Higher 25-hydroxyvitamin Research Articles

Efficacy of Vitamin-D supplementation in improving the prognosis of H-type hypertension in elderly patients.

To investigate the correlation between 25-hydroxyvitamin D and H-type hypertension in elderly patients, and to observe the clinical efficacy of vitamin D supplementation in those patients. This was a retrospective study. One hundred and twenty elderly hypertensive patients treated at The Affiliated Hospital of Hebei University from June 2022 to June 2023 were randomly divided into Group-A (n=60) with hypertension and elevated homocysteine (Hcy) levels (H-type hypertension), and Group-B(n=60) with hypertension and normal Hcy levels. Blood levels of 25-hydroxyvitamin D and 24 hours ambulatory blood pressure were assessed in both groups of patients upon admission, with the correlation analysis performed simultaneously. The therapeutic effects were compared between the two groups. Through Pearson correlation analysis, there were negative correlations of serum 25-hydroxyvitamin D levels with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP(all p<0.05). After 12 weeks of treatment, the treatment group had higher 25-hydroxyvitamin D levels and lower 24 hours SBP, 24h DBP, dSBP, dDBP, nSBP, nDBP levels than those of the control group(p<0.05). After treatment, the treatment group had lower blood Hcy, IMT, TC, TG, and LDL-C levels(p<0.05), and higher HDL-C levels(p<0.05) than those of the control group. Serum 25-hydroxyvitamin D levels in elderly patients with H-type hypertension have negative correlations with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP. Oral vitamin D supplementation for H-type hypertensive patients exhibits significant therapeutic effects, with improvements in 24 hours ambulatory blood pressure monitoring results, blood lipid levels, IMT, and blood Hcy levels after treatment.

5043 Skeletal Microstructure in Men with Celiac Disease

Abstract Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p&amp;lt;0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were &amp;lt; 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p&amp;lt;0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD. Presentation: 6/3/2024

The Safety Profile of Vitamin D Supplements Using Real-World Data from 445,493 Participants of the UK Biobank: Slightly Higher Hypercalcemia Prevalence but Neither Increased Risks of Kidney Stones nor Atherosclerosis.

Background: Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

Low 25-hydroxyvitamin D concentrations in wild rabbits (Oryctolagus cuniculus) in southern Finland

BackgroundDiet and endogenous vitamin D synthesis are possible sources of vitamin D in wild rabbits. Higher 25-hydroxyvitamin D (25(OH)D) concentrations have been reported in rabbits after artificial UVB light exposure than in rabbits without this exposure, suggesting that endogenous vitamin D synthesis occurs in the former group. In Finnish pet rabbits, diet was reported as main source of vitamin D, while outdoor access was not. Finland’s northern location only enables endogenous synthesis from mid-March to mid-October in people with light skin type. Living conditions during winter are challenging for Finnish wild rabbits. This study aimed to measure serum 25(OH)D concentrations and possible natural seasonal variation of vitamin D concentrations in Finnish wild rabbits.ResultsPost-mortem blood samples (n = 78) were collected between 2013 and 2021 from wild rabbits hunted for reduction of the wild rabbit population. Separated sera were stored at − 80 °C until 25(OH)D concentrations were measured by enzyme immunoassay. Data regarding sex were available from 50 rabbits, 29 (58%) of which were females. Mean 25(OH)D concentration was 3.3 (range 0.3–7.1) ng/ml. 25(OH)D concentration was statistically similar between season (autumn, winter, summer), month or year of sample collection, and sex.ConclusionsWild rabbits living in Finland have very low serum 25(OH)D concentrations. This is far below the previously suggested threshold of vitamin D deficiency in rabbits (17 ng/mL) or the mean 25(OH)D concentration reported in Finnish pet rabbits (26.0 ng/mL). Seasonal variation was not observed in 25(OH)D concentrations between winter and summer months. Even though rabbits are crepuscular animals and may spend the mid-day in underground burrows, the very low observed 25(OH)D concentrations raise doubt about whether vitamin D synthesis occurs efficiently in the skin of rabbits and whether the diet of wild rabbits provides adequate amounts of vitamin D. Cutaneous vitamin D synthesis, possible long-term consequences of low 25(OH)D concentrations, and the association of low vitamin D status with other health disorders warrant further investigations in rabbits.

Vitamin D and human health: evidence from Mendelian randomization studies.

We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.

High serum 25-hydroxyvitamin D levels are associated with greater lean tissue mass and skeletal muscle mass:a cross-sectional study on young healthy Japanese women.

Studies have shown that low serum 25(OH)D levels in young women may affect not only their own health but also the health of next generation through pregnancy and childbirth. The aim of this study is to assess the serum 25(OH)D levels in young Japanese women and to determine the factors influencing the changes in their serum 25(OH)D levels. Herein, 83 healthy young Japanese women were included. Early morning fasting blood samples, habitual food intake survey, eating habits survey, and anthropometric measurements were used to analyze the relationship between the serum 25(OH)D levels and nutrient intake, intake of food groups, dietary habits, and body composition. The findings revealed that about 50% of the study participants had an adequate intake (AI) of vitamin D (8.5 µg), whereas about 88% of the study participants were vitamin D deficient and about 12% were insufficient in serum 25(OH) levels. No significant association was observed between the serum 25(OH)D levels and nutrient intake or intake of food groups. Furthermore, higher serum 25(OH)D levels were associated with higher percentages of muscle and lean tissue, indicating that regulating the serum 25(OH)D levels helps maintain muscle mass and lowers the risk of sarcopenia and locomotive syndrome. J. Med. Invest. 71 : 260-266, August, 2024.

Serum 25-hydroxyvitamin D, type 2 diabetes, and liver-related outcomes: Secondary data analysis of a prospective recruited cohort.

The association of vitamin D deficiency, which is prevalent in type 2 diabetes mellitus (T2DM), with liver disease and related mortality has not been quantified. Our study aimed to (1) investigate whether there is a synergistic association of vitamin D deficiency and T2DM with liver-related outcomes and (2) explore whether high 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a lower risk of liver-related outcomes in T2DM. Leveraging the data from UK Biobank, we conducted 2 studies: study I assessed the joint associations of vitamin D deficiency [25(OH)D <50nmol/L] and T2DM with liver-related outcomes among 439,276 participants, and study II explored the associations of vitamin D status with liver-related outcomes among 21,519 individuals with T2DM. Baseline T2DM was identified through medication, laboratory test, and electronic health-related records. Serum 25(OH)D was measured by direct competitive chemiluminescent immunoassay. Liver-related outcomes included 6 liver disease end points and mortality by overall liver disease, chronic liver disease, and severe liver disease. During an average follow-up duration of 11.6 years, we observed a significant positive additive interaction effect (all synergy index>1.0) of T2DM and vitamin D deficiency on the risk of liver-related outcomes. Compared with participants without either T2DM or vitamin D deficiency, the multivariable-adjusted HRs of overall liver diseases were 1.29 for participants without T2DM but with vitamin D deficiency, 1.73 for participants with T2DM but without vitamin D deficiency, and 2.19 for participants with both T2DM and vitamin D deficiency. In individuals with T2DM, we observed that participants without vitamin D deficiency were inversely associated with incident liver disease and related mortality (multivariable-adjusted HRs 0.41-0.81) when compared with individuals with vitamin D deficiency. There are positive synergistic associations of vitamin D deficiency and T2DM with liver-related outcomes. Inverse associations between serum 25(OH)D concentrations and liver-related outcomes were observed in individuals with T2DM.

THU406 24-hydroxylase Deficiency, A Rare Cause Of Hypercalcemia

Abstract Disclosure: J. Hodge: None. M. Gortakowski: None. N. Barua: None. Background: 24-hydroxylase is encoded by CYP24A1 and functions to convert 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D to their inactive metabolites[1]. 24-hydroxylase deficiency due to CYP24A1 variants is rare and clinical presentation is characterized by hypercalcemia, nephrolithiasis and nephrocalcinosis. Treatment may include thiazide diuretics, sodium cellulose phosphate and ketoconazole.[1] We present a case of hypercalcemia due to 24-hydroxylase deficiency. Clinical Case: A 56-year-old male with chronic kidney disease initially presented with hypercalcemia at age 48 to another institution. He was initially diagnosed with primary hyperparathyroidism in the setting of an inappropriately normal parathyroid hormone (PTH) with hypercalcemia. He subsequently had one parathyroid gland removed a year after diagnosis, then another two years later due to continued hypercalcemia. However, he continued to have persistent hypercalcemia, 10.9-12.7 mg/dL but now in the setting of low PTH. In addition, his 1,25 dihydroxyvitamin D was high normal and 25-hydroxyvitamin D was high off exogenous vitamin D supplementation, which raised the suspicion for 24-hydroxylase deficiency. He presented to our institution eight years later. Initial evaluation revealed, calcium 12.4 (8.6-10.5 mg/dL), phosphorous 2.9 (2.5-4.5 mg/dL), normal albumin, PTH 13 (15-65 pg/mL), 1,25 dihydroxyvitamin D 87.2 (19-79.3 pg/mL) and 25-hydroxyvitamin D 38.3 (20-50 ng/mL), 24hr urine calcium 0.23 (0.05-0.30 g/24hr), fractional excretion calcium 0.02. His 25-hydroxyvitamin D:24,25 dihydroxy vitamin D ratio was unable to be calculated, since 24,25 dihydroxy vitamin D was below the limit of quantification. He also had evidence of nephrocalcinosis on renal ultrasound. Evaluation of other causes of non-PTH mediated hypercalcemia included normal angio converting enzyme, PTHrP level, vitamin A level, SPEP and UPEP. Chest X-ray did not demonstrate any evidence of granulomatous disease. He has been managed conservatively for suspected 24-hydroxylase deficiency. He has been advised to limit calcium and vitamin D intake, as well as sun exposure, with close monitoring of his calcium levels. His calcium levels have ranged from 10.7-12.4 mg/dL and he has had one hospitalization in the setting of heart failure where his calcium levels improved with furosemide to 8.7-9.9 mg/dL. Conclusion: In patients with persistent non-PTH dependent hypercalcemia, 24-hydroxylase deficiency should be a differential diagnosis when other common causes are excluded.

Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Prediagnostic 25-Hydroxyvitamin D in Association with Cancer-specific and All-cause Mortality among Low-income, Non-Hispanic Black Americans with Colorectal Cancer.

Observational studies show high prediagnosis 25-hydroxyvitamin D is associated with lower mortality after colorectal cancer diagnosis. Results from clinical trials suggest vitamin D supplementation may improve outcomes among patients with colorectal cancer. Most studies included few Black Americans, who typically have lower 25-hydroxyvitamin D. We evaluated associations between serum 25-hydroxyvitamin D and mortality after colorectal cancer diagnosis among Black American cases. Data arose from 218 Black Americans from the Southern Community Cohort Study diagnosed with colorectal cancer during follow-up (age 40-79 at enrollment). Prediagnostic 25-hydroxyvitamin D was measured at enrollment and categorized as deficient (<12 ng/mL), insufficient (12-19.9 ng/mL), or sufficient (≥20 ng/mL). Mortality was determined from the National Death Index. Cox proportional hazards were used to estimate HRs and 95% confidence intervals (CI) for associations between 25-hydroxyvitamin D and mortality. As a continuous exposure, higher 25-hydroxyvitamin D was associated with overall mortality [HR = 0.79 (0.65-0.96) per-SD increase, Ptrend = 0.02] and colorectal cancer-specific mortality [HR = 0.83 (0.64-1.08), Ptrend = 0.16]. For overall mortality, associations were strongest among females [HR = 0.65 (0.42-0.92)], current smokers [HR = 0.61 (0.38-0.98)], and obese participants [HR = 0.47 (0.29-0.77)]. Compared with those with deficiency, participants with sufficient 25-hydroxyvitamin D had lower overall mortality after multivariable adjustment [HR: 0.61 (0.37-1.01)]. Prediagnosis 25-hydroxyvitamin D is inversely associated with overall and colorectal cancer-specific mortality among Black Americans with colorectal cancer. Correcting vitamin D deficiency may improve survival of these patients, particularly for obese individuals and smokers. Our results support including more Black Americans in trials of vitamin D supplementations to improve colorectal cancer outcomes.

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.

Associations between serum vitamin D biomarkers and tumor expression of Ki67, p53, and COX-2 in colorectal cancer cases from the Southern Community Cohort Study

Higher 25-hydroxyvitamin D is associated with lower colorectal cancer (CRC) risk, with limited data from African Americans (AAs), who have greater risk for CRC and 25-hydroxyvitamin D deficiency. In a predominantly AA sample of CRC cases from the Southern Community Cohort Study (SCCS), we report associations between vitamin D biomarkers and tumor expression of proteins implicated in vitamin D’s anti-tumorigenic pathways (e.g. proliferation and inflammation) and CRC prognosis. SCCS participants with incident CRC were identified via state cancer registries. Serum 25-hydroxyvitamin D and vitamin D binding protein (VDBP) were measured at enrollment. ‘Free’ 25-hydroxyvitamin D was calculated via standard equation. Cellular Ki67, p53, and COX-2 were measured from tumor samples and categorized using literature-defined cut-points related to survival. Generalized linear models were used to measure associations between vitamin D exposures, tumor biomarkers, and stage. In total, 104 cases (40–79 years) were analyzed. 25-hydroxyvitamin D was not associated with high Ki67 (odds ratio (OR) per 1-standard deviation (SD) increase [95% confidence interval] 1.35[0.86–2.11]), p53 (0.75[0.47–1.20]), or COX-2 expression (1.25[0.78–2.01]), or metastatic disease (1.04[0.59–1.81]). Mean biomarker expression was unrelated to 25-hydroxyvitamin D (p-trend ≥.09). Null associations were observed for VDBP and free 25-hydroxyvitamin D. In AAs (n = 70), higher VDBP was associated with lower odds of high Ki67 expression (0.53[0.28–0.98], p-trend =.04). In conclusion, we observed no associations between 25-hydroxyvitamin D and prognostic marker expression in CRC. An inverse association between VDBP and tumor Ki67 in AAs is consistent with reports showing relationships with reduced CRC mortality.

Low serum 25-hydroxyvitamin D (vitamin D) level among children with ventricular septal defect: how big is the risk for pulmonary hypertension?

Ventricular septal defect is the most common CHD, leading to pulmonary hypertension. Significantly lower 25-hydroxyvitamin D level was reported in children with CHD compared with healthy controls. The current study aimed to investigate the correlation between 25-hydroxyvitamin D level and pulmonary hypertension in children with ventricular septal defect. A cross-sectional study was conducted on ventricular septal defect paediatric patients from January to June, 2019. Serum 25-hydroxyvitamin D was measured using electrochemiluminescence. Pulmonary hypertension was defined as mean pulmonary artery systolic pressure > 20 mmHg for children >3 months of age at sea level, measured by Doppler echocardiography. From forty-four subjects, the majority of the subjects were female (56.8%) with normal nutritional status and perimembranous ventricular septal defect. Bivariate analysis showed that 25-hydroxyvitamin D level was associated with pulmonary hypertension (p < 0.01), type and size of ventricular septal defect (p = 0.02), and heart failure (p < 0.01). Higher 25-hydroxyvitamin D level was correlated with better nutritional status (p = 0.04, r = 0.26), and lower 25-hydroxyvitamin D level was correlated with the occurence of perimembranous ventricular septal defect (p = 0.01, r = -0.39), larger defect size (p < 0.01, r = -0.70), history of pneumonia (p = 0.02, r = -0.31), and heart failure (p < 0.01, r = -0.64). Subjects with 25-hydroxyvitamin D deficiency had prevalence ratio of 24.0 times for pulmonary hypertension. Higher pulmonary artery pressure was correlated to the occurence perimembranous ventricular septal defect (p = 0.01, r = 0.47), larger defect size (p < 0.01, r = 0.78), history of pneumonia (p = 0.01, r = 0.38), and heart failure (p < 0.01, r = 0.75). Children with ventricular septal defect who had low 25-hydroxyvitamin D level posed a higher risk of having pulmonary hypertension.

Safety of Vitamin D Food Fortification and Supplementation: Evidence from Randomized Controlled Trials and Observational Studies.

The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was <10% when vitamin D supplements were administered, and <0.1% for fortified foods. Elevated serum calcium was observed among <0.5% in both administration types. No ODIN RCT participants exceeded the age-specific ULs. In observational studies (n = 61,082), the prevalence of high 25(OH)D among children/adolescents, adults, and older adults was <0.3%, with no evidence of adverse effects. In conclusion, high S-25(OH)D concentrations >125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.

Relatively low and moderate pre-fracture serum 25-hydroxyvitamin D levels associated with the highest survival in elderly hip fracture patients in Finland: a minimum 3-year follow-up.

SummaryThe association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50–74 nmol/L.PurposeTo explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland.MethodsA prospectively collected cohort of hip fracture patients (n = 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified: < 50, 50–74, 75–99, and ≥ 100 nmol/L. Survival was analyzed with a Bayesian multivariate model. Relative survival was explored with the life table method according to serum 25-hydroxyvitamin D. Mortality according to serum 25-hydroxyvitamin D level and to the hospital was calculated.ResultsMortality in the patients with serum 25-hydroxyvitamin D level of 50–74 nmol/L was significantly lower than in all other patients together at every post-fracture year. The most important factors for survival were age under 85 years; living in an actual/private home; serum 25-hydroxyvitamin D level of 50–74 nmol/L, followed by 75–99 nmol/L; ASA classes 1–2 and 3; and female sex. The mean age of patients with serum 25-hydroxyvitamin D level of 50–99 nmol/L was significantly higher than in other levels. Relative survival was highest in men, women, and patients in hospital B with serum 25-hydroxyvitamin D level of 50–74 nmol.ConclusionThe highest 3-year survival and the lowest mortality in this cohort appeared in patients with pre-fracture serum 25-hydroxyvitamin D level of 50–74 nmol/L. This result differs from similar studies and is lower than the recommended level of 25-hydroxyvitamin D among hip fracture patients. The results should be examined in future research with larger data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00198-021-06094-z.

Neonatal nicotine exposure changes insulin status in fat depots: sex-related differences.

Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRβ), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRβ, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer’s disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial

BackgroundThe vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population.MethodsWe conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence.ResultsForty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3–43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5–29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11–0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial.ConclusionsPre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose.Trial registrationClinicalTrials.gov, NCT01838447. Registered on April 24, 2013

Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis.

A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases. Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

The effect of lipid disturbance and vitamin D on the fertility in male albino rats

ABSTRACT Background: Vitamin D has multiple biological effects on male reproductive system. Vitamin D deficiency (VD−) and disturbance of lipid metabolism can induce changes in testicular hormone production and seminal parameters that relate to male infertility. Objective: To investigate the role of vitamin D and lipid metabolism on fertility in male albino rats. Methods: The study was performed on 60 male rats, divided into 6 groups; GI: control group, GII: orlistat group, GIII: orlistat and vitamin D group, GIV: hyperlipidemic group, GV: hyperlipidemic orlistat group and GVI: hyperlipidemic orlistat and vitamin D group. Serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c), 25-hydroxyvitamin D (25(OHD), testosterone (T), inhibin B, follicle-stimulating hormone (FSH) and estradiol (E) levels were determined. Sperm count and viability were also analyzed. Results: Administration of orlistat in GII caused significant alterations of the serum lipid profile, compared to control group. There was interaction between dietary fat and VD− on serum 25 (OHD). A significant VD− was occurred in both GII and GIV, compared to GI. VD− in these groups consequently caused significant decrease in serum T, inhibin B, sperm count and viability and significant increase in FSH and E levels. Administration of orlistat in GV caused significant changes in serum lipid profile, a decrease in E, increase in 25(OHD) and inhibin B, compared to IV. On the other hand, administration of vitamin D with orlistat in GIII and GVI caused significant increase in HDL-c, 25(OHD), T, sperm count and viability and significant decrease in TC, TG, LDL-c, FSH and E. Conclusion: Both hyperlipidemia and hypolipidemia were associated with vitamin D deficiency. Moreover, vitamin D has a positive potential effect on male fertility in either hyperlipidemic or hypolipidemic rats.