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Review
. 2022 Mar 30;14(7):1448.
doi: 10.3390/nu14071448.

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Alberto Muñoz  1 , William B Grant  2
Affiliations
Review

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Alberto Muñoz et al. Nutrients. .

Abstract

This is a narrative review of the evidence supporting vitamin D's anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)2D3 and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.

Keywords: 1,25-(OH)2D3; 25-hydroxyvitamin D; UVB; antitumor action; breast cancer; case-control studies; cohort studies; colorectal cancer; ecological studies; epidemiological studies; randomized controlled trials; vitamin D.

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Conflict of interest statement

W.B.G.’s nonprofit organization, Sunlight, Nutrition and Health Research Center, receives funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR, USA). A.M. has no conflict of interest to declare.

Figures

Figure 1
Figure 1
Plot of odds ratio (OR) for CRC against median years to diagnosis for data for men and women used in McCullough and colleagues [47].
Figure 2
Figure 2
Plot of OR for cancer incidence versus the difference between minimum and maximum 25(OH)D concentration, using data from Table 7, omitting data for all cancer, breast cancer in McDonnell and colleagues [69], and data for prostate cancer.
Figure 3
Figure 3
Time flow-chart of studies on the anticancer mechanisms of vitamin D compounds with some key references that are discussed in the text.
See this image and copyright information in PMC

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