Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2019; 25(14): 1729-1740
Published online Apr 14, 2019. doi: 10.3748/wjg.v25.i14.1729
Chronic functional constipation is strongly linked to vitamin D deficiency
Alba Panarese, Francesco Pesce, Piero Porcelli, Giuseppe Riezzo, Palma Aurelia Iacovazzi, Carla Maria Leone, Massimo De Carne, Caterina Mammone Rinaldi, Endrit Shahini
Alba Panarese, Massimo De Carne, Endrit Shahini, Department of Gastroenterology and Digestive Endoscopy, Scientific Institute for Digestive Disease "Saverio de Bellis" Hospital, Castellana Grotte (Bari) 70013, Italy
Francesco Pesce, Nephrology section, Department of Emergency and Organ Transplantation, University of Bari, Bari 70013, Italy
Piero Porcelli, Department of Psychological, Health, and Territorial Sciences, D'Annunzio University of Chieti-Pescara, Chieti 70013, Italy
Giuseppe Riezzo, Palma Aurelia Iacovazzi, Carla Maria Leone, Department of Clinical Pathology, Scientific Institute for Digestive Disease "Saverio de Bellis" Hospital, Castellana Grotte (Bari) 70013, Italy
Caterina Mammone Rinaldi, Department of Radiology, Scientific Institute for Digestive Disease "Saverio de Bellis" Hospital, Castellana Grotte (Bari) 70013, Italy
Endrit Shahini, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
Author contributions: Panarese A has conceived the protocol; Shahini E and Panarese A drafted the initial and final manuscript; Panarese A enrolled patients; Panarese A, and Leone CM collected in a database the baseline and on-treatment information; Shahini E, Pesce F and Porcelli P systematically reviewed the data entries for completeness and consistency, checked for completeness of information and performed the statistical analysis; all the authors reviewed and approved the final draft.
Institutional review board statement: National Institute of Gastroenterology “S. De Bellis” Research Hospital (0807/16) and by the Research Ethics Committee of the National Oncological Institute of Bari (CAAE:147/16) (Trial registration number: NCT03096704).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All authors declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Corresponding author: Alba Panarese, MD, Doctor, Department of Gastroenterology and Digestive Endoscopy, Scientific Institute for Digestive Disease "Saverio de Bellis" Hospital, Turi Street n. 27, Castellana Grotte (Bari) 70013, Italy.
Telephone: +39-3471401487; +39-0804994251 Fax: +39-0804994250
Received: February 16, 2019
Peer-review started: February 18, 2019
First decision: February 26, 2019
Revised: March 11, 2019
Accepted: March 24, 2019
Article in press: March 25, 2019
Published online: April 14, 2019
Research background

Functional chronic constipation is a gastrointestinal disorder that affects more commonly women and older subjects, with a deep impact on global health-care system. Nowadays, only few studies have examined intestinal motility disorders, which are severe clinical conditions associated with chronic functional constipation, whose pathogenesis and prevalence are actually partially known. In this subgroup are inclued patients with slow transit constipation, as well as with slow oro-cecal transit time, whereas their extreme clinical form, could be considered chronic intestinal pseudo-obstruction, which has been related to the structural damage of neural and smooth muscle cells of gut.

Research motivation

Although some studies have shown a possible link between vitamin D deficiency and irritable bowel syndrome (IBS), as well as with depression (and with several other diseases), the same link has never been detected before in patients affected by intestinal motility disorders, and the indications to look for vitamin D in these patients relied only of opinions of experts in the field. Therefore we investigated this relationship and the psychological aspects in this subgroup of patients.

Research objectives

To investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation linked to intestinal motility disorders.

Research methods

Herein, we applied rigorous statistical methods to elucidate this relationship. We performed a prospective case-control study, from May-June to November 2017. We used Glucose/lactulose breath tests, radiopaque markers (multiple capsule techniques) and wireless motility capsule analysis to estimate both oro-cecal and colonic transit time. After receiving a diagnosis of intestinal motility disorders, patients underwent to blood sampling, for checking 25-hydroxyvitamin D levels. Furthermore, we evaluated for these patients the influence on psychological features and on their quality of life, which were estimated by using validated questionnaires, the IBS Quality of life (IBS-QOL), the Short Form Health Survey 12 (SF-12), and the Hospital Anxiety and Depression Scale 14 (HADS-14 A and HADS-14 D).

Research results

Our cohort included 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 age, sex, body mass index (BMI)-matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels (P < 0.001), and they showed a significant impairment of all health-related quality of life domains and psychological tests (IBS-QOL, SF12-PCS, SF12-MCS, HADS-14 A and HADS-14 D), as compared to the control group (P < 0.001). Moreover, the latter tests significantly correlated with reduced vitamin D levels (r = - 0.57, P < 0.001; r = 0.21, P = 0.01; r = - 0.48, P < 0.001; r = - 0.57, P < 0.001; r = - 0.29, P < 0.001, respectively). In multivariate analysis, vitamin D low levels remained significantly associated with the occurrence of intestinal motility disorder, after adjusting for BMI (odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001).

Research conclusions

We demonstrated for the first time a strong association between vitamin D deficiency and intestinal motility disorders. Moreover, these patients are very commonly affected by anxiety and depression symptoms which deeply impact on their quality of life. These findings suggest that vitamin D serum levels should be routinely measured in this category of patients and consequently vitamin D supplementation could represent a further therapeutic aid for this clinical condition.

Research perspectives

Our findings may confirm how vitamin D deficiency could exert a wide spectrum of action in many gastrointestinal (or not) diseases, being highly associated with intestinal motility disorders and with certain neuropsychiatric symptoms, but remains unclear if it could have a causative role in this process, and for this reason, future cross-sectional studies are needed, also to investigate if anxiety and depression symptoms are caused by intestinal factors.