Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer

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Abstract

In observational studies, higher plasma 25-hydroxyvitamin D (25[OH]D) levels have been associated with improved survival in metastatic colorectal cancer (CRC).

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Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier.

Juan Kong, Zhongyi Zhang, Mark W. Musch … (2008)

Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.

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Where is the vitamin D receptor?

Yongji Wang, Jinge Zhu, Hector F DeLuca (2012)

The vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and plays a central role in the biological actions of vitamin D. VDR regulates the expression of numerous genes involved in calcium/phosphate homeostasis, cellular proliferation and differentiation, and immune response, largely in a ligand-dependent manner. To understand the global function of the vitamin D system in physiopathological processes, great effort has been devoted to the detection of VDR in various tissues and cells, many of which have been identified as vitamin D targets. This review focuses on the tissue- and cell type-specific distribution of VDR throughout the body. Copyright © 2012. Published by Elsevier Inc.

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Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994.

Shanna Nesby-O'Dell, Kelley Scanlon, Mary Cogswell … (2002)

Recent reports of rickets among African American children drew attention to the vitamin D status of these infants and their mothers. African American women are at higher risk of vitamin D deficiency than are white women, but few studies have examined determinants of hypovitaminosis D in this population. We examined the prevalence and determinants of hypovitaminosis D among African American and white women of reproductive age. We examined 1546 African American women and 1426 white women aged 15-49 y who were not pregnant and who participated in the third National Health and Nutrition Examination Survey (1988-1994). Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D concentration < or =37.5 nmol/L. Multiple logistic regression was used to examine the independent association of dietary, demographic, and behavioral determinants of hypovitaminosis D. The prevalence of hypovitaminosis D was 42.4 +/- 3.1% ( +/- SE) among African Americans and 4.2 +/- 0.7% among whites. Among African Americans, hypovitaminosis D was independently associated with consumption of milk or breakfast cereal <3 times/wk, no use of vitamin D supplements, season, urban residence, low body mass index, and no use of oral contraceptives. Even among 243 African Americans who consumed the adequate intake of vitamin D from supplements (200 IU/d), 28.2 +/- 2.7% had hypovitaminosis D. The high prevalence of hypovitaminosis D among African American women warrants further examination of vitamin D recommendations for these women. The determinants of hypovitaminosis D among women should be considered when these women are advised on dietary intake and supplement use.

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Author and article information

Journal

Title: JAMA

Abbreviated Title: JAMA

Publisher: American Medical Association (AMA)

ISSN (Print): 0098-7484

Publication date Created: April 09 2019

Publication date (Print): April 09 2019

Volume: 321

Issue: 14

Page: 1370

Affiliations

[1 ]Dana-Farber Cancer Institute, Boston, Massachusetts

[2 ]Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois

[3 ]Beth Israel Deaconess Medical Center, Boston, Massachusetts

[4 ]Massachusetts General Hospital, Boston

[5 ]St Luke’s Mountain States Tumor Institute, Boise, Idaho

[6 ]Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee

[7 ]Dana-Farber at Milford Regional Medical Center, Milford, Massachusetts

[8 ]New Hampshire Oncology Hematology, Hookset

[9 ]Dana-Farber at South Shore Hospital, South Weymouth, Massachusetts

[10 ]New England Cancer Specialists, Scarborough, Maine

[11 ]Newton-Wellesley Hospital, Newton, Massachusetts

[12 ]Medical University of South Carolina, Charleston

[13 ]Yale Cancer Center, New Haven, Connecticut

Article

DOI: 10.1001/jama.2019.2402

PMC ID: 6459117

PubMed ID: 30964527

SO-VID: 75c53d0d-9f87-4abf-a087-1360dd090281

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Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer : The SUNSHINE Randomized Clinical Trial

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Most cited references 21

Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier.

Where is the vitamin D receptor?

Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994.

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