Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs &lt;20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort

McDonnell, Sharon L.; Baggerly, Carole A.; French, Christine; Baggerly, Leo L.; Garland, Cedric F.; Gorham, Edward D.; Hollis, Bruce W.; Trump, Donald L.; Lappe, Joan M.

doi:10.1371/journal.pone.0199265

Cited by 89 publications

(71 citation statements)

References 39 publications

(40 reference statements)

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“…When findings of breast cancer odds ratio versus 25(OH)D concentration from 11 studies from seven countries are plotted over each other, the data points overlap well and show a power-law fit (13,16). The results agree well with those from an observational study using pooled data from two vitamin D clinical trials and one open-label observational study in which serum 25(OH)D concentration was measured every 6 months (21).…”

Section: Prospective Observational Studies Of Cancer Incidence Relatesupporting

confidence: 65%

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer

Grant

2019

Anticancer Res

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This article is a narrative review of recent epidemiological findings regarding ultraviolet-B (UVB) dose or exposure, serum 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D supplementation, and genetic variations in 25(OH)D concentration for incidence, survival, and mortality rates of overall and breast, colorectal, and prostate cancer. According to ecological studies, solar UVB doses are inversely correlated with incidence/mortality rates for about 20 cancer types. Observational studies support a role of higher 25(OH)D concentrations in reducing risk of breast and colorectal cancer incidence and mortality rates but, for prostate cancer, in increasing incidence rates while reducing mortality rates. Mendelian randomization studies offer little support for vitamin D in reducing cancer risk. Their primary limitation is that they only investigate small variations in genetically predicted 25(OH)D concentration near the population mean value. The secondary analyses from the VITAL clinical trial indicated significant reductions from 2000 IU/d of vitamin D 3 supplementation in all-cancer incidence and mortality rates for selected subgroups. Thus, Hill's criteria for causality in a biological system are now largely satisfied for supporting the claim that vitamin D reduces the risk of cancer incidence and death.

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Section: Prospective Observational Studies Of Cancer Incidence Relatesupporting

confidence: 65%

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer

Grant

2019

Anticancer Res

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“…However, there is a breakdown of vitamin D in tumor cells, causing resistance to the antitumor effects of vitamin D [22]. We found the majority of participant BC women in this study to have vitamin D levels as low as <32 ng/ml, prior to initiating CAF chemotherapy, findings which are similar to recent pooled analysis of three trials showing that BC risk is markedly higher with serum vitamin D concentrations <20 ng/ml [10].…”

Section: Discussionsupporting

confidence: 87%

“…Compared to healthy postmenopausal women who may lose ∼1% of their BMD per year, women with BC lose 2-3 fold more BMD, increasing the risk of hip and vertebral fractures, which are associated with a significant decline in function, quality of life, and higher mortality rates [9]. Recently, there has been considerable interest in the potential effects of serum vitamin D [25-hydroxyvitamin D; 25(OH)D] concentrations in the etiology of BC [10]. Besides the essential role of vitamin D in calcium homeostasis and bone metabolism, vitamin D can induce cell differentiation, inhibit cell growth and regulate apoptosis in normal and malignant cells, including human BC cells [11,12].…”

Section: Introductionmentioning

confidence: 99%

A Longitudinal Study for the Effect of Vitamin D Adjunct to Chemotherapy on Non-Metastatic Breast Cancer Patients after Mastectomy

Mohamed¹,

Helal²,

Awad³

et al. 2019

Breast Cancer Rep

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Background: Women with BC are at increased risk for the development of osteoporosis and skeletal fractures. We investigated the effect of CAF chemotherapy alone and adjunct to vitamin D treatment on biochemical markers of bone formation and on segmental and total bone mineral density (BMD) for non-metastatic breast cancer (NMBC) postmenopausal women who had gone through a mastectomy. Methods: The study population was comprised of 200 NMBC women who were divided into two equal groups; before and after treatment with CAF chemotherapy alone and before and after treatment with CAF+Vitamin D treatment protocols. Other 100 healthy participants served as the Control group. All participant women were subjected to blood biochemical analysis and segmental and total BMD measurements using Dual-energy X-ray Absorptiometry technique. Results: We found that CAF chemotherapy alone had no effect on women's body weight, BMI, tumor marker CA15-3, PTH, ALP and Ca levels as compared to the initial state, while CAF+Vitamin D adjunct treatment caused significant reductions in their levels as compared to the initial state and Healthy Controls. We found also that CAF chemotherapy alone had no effect on plasma levels of P and Vitamin D as compared to initial state yet, CAF+Vitamin D adjunct treatment caused significant elevations in their levels as compared to the initial state and Healthy Controls. Conclusions: Vitamin D may decrease the risk of BC recurrence by decreasing risk factors like body weight and serum levels of CA15-3, PTH, ALP, and Ca, thus increasing segmental and total BMD and decreasing the risk of osteoporosis.

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“…Some data suggest that a higher 25(OH)D level than 50 nmol/L (or 20 ng/mL) may be required for optimal risk reduction for various endpoints [41][42][43][44].…”

Section: Interval Target Level and Dosementioning

confidence: 99%

Vitamin D deficiency 2.0: an update on the current status worldwide

et al. 2020

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Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L or 20 ng/ml) is associated with unfavorable skeletal outcomes, including fractures and bone loss. A 25(OH)D level of >50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.

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Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort

Cited by 89 publications

References 39 publications

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer

Review of Recent Advances in Understanding the Role of Vitamin D in Reducing Cancer Risk: Breast, Colorectal, Prostate, and Overall Cancer

A Longitudinal Study for the Effect of Vitamin D Adjunct to Chemotherapy on Non-Metastatic Breast Cancer Patients after Mastectomy

Vitamin D deficiency 2.0: an update on the current status worldwide

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