Circulating 25-Hydroxy Vitamin D Relative to Vitamin D Receptor Polymorphism after Vitamin D3 Supplementation in Breast Cancer Women: A Randomized,Double-Blind Controlled Clinical Trial

Objective: The influence of vitamin D receptor (VDR) genetic variation on serum 25-hydroxyvitamin D levels [25(OH)D] after vitamin D3 supplementation remains unclear. We aimed to investigate changes of 25(OH)D in a randomized, double-blind, placebo-controlled clinical trial, according to VDR genotype, after provision of vitamin D3 to breast cancer cases for a 2-month period. Methods: Participants were assigned to two treatment arms: placebo (n = 28) and vitamin D3 supplementation (n =28). The supplementation group received 50,000 IU of vitamin D every week for 2 months. Blood samples were collected at baseline and after intervention to measure serum 25(OH) D3. Genotypes were assessed for FokI, BsmI, ApaI, and TaqI polymorphisms. Results: After eight weeks supplementation, the rvention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004). Subjects were then classified into twelve subgroups according to different VDR genotypes. Subjects with ff/Ff, TT/Tt, and Bb genotypes had significantly higher increases in serum 25(OH)D compared to those with FF, tt, and BB/bb genotypes post-intervention. Serum vitamin D3 levels with the AA genotype were lower than with aa/ Aa. No differences were found among other subgroups. Conclusion: Vitamin D3 supplementation increases serum 25(OH)D in women with breast cancer. Serum vitamin D3 in TT/Tt, ff/Ff, and Bb carriers was more responsive to vitamin D supplementation than in those with FF/ff and tt genotypes. Other subgroups might gain less from vitamin D3 supplementation.     

Association between Circulating Vitamin D,the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form 1,25(OH)2D to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by pairedt-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancerpatients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT (8.91±4.31) and Tt (9.15±5.25) genotypescompared to control ((21.3±8.31) and (19.3±7.68); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.     

Feasibility of a randomized controlled trial of vitamin D vs. placebo in women with recently diagnosed breast cancer

Low serum vitamin D levels have been associated with poor outcomes in women diagnosed with early breast cancer. However, no randomized controlled trials (RCTs) have been performed to determine whether vitamin D supplementation might be an effective intervention in this population. We prospectively evaluated vitamin D adequacy and supplementation rates in a contemporary cross-sectional sample of breast cancer patients from 2 large urban centers and examined the feasibility of an RCT of vitamin D supplementation. Women with recently diagnosed early breast cancer were prospectively identified and recruited in Toronto and Los Angeles between March 2009 and January 2010. Anthropometric measurements, dietary, lifestyle, and medication histories were obtained by means of structured questionnaires and interviews. Tumor and treatment characteristics were abstracted from clinical records and blood samples were collected for analysis of 25-OH vitamin D. 173 eligible patients (median age 57) were enrolled. Clinical and treatment characteristics were similar between centres. 84.4 % of women reported use of vitamin D-containing supplements with median daily doses of 1,400 IU. Median 25-OH vitamin D levels were 85.5 and 98.5 nmol/L (P = 0.1), and levels of deficiency (<50 nmol/L), insufficiency (50-72 nmol/L), and adequacy (>72 nmol/L) were 3.8, 23.8, 72.5 % (Toronto) and 4.3, 20.7, 75 % (Los Angeles). 25-OH vitamin D levels were strongly correlated with vitamin D supplement use (r = 0.41, P < 0.0001). 68 % of women expressed willingness to participate in a vitamin D supplementation RCT; however, only 12.7 % of the study population met the pre-specified feasibility criteria (25-OH vitamin D <72 nmol/L, willing to participate, and taking ≤1,000 IU vitamin D supplement/day). Both vitamin D levels and supplementation rates are higher than in previous reports. While the majority of women would be willing to participate in an RCT of vitamin D supplementation, low levels of deficiency/insufficiency and high rates of supplement use would limit the feasibility of such a study.     

Postmenopausal breast cancer risk and interactions between body mass index,menopausal hormone therapy use,and vitamin D supplementation: Evidence from the E3N cohort

Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, but epidemiological evidence is not conclusive. Body mass index (BMI) has been shown to modulate the effect of supplementation on the vitamin D status, but its potential influence on the relationship with breast cancer risk has been little studied. We investigated a potential interaction between BMI and vitamin D supplementation on breast cancer risk while considering an already reported interaction between vitamin D supplementation and menopausal hormone therapy (MHT) use. Vitamin D supplementation was prospectively investigated in 57,403 postmenopausal women from the French E3N cohort including 2,482 incident breast cancer cases diagnosed between 1995 and 2008. Multivariable hazard ratios (HR) for primary invasive breast cancer and 95% confidence intervals (CI) were estimated using Cox models. Among MHT ever users, vitamin D supplementation was associated with decreased breast cancer risk, similarly across BMI strata (P_homogeneity = 0.83). Among MHT never users, ever vitamin D supplementation was associated with increased postmenopausal breast cancer risk in women with baseline BMI <25 kg/m² (HR = 1.51, 95% CI: 1.13, 2.02), but not in women with higher BMI (0.98, 95% CI: 0.62, 1.56), P_homogeneity = 0.12. In conclusion, our findings suggest that vitamin D supplementation may reduce the excess breast cancer risk in MHT users, but draw attention on a potential risk in postmenopausal women not exposed to high exogenous or endogenous hormones, i.e. non‐overweight MHT‐non users, especially in the present context of increasing vitamin D supplement use and decreasing MHT use.     

Change in Adiponectin and Oxidative Stress after Modifiable Lifestyle Interventions in Breast Cancer Cases

Background: Breast cancer is one of the most frequent diseases in women today. Little information exists onmodifiable lifestyle factors including effects of ginger supplements (as an anti-oxidant and anti-inflammatoryherbal) and water-based exercise on biomarkers related to oxidative stress such as malondialdehyde (MDA),nitric oxide (NO) and glutathione peroxidase (GPx) and adiponectin in obese women with breast cancer. Theaim of this study was to determine the single and concomitant effect of 6-wks water-based exercise and oralginger supplement on the aforesaid markers in obese women with breast cancer. Materials and Methods: Fortywomen diagnosed with breast cancer (48±5.4 years, 76±9 kg, fat mass 41.8±4%), volunteered to participate in thestudy. Subjects were randomly assigned into four groups; placebo, water-based exercise, ginger supplement andwater-based exercise+ginger supplement groups. Subjects in the ginger supplement group and the water-basedexercise+ginger supplement group orally received 4 capsules (each capsule contained 750 mg), 7 days a week for 6weeks. The water-based exercise program featured progressive increase in intensity and time, ranging from 50%to 75% of heart rate reserve, in a pool with 15 meters width, 4 times a week for 6 weeks. Fasting blood sampleswere collected at pre-test and post-test time points. Results: The ginger supplementation and or the water-baseexercise resulted in an increase of adiponectin, NO and GPx and reduction MDA, as compared to pre-test values.However, the combined intervention (water-base exercise and ginger supplement) group showed significantly afar better effect on the biomarkers related to oxidative stress and adiponectin levels, as compared to the waterbaseexercise or ginger supplement alone groups and the age-matched placebo group. Conclusions: Our resultsrevealed that water-base exercise is a non-drug therapeutic strategy to reduce systemic stress in obese womensuffering from breast cancer. Further, ginger supplementation alone or in combination with training, also playan important role in the pathogenesis of oxidative stress in obese women diagnosed with breast cancer.     

Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: a randomized, controlled clinical trial

Vitamin D and calcium affect several pathways involved in inflammation, tumor growth, and immune surveillance relevant to carcinogenesis. Also, epidemiologic evidence indicates that calcium and vitamin D may reduce risk for developing colorectal adenomas and cancer. To investigate the effects of calcium and vitamin D on biomarkers of inflammation in colorectal adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92) of 2 g/d calcium and/or 800 IU/d vitamin D(3) supplementation versus placebo over 6 months. Plasma concentrations of proinflammatory markers [C-reactive protein (CRP), TNF-α, interleukin (IL)-6, IL-1β, and IL-8] and an anti-inflammatory marker (IL-10) were measured using ELISAs. After 6 months of treatment, in the vitamin D(3) supplementation group, CRP decreased 32% overall (P = 0.11), 37% in men (P = 0.05), and 41% among non-nonsteroidal anti-inflammatory drug (NSAID) users (P = 0.05) relative to placebo. In the vitamin D(3) supplementation group, TNF-α decreased 13%, IL-6 32%, IL-1β 50%, and IL-8 15%; in the calcium supplementation group, IL-6 decreased 37%, IL-8 11%, and IL-1β 27%. Although these changes were not statistically significant, a combined inflammatory markers z-score decreased 77% (P = 0.003) in the vitamin D(3) treatment group overall, 83% (P = 0.01) among men, and 48% among non-NSAID users (P = 0.01). There was no evidence of synergy between vitamin D(3) and calcium or effects on IL-10. These preliminary results are consistent with a pattern of reduction in tumor-promoting inflammation biomarkers with vitamin D(3) or calcium supplementation alone and support further investigation of vitamin D(3) as a chemopreventive agent against inflammation and colorectal neoplasms.     

The effect of various vitamin D supplementation regimens in breast cancer patients

Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D₂ + D₃) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml, insufficiency as 20–31 ng/ml, and sufficiency as ≥32 ng/ml. BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment. Based on the participants’ baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8–16 weeks. Approximately 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (P < 0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (P = 0.03). Compared to the no-supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine. Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients.     

Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study

Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation activity, is thought to act as a cancer chemopreventive agent. This study evaluated the association between vitamin D intake and breast cancer risk among women in a large prospective cohort study. A total of 34,321 postmenopausal women who had completed a questionnaire that included diet and supplement use were followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for breast cancer were calculated for dietary, supplemental, and total vitamin D intake among all women. The adjusted RR of breast cancer for women consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77–1.03). RRs were stronger among women with negative than positive ER or PR status. The association of high vitamin D intake with breast cancer was strongest in the first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46–0.94 compared with lowest-intake group), and diminished over time. Changes in vitamin D intake over time might have contributed to the diminished association observed in later years. Vitamin D intake of >800 IU/day appears to be associated with a small decrease in risk of breast cancer among postmenopausal women. Studies evaluating all sources of vitamin D, especially sun exposure, are needed to fully understand the association between vitamin D and breast cancer risk.     

A randomized controlled trial of calcium plus vitamin D supplementation and risk of benign proliferative breast disease

Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease, a condition which is associated with increased risk of breast cancer. We used the Women’s Health Initiative randomized controlled trial. The 36,282 participants were randomized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D₃ (GlaxoSmithKline) twice daily (n = 18,176) or to placebo (n = 18,106). Regular mammograms and clinical breast exams were performed. We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. After an average follow-up period of 6.8 years, 915 incident cases of benign proliferative breast disease had been ascertained, with 450 in the intervention group and 465 in the placebo group. Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall (hazard ratio = 0.99, 95% confidence interval = 0.86–1.13), or by histologic subtype. Risk varied significantly by levels of age at baseline, but not by levels of other variables. Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D₃ for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease.     

Haplotype and genotypes of the VDR gene and cutaneous melanoma risk in non-Hispanic whites in Texas: a case-control study

In a hospital-based case-control study of 805 non-Hispanic whites with cutaneous melanoma and 841 cancer-free age-, sex- and ethnicity-matched control subjects, 3 VDR polymorphisms (i.e., TaqI, BsmI and FokI) were genotyped using blood samples collected between 1994 and 2006. We tested the hypothesis that the haplotypes and combined genotypes of these polymorphisms were associated with melanoma risk by interacting with known risk factors. Haplotypes t-B-F (adjusted odds ratio [OR], 0.52; 95% confidence interval [CI], 0.34-0.80) and t-B-f (adjusted OR, 0.51; CI, 0.27-0.94) were associated with a reduced risk when compared to T-b-f. The combined genotypes Tt+tt/Bb+BB/Ff+ff (adjusted OR, 0.69; CI, 0.52, 0.90) and Tt+tt/Bb+BB/FF (adjusted OR, 0.58; CI, 0.43, 0.78) were also associated with reduced risk, whereas the combined genotype TT/Bb+BB/Ff+ff genotype (adjusted OR, 2.35; CI, 1.13, 4.98) was associated with increased risk when compared to TT/bb/Ff+ff genotypes. On multivariate analysis, only the TaqI polymorphism was an independent risk factor, while the FokI polymorphism interacted with skin color (p = 0.029), moles (p = 0.017) and first-degree relatives with any cancer (p = 0.013) in modifying risk. Together, these findings suggest that VDR polymorphisms may directly affect or modify the risk associated with known melanoma risk factors. Larger, population-based studies are needed to replicate our findings.     

Vitamin D Levels in Patients with Breast Cancer: Importance of Dressing Style

Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer(BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was todetermine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levelsin patients with BC and to evaluate its correlations with life-style and treatments. Materials and Methods: Thisstudy included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlationbetween serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usageof bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments andradiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). Results: The median age of the patients was 51 years(range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitaminD deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at thebaseline, high BMI (≥25), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis,none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing stylewere found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4(p=0.003) fold, respectively. Conclusions: The prevalence of serum 25-OHD deficiency/insufficiency is high in ourBC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservativedressing style, as part of regular preventive care, and they should take supplemental vitamin D.     

A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer

Vitamin D deficiency and insufficiency may contribute to musculoskeletal symptoms and bone loss observed in women taking aromatase inhibitors (AIs). This study was conducted to determine the prevalence of suboptimal vitamin D levels in women initiating adjuvant letrozole for breast cancer and to determine whether supplementation with 50,000 IU of vitamin D3 weekly could reduce musculoskeletal symptoms and fatigue in women who have suboptimal vitamin D levels. Sixty women about to begin an adjuvant AI were enrolled. Baseline 25OHD levels were obtained, and women completed symptom questionnaires. They were then started on letrozole, along with standard dose calcium and vitamin D. Four weeks later, women with baseline 25OHD levels ≤40 ng/ml started additional vitamin D3 supplementation at 50,000 IU per week for 12 weeks. 25OHD levels were re-assessed at 4, 10, and 16 weeks; the questionnaires were repeated at weeks 4 and 16. At baseline, 63% of women exhibited vitamin D deficiency (<20 ng/ml) or insufficiency (20–31 ng/ml). 25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects. After 16 weeks of letrozole, more women with 25OHD levels >66 ng/ml (median level) reported no disability from joint pain than did women with levels <66 ng/ml (52 vs. 19%; P = 0.026). Vitamin D deficiency and insufficiency are prevalent in post-menopausal women initiating adjuvant AI. Vitamin D3 supplementation with 50,000 IU per week is safe, significantly increases 25OHD levels, and may reduce disability from AI-induced arthralgias.     

A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases

BACKGROUND:

Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000‐IU oral dose of vitamin D₃. This study therefore aimed to assess the effect of this dose of vitamin D₃ in patients with bone metastases from breast cancer.

METHODS:

Patients with bone metastases treated with bisphosphonates were enrolled into this single‐arm phase 2 study. Patients received 10,000 IU of vitamin D₃ and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter.

RESULTS:

Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity.

CONCLUSIONS:

Daily doses of 10,000 IU vitamin D₃ for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long‐term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2010 American Cancer Society.     

Clinical and Metabolic Response to Vitamin D Supplementation in Endometrial Hyperplasia: a Randomized,Double-Blind,Placebo-Controlled Trial

There was inconsistent evidence showing that vitamin D intake may be associated with reduced cancer risk due to optimized metabolic profile and reduced oxidative stress. However, we are not aware of any study evaluating the effects of vitamin D supplementation on clinical response and metabolic status of patients with endometrial hyperplasia (EH). This research was done to evaluate the effects of vitamin D supplementation on clinical response and metabolic status of patients with EH. This randomized, double-blind, placebo-controlled trial was conducted among 60 women diagnosed with EH. EH diagnosis was made based on specific diagnostic procedures of biopsy. Participants were randomly assigned into two groups to intake either 50,000 IU vitamin D3 supplements (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. After the 12-week intervention, compared with the placebo, vitamin D supplementation increased serum-25(OH) vitamin D levels (+12.0 ± 10.4 vs. +1.9 ± 7.1 ng/mL, P < 0.001). In addition, vitamin D administration was associated with significant decreases in fasting plasma glucose (FPG) (?1.6 ± 7.0 vs. +2.1 ± 6.1 mg/dL, P = 0.03), serum insulin levels (?0.8 ± 1.9 vs. +1.1 ± 3.5 μIU/mL, P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (?0.2 ± 0.6 vs. +0.3 ± 0.8, P = 0.01), and a significant increase in the quantitative insulin sensitivity check index (QUICKI) (+0.003 ± 0.01 vs. ?0.01 ± 0.02, P = 0.02) compared with the placebo. Additionally, a significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (?1.9 ± 2.8 vs. ?0.003 ± 2.0 μg/mL, P = 0.003) and a significant rise in plasma total antioxidant capacity (TAC) values (+62.5 ± 53.5 vs. +7.5 ± 34.1 mmol/L, P < 0.001) were observed following supplementation with vitamin D compared with the placebo. In conclusion, vitamin D3 supplementation for 12 weeks among women with EH had beneficial effects on glucose metabolism, serum hs-CRP, and plasma TAC concentrations. In addition, vitamin D may have played an indirect role in reducing complications of EH due to its effect on improved glycemic control, hs-CRP, and TAC concentrations.     

The Relationship Between Vitamin D and Breast Cancer Incidence and Natural History

Endocrine action of vitamin D and its role in calcium homeostasis and bone health are well known. The discovery that breast epithelial cells possess the same enzyme system as the kidney, permitting local manufacture of active vitamin D (1,25 dihydroxyvitamin D, or 1,25[(OH)₂D]) from circulating precursors 25 hydroxyvitamin D [25(OH)D], has suggested an autocrine role for vitamin D, as well. Preclinical and ecologic studies support a role of vitamin D in prevention of breast cancer. Correlative study results of vitamin D intake or measurement of 25(OH)D, the long-lived precursor, are mixed but suggest a protective effect in premenopausal women. The large Women’s Health Initiative failed to show any reduction in breast cancer incidence in postmenopausal women with a modest amount of vitamin D supplementation. Lack of effect, however, may have been related to trial design. A recent report also suggests that vitamin D may reduce breast cancer recurrence and mortality. Finally, vitamin D is being investigated as a means to reduce aromatase inhibitor-induced joint symptoms.     

Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients

There has been concern that long-term supplementation with high-dose antioxidant vitamins, especially vitamin E (alpha-tocopherol), may increase all-cause mortality. We conducted a randomized controlled trial with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) supplements among 540 head and neck cancer patients treated by radiation therapy. Supplementation with beta-carotene was discontinued during the trial. The supplements were given during radiation therapy and for 3 additional years. During the follow-up (median 6.5 years), 179 deaths were recorded. All death certificates were obtained. All-cause and cause-specific mortality rates were compared between the 2 arms of the trial by Cox regression. All-cause mortality was significantly increased in the supplement arm: hazard ratio: 1.38, 95% confidence interval 1.03-1.85. Cause-specific mortality rates tended to be higher in the supplement arm than in the placebo arm. Our results concur with previous reports to suggest that high-dose vitamin E could be harmful.     

Vitamin D and breast cancer

In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention.     

Role of Vitamin D Deficiency and Lack of Sun Exposure in the Incidence of Premenopausal Breast Cancer: a Case Control Study in Sabzevar,Iran

Background: Vitamin D has been suggested as one of the critical factors for female reproductive health withprotective activities against different cancers but there are conflicting facts regarding its role on breast cancerwithout any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietarysources and sunlight exposure on the incidence of premenopausal breast cancer. Materials and Methods: Weconducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normalwomen who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area ofIran. Results: The mean concentrations of 25-OH vitamin D in cases and controls were 15.2±8.15 vs 15.5±7/45ng/ml, both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe orsevere vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitaminD and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115,CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232,CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack ofsunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131,CI 98% 0.314-78.102). Conclusion: This study pointed out the role of vitamin D and other possible risk factorson the development and growth of breast tumors in this special geographical region. Although this study hasrevealed the interactions between hormonal and environmental factors in this province of Iran, understandingthe deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary.     

Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study

Objective The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk. Methods The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use. Results Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07). Conclusions This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.