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Int. J. Environ. Res. Public Health 2019, 16(2), 189;

Controversies Surrounding Vitamin D: Focus on Supplementation and Cancer

Department of Internal Medicine and Medical Disciplines, “Sapienza” Rome University, 00161 Rome, Italy
Author to whom correspondence should be addressed.
Received: 18 October 2018 / Revised: 3 January 2019 / Accepted: 4 January 2019 / Published: 11 January 2019
(This article belongs to the Special Issue Vitamin D and Public Health)
PDF [290 KB, uploaded 11 January 2019]


There has recently been a huge number of publications concerning various aspects of vitamin D, from the physiological to therapeutic fields. However, as a consequence of this very fast-growing scientific area, some issues still remain surrounded by uncertainties, without a final agreement having been reached. Examples include the definitions of vitamin D sufficiency and insufficiency, (i.e., 20 vs. 30 ng/mL), the relationship between 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone, (i.e., linear vs. no linear), the referent to consider, (i.e., total vs. free determination), the utility of screening versus universal supplementation, and so on. In this review, the issues related to vitamin D supplementation in subjects with documented hypovitaminosis, and the role of vitamin D in cancer will be concisely considered. Daily, weekly, or monthly administration of cholecalciferol generally leads to essentially similar results in terms of an increase in 25(OH)D serum levels. However, we should also consider possible differences related to a number of variables, (i.e., efficiency of intestinal absorption, binding to vitamin D binding protein, and so on). Thus, adherence to therapy may be more important than the dose regimen chosen in order to allow long-term compliance in a sometimes very old population already swamped by many drugs. It is difficult to draw firm conclusions at present regarding the relationship between cancer and vitamin D. In vitro and preclinical studies seem to have been more convincing than clinical investigations. Positive results in human studies have been mainly derived from post-hoc analyses, secondary end-points or meta-analyses, with the last showing not a decrease in cancer incidence but rather in mortality. We must therefore proceed with a word of caution. Until it has been clearly demonstrated that there is a causal relationship, these positive “non-primary, end-point results” should be considered as a background for generating new hypotheses for future investigations. View Full-Text
Keywords: vitamin D; supplementation; cancer incidence; cancer mortality vitamin D; supplementation; cancer incidence; cancer mortality
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Minisola, S.; Ferrone, F.; Danese, V.; Cecchetti, V.; Pepe, J.; Cipriani, C.; Colangelo, L. Controversies Surrounding Vitamin D: Focus on Supplementation and Cancer. Int. J. Environ. Res. Public Health 2019, 16, 189.

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