Alimentary Pharmacology and Therapeutics

Letters to the Editors Letter: chronic constipation – a warning sign for oxidative stress? A. Vermorken*,†, E. Andr es‡ & Y. Cui*,† *College of Life Sciences, Northwest University, Xi’an, Shaanxi, China. † National Engineering Research Center for Miniaturized Detection Systems, Xi’an, Shaanxi, China. ‡ Internal Medicine and Nutrition, University of Strasbourg, Strasbourg, France. E-mail: [email protected] doi:10.1111/apt.13257

SIRS, Current Rome III criteria distinguish functional constipation and constipation predominant irritable bowel syndrome. The interesting paper by Koloski et al.,1 strengthens, however, recent views that both conditions are similar in terms of symptomatology and pathophysiology. The majority of patients with chronic constipation therefore form a large, homogeneous group. Consequently, associations with other diseases, including colorectal cancer and benign colorectal neoplasms, as recently reported by Guerin et al.,2 significantly gain impact. Severe constipation has also been associated with growth retardation in children,3 with gastroesophageal reflux disease,4and with cardiovascular risk in post-menopausal women.5 Guerin et al.2 proposed an increased contact time of carcinogens in the lumen as a possible mechanism for the association between constipation and colorectal cancer. We propose another mechanism for the association: oxidative stress. This mechanism could also explain the association with the other diseases. Oxidative stress is found in constipated children,6 in oesophageal tissue, even after successful anti-reflux surgery7 and it is associated with risk for both cardiovascular disease8 and for colorectal cancer.9 The vital question is: will adequate management of constipation reduce both oxidative stress and the risk for associated conditions? In an animal model, provoking

constipation led to oxidative stress.10 Prebiotics attenuated both constipation and oxidative stress. Effective management of constipation in children appeared beneficial to their growth status.3 It is thus plausible that adequate management of constipation may help reducing oxidative stress and the risk for constipation-associated diseases. The consequences would be far-reaching. The disease burden from the associated diseases is considerably higher than that from chronic constipation. Chronic constipation-related symptoms might be a warning sign for oxidative stress. This could be translated into a very powerful public health promotion message that may have a significant impact on the prevention of a number of major health problems, many of which are becoming more prevalent in our ageing societies.

ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Koloski NA, Jones M, Young M, Talley NJ. Differentiation of functional constipation and constipation predominant irritable bowel syndrome based on Rome III criteria: a population-based study. Aliment Pharmacol Ther 2015; 41: 856–66. 2. Guerin A, Mody R, Fok B, et al. Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation. Aliment Pharmacol Ther 2014; 40: 83–92. 3. Chao HC, Chen SY, Chen CC, et al. The impact of constipation on growth in children. Pediatr Res 2008; 64: 308–11. 4. Jansson C, Nordenstedt H, Wallander MA, et al. Severe symptoms of gastro-oesophageal reflux disease are associated with cardiovascular disease and other gastrointestinal symptoms, but not diabetes: a population-based study. Aliment Pharmacol Ther 2008; 27: 58–65. 5. Salmoirago-Blotcher E, Crawford S, Jackson E, et al. Constipation and risk of cardiovascular disease among postmenopausal women. Am J Med 2011; 124: 714–23. 6. Zhou JF, Lou JG, Zhou SL, Wang JL. Potential oxidative stress in children with chronic constipation. World J Gastroenterol 2005; 11: 368–71. 7. R€as€anen JV, Sihvo EI, Rantanen TK, et al. Gastroesophageal reflux patients’ defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4year follow-up. Ann Med 2008; 40: 74–80.

AP&T invited editorial and correspondence columns are restricted to letters discussing papers that have been published in the journal. A letter must have a maximum of 300 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.

ª 2015 John Wiley & Sons Ltd

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Letters to the Editors 8. Bonomini F, Rodella LF, Rezzani R. Metabolic syndrome, aging and involvement of oxidative stress. Aging Dis. 2015; 6: 109–20. 9. Suzuki K, Ito Y, Wakai K, et al. Serum oxidized low-density lipoprotein levels and risk of colorectal cancer: a case-control

Letter: chronic constipation – a warning sign for oxidative stress? Author’s reply N. J. Talley University of Newcastle, New Lambton, NSW, Australia. E-mail: [email protected] doi:10.1111/apt.13284

SIRS, We have previously observed chronic constipation is associated with increased mortality in two independent population-based studies. In an Australian populationbased study of 5107 women from the Australian Longitudinal Study on Women’s Health followed up for over 15 years, 21% had persistent constipation and their mortality rates were 30% higher when compared with women with no reported constipation despite controlling for confounders.1 Similarly, in Olmsted County, MN, USA, among 3933 eligible subjects, 16% reported chronic constipation and this was associated with a 23% reduced survival.2 While any link between chronic constipation and colon cancer is controversial,3, 4 this does not appear to explain the increased mortality.2, 4 Vermorken et al. suggest oxidative stress may provide a possible explanation for the associations described above.5 Oxidative stress, where the normal antioxidant

Letter: usefulness of HCC risk scores in HCV patients who fail pegylated interferon/ribavirin T.-M. Chen* & C.-C. Lin†,‡ *Division of Hepato-Gastroenterology, Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan. † Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. ‡ Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan. E-mail: [email protected] doi:10.1111/apt.13270

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study nested in the Japan Collaborative Cohort Study. Cancer Epidemiol Biomarkers Prev 2004; 13: 1781–7. 10. Li Y, Zong Y, Qi J, Liu K. Prebiotics and oxidative stress in constipated rats. J Pediatr Gastroenterol Nutr 2011; 53: 447–52.

defences are unable to deal with the excess production of reactive oxygen species that at high enough levels can cause cellular damage, is emerging as a mechanism that may induce intestinal dysmotility and cardiovascular disease.6 Further research is needed to test this intriguing concept.

ACKNOWLEDGEMENT The author’s declarations of personal and financial interests are unchanged from those in the original article.3 REFERENCES 1. Koloski NA, Jones M, Wai R, Gill RS, Byles J, Talley NJ. Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol 2013; 108: 1152–8. 2. Chang JY, Locke GR 3rd, McNally MA, et al. Impact of functional gastrointestinal disorders on survival in the community. Am J Gastroenterol 2010; 105: 822–32. 3. Guerin A, Mody R, Fok B, et al. Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation. Aliment Pharmacol Ther 2014; 40: 83–92. 4. Power AM, Talley NJ, Ford AC. Association between constipation and colorectal cancer: systematic review and meta-analysis of observational studies. Am J Gastroenterol 2013; 108: 894–903. 5. Vermorken A, Andres E, Cui Y. Chronic constipation: a warning sign for oxidative stress? Aliment Pharmacol Ther 2015; 42: 385–6. 6. Kashyap P, Farrugia G. Oxidative stress: key player in gastrointestinal complications of diabetes. Neurogastroenterol Motil 2011; 23: 111–4.

SIRS, We read with interest the article by Younossi et al. which reported that hepatitis C virus (HCV)-infected patients suffer substantial patient-reported outcome burden during treatment with pegylated interferon/ribavirin (PR).1 With the advent of new directly acting antivirals (DAAs), not only was there an improvement in sustained virological response (SVR) rates but also the tolerance for interferon-free DAAs was also better.1 Conceivably, patients with prior PR treatment failure are in need of these new drugs. Inflammation has long been associated with the development of cancer.2 We studied whether the post-treatment absolute monocyte count (AMC) could predict risk

Aliment Pharmacol Ther 2015; 42: 385–389 ª 2015 John Wiley & Sons Ltd

Letter: chronic constipation - a warning sign for oxidative stress?

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