Widespread vitamin D deficiency in urban Massachusetts newborns and their mothers.

OBJECTIVE: To determine vitamin D status and associated factors in a cohort of newly delivered infants and their mothers in Boston, Massachusetts. PATIENTS AND METHODS: Enrollment in this cross-sectional study took place from 2005 to 2007 in an urban Boston teaching hospital with 2500 births per year. A questionnaire and medical-record data were used to identify variables that are potentially associated with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 20 ng/mL). Infant and maternal blood was obtained by venipuncture within 72 hours of birth. The main outcome measure was infant and maternal 25(OH)D status, assessed by competitive protein binding. RESULTS: We enrolled 459 healthy mother/infant pairs. After subsequent exclusions, analyses were performed on 376 newborns and 433 women. The median infant 25(OH)D level was 17.2 ng/mL (95% confidence interval [CI]: 16.0-18.8; range: <5.0 to 60.8 ng/mL). The median maternal 25(OH)D level was 24.8 ng/mL (95% CI: 23.2-25.8; range: <5.0 to 79.2 ng/mL). Overall, 58.0% of the infants and 35.8% of the mothers were vitamin D deficient (25[OH]D < 20 ng/mL); 38.0% of the infants and 23.1% of the mothers were severely deficient (25[OH]D < 15 ng/mL). Risk factors for infant vitamin D deficiency included maternal deficiency (adjusted odds ratio [aOR]: 5.28 [95% CI: 2.90-9.62]), winter birth (aOR: 3.86 [95% CI: 1.74-8.55]), black race (aOR: 3.36 [95% CI: 1.37-8.25]), and a maternal BMI of >/=35 (aOR: 2.78 [95% CI: 1.18-6.55]). Maternal prenatal-vitamin use throughout the second and third trimesters was protective against infant deficiency (aOR: 0.30 [95% CI: 0.16-0.56]). Similarly, prenatal-vitamin use of > or =5 times per week in the third trimester was protective for mothers (aOR: 0.37 [95% CI: 0.20-0.69]). Despite this, >30% of the women who took prenatal vitamins were still vitamin D deficient at the time of birth. CONCLUSIONS: A high proportion of infants and their mothers in New England were vitamin D deficient. Prenatal vitamins may not contain enough vitamin D to ensure replete status at the time of birth.

Evaluation of 19-nor-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3 as a therapeutic agent for androgen-dependent prostate cancer.

The high incidence of prostate cancer and lack of an effective, long-term treatment for metastatic disease highlights the need for more potent non-calcemic vitamin D analogs as potential alternative or combinational prostate cancer therapies. Among the analogs, 19-nor-1alpha,25-dihydroxyvitamin D2 (19-nor-1alpha,25(OH)2D2) known as paricalcitol or Zempler, has less calcemic effects and an equipotential activity as 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) in several in vivo and in vitro systems. It was recently demonstrated that a modified analog of paricalcitol, 19-nor-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3 (MART-10) compared to 1alpha,25(OH)2D3 was more effective in inhibiting proliferation of an immortalized normal prostate cell line (PZ-HPV-7) (1,000-fold) and invasion of PC-3 prostate cancer cells (10-fold). In this study, the effects of MART-10 and 1alpha,25(OH)2D3 on proliferation, vitamin D receptor transactivation, vitamin D-binding protein (DBP) binding, CYP24A1 (24-OHase) substrate hydroxylation kinetics, and induction of CYP24A1 gene expression were compared in an androgen-dependent prostate cancer cell model, LNCaP. The results demonstrated that MART-10 was 1,000-fold more active than 1alpha,25(OH)2D3 in inhibiting LNCaP cell proliferation. MART-10 was more active than 1alpha,25(OH)2D3 in up-regulating a vitamin D receptor-responsive Luciferase construct and inducing CYP24A1 gene expression in LNCaP prostate cancer cells. In addition, MART-10 has a lower affinity for DBP and less substrate degradation by CYP24A1 compared to 1alpha,25(OH)2D3, indicating that MART-10 has more bioavailability and a longer half-life. Thus, these data suggest that MART-10 may be a potential candidate as a therapeutic agent for prostate cancer, especially for patients who fail in conventional therapies.

Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.

BACKGROUND: Prostate cells can produce 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3) to regulate their own growth. Here, the questions of whether prostate cells express vitamin D-25-hydroxylase (25-OHase) and can convert vitamin D3 to 1alpha,25(OH)2D3 were investigated. MATERIALS AND METHODS: Protein and receptor binding assays were used to determine 25(OH)D3 and 1alpha,25(OH)2D3, respectively. Measurements of proliferation by 3H-thymidine incorporation, and 1alpha,25(OH)2D-responsive gene expression by real-time qPCR and by Western blot were used as functional assays for the presence of 25-OHase activity. RESULTS: Prostate cells metabolized vitamin D3 to 1alpha,25(OH)2D3. Vitamin D3 up-regulated 25(OH)D-24R-hydroxylase and IGFBP3, two 1alpha,25(OH)2D-responsive genes, in prostate cells. CYP2R1 was the major form of 25-OHase expressed in normal and cancerous prostate cells as determined by qPCR. CONCLUSION: The autocrine synthesis of 1alpha,25(OH)2D3 from vitamin D3 suggests that maintaining adequate levels of serum vitamin D could be a safe and effective chemo-preventive measure to decrease the risk of prostate cancer.