Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications
<p>Vitamin D is synthesized in the skin in response to ultraviolet light or provided by the diet. It is first converted to 25-hydroxyvitamin D3 by hydroxylation occurring in the liver and then further converted into its active metabolite, 1,25-dihydroxyvitamin D3, in the kidney. Ca = calcium; P = phosphate; CYP2R1 = Cytochrome P450 Family 2 Subfamily R Member 1; CYP27B1= Cytochrome P450 Family 27 Subfamily B Member 1; 25(OH) vitamin D = 25-hydroxyvitamin D; 1,25 (OH) Vitamin D = 1,25-dihydroxyvitamin D.</p> "> Figure 2
<p>Vitamin D signaling affects the expression of several genes, regulates the immune system, and modulates the inflammatory response. It helps maintain epithelial integrity, through the regulation of tight junctions and adherens junctions’ components, as well as the release of antimicrobial peptides like the defensins. A role in the integrity of the mucus layer, as well as the composition of the gut microbiome, has been advocated. Th = T helper cells; NKT = natural killer T cells; Tregs = regulatory T cells; sIgA = secretory immunoglobulin A; VDR = vitamin D receptor.</p> "> Figure 3
<p>Vitamin D exerts its biological effects on the intestine in IBD maintaining mucosal barrier integrity, modulating the immune system and the composition of the gut microbiota. Emerging evidence suggests that vitamin D deficiency may unfavorably affect response to biological therapy, being associated with an increased risk of both primary non-response and secondary loss of response to the drugs. Furthermore, vitamin D deficiency may worsen corticosteroid-related osteopenia/osteoporosis and increase the risk of immunomodulator-related infections.</p> ">
Abstract
:1. Introduction
2. Methods
3. Vitamin D deficiency
4. Vitamin D and Inflammation
4.1. Intestinal Epithelial Cells and Vitamin D
4.2. Immune System and Vitamin D
4.3. Gut Microbiota and Vitamin D
5. Vitamin D Supplementation and Disease Course
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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STUDY | Country | Patients Included | Disease | Intervention Group | Vitamin D Doses in the Intervention Group | Control Group | Control Group (Placebo or VitD) | Difference in the Mean Daily Dose * | Follow-Up | Outcomes (Disease Activity Evaluation) | Outcomes (Adverse Events; Vitamin D Levels) | Relapse Intervention vs. Control |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Bafutto 2017 [101] | Brazil | 30 moderate to severe and VitD levels < 30 ng/mL | CD | 20 | 50,000 IU/die 10.000 IU/die | 10 | 2000 UI/die | 48,000 IU 8000 IU | 8 weeks | ↓CRP; ↓FC; ↑IBDQ | ↑VitD | n.a. |
Ahamed 2019 [102] | India | 60 with UCDAI >3 and VitD levels < 40 ng/mL | UC | 30 | 60,000 IU/d for 8 days | 30 | placebo | 17,142 IU | 4 weeks | ↓UCDAI; ↓CRP; ↓FC | ↑VitD; =AE | n.a. |
Narula 2017 [103] | Canada | 34 in remission | CD | 18 | 10,000 IU/die | 16 | 1000 IU/die | 9000 IU | 12 months | =CRP; ↓relapse ** | ↑VitD; =AE | 0 vs. 3 ** |
Dadaei 2015 [104] | Ireland | 108 and VitD levels < 30 ng/mL | IBD | 53 (10 CD; 43UC) | 50,000/week | 55 (6 CD; 49UC) | placebo | 7142 UI | 12 weeks | none | ↑VitD | n.a. |
de Bruyn 2021 ** [105] | Netherlands and Belgium | 143 with ileocolonic resection | CD | 72 | 25,000/week | 71 | placebo | 3571 UI | 26 weeks | =Rutgerts score; =IBDQ; =CRP; =FC | ↑VitD; =AE | n.a. |
Sharifi 2016 [106] | Iran | 86 in remission | UC | 46 | 300,000 IU/90 die | 40 | placebo | 3300 IU | 3 months | ↓ESR; ↓CRP | ↑VitD | n.a. |
Mathur 2017 [107] | U.S.A. | 18 and VitD < 30 ng/mL | UC | 10 | 4000 IU/die | 8 | 2000 IU/die | 2000 IU | 3 months | =CRP; =pMayo; ↑SIBDQ | ↑VitD; =AE | n.a. |
Raftery 2015 [54] | Ireland | 27 in remission | CD | 13 | 2000 IU/die | 14 | placebo | 2000 IU | 3 months | =CDAI; =CRP; =FC; =QoL | ↑VitD | 0 vs. 0 |
Tan 2018 [108] | China | 91 with VitD levels < 20 ng/mL | IBD | 23 CD 24 UC | 150,000 IU/90 die | 19 CD 25 UC | placebo | 1666 IU | 12 months | =CRP; =ESR; =CDAI; =pMayo | ↑VitD; =AE | n.a. |
Bendix 2015 ‡ [109] | Denmark | 18 | CD | 9 largest VitD increase ‡ | 1200 IU/die | 9 seasonally matched ‡ | placebo | 1200 IU | 26 weeks | =CRP; =HBI; =CDAI | ↑VitD | 0 vs. 1 |
Bendix-Struve 2010‡ [110] | Denmark | 20 | CD | 10 largest VitD increase ‡ | 1200 IU/die | 10 seasonally matched | placebo | 1200 IU | 12 months | =CDAI | ↑VitD | 0 vs. 1 |
Jorgensen 2010 [92] | Denmark | 94 in remission | CD | 46 | 1200 IU/d | 48 | placebo | 1200 IU | 12 months | ↓relapse rate † | ↑VitD; ↓AE | 6 vs. 14 |
Bartels 2014 [111] | Denmark | 19 in remission | CD | 10 with increased in vitD levels | 1200 IU/die | 9 seasonally matched ‡ | placebo | 1200 IU | 26 weeks | =CRP =CDAI | n.a. | 0 vs. 1 |
Karimi 2019 [112] | Iran | 46 II mild to moderate disease | UC | 24 | 2000 IU/die | 22 | 1000 IU/die | 1000 IU | 12 weeks | ↓CDAI; ↓IBDQ | ↑VitD; =AE | n.a. |
Arihiro 2018 [113] | Japan | 223 | IBD | 108 | 500/die | 115 | placebo | 500 IU | 2 months | ↑UCDAI; ↓Lichtiger score; | ↑VitD; =AE | n.a. |
Different populations –Age –Ethnicity –Country –Sun exposure –Comorbidities |
Small number of patients |
Partial data according to –Disease subtype –Disease progression –Medical treatment –IBD-related surgery –Dietary pattern |
Limited data on changes in disease activity |
Different vitamin D dosage regimens and treatment duration |
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Vernia, F.; Valvano, M.; Longo, S.; Cesaro, N.; Viscido, A.; Latella, G. Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications. Nutrients 2022, 14, 269. https://doi.org/10.3390/nu14020269
Vernia F, Valvano M, Longo S, Cesaro N, Viscido A, Latella G. Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications. Nutrients. 2022; 14(2):269. https://doi.org/10.3390/nu14020269
Chicago/Turabian StyleVernia, Filippo, Marco Valvano, Salvatore Longo, Nicola Cesaro, Angelo Viscido, and Giovanni Latella. 2022. "Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications" Nutrients 14, no. 2: 269. https://doi.org/10.3390/nu14020269