Safety, Feasibility, and Biomarker Effects of High-Dose Vitamin D Supplementation Among Women at High Risk for Breast Cancer

Abstract

Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention. We examined the safety, feasibility, and biomarker effects of high-dose vitamin D among women at high risk for breast cancer. Forty high-risk women, defined as a 5-year breast cancer risk ≥1.67% per the Gail model, lobular or ductal carcinoma in situ, were assigned to a 1-year intervention of vitamin D3 20,000 IU or 30,000 IU weekly. Participants were monitored for toxicity every 3 months, underwent serial blood draws at baseline, 6 and 12 months, and a digital mammogram at baseline and 12 months. Biomarker endpoints included serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), insulin-like growth factor (IGF-1), IGF binding protein (IGFBP-3), and mammographic density (MD) using Cumulus software. From November 2007 to January 2011, we enrolled 40 women; 37 were evaluable at 6 months and 30 at 12 months. One patient was taken off study for hypercalciuria; otherwise, the intervention was well tolerated. From baseline to 12 months, mean serum 25(OH)D and 1,25(OH)2D rose from 20.0 to 46.9 ng/ml and 69.7 to 98.1 pg/ml, respectively (p<0.01). Serum PTH decreased by 12% at 6 months and IGF-1/IGFBP-3 ratio decreased by 4.3% at 12 months (p<0.05). There was no significant change in MD regardless of menopausal status or dose level. We demonstrated that 1 year of high-dose vitamin D3 was associated with a significant increase in circulating vitamin D levels and favorable effects on IGF signaling, but no significant change in MD.

Vitamin D Deficiency Is Associated with Muscle Atrophy and Reduced Mitochondrial Function in Patients with Chronic Low Back Pain

“…Moreover, when vitamin D was administered to humans, IGF-1 levels in the blood increased [33]. On the other hand, another study showed that one year of high-dose vitamin D supplementation did not significantly alter serum IGF-1 among women at a high risk of breast cancer [34] nor in prediabetes subjects [35]. Our results revealed that patients in the SUF group had higher serum IGF-1 level than patients in the DEF and SUPL groups, both before and after the supplementation period.…”

<p>Potential risk factors for celiac disease in childhood: a case-control epidemiological survey</p>

“…Vitamin D supplementation in extremely high doses in mice increases susceptibility to colitis,83 and vitamin D supplementation in lethal doses in rats causes sloughing of the intestinal villi 84. In humans, supplementation in extremely high doses can have negative effects on digestion as exhibited through constipation 85,86…”

Reassessing the Association between Circulating Vitamin D and IGFBP-3: Observational and Mendelian Randomization Estimates from Independent Sources

“…Our MR results suggesting that 25(OH)D does not have a causal effect on IGFBP-3 levels in the circulation are in agreement with the results from a randomized phase II trial of men with localised PCa and high grade prostatic intraepithelial neoplasia which found that supplementation with the vitamin D analog,1-alpha-hydroxyvitamin D2, did not have an effect on circulating IGFBP-3 levels 49 . Another vitamin D supplementation trial conducted among women with high risk of breast cancer also found little evidence that circulating IGFBP-3 levels changed after supplementation with 25(OH)D 50 . This does not preclude that increasing the availability of 25(OH)D with supplementation may lead to increased production of 1,25(OH) 2 D within tissues that could then stimulate the local production of IGFBP-3 that is not detected in the circulation.…”