Relief From Irritable Bowel SyndromeJuly 2015
By Susan Trainor
Few people realize that the intestinal tract has its own nervous system that communicates directly with the brain. Because of this unique nervous system,1-3 people with irritable bowel syndrome often have intensified responses to abdominal distension or movement that can result in the brain receiving distressingly strong pain signals.4-6
Nearly 20% of Americans suffer from irritable bowel syndrome, a chronic disorder that causes painful symptoms such as cramping, abdominal pain, bloating, gas, diarrhea, and constipation.7-10
Despite its prevalence, there is no universally accepted medical treatment that directly addresses irritable bowel syndrome symptoms in all people.11,12
However, cutting-edge research has determined that there are five major biological changes that contribute to the symptoms associated with irritable bowel syndrome. With this knowledge, scientists from around the world have combined two specific compounds that work together to address all of these changes.
This unique formulation is composed of an extract from the Perilla leaf that is rich in beneficial flavonoids.13,14 The second constituent, a patented probiotic organism, S. cerevisiae, helps normalize the intestinal microbial community by reducing the presence of deleterious or disease-causing bacteria.15,16 Together, these compounds are showing relief of painful symptoms for the five major causes of irritable bowel syndrome.
What Causes Irritable Bowel Syndrome?
Irritable bowel syndrome has multiple potential mechanisms in different individuals—all of which produce approximately the same set of symptoms.17-19 Potential causes can include everything from hidden food allergies or sensitivities20 to insufficient function of the pancreas21 to infection with a number of common intestinal parasites.22-25
Regardless of the specific underlying cause of irritable bowel syndrome symptoms, there are five major biological changes that contribute to the symptoms:
- Disordered gut motility (abnormal movements of the muscles in the intestine),26,27
- Visceral hypersensitivity (exceptionally brisk pain responses in the intestine),27-30
- Inflammation (very low grade, present in intestinal walls of some irritable bowel syndrome patients),31-33
- “Food sensitivities and leaky gut” (increased intestinal permeability),20,34,35 and
- Dysbiosis (disruption of the normal balance of intestinal microorganisms).36-39
We now recognize that all five of these processes interact with each other in order to produce the symptoms associated with irritable bowel syndrome. For example, dysbiosis can produce inflammatory changes, which can lead to loss of intestinal barrier function, resulting in “leaky gut.”34,37,39 Inflammation and dysbiosis are involved in altered pain perception and disordered bowel motility.29,40,41 These are only a few of the dizzying number of interactions that ultimately produce the suite of symptoms that we define as irritable bowel syndrome.
Because these five processes are so interconnected, it’s necessary to address all of them simultaneously in order to have an impact on symptoms.
Modern mainstream medicine offers irritable bowel syndrome treatments such as the Fermentable Oligo-Di-Monosaccharides and Polyols diet that eliminates foods like carbohydrates, fructose, lactose, and more in an effort to remove irritants from the stomach as well as anti-inflammatory42 or antispasmodic drugs,43 but no single treatment works in a majority of cases.8,27,44-46 No doubt this is due to the fact that none of these approaches addresses the five major disturbances that are intrinsic to the full irritable bowel syndrome picture.
If we could control or reverse these five changes, we’d likely be able to control irritable bowel syndrome symptoms themselves. The good news is that a pair of simple, natural compounds does what no modern drugs can do: directly address each of those five components in the irritable bowel syndrome puzzle. The result is helpful relief from irritable bowel syndrome symptoms.
Two Natural Compounds Fight Irritable Bowel Syndrome On Five Major Fronts
One of the benefits of natural compounds is that they often work via a variety of mechanisms that add to the overall desired effect.47,48 That is precisely the case with a novel combination of two compounds specifically developed for people with irritable bowel syndrome and related abdominal complaints.
An extract from the Perilla leaf and a probiotic strain of a natural organism called S. cerevisiae have been used for both culinary and health-promoting ingredients.49,50 Together, these two compounds work in harmony to reverse or mitigate all five of the major factors that can produce irritable bowel syndrome symptoms. As a result, human studies show that these two compounds significantly improve the symptoms of irritable bowel syndrome, including bloating and distension, passage of gas, gastrointestinal rumbling, feelings of fullness, and abdominal discomfort.
Perilla frutescens is an herb in the mint family that is found in much of Asia and North America. The green or dark red leaves of Perilla are used in Japanese and Korean cuisine (where they are known as Shiso, Japanese basil, or Japanese Melissa), and have a long history in traditional medical systems, especially for their properties at relieving digestive symptoms.13,51
Perilla leaves are laden with beneficial biomolecules, most notably a unique flavonoid compound called vicenin-2.13,52 A newly developed, proprietary extract of green Perilla leaves contains a specific ratio of vicenin-2 in combination with rosmarinic acid, another flavonoid that is especially noted for its relaxing properties (it promotes activity of the neurotransmitter GABA, the target of antianxiety drugs such as Valium®).14,53
The second compound, a specific strain of S. cerevisiae, has been used for millennia in baking (especially sourdough bread).54 It is a probiotic organism that helps to normalize the intestinal microbial community by reducing the presence of deleterious or disease-causing bacteria.15,16
Unlike drugs, which only mask the symptoms, this natural combination modifies each of the following five major biological changes that contribute to the symptoms.
1. Disordered Gut Motility
Perilla leaf extract has been shown to address four of the five major irritable bowel syndrome symptom-producing processes. The first of these is disordered gut motility. This refers to alterations in the normal coordinated waves of muscle contractions and relaxations in the intestinal wall that propel food/fecal contents through the gastrointestinal tract.26,27 Both increased and decreased motility may occur in the various forms of irritable bowel syndrome,27,55 and may be related to disturbances in distribution of certain important hormone-producing (endocrine) cells in the stomach and intestinal walls.56-58 Disordered motility can result in symptoms such as cramping, bloating, and urgency to defecate soon after food intake—all of which are reported by irritable bowel syndrome patients.26,27,59
Studies show that vicenin-2 and Perilla leaf extract help improve disordered gut motility by producing relaxation in the muscles of the intestinal wall. This effect is achieved by inhibiting excessive excitatory nerve and muscle activity in the intestine.14,52 The Perilla extract also has a “prokinetic” effect, meaning that it promotes normal motility to allow intestinal contents to move along smoothly without cramping or bloating.
It’s important to note that unlike antispasmodic drugs, Perilla extract acts only when neurotransmitters in the intestine are imbalanced, so they do not have a negative effect on gut motility in any way.52
2. Visceral Hypersensitivity
Through its antispasmodic effects,52 Perilla leaf extract may also help alleviate visceral hypersensitivity, another alteration in physiology known to produce irritable bowel syndrome symptoms.27,60 Visceral hypersensitivity is an overreaction to stimuli in the bowel.
The intestinal tract has its own nervous system. Networks of sensory and motor nerves throughout the walls of the intestine communicate with the brain, sending signals about fullness, stretching, and motion of the intestine. People with irritable bowel syndrome often have very brisk responses to abdominal distension or movement that can result in the brain receiving a pain signal.4-6
Research shows that Perilla extract affects areas in the brain where pain processing occurs,61 suggesting that it may play a further role in reducing the abnormal pain perception that results from visceral hypersensitivity.62
3. Chronic, Low-Grade Inflammation
The third major trigger of irritable bowel syndrome symptoms is chronic, low-grade inflammation.
This is separate from the major, high-grade inflammation in the intestine that produces “inflammatory bowel disease.” These conditions, primarily Crohn’s disease and ulcerative colitis, involve major inflammation of the gut, with severe pain, blood and pus in the stools, and immunological changes throughout the body.63-68
For many years, scientists have worked to distinguish inflammatory bowel disease from irritable bowel syndrome, suggesting that irritable bowel syndrome is free of inflammation. But more recently, studies have demonstrated that many irritable bowel syndrome patients indeed suffer from subtle inflammatory changes in the large intestine that can create symptoms.31,32
Perilla leaf extract fights the chronic, low-grade inflammation that produces irritable bowel syndrome symptoms through reduction in expression and activity of inflammatory signaling molecules.69,70 In fact, the rosmarinic acid component of Perilla leaf extract inhibits one of the major inflammation-regulating molecular complexes, known as high-mobility group box 1.71,72
4. Increased Intestinal Permeability
In addition to reducing inflammation, Perilla leaf extract’s ability to inhibit high-mobility group box 1, a protein involved in inflammation, also reduces intestinal permeability (“leaky gut”)—the fourth important pathological process associated with irritable bowel syndrome.34,72
Under normal circumstances, our intestines do a fine job of keeping what is in the intestine contained within the intestine. That way, food molecules, microorganisms, toxins, and other biologically active substances cannot enter the bloodstream without specific transport mechanisms. To maintain the integrity of that barrier, our intestines are equipped with specialized proteins linking intestinal cells together at so-called “tight junctions.”31,60,73
Studies show that people with irritable bowel syndrome have an unexplained increase in intestinal permeability. Their “tight junctions” are no longer as tight as they should be, allowing intact, undigested food molecules and other materials to enter the circulation, contributing to food allergy/sensitivity-like reactions that can induce irritable bowel syndrome symptoms.73,74
Evidence that Perilla leaf extract can support the intestinal barrier layer comes from a study showing that the extract could reduce manifestations of the allergic responses in mice; food allergy/sensitivity is a known potential cause of symptoms in irritable bowel syndrome patients.75
We’ve seen that Perilla extracts address four of the five underlying processes behind irritable bowel syndrome symptoms. For comprehensive treatment, the fifth must be addressed as well. That’s where S. cerevisiae comes in; it reverses dysbiosis, the fifth leading contributor to irritable bowel syndrome symptoms.
Dysbiosis is the disruption of the normal balance of the trillions of microorganisms that populate the human intestinal tract. Those organisms occur in large communities, each of which should be as diverse as possible. Recent studies show that the greater the overall diversity among bacterial groups, the healthier the individual.36-39
S. cerevisiae is a probiotic organism that is capable of reversing dysbiosis. S. cerevisiae helps normalize the intestinal microbial community by reducing the presence of deleterious or disease-causing bacteria.15,16 Mice deliberately infected with an invasive form of E. coli, a common “bad guy” in the intestinal tract, gained back healthy body weight after supplementation with this probiotic and demonstrated an astonishing 43-fold reduction in colonization by the bacteria just five days after treatment began.16
Studies also show that, following intestinal tract colonization with live S. cerevisiae organisms, inflammation produced by unhealthful bacteria in the intestinal tract is reduced, demonstrating powerful overlap with the anti-inflammatory properties of Perilla leaf extract.15,69,70
Human Studies Validate Effectiveness
With its ability to address four of the five major irritable bowel syndrome symptom-producing processes, Perilla extract is an ideal treatment for stubborn irritable bowel syndrome symptoms.
In a study of 50 otherwise healthy adults who all suffered from frequent gastrointestinal discomfort (bloating, rumbling, gas, etc.), subjects received either placebo or a 150 mg capsule of Perilla frutescens leaf extract.13 Subjects took one capsule twice daily (before breakfast and dinner) for four weeks, rating each of their symptoms on a scale of 0 (none) to 4 (extreme).
The study showed that patients taking the Perilla extract had significant improvements in all symptoms—including bloating/distension, passage of gas, gastrointestinal rumbling, feeling of fullness, and abdominal discomfort—over the four-week study period, while the placebo recipients only reported improvement in general abdominal discomfort. Interestingly, women, who make up the majority of irritable bowel syndrome sufferers, reported even stronger improvements than the group as a whole.
This study’s results are especially important in light of the known strong placebo effect in studies of gastrointestinal effects; showing a significant difference from placebo is a challenging bar to clear for many treatments.
A 2015 human study has validated the benefits of a specific strain of S. cerevisiae in irritable bowel syndrome patients. Of 179 adults with irritable bowel syndrome, 86 received S. cerevisiae capsules, 500 mg once daily (that’s a dose of 4 billion viable organisms), and 93 adults received a placebo capsule.76
After the eight-week study period, 63% of the supplemented group experienced improvement in abdominal pain or discomfort, while only 47% of placebo patients experienced this kind of improvement. Best of all, the supplement was well tolerated by all subjects.
Irritable bowel syndrome may affect up to one-fifth of the US adult population. It is not fatal, but has a huge impact on quality of life, depressive symptoms,77 and job performance. Sufferers report not only the pain and discomfort of the disorder, but also embarrassment and humiliation when their bowel patterns and symptoms become evident to others.
Mainstream medicine offers treatments that are helpful for alleviating symptoms; however, some medications work for some people, but none are effective in all.78
Experts have identified five major biological processes that are underlying the symptom complex of irritable bowel syndrome.
Two natural compounds, Perilla leaf extract and the probiotic organism S. cerevisiae, work together to address all five of these major pathological processes now recognized.
Together, these ingredients directly alleviate disordered intestinal motility, reduce visceral hypersensitivity, suppress low-level inflammation, decrease increased gut permeability, and rectify dysbiosis, the abnormal composition of the vital intestinal microbial community. Human studies show that these compounds help improve the major symptoms of irritable bowel syndrome.
There is no reason to continue to suffer with irritable bowel syndrome. Using this new and natural combination of ingredients will help your body restore its natural balance, and give you long-lasting sense of intestinal tranquility.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014 Oct 21;20(39):14105-25.
- Coss-Adame E, Rao SS. Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings. Curr Gastroenterol Rep. 2014 Apr;16(4):379.
- Fichna J, Storr MA. Brain-gut interactions in IBS. Front Pharmacol. 2012 Jul 5;3:127.
- Crouzet L, Gaultier E, Del’Homme C, et al. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil. 2013 Apr;25(4):e272-82.
- Moloney RD, O’Leary OF, Felice D, Bettler B, Dinan TG, Cryan JF. Early-life stress induces visceral hypersensitivity in mice. Neurosci Lett. 2012 Mar 23;512(2):99-102.
- Balestra B, Vicini R, Cremon C, et al. Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons. Neurogastroenterol Motil. 2012 Dec;24(12):1118-e570.
- Available at: http://womenshealth.gov/publications/our-publications/fact-sheet/irritable-bowel-syndrome.html. Accessed April 10, 2015.
- Magge S, Lembo A.Low-FODMAP Diet for Treatment of Irritable Bowel Syndrome. Gastroenterol Hepatol (N Y). 2012 Nov;8(11):739-45.
- Lacy BE, Weiser K, De Lee R. The treatment of irritable bowel syndrome. Therap Adv Gastroenterol. 2009 Jul;2(4):221-38.
- Basseri RJ, Kunkel D, Low K, Conklin JL, Pimentel M. Importance of diarrhea in evaluating constipation in irritable bowel syndrome clinical studies. J Clin Gastroenterol. 2011 Oct;45(9):790-3.
- Farthing MJ. Treatment options in irritable bowel syndrome. Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):773-86.
- Scarpignato C, Pelosini I. Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. Can J Gastroenterol. 1999 Mar;13 Suppl A:50A-65A.
- Buchwald-Werner S, Fujii H, Reule C, Schoen C. Perilla extract improves gastrointestinal discomfort in a randomized placebo controlled double blind human pilot study. BMC Complement Altern Med. 2014;14:173.
- Coelho VR, Vieira CG, de Souza LP, et al. Antiepileptogenic, antioxidant and genotoxic evaluation of rosmarinic acid and its metabolite caffeic acid in mice. Life Sci. 2015 Feb 1;122:65-71.
- Etienne-Mesmin L, Livrelli V, Privat M, et al. Effect of a new probiotic Saccharomyces cerevisiae strain on survival of Escherichia coli O157:H7 in a dynamic gastrointestinal model. Appl Environ Microbiol. 2011 Feb;77(3):1127-31.
- Sivignon A, Vandekerckove P, Barnich N, Pignède G, Darfeuille-Michaud A. Saccharomyces cerevisiae as a therapeutic tool to prevent colonization of the gut by adherent-invasive E. coli in Crohn’s disease patients. Gastroenterology. 2010 May;138(5):S-51.
- Lacy BE, Weiser K, De Lee R. The treatment of irritable bowel syndrome. Therap Adv Gastroenterol. 2009 Jul;2(4):221-38.
- Talley NJ. Dietary modification as a treatment for irritable bowel syndrome. Gastroenterol Hepatol (N Y). 2012 Aug;8(8):552-4.
- Neal KR, Barker L, Spiller RC. Prognosis in post-infective irritable bowel syndrome: a six-year follow up study. Gut. 2002 Sep;51(3):410-3.
- Isolauri E, Rautava S, Kalliomäki M. Food allergy in irritable bowel syndrome: new facts and old fallacies. Gut. 2004 Oct;53(10):1391-3.
- Leeds JS, Hopper AD, Sidhu R, et al. Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency. Clin Gastroenterol Hepatol. 2010 May;8(5):433-8.
- Stark D, van Hal S, Marriott D, Ellis J, Harkness J. Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis. Int J Parasitol. 2007 Jan;37(1):11-20.
- Nagel R, Bielefeldt-Ohmann H, Traub R. Clinical pilot study: efficacy of triple antibiotic therapy in Blastocystis positive irritable bowel syndrome patients. Gut Pathog. 2014 Aug 20;6:34.
- Goepp JG, McBride T, Fowler E, Peace-Brewer A, Landis D. Fecal biomarker testing identifies exocrine pancreatic insufficiency in patients with possible irritable bowel syndrome. AACC 2014 Annual Meeting and Clinical Lab Expo. 2014.
- Goepp J, Fowler E, McBride T, Landis D. Frequency of abnormal fecal biomarkers in irritable bowel syndrome. Glob Adv Health Med. 2014 May;3(3):9-15.
- Bouchoucha M, Devroede G, Raynaud JJ, Bon C, Bejou B, Benamouzig R. Is the colonic response to food different in IBS in contrast to simple constipation or diarrhea without abdominal pain? Dig Dis Sci. 2011 Oct;56(10):2947-56.
- Lee YJ, Park KS. Irritable bowel syndrome: emerging paradigm in pathophysiology. World J Gastroenterol. 2014 Mar 14;20(10):2456-69.
- Zhou Q, Verne GN. New insights into visceral hypersensitivity-clinical implications in IBS. Nat Rev Gastroenterol Hepatol. 2011 Jun;8(6):349-55.
- Kanazawa M, Hongo M, Fukudo S. Visceral hypersensitivity in irritable bowel syndrome. J Gastroenterol Hepatol. 2011 Apr;26 Suppl 3:119-21.
- Dong WZ, Zou DW, Li ZS, et al. Study of visceral hypersensitivity in irritable bowel syndrome. Chin J Dig Dis. 2004;5(3):103-9.
- Barbara G, Cremon C, Annese V, et al. Randomised controlled trial of mesalazine in IBS. Gut. 2014 Dec 22.
- Matricon J, Meleine M, Gelot A, et al. Associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther. 2012 Dec;36(11-12):1009-31.
- Bercik P, Verdu EF, Collins SM. Is irritable bowel syndrome a low-grade inflammatory bowel disease? Gastroenterol Clin North Am. 2005 Jun;34(2):235-45.
- Turcotte JF, Kao D, Mah SJ, et al. Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointest Endosc. 2013 Jan 25.
- Locke GR 3rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ. Risk factors for irritable bowel syndrome: role of analgesics and food sensitivities. Am J Gastroenterol. 2000 Jan;95(1):157-65.
- Sundin J, Rangel I, Fuentes S, et al. Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress. Aliment Pharmacol Ther. 2015 Feb;41(4):342-51.
- Tojo R, Suarez A, Clemente MG, et al. Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol. 2014 Nov 7;20(41):15163-76.
- Jalanka-Tuovinen J, Salojarvi J, Salonen A, et al. Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut. 2014 Nov;63(11):1737-45.
- Collins SM, Denou E, Verdu EF, Bercik P. The putative role of the intestinal microbiota in the irritable bowel syndrome. Dig Liver Dis. 2009 Dec;41(12):850-3.
- La JH, Kim TW, Sung TS, Kang JW, Kim HJ, Yang IS. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World J Gastroenterol. 2003 Dec;9(12):2791-5.
- Hong SN, Rhee PL. Unraveling the ties between irritable bowel syndrome and intestinal microbiota. World J Gastroenterol. 2014 Mar 14;20(10):2470-81.
- Barbara G, Stanghellini V, Cremon C, et al. Aminosalicylates and other anti-inflammatory compounds for irritable bowel syndrome. Dig Dis. 2009;27 Suppl 1:115-21.
- Sainsbury A, Ford AC. Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents. Therap Adv Gastroenterol. 2011 Mar;4(2):115-27.
- Chey WD, Eswaran S, Kurlander J. JAMA patient page. Irritable bowel syndrome. JAMA. 2015 Mar 3;313(9):982.
- Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014 Jan;146(1):67-75.e5.
- Ladabaum U, Boyd E, Zhao WK, et al. Diagnosis, comorbidities, and management of irritable bowel syndrome in patients in a large health maintenance organization. Clin Gastroenterol Hepatol. 2012 Jan;10(1):37-45.
- Wang Z, Fan J, Liu M, et al. Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application. Expert Opin Investig Drugs. 2013 Dec;22(12):1613-26.
- Ferrari CK. Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging. Biogerontology. 2004;5(5):275-89.
- Bachheti RK, Joshi A, Ahmed T. A phytopharmacological overview of perilla frutescens. Int J Pharm Sci Rev Res. May- Jun 2014; 26(2):55-61.
- Legras JL, Merdinoglu D, Cornuet JM, Karst F. Bread, beer and wine: Saccharomyces cerevisiae diversity reflects human history. Mol Ecol. 2007 May;16(10):2091-102.
- Available at: http://www.itmonline.org/articles/perilla/perilla.htm. Accessed April 21, 2015.
- Verspohl EJ, Fujii H, Homma K, Buchwald-Werner S. Testing of Perilla frutescens extract and Vicenin 2 for their antispasmodic effect. Phytomedicine. 2013 Mar 15;20(5):427-31.
- Atack JR. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. Expert Opin Investig Drugs. 2005 May;14(5):601-18.
- Albertin W, Marullo P, Aigle M, Dillmann C, de Vienne D, Bely M, Sicard D. Population size drives industrial Saccharomyces cerevisiae alcoholic fermentation and is under genetic control. Appl Environ Microbiol. 2011 Apr;77(8):2772-84.
- Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009 Jan;104 Suppl 1:S1-35.
- El-Salhy M, Gilja OH, Hatlebakk JG, Hausken T. Stomach antral endocrine cells in patients with irritable bowel syndrome. Int J Mol Med. 2014 Oct;34(4):967-74.
- El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG, Hausken T. Endocrine cells in the ileum of patients with irritable bowel syndrome. World J Gastroenterol. 2014 Mar 7;20(9):2383-91.
- El-Salhy M, Gundersen D, Hatlebakk JG, Gilja OH, Hausken T. Abnormal rectal endocrine cells in patients with irritable bowel syndrome. Regul Pept. 2014 Jan 10;188:60-5.
- Agah S, Taleb AM, Moeini R, Gorji N, Nikbakht H. Cumin extract for symptom control in patients with irritable bowel syndrome: a case series. Middle East J Dig Dis. 2013 Oct;5(4):217-22.
- Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012 Oct;303(7):G775-85.
- Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005 Aug;9(4):463-84. Epub 2005 Jan 21. Review.
- Buchwald-Werner S, Fujii H. Prokinetic and antispasmodic constituent discovered in Perilla Frutescens – Development of a gut health ingredient. Planta Med. 2012; 78 - CL61.
- Available at: http://www.mayoclinic.org/diseases-conditions/crohns-disease/basics/symptoms/con-20032061. Accessed April 17, 2015.
- Yang GY, Taboada S, Liao J. Inflammatory bowel disease: a model of chronic inflammation-induced cancer. Methods Mol Biol. 2009;511:193-233.
- Rubin DC, Shaker A, Levin MS. Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol. 2012 May 8;3:107.
- Available at: http://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/basics/symptoms/con-20043763. Accessed April 17, 2015.
- Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996 Jul;23(1):29-34.
- Fiocchi C. The immune system in inflammatory bowel disease. Acta Gastroenterol Belg. 1997 Apr-Jun;60(2):156-62.
- Banno N, Akihisa T, Tokuda H, et al. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem. 2004 Jan;68(1):85-90.
- Huang BP, Lin CH, Chen YC, Kao SH. Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccharide-stimulated RAW264.7 cells. Mol Med Rep. 2014 Aug;10(2):1077-83.
- Osakabe N, Yasuda A, Natsume M, Yoshikawa T. Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model. Carcinogenesis. 2004 Apr;25(4):549-57.
- Yang EJ, Ku SK, Lee W, et al. Barrier protective effects of rosmarinic acid on HMGB1-induced inflammatory responses in vitro and in vivo. J Cell Physiol. 2013 May;228(5):975-82.
- Camilleri M, Madsen K, Spiller R, Greenwood-Van Meerveld B, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil. 2012 Jun;24(6):503-12.
- Lillestol K, Helgeland L, Arslan Lied G, et al. Indications of ‘atopic bowel’ in patients with self-reported food hypersensitivity. Aliment Pharmacol Ther. 2010 May;31(10):1112-22.
- Makino T, Furuta A, Fujii H, et al. Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice. Biol Pharm Bull. 2001 Oct;24(10):1206-9.
- Pineton de Chambrun G, Neut C, Chau A, et al. A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome. Dig Liver Dis. 2015 Feb;47(2):119-24.
- Thijssen AY, Jonkers DM, Leue C, et al. Dysfunctional cognitions, anxiety and depression in irritable bowel syndrome. J Clin Gastroenterol. 2010 Nov-Dec;44(10):e236-41.
- Madisch A, Hotz J. Symptomatic therapy of irritable bowel syndrome. Which drug for which symptoms? MMW Fortschr Med. 2001 Sep 27;143(39):28-30.
- Cash B, Sullivan S, Barghout V. Total costs of IBS: employer and managed care perspective. Am J Manag Care. 2005 Apr;11(1 Suppl):S7-16.
- Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 Apr;130(5):1377-90.
- Palsson OS, Baggish JS, Turner MJ, Whitehead WE. IBS patients show frequent fluctuations between loose/watery and hard/lumpy stools: implications for treatment. Am J Gastroenterol. 2012 Feb;107(2):286-95.