Concentrations Of 25-hydroxyvitamin Research Articles

Abstract 2629: Common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

Abstract Experimental and clinical evidence suggest that vitamin D protects against several types of cancer by promoting cell differentiation and apoptosis and by inhibiting cell proliferation and angiogenesis. In vitro evidence supports a similar protective function in glioma; however, no study has examined whether common genetic variants in the vitamin D pathway are related to glioma risk or patient outcome. We evaluated these potential associations in a clinic-based case-control study conducted at medical centers in the southeastern US. Genotyping was performed in 623 newly diagnosed (eg. nonrecurrent) glioma cases (including 343 WHO grade IV glioblastomas (GBM); 148 WHO grade II or III astrocytomas, 95 oligoastrocytomas and oligodendrogliomas, and 37 gliomas with unspecified histology) and 631 healthy controls with no history of brain tumors. A total of 7 candidate tagging single nucleotide polymorphisms (SNPs) were genotyped in the vitamin D receptor (VDR at 12q13) including rs2107301, rs2238135, rs4516035, rs731236 (Taq1), rs1544410 (Bsm1), rs11568820 (Cdx2), and rs2228570 (Fok1). SNPs associated with serum concentrations of 25-hydroxy vitamin D in genome-wide association studies (GWAS) were also evaluated including rs1155563, rs12512631, rs2282679, and rs7041 in GC (4q12-q13), rs10741657 in CYP2R1 (11p15), rs6013897 in CYP24A1 (20q13), rs3829251 in NADSYN1 (11q13), and rs6599638 at C10orf88 (10q26). Genotyping was performed in oral DNA samples using Illumina GoldenGate and Taqman OpenArray assays. Logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for glioma-related death among 439 patients with high grade tumors including GBM and high grade astrocytomas (331 deaths; median Kaplan-Meier survival: 15.0 months). GWAS SNPs in NADSYN1, GC, and C10ORF88 were not associated with glioma risk or patient survival. Risk associations limited to GBM were observed for rs2238135 in the VDR (G>C; minor allele frequency (MAF) = 0.20) (per variant allele OR = 1.31; 95% CI: 1.01 to 1.71; p for trend = 0.04) and for GWAS SNP rs10741657 located near CYP2R1 (G>A; MAF = 0.40) (per variant allele OR = 0.79; 95% CI: 0.63 to 0.98; p for trend = 0.03). The variant allele in CYP24A1 rs6013897 (T>A; MAF = 0.20) was associated with prolonged survival among patients with high grade tumors (per variant allele HR = 0.79; 95% CI: 0.59 to 0.97; p for trend = 0.03) in patients uniformly treated with the current standard of care (surgery, radiation and temozolomide). To our knowledge this is the first report suggesting that genetic variation in vitamin D related genes may be a determinant of glioma risk and outcome. Further studies are needed to confirm these results and identify the putative causal variant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2629. doi:1538-7445.AM2012-2629

Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation

<u>Background:</u> Vitamin D insufficiency is common in cystic fibrosis (CF) and vitamin D repletion may have an important role in improving clinical outcomes in CF. This randomized, placebo-controlled, pilot study examined the feasibility and impact of a single, large dose of cholecalciferol on vitamin D status and clinical outcomes in subjects with CF. <u>Methods:</u> Thirty adults with were randomized in a double-blinded, pilot study to receive 250,000 IU cholecalciferol or placebo within 48 h of hospital admission for a pulmonary exacerbation. Concentrations of 25-hydroxyvitamin D (25(OH)D), clinical outcomes and potential adverse events were assessed up to one year after randomization. Mixed effects linear regression models were used to evaluate the difference in mean serum concentrations and log-rank analyses were used to evaluate survival. <u>Results:</u> Data from all subjects was analyzed. Serum 25(OH)D concentrations increased from a mean of 30.6 ± 3.2 ng/mL to 58.1 ± 3.5 ng/mL (p < 0.001) at one week and 36.7 ± 2.6 ng/mL by 12 weeks (p = 0.06) in the vitamin D group; in contrast, serum 25(OH)D concentrations remained unchanged in the placebo group. Unadjusted, one-year survival and hospital-free days were increased in the vitamin D group (p = 0.029, p = 0.036; respectively). There was also a trend toward increased IV antibiotic therapy-free days in the vitamin D group (p = 0.073). There were no signs of hypervitaminosis D or adverse events. Serum PTH and calcium concentrations were similar across both groups. <u>Conclusions:</u> In this pilot study, a single, oral bolus of cholecalciferol increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation. Further investigation is needed into the clinical impact of improved vitamin D status in patients with CF.

Vitamin D Deficiency Is Widespread in Cancer Patients and Correlates With Advanced Stage Disease: A Community Oncology Experience

The purpose of this study was to correlate serum vitamin D levels with potential clinical variables and to determine the extent of vitamin D deficiency in a large, outpatient oncology practice. One hundred ninety-five consecutive patients referred for consultation at a community radiation oncology center from October 8, 2008 to March 17, 2010 had vitamin D levels ordered. Patients who were deficient in vitamin D were treated with replacement therapy. Demographic and medical data were collected prospectively and subsequently analyzed. Pretreatment baseline patient and tumor characteristics were evaluated with respect to vitamin D concentrations. One hundred and sixty patients were analyzed. A total of 74% of patients had 25-hydroxyvitamin D concentrations considered either deficient (<20 ng/mL) or suboptimal (20–30 ng/mL). Replacement therapy raised serum vitamin D levels by an average of 15 ng/mL (95% CI = 11–18, P < 0.01). Lower than median serum vitamin D levels were associated with stage III disease in univariate analysis [OR = 2.6 (95% CI = 1.1–6.2), p = 0.04] as well as multivariate analysis adjusted for age, sex, body mass index, and season of draw [OR = 3.3 (95% CI = 1.1–9.7), P = 0.03]. Three-quarters of patients in our series had suboptimal or deficient circulating concentrations of 25-hydroxyvitamin D. Low serum vitamin D levels, independent of age, sex, and body mass index, predicted advanced stage disease.

Physical activity benefits bone density and bone-related hormones in adult men with cervical spinal cord injury

Severe bone loss is a recognized complication of chronic spinal cord injury (SCI). Physical exercise contributes to bone health; however, its influence on bone mass of cervical SCI individuals has not been investigated. The aim of this study was to investigate the influence of physical activity on bone mass, bone metabolism, and vitamin D status in quadriplegics. Total, lumbar spine (L1-L4), femur and radius bone mineral density (BMD) were assessed in active (n = 15) and sedentary (n = 10) quadriplegic men by dual energy X-ray absorptiometry. Concentrations of 25-hydroxyvitamin D [25(OH)D], PTH, IGF1, osteocalcin and NTx were measured in serum. After adjustments for duration of injury, total body mass, and habitual calcium intake, bone indices were similar between groups, except for L1-L4 BMD Z score that was higher in the sedentary group (P < 0.05). Hours of physical exercise per week correlated positively with 25(OH)D (r = 0.59; P < 0.05) and negatively with PTH (r = -0.50; P < 0.05). Femur BMD was negatively associated with the number of months elapsed between the injury and the onset of physical activity (r = -0.60; P < 0.05). Moreover, in the active subjects, both L1-L4 BMD Z score (r = 0.72; P < 0.01) and radius BMD (r = 0.59; P < 0.05) were positively associated with calcium intake. In this cross-sectional study, both the onset of physical activity after injury and the number of hours dedicated to exercise were able to influence bone density and bone-related hormones in quadriplegic men. Our results also suggest a positive combined effect of exercise and calcium intake on bone health of quadriplegic individuals.

P1-08-08: Higher Prediagnostic Serum 25-Hydroxyvitamin Is Associated with Substantially Lower Incidence of Breast Cancer: Prospective Study.

Abstract Background: Recent studies have found lower risk of breast cancer in women with higher serum concentrations of 25-hydroxyvitamin D (25[OH]D), with few exceptions. To help resolve remaining differences, a nested case-control study was conducted. Material and Methods: Serum was provided by the Department of Defense Serum Repository for 600 new cases of breast cancer and 600 controls individually matched on age ±6 months; date blood was drawn ±2 days; and active-duty status; and were analyzed for 25(OH) D by a chemiluminescent assay. Mean age was 40 years (SD ±7 years, range 20–56 years). The individuals were 55% white, 33% African-American, and 11% other races. Mean serum 25(OH)D concentrations by quintile, from lowest to highest, were 11, 18, 24, 30 and 42 ng/ml. Dividing points were &amp;lt;15, 15–21, 22–27, 28–35, and &amp;gt;35 ng/ml. Results: Race-adjusted odds ratios for breast cancer, from lowest to highest quintile of serum 25(OH)D, were 1.0 (reference), 0.58, 0.78, and 0.52 (ptrend &amp;lt; 0.05). The difference between risk of breast cancer in the lowest and highest 25(OH)D quintiles was significant (p &amp;lt; 0.05). The association of low serum 25(OH)D with high risk of breast cancer was strongest for serum drawn during the 3 month period preceding diagnosis of breast cancer, and in white women. There was a strong linear inverse relationship between serum 25(OH) D and risk of breast cancer in this group. A similar trend was present for overall data including all intervals and races, but was weaker and not as clearly linear. Discussion: Consistent with most previous research, women whose serum 25(OH)D concentration was high (42 ng/ml) had approximately half the risk of breast cancer as those whose serum 25(OH)D was low (11 ng/ml). The trend was similar after adjustment for race. The favorable association of serum 25(OH)D with risk of breast cancer apparently was strongest during the final few doublings of the tumor mass preceding diagnosis in this population. (An alternative, far less likely, interpretation, is that the tumor mass might adversely influence 25(OH)D concentration). A serum 25(OH)D concentration of 42 ng/ml can be achieved with vitamin D3 intake of 4000 IU/day. This is the safe daily upper level intake of the National Academy of Sciences-Institute of Medicine (NAS-IOM December 2010 monograph). While further research would be beneficial, such intake should be recommended as a useful tool for prevention of breast cancer. Serum 25(OH)D should be monitored on a routine basis, when feasible, to ensure that at least 40 ng/ml is maintained throughout the year, and 150 ng/ml is not exceeded. This hygienic measure could prevent approximately 50% of breast cancer in the US. (The views expressed in this abstract are those of the authors and do not represent positions of the Department of the Navy, Department of the Army, the Department of Defense or the US Government.) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-08.

Vitamin D Inadequacy Is Associated with Significant Coronary Artery Stenosis in a Community-Based Elderly Cohort: The Korean Longitudinal Study on Health and Aging

Recent studies suggest an association between vitamin D activity and cardiometabolic risk. We investigated vitamin D status and its association with subclinical atherosclerosis in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA). Participants were 439 men and 561 women aged 65 yr or older who were recruited by random stratified sampling for KLoSHA. Anthropometric and biochemical parameters, the concentration of 25-hydroxyvitamin D (25-OHD), and intact PTH were measured. We evaluated the coronary artery calcium score and stenosis using multidetector-row cardiac computed tomography, the intima-media thickness using carotid sonography, pulse wave velocity, and the ankle-brachial index. Among the participants, 49.8, 44.2, and 6.0% had 25-OHD deficiency (<15 ng/ml), insufficiency (15-29.9 ng/ml), and adequacy (≥30 ng/ml), respectively. The frequency of coronary artery stenosis (>50%) differed between 25-OHD categories: 18.5, 12.9, and 1.9% in the 25-OHD-deficient, -insufficient, and -adequate groups, respectively (P < 0.05). After adjusting for cardiometabolic risks and intact PTH concentration, multivariate regression analysis showed that participants with a low 25-OHD concentration had a higher risk of significant coronary artery stenosis; the odds ratios were 2.08 for 25-OHD concentration of 15-29.9 ng/ml vs. at least 30 ng/ml and 3.12 for 25-OHD concentration below 15 ng/ml vs. at least 30 ng/ml (both P < 0.05). The association between 25-OHD inadequacy and subclinical atherosclerosis underscores the clinical implications of vitamin D status. An intervention strategy to increase vitamin D level through vitamin D-fortified diet and adequate sun exposure may mitigate the consequences of vitamin D deficiency.

Vitamin D Serum Levels and Markers of Asthma Control in Italian Children

I Chinellato, M Piazza, M Sandri, D Peroni, G Piacentini, AL Boner. J Pediatr. 2011;158(3):437–441 Recent data indicate that increased serum concentrations of 25-hydroxyvitamin D are associated with higher percent-predicted forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). These researchers sought to establish the relationship between serum vitamin D levels, pulmonary function, and asthma control. This was a cross-sectional analysis of Italian children aged 5 to 11 years with asthma (intermittent or persistent) consecutively evaluated at a …

Vitamin D Status and Indices of Bone Turnover in Older European Adults

An increased rate of bone turnover increases risk of osteoporotic fracture later in life. The concentration of 25-hydroxyvitamin D that contributes to an elevated rate of bone turnover in older adults is unclear. The objective of this study was to investigate the associations between 25-hydroxyvitamin D and biochemical markers of bone turnover in an older, pan-European cohort. 25-hydroxyvitamin D and serum markers of bone-formation (osteocalcin and bone-specific alkaline phosphatase) were assessed by ELISA, while urinary markers of bone-resorption (pyridinoline and deoxypyridinoline) were assessed by HPLC. Six percent, 36 %, and 64 % of subjects had 25-hydroxyvitamin D concentrations < 25, < 50, and < 80 nmol/L throughout the year, respectively. 25-hydroxyvitamin D was significantly and inversely correlated with serum bone-specific alkaline phosphatase (r = 0.119; p = 0.022) and urinary pyridinoline (r = 0.207; p < 0.0001) and deoxypyridinoline (r = 0.230; p < 0.0001). Stratification on the basis of tertiles [T] of 25-hydroxyvitamin D (< 47.6 [T(1)]; 47.6 - 85.8 [T₂]; > 85.8 [T₃] nmol/L), showed that urinary pyridinoline and deoxypyridinoline were significantly lower in subjects in the 2(nd) and 3(rd) compared to the 1(st) tertile (p < 0.015). Low vitamin D status (< 50 nmol/L) was associated with an increased rate of bone turnover in this older pan-European cohort.

Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis

Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen. The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations < 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P = .009). Neonates born with 25-OHD concentrations <50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P = .01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥ 75 nmol/L. Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy.

Similarities in solar ultraviolet irradiance and other environmental factors may explain much of the family link between uveal melanoma and other cancers

Sir: The recent paper [1], exploring the family history of cancer for persons diagnosed with uveal melanoma (UM) was aimed at elucidating a hypothesis that there may increased risk for some cancers in carriers of yet unidentified UM predisposition genetic alteration. While that is certainly a hypothesis worthy of further study, it has to be acknowledged that a familial predisposition can also be due to shared environmental factors. Dietary factors play a major role in cancer risk in general [2]. In the case of UM it seems that dietary factors may improve the survival rate [3]. Smoking and alcohol consumption increase cancer risk, and the same has recently been found to be true for a low serum concentration of 25-hydroxyvitamin D [25(OH)D]. Solar ultraviolet-B (UVB) radiation is the primary human source of vitamin D [4], and solar UVB dose has been found to be inversely correlated with risk of uveal melanoma based on an ecological study [5]. Nearly all of the cancers among those diagnosed with UM and their first and second degree relatives listed in Table 3 of Abdel-Rahman[1] are vitamin D sensitive [6–10], possibly with the exception of prostate cancer in terms of incidence [11, 12], although vitamin D status plays a role in survival for this cancer [13]. Still, diet and genetics certainly play important roles in risk for prostate cancer risk [12, 14]. Related to this study [1] are investigations of second cancers for persons diagnosed with non-melanoma skin cancer (NMSC). At latitudes below about 35–40 , NMSC is generally inversely correlated with risk of second cancer [8, 15], while at higher latitudes, NMSC seems to be positively correlated with risk of many types of cancer [15]. This finding was tentatively explained in terms of the skin surface exposed to the sun: At lower latitudes, larger skin surfaces are probably exposed, so that more vitamin D is produced [16]. In addition, diet and smoking are risk factors for both NMSC and many internal cancers, further explaining the correlations at higher latitudes [16]. Thus, any study looking for genetic risk factors for a cancer based on second primary cancers or cancers in first and second degree relatives, should also take into account whether environmental risk factors such as diet, smoking, and solar UVB exposure (producing vitamin D) might, at least partly, explain the links.

HYPOVITAMINOSIS D IN THAILAND WAS ASSOCIATED WITH DECREASED RISK FOR HYPERTENSION: PP.7.274

Background: Low serum concentration of 25-hydroxyvitamin D [25(OH)D] is associated with hypertension. Hypovitaminosis D has been observed in tropical regions, its association with hypertension is unknown. Objective: The purpose of this study was to explore the existence of hypovitamnosis D and its association with hypertension in Thailand. Design: A matched nested case-control study was conducted on participants from a cardiovascular study. Serum 25(OH) D concentrations in 1985 from randomly selected 137 cases and controls were used to determine vitamin D status and calculate the odd ratios (OR) of having hypertension in 1997. Serum 25(OH)D ≤ 28 ng/dL was used as a cutoff value. Cases and controls were matched for age and gender. Body mass index (BMI), HDL, LDL, triglyceride were used as covariates. Results: 36% of the participants had suboptimal 25(OH)D concentration. Controls had a significantly higher proportion of vitamin D deficiency than cases. Adjusted for matching variables, the odd ratios (OR) of having hypertension were marginally significant for hypovitaminosis D (OR, 0.59; 95%CI, 0.35–0.99; p = .05) but statistically significant for higher BMI (OR, 2.07; 95%CI, 1.12–3.83; p = .02). The OR of having hypertension for hypovitaminosis D was slightly attenuated but remained marginally significant after further adjustment for BMI, HDL and triglyceride (OR, 0.58; 95%CI, 0.34–0.99; p = .05). Stepwise regression identified BMI as the only variable of significance in relation to hypertension. Conclusion: Although not a rarity in Thailand, hypovitamonisis D was associated with decreased risk of hypertension in Thais.

Calcium and vitamin D supplementation in underprivileged indian toddlers using enriched “ladoos”

Vitamin D deficiency is common among children in India, in spite of abundance in sunshine. Calcium intake among such children is often low. These children might benefit from calcium and vitamin D supplementation; however, oral pharmacological preparations of these nutrients are often unpalatable. The authors used “Ladoo”, a much cherished Indian sweet, as a novel vehicle for administering calcium and vitamin D supplements. Toddlers from an urban slum in Pune, India, with low dietary calcium intake ( Ladoo containing, 700 mg elemental calcium (n=30; 2.9±0.5 years), or a control Ladoo , containing 170 mg of elemental calcium (n=30; 2.6±0.5 years), for one year. Subjects in both groups also ate a Ladoo supplemented with 30.000 i.u. of Cholecalciferol, once a month, during the trial. The main outcome measure was the increment in size adjusted total body bone mineral content (TBMC), measured using the GE-Lunar DPX Pro dual energy x-ray absorptiometry. Serum concentration of 25-hydroxy vitamin D in the calcium enriched Ladoo group increased from 25±27 nmol/l to 40±39 nmol/l, and in the control group from 25±27 nmol/l to 39±27 nmol/l. At the end of the trial the change in serum ionised calcium concentration in the calcium enriched Ladoo group (+0.14±0.23 mmol/l) was greater (p=0.004) than in the control group (−0.07±0.19). Serum parathyroid hormone concentration and alkaline phosphatase activity fell in the both groups; however, the change was not statistically different between the groups. The increment in size adjusted TBMC in the calcium enriched Ladoo group was greater (p From these results we conclude that monthly consumption of a cholecalciferol fortified Ladoo can be used to improve the vitamin D status of underprivileged Indian toddlers. Daily consumption of a calcium fortified Ladoo has the potential of improving skeletal mineralisation of toddlers with low dietary calcium intake.

PTH-061 Vitamin D is associated with an increased risk of oesophageal adenocarcinoma but not its pre-cursor conditions

Introduction Evidence is accumulating that vitamin D may be protective against the development of many cancers.[1][1] There are notable exceptions in the literature though, demonstrating increased risks of oesophageal squamous cell carcinoma and oesophageal squamous dysplasia for individuals with the highest serum concentrations of 25-hydroxyvitamin D.[2][2] ,[3][3] Our aim was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma (OAC) and its pre-cursor conditions, Barrett's oesophagus (BO) and reflux oesophagitis (RO). Methods In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 OAC patients, 212 long-segment BO patients, 208 RO patients and 252 healthy population-based controls completed a 101-item food frequency questionnaire, in addition to providing other lifestyle information and medical histories. Multiple logistic regression analysis was applied to examine the association between vitamin D, calcium and dairy intake and disease risk, prior to and after adjustment for potential confounders. Stratified analyses were also conducted by body mass index status. Results OAC risk was significantly greater for individuals in the highest compared with the lowest tertile of vitamin D intake (OR 1.99, 95% CI 1.03 to 3.86, p for trend=0.02) after adjustment for potential confounders. This elevated risk appeared to be accentuated in overweight (OR 2.49, 95% CI 1.16 to 5.37) OAC patients, although formal tests for interaction were not significant. Vitamin D intake was unrelated to RO and BO risk. There were no significant associations observed for calcium or dairy intake and RO, BO or OAC risk. Conclusion A significant direct association was observed between vitamin D intake and OAC risk, which concurs with previous findings for oesophageal squamous cell carcinoma. Vitamin D intake was unrelated to RO and BO risk. No significant associations were found between calcium or dairy intake and the risk of these oesophageal lesions. Further research is needed before recommendations to establish dietary vitamin D guidelines are implemented. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3

Abstract PL04-05: Vitamin D: Panacea or a Pandora's box for prevention?

Abstract Widespread interest in the possible preventive role of vitamin D against cancer emerged from ecological studies of the association between latitude and cancer mortality, in-vitro studies of the effects of vitamin D on proliferation and apoptosis, and presence of vitamin D receptors in many tissues. Observational studies of colorectal cancer provide the most promising data supporting a potential preventive benefit for vitamin D but this effect, so far, is not supported by results from randomized trials. Observational studies for other common cancers such as prostate and breast provide little support for a significant preventive effect of vitamin D. The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) is a consortial effort including 10 prospective cohorts from the United States, Finland and China to examine the association between concentrations of 25-hydroxyvitamin D (25(OH)D) and risk of seven types of rarer cancers: endometrial, esophageal, gastric, kidney, non-Hodgkin's lymphoma, pancreatic and ovarian. No associated benefit, and potential harms, were observed including confirmation of prior reports of an increased risk of pancreatic cancer with higher concentrations of 25(OH)D. The association between mortality and 25(OH)D concentrations was examined in the Third National Health and Nutrition Examination Survey (NHANES III). The mortality rate ratio was statistically significantly higher for those with vitamin D concentrations in the deficient range, defined as &amp;lt;45nmol/L. Among women, an increased rate of mortality was observed both for deficient concentrations and very high concentrations (&amp;gt;124nmol/L). Results suggest that caution should be exercised in using very high dose vitamin D supplementation in prevention trials that may result in high concentrations of vitamin D (&amp;gt;100nmol/L). Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-05.

Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: A descriptive cross-sectional study

The aim of this descriptive cross-sectional study was to describe the prevalence of hypovitaminosis D in a cohort of HIV-seropositive males. Blood samples were collected in November and December 2004 and analyzed in the hospital laboratory. The concentration of 25-hydroxyvitamin D (25(OH)D) was defined as excellent when >75 nmol/l, normal when >50 nmol/l, insufficient when <50 nmol/l, deficient when <25 nmol/l and severely deficient when <12.5 nmol/l. Patient information was extracted from the medical records. A total of 115 males, median age 44 y (range 19-63 y), were included in the study. The median 25(OH)D concentration was 43.0 nmol/l (range 8-163 nmol/l) and the 25(OH)D level was excellent in 13%, normal in 27%, insufficient in 36%, deficient in 20%, and severely deficient in 4% of the cases. Vitamin D level was not associated with age, y with HIV infection, highly active antiretroviral therapy (HAART) or CD4 count. Compared to patients not in treatment, patients on HAART (n = 71) had higher levels of total alkaline phosphatase (median 83.0 vs 75.5 U/l; p = 0.031) and lower, though not significantly, total body mineral density (1.055 vs 1.107 g/cm(2); p = 0.077). This study confirms that the prevalence of hypovitaminosis is high among HIV-infected patients.

Revolutionary Advances in the Diagnosis of Vitamin D Deficiency

Vitamin D deficiency has bee associated with bone diseases, cardiovascular diseases, cancer, and multiple sclerosis. Recent clinical studies have pointed out that these diseases could be prevented by either adequate sun exposure or oral vitamin D3 supplementation. In an effort to prevent these illnesses, emergency physicians and other clinicians must be aware of technological advances in the measurement of serum concentrations of 25-hydroxyvitamin D. Realizing the importance of diagnosing vitamin D deficiency, we reviewed the following advanced diagnostic techniques: liquid chromatography tandem mass spectrometry, radioimmunoassay, and DiaSorin's immunochemiluminometric automated analyzer LIASION®. On the basis of this review, we have found that each of these diagnostic tests has documented limitations, and therefore we recommend an international standardization of these assays to accurately diagnose vitamin D deficiency.

A descriptive cross-sectional study of the prevalence of 25-hydroxyvitamin D deficiency and association with bone markers in a hospitalized population

Patients with gastrointestinal disease may be in particular risk of hypovitaminosis D because of reduced intestinal uptake or metabolism in the liver. The aim of the present study was to evaluate the prevalence of vitamin D deficiency in several groups of patients with various gastroenterologic diseases compared with patients without any chronic disease. We tested the hypothesis that persons with a gastrointestinal disease are at higher risk of hypovitaminosis D than persons with no chronic disease and whether this group needs special attention regarding their nutrition. We included patients admitted to our department of gastroenterology. The concentration of 25-hydroxyvitamin D (25(OH)D2+D3) was defined as insufficient when less than 50 nmol/L, deficient when less than 25 nmol/L, and severely deficient when less than 12.5 nmol/L. We included 146 patients with a mean age of 55 years (range, 16-93 years). 25(OH)D was sufficient in 47%, insufficient in 29%, deficient in 12%, and severely deficient in 11% of the population. Participants without chronic disease had a significantly higher mean level of 25(OH)D (57 nmol/L) compared to participants with cirrhosis (15 nmol/L, P = .002) and alcoholism (31 nmol/L, P = .003). A linear relationship between 25(OH)D and alkaline phosphatase could be demonstrated (Spearman rho, -0.299; P < .001). Participants with severe 25(OH)D deficiency had higher levels of total alkaline phosphatase (149.5 vs 76 U/L, P = .001) and parathyroid hormone (5.1 vs 2.8 pmol/L; P = .001). We recommend measuring the level of 25(OH)D and parathyroid hormone in patients with chronic diseases, especially alcoholism and cirrhosis.

Vitamin D status and optimal supplementation in institutionalized adults with intellectual disability

Background Adults with intellectual disability (ID) have several risk factors for osteoporosis. Feeding problems with consequent nutritive deficiencies, and lack of sunshine exposure may lead to vitamin D deficiency. The purpose of this study was to evaluate vitamin D status in adults with ID living in nursing homes and to compare two different means to administer vitamin D in adults with ID. Methods The study included 13 8 adults ( 95 males and 43 females) with ID living in nursing homes of paajarvi Inter-Municipal Association. Clinical data on the etiology and severity of ID, other illnesses, medications, anthropometry and fractures during the preceding 5 years were collected from medical records. The participants were alternately allocated to receive vitamin D 3 either per orally 8 00 IU daily for 6 months (PO group, n = 72 ) or as a single intramuscular injection of 150 000 IU (IM group, n = 66). Blood samples were obtained at baseline and at 6 months for parameters of calcium homeostasis, including serum concentrations of 25-hydroxyvitamin D (S- 25 -OHD) and parathyroid hormone (P-PTH). Results At baseline, the mean S- 25 -OHD was low, 40 nmol/L in the PO group and 41 nmol/L in the IM group. The low vitamin D levels were associated with secondary hyperparathyroidism in 17 % . At 6 months the mean S- 25 -OHD was 8 2 nmol/L in the PO group (P 8o nmol/L) was attained in 42 %, but with intramuscular dose only in 12%. S- 25 -OHD was >Ioo nmol/L in 14 participants in the PO group and in one participant in the IM group; these high values were associated with hypercalcemia in two and hyperphosphatemia in six participants. Participants with S- 25 -OHD >ioo nmol/L at 6 months were lighter (51.9 kg vs. 67.5 kg, P= 0 . 002 ) and had smaller body mass index than participants with lower S- 25 -OHD ( 20 . 5 kg/m 2 and 24 . 4 kg/m 2 , P= 0.017). Conclusions Vitamin D insufficiency was common in adults with ID living in nursing homes. Both oral and intramuscular administrations of vitamin D 3 improved vitamin D status without adverse effects. The treatment response at 6 months was better in the PO group. High-dose intramuscular vitamin D 3 injections may be a convenient way to maintain sufficient vitamin D status in adults with ID but further studies are needed to establish the optimal dose and interval as well as subsequent potential health benefits in these patients. Based on this study, vitamin D supplementation with per oral 8 00 IU/day is recommended to all adults with ID living in nursing homes.

Serum 25-hydroxyvitamin D Concentrations in Captive and Free-ranging, White-tailed Deer (Odocoileus virginianus)

Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were determined for free-ranging and captive white-tailed deer (WTD). Effects of gender, season, and age on 25(OH)D concentrations were determined as well as comparisons to concentrations in serum from captive reindeer and elk. Seasonal variations in 25(OH)D concentrations were detected for both captive and free-ranging WTD with greatest concentrations detected in August/September (approximately 25 ng/mL) and lowest concentrations in February (approximately 5 - 10 ng/mL). Free-ranging WTD < 1 year of age had lower 25(OH)D concentrations (approximately 6 ng/mL) than did free-ranging WTD > 1 year of age (approximately12 ng/mL). For captive WTD fawns, 25(OH)D concentrations increased from 1 to 9 days of age (exceeding 100 ng/mL) and then steadily declined to approximately 10 ng/mL by 3 months of age. In general, differences in 25(OH)D concentrations based on gender were not detected. 25(OH)D concentrations in captive WTD did not differ from that of captive reindeer; yet, 25(OH)D concentrations were lower in WTD than in captive elk. Additional research is necessary to determine if low serum 25(OH)D concentrations during the winter or pre-weaning period are associated with increased rates of infectious and metabolic disease.

Vitamin D Deficiency in Older Men

Vitamin D deficiency is not adequately evaluated in older men. The aim of the study was to determine the prevalence of vitamin D deficiency and identify risk factors for its occurrence. We conducted a cross-sectional evaluation of 1606 older men in the general community who were enrolled in the Osteoporotic Fractures in Men Study. A randomly selected subcohort of a large population of men from six U.S. communities participated in the study. Serum concentrations of 25-hydroxyvitamin D(2) [25(OH)D(2)] and 25(OH)D(3) were measured using mass spectrometry. Deficiency [25(OH)D <20 ng/ml] was present in 26%, and insufficiency (<30 ng/ml) was present in 72%. Deficiency was particularly common among men during the winter and spring (especially in the northern communities) and in the oldest and more obese men. For instance, in Caucasian men in winter or spring who were >80 yr old, did not engage in lawn/garden work, and had a body mass index greater than 25 kg/m(2) and vitamin D intake below 400 IU/d, the prevalence of vitamin D deficiency was 86%. 25(OH)D(2) levels were present in a small fraction of men and accounted for a low proportion of total 25(OH)D levels. The use of vitamin D supplements was reported by 58% of men, but supplement use had a small effect on total 25(OH)D levels and, despite supplement use, low levels remained frequent. Vitamin D deficiency is common in older men and is especially prevalent in obese, sedentary men living at higher latitudes. Use of vitamin D supplements at levels reported here did not result in adequate vitamin D nutrition.