Standardized serum 25-hydroxyvitamin D concentrations are inversely associated with cardiometabolic disease in U.S. adults: a cross-sectional analysis of NHANES, 2001-2010.

BACKGROUND: Previously reported associations between vitamin D status, as measured by serum 25-hydroxyvitamin D [25(OH)D] concentrations, and cardiometabolic risk factors were largely limited by variability in 25(OH)D assay performance. In accordance with the Vitamin D Standardization Program, serum 25(OH)D measurement was recently standardized in the National Health and Nutrition Examination Survey (NHANES) to reduce laboratory and method related differences in serum 25(OH)D results. We evaluated the overall and ethnic-specific associations between the newly standardized serum 25(OH)D concentrations and cardiometabolic risk in U.S. adults. METHODS: This study examined standardized 25(OH)D data from five cycles of the NHANES (2001-2010). The total sample included 7674 participants (1794 Mexican-Americans, 4289 non-Hispanic whites, and 1591 non-Hispanic blacks) aged ≥ 20 years who were examined in the morning after overnight fasting. Serum 25(OH)D was directly measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 2007-2010, and was predicted from LC-MS/MS equivalents for 2001-2006. Serum 25(OH)D levels were categorized into quartiles (<43.4, 43.4-58.6, 58.7-74.2, ≥74.3 nmol/L). Cardiometabolic risk was defined by the homeostatic model assessment of insulin resistance (HOMA-IR), metabolic syndrome (MetS), and Framingham cardiovascular disease (CVD) risk. Prevalence ratios and 95% confidence intervals were calculated using modified Poisson regression. RESULTS: After full adjustment for confounders, serum 25(OH)D ≥74.3 nmol/L was associated with lower cardiometabolic risk compared to 25(OH)D <43.4 nmol/L in the overall sample [HOMA-IR: 0.70 (0.59, 0.84); MetS: 0.82 (0.74, 0.91); CVD risk: 0.78 (0.66, 0.91)]. These associations remained significant in Mexican-Americans [HOMA-IR: 0.54 (0.35, 0.82); MetS: 0.73 (0.55, 0.96)], non-Hispanic whites [HOMA-IR: 0.81 (0.68, 0.96); MetS: 0.84 (0.73, 0.95); CVD risk: 0.78 (0.64, 0.93)]; and in non-Hispanic blacks [HOMA-IR: 0.67 (0.45, 0.99); MetS: 0.75 (0.56, 0.97); CVD risk: 0.58 (0.41, 0.81)]. CONCLUSIONS: Low vitamin D status is a significant risk factor for cardiometabolic disease in U.S. adults based on standardized serum 25(OH)D results, irrespective of ethnic background. Future studies using standardized 25(OH)D data are needed to confirm these results, particularly amongst U.S. blacks with 25(OH)D concentrations above 75 nmol/L.

Exposure to a Vitamin D Best Practices Toolkit, Model, and E-Tools Increases Knowledge, Confidence, and the Translation of Research to Public Health and Practice.

Preventable vitamin D deficiency (VDD) is a global health concern. The prevention, early detection, and treatment of vitamin D deficiency aligning with serum 25-hydroxyvitamin D concentration recommendations of 40-60 ng/mL (100-150 nmol/L), provided by an international panel of 48 vitamin D researchers, would result in significant health benefits and cost savings to individuals and society. However, research shows that healthcare professionals lack knowledge and confidence in best practices with respect to vitamin D. A vitamin D toolkit was developed that included a model for decision-making support, e-tools, and accompanying resources and was implemented using an online, asynchronous learning management system. This pre-test, post-test, and follow-up survey study design aimed to increase nurses' and dietitians' levels of knowledge and confidence regarding vitamin D, aid in their translation of evidence into spheres of practice and influence, and help them identify translation barriers. The completion of the toolkit increased the participants' (n = 119) knowledge from 31% to 65% (p < 0.001) and their confidence from 2.0 to 3.3 (p < 0.001) on a scale of 1-5. Respondents reported using the model (100%) as a framework to successfully guide the translation of vitamin D knowledge into their sphere of influence or practice (94%) and identifying translation barriers. The toolkit should be included in interdisciplinary continuing education, research/quality improvement initiatives, healthcare policy, and institutions of higher learning to increase the movement of research into practice.

Official recommendations for vitamin D through the life stages in developed countries.

Inadequate vitamin D nutritional status is prevalent worldwide and has been associated with autoimmune disorders, heart disease, deadly cancers, insulin resistance, inflammation, neurological disorders, adverse outcomes in pregnancy, and increased risk for mortality. Expert recommendations for vitamin D intake differ between governmental agencies and practice guidelines from medical societies due to differences in the definition of vitamin D deficiency, insufficiency and sufficiency based on serum 25-hydroxyvitamin D [25(OH)D] concentrations. In addition, separate health promotion bodies also provide targeted recommendations for the prevention of specific disorders such as reducing risk for developing some cancers and autoimmune diseases. We review and provide perspectives regarding various recommendations from the Institute of Medicine (IOM, United States) and Health Canada, the European Food Safety Authority (EFSA), the Scientific Advisory Committee on Nutrition (SACN; United Kingdom), the World Health Organization, the Endocrine Society and other expert groups by life stage as a guide intended for clinician use.

Effectiveness and safety of steady versus intermittent high dose vitamin D supplementation for the prevention of falls and fractures among adults: a protocol for systematic review and network meta-analysis.

INTRODUCTION: Clinical trials and systematic reviews of trials involving vitamin D supplementation have mainly focused on defining the optimal amount of vitamin D dosage. However, the comparative effectiveness of different dosing schedules (ie, daily vs bolus dosing schedule) has been largely unexplored; and currently, there is no consensus regarding the optimal vitamin D dosing schedule. Our objective is to conduct a systematic review and network meta-analysis (NMA) to evaluate the comparative effectiveness and safety of steady (eg, daily, weekly) and intermittent high-dose (eg, monthly, yearly) vitamin D dosing schedules; and to determine the effectiveness of the various dosing schedules and combinations of treatments. METHODS AND ANALYSIS: We will conduct a systematic search and review of literature from major medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) involving studies that compare vitamin D supplementation alone or in combination with calcium. Only randomised controlled trials (RCTs) will be considered. We will, however, consider various settings (eg, community, institutional care) and study designs (eg, cluster RCTs, cross-over trials). Our primary outcomes include falls and fractures including hip-fracture and non-vertebral fractures. Secondary outcomes will include muscle strength, physical performance, gait and mobility limitation. A Bayesian NMA will be conducted, and the results will be presented in the form of treatment effect estimates and ranking probabilities, with corresponding CIs. Pairwise meta-analysis will also be conducted for studies reporting head-to-head comparisons. Subgroup analysis will be performed with respect to pre-determined subgroups; including vitamin D status as measured by serum 25-hydroxyvitamin D levels, age and follow-up time. Sensitivity analysis will also be performed with respect to risk of bias. ETHICS AND DISSEMINATION: This study is a systematic review and meta-analysis of published RCTs; therefore, no ethical approval is required. Results will be disseminated through open access peer-reviewed publications. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018112662.

Metabolically healthy obesity, vitamin D, and all-cause and cardiometabolic mortality risk in NHANES III.

BACKGROUND & AIMS: Previous studies assessing the prognosis of metabolically healthy obesity (MHO) have been limited by a lack of a harmonized definition of MHO phenotype. Furthermore, obesity is a risk factor for vitamin D deficiency and low vitamin D status has been associated with a higher risk of mortality; however, few studies have evaluated the joint association between vitamin D, metabolic health phenotype, and mortality risk. Using a harmonized definition, we investigated whether MHO is associated with subsequent all-cause and cardiometabolic mortality, and whether serum 25-hydroxyvitamin D [25(OH)D] modifies these associations. METHODS: This study included participants aged ≥20 years from the Third National Health and Nutrition Examination Survey (NHANES III). MHO phenotype was defined as a combination of obesity (≥30 kg/m2) and zero component of metabolic syndrome. Multivariable Cox regression was used to assess the risk of mortality across metabolic phenotypes, and the joint association between metabolic phenotype and 25(OH)D. Fine and Gray regression was performed to account for competing risk events. RESULTS: Among 11,333 participants, a total of 2980 deaths (937 cardiometabolic death outcomes) occurred during a median follow-up of 19.1 years. In the absence of any metabolic abnormality, obesity (MHO) was not associated with a higher risk of all-cause (hazard ratio [HR], 0.89 [95% CI, 0.52-1.51]) or cardiometabolic mortality (cause-specific HR, 1.21 [95% CI 0.33-4.46]). Similar results were obtained from competing risk analysis. No significant differences in average 25(OH)D levels were observed between MHO and non-MHO participants; however, there was a significant interaction between metabolic health phenotype and serum 25(OH)D in relation to cardiometabolic mortality such that levels of serum 25(OH)D < 50 nmol/L were associated with increased risk of cardiometabolic mortality, particularly in participants within the normal-weight and obese BMI ranges. CONCLUSIONS: Our results support the hypothesis that MHO phenotype is a benign health condition. Vitamin D deficiency may exacerbate the risk of cardiometabolic death outcomes associated with metabolic dysfunction in normal weight and obese individuals. Further research is warranted to validate our findings.

Retrospective Analysis of Cardiovascular Disease Risk Parameters in Participants of a Preventive Health and Wellness Program.

Lifestyle, dietary, and nutritional choices are important influencing parameters of cardiovascular disease (CVD) risk, the number one cause of morbidity and mortality globally. Our aims were to i) characterize CVD risk parameters using data from 7939 participants enrolled in a preventive health and wellness program between March 2010 and January 2017; and ii) evaluate intervention effects in 3,020 participants who returned for follow-up. Blood measurements (nutrient markers), CVD risk parameters (abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein (HDL), insulin resistance, and inflammation), glycemic status (HbA1c), and insulin resistance (HOMA-IR) were assessed. Framingham and Reynold's risk scores were also calculated. After approximately one year of treatment (n = 3 020), mean arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio, homocysteine, and HbAlc concentrations were significantly reduced; other risk parameters did not improve but mean values remained within reference ranges. Excluding participants taking related medications, 38.8%, 37.2%, 38.0%, 42.5%, and 59.7% of those with hyperglycemia, hypertriglyceridemia, low HDL, insulin resistance, or prediabetes, respectively, at baseline no longer had the condition at follow-up. In contrast, of individuals within the reference range at baseline, new cases at follow-up were found for 10.1%, 12.2%, 6.3%, 8.2%, and 7.6% (as above, respectively). Regression models revealed a significant association between serum 25-hydroxyvitamin D concentrations ≥100 nmol/L and reductions in many CVD risk parameters after adjustment for confounding variables. These findings suggest that a preventive approach to health and wellness focused on nutrients, optimal serum 25-hydroxyvitamin D concentrations, and lifestyle changes has the potential to reduce the risk of CVD.

Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children.

BACKGROUND: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D(3) administered to apparently healthy schoolchildren. METHODS: To assess short-term safety, 25 subjects randomly received placebo or vitamin D(3) at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D(3) as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. RESULTS: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (+/- 11) to 54 (+/- 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 +/- 8 to 19 +/- 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 +/- 7 to 36 +/- 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication. CONCLUSION: Vitamin D(3) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels.

Vitamin D: a growing perspective.

Vitamin D deficiency has been widely reported in all age groups in recent years. Rickets has never been eradicated in developed countries, and it most commonly affects children from recent immigrant groups. There is much evidence that current vitamin D guidelines for the neonatal period, 5-10 microg (200-400 IU)/day, prevent rickets at the typical calcium intakes in developed countries. The annual incidence of vitamin D-deficiency rickets in developed countries ranges between 2.9 and 7.5 cases per 100,000 children. The prevalence of vitamin D deficiency in mothers and their neonates is remarkable, and the results of one study suggest that third-trimester 25-hydroxyvitamin D (25(OH)D) is associated with fetal bone mineral accrual that may affect prepubertal bone mass accumulation. Beyond infancy, the evidence indicates that 5 microg (200 IU)/day of vitamin D has little effect on vitamin D status as measured by the serum 25(OH)D concentration. Two randomized clinical trials show that higher vitamin D intake improves one-year gain in bone density in adolescent girls. The functions of vitamin D extend beyond bone to include immune system regulation and anti-proliferative effects on cells. Early life vitamin D inadequacy is implicated in the risk of bone disease, autoimmune disease, and certain cancers later in life; however, long-term interventional studies do not exist to validate the widespread implementation of greater vitamin D consumption. Here we review the available data concerning vitamin D status and health effects of vitamin D in pregnancy through to and including adolescence.

Self-prescribed high-dose vitamin D3: effects on biochemical parameters in two men.

The lowest observed adverse effect level for vitamin D, said to cause hypercalcaemia in normal adults, is officially 95 microg/day. Serum 25-hydroxyvitamin D (25[OH]D) concentrations associated with hypervitaminosis D remain undefined. Reported 25(OH)D concentrations resulting from prolonged excessive vitamin D3 intakes have exceeded 700 nmol/L. We report self-prescribed high dose of vitamin D3 over 5-6 years by two men. Subject 1 had been taking 100 microg/day for 3 years followed by 3 years of 200 microg/day. Serum 25(OH)D concentrations averaged 130 nmol/L while taking 100 microg/day of vitamin D3. While taking 200 microg/day of vitamin D3, mean serum 25(OH)D concentrations were 260 nmol/L with no hypercalcaemia or hypercalcuria over the 6 years of vitamin D3 intake. Subject 2 was a 39-year-old man diagnosed with multiple sclerosis. He initiated his own dose-escalation schedule. His vitamin D3 intake increased from 200 to 2200 microg/day over 4 years. The first evidence of a potential adverse effect was that urinary calcium:creatinine ratios showed an increasing trend, which preceded serum calcium concentrations above the reference range (2.2-2.6 mmol/L). His serum 25(OH)D concentration was 1126 nmol/L when total serum calcium reached 2.63 mmol/L. He stopped vitamin D3 supplementation at this point. Two months later, all biochemistry values were within reference ranges; serum 25(OH)D concentrations fell by about one-half, to 656 nmol/L. These results help to clarify the human response to higher intakes of vitamin D3. Close monitoring of biochemical responses confirmed that an increase in urinary calcium:creatinine ratio precedes hypercalcaemia as serum 25(OH)D concentrations rise.

Database Analysis of Depression and Anxiety in a Community Sample-Response to a Micronutrient Intervention.

BACKGROUND: Depression and anxiety are common mental health concerns worldwide. Broad-spectrum multi-vitamin/mineral approaches have been found to alleviate a number of psychiatric symptoms. We investigated the effects of a nutrient intervention program, which includes optimizing vitamin D levels, on depression and anxiety outcomes from community-based program. METHODS: We evaluated self-reported health measures of depression and anxiety collected as part of a community-based program focused on optimizing overall health through nutritional supplementation, education and lifestyle advice. RESULTS: Data were collected from 16,020 participants, with measures including European Quality of Life Five Dimensions (EQ-5D) and Targeted Symptoms List (TSL) providing self-reported depression and anxiety. More than 56% of participants were identified as having elevated levels of depression and anxiety at baseline as reported on the EQ-5D. After one year in the program, 49.2% (n = 7878) of participants who reported any level of depression or anxiety at baseline reported improvement at follow-up. Of those who reported severe/extreme depression at baseline (n = 829), 97.2% reported improvement after one year. Regression analyses revealed a significant association of improvement in depression and anxiety with higher vitamin D status (>100 nmol/L) and more strenuous physical activity. CONCLUSION: Overall, people from the general population who suffer from mood and anxiety problems may benefit from improved nutritional status achieved with nutritional supplements.

Vitamin D Supplementation, Serum 25(OH)D Concentrations and Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis.

Background: Cardiovascular disease (CVD) risk factors are associated with low serum 25 hydroxyvitamin D (25(OH)D) concentrations in observational studies; however, clinical trial findings are inconsistent. Objective: We assessed the effect of vitamin D supplementation and increased serum 25(OH)D concentrations on CVD risk factors in a systemic review and meta-analysis of randomized controlled trials (RCTs). Design: MEDLINE, CINAHL, EMBASE, and Google Scholar were searched for RCTs that evaluated vitamin D supplementation and cardiovascular outcomes [blood pressure, parathyroid hormone (PTH), serum high-sensitivity C-reactive protein (hs-CRP), total cholesterol, high and low density lipoprotein (HDL and LDL, respectively), triglycerides, peak wave velocity (PWV) and Augmentation Index (AI)] from 1992 through 2017. Meta-analysis was based on a random-effects model and inverse variance method to calculate standardized mean difference (SMD) as effect sizes, followed by a leave-one-out method for sensitivity analysis. Risk of publication bias was assessed using Cochrane checklist and Begg funnel plots. The systematic review is registered as CRD42015025346. Results: We identified 2341 studies from which 81 met inclusion criteria. The meta-analysis indicated a significant reduction in systolic blood pressure (SMD = -0.102 ± 0.04 mmHg, 95% confidence interval (CI), -0.20 to -0.03), diastolic blood pressure (SMD = -0.07 ± 0.03 mmHg, 95% CI, -0.14 to -0.006), serum PTH (SMD = -0.66 ± 0.08 ng/L, 95% CI, -0.82 to -0.49), hs-CRP (SMD = -0.20 ± 0.07 mg/L, 95% CI, -0.34 to -0.06), total cholesterol (SMD = -0.15 ± 0.06 mmol/L, 95% CI, -0.25 to -0.04), LDL (SMD = -0.10 ± 0.05 mmol/L, 95% CI, -0.20 to -0.003), triglycerides (SMD = -0.12 ± 0.06 mmol/L, 95% CI, -0.23 to -0.003) and a significant increase in HDL (SMD = 0.09 ± 0.04 mmol/L, 95% CI, 0.00 to 0.17) with vitamin D supplementation. These findings remained significant in sensitivity analyses for blood pressure, lipid profile, serum PTH, and serum hs-CRP. There was no significant effect of vitamin D supplementation on PWV (SMD = -0.20 ± 0.13 m/s, 95% CI, -0.46 to 0.06, p = 0.14) and AI (SMD = -0.09 ± 0.14%, 95% CI, -0.37 to 0.19, p = 0.52) for vitamin D supplemented groups. Conclusion: These findings suggest that vitamin D supplementation may act to protect against CVD through improving risk factors, including high blood pressure, elevated PTH, dyslipidemia, and inflammation.

Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in Prediabetics: A Meta-Analysis.

Diabetes prevention is a public health priority. Vitamin D supplementation may help prevent the development of diabetes in persons at increased risk. We performed a meta-analysis of controlled clinical trials that assessed glycemic outcome measures among adults at risk for type 2 diabetes, including prediabetes, overweight, or obesity. We searched PUBMED/ MEDLINE, CINAHL, and Google Scholar databases for trials published prior to April 2017. Placebo-controlled clinical trials with random allocation to vitamin D with or without calcium supplementation were selected. Data collection included country, study design, inclusion criteria, sample size, form, and dose of vitamin D, supplementation interval, control group, duration, participant characteristics, comorbidities, baseline and follow-up serum 25-hydroxyvitamin D [25(OH)D] concentration, and available outcome measures [glycosylated hemoglobin (HbA1c), fasting plasma glucose, plasma glucose after 2-hour oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR)]. Data synthesis was conducted using random-effect models (PROSPERO registration no. CRD42017055326). Twenty-eight trials, representing 3848 participants, met the eligibility criteria. Compared with the control group, vitamin D supplementation significantly reduced HbA1c level by -0.48% (95% CI, -0.79 to -0.18), fasting plasma glucose level by -0.46 mmol/L (95% CI, -0.74 to -0.19), and HOMA-IR level by -0.39 (95% CI, -0.68 to -0.11). Subgroup analysis revealed that the effects of vitamin D supplementation on different glycemic measures were influenced by age, calcium coadministration, vitamin D deficiency, serum 25(OH)D level after supplementation, and duration of supplementation. Vitamin D supplementation and improved vitamin D status improved glycemic measures and insulin sensitivity and may be useful as part of a preventive strategy for type 2 diabetes.

A Critical Appraisal of the Recent Reports on Sunbeds from the European Commission's Scientific Committee on Health, Environmental and Emerging Risks and from the World Health Organization.

The European Commission's Scientific Committee on Health, Environmental and Emerging Risks and the World Health Organization recently published reports which concluded that a large proportion of melanoma and non-melanoma skin cancer is attributable to sunbed use, and that there is no need to use sunbeds as there are no health benefits and they are not needed to achieve an optimal vitamin D level. The overall conclusion from both bodies was that there is no safe limit for UV irradiance from sunbeds. We are, however, deeply concerned that these assessments appear to be based on an incomplete, unbalanced and non-critical evaluation of the literature. Therefore, we rebut these conclusions by addressing the incomplete analysis of the adverse health effects of UV and sunbed exposure (what is 'safe'?) and the censored representation of beneficial effects, not only but especially from vitamin D production. The stance taken by both agencies is not sufficiently supported by the data and in particular, current scientific knowledge does not support the conclusion sunbed use increases melanoma risk.

Safety of vitamin D3 in adults with multiple sclerosis.

BACKGROUND: Vitamin D3 may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D(3) may be required for therapeutic efficacy, and yet tolerability--in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia--remains poorly characterized. OBJECTIVE: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. DESIGN: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 microg/wk (from 28 000 to 280 000 IU/wk). RESULTS: Mean (+/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03). CONCLUSIONS: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

A comparison of automated methods for the quantitation of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

OBJECTIVE: To compare automated platforms with the routinely used methods in our clinical laboratory for the quantitation of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D]. METHOD: The NEXgen Four and Triturus ELISA platforms, utilizing the IDS enzyme immunoassay (EIA) kit for 25(OH)D, and the DiaSorin Liaison 25(OH)D methods were compared with the DiaSorin radio immunoassay (RIA) kit. The NEXgen Four and the Triturus, utilizing IDS EIA for 1,25(OH)2D, were compared with the thymus radioreceptor assay (RRA) for measurement of 1,25(OH)2D. RESULTS: NEXgen correlated best with DiaSorin RIA (r(2)=0.652). NEXgen correlated best with the thymus RRA method (r(2)=0.541). Imprecision CV values for NEXgen 1,25(OH)2D were 2.8-9.4% within-run and 10.2-13.9% between-run compared with a between-run precision of 14.0-16.9% with the thymus RRA method. CONCLUSION: NEXgen correlated best with DiaSorin RIA for measurement of 25(OH)D. NEXgen correlated best and demonstrated better precision than thymus RRA for quantitation of 1,25(OH)2D.

Sunbeds with UVB radiation can produce physiological levels of serum 25-Hydroxyvitamin D in healthy volunteers.

Vitamin D3 is produced in the skin in response to UVB irradiation, from either sun exposure or UVB sunbeds. The objective of the current study was to characterize serum 25(OH)D response to regular sunbed use from several lamp outputs following their respective time exposure recommendations. There were three groups that tanned over 12 weeks during the winter months in dedicated sunbeds based on lamp outputs (100 W and 160 W low pressure fluorescent and 700 W high pressure filtered metal halide lamps) and a control group provided serum 25(OH)D samples at baseline and end-of-study. Tanning session lengths were calculated based on Health Canada guidelines to stay below the erythema levels. Mean 25(OH)D were increased by an average of 42 nmol/L in the sunbeds that used 100 W and 160 W fluorescents. Change in 25(OH)D was dependent on baseline 25(OH)D levels and sunbed (p = 0.003) and age (p = 0.03), but was not affected by gender, BMI, Fitzpatrick type or cumulative length of tanning sessions. There was no significant increase in 25(OH)D levels in participants using the 700 W filtered metal halide lamp sunbed or in the control participants. Skin pigmentation, [Formula: see text], was markedly increased in all tanners and skin lightness, L*, significantly decreased at 12 weeks. Both L* and [Formula: see text] were significantly correlated with 25(OH)D concentrations for the sunbeds with fluorescent lamps emitting UVB (100 W and 160W). Participants following standardized exposure schedules meeting Health Canada regulations in sunbeds irradiating adequate UVB showed continuous increases of 25(OH)D to physiological levels even after producing a tan in a controlled manner. ClinicalTrials.gov Registration: NCT02334592.

The Association between Serum 25(OH)D Status and Blood Pressure in Participants of a Community-Based Program Taking Vitamin D Supplements.

BACKGROUND: Vitamin D deficiency is a risk factor for hypertension. METHODS: We assessed 8155 participants in a community-based program to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) status and blood pressure (BP) and the influence of vitamin D supplementation on hypertension. Participants were provided vitamin D supplements to reach a target serum 25(OH)D > 100 nmol/L. A nested case-control study was conducted to examine the effect of achieving physiological vitamin D status in those who were hypertensive and not taking BP-lowering medication, and hypertensive participants that initiated BP-lowering medication after program entry. RESULTS: At baseline, 592 participants (7.3%) were hypertensive; of those, 71% were no longer hypertensive at follow-up (12 ± 3 months later). There was a significant negative association between BP and serum 25(OH)D level (systolic BP: coefficient = -0.07, p < 0.001; diastolic BP: coefficient = -0.1, p < 0.001). Reduced mean systolic (-18 vs. -14 mmHg) and diastolic (-12 vs. -12 mmHg) BP, pulse pressure (-5 vs. -1 mmHg) and mean arterial pressure (-14 vs. -13 mmHg) were not significantly different between hypertensive participants who did and did not take BP-lowering medication. CONCLUSION: Improved serum 25(OH)D concentrations in hypertensive individuals who were vitamin D insufficient were associated with improved control of systolic and diastolic BP.

Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program.

PURPOSE: Vitamin D deficiency has been associated with an increased risk of hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the influence of vitamin D supplementation on thyroid function and anti-thyroid antibody levels. METHODS: We constructed a database that included 11,017 participants in a health and wellness program that provided vitamin D supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D] concentrations (>100 nmol/L). Participant measures were compared between entry to the program (baseline) and follow-up (12 ± 3 months later) using an intent-to-treat analysis. Further, a nested case-control design was utilized to examine differences in thyroid function over 1 year in hypothyroid individuals and euthyroid controls. RESULTS: More than 72% of participants achieved serum 25(OH)D concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L. Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum 25(OH)D concentrations ≥125 nmol/L were associated with a 30% reduced risk of hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies. Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at follow-up, which was a significant positive predictor of improved thyroid function. CONCLUSION: The results of the current study suggest that optimal thyroid function might require serum 25(OH)D concentrations above 125 nmol/L. Vitamin D supplementation may offer a safe and economical approach to improve thyroid function and may provide protection from developing thyroid disease.

The Effect of Improved Serum 25-Hydroxyvitamin D Status on Glycemic Control in Diabetic Patients: A Meta-Analysis.

Background: Type 2 diabetes is a global health concern, with an increased prevalence and high cost of treatment. Objective: The aim of this systematic review and meta-analysis was to determine the effect of vitamin D supplementation and improved vitamin D status on glycemia and insulin resistance in type 2 diabetic patients. Data Source: We searched PUBMED/Medline, Cumulative Index to Nursing and Allied Health, and Cochrane Library (until January 2017). Study Selection: Prospective clinical trials were selected evaluating the impact of vitamin D supplementation on glycosylated hemoglobin (HbA1c), serum fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) in diabetic patients. Data Extraction and Synthesis: We used a random-effects model to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration was CRD42017059555. From a total of 844 entries identified via literature search, 24 controlled trials (1528 individuals diagnosed with type 2 diabetes) were included. The meta-analysis indicated a significant reduction in HbA1c [mean difference: -0.30%; 95% confidence interval (CI): -0.45 to -0.15, P < 0.001], FPG [mean difference: -4.9 mg/dL (-0.27 mmol/L); 95% CI: -8.1 to -1.6 (-0.45 to -0.09 mmol/L), P = 0.003], and HOMA-IR (mean difference: -0.66; 95% CI: -1.06 to -0.26, P = 0.001) following vitamin D supplementation and significant increase in serum 25-hydroxyvitamin D levels [overall increase of 17 ± 2.4 ng/mL (42 ± 6 nmol/L)]. Conclusions: Vitamin D supplementation, a minimum dose of 100 µg/d (4000 IU/d), may significantly reduce serum FPG, HbA1c, and HOMA-IR index, and helps to control glycemic response and improve insulin sensitivity in type 2 diabetic patients.