Increase In 25-hydroxyvitamin Research Articles

Vitamin D and hyperemesis gravidarum: A mendelian randomization study

BackgroundThe causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method. MethodsIndependent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum. ResultsWe found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403–0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population. ConclusionsThe large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.

Abstract #1401609: A Case of Vitamin D Toxicity Associated with Weight Loss During a Low Carbohydrate Diet

Vitamin D is a commonly prescribed, fat-soluble vitamin important for calcium homeostasis and bone health. Vitamin D Toxicity (VDT) is rare and typically caused by aggressive supplementation or manufacturing errors. In epidemiologic studies, vitamin D levels correlate inversely with adiposity, and dietary weight loss is associated with increases in 25-hydroxyvitamin D [25(OH)D] level. Vitamin D is stored in adipose tissue and it is postulated that weight loss is a risk factor for the development of VDT. Here we present a case of VDT associated with weight loss during a low carbohydrate diet. A 74-year-old man with CKD stage 3a and benign prostatic hyperplasia presented to the ED with intractable emesis preceded by subacute nausea, anorexia, and constipation. He reported following a very low carbohydrate diet with intentional weight loss from 83.9kg (BMI 25.86) to 71.9kg (BMI 21.7) over five months. He reported taking Vitamin D3 250μg (10,000 IU) daily which was self-prescribed prior to admission for at least 12 months. On admission, he was mildly bradycardic and hypertensive. Laboratory evaluation in the ED revealed serum creatinine (sCr) 5.2 mg/dL (0.66-1.28, baseline 1.24 mg/dL 3 months prior), calcium 12.9 mg/dL (8.4-10.2), albumin 3.8 g/dL (3.2-4.8), and 25(OH)D >150 ng/dL (30-100). Intact PTH was suppressed at 13.2 pg/mL (14-72) and 1,25-dihydroxyvitamin D was 71 pg/mL (18-72). PTH-related protein, and serum and urine electrophoresis were within reference ranges. The patient was treated for hypercalcemia with intravenous fluids, prednisone 20mg daily, and on hospital day eight, intravenous pamidronate 30mg. Upon discharge on hospital day nine, calcium was 10.5 mg/dL. He was instructed to stop all vitamin D containing supplements. One month after discharge, sCr was 1.9 mg/dL and calcium was 8.7 mg/dL. Vitamin D is theorized to be stored in adipose tissue in clinically relevant quantities and released during weight loss. Due to the rare presentation of VDT in the setting of dietary weight loss, there are a limited number of cases described. Few clinical trials measuring serum 25(OH)D concentrations in people with obesity following weight loss have been performed. One study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss. Here we present a case of acute VDT causing symptomatic hypercalcemia after intentional dietary weight loss in the setting of chronic supratherapeutic vitamin D supplementation. As illustrated in this case, rapid weight loss in the setting of supratherapeutic doses of Vitamin D can result in VDT. Additional studies are needed to clarify the mechanisms that regulate the kinetics of vitamin D in the adipose tissue of persons with obesity.

Community pharmacy is the key to improving vitamin D levels

IntroductionVitamin D is an essential micronutrient that participates in the body's fundamental physiological processes. The pharmacist should involve the patient in his medication adherence, leading to a change in the patient's attitude towards his medication and towards his health problem, in order to achieve the pharmacological objective set. MethodsQuasi-experimental multicenter study design with non-probabilistic convenience sampling. A pharmacist-led intervention in health education was carried out, divided in two groups, face-to-face interview and on-line survey, and the results were evaluated 3 months later to observe if there was any change in the patient's health status or in their vitamin D levels. ResultsThe study was conducted in four pharmacies through face-to-face interviews (n = 49 patients) and online surveys (n = 23). Pharmaceutical intervention improved habits of exercise (0.81 ± 1.44 days/week face-to-face interviews vs −0.09 ± 2.35 days/week online surveys (p = 0.048)). In face-to-face interviews, consumption of vitamin D-rich foods was increased (0.55 unit of tuna/week; p = 0.035 and 0.56 unit of avocado/week; p = 0.001) and was improved correct intake of vitamin D supplements (32.5% baseline to 69.8% at 3 months). The increase in 25-hydroxyvitamin D levels (11.5 ng/mL after 3 months (p = 0.021)) was correlated to salmon consumption (0.951; p = 0.013) and the improvement of quality of life was correlated to avocado consumption (1; p < 0.001). ConclusionThere are habits that improve vitamin D production such as increased physical activity, the correct use of vitamin D supplements and the consumption of foods with high vitamin D levels. The role of the pharmacist is crucial, involving the patient in the treatment making aware of the benefits for his/her health status of increasing vitamin D levels.

Seasonal variations in vitamin D do not change the musculoskeletal health of physically active ambulatory men with cerebral palsy: a longitudinal cross-sectional comparison study

Increased levels of vitamin D in the summer months from natural seasonal variations in sun exposure have been linked to improvements in musculoskeletal health and function in UK populations; however, studies have shown that differences in lifestyles because of disability can inhibit the natural vitamin D increase in these populations. We hypothesized that men with cerebral palsy (CP) will experience smaller increases in 25-hydroxyvitamin D (25(OH)D) from winter to summer and men with CP will not experience any improvements in musculoskeletal health and function during the summer. A longitudinal observational study in 16 ambulant men with CP aged 21.0 ± 1.3 years and 16 healthy, physical activity matched, typically developed controls aged 25.4 ± 2.6 years, completed assessments of serum 25(OH)D and parathyroid hormone during winter and summer. Neuromuscular outcomes included vastus lateralis size, knee extensor strength, 10-m sprint, vertical jumps, and grip strength. Bone ultrasounds were performed to obtain radius and tibia T and Z scores. Men with CP and typically developed controls showed a 70.5% and 85.7% increase in serum 25(OH)D from winter to summer months, respectively. Neither group showed seasonal effect on neuromuscular outcomes muscle strength, size, vertical jump, or tibia and radius T and Z scores. A seasonal interaction effect was seen in the tibia T and Z scores (P < .05). In conclusion, there were similar seasonal increases in 25(OH)D observed in men with CP and typically developed controls, but serum 25(OH)D levels were still considered insufficient to improve bone or neuromuscular outcomes.

Influence of Vitamin D Status on the Maintenance Dose of Warfarin in Patients Receiving Chronic Warfarin Therapy.

IntroductionConsidering the anticoagulant actions of vitamin D, we hypothesize that vitamin D status might affect the required dose of warfarin for maintaining the therapeutic international normalized ratio (INR).MethodsIn a retrospective single-center cohort study, serum levels of 25-hydroxyvitamin D were assessed for 89 subjects receiving a stable dose of warfarin for 3 months or longer and had a stable INR between 2 and 3.5 for at least three consecutive visits. A warfarin sensitivity index (WSI), defined as the steady-state INR divided by the mean daily warfarin dose, was used for measuring the warfarin dose response. The relation between the serum level of 25-hydroxyvitamin D and WSI value and the difference in the mean WSI value between the subjects with different vitamin D status categories (sufficient, insufficient, and deficient) were assessed.ResultsTwenty-one subjects had vitamin D deficiency, 43 had vitamin D insufficiency, and only 25 had normal levels of 25-hydroxyvitamin D. Based on the multiple linear regression analysis, there was a significant but weakly positive correlation between WSI and 25-hydroxyvitamin D serum levels, as the value of WSI increases by almost 0.0027434 for every unit increase in 25-hydroxyvitamin D serum level (p value = 0.041). Using one-way ANOVA analysis, there was a trend in a significant difference between the groups with different vitamin D status categories regarding the mean WSI value (F = 2.95, p value = 0.057), as subjects with sufficient vitamin D state compared to those with vitamin D deficiency had a higher WSI value.ConclusionsAlthough the study’s limitations limit our ability to draw definite conclusions, the present data suggest that in addition to other traditional factors, vitamin D status might also affect warfarin sensitivity and maintenance dose requirement. However, to more clearly explain this link, further studies with high involvement subjects are required.

Evaluation effects of sleeve gastrectomy to bone metabolism and bone mineral densitometry in patients over 50 years

Background: Despite the improvement in health, function and quality of life of patients with morbid obesity following bariatric surgery, such intervention may result in some potential complications such as metabolic disturbances especially involving bone motabolism. The aim of this study was to evaluate the extent of Bone Mineral Density (BMD) changes in older patients with morbid obesity and its relation with bone metabolism indices. Methods: This study was a single-center cross-sectional study on 50 new morbidly obese patients over 50 years old of age who were candidates for bariatric surgery. Before and 6 months after surgery, the values of BMD, anthropometric indices and metabolic serum biomarkers were assessed. Results: BMD examination before and 6 months after surgery showed decrease in the BMD in hip region from 1.242 ± 0.136 to 1.117 ± 0.112 g/cm2, in the femoral neck from 1.109 ± 0.131 to 0.987 ± 0.127 g/cm2, in the lumbar spine from 1.253 ± 0.146 to 1.190 ± 0.135 g/cm2. The analysis of BMD changes showed significant decrease in the bone density of all site measurement but with variable amounts. The decrement of BMD in the hip and femoral neck was significant but in the spine was not significant. The analysis on bone metabolism markers showed significant increase in 25-Hydroxy vitamin D and Alkaline phosphatase levels but decrease in calcium and parathyroid hormone (PTH) during 6 month follow up. Conclusion: There is significant decrease in BMD at various skeletal areas including femoral neck and hip region. Such changes can be in line with the changes in some serum metabolic and hormonal biomarkers such as calcium, PTH, vitamin D and alkaline phosphatase.

Effect of Vitamin D Supplementation on Outcomes in People With Early Psychosis

People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes. To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP. This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019. Monthly augmentation with 120 000 IU of cholecalciferol or placebo. The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline. A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 to 4.94); Global Assessment of Function disability score (mean difference, -0.01; 95% CI, -5.25 to 5.23), or Calgary Depression Scale score (mean difference, -0.39; 95% CI, -2.05 to 1.26) at 6 months. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies. isrctn.org Identifier: ISRCTN12424842.

The impact of exogenous vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia

BackgroundEarly-onset androgenic alopecia is regarded as the phenotypic equivalent of polycystic ovary syndrome in men. Women with polycystic ovary syndrome are at high risk of autoimmune thyroiditis. The aim of the current study was to investigate whether early-onset androgenic alopecia determines the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in men with autoimmune thyroiditis.MethodsThe study included 67 young men with autoimmune thyroiditis, 25 of whom had early-onset androgenic alopecia (group A). All 25 men with alopecia and 23 out of the 42 men with no evidence of hair loss, matched for age, antibody titers and thyrotropin levels (group B), were then treated with vitamin D (100 μg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, total and calculated free testosterone, dehydroepiandrosterone-sulfate, estradiol, prolactin and 25-hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis were assessed before vitamin D treatment and 6 months later.ResultsAt baseline, thyroid antibody titers were higher in subjects with than without alopecia and correlated with calculated free testosterone levels. Vitamin D reduced antibody titers in both groups but this effect was stronger in group B than group A. Only in group B, vitamin D increased SPINA-GT. The impact of vitamin D on antibody titers correlated with 25-hydroxyvitamin D levels, calculated free testosterone, treatment-induced increase in 25-hydroxyvitamin D levels and the improvement in insulin sensitivity.ConclusionThis study suggests that euthyroid men with early-onset androgenic alopecia may benefit to a lesser degree from vitamin D treatment than other subjects with autoimmune thyroiditis.

The impact of hypotestosteronemia on cardiometabolic effects of atorvastatin in men with hypercholesterolemia: a pilot study.

BackgroundHypothyroidism, hyperprolactinemia, macroprolactinemia and low vitamin D status were found to impair pleiotropic effects of hypolipidemic agents. The aim of the current study was to investigate whether cardiometabolic effects of atorvastatin in men are determined by endogenous testosterone.MethodsWe studied three groups of men matched for age, BMI, plasma lipids and blood pressure: 19 untreated subjects with low testosterone levels (group A), 19 normotestosteronemic men receiving testosterone preparations (group B) and 21 untreated men with testosterone levels within the reference range (group C). Because of coexistent hypercholesterolemia, all subjects were managed with atorvastatin (40 mg daily) for 6 months. Glucose homeostasis markers, plasma lipids, as well as circulating levels of testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined at the beginning and at the end of the study.ResultsAt baseline, group A was more insulin-resistant and was characterized by higher levels of hsCRP, fibrinogen and homocysteine, and lower levels of 25-hydroxyvitamin D than the remaining groups of patients. Despite reducing total and low-density lipoprotein cholesterol and hsCRP levels in all treatment groups, this effect was stronger in groups B and C than in group A. In groups B and C, atorvastatin use was also associated with a decrease in uric acid, fibrinogen and homocysteine concentrations and with an increase in 25-hydroxyvitamin D levels. In group A, but not in the remaining groups, the drug decreased insulin sensitivity.ConclusionThe obtained results suggest that untreated hypotestosteronemia may attenuate cardiometabolic effects of atorvastatin in men.

Cholecalciferol therapy; is it the gold standard for vitamin D deficiency and mineral disorders in hemodialysis?

Introduction: Vitamin D deficiency is frequently observed among dialysis patients. Previous studies suggested that 50 to 90% of end-stage renal disease patients are deficient in vitamin D. In Tunisia, studies regarding hypovitaminosis D in patients on dialysis are not numerous. Actually, many data support the use of native vitamin D in hemodialysis (HD) patients. In Tunisia, using native vitamin D is not part of therapeutic habits of all dialysis centers. Objectives: The aim of this study was to determine the prevalence of vitamin D deficiency in patients with chronic kidney disease stage 5 undergoing HD and to evaluate the effect of oral cholecalciferol supplementation, in intact parathormone (iPTH), serum calcium and serum phosphorus. Patients and Methods: We conducted a pre-experimental study among HD patients. Monthly oral supplementation with Cholecalciferol, was instituted for six months. Results: Forty-three participants were included. The mean 25-hydroxy vitamin D concentration was 17.89 ng/mL. Vitamin D deficiency was observed in 83.7% of our patients. We observed a significant increase in 25-hydroxy vitamin D and calcium levels and a significant decline in iPTH levels. No evidence of toxicity, nor severe hypercalcemia or hyperphosphatemia was noted. Conclusion: The supplementation with cholecalciferol seems reasonable and well tolerated in HD patients if reasonable doses are used with regular monitoring.

Dehydroepiandrosterone potentiates the effect of vitamin D on thyroid autoimmunity in euthyroid women with autoimmune thyroiditis: A pilot study.

The impact of androgens on the thyroid in women is poorly understood. The aim of the present study was to investigate whether vitamin D/dehydroepiandrosterone (DHEA) combination therapy is superior to vitamin D alone in affecting thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroid disease. The study included 35 euthyroid women with untreated Hashimoto's thyroiditis and reduced sexual drive, allocated to one of two treatment groups. The first group (n=19) received both vitamin D and DHEA, while the second (n=16) was treated with only vitamin D. Serum thyroid antibody titres and concentrations of thyrotropin, free thyroid hormones, dehydroepiandrosterone-sulphate (DHEA-S), 25-hydroxyvitamin D, testosterone and estradiol were measured at baseline and 6months later. Vitamin D administered alone or in combination with DHEA decreased serum titres of thyroid peroxidase and thyroglobulin antibodies, which correlated with baseline antibody titres, baseline 25-hydroxyvitamin D levels and treatment-induced increase in 25-hydroxyvitamin D levels. Apart from a stronger effect on antibody titres, vitamin D/DHEA combination therapy slightly decreased thyrotropin levels, as well as increased DHEA-S and testosterone levels. In this group of women, treatment-induced changes in antibody titres and thyrotropin levels correlated with the impact on DHEA-S and testosterone. The obtained results suggest that vitamin D/DHEA combination therapy may be a better treatment option for euthyroid women with Hashimoto's thyroiditis than vitamin D alone.

Metabolomic basis for response to high dose vitamin D in critical illness

It is unclear if intervention can mitigate the dramatic alterations of metabolic homeostasis present in critical illness. Our objective was to determine the associations between increased 25-hydroxyvitamin D levels following high dose vitamin D3 and more favorable metabolomic profiles in critical illness. We performed a post-hoc metabolomics study of the VITdAL-ICU randomized double-blind, placebo-controlled trial. Trial patients from Medical and Surgical Intensive Care Units at a tertiary university hospital with 25-hydroxyvitamin D level ≤20ng/mL received either high dose oral vitamin D3 (540,000 IU) or placebo. We performed an analysis of 578 metabolites from 1215 plasma samples from 428 subjects at randomization (day 0), day 3 and 7. Using mixed-effects modeling, we studied changes in metabolite profiles in subjects receiving intervention or placebo relative to absolute increases in 25-hydroxyvitamin D levels from day 0 to day 3. 55.2% of subjects randomized to high dose vitamin D3 demonstrated an absolute increase in 25-hydroxyvitamin D≥15ng/ml from day 0 to day 3. With an absolute increase in 25-hydroxyvitamin D≥15ng/ml, multiple members of the sphingomyelin, plasmalogen, lysoplasmalogen and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time. Further, multiple representatives of the acylcarnitine and phosphatidylethanolamine metabolite classes had significantly negative Bonferroni corrected associations over time with an absolute increase in 25-hydroxyvitamin D≥15ng/ml. Changes in these highlighted metabolite classes were associated with decreased 28-day mortality. Increases in 25-hydroxyvitamin D following vitamin D3 intervention are associated with favorable changes in metabolites involved in endothelial protection, enhanced innate immunity and improved mitochondrial function.

The impact of combination therapy with metformin and exogenous vitamin D on hypothalamic-pituitary-thyroid axis activity in women with autoimmune thyroiditis and high-normal thyrotropin levels.

Metformin was found to decrease thyrotropin levels in subjects with non-autoimmune but not with autoimmune hypothyroidism. Vitamin D reduced thyroid autoimmunity without affecting thyrotropin and thyroid hormone levels. The aim of the current study was to investigate whether exogenous vitamin D modulates the impact of metformin on hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroiditis. This case-control study included 32 prediabetic women with Hashimoto's thyroiditis, high-normal thyrotropin levels (2.5-4.5mIU/L) and vitamin D insufficiency. Based on patient preference, these individuals received either metformin (3g daily) plus vitamin D (4000IU daily) (n=17) or were treated with only metformin (3g daily) (n=15). Plasma levels of glucose, serum levels of insulin, thyrotropin, total and free thyroid hormones and 25-hydroxyvitamin D, as well as serum titres of thyroid antibodies, were assessed at baseline and 6months later. Thirty-one women completed the study. At baseline, there were no differences between the treatment groups. In both study arms, metformin reduced plasma glucose levels and improved insulin sensitivity but this effect was stronger in subjects receiving vitamin D. Only metformin administered with vitamin D decreased thyrotropin levels, increased 25-hydroxyvitamin D levels and reduced thyroid antibody titres. The impact on thyrotropin and antibody titres correlated with the increase in 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. This study has shown for the first time that exogenous vitamin D potentiates the impact of metformin on thyrotropin levels in women with autoimmune thyroiditis.

An Update on Vitamin D and Disease Activity in Multiple Sclerosis.

Vitamin D and its main active metabolite 1,25-dihydroxyvitamin D serve a crucial role in maintenance of a healthy calcium metabolism, yet have additional roles in immune and central nervous system cell homeostasis. Serum levels of 25-hydroxyvitamin D are a biomarker of future disease activity in patients with early relapsing–remitting multiple sclerosis (RRMS), and vitamin D supplementation in patients with low circulating 25-dihydroxyvitamin D levels has been anticipated as a potential efficacious treatment strategy. The results of the first large randomized clinical trials (RCTs), the SOLAR and CHOLINE studies, have now been published. The SOLAR study compared 14,000 IU of vitamin D3 (cholecalciferol) per day with placebo for 48 weeks in 232 randomized patients, whereas CHOLINE compared vitamin D3 100,000 IU every other week with placebo for 96 weeks in 129 randomized patients. All patients in both studies also used interferon-β-1a. None of the studies met their primary endpoints, which were no evidence of disease activity (NEDA-3) at 48 weeks in SOLAR and annualized relapse rate at 96 weeks in CHOLINE. Both studies did, however, suggest modest effects on secondary endpoints. Thus, vitamin D reduced the number of new or enlarging lesions and new T2 lesions in SOLAR, and the annualized relapse rate and number of new T1 lesions, volume of hypointense T1 lesions, and disability progression in the 90 patients who completed 96 weeks’ follow-up in CHOLINE. We conclude that none of the RCTs on vitamin supplementation in MS have met their primary clinical endpoint in the intention to treat cohorts. This contrasts the observation studies, where each 25 nmol/l increase in 25-hydroxyvitamin D levels were associated with 14–34% reduced relapse risk and 15–50% reduced risk of new lesions on magnetic resonnance imaging. This discrepancy may have several explanations, including confounding and reverse causality in the observational studies. The power calculations of the RCTs have been based on the observational studies, and the RCTs may have been underpowered to detect less prominent yet important effects of vitamin D supplementation. Although the effect of vitamin D supplementation is uncertain and less pronounced than suggested by observational studies, current evidence still support that people with MS should avoid vitamin D insufficiency, and preferentially aim for vitamin D levels around 100 nmol/L or somewhat higher.

Temporal increases in 25-hydroxyvitamin D in midlife women: Longitudinal results from the Study of Women's Health Across the Nation.

25-hydroxyvitamin D (25(OH)D) is critical for bone mineralization and may prevent fractures. Understanding vitamin D deficiency trends in midlife women is particularly important given their concurrent menopausal changes that increase risk for fracture. We aimed to evaluate changes in mean 25(OH)D over time and their determinants in a racially, ethnically and socioeconomically diverse cohort of midlife women. A multi-centre prospective cohort study. 1585 women ages 42-52years at baseline. We measured serum 25(OH)D at 2 time points (1998-2000 and 2009-2011). Between-visit change was assessed in the whole cohort and in socioeconomic and demographic subgroups. Among those with vitamin D deficiency (25(OH)D <30nmol/L) at baseline, we evaluated determinants of persistent deficiency at follow-up. Mean 25(OH)D increased from 53.8 to 70.0nmol/L (P<0.001), and the prevalence of deficiency decreased from 20.4% to 9.7% (P<0.001). While baseline 25(OH)D differed among subgroups, the changes in 25(OH)D were similar among groups. The proportion of women reporting dietary supplement use increased from 40.8% to 67.1% (P<0.001), and the increase in 25(OH)D was significantly higher in supplement users. Among women with vitamin D deficiency at baseline, White women and supplement users were less likely to remain deficient at follow-up. Among midlife women, temporal increases in 25(OH)D concentrations are driven largely by increases in supplement use. The proportion of women with 25(OH)D <30nmol/L and thus at high risk for skeletal consequences remains substantial. Targeted screening for vitamin D deficiency in populations at risk for fragility fracture may be advisable.

25-Hydroxyvitamin D Levels and the Risk of Dementia and Alzheimer's Disease: A Dose-Response Meta-Analysis.

Background and Purpose: Conclusions of previous cohort studies on the relationship between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease were not consistent. Thus, we performed a dose–response meta-analysis to evaluate this relationship by summarizing cohort studies.Methods: Pubmed, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Cohort studies concerning the association between 25-hydroxyvitamin D level and dementia or Alzheimer's disease were included. Results of studies were pooled and the dose–response relationship was determined using a random-effect model.Results: Ten cohort studies, with 28,640 participants were included. A significant inverse relationship was found between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease. In addition, we found a linear dose–response relationship in that a 10 nmol/L increase in 25-hydroxyvitamin D level may lead to a 5% decrease in the risk of dementia (relative risk, 0.95; 95% confidence interval, 0.93–0.98) and 7% in the risk of Alzheimer's disease (relative risk, 0.93; 95% confidence interval, 0.89–0.97).Conclusion: Plasma or serum 25-hydroxyvitamin D concentration was inversely related to the risk of dementia and Alzheimer's disease, consistent with a linear dose–response relationship.

The Association of Fibroblast Growth Factor-23 with Mineral Factors (Ca, P, and Mg), Parathyroid Hormone, and 25-Hydroxyvitamin D in Hemodialysis Patients: A Multicenter Study

Background: Fibroblast growth factor-23 (FGF23) is a phosphaturic factor that is released from bone. A variety of bone diseases can occur in renal diseases. Objectives: This study aimed to investigate the association of FGF23 with mineral factors, PTH, and 25-hydroxyvitamin D among hemodialysis patients. Methods: This cross-sectional multicenter study was performed on 135 patients aged 18 years or over with end-stage renal disease treated with hemodialysis maintenance. FGF-23, phosphorus, Ca, Mg, PTH, 25-hydroxyvitamin D, Uric Acid, Na, and K were measured in each patient’s fasting blood sample. We used univariate and multivariate linear regressions. Results: The mean age of patients was 56.45 ± 13.64 years. The mean and median FGF23 concentration in patients were 855.07 ± 43.33 and 762.6 (IQR = 456.6 - 1430.3) pg/mL, respectively. Different variables did not show any significant difference between the two sexes. After adjustment for age, sex, dialysis time, uric acid, Na, K, and kt/V, FGF23 had a linear association with 25-hydroxyvitamin D and every 10-unit (pg/mL) increase in FGF23 was significantly associated with a 0.03 mg/mL increase in 25-hydroxyvitamin D (P = 0.04). In addition, other variables showed no significant association with FGF23. Conclusions: According to the results, FGF23 had a linear association with vitamin D and an increase in FGF23 was significantly associated with an increase in vitamin D. In addition, there was no significant association between mineral factors and PTH, and FGF23.

Price of High-Throughput 25-Hydroxyvitamin D Immunoassays: Frequency of Inaccurate Results.

With a 10-year sustained increase in 25-hydroxyvitamin D [25(OH)D] testing, laboratories have swapped their LC-MS/MS methods for high-throughput automated immunoassays. Although it is generally well-known that immunoassays have poor recoveries for 25-hydroxyvitamin D2 [25(OH)D2], the frequency and extent to which this impacts total 25(OH)D have not been previously demonstrated. We evaluated 3 automated immunoassays against the first FDA-cleared CDC/NIST-traceable LC-MS/MS method. Method comparison was performed for the Siemens ADVIA Centaur, Roche Elecsys Cobas, and Abbott Architect 25(OH)D immunoassay methods in real patient samples (n = 105). We calculated the mean bias in samples containing >20 ng/mL 25(OH)D2 and estimated the percent 25(OH)D2 cross-reactivities. We determined the prevalence of appreciable concentrations of 25(OH)D2 in our patient population through random sampling (n = 120) and projected the frequency of inaccurate 25(OH)D immunoassay results. Linear regression for 25(OH)D was y = 1.09x - 4.44 (Centaur), y = 0.84 + 0.43 (Cobas), and y = 0.83x - 0.48 (Architect). The mean biases of 25(OH)D concentrations were 5.6 (11.0) ng/mL (Centaur), -17.5 (7.2) ng/mL (Cobas), and -20.3 (9.8) ng/mL (Architect) in samples containing >20 ng/mL 25(OH)D2. The observed percent cross-reactivities for 25(OH)D2 were 115% (Centaur), 52% (Cobas), and 44% (Architect). We estimate that 8% of our population has >20 ng/mL 25(OH)D2, thereby compromising the accuracy of 25(OH)D results in >3000 samples annually. We demonstrate that immunoassay manufacturer package inserts indicate much better recoveries of 25(OH)D2 than what is observed in unadulterated real patient samples. We estimate the frequency of inaccurate total 25(OH)D determination by these immunoassay methods to be largely dependent on the concentration of 25(OH)D2 in each sample.

Prospective cohort study of vitamin D and autism spectrum disorder diagnoses in early childhood.

Several studies have suggested an association between vitamin D in childhood and autism spectrum disorder. No prospective studies have evaluated whether lower vitamin D levels precede ASD diagnoses - a necessary condition for causality. The objective of this study was to prospectively evaluate whether vitamin D serum levels in early childhood was associated with incident physician diagnosed ASD. A prospective cohort study was conducted using data from preschool-aged children in the TARGet Kids! practice-based research network in Toronto, Canada, from June 2008 to July 2015. 25-hydroxyvitamin D concentration was measured through blood samples and vitamin D supplementation from parent report. Autism spectrum disorder diagnosis was determined from medical records at follow-up visits. Covariates included age, sex, family history of autism spectrum disorder, maternal ethnicity, and neighborhood household income. Unadjusted and adjusted relative risks and 95% confidence intervals were estimated using Poisson regression with a robust error variance. In this study, 3852 children were included. Autism spectrum disorder diagnosis was identified in 41 children (incidence = 1.1%) over the observation period (average follow-up time = 2.5 years). An association between 25-hydroxyvitamin D concentration and autism spectrum disorder was not identified in the unadjusted (relative risk = 1.04, 95% confidence interval: 0.97, 1.11 per 10 nmol/L increase in 25-hydroxyvitamin D concentration) or adjusted models (adjusted relative risk = 1.06; 95% confidence interval: 0.95, 1.18). An association between vitamin D supplementation in early childhood and autism spectrum disorder was also not identified (adjusted relative risk = 0.86, 95% confidence interval: 0.46, 1.62). Vitamin D in early childhood may not be associated with incident physician diagnoses of autism spectrum disorder.

Sun Exposure and Behavioral Activation for Hypovitaminosis D and Depression: A Controlled Pilot Study.

Several independent meta-analytic reviews suggest a relationship between vitamin D (VTD) deficiency and depressive symptoms. Theoretically, behavioural withdrawal (staying home, discontinuing outdoor activities etc.) is likely to exacerbate VTD deficiency. This pilot study assessed the efficacy of a modified form of behavioral therapy designed to simultaneously target VTD deficiency and depressive symptoms. College women (N = 114), all citizens of the United Arab Emirates, were screened for depressive symptoms and VTD deficiency. Those participants who were severely VTD deficient and experiencing clinically significant depressive symptoms, were randomly allocated to either a 12-week program of behavioral activation, emphasizing safe-sun exposure (N = 10), or a waiting list control group (N = 10). At time 2 the sun exposure and behavioral activation (SEBA) group showed a significant increases in 25-hydroxyvitamin D and were, on average, no longer VTD deficient, whereas the control group deteriorated in terms of VTD. Similarly positive results were observed for depressive symptoms. Sun exposure and behavioral activation (SEBA) may be an effective approach to improving VTD status and alleviating depressive symptoms.