|
1
|
Koureta E, Karatzas P, Kanellopoulos P, Papapanagiotou A, Lekakis V, Bamias G, Koutsoumpas A, Karamanolis G, Vlachogiannakos J, Papavassiliou AG, Papatheodoridis GV. The importance of vitamin D levels in patients with inflammatory bowel disease. J Physiol Biochem 2025:10.1007/s13105-025-01096-5. [PMID: 40418498 DOI: 10.1007/s13105-025-01096-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Accepted: 05/13/2025] [Indexed: 05/27/2025]
Abstract
The possible role of vitamin D (VD) in the pathogenesis of inflammatory bowel disease (IBD) and the associations between VD levels and IBD activity remain unclarified. We aimed to assess VD levels in IBD patients and their associations with IBD activity. We evaluated VD levels in Greek patients aged 18-75 years old with Crohn's disease (CD) or ulcerative colitis (UC). Patients were ineligible under the following conditions: history of enterectomy/right colectomy, receiving VD or agent(s) interfering with VD metabolism during the last three months and any comorbidities that influence VD levels. Epidemiologic characteristics, clinical course, laboratory investigations, endoscopic and histologic findings were recorded. In total, 122 patients with CD and 71 with UC were included. Most of them had low levels of VD (90% of CD and 91.5% of UC patients). Patients with clinically active CD or UC had lower levels of VD compared to those in remission (p = 0.009 and p = 0.033, respectively).CD patients with low levels of VD had higher CRP and stool calprotectin compared to those with normal levels of VD (P = 0.032 and P = 0.002, respectively). In UC, patients with pancolitis had lower VD levels compared to patients with proctitis (P = 0.036). In conclusion, the majority of Greek IBD patients have low levels of VD. Clinical activity is related to lower levels of VD. Low compared to normal levels of VD in CD patients are associated with higher CRP and calprotectin levels, so VD levels might serve as an activity marker.
Collapse
Affiliation(s)
- Evgenia Koureta
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Pantelis Karatzas
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Panagiotis Kanellopoulos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Angeliki Papapanagiotou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Vasileios Lekakis
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Giorgos Bamias
- GastreonteroIogy Unit, 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Sotiria", Athens, Greece
| | - Andreas Koutsoumpas
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George Karamanolis
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Jiannis Vlachogiannakos
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George V Papatheodoridis
- 1st Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
| |
Collapse
|
|
2
|
Vernia F, Ribichini E, Burrelli Scotti G, Latella G. Nutritional Deficiencies and Reduced Bone Mineralization in Ulcerative Colitis. J Clin Med 2025; 14:3202. [PMID: 40364233 PMCID: PMC12072929 DOI: 10.3390/jcm14093202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 05/03/2025] [Accepted: 05/04/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Inadequate dietary intake of vitamin D, vitamin K, and calcium, as well as sub-optimal sunlight exposure, can lead to bone loss in the general population, and more so in patients with ulcerative colitis, who are burdened by additional predisposing factors for osteoporosis, such as chronic inflammation and cortisone use. However, micronutrient deficiencies, if present, are easily corrected by nutritional intervention. While the relation between calcium and vitamin D and bone metabolism is well known, fewer data are available for vitamin K, for both healthy individuals and patients. The aim of this review is to provide an overview of recent reports focusing on nutritional deficits relevant to the development of osteoporosis/osteopenia in patients affected by ulcerative colitis. Methods: A systematic electronic search of the English literature up to January 2025 was performed using Medline and the Cochrane Library. Results: Despite being central in bone mineralization, data on dietary calcium intake in ulcerative colitis are relatively scarce, deriving mostly from mixed inflammatory bowel disease cohorts. Although lower than controls, dietary calcium intake approaches the recommended daily allowance, which establishes the necessary daily intake of nutrients. Conversely, vitamin D and vitamin K deficiencies are highly prevalent in ulcerative colitis patients. The widely shared opinion that milk and lactose-containing foods, as well as vegetables, worsen diarrhea is a prime determinant of inadequate vitamin D and vitamin K intake. Conclusions: Increased awareness of the importance of nutrition and the common occurrence of nutritional deficits represents the first step for the development of dietary intervention strategies to counteract the increased risk of osteoporosis in ulcerative colitis patients.
Collapse
Affiliation(s)
- Filippo Vernia
- Department of Life, Health, and Environmental Sciences, Division of Gastroenterology, Hepatology, and Nutrition, University of L’Aquila, Piazza S. Tommasi, 1-Coppito, 67100 L’Aquila, Italy;
| | - Emanuela Ribichini
- Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy; (E.R.); (G.B.S.)
| | - Giorgia Burrelli Scotti
- Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy; (E.R.); (G.B.S.)
| | - Giovanni Latella
- Department of Life, Health, and Environmental Sciences, Division of Gastroenterology, Hepatology, and Nutrition, University of L’Aquila, Piazza S. Tommasi, 1-Coppito, 67100 L’Aquila, Italy;
| |
Collapse
|
|
3
|
Wang K, Zhu S, Yao L, Cao Q, Shao B. Association of vitamin D and platelet-to-lymphocyte ratio in treatment escalation risk for newly diagnosed Crohn's disease adults. Nutr J 2025; 24:49. [PMID: 40155983 PMCID: PMC11951787 DOI: 10.1186/s12937-025-01115-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 03/14/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Accumulating research has implicated that vitamin D (VD) may be important in the pathogenesis of Crohn's disease (CD), while the platelet-to-lymphocyte ratio (PLR) is emerging as a biomarker in immune disorders. However, the synergistic effect of VD and PLR on treatment escalation in newly diagnosed CD patients remains unclear. Therefore, this study aims to assess the interaction between PLR and VD on the subsequent use of infliximab and/or immunosuppressants in patients with CD. METHODS Newly diagnosed CD patients were selected from the Sir Run Run Shaw Hospital Inflammatory Bowel Disease Biobank (SRRSH-IBC). COX proportional hazards models were employed to assess the association between VD, PLR, and treatment escalation among CD patients. RESULTS Among 108 newly diagnosed CD adult patients, vitamin D deficiency (VDD) was prevalent (78.7%). Compared to CD patients without VDD, those with VDD exhibited a higher risk of treatment escalation, i.e., using infliximab and/or immunosuppressants (HR = 3.22, 95% CI = 1.24-8.35, P = 0.016). There is a clear trend of decreasing risk of treatment escalation as VD levels elevating (HR = 0.26, 95% CI = 0.09-0.76, P for trend = 0.014). The stratified analysis revealed a noteworthy interaction between PLR and VD levels concerning treatment escalation. Baseline VDD amplified the risk of treatment escalation among patients with elevated PLR (HR = 4.17, 95% CI = 1.51-11.53, Pinteraction = 0.031). Similar trends were observed when VD levels were stratified into quartiles (highest quartile vs. lowest quartile: HR = 0.18, 95% CI = 0.05-0.62, P for trend = 0.014). CONCLUSION This study underscores a significant interplay between VD levels and PLR in influencing treatment outcomes in CD. VDD exacerbates the risk of treatment escalation primarily in individuals with heightened PLR levels, highlighting the combined impact of vitamin D status and inflammation on disease progression of CD.
Collapse
Affiliation(s)
- Kan Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China
| | - Shichen Zhu
- Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China
| | - Lingya Yao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
| | - Bule Shao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
| |
Collapse
|
|
4
|
Latini A, De Benedittis G, Conigliaro P, Bonini C, Morgante C, Iacovantuono M, D’Antonio A, Bergamini A, Novelli G, Chimenti MS, Ciccacci C, Borgiani P. The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors. Genes (Basel) 2024; 15:234. [PMID: 38397223 PMCID: PMC10887840 DOI: 10.3390/genes15020234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/07/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.
Collapse
Affiliation(s)
- Andrea Latini
- Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy; (A.L.); (G.D.B.); (C.M.); (G.N.)
| | - Giada De Benedittis
- Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy; (A.L.); (G.D.B.); (C.M.); (G.N.)
| | - Paola Conigliaro
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Chiara Bonini
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Chiara Morgante
- Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy; (A.L.); (G.D.B.); (C.M.); (G.N.)
| | - Maria Iacovantuono
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Arianna D’Antonio
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Alberto Bergamini
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Giuseppe Novelli
- Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy; (A.L.); (G.D.B.); (C.M.); (G.N.)
- School of Medicine, Department of Pharmacology, University of Nevada, Reno, NV 89557, USA
- IRCCS NEUROMED, 86077 Pozzilli, Italy
| | - Maria Sole Chimenti
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (P.C.); (C.B.); (M.I.); (A.D.); (A.B.); (M.S.C.)
| | - Cinzia Ciccacci
- UniCamillus, Saint Camillus International University of Health Sciences, 00131 Rome, Italy;
| | - Paola Borgiani
- Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy; (A.L.); (G.D.B.); (C.M.); (G.N.)
| |
Collapse
|
|
5
|
Song X, Zhang H, Wang H, Li Z, Zhou X, Guo H. Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn's Disease. Gastroenterol Res Pract 2023; 2023:6675401. [PMID: 37842203 PMCID: PMC10575748 DOI: 10.1155/2023/6675401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 05/29/2023] [Accepted: 09/09/2023] [Indexed: 10/17/2023] Open
Abstract
Background The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD) remains controversial. Objective To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. Methods This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. Results The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (P < 0.001). CD activity index (CDAI) (120, range, 93-142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0-4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25-196; SES-CD 13, range, 5-23) (P < 0.001). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (P = 0.024). IFX serum TC was related to BR (P = 0.036), CR (P = 0.032) at week 14, and ERe (P = 0.009) at week 38. Conclusion Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.
Collapse
Affiliation(s)
- Xiaomei Song
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| | - Huihui Zhang
- Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing, China
| | - Hao Wang
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| | - Zhongyue Li
- Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing, China
| | - Xiaoqin Zhou
- Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing, China
| | - Hong Guo
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| |
Collapse
|
|
6
|
Valvano M, Capannolo A, Cesaro N, Stefanelli G, Fabiani S, Frassino S, Monaco S, Magistroni M, Viscido A, Latella G. Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease. Nutrients 2023; 15:3824. [PMID: 37686856 PMCID: PMC10489664 DOI: 10.3390/nu15173824] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.
Collapse
Affiliation(s)
- Marco Valvano
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
- Division of Gastroenterology, Galliera Hospital, 16128 Genoa, Italy;
| | - Annalisa Capannolo
- Diagnostic and Surgical Endoscopy Unit, San Salvatore Academic Hospital, 67100 L’Aquila, Italy;
| | - Nicola Cesaro
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | | | - Stefano Fabiani
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Sara Frassino
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Sabrina Monaco
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Marco Magistroni
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Angelo Viscido
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Giovanni Latella
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| |
Collapse
|
|
7
|
Chanchlani N, Lin S, Smith R, Roberts C, Nice R, McDonald TJ, Hamilton B, Bishara M, Bewshea C, Kennedy NA, Goodhand JR, Ahmad T. Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients With Active Luminal Crohn's Disease. CROHN'S & COLITIS 360 2023; 5:otad026. [PMID: 37265586 PMCID: PMC10231451 DOI: 10.1093/crocol/otad026] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Indexed: 06/03/2023] Open
Abstract
Background and Aims Vitamin D has a regulatory role in innate and adaptive immune processes. Previous studies have reported that low pretreatment vitamin D concentrations are associated with primary non-response (PNR) and non-remission to anti-TNF therapy. This study aimed to assess whether pretreatment 25-hydroxyvitamin D concentrations predicted PNR and non-remission to infliximab and adalimumab in patients with active luminal Crohn's disease. Methods 25-Hydroxyvitamin D concentrations were measured in stored baseline samples from 659 infliximab- and 448 adalimumab-treated patients in the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study. Cut-offs for vitamin D were deficiency <25 nmol/L, insufficiency 25-50 nmol/L, and adequacy/sufficiency >50 nmol/L. Results About 17.1% (189/1107; 95% CI, 15.0-19.4) and 47.7% (528/1107; 95% CI, 44.8-50.6) of patients had vitamin D deficiency and insufficiency, respectively. 22.2% (246/1107) of patients were receiving vitamin D supplementation. Multivariable analysis confirmed that sampling during non-summer months, South Asian ethnicity, lower serum albumin concentrations, and non-treatment with vitamin D supplementation were independently associated with lower vitamin D concentrations. Pretreatment vitamin D status did not predict response or remission to anti-TNF therapy at week 14 (infliximab Ppnr = .89, adalimumab Ppnr = .18) or non-remission at week 54 (infliximab P = .13, adalimumab P = .58). Vitamin D deficiency was, however, associated with a longer time to immunogenicity in patients treated with infliximab, but not adalimumab. Conclusions Vitamin D deficiency is common in patients with active Crohn's disease. Unlike previous studies, pretreatment vitamin D concentration did not predict PNR to anti-TNF treatment at week 14 or nonremission at week 54.
Collapse
Affiliation(s)
| | | | - Rebecca Smith
- Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Christopher Roberts
- Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Rachel Nice
- Biochemistry, Exeter Clinical Laboratory International, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
| | - Timothy J McDonald
- Biochemistry, Exeter Clinical Laboratory International, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
| | - Benjamin Hamilton
- Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Maria Bishara
- Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Claire Bewshea
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | - Nicholas A Kennedy
- Gastroenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
| | | | - Tariq Ahmad
- Address correspondence to: Tariq Ahmad, DPhil, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, RILD building, Barrack Road, Exeter EX2 5DW, UK ()
| |
Collapse
|
|
8
|
Rotondo C, Cantatore FP, Cici D, Erroi F, Sciacca S, Rella V, Corrado A. Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival-A Retrospective Study. Int J Mol Sci 2023; 24:5368. [PMID: 36982443 PMCID: PMC10049319 DOI: 10.3390/ijms24065368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 02/28/2023] [Accepted: 03/08/2023] [Indexed: 03/15/2023] Open
Abstract
A growing body of evidence on the importance of vitamin D in immune modulation has increased the interest in its possible impact on the course of rheumatological diseases. The scope of our study is to assess if the presence of different statuses of vitamin D could interfere in the clinical subsets, in methotrexate monotherapy discontinuation, and biological drug (b-DMARDs) survival in psoriatic arthritis patients (PsA). We conducted a retrospective study on PsA patients and split them into three groups based on their vitamin D status: the group with 25(OH)D ≤ 20 ng/mL, the group with levels of 25(OH)D between 20 and 30 ng/mL, and the group with serum levels of 25(OH)D ≥ 30 ng/mL. All patients were required to fulfill the CASPAR criteria for psoriatic arthritis and to have the evaluation of vitamin D serum levels at baseline visit and at clinical follow-up visits. The exclusion criteria were ages less than 18 years old, the presence of HLA B27, and satisfaction of rheumatoid arthritis classification criteria (during the study time). Statistical significance was set at p ≤ 0.05. Furthermore, 570 patients with PsA were screened and 233 were recruited. A level of 25(OH)D ≤ 20 ng/mL was present in 39% of patients; levels of 25(OH)D between 20 and 30 ng/mL presented in 25% of patients; 65% of patients with sacroiliitis presented 25 (OH)D ≤ 20 ng/mL. Methotrexate monotherapy discontinuation for failure was higher in the group with 25 (OH)D ≤ 20 ng/mL (survival time: 92 ± 10.3 weeks vs. 141.9 ± 24.1 weeks vs. 160.1 ± 23.6 weeks; p = 0.02) with higher discontinuation risk (HR = 2.168, 95% CI 1.334, 3.522; p = 0.002) than those with 25(OH)D between 20 and 30 ng/mL and those with 25(OH)D ≥ 30 ng/mL. Significantly shorter survival of first b-DMARDs was assessed in the group with 25 (OH)D ≤ 20 ng/mL versus the other groups (133.6 ± 11 weeks vs. 204.8 ± 35.8 weeks vs. 298.9 ± 35.4; p = 0.028) (discontinuation risk 2.129, 95% CI 1.186, 3.821; p = 0.011). This study highlights significant differences in clinical presentation, in particular sacroiliac involvement and on drug survival (methotrexate and b-DMARDs) in PsA patients with vitamin D deficiency. Further prospective studies, including a larger sample of patients, are needed to validate these data and to assess if the supplementation of vitamin D could improve the b-DMARDs response in PsA patients.
Collapse
|
|
9
|
Kaliora AC. Nutrition in inflammatory bowel diseases; Is there a role? Best Pract Res Clin Gastroenterol 2023; 62-63:101827. [PMID: 37094912 DOI: 10.1016/j.bpg.2023.101827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/10/2023] [Accepted: 02/15/2023] [Indexed: 04/26/2023]
Abstract
Nutrition is of paramount importance not only for healthy individuals, but all the more for the ones with pathologies interlinked with the diet. In that light, diet, when used accordingly can act in a protective manner in inflammatory bowel diseases. The interplay of diet and IBD is not thoroughly defined, and guidelines are a work in progress. However, significant knowledge has been gained with regard to foods and nutrients that may exacerbate or alleviate the core symptoms. Patients with IBD restrict from their diet a plethora of foods often arbitrary, thus depriving themselves from valuable constituents. Careful navigation into the newfound field of genetic variants and personalization of diet should be employed with avoidance of the Westernized diet, processed foods and additives, and focus on a holistic approach with a balanced diet rich in bioactive compounds in order to improve the quality of life of these patients and address diet-related deficiencies.
Collapse
Affiliation(s)
- Andriana C Kaliora
- Human Nutrition and Foods, Department of Dietetics-Nutrition Science, School of Health and Education Sciences, Harokopio University, 70 El. Venizelou Ave., 17676, Athens, Greece.
| |
Collapse
|
|
10
|
Fan X, Yin J, Yin J, Weng X, Ding R. Comparison of the anti-inflammatory effects of vitamin E and vitamin D on a rat model of dextran sulfate sodium-induced ulcerative colitis. Exp Ther Med 2023; 25:98. [PMID: 36761001 PMCID: PMC9893224 DOI: 10.3892/etm.2023.11797] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 11/09/2022] [Indexed: 01/15/2023] Open
Abstract
The present study aimed to compare the clinical effects of vitamin E and vitamin D on a rat model of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), and to elucidate the underlying mechanisms associated with changes in the levels of cytokines. After successful establishment of the rat model of DSS-induced UC, prednisolone (1 mg/kg), vitamin D (50 ng) and vitamin E (6, 30 and 150 IU/kg) were orally administered for 1 week. The pharmacodynamics were evaluated by a daily combination of clinical observation (CO) scores, histopathological evaluations and assessment of molecular markers of inflammation. Administration of vitamin D, vitamin E (30 and 150 IU/kg), prednisolone, and the combination of vitamin D and vitamin E resulted in a decrease in CO scores. The severity of inflammation of the colon was markedly alleviated in the treatment groups compared with that in the untreated DSS group according to the results of histopathological examination; however, they showed different inhibitory effects on the levels of some cytokines. In conclusion, the present results indicated that oral administration of vitamin E could promote recovery of DSS-induced UC by the inhibition of proinflammatory cytokines, and that its underlying mechanism may differ from that of vitamin D and glucocorticoid drugs.
Collapse
Affiliation(s)
- Xing Fan
- National Beijing Center for Drug Safety Evaluation and Research, State Key Laboratory for Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China,Office of Laboratory Management, Beijing Technology and Business University, Beijing 100048, P.R. China
| | - Jie Yin
- Department of Neuroscience, Beijing Institute of Basic Medical Sciences, Beijing 100850, P.R. China
| | - Jiye Yin
- National Beijing Center for Drug Safety Evaluation and Research, State Key Laboratory for Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China
| | - Xiechuan Weng
- Department of Neuroscience, Beijing Institute of Basic Medical Sciences, Beijing 100850, P.R. China,Correspondence to: Dr Xiechuan Weng, Department of Neuroscience, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, P.R. China NULL
| | - Rigao Ding
- National Beijing Center for Drug Safety Evaluation and Research, State Key Laboratory for Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China,Correspondence to: Dr Xiechuan Weng, Department of Neuroscience, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, P.R. China NULL
| |
Collapse
|
|
11
|
Paliu IA, Ianosi SL, Turcu-Stiolica A, Pisoschi CG, Predoi LG, Tica AA. Vitamin D May Be Connected with Health-Related Quality of Life in Psoriasis Patients Treated with Biologics. J Pers Med 2022; 12:1857. [PMID: 36579586 PMCID: PMC9695623 DOI: 10.3390/jpm12111857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/02/2022] [Accepted: 11/04/2022] [Indexed: 11/09/2022] Open
Abstract
Suboptimal states of vitamin D may play a role in psoriasis evolution, but the interconnections have been studied over the past years with controversial results. Although a peerless therapy among moderate to severe types of psoriasis, the therapeutic effectiveness of biological therapy may vary unforeseeably between patients and leads to biologics switch. We conducted a pilot study in patients diagnosed with psoriasis and treated with biologics, the purpose of which was to explore the prevalence of suboptimal states of vitamin D, especially in the group of patients characterized by the failure of previous biologics, and to investigate the associations between vitamin D levels and psoriasis, regarding aspects such the severity of the disease and quality of life. Their current result of latent tuberculosis infection (LTBI) was also considered concerning a feasible relationship with vitamin D levels. From July to December 2021, 45 patients corresponding to our inclusion criteria were assessed. Variables such as Psoriasis Area and Severity Index (PASI) score and the Dermatology Life Quality Index (DLQI) score, as well as vitamin D serum concentrations and their LTBI result, were recorded for them. Lower serum concentrations of vitamin D were not more common in patients characterized by failure to previous biologics (p = 0.443), but we concluded a weak correlation between the DLQI score and vitamin D (rho = -0.345, p-value = 0.020), although a statistically insignificant result was obtained between vitamin D and the PASI score (rho = -0.280, p-value = 0.062), and with the LTBI result (rho = -0.053, p-value = 0.728). These results establish a connection between higher levels of vitamin D and a better outcome of psoriasis from the perspective of the patient's quality of life, with no significant association with psoriasis severity and no significant prevalence of suboptimal states among patients that failed previous biologics compared to those with a continuously good response.
Collapse
Affiliation(s)
- Iulia-Alexandra Paliu
- Department of Pharmacology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Simona-Laura Ianosi
- Department of Dermatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Adina Turcu-Stiolica
- Department of Pharmacoeconomics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - Luminita-Georgeta Predoi
- Dermatology Ambulatory Office, Clinical Emergency County Hospital of Craiova, 200642 Craiova, Romania
| | - Andrei-Adrian Tica
- Department of Pharmacology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| |
Collapse
|
|
12
|
Szymczak-Tomczak A, Ratajczak AE, Kaczmarek-Ryś M, Hryhorowicz S, Rychter AM, Zawada A, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Pleiotropic Effects of Vitamin D in Patients with Inflammatory Bowel Diseases. J Clin Med 2022; 11:jcm11195715. [PMID: 36233580 PMCID: PMC9573215 DOI: 10.3390/jcm11195715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/18/2022] [Accepted: 09/21/2022] [Indexed: 12/07/2022] Open
Abstract
The multifaceted activity of vitamin D in patients with inflammatory bowel disease (IBD) presents a challenge for further research in this area. Vitamin D is involved in the regulation of bone mineral metabolism, it participates in the regulation of the immune system, and it is an underlying factor in the pathogenesis of IBD. Additionally, vitamin D affects Th1 and Th2 lymphocytes, influencing the release of cytokines and inhibiting tumor necrosis factor (TNF) expression and the wnt/β-catenin pathway. As far as IBDs are concerned, they are associated with microbiota dysbiosis, abnormal inflammatory response, and micronutrient deficiency, including vitamin D hypovitaminosis. In turn, the biological activity of active vitamin D is regulated by the vitamin D receptor (VDR) which is associated with several processes related to IBD. Therefore, in terms of research on vitamin D supplementation in IBD patients, it is essential to understand the metabolic pathways and genetic determinants of vitamin D, as well as to identify the environmental factors they are subject to, not only in view of osteoporosis prevention and therapy, but primarily concerning modulating the course and supplementation of IBD pharmacotherapy.
Collapse
Affiliation(s)
- Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Correspondence: (A.S.-T.); (A.E.R.); Tel.: +48-8691-343 (A.S.-T.); +48-667-385-996 (A.E.R.); Fax: +48-8691-686 (A.E.R.)
| | - Alicja Ewa Ratajczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Correspondence: (A.S.-T.); (A.E.R.); Tel.: +48-8691-343 (A.S.-T.); +48-667-385-996 (A.E.R.); Fax: +48-8691-686 (A.E.R.)
| | - Marta Kaczmarek-Ryś
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Szymon Hryhorowicz
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| |
Collapse
|
|
13
|
Di Vincenzo F, Puca P, Lopetuso LR, Petito V, Masi L, Bartocci B, Murgiano M, De Felice M, Petronio L, Gasbarrini A, Scaldaferri F. Bile Acid-Related Regulation of Mucosal Inflammation and Intestinal Motility: From Pathogenesis to Therapeutic Application in IBD and Microscopic Colitis. Nutrients 2022; 14:nu14132664. [PMID: 35807844 PMCID: PMC9268369 DOI: 10.3390/nu14132664] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/23/2022] [Accepted: 06/25/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) and microscopic colitis are chronic immune-mediated inflammatory disorders that affect the gastroenterological tract and arise from a complex interaction between the host’s genetic risk factors, environmental factors, and gut microbiota dysbiosis. The precise mechanistic pathways interlinking the intestinal mucosa homeostasis, the immunological tolerance, and the gut microbiota are still crucial topics for research. We decided to deeply analyze the role of bile acids in these complex interactions and their metabolism in the modulation of gut microbiota, and thus intestinal mucosa inflammation. Recent metabolomics studies revealed a significant defect in bile acid metabolism in IBD patients, with an increase in primary bile acids and a reduction in secondary bile acids. In this review, we explore the evidence linking bile acid metabolites with the immunological pathways involved in IBD pathogenesis, including apoptosis and inflammasome activation. Furthermore, we summarize the principal etiopathogenetic mechanisms of different types of bile acid-induced diarrhea (BAD) and its main novel diagnostic approaches. Finally, we discuss the role of bile acid in current and possible future state-of-the-art therapeutic strategies for both IBD and BAD.
Collapse
Affiliation(s)
- Federica Di Vincenzo
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
- Correspondence:
| | - Pierluigi Puca
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Loris Riccardo Lopetuso
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
| | - Valentina Petito
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
| | - Letizia Masi
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
| | - Bianca Bartocci
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Marco Murgiano
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Margherita De Felice
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Lorenzo Petronio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Antonio Gasbarrini
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| | - Franco Scaldaferri
- IBD Unit—UOS Malattie Infiammatorie Croniche Intestinali, CEMAD, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L. Go A. Gemelli 8, 00168 Rome, Italy; (P.P.); (L.R.L.); (V.P.); (L.M.); (A.G.); (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, L. Go F. Vito 1, 00168 Rome, Italy; (B.B.); (M.M.); (M.D.F.); (L.P.)
| |
Collapse
|
|
14
|
JABEEN S, KHAN HF, ALI S, SIDDIQUE AH, MAJEED S, SAFDER S, SHAMSHAD F. Role of Vitamin D Supplementation in Improving Cytokine Profile in Patients of Non-ST-Elevation Acute Coronary Syndrome. J Nutr Sci Vitaminol (Tokyo) 2022; 68:1-7. [DOI: 10.3177/jnsv.68.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Sidra JABEEN
- Department of Physiology, Islamic International Medical College
| | | | - Shazia ALI
- Department of Physiology, Islamic International Medical College
| | - Abdul Hamid SIDDIQUE
- Head of Cardiology Department, Armed Forces Institute of Cardiology/National Institute of Heart Diseases
| | - Sana MAJEED
- Department of Physiology, Islamic International Medical College
| | - Saira SAFDER
- Department of Physiology, Islamic International Medical College
| | - Fozia SHAMSHAD
- Department of Physiology, Islamic International Medical College
| |
Collapse
|
|
15
|
Szilagyi A. Relationships between Western Non Communicable Diseases and Geographic Pattern Modifiers Based on Latitude and Lactase Distributions. Med Hypotheses 2022. [DOI: 10.1016/j.mehy.2022.110797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
16
|
Bamias G, Rivera-Nieves J. Vitamin D Levels May Predict Response to Vedolizumab. J Crohns Colitis 2021; 15:1978-1979. [PMID: 34185075 PMCID: PMC8684447 DOI: 10.1093/ecco-jcc/jjab105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Giorgos Bamias
- GI Unit, 3rd Academic Dept. of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Jesús Rivera-Nieves
- Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego [UCSD], La Jolla, CA, USA
- San Diego VA Medical Center [SDVAMC], San Diego, CA, USA
| |
Collapse
|
|
17
|
Vandikas MS, Landin-Wilhelmsen K, Polesie S, Gillstedt M, Osmancevic A. Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis. Acta Derm Venereol 2021; 101:adv00604. [PMID: 34643740 PMCID: PMC9455319 DOI: 10.2340/actadv.v101.359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive Creactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks’ treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.
Collapse
Affiliation(s)
- Maria Siekkeri Vandikas
- Dermatology and Venereology Unit, Karolinska University Hospital, Solna, Eugeniavägen 3, A6:01, SE-171 76, Stockholm, Sweden.
| | | | | | | | | |
Collapse
|
|
18
|
Xia SL, Min QJ, Shao XX, Lin DP, Ma GL, Wu H, Cao SG, Jiang Y. Influence of Vitamin D3 Supplementation on Infliximab Effectiveness in Chinese Patients With Crohn's Disease: A Retrospective Cohort Study. Front Nutr 2021; 8:739285. [PMID: 34746207 PMCID: PMC8568764 DOI: 10.3389/fnut.2021.739285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/21/2021] [Indexed: 12/31/2022] Open
Abstract
Background: It remains uncertain whether vitamin D3 (vitD3) supplementation is beneficial for remission of Crohn's disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) effectiveness was analyzed in Chinese CD patients. Methods: In this retrospective cohort study, moderate-to-severe CD patients, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks, were recorded from January 2014 to December 2019. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention. Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (20.33 vs. 15.07 ng/mL, P < 0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (83.8 vs. 61.6%, P = 0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (7.41 ± 3.0 vs. 6.28 ± 2.75, P = 0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (β = −1.667, P = 0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3 (all P < 0.05), but not in non-deficient vitD3. A total of nine patients (four non-D3-patients and five D3-patients) were selected to determine serum cytokine profiles after 54-week IFX treatment. In non-D3-patients, the decreases of TNF-α and IL-6 at 54-week were more obvious than at baseline (P = 0.032, 0.022, respectively). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P = 0.037). Conclusions: VitD3 supplementation could improve IFX effectiveness in CD patients, especially for patients with vitD3 deficiency. This beneficial effect of vitD3 supplementation probably arose from the up-regulation of IL-10. Trial Registration: NCT04606017.
Collapse
Affiliation(s)
- Sheng-Long Xia
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Quan-Jia Min
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiao-Xiao Shao
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Dao-Po Lin
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guo-Long Ma
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hao Wu
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shu-Guang Cao
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yi Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
|
19
|
Matthews SW, Heitkemper MM, Kamp K. Early Evidence Indicates Vitamin D Improves Symptoms of Irritable Bowel Syndrome: Nursing Implications and Future Research Opportunities. Gastroenterol Nurs 2021; 44:426-436. [PMID: 34690298 DOI: 10.1097/sga.0000000000000634] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 07/21/2021] [Indexed: 11/26/2022] Open
Abstract
Irritable bowel syndrome (IBS) affects approximately 11.2% of the population. Yet, full understanding of its etiology and optimal treatment remains elusive. Understanding of the underlying pathophysiology of IBS has been limited. However, research is beginning to identify the cause as multifactorial (e.g., low-grade local mucosal inflammation, systemic immune activation, altered intestinal permeability, intestinal hypersensitivity, altered central nervous system processing, changes in intestinal microbiota). Understanding of the role of vitamin D in intestinal inflammation, immunity, and gastrointestinal conditions is increasing but is not yet fully understood. Growing evidence has linked vitamin D deficiency with a variety of gastrointestinal disorders, including inflammatory bowel disease, diverticulitis, colorectal cancer, and IBS. Several studies have demonstrated that individuals with IBS are more likely to have vitamin D deficiency than healthy controls. Recent vitamin D supplementation studies have shown improvement in quality of life and reduction in IBS symptoms (including abdominal pain, distention, flatulence, constipation, and visceral sensitivity) but the mechanism remains unclear. Nurses are well positioned to educate patients about the importance of sufficient vitamin D for overall health in individuals with IBS as well as participate in well-designed therapeutic studies to explore whether enhanced vitamin D status will ultimately help treat IBS more effectively.
Collapse
Affiliation(s)
- Sarah W Matthews
- Sarah W. Matthews, DNP, MN, BSN, APRN, FNP-BC, is Assistant Professor, Department of Child, Family, and Population Health Nursing, University of Washington, School of Nursing, Seattle; and Nurse Practitioner, Kaiser Permanente Washington, Bellevue
- Margaret M. Heitkemper, PhD, MN, BSN, RN, FAAN, is Professor and Chairperson, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
- Kendra Kamp, PhD, BSN, RN, is Assistant Professor, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
| | - Margaret M Heitkemper
- Sarah W. Matthews, DNP, MN, BSN, APRN, FNP-BC, is Assistant Professor, Department of Child, Family, and Population Health Nursing, University of Washington, School of Nursing, Seattle; and Nurse Practitioner, Kaiser Permanente Washington, Bellevue
- Margaret M. Heitkemper, PhD, MN, BSN, RN, FAAN, is Professor and Chairperson, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
- Kendra Kamp, PhD, BSN, RN, is Assistant Professor, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
| | - Kendra Kamp
- Sarah W. Matthews, DNP, MN, BSN, APRN, FNP-BC, is Assistant Professor, Department of Child, Family, and Population Health Nursing, University of Washington, School of Nursing, Seattle; and Nurse Practitioner, Kaiser Permanente Washington, Bellevue
- Margaret M. Heitkemper, PhD, MN, BSN, RN, FAAN, is Professor and Chairperson, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
- Kendra Kamp, PhD, BSN, RN, is Assistant Professor, Department of Biobehavioral Nursing and Health Informatics, University of Washington, School of Nursing, Seattle
| |
Collapse
|
|
20
|
The Impact of Vitamin D on Response to Anti-tumor Necrosis Factor-α Therapy in Children With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2021; 72:e125-e131. [PMID: 33847289 DOI: 10.1097/mpg.0000000000003064] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. METHODS This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. RESULTS Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034). CONCLUSIONS Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.
Collapse
|
|
21
|
Bendix M, Dige A, Jørgensen SP, Dahlerup JF, Bibby BM, Deleuran B, Agnholt J. Seven Weeks of High-Dose Vitamin D Treatment Reduces the Need for Infliximab Dose-Escalation and Decreases Inflammatory Markers in Crohn's Disease during One-Year Follow-Up. Nutrients 2021; 13:nu13041083. [PMID: 33810258 PMCID: PMC8065492 DOI: 10.3390/nu13041083] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/20/2021] [Accepted: 03/23/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Seven weeks of high-dose vitamin D treatment decreases intestinal IL17A and IFN-γ mRNA expression in active Crohn's disease (CD). In this follow-up study, we investigated whether seven-week vitamin D treatment affected the infliximab response in the following 45 weeks compared to placebo. METHODS CD patients (n = 40) were initially randomised into four groups: infliximab + vitamin-D; infliximab + placebo-vitamin-D; placebo-infliximab + vitamin-D; and placebo-infliximab + placebo-vitamin-D. Infliximab (5 mg/kg) or placebo-infliximab was administered at weeks 0, 2 and 6. Vitamin D (5 mg bolus followed by 0.5 mg/day for 7 weeks) or placebo-vitamin D was handed out. After the 7-week vitamin D period, all patients received infliximab during follow-up. Results are reported for Group D+ (infliximab + vitamin-D and placebo-infliximab + vitamin-D) and Group D- (infliximab + placebo-vitamin-D and placebo-infliximab + placebo-vitamin-D). RESULTS Group D- patients had greater needs for infliximab dose escalation during follow-up compared to group D+ (p = 0.05). Group D+ had lower median calprotectin levels week 15 (p = 0.02) and week 23 (p = 0.04) compared to group D-. Throughout follow-up, group D+ had 2.2 times (95% CI: 1.1-4.3) (p = 0.02) lower median CRP levels compared with group D-. CONCLUSIONS Seven weeks high-dose vitamin D treatment reduces the need for later infliximab dose-escalation and reduces inflammatory markers. EudraCT no. 2013-000971-34.
Collapse
Affiliation(s)
- Mia Bendix
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; (A.D.); (S.P.J.); (J.F.D.); (J.A.)
- Medical Department, Randers Regional Hospital, 8930 Randers, Denmark
- Correspondence:
| | - Anders Dige
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; (A.D.); (S.P.J.); (J.F.D.); (J.A.)
| | - Søren Peter Jørgensen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; (A.D.); (S.P.J.); (J.F.D.); (J.A.)
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; (A.D.); (S.P.J.); (J.F.D.); (J.A.)
| | - Bo Martin Bibby
- Department of Public Health—Department of Biostatistics, Aarhus University, 8000 Aarhus, Denmark;
| | - Bent Deleuran
- Department of Rheumatology, Aarhus University Hospital, 8200 Aarhus, Denmark;
- Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
| | - Jørgen Agnholt
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; (A.D.); (S.P.J.); (J.F.D.); (J.A.)
| |
Collapse
|
|
22
|
Valvano M, Magistroni M, Mancusi A, D’Ascenzo D, Longo S, Stefanelli G, Vernia F, Viscido A, Necozione S, Latella G. The Usefulness of Serum Vitamin D Levels in the Assessment of IBD Activity and Response to Biologics. Nutrients 2021; 13:323. [PMID: 33499406 PMCID: PMC7910959 DOI: 10.3390/nu13020323] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/17/2021] [Accepted: 01/20/2021] [Indexed: 12/28/2022] Open
Abstract
The main role of vitamin D is calcium homeostasis and bone metabolism, although its activity as an immuno-modulator and its anti-inflammatory effect is well-known. Low blood vitamin D levels are common among patients with inflammatory bowel disease (IBD). Whether low vitamin D levels could affect the disease activity or it is an effect of a worse condition of the disease is still unclear. This study aimed to investigate the role of blood vitamin D levels to identify the clinical, endoscopic, and histological activity in a cohort of patients with ulcerative colitis (UC) or Crohn's disease (CD) on therapy with biological drugs. In this retrospective cohort study, 50 IBD patients (24 UC and 26 CD) that underwent colonoscopy from January 2017 to January 2020 with a concomitant serological evaluation of vitamin D were included. Patients with clinical, endoscopic, and histological activity and those who lost their clinical response to the biological drug had lower vitamin D levels compared to patients in remission or patients that did not change therapeutic regimens. A receiver operating characteristic (ROC) analysis and Youden's Index were performed to assess the optimal vitamin D levels to identify patients with the active disease. The ROC analysis showed an area under the curve (AUC) of 0.709 (p = 0.005; confidence interval (CI): 0.564-0.829), 0.769 (p < 0.001; CI: 0.628-0.876), and 0.810 (p < 0.001; CI: 0.670-0.910) for the clinical, endoscopic, and histological outcomes, respectively. The optimal vitamin D cut-off was ≤25 ng/mL. The vitamin D level is an additional useful tool in the evaluation of IBD patients with good accuracy to predict their endoscopic and histological activity and clinical response to biologics.
Collapse
Affiliation(s)
- Marco Valvano
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Marco Magistroni
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Antonio Mancusi
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Debora D’Ascenzo
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Salvatore Longo
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Gianpiero Stefanelli
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Filippo Vernia
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Angelo Viscido
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| | - Stefano Necozione
- Epidemiology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
| | - Giovanni Latella
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (M.V.); (M.M.); (A.M.); (D.D.); (S.L.); (G.S.); (F.V.); (A.V.)
| |
Collapse
|
|
23
|
Abstract
Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol breakdown in the host liver, secondary bile acids are the products of microbial metabolism. Primary and secondary bile acids along with their oxo derivatives have been identified as signaling molecules acting on a family of cell membrane and nuclear receptors collectively known as "bile acid-activated receptors." Members of this group of receptors are highly expressed throughout the gastrointestinal tract and mediate the bilateral communications of the intestinal microbiota with the host immune system. The expression and function of bile acid-activated receptors FXR, GPBAR1, PXR, VDR, and RORγt are highly dependent on the structure of the intestinal microbiota and negatively regulated by intestinal inflammation. Studies from gene ablated mice have demonstrated that FXR and GPBAR1 are essential to maintain a tolerogenic phenotype in the intestine, and their ablation promotes the polarization of intestinal T cells and macrophages toward a pro-inflammatory phenotype. RORγt inhibition by oxo-bile acids is essential to constrain Th17 polarization of intestinal lymphocytes. Gene-wide association studies and functional characterizations suggest a potential role for impaired bile acid signaling in development inflammatory bowel diseases (IBD). In this review, we will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile acid signaling in these disorders.
Collapse
|
|
24
|
L Bishop E, Ismailova A, Dimeloe S, Hewison M, White JH. Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory. JBMR Plus 2021; 5:e10405. [PMID: 32904944 PMCID: PMC7461279 DOI: 10.1002/jbm4.10405] [Citation(s) in RCA: 169] [Impact Index Per Article: 42.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 08/05/2020] [Indexed: 02/06/2023] Open
Abstract
Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic T-regulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Emma L Bishop
- Institute of Immunology and ImmunotherapyUniversity of BirminghamBirminghamUK
| | - Aiten Ismailova
- Department of PhysiologyMcGill UniversityMontrealQuebecCanada
| | - Sarah Dimeloe
- Institute of Immunology and ImmunotherapyUniversity of BirminghamBirminghamUK
- Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
| | - Martin Hewison
- Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
| | - John H White
- Department of PhysiologyMcGill UniversityMontrealQuebecCanada
- Department of MedicineMcGill UniversityMontrealQuebecCanada
| |
Collapse
|
|
25
|
Kim KB, Kim HW, Lee JS, Yoon SM. [Inflammatory Bowel Disease and Vitamin D]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 76:275-281. [PMID: 33361704 DOI: 10.4166/kjg.2020.160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 12/18/2022]
Abstract
Vitamin D contributes to bone metabolism and acts as an immune modulator for both innate and adaptive immunity. The serum level of vitamin D has been associated with inflammatory diseases, such as inflammatory bowel disease (IBD). In epidemiologic studies, IBD patients have been shown to have low levels of vitamin D. The suboptimal circulating levels of vitamin D in IBD patients may be caused by low exposure to sunlight, dietary malabsorption, and the impaired conversion of active metabolites (1,25[OH]2D). Recent studies have demonstrated that vitamin D deficiency in IBD can increase the chance of disease recurrence, IBD-related hospitalization or surgery, and deterioration of quality of life. Supplementation with vitamin D is therefore thought to reduce the risk of flare-ups and the improvement of the quality of life in IBD patients. This review aims to summarize the latest knowledge on the effects of vitamin D deficiency on IBD and the possible benefits of vitamin D supplementation in IBD patients.
Collapse
Affiliation(s)
- Ki Bae Kim
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Hyoung Woo Kim
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jun Su Lee
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Soon Man Yoon
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| |
Collapse
|
|
26
|
Caballero Mateos AM, Olmedo-Martín RV, Roa-Colomo A, Díaz Alcázar MDM, Valenzuela Barranco M. Vitamin D and inflammatory bowel disease: what do we know so far? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 112:935-940. [PMID: 33054287 DOI: 10.17235/reed.2020.7061/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In the last years,several studies have focused on the involement of vitamin D in different physiological and pathological processes. One of the most interesting actions occurs in the Inflammatory bowel disease, where a higher prevalence of vitamin D deficiency has been observed. This study aimed to review the literature in order to explain its relationship with the disease, the risk factors, measuring the importance of sun exposure, describing how treatments are affected or observing the effect of vitamin supplementation in this type of patients.
Collapse
|
|
27
|
Decrease in Mucosal IL17A, IFNγ and IL10 Expressions in Active Crohn's Disease Patients Treated with High-Dose Vitamin Alone or Combined with Infliximab. Nutrients 2020; 12:nu12123699. [PMID: 33266022 PMCID: PMC7759913 DOI: 10.3390/nu12123699] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 11/24/2020] [Accepted: 11/26/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Vitamin D treatment may reduce Crohn’s disease (CD) activity by modulating the mucosal immune function. We investigated if high-dose vitamin D +/− infliximab modulated the mucosal cytokine expression in active CD. Methods: Forty CD patients were randomized into: infliximab + vitamin D; infliximab + placebo-vitamin D; placebo-infliximab + vitamin D or placebo-infliximab + placebo-vitamin D. Infliximab (5 mg/kg) and placebo-infliximab were administered at weeks 0, 2 and 6. Oral vitamin D was administered as bolus 200,000 international units (IU) per week 0 followed by 20,000 IU/day for 7 weeks or placebo. Endoscopy with biopsies was performed at weeks 0 and 7 where endoscopic activity was measured and mucosal mRNA cytokine expression was examined. C-reactive protein (CRP), fecal calprotectin and Harvey-Bradshaw Index (HBI) were measured at weeks 0, 2 and 6. Results: High-dose vitamin D treatment alone and combined with infliximab decreased the IL17A, IFNγ and IL10 expression. High-dose vitamin D alone did not significantly decrease the disease activity, CRP or calprotectin. Combined infliximab and vitamin D treatment was not clinically significantly superior to monotherapy with infliximab. Conclusions: High-dose vitamin D as monotherapy and combined with infliximab decreases IL17A, IFNγ and IL-10 expression in mucosa within treatment groups. This did not induce a statistically significant decreased disease activity. EudraCT no.2013-000971-34.
Collapse
|
|
28
|
Palchaudhuri S, Albenberg L, Lewis JD. Diet Recommendations for Hospitalized Patients With Inflammatory Bowel Disease: Better Options Than Nil Per Os. CROHN'S & COLITIS 360 2020; 2:otaa059. [PMID: 33954288 PMCID: PMC8096188 DOI: 10.1093/crocol/otaa059] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hospitalizations are a time when providers often have uncertainty about what to feed patients with inflammatory bowel disease (IBD). While there are many trials evaluating the role of diet in the management of IBD, the role of diet for the hospitalized patient is less clear. The hospitalization may serve as an opportunity to educate patients about the role of diet, try different diets, and develop dietary recommendations for after discharge. Here, we review the literature for dietary considerations during hospitalizations and acute settings, as well as upon discharge. Patients with IBD benefit from screening and nutritional support for malnutrition and nutritional deficiencies. Enteral nutrition and exclusion diets are promising as induction and maintenance therapies, but no specific recommendations during hospitalization for adult patients are available currently. There are very few reasons to enforce bowel rest or clear liquids other than bowel obstruction, uncontrolled sepsis, or need for urgent or emergent surgery; most patients - including many with penetrating or stricturing disease - benefit from feeding in whichever capacity is tolerated, with enteral and parenteral nutrition used as needed to reach nutritional goals. Future studies are needed to define how the use of different diets can influence the outcomes of patients hospitalized for IBD.
Collapse
Affiliation(s)
- Sonali Palchaudhuri
- Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA,Address correspondence to: Sonali Palchaudhuri, MD, Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104 ()
| | - Lindsey Albenberg
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - James D Lewis
- Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
29
|
Myint A, Sauk JS, Limketkai BN. The role of vitamin D in inflammatory bowel disease: a guide for clinical practice. Expert Rev Gastroenterol Hepatol 2020; 14:539-552. [PMID: 32543306 DOI: 10.1080/17474124.2020.1775580] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that carries significant morbidity and mortality. Given the need to identify modifiable risk factors to prevent IBD development and to mitigate disease severity, vitamin D has become a major candidate of interest. AREAS COVERED In this review, we discuss the regulatory role played by vitamin D in intestinal immune homeostasis, updates in the recent literature exploring its role in de novo IBD pathogenesis and established IBD activity. We also discuss societal recommendations on its therapeutic role in maintaining bone health and future directions for studying its role in regulating disease activity. EXPERT OPINION In contrast to findings from earlier studies suggesting a causal role in IBD, recent findings indicate that vitamin D deficiency may be a sequela rather than a cause of IBD. Additionally, clinical trials exploring vitamin D therapy in reducing disease activity remain inconclusive thus far, with the current evidence best supporting a therapeutic role of vitamin D in bone health. Future studies are needed to clarify the role of vitamin D in IBD development and disease activity and to determine its therapeutic potential for IBD disease activity.
Collapse
Affiliation(s)
- Anthony Myint
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA, USA
| | - Jenny S Sauk
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA, USA
| | - Berkeley N Limketkai
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA, USA
| |
Collapse
|
|
30
|
Bafutto M, Oliveira EC, Rezende Filho J. Use of Vitamin D With Anti-Tumor Necrosis Factor Therapy for Crohn's Disease. Gastroenterology Res 2020; 13:101-106. [PMID: 32655726 PMCID: PMC7331853 DOI: 10.14740/gr1264] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 05/14/2020] [Indexed: 12/23/2022] Open
Abstract
Background Vitamin D (VD) has an important role in regulating gut mucosal immunity, and seems to be inversely linked to disease activity and more frequent relapses in inflammatory bowel disease. In this study, we evaluated patients with Crohn’s disease (CD) treated with anti-tumor necrosis factor (TNF) in association with VD. Methods A double-blind, randomized, prospective study was conducted. Thirty patients with a history of moderate to severe CD, in use of anti-TNF, of both sexes, 18 to 70 years, with the dosage of VD < 75 nmol/L (30 ng/mL) were randomized and divided into three groups: group 1 (G1): 10 patients received 2,000 IU VD, per os (PO)/week for 8 weeks; group 2 (G2): 10 patients received 10,000 IU VD, PO/week for 8 weeks; group 3 (G3): 10 patients received 50,000 IU VD, PO/week for 8 weeks. Before and at the end of 8 weeks patients were submitted to VD, fecal calprotectin (FC) and C-reactive protein (CRP) dosage. Follow-up period was 52 weeks, and they are checked for disease activity recurrence (Crohn’s disease activity index (CDAI) > 150, FC > 300 and computerized tomography (CT) scan), FC, CRP, and VD levels. Results Increased VD levels were observed in all groups (P < 0.0001). CRP did not change. There was a significant decrease of FC in G3 (1,014 ± 850 vs. 483 ± 564; P = 0.04), no significant decrease in G2 (76,767 ± 751 vs. 535 ± 823; P = 0.2) and increase in G1 (1,101 ± 744 vs. 1,357 ± 819; P = 0.4). During the 52-week follow-up period, it was showed that recurrent disease activity (CDAI > 150, FC > 200 and CT scan) was predominant in patients with VD < 30 group, and the remission rate was predominant in patients with VD > 30 group (P = 0.0001). A statistically significant difference in VD levels was noted in CD patients after 52 weeks that presented flare or disease remission (P = 0.001). Conclusions Use of VD associated with anti-TNF treatment may improve clinical response in CD. VD levels greater than 30 ng/mL have better rates of remission.
Collapse
Affiliation(s)
- Mauro Bafutto
- Instituto Goiano de Gastroenterolgoia, Goiania, Brazil.,Department of Internal Medicine, School of Medicine, Universidade Federal de Goias, Goiania, Brazil
| | - Enio Chaves Oliveira
- Instituto Goiano de Gastroenterolgoia, Goiania, Brazil.,Department of Surgery, School of Medicine, Universidade Federal de Goias, Goiania, Brazil
| | - Joffre Rezende Filho
- Instituto Goiano de Gastroenterolgoia, Goiania, Brazil.,Department of Internal Medicine, School of Medicine, Universidade Federal de Goias, Goiania, Brazil
| |
Collapse
|
|
31
|
Kojecky V, Matous J, Kianicka B, Dite P, Zadorova Z, Kubovy J, Hlostova M, Uher M. Vitamin D levels in IBD: a randomised trial of weight-based versus fixed dose vitamin D supplementation. Scand J Gastroenterol 2020; 55:671-676. [PMID: 32538182 DOI: 10.1080/00365521.2020.1774921] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: Body weight is one of the factors affecting blood levels of 25-hydroxyvitamin D (25OHD). The aim of this study was to establish whether a vitamin D (vitD) weight-based dosing is more appropriate to a fixed daily dose in patients with inflammatory bowel disease (IBD).Materials/methods: This was an open label randomised trial. Patients with IBD were assigned to receive oral cholecalciferol at a dose of 28 IU/kg (IU/kg) or 2000 IU per day (IU/day) for 12 weeks during winter months. 25OHD plasma levels and other biochemical parameters were measured at baseline and after supplementation period. The primary outcome measure was 25OHD level after a follow-up period.Results: A total of 173 patients were analysed. The mean BMI was 25.5 ± 5.1 and initial mean 25OHD level was 62.7 ± 25.5 nmol/l. A similar increase (9.7 ± 26.9 vs 9.8 ± 26.7 nmol/l) in 25OHD levels occurred both in IU/kg and IU/day group. The proportion of subjects with normal and sub-normal levels following the substitution was comparable irrespective of body weight. The change in 25OHD level correlated positively only with the dose of vitD (p < .001) and negatively with the baseline 25OHD level (p < .001). A sustained 25OHD level of 75 nmol/l corresponds with a calculated daily vitD dose of 2034 IU.Conclusions: Weight-based dosing of vitamin D is not superior to a fixed dose in order to maintain stable 25OHD levels in IBD patients. Cholecalciferol dose of 2,000 IU/day is safe and sufficient during winter period.
Collapse
Affiliation(s)
- Vladimir Kojecky
- Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.,Internal Department, Bata Regional Hospital, Zlin, Czech Republic
| | - Jan Matous
- 2nd Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Bohuslav Kianicka
- 2nd Department of Internal Medicine/Department of Gastroenterology, St. Anne´s University Hospital, Brno, Czech Republic
| | - Petr Dite
- Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Zdena Zadorova
- 2nd Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Kubovy
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Martina Hlostova
- Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
| | - Michal Uher
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| |
Collapse
|
|
32
|
Vitamin D suppresses proangiogenic factors in patients with ulcerative colitis: A randomized double blind placebo controlled clinical trial. Complement Ther Clin Pract 2020; 39:101086. [DOI: 10.1016/j.ctcp.2020.101086] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 01/04/2020] [Accepted: 01/04/2020] [Indexed: 02/08/2023]
|
|
33
|
Chen P, Zhou G, Lin J, Li L, Zeng Z, Chen M, Zhang S. Serum Biomarkers for Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:123. [PMID: 32391365 PMCID: PMC7188783 DOI: 10.3389/fmed.2020.00123] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
Collapse
Affiliation(s)
- Peng Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Gaoshi Zhou
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingxia Lin
- Division of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
34
|
Domislović V, Vranešić Bender D, Barišić A, Brinar M, Ljubas Kelečić D, Rotim C, Novosel M, Matašin M, Krznarić Ž. HIGH PREVALENCE OF UNTREATED AND UNDERTREATED VITAMIN D DEFICIENCY AND INSUFFICIENCY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Acta Clin Croat 2020; 59:109-118. [PMID: 32724281 PMCID: PMC7382878 DOI: 10.20471/acc.2020.59.01.13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Inflammatory bowel disease (IBD) patients with vitamin D deficiency show an increased risk of hospital admission, surgery, and loss of response to biologic therapy while high vitamin D levels are identified as a protective factor. Our goal was to investigate the prevalence of untreated and undertreated vitamin D deficiency and factors associated with vitamin D deficiency. In this cross-sectional study, we measured serum vitamin D in a random sample of Caucasian IBD patients. Vitamin D deficiency was defined as <50 nmol/L and insufficiency as 50-75 nmol/L. Supplementation was defined as taking 800-2000 IU vitamin D daily. Untreated patients were defined as not taking supplementation and undertreated group as receiving supplementation but showing vitamin D deficiency or insufficiency despite treatment. Our study included 185 IBD patients, i.e. 126 (68.1%) with Crohn’s disease (CD) and 59 (31.9%) with ulcerative colitis (UC). Overall, 108 (58.4%) patients had vitamin D deficiency and 60 (32.4%) patients vitamin D insufficiency. There were 16 (14.8%) and 11 (18.3%) treated patients in vitamin D deficiency and vitamin D insufficiency group, respectively. The rate of untreated patients was 81.7% (n=49) in vitamin D deficiency group and 85.2% (n=92) in vitamin D insufficiency group. Tumor necrosis factor alpha inhibitors were associated with higher serum vitamin D levels in CD and UC, and ileal involvement, ileal and ileocolonic resection with lower levels. In conclusion, not only is vitamin D deficiency common in IBD patients but the proportion of untreated and undertreated patients is considerably high. We suggest regular monitoring of vitamin D levels in IBD patients regardless of receiving vitamin D supplementation therapy.
Collapse
Affiliation(s)
- Viktor Domislović
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Darija Vranešić Bender
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Ana Barišić
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Marko Brinar
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Dina Ljubas Kelečić
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Cecilija Rotim
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Martin Novosel
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Marija Matašin
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Željko Krznarić
- 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Zagreb University Hospital Centre, Zagreb, Croatia; 2Unit of Clinical Nutrition, Zagreb University Hospital Centre, Zagreb, Croatia; 3Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia; 4School of Medicine, University of Zagreb, Zagreb, Croatia; 5Andrija Štampar Teaching Institute of Public Health, Zagreb, Croatia
| |
Collapse
|
|
35
|
Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1509] [Impact Index Per Article: 251.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
Collapse
Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | | |
Collapse
|
|
36
|
Gubatan J, Chou ND, Nielsen OH, Moss AC. Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease. Aliment Pharmacol Ther 2019; 50:1146-1158. [PMID: 31647134 DOI: 10.1111/apt.15506] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 07/29/2019] [Accepted: 08/28/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting. AIM To perform a systematic review and meta-analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD. METHODS We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model. RESULTS Twenty-seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32-1.77, I2 = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06-1.47, I2 = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06-1.60, I2 = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03-1.47, I2 = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36-2.03, I2 = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03-1.85, I2 = 0%), clinical relapse (OR 1.35, 95% CI 1.14-1.59, I2 = 0%), and low QOL scores (OR 1.25, 95% CI 1.04-1.50, I2 = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03-2.09, I2 = 0%) and clinical relapse (OR 1.20, 95% 1.01-1.43, I2 = 0%). CONCLUSIONS Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.
Collapse
Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Naomi D Chou
- Division of Gastroenterology and Hepatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Alan C Moss
- Division of Gastroenterology and Hepatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| |
Collapse
|
|
37
|
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
Collapse
|
|
38
|
Yoon JY. Nutritional approach as therapeutic manipulation in inflammatory bowel disease. Intest Res 2019; 17:463-475. [PMID: 31665832 PMCID: PMC6821940 DOI: 10.5217/ir.2019.00078] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is observed more frequently in patients with inflammatory bowel disease (IBD) than in the general population and associated with adverse clinical outcomes. This study aimed to review the current knowledge regarding the efficacy of dietary and nutritional intervention in IBD patients. Exclusive enteral nutrition might be inferior to corticosteroid treatment in adults with active Crohn’s disease (CD) but might even be superior considering the adverse effects of corticosteroid treatment in children. Total parenteral nutrition has no advantage over enteral nutrition, which is considered a more physiologic modality in organ function. Current guidelines do not yet recommend ω3-polyunsaturated fatty acid supplementation for the prevention and maintenance of remission in IBD patients. Dietary fiber supplementation could be effective in the relief of symptoms and maintenance of remission in ulcerative colitis (UC). Although vitamin D may be favorable to clinical course of IBD and bone density. Probiotic supplementation has proven to be effective in preventing and treating pouchitis for UC but is less effective in treating CD. Nutritional interventions not only correct nutritional deficiencies but also improve symptoms and clinical courses of the disease. Hence, nutritional approaches need to be developed to significantly evaluate the effectiveness of dietary interventions used to treat IBD.
Collapse
Affiliation(s)
- Jin Young Yoon
- Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| |
Collapse
|
|
39
|
Nielsen OH, Hansen TI, Gubatan JM, Jensen KB, Rejnmark L. Managing vitamin D deficiency in inflammatory bowel disease. Frontline Gastroenterol 2019; 10:394-400. [PMID: 31656565 PMCID: PMC6788352 DOI: 10.1136/flgastro-2018-101055] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 12/04/2018] [Accepted: 12/07/2018] [Indexed: 02/04/2023] Open
Abstract
Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is generally cumbersome for patients and is a massive health-economic burden. In recent years, the immunomodulating effects of vitamin D have gained a huge interest in its possible pathogenic influence on the pathophysiology of IBD. Vitamin D deficiency is frequent among patients with IBD. Several clinical studies have pointed to a critical role for vitamin D in ameliorating disease outcomes. Although causation versus correlation unfortunately remains an overwhelming issue in the illusive chicken versus egg debate regarding vitamin D and IBD, here we summarise the latest knowledge of the immunological effects of vitamin D in IBD and recommend from available evidence that physicians regularly monitor serum 25(OH)D levels in patients with IBD. Moreover, we propose an algorithm for optimising vitamin D status in patients with IBD in clinical practice. Awaiting well-powered controlled clinical trials, we consider vitamin D supplementation to be an affordable and widely accessible therapeutic strategy to ameliorate IBD clinical outcomes.
Collapse
Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
| | - Thomas Irgens Hansen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
| | - John Mark Gubatan
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Kim Bak Jensen
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark,Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Stem Cell Research, University of Copenhagen, Copenhagen, Denmark
| | - Lars Rejnmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
40
|
Szilagyi A. Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms. Clin J Gastroenterol 2019; 13:139-152. [PMID: 31452062 PMCID: PMC7101293 DOI: 10.1007/s12328-019-01037-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 08/15/2019] [Indexed: 12/17/2022]
Abstract
The inflammatory bowel diseases, Crohn's and ulcerative colitis have increased in incidence and prevalence from the mid-eighteen to the late nineteen centuries. From then to the current twenty-first century there has been a more rapid expansion of these disease to areas previously experiencing low rates. This latter expansion coincides with the current obesity pandemic which also began toward the end of the last century. Although the two diseases have radically different frequencies, there are interesting links between them. Four areas link the diseases. On an epidemiological level, IBD tends to follow a north-south gradient raising the importance of vitamin D in protection. Obesity has very weak relationship with latitude, but both diseases follow adult lactase distributions colliding in this plane. Is it possible that obesity (a low vitamin D condition with questionable response to supplements) reduces effects in IBD? On a pathogenic level, pro-inflammatory processes mark both IBD and obesity. The similarity raises the question of whether obesity could facilitate the development of IBD. Features of the metabolic syndrome occur in both, with or without obesity in IBD. The fourth interaction between the two diseases is the apparent effect of obesity on the course of IBD. There are suggestions that obesity may reduce the efficacy of biologic agents. Yet there is some suggestion also that obesity may reduce the need for hospitalization and surgery. The apparent co-expansion of both obesity and IBD suggests similar environmental changes may be involved in the promotion of both.
Collapse
Affiliation(s)
- Andrew Szilagyi
- Division of Gastroenterology, Department of Medicine, Jewish General Hospital, McGill University Medical School, 3755 Cote St Catherine Rd, Room E110, Montreal, QC, H3T 1E2, Canada.
| |
Collapse
|
|
41
|
Torres J, Ellul P, Langhorst J, Mikocka-Walus A, Barreiro-de Acosta M, Basnayake C, Ding NJS, Gilardi D, Katsanos K, Moser G, Opheim R, Palmela C, Pellino G, Van der Marel S, Vavricka SR. European Crohn's and Colitis Organisation Topical Review on Complementary Medicine and Psychotherapy in Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:673-685e. [PMID: 30820529 DOI: 10.1093/ecco-jcc/jjz051] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 02/26/2019] [Indexed: 12/11/2022]
Abstract
Patients with inflammatory bowel disease [IBD] increasingly use alternative and complementary therapies, for which appropriate evidence is often lacking. It is estimated that up to half of all patients with IBD use various forms of complementary and alternative medicine during some point in their disease course. Considering the frequent use of such therapies, it is crucial that physicians and patients are informed about their efficacy and safety in order to provide guidance and evidence-based advice. Additionally, increasing evidence suggests that some psychotherapies and mind-body interventions may be beneficial in the management of IBD, but their best use remains a matter of research. Herein, we provide a comprehensive review of some of the most commonly used complementary, alternative and psychotherapy interventions in IBD.
Collapse
Affiliation(s)
- Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - Jost Langhorst
- Department of Internal Medicine and Integrative Gastroenterology, Kliniken Essen-Mitte and Chair for Integrative Medicine and Translational Gastroenterology, Klinikum Bamberg, University Duisburg-Essen, Germany
| | | | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), Santiago De Compostela, Spain
| | - Chamara Basnayake
- Department of Gastroenterology, St. Vincent's Hospital Melbourne, Fitzroy, Melbourne, Australia
| | - Nik John Sheng Ding
- Department of Gastroenterology, St. Vincent's Hospital Melbourne, Fitzroy, Melbourne, Australia
| | - Daniela Gilardi
- IBD Centre, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan, Italy
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Gabriele Moser
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Randi Opheim
- Department of Gastroenterology, Oslo University Hospital, and Department of Nursing Science, Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Carolina Palmela
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Sander Van der Marel
- Department of Gastroenterology and Internal Medicine, Haaglanden Medisch Centrum, The Hague, The Netherlands
| | | |
Collapse
|
|
42
|
Fletcher J, Cooper SC, Ghosh S, Hewison M. The Role of Vitamin D in Inflammatory Bowel Disease: Mechanism to Management. Nutrients 2019; 11:E1019. [PMID: 31067701 PMCID: PMC6566188 DOI: 10.3390/nu11051019] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 04/26/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
Vitamin D has been linked to human health benefits that extend far beyond its established actions on calcium homeostasis and bone metabolism. One of the most well studied facets of extra-skeletal vitamin D is its activity as an immuno-modulator, in particular its potent anti-inflammatory effects. As a consequence, vitamin D deficiency has been associated with inflammatory diseases including inflammatory bowel disease (IBD). Low serum levels of the major circulating form of vitamin D, 25-hydroxyvitamin D (25-OH-D) are significantly more prevalent in patients with IBD, particularly in the winter and spring months when UV-induced synthesis of vitamin D is lower. Dietary malabsorption of vitamin D may also contribute to low serum 25(OH)D in IBD. The benefits of supplementation with vitamin D for IBD patients are still unclear, and improved vitamin D status may help to prevent the onset of IBD as well as ameliorating disease severity. Beneficial effects of vitamin D in IBD are supported by pre-clinical studies, notably with mouse models, where the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses. The current narrative review aims to summarise the different strands of data linking vitamin D and IBD, whilst also outlining the possible beneficial effects of vitamin D supplementation in managing IBD in humans.
Collapse
Affiliation(s)
- Jane Fletcher
- Nutrition Nurses, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TH 1, UK.
| | - Sheldon C Cooper
- Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB 2, UK.
| | - Subrata Ghosh
- NIHR Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TH, UK.
- Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TH, UK.
| | - Martin Hewison
- Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham B15 2TT, UK.
| |
Collapse
|
|
43
|
Burrelli Scotti G, Afferri MT, De Carolis A, Vaiarello V, Fassino V, Ferrone F, Minisola S, Nieddu L, Vernia P. Factors affecting vitamin D deficiency in active inflammatory bowel diseases. Dig Liver Dis 2019; 51:657-662. [PMID: 30587439 DOI: 10.1016/j.dld.2018.11.036] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 10/04/2018] [Accepted: 11/29/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity. AIM This study evaluated vitamin D (VitD) status in an Italian cohort of IBD patients, not taking VitD supplementation. We investigated risk factors for VitD deficiency and its correlation with disease activity. METHODS VitD levels were measured in 300 consecutive outpatients (42% with Crohn's Disease (CD) and 58% with ulcerative colitis (UC), 56% male) from a tertiary referral center. Data from the IBD cohort were compared with those of 234 healthy controls, matched by sex, age, and the month in which VitD levels were measured. RESULTS The mean VitD level in IBD patients was significantly lower than in controls (18.9 ng/ml vs. 25 ng/ml, p < 0.001) when accounting for gender, age, and season. VitD deficiency was present in 62% of IBD patients. Risk factors for deficiency were: age <40 and ≥60 years, winter, previous surgery, C-reactive protein (CRP) ≥0.5 mg/dl, and erythrocyte sedimentation rate ≥20 mm/h. In multivariate analysis, VitD levels were negatively influenced by disease location and CRP in UC. CONCLUSIONS Although VitD deficiency was more prevalent than expected in healthy controls living in a Mediterranean country not at high risk of hypovitaminosis D, it was more common and severe in IBD patients. This study also found an association between VitD status and disease activity.
Collapse
Affiliation(s)
- Giorgia Burrelli Scotti
- Department of Internal Medicine and Medical Specialties, Gastroenterology, Sapienza University of Rome, Rome, Italy.
| | - Maria Teresa Afferri
- Department of Internal Medicine and Medical Specialties, Gastroenterology, Sapienza University of Rome, Rome, Italy
| | - Aurora De Carolis
- Department of Internal Medicine and Medical Specialties, Gastroenterology, Sapienza University of Rome, Rome, Italy
| | - Valentina Vaiarello
- Department of Internal Medicine and Medical Specialties, Gastroenterology, Sapienza University of Rome, Rome, Italy
| | - Valeria Fassino
- Department of Internal Medicine and Medical Specialties, Internal Medicine A and Metabolic Bone Diseases, Sapienza University of Rome, Rome, Italy
| | - Federica Ferrone
- Department of Internal Medicine and Medical Specialties, Internal Medicine A and Metabolic Bone Diseases, Sapienza University of Rome, Rome, Italy
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Specialties, Internal Medicine A and Metabolic Bone Diseases, Sapienza University of Rome, Rome, Italy
| | - Luciano Nieddu
- Faculty of Economics, UNINT University of International Studies, Rome, Italy
| | - Piero Vernia
- Department of Internal Medicine and Medical Specialties, Gastroenterology, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
44
|
Barbalho SM, Goulart RDA, Araújo AC, Guiguer ÉL, Bechara MD. Irritable bowel syndrome: a review of the general aspects and the potential role of vitamin D. Expert Rev Gastroenterol Hepatol 2019; 13:345-359. [PMID: 30791775 DOI: 10.1080/17474124.2019.1570137] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Irritable Bowel Syndrome (IBS) is a bowel disorder leading to symptoms such as abdominal pain, modifications in the motility and bowel habits, distention, bloating, and gas. Vitamin D (VD) may interfere in a plethora of cellular mechanisms, and act directly or indirectly in the regulation of the microbiome, the release of anti-microbial peptides, modulation of the immune system and inflammation processes; which in turn, may positively interfere with the altered gut function. The main purpose of this review was to survey studies involving the impacts of VD on IBS. Area covered: Eligible studies including the term VD and IBS were searched in the MEDLINE-PubMed and EMBASE (2009-2018). VD may act direct or indirectly in the regulation of the gut microbiome, immune response, and psychosocial factors that may be included in the list of IBS triggering factors. Expert opinion: Once VD plays an essential role in many processes associated with IBS, its deficiency may be associated with IBS, and the supplementation could help in the therapeutic approach for this condition. For these reasons, the understanding of the association of VD in IBS is indispensable for the development of new strategies that could improve the quality of life of the patient.
Collapse
Affiliation(s)
- Sandra Maria Barbalho
- a Medical School of Marília , UNIMAR , São Paulo , Brazil.,b Department of Nutrition , Food Technology School , São Paulo , Brazil
| | | | | | - Élen Landgraf Guiguer
- a Medical School of Marília , UNIMAR , São Paulo , Brazil.,b Department of Nutrition , Food Technology School , São Paulo , Brazil
| | | |
Collapse
|
|
45
|
Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease. Mediators Inflamm 2019; 2019:2624941. [PMID: 30804707 PMCID: PMC6360586 DOI: 10.1155/2019/2624941] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 12/01/2018] [Accepted: 12/23/2018] [Indexed: 12/12/2022] Open
Abstract
Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPARγ) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPARγ, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORγt), in the pathogenesis of IBD and management strategies based on targeting these receptors.
Collapse
|
|
46
|
Olmedo Martín RV, González Molero I, Olveira Fuster G, Amo Trillo V, Jiménez Pérez M. Vitamin D deficiency in outpatients with inflammatory bowel disease: prevalence and association with clinical-biological activity. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 111:46-54. [PMID: 30284908 DOI: 10.17235/reed.2018.5714/2018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
INTRODUCTION there are few data on the prevalence of vitamin D deficiency in patients with inflammatory bowel disease (IBD) in Spain. A deficiency could be associated with a worse course of the disease. AIM to determine the prevalence of 25-hydroxyvitamin D (25OHD) deficiency in a cohort of outpatients with IBD and assess its association with clinical and biological activity, quality of life and psychological symptoms. METHODS a cross-sectional, single-center observational study was performed. The study variables were obtained via clinical interviews, medical chart review and validated questionnaires (Hospital Anxiety and Depression Scale and Short Quality of Life in Inflammatory Bowel Disease Questionnaire). 25OHD was measured in the same laboratory by an electro-chemiluminescence immunoassay. RESULTS the study included 224 patients. The prevalence of vitamin D deficiency in Crohn's disease and ulcerative colitis was 33.3% and 20.3%, respectively. In Crohn's disease, vitamin D deficiency was associated with a higher clinical activity (p < 0.001) and a higher concentration of fecal calprotectin (p = 0.01). In ulcerative colitis, it was associated with clinical activity (p < 0.001), the use of steroids during the last six months (p = 0.001) and hospital admission during the previous year (p = 0.003). A sub-analysis of 149 patients failed to detect an association between vitamin D and quality of life or the scores of the Hospital Anxiety and Depression Scale. CONCLUSIONS vitamin D deficiency is common in patients with inflammatory bowel disease. An association was found between vitamin D concentration and clinical activity indexes, as well as fecal calprotectin levels in Crohn's disease.
Collapse
Affiliation(s)
| | | | | | - Víctor Amo Trillo
- UGC Aparato Digestivo, Hospital Regional Universitario de Málaga, España
| | | |
Collapse
|
|
47
|
Olmedo-Martín RV, González-Molero I, Olveira G, Amo-Trillo V, Jiménez-Pérez M. Vitamin D in Inflammatory Bowel Disease: Biological, Clinical and Therapeutic Aspects. Curr Drug Metab 2019; 20:390-398. [PMID: 31109269 DOI: 10.2174/1389200220666190520112003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 04/13/2019] [Accepted: 04/25/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Vitamin D has an immunoregulatory action in Inflammatory Bowel Disease (IBD) as well as other immune-mediated disorders. Its influence on intestinal permeability, innate and adaptive immunity, and the composition and diversity of the microbiota contribute to the maintenance of intestinal homeostasis. Patients with IBD have a greater prevalence of vitamin D deficiency than the general population, and a possible association between this deficit and a worse course of the disease. However, intervention studies in patients with IBD have proved inconclusive. OBJECTIVE To review all the evidence concerning the role of vitamin D as an important factor in the pathophysiology of IBD, review the associations found between its deficiency and the prognosis of the disease, and draw conclusions for the practical application from the main intervention studies undertaken. METHODS Structured search and review of basic, epidemiological, clinical and intervention studies evaluating the influence of vitamin D in IBD, following the basic principles of scientific data. RESULTS Vitamin D deficiency is associated with disease activity, quality of life, the consumption of social and healthcare resources, and the durability of anti-TNFα biological treatment. Determination of new metabolites of vitamin D, measurement of its absorption capacity and questionnaires about sun exposure could help identify groups of IBD patients with a special risk of vitamin D deficiency. CONCLUSION Well-designed intervention studies are needed in IBD, with probably higher objective plasma doses of vitamin D to establish its efficacy as a therapeutic agent with immunomodulatory properties. Meanwhile, vitamin D deficiency should be screened for and corrected in affected patients in order to achieve adequate bone and phosphocalcic metabolism.
Collapse
Affiliation(s)
- Raúl Vicente Olmedo-Martín
- Clinical Management Unit of Digestive Diseases, Regional University Hospital of Malaga, Malaga, Spain; Faculty of Medicine, University of Malaga, Malaga, Spain
- Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain
| | - Inmaculada González-Molero
- Clinical Management Unit of Endocrinology and Nutrition, Regional University Hospital of Malaga; Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain; Faculty of Medicine, University of Malaga; CIBERDEM, Malaga, Spain
| | - Gabriel Olveira
- Clinical Management Unit of Endocrinology and Nutrition, Regional University Hospital of Malaga; Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain; Faculty of Medicine, University of Malaga; CIBERDEM, Malaga, Spain
| | - Víctor Amo-Trillo
- Clinical Management Unit of Digestive Diseases, Regional University Hospital of Malaga, Malaga, Spain; Faculty of Medicine, University of Malaga, Malaga, Spain
- Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain
| | - Miguel Jiménez-Pérez
- Clinical Management Unit of Digestive Diseases, Regional University Hospital of Malaga, Malaga, Spain; Faculty of Medicine, University of Malaga, Malaga, Spain
- Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain
| |
Collapse
|
|
48
|
Zhou YQ, Xu RY, Wan YP. The role of dietary factors in inflammatory bowel diseases: New perspectives. J Dig Dis 2019; 20:11-17. [PMID: 30444028 DOI: 10.1111/1751-2980.12686] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 09/01/2018] [Accepted: 11/08/2018] [Indexed: 12/11/2022]
Abstract
The current review aimed to elucidate the role of diet in every stage of inflammatory bowel diseases, from aspects of prevention, treatment and rehabilitation. Western diet, characterized by overconsumption of refined sugar and saturated fat and low consumption of dietary fiber, may partly be blamed for its pathogenesis. Some immune-modulated nutrients (fibers, monounsaturated fatty acids, n-3 polyunsaturated fatty acids and vitamin D) exert their potential beneficial effects on gut microbiota and immune function, resulting in clinical remission and/or preventing relapse. However, data is limited to conclude optimal micronutrient levels and therapeutic implications. Further, diet itself is complex; therefore, it is reasonable to evaluate diet as a whole rather than a single type of food. Some specific dietary patterns are generated for the management of inflammatory bowel diseases with controversial results. Only exclusive enteral nutrition has been widely recommended for pediatric patients with non-stricturing active Crohn's disease. Self-monitoring, avoidance of certain types of foods, limited intake of alcohol and smoking, supplementation of minerals and vitamins if deficiency is confirmed, and adherence to the diet enriched in vegetables and fruits and low in animal food and un-digested fiber during flares are the most common dietary recommendation. Further clinical trials with a high evidence rank are warranted.
Collapse
Affiliation(s)
- Yi Quan Zhou
- Department of Clinical Nutrition, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ren Ying Xu
- Department of Clinical Nutrition, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Ping Wan
- Department of Clinical Nutrition, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
49
|
Stevens TW, Matheeuwsen M, Lönnkvist MH, Parker CE, Wildenberg ME, Gecse KB, D'Haens GR. Systematic review: predictive biomarkers of therapeutic response in inflammatory bowel disease-personalised medicine in its infancy. Aliment Pharmacol Ther 2018; 48:1213-1231. [PMID: 30378142 DOI: 10.1111/apt.15033] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 07/19/2018] [Accepted: 09/29/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is characterised by substantial heterogeneity in treatment response. With an expanding number of therapeutic agents, identifying optimal treatment at the patient level remains a major challenge. AIM To systematically review the available literature on predictive biomarkers of therapeutic response in IBD. METHODS An electronic literature search was performed on 30 January 2018 using MEDLINE, EMBASE and the Cochrane Library. Retrospective, prospective, uncontrolled and controlled studies reporting on biomarkers predicting therapeutic response in paediatric and adult IBD populations were eligible for inclusion. The methodological quality of the included studies was assessed using the QUIPS tool. Due to anticipated heterogeneity and limited data, a qualitative, rather than quantitative, assessment was planned. RESULTS Of the 10 638 citations identified, 92 articles met the inclusion criteria. Several potential DNA, mRNA and protein markers were evaluated as predictive biomarkers. Most studies focused on predicting response to anti-TNF agents. Substantial between-study heterogeneity was identified with respect to both the biomarkers studied and the definition of response. None of the included studies received a low risk of bias rating for all six domains. Currently, none of the biomarkers is sufficiently predictive for clinical use. CONCLUSIONS The search for predictive biomarkers is still in its infancy and current evidence is limited. Future research efforts should take into account the high patient heterogeneity within prospective trials with objective response assessment. Predictive models will most likely comprise a combination of several molecular markers from integrated omics-levels and clinical characteristics.
Collapse
Affiliation(s)
- Toer W Stevens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Mijntje Matheeuwsen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Maria H Lönnkvist
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Manon E Wildenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Amsterdam, The Netherlands
| | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Geert R D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
50
|
Abstract
BACKGROUND Vitamin D (VitD) deficiency is prevalent in patient with inflammatory bowel disease (IBD). Recent studies have found that VitD can induce and maintain IBD remission through antibiosis, anti-inflammatory, and repair of intestinal mucosal barriers, thus improving the patient's disease activity and quality-of-life. The purpose of this meta-analysis is to evaluate the therapeutic effect and safety of VitD in the treatment of IBD. METHODS Published randomized controlled trials (RCTs) were included from electronic databases (PubMed, Embase, Cochrane library, Web of Science, and so forth). Cochrane handbook was applied to evaluate the methodological quality. The levels of 25(OH)D3, relapse rate, inflammation index, and adverse events were compared between the experimental group and the control group (placebo group). All statistical analyses were directed by Revman 5.3 software and statistical significance was defined as P < .05. RESULTS Eighteen RCTs involved 908 patients were included. Meta-analysis showed that VitD improved the 25(OH)D3 levels more significantly than the control group (ng/mL, weighted mean deviation [WMD] = 7.85, 95% CI (5.52, 10.18), P < .000001), and compared with lower doses, there were significant differences increasing 25(OH)D3 levels (WMD = 11.19, 95% CI [4.73, 17.65], P = .0007) in high-dose VitD treatment while there was no significant difference in the adverse events between 2 groups (WMD = 1.56, 95% CI [0.74, 3.29], P = .24). VitD reduced the relapse rate more significantly than the control group, but there were no significant differences between the low-dose and high-dose vitamin D treatment. The erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hsCRP) of the VitD and the control group showed no statistically significant difference (ESR [mm/h]: WMD = -0.22, 95% CI [-5.73, 5.29], P = .94; hsCRP (mg/dL): WMD = -0.53, 95% CI [-1.68, 0.62], P = .37). CONCLUSIONS The treatment of VitD in patients with IBD can improve the level of 25(OH)D3 and control the relapse rate of the disease, whose clinical curative effect is more accurate. Thus VitD should be recommended for the treatment of IBD, at least as an adjunctive treatment.
Collapse
Affiliation(s)
| | - Ning Chen
- Department of General Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China
| | | | - Jie Zhang
- Department of General Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China
| | | |
Collapse
|