Context: Vitamin D₃ might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. Objective: Our objective was to determine the effects of oral vitamin D₃ on vitamin D metabolites and PCa proliferative activity in prostate tissue. Design and Setting: We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. Patients: PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. Intervention: Vitamin D₃ (400, 10 000, or 40 000 IU/d) was orally administered before radical prostatectomy. Main Outcome Measures: We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. Results: Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P < .03) and were significantly higher in the 40 000-IU/d group than in every other dose group (P < .03). Prostate vitamin D metabolites correlated positively with serum levels (P < .0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P < .05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P < .02). Conclusions: Oral vitamin D₃ raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research.

Fluoride has the potential to increase skeletal mass to a greater extent than any other pharmacologic agent, yet it has proven difficult to translate this into therapeutic benefit for patients with low bone mass in diseases such as osteoporosis. This apparent paradox can be explained in part by toxic actions of the ion on skeletal mineralization, impairment of the normal processes of bone resorption, and flourideinduced decreases in strength per unit of bone (mass or volume). In part, the paradox can be explained by the late stage of osteoporosis in most patients enrolled in controlled clinical trials of flouride, with alterations in skeletal microarchitecture beyond which restoration of mechanical integrity is not likely. Exposure of calcified tissues to environmental fluoride (water supply, dentifrices) also offers paradoxes. The anticaries effects are well documented as are the deleterious skeletal effects of endemic fluorosis when environmental exposure is too high. More controversial is the effect of seemingly nontoxic levels of exposure on the prevalence of osteoporotic fractures of the hip. This review attempts to provide a balanced overview of the conflicting literature concerning therapeutic and environmental effects of fluoride on the skeleton.

We conducted a single-arm clinical trial in institutionalized seniors, on the effects of high-dose vitamin D3-fortified bread daily intake (clinicaltrials.gov registration NCT00789503).

To obtain reliable data that allow health authorities to re-evaluate recommendations for oral vitamin D uptake, we conducted a meta-analysis to investigate the impact of supplementation on serum 25-hydroxyvitamin D (25(OH)D) levels in healthy adults in Europe. Of the publications identified (n = 4005) in our literature search (PUBMED, through 2 January 2022), 49 primary studies (7320 subjects, 73 study arms) were eligible for inclusion in our meta-analysis. The risk of bias was assessed using the Cochrane RoB tool based on seven categories, according to which each study is rated using three grades, and overall was rated as rather low. The median duration of intervention was 136.78 days (range, 1088 days); the mean weighted baseline 25(OH)D concentration and mean age were 33.01 vs. 33.84 nmol/L and 46.8 vs. 44.8 years in the vitamin D and placebo groups, respectively. Using random-effects models, 25(OH)D levels were increased by 36.28 nmol/L (95% CI 31.97–40.59) in the vitamin D group compared to the placebo, with a relative serum increment of 1.77 nmol/L per 2.5 μg of vitamin D daily. Notably, the relative serum 25(OH)D increment was affected by various factors, including the dosage and baseline serum 25(OH)D concentration, decreasing with increasing vitamin D doses and with increasing baseline serum levels. We estimate that supplementation in all healthy adults in Europe with appr. 25 μg of vitamin D (1000 IU) daily would raise serum 25(OH)D levels in 95% of the population to ≥50 nmol/L. Our work provides health authorities with reliable data that can help to re-evaluate recommendations for oral vitamin D supplementation.

Context and purpose Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D₃-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. Methods IPD analysis using data from 1429 participants (ages 2–89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. Results Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). Conclusions IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.