kline J, DiPalma J, Barbero C. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr. 2001;138:125-128.

(32.) Liu J, Chen C, Yeh H, Huang C, Poon S. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32:765-768.

(33.) Pittler M, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am I Gastroenterol. 1998;93:1131-1135.

(34.) Liu H, Chen G, Yeh H, et al. Enteric-coated peppermint oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32:765-768.

(35.) Walker A, Middleton R, Petrowicz O. Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study. Phytother Res. 2001;15:58-61.

(36.) Bundy R, Walker A, Middleton R, et al. Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: A subset analysis. J Altern Complement Med. 2004;10(4):667-669.

(37.) Bundy R, Walker A, Middleton R, Booth J. J Altern and Comp Med. 2004; 10(6): 1015-1018.

(38.) Madisch A, Holtmann G, Pelein K, Hotz ). Treatment of irritable bowel syndrome with herbal preparations: Results of a double-blind, randomized, placebo-controlled, multicentre trial. Alimentary Pharmacol Ther. 2004;19:271-279.

(39.) Fleming T, ed. Marshmallow. In: PDR for Herbal Medicines. 3rd ed. Montvale, NJ: Medical Economics Company; 2004:556-557.

(40.) Gerson M, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterol. 2007;132:397-414.

(41.) Delvaux M, Louvel D, Mamet J, et al. Effect of alosetron on responses to colonic distention in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 1998;12:849-855.

(42.) Houghton L, Forster J, Whorwell P. Alosetron, a [5HT.sub.3] antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther. 2000;14:775-782.

(43.) Mayer E, Berman S, Derbyshire S, et al. The effect of the [5-HT.sub.3] receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Aliment Pharmacol Ther. 2002;16:1357-1366.

(44.) Ford A, Brandt L, Foxx-Orenstein A, et al. Efficacy of 5HT4-agonists in non-diarrhea predominant irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2008;103(suppl 1):S478 (1222).

(45.) Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol. 2007;41(11):29-32.

(46.) Song G, Leng P, Gwee K, et al. 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.

(47.) Lu W, Gwee K, Moochhalla S, Ho K. 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.

(48.) Massey A. Combination of fiber, probiotics, and melatonin for the relief of symptoms associated with irritable bowel syndrome [technical sheet). Therapeutics Inc. September 2007.

by Tori Hudson, ND

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