For patients, irritable bowel syndrome (IBS) can be a tricky diagnosis to understand and an even tougher condition to treat. Unlike inflammatory bowel diseases (IBD), which are relatively well-characterized based on the physiological processes that underpin their symptoms, IBS is a functional bowel disorder. That means it is diagnosed based on the patient’s specific symptomatic complaints. As a result, IBS can manifest differently in every patient, with possible symptoms including constipation, diarrhea, bloating, gas, abdominal pain, and every gastrointestinal (GI) complaint in between. Moreover, the causes of these symptoms can vary considerably between patients, so even if several patients’ symptoms are similar, there’s no guarantee that a single treatment will work for all of them. For instance, one patient with IBS may experience chronic constipation because of a food intolerance, while another may have the same symptom because of a microbiome-related problem. This makes IBS treatment a particularly complicated challenge for IBS sufferers and their healthcare providers.
For patients and practitioners, the good news is that recent research has led to better understandings of the possible causes of functional GI symptoms that don’t fall neatly into the category of an established IBD and are therefore diagnosed as IBS. In some cases, the physiological underpinnings overlap, which indicates that some of the same treatments used to treat IBD may be just as effective for IBS. One such promising option is glutathione, an antioxidant supplement that may help combat the oxidative stress that plays a role in some cases of IBS.
Inflammation in Irritable Bowel Syndrome
Among the variety of factors that may contribute to IBS, inflammation is increasingly recognized within the research community as a possible cause. Although the level of inflammation in the GI tract of a patient with IBS may not be as high as it is in patients with IBD, low-grade inflammation still has the potential to contribute to the intestinal damage in the GI tract that leads to gastrointestinal motor dysfunction. Like so many other aspects of the condition, the reason for low-grade inflammation in some patients with IBS is not fully understood: some studies suggest that the low-grade inflammation may result from immune system dysfunction, while others indicate a possible role for the internal microenvironment, with altered microbial composition contributing to the vulnerability of the intestinal lining to harm caused by free radical species. Whatever the source of the inflammation in a particular IBS patient, it may be worth exploring the use of therapeutics that combat oxidative damage induced by inflammatory processes.
Preliminary Research Relevant to the Use of Glutathione for IBS
Glutathione plays an important antioxidant role in the body. The compound is a tripeptide consisting of cysteine, glycine, and glutamic acid, and it exists in two states: the reduced state (GSH) and the oxidized state (GSSG). When GSH, the naturally more abundant form of the compound, encounters free radicals—including singlet oxygen, hydroxyl radicals, and superoxide radicals, all of which have the potential to damage cells and tissues—it can be oxidized to GSSG. However, it is important to note that glutathione’s antioxidant activities are not limited to the direct oxidation of the compound; rather, glutathione also acts as a cofactor for several antioxidant enzymes. Without its facilitation, these enzymes are unable to catalyze essential antioxidant processes.
The primary reason patients and practitioners are increasingly interested in using glutathione for the treatment of IBS is that initial research suggests that it may be effective for reducing inflammation and ameliorating symptoms in IBD patients. Thus, in cases where the underlying mechanisms of the condition do overlap, taking a glutathione supplement could be just as effective for a patient with IBS as it is for a patient with IBD. When glutathione facilitates antioxidant processes, it protects tissues from the inflammation that would otherwise result from their exposure to damaging free radicals, which can trigger inflammation. If inflammation is involved in either IBS or IBD, a glutathione supplement may be an appropriate choice for patients. Indeed, as far back as 1998, scientists have recognized that intestinal glutathione synthesis is impaired in patients with IBD, and this dysregulation may play a role in the etiology and progression of a patient’s condition. Thus, supplementation with glutathione may help effectively address this deficiency.
Although researchers have not yet conducted any specific studies on treating IBD with glutathione in either animal models or in humans, there is evidence that other antioxidant therapies can reduce symptoms—possibly by raising levels of glutathione. For instance, in a 2012 study published in the European Journal of Pharmacology, researchers treated mouse models of IBD with N-acetylcysteine, a well-known antioxidant. The treatment had a variety of physiological effects, including the initiation of a rise in glutathione, which may have further contributed to the positive functional effects of the therapy. Researchers have also found that other natural antioxidants, including multiple dietary polyphenols, can reduce inflammation and combat symptoms in mouse models of IBD. Given that glutathione is the most abundant antioxidant in the body, it stands to reason that it could have similar effects as other naturally derived antioxidant compounds, like curcumin, quercetin, naringenin, and hesperetin.
The Absence of Debilitating Side Effects
Given the multifactorial, complex nature of IBS, it is common for patients to be particularly sensitive to the side effects of supplements and pharmaceuticals. As a result, patients with an IBS diagnosis tend to be particularly skeptical about novel therapeutics that have a long list of potentially adverse impacts. Indeed, since IBS is a functional gastrointestinal disorder, patients and practitioners have to be cognizant about how any potential treatment impacts other functional aspects of the patient’s health. If an adverse effect, or even the inconvenience, of a particular treatment, outweighs the benefits for the patient, it may not be worthwhile to include it in a therapeutic strategy. Therefore, it is promising to note that, in the human studies that have examined the use of glutathione for non-GI conditions, the results indicate a positive safety profile for the supplement. Few side effects have been reported, and those that have been observed are relatively mild. Thus, for patients and practitioners considering trying glutathione for IBS, side effects are not likely to be a major concern.
Overall, despite the absence of specific research on glutathione for IBS, the broader scholarly literature on the topic suggests that it may be a worthwhile option for patients and practitioners to consider. Underpinned by early research on the role of inflammation in IBS and the possible benefits of antioxidant therapy for IBD patients, the possibility of glutathione as an effective supplement for IBS patients is becoming increasingly prominent. Future research in both humans and animals will help confirm the value of this supplement for both IBS and IBD, but patients today can begin by working with clinicians to explore how glutathione supplementation might play a role in their unique therapeutic strategy.
Akiho H, Ihara E, Nakamura K. 2010. Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome. World Journal of Gastrointestinal Pathophysiology. 1(3):97-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097950/
Allen J, Bradley RD. 2011. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. Journal of Alternative and Complementary Medicine. 17(9):827-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162377/
Amrouche-Mekkioui I, Djerdjouri B. 2012. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice. European Journal of Pharmacology 68(1-3):209-17. https://www.ncbi.nlm.nih.gov/pubmed/22732651
Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biological Chemistry, 390(3):191-214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756154/
Colgan SP, Curtis VF, Campbell EL. 2013. The inflammatory tissue microenvironment in IBD. Inflammatory Bowel Diseases. 19(10):2238-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749286/
Long MD, Drossman DA. Inflammatory bowel disease, irritable bowel syndrome, or what? A challenge to the functional-organic dichotomy. American Journal of Gastroenterology. 105(8):1796-8. https://www.ncbi.nlm.nih.gov/pubmed/20686466
Moura FA, de Andrade KQ, Dos Santos JCF, Araujo ORP, Goulari MOF. 2015. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work? Redox Biology. 6:617-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637335/
Pallone F, Monteleone G. 2001. Mechanisms of tissue damage in inflammatory bowel disease. Current Opinion in Gastroenterology. 17(4):307-12. https://www.ncbi.nlm.nih.gov/pubmed/17031175
Pizzorno, J. 2014. Glutathione! Integrative Medicine: A Clinician’s Journal. 13(1):8-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/
Rani RA, Ali RAR, Lee YY. 2016. Irritable bowel syndrome and inflammatory bowel disease overlap syndrome: Pieces of the puzzle are falling into place. Intestinal Research. 14(4):297-304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083258/
Shigeshiro M, Tanabe S, Suzuki T. 2013. Dietary polyphenols modulate intestinal barrier defects and inflammation in a murine model of colitis. Journal of Functional Foods. 5(2):949-55. https://www.sciencedirect.com/science/article/pii/S1756464613000662
Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W. 1998. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut. 42(4):485-92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1727080/
Sinagra E, Pompei G, Tomasello G, Capello F, Morreale GC, et al. 2016. Inflammation in irritable bowel syndrome: Myth or new treatment target? World Journal of Gastroenterology. 22(7):2242-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734999/