Serum Total 25-hydroxyvitamin Research Articles

Total and bioavailable 25-hydroxyvitamin D is not associated with improved sexual dysfunction following vitamin D supplementation in women with polycystic ovarian syndrome: a pilot study.

Vitamin D (Vit D) deficiency has been linked to symptoms of polycystic ovary syndrome (PCOS), yet little is known about Vit D supplementation as a treatment for sexual dysfunction (SDy) in women with PCOS. To explore the implications of serum total 25-hydroxyvitamin D (25[OH]D) and bioavailable 25[OH]D (bio-25[OH]D) status and replacement on women with PCOS and SDy. Reproductive-age women with PCOS who were not desiring fertility were eligible provided that they also had SDy, as assessed by the Female Sexual Function Index (FSFI), and were without severe depression, as evaluated by the Beck Depression Inventory II (BDI-II). Participants were given the recommended dietary allowance of Vit D (600IU daily) plus hormonal contraception (HC; cyclic ethinyl estradiol/drospirenone) or no HC for 6months. Comparisons between groups were analyzed by chi-square test and t-test, and Pearson's correlation coefficient analyzed correlations between FSFI with demographics, BDI-II, androgen levels, and total and bio-25[OH]D. The outcomes included SDy (FSFI <26.55), total and serum bio-25[OH]D levels, and total and free testosterone. A total of 42 women without severe depression completed the FSFI, with 28 (66.7%) having SDy. All FSFI domains, including arousal, lubrication, orgasm, and pain, were significantly lower as compared with women without SDy, with no associations with respect to demographics, total and free testosterone, or total and bio-25[OH]D. Vit D replacement was initiated with HC (n = 18) or no HC (n = 10), and for those completing the study, FSFI improved (score >26.55) in 61% (11/18) regardless of the treatment group. A time-treatment effect showed a significant change for the domain of orgasm, suggesting that HC had more of an impact than Vit D replacement. Improvement in sexual function as a dichotomous variable was not associated with age, body mass index, other demographics, total and free testosterone, total and bio-25[OH]D, or HC use. Due to the prevalence of SDy in women with PCOS, efficacious treatment options are necessary. This study is the first to analyze the effect of Vit D supplementation on SDy in women with PCOS. Limitations included the small number of participants who completed the study, thus limiting meaningful conclusions and generalizability. Vit D status was not associated with SDy and BDI-II. While HC may have played a role, standard Vit D supplementation could not account for the noted improvement in FSFI in women with PCOS.

Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.

Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [β = −0.092; 95 % confidence interval (CI): −0.149, −0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 μg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 μg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Prevalence and risk factors of vitamin D deficiency among patients with chronic myofascial pain syndrome: a cross-sectional study

BackgroundMyofascial pain syndrome (MPS) is a common muscle condition characterized by painful trigger points. Vitamin D deficiency has been recognized as a precipitating factor of MPS. The present study aimed to determine the prevalence and risk factors of vitamin D deficiency in patients with chronic MPS.MethodsA cross-sectional study was conducted, using a structured face-to-face interview to collect demographic information, clinical characteristics, pain duration and location, as well as the bodily pain subscale of SF36 and EQ-5D-5 L. The Elecsys vitamin D total II assay was used to measure serum total 25-hydroxyvitamin D level.ResultsOf 120 participants, vitamin D insufficiency (20 to 29.9 ng/ml) and deficiency (< 20 ng/ml) were 47.5% (95% CI: 38.3–56.8%) and 34.2% (95% CI: 25.8–43.4%), respectively. The adjusted odds ratios for vitamin D deficiency of participants aged < 45 years and who reported having ≤ 15 min sunlight exposure per day were 3.5 (95% CI: 1.54 to 7.98) and 2.38 (95% CI: 1.05 to 5.26), respectively. The bodily pain score (r = − 0.02, P = 0.86) and EQ-5D-5 L utility (r = 0.04, P = 0.66) did not significantly correlate with vitamin D levels.ConclusionApproximately one third of patients with chronic MPS had vitamin D deficiency. Age < 45 years and sunlight exposure ≤ 15 min/day were identified as potential risk factors for vitamin D deficiency in MPS patients.

Joint association of sedentary behavior and vitamin D status with mortality among cancer survivors

BackgroundSedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated.MethodsWe analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007–2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels.ResultsAmong 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54–2.72), cancer (HR, 2.33; 95% CI, 1.47–3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33–2.74) than those with neither risk factor after adjustment for potential confounders.ConclusionsIn a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.

Vitamin D deficiency in Ukraine: current evidence

BackgroundData from numerous studies demonstrate the high frequency of vitamin D deficiency (VDD) and insufficiency (VDI) in many countries worldwide that depend on age and sex, seasons, country, and concomitant pathology. This research aimed to study vitamin D status in the Ukrainian population during 2016–2022 years depending on age, sex, month, and year of the observation, and compare the results with the data of previous Ukrainian epidemiologic studies.MethodsIn a single-center cohort study, we analyzed the serum total 25-hydroxyvitamin D (25(OH)D) level in 7,418 subjects aged 20–99 years. The analysis was performed depending on age, sex, month, season, and year of the observation. Also, we compared the results with the data of previous Ukrainian studies. 25(OH)D level was measured using the electrochemiluminescence method.ResultsThe mean serum 25(OH)D level in the total group was 31.0 [22.3–41.1] ng/mL, the lowest level was in the age group 90–99 years old. No gender differences were found in 25(OH)D levels, except the one for the women aged 60–69 years old who had higher vitamin D levels compared to male parameters. 41.6% of the subjects had an optimal (> 30–50 ng/mL) 25(OH)D level, 27.3% had VDI, and 19.5% had a VDD. The suboptimal and high serum concentration of 25(OH)D (> 50–100 ng/mL) was found in 11.4% of the subjects. Also, we established the increase of serum 25(OH)D level from 2016 to 2022 with the highest values in 2020–2022. Seasonal variations of 25(OH)D concentration confirmed the highest index in autumn (33.0 [24.0–42.4] ng/mL) and the lowest one in the spring (28.5 [19.7–38.7] ng/mL) with the highest 25(OH)D level in September and the lowest one in March.ConclusionOur results confirmed a decrease in VDD and VDI in 2020–2022 in the Ukrainian population compared to the previous years (2016–2019) and previous Ukrainian studies with similar age and seasonal particularities. It may be the consequence of an improvement in public awareness of global vitamin D deficiency, its positive skeletal and extra-skeletal effects, as well as more intensive vitamin D supplementation due to the COVID-19 pandemic in the recent years.

Increased Serum Total and Free 25-Hydroxyvitamin D with Daily Intake of Cholecalciferol-Fortified Skim Milk: A Randomized Controlled Trial in Colombian Adolescents

BackgroundThe efficacy of cholecalciferol (vitamin D3) food fortification in low- and middle-income countries near the Equator is unknown. ObjectivesWe examined the effects of providing cholecalciferol-fortified skim milk to adolescents and their mothers on serum total 25(OH)D, free 25(OH)D, and vitamin D–binding protein (DBP) concentrations in a randomized controlled trial. MethodsWe randomly assigned 80 Colombian families each with a child aged 12–14.5 y and their mother 1 L of skim milk daily, either fortified with 2400 IU (60 μg) cholecalciferol or unfortified, for 6 wk. We prescribed 500 mL of milk daily to adolescents; mothers consumed the remainder ad libitum. We estimated intent-to-treat effects as the between-arm difference in the change in serum total and free 25(OH)D and DBP concentrations from baseline to the end of follow-up. Secondary analyses included stratification by baseline characteristics and per-protocol comparisons. ResultsAmong adolescents, fortification effects (95% CI) on serum total 25(OH)D, free 25(OH)D, and DBP concentrations were 5.4 nmol/L (2.1, 8.8 nmol/L), 0.6 pmol/L (−0.2, 1.4 pmol/L), and −416 nmol/L (−944, 112 nmol/L), respectively. Effects on total 25(OH)D were stronger in adolescents with lower DBP concentrations, darker skin, less sunlight exposure, and higher compliance than in their respective counterparts. Fortification increased free 25(OH)D concentrations in high compliers. Among mothers, the effects (95% CI) on total 25(OH)D and DBP concentrations were 4.0 nmol/L (0.6, 7.5 nmol/L) and −128 nmol/L (−637, 381 nmol/L), respectively. There were no adverse events. ConclusionsProvision of cholecalciferol-fortified skim milk increases serum total 25(OH)D concentrations in Colombian adolescents and adult women.

Evaluation of Therapies for Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

Introduction: Parathyroid hormone-lowering responses after administration of three different therapies capable of raising serum total 25-hydroxyvitamin D (25OHD) were evaluated in patients with secondary hyperparathyroidism (SHPT), vitamin D insufficiency (VDI), and stage 3 or 4 chronic kidney disease (CKD). Methods: Sixty-nine adult subjects with intact parathyroid hormone (iPTH) ≥85 and <500 pg/mL and VDI (25OHD <30 ng/mL) were randomized after ≥4-week washout to 2 months of open-label treatment with: (1) extended-release calcifediol (ERC) 60 μg/day; (2) immediate-release calcifediol (IRC) 266 μg/month; (3) high-dose cholecalciferol (HDC) 300,000 IU/month; or (4) paricalcitol plus low-dose cholecalciferol (PLDC) 1 or 2 μg and 800 IU/day, used as reference hormone replacement therapy. Serum 25OHD, calcium (Ca), phosphorus (P), plasma iPTH, and adverse events were monitored weekly. No clinically significant differences were observed at baseline between treatment groups. Results: Sixty-two subjects completed the study per protocol (PP; 14–17 per group). Mean (SD) 25OHD and iPTH at baseline were 20.6 (6.6) ng/mL and 144.8 (90) pg/mL, respectively. Mean 25OHD increased at end of treatment (EOT) to 82.9 (17.0) ng/mL with ERC (p < 0.001) and 30.8 (11.6) ng/mL with HDC (p < 0.05), but remained unchanged with IRC and PLDC. EOT 25OHD levels reached ≥30 ng/mL in all subjects treated with ERC and in 44% with HDC. All subjects attained EOT 25OHD levels ≥50 ng/mL with ERC versus none with other therapies. iPTH response rates at EOT (≥10, 20 or 30% below baseline) were similar for ERC and PLDC; rates for IRC and HDC were much lower. No significant changes from baseline were observed in ionized or corrected total Ca or P in any group. One episode of hypercalcemia (>10.3 mg/dL) occurred with PLDC. Hyperphosphatemia (>5.5 mg/dL) occurred once with ERC, eight times with HDC, 3 times with IRC, and twice with PLDC. Conclusion: ERC was highly effective in both raising serum 25OHD and decreasing iPTH in patients with SHPT, VDI, and stage 3 or 4 CKD. iPTH-lowering response rates with ERC were similar to daily PLDC, the reference therapy; rates with IRC or HDC were significantly lower. ERC is an attractive alternative to vitamin D hormone therapy in CKD patients.

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients

IntroductionExtended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3–4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D.MethodsMedical records of 376 adult patients with stage 3–4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8–23.5 ng/mL), calcium (Ca: 9.1–9.3 mg/dL), phosphorus (P: 3.7–3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3–35.7 mL/min/1.73m2). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks.ResultsSerum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged.ConclusionsReal-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.

LBSAT229 Extended-release Calcifediol Effectively Raised 25-hydroxyvitamin D In CKD Despite Obesity

Abstract Inadequate levels of serum total 25-hydroxyvitamin D (25D) in chronic kidney disease (CKD) are associated with an increased risk of secondary hyperparathyroidism (SHPT). Serum 25D can be difficult to raise sufficiently with vitamin D supplements (cholecalciferol or ergocalciferol) to effectively lower elevated parathyroid hormone (PTH) levels especially in overweight patients. Obesity is common in CKD and requires attention when vitamin D repletion is considered. Vitamin D supplements are fat-soluble molecules which accumulate in adipose tissue. They have low affinity for serum vitamin D binding protein and are poorly mobilized from adipose tissue into circulation for hepatic activation. Recent studies suggest that serum 25D levels of ≥50 ng/mL are necessary to produce significant PTH reductions in nondialysis patients. Data were analyzed from two identical randomized clinical trials investigating the efficacy and safety of treating adult nondialysis patients with extended-release calcifediol (ERC; n=285) or placebo (n=144) to see if ERC raised 25D to at least 50 ng/mL in all body weight categories, with subgroup analyses by race, gender and age. On enrollment, subjects had eGFR of ≥15 and &amp;lt;60 mL/min/1.73 m2, PTH ≥85 and &amp;lt;500 pg/mL, serum 25D ≥10 and &amp;lt;30 ng/mL, corrected serum calcium ≥8.4 and &amp;lt;9.8, serum phosphorus ≥2. 0 and &amp;lt;5. 0, absence of nephrotic range proteinuria (&amp;gt;3 mg/mg creatinine) and no history of parathyroidectomy or renal transplantation. These subjects had mean (SD) age of 65.4 (10.9) years, serum 25D at baseline of 19.6 (5.4) ng/mL, body weight of 97.8 (24.3) kg and BMI of 34.7 (7.9) kg/m2. Fifty percent were male, 64. 0% White, 32.9% African-American or Black, and 3.1% Other, and 20% were Hispanic. A total of 356 subjects completed a 20- to 26-week treatment period per-protocol and were included in the analysis. Enrolled subjects ingested a 30 mcg capsule of ERC (OPKO Pharmaceuticals, Miami) daily for 12 weeks followed by one or two capsules (30 or 60 mcg) daily for a 14 more weeks. Control subjects received matching placebo. Mean (SD) serum 25D remained unchanged with placebo treatment but rose progressively with ERC treatment to 67.1 (21.6) ng/mL (mean of weeks 20-26). The observed increases in serum 25D were inversely related to body weight but exceeded 50 ng/mL in all body weight categories, irrespective of race (White vs. African-American or black), gender or age (&amp;lt;70 vs. ≥70 years). Side effects observed at these levels were similar to placebo. These data showed that ERC successfully raised mean serum 25D to at least 50 ng/mL irrespective of body weight, race, gender or age. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT131 Extended-release Calcifediol Reduced Ipth And Normalized 1,25-dihydroxyvitamin D In Esrd.

Abstract Background Extended-release calcifediol (ERC) has been shown in randomized clinical trials to effectively and safely treat secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency when administered at 210 or 420 mcg per week (30 or 60 mcg/day), doses which gradually raise serum total 25-hydroxyvitamin D (25D) to mean steady-state levels of 50-56 ng/mL. Clinical Case A 41-year-old male Caucasian with end-stage renal disease (ESRD) requiring regular hemodialysis (HD) experienced an overdose during participation in a phase 2 study of ERC for treating SHPT. Medical history included hypertension, type II diabetes, glomerulonephritis, bilateral lower extremity edema, muscle cramps, pruritus, shortness of breath, sporadic hypercalcemia and hyperphosphatemia, and iron deficiency anemia. Treatment with ERC began at an incorrect dosage of 2,700 mcg per week (900 mcg per HD) for 10 weeks as the study coordinator misunderstood the protocol-specified dose of 900 mcg per week. A 2.5% calcium dialysate was used during the study. Serum 25D gradually increased from 19 to 339 ng/mL (32-100), serum total 1,25-dihydroxyvitamin D (1,25D) increased from 6.3 to 137 pg/mL (24-86), plasma iPTH decreased from 440 to 146 pg/mL (15-65), and corrected serum calcium (Ca) decreased from 9.3 to 9.1 mg/dL (8.6-10.4). The subject remained asymptomatic throughout. Discovery of the overdose was delayed due to limited monitoring access during the pandemic and occurred when the ERC supply was prematurely exhausted. A physical exam and retrospective review of study records were promptly undertaken with no abnormalities noted. ERC administration, after a 1-dose hiatus, resumed at the correct dose (900 mcg per week). Serum 25D decreased over the next 4 weeks to 251 ng/mL, 1,25D decreased to 46. 0 pg/mL, iPTH increased to 186 pg/mL, and Ca remained stable (9. 0 mg/dL). The subject completed the full 6-month treatment period without adverse events. Clinical Lessons Gradual elevation of serum 25D and 1,25D with ERC to high levels had no impact on serum Ca or adverse events in the described subject suggesting that hypercalcemia observed with other vitamin D therapies used during HD results from abrupt increases in these metabolites. Serum 1,25D normalized with 25D elevation despite the lack of functional kidneys, indicating that extra-renal 1,25D production can become sufficient to control increased iPTH in ESRD when serum 25D is elevated well above the current clinical practice target of 30 ng/mL. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT230 Daily Variation In Serum Calcifediol In Japanese And Non-japanese Adults

Abstract Circadian rhythm and 24-hour intra-subject variation in serum calcifediol (25-hydroxyvitamin D3) in the absence of vitamin D supplementation or treatment are poorly studied in healthy adults of any race. To address this dearth of information, a single-center, open-label study was completed in the US to evaluate both of these parameters in 67 male and female (balanced for gender) first generation Japanese (n=35) and non-Japanese (n=32) subjects, aged between 18 and 55 years. "First generation" was defined as: born in Japan; had 2 Japanese biological parents and 4 Japanese biological grandparents; had lived outside of Japan for less than 5 years; and, had made no significant changes in lifestyle, including diet, since leaving Japan. "Non-Japanese" was defined as: not of Japanese or Asian descent; and, parents and grandparents were not born in Japan or in any Asian countries. Enrolled subjects had a body mass index within 18. 0 to 30. 0 kg/m2 (inclusive) and body weight not less than 50 kg. The body weight for non-Japanese subjects was 9% to 17% higher than that of Japanese subjects (60.3 to 92.9 kg versus 51.2 to 84.9 kg). Exclusion criteria included consumption of a vitamin D supplement within the previous 28 days, consumption of grapefruit or oranges, alcohol, medications or tobacco within the previous 72 hours, and participation in strenuous physical activity within the previous 72 hours. Subjects were housed in a Phase 1 unit for 2 days where they received only standardized diets. Blood samples were collected on the second day at 0, 2, 4, 6, 8, 10, 12, 16 and 24 hours for determination of serum calcifediol by LC/MS/MS (mean accuracy: 0.37%; mean precision: 3. 07%) at Syneos Laboratories (Quebec, Canada). For all subjects, mean serum calcifediol levels ranged from 20.90 to 22.24 ng/mL over the 24-hour collection period with an average inter-subject variation (SD) of 6.79 ng/mL. A circadian rhythm was not evident either in the total population or in the racial subgroups. Mean intra-subject variation over 24 hours was 1. 08 ng/mL (SD; range: 0.27-3.22) or 5. 05% (CV; range: 2.36-14.81). Differences in 24-hour intra-subject variation between races were not significant (P&amp;gt;0. 05). These data support the conclusions that: (1) clinically meaningful circadian rhythms in serum calcifediol are absent in healthy first generation Japanese and non-Japanese adults living in the US; (2) the mean diurnal variation in serum calcifediol is small (approximately 5%); and (3) vitamin D therapies may appropriately be considered "physiological" if they raise serum total 25-hydroxyvitamin D after each dose only within the bounds of normal diurnal variation thereby allowing gradual adaptation to repletion. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

An Observational Study of Serum Vitamin D Status in Critically Ill Children Admitted to the Pediatric Intensive Care Unit

Introduction Vitamin D is a pleiotropic hormone involved in the functioning of organ systems including those central to critical illness pathophysiology. We evaluated the longitudinal vitamin D status in the pediatric intensive care unit (PICU) and its relevance to patient outcomes. Material and methods Thirty-six PICU-admitted patients, and 40 age- and sex-matched healthy children were enrolled. Serum total 25-hydroxyvitamin D [25(OH)D] levels were analyzed on PICU days 1, 5, and 10 in the patient group, and once in the control group. Patients were divided into sufficient (&gt;30 ng/mL), insufficient (20–30 ng/mL), and deficient (&lt;20 ng/mL) subgroups. Outcome measures between the subgroups and alterations in 25(OH)D levels were examined. Results The mean 25(OH)D levels of PICU patients initially and control cases were not different (25.4±6.0 and 25.9±5.8 ng/mL, respectively). Although all patients with vitamin D deficiency were hospitalized for infectious diseases, the mean 25(OH)D level of patients hospitalized for infections was not different from other patients. There was no difference between vitamin D subgroups in demographic variables, admission season, illness severity, respiratory/inotropic support, duration of stay, and mortality. Vitamin D deficient patients had lower albumin concentrations (p˂0.05). On days 5 and 10, the mean 25(OH)D levels of the patients were 24.5±5.7 and 23.6±5.8 ng/mL, respectively, both different from the admission level (p˂0.001). Conclusions Hypovitaminosis D, which is common in healthy children, is also common in PICU admission and tends to be more profound during the stay. Further studies are required to evaluate the bioavailability of vitamin D in critical illness.

Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis.

Introduction: Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however, that bioavailable or free 25(OH)D may be even better predictors of mortality. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence on associations of vitamin D-binding protein (VDBP), albumin-bound, bioavailable, and free 25(OH)D, with mortality. Methods: We systematically searched PubMed and Web of Science, up to 27 May 2022. Predictors of interest included serum or plasma concentrations of VDBP, albumin-bound, bioavailable, and free 25(OH)D. Assessed health outcomes were all-cause and cause-specific mortality. We included studies reporting associations between these biomarkers and mortality outcomes. We applied random-effects models for meta-analyses to summarize results from studies assessing the same vitamin D biomarkers and mortality outcomes. Results: We identified twelve eligible studies, including ten on VDBP, eight on bioavailable 25(OH)D, and eight on free 25(OH)D. No study reported on albumin-bound 25(OH)D and mortality. In meta-analyses, the highest levels of bioavailable and free 25(OH)D were associated with 37% (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46, 0.87), and 29% (HR: 0.71, 95% CI: 0.53, 0.97) decrease in all-cause mortality, respectively, compared with the lowest levels. These estimates were similar to those for total 25(OH)D (HR: 0.67, 95% CI: 0.56, 0.80) observed in the same studies. Higher VDBP levels were associated with lower all-cause mortality in cancer patient cohorts. However, no such association was observed in general population cohorts. Conclusions: Similar inverse associations of total, bioavailable, and free 25(OH)D with mortality suggest that bioavailable and free 25(OH)D do not provide incremental value in predicting mortality.

Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study.

The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women. Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month. There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment. Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.

Comparison of the Serum Total 25-Hydroxyvitamin D Concentrations Using Chemiluminescent Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry in Children.

We aimed to assess the difference and agreement between the CL-series Vitamin D Total assay (Mindray), which was a kind of chemiluminescent immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the measurement of serum 25-hydroxyvitamin D [25(OH)D] concentrations in children. We compared the 25(OH)D concentrations of 92 children using the CLIA and LC-MS/MS. Paired samples t-test was used to compare the two groups. Linear regression was used to show the correlation between CLIA and LC-MS/MS. The difference and bias between 2 methods were revealed in Bland-Altman plot. Agreement in classification of deficiency between CLIA and LC-MS/MS was assessed using Cohen's Kappa. p value<0.05 was considered statistically significant. Using Shapiro-Wilk Test to assess whether the data follows a normal distribution. Using 95% children's serum 25(OH)D concentrations by LC-MS/MS as the reference interval. The regression equation was CLIA=1.185×LC-MS/MS-3.328. The fitness adjusted r2 was 0.589. The CLIA showed positive bias compared to LC-MS/MS, p<0.05, bias=(1.94±16.56) ng/mL. Cohen's Kappa=0.53, p<0.001. The agreement of 2 methods in diagnosing "deficiency" was good. According to Shapiro-Wilk Test, the data followed a normal distribution (W=0.99). The reference interval of children's serum 25(OH)D concentrations by LC-MS/MS was 11.35-44.57 ng/mL. In measuring 25(OH)D concentration of children, CLIA represented higher levels than LC-MS/MS. The two methods were consistent in diagnosing vitamin D deficiency. The reference interval of children's serum 25(OH)D concentrations by LC-MS/MS was 11.35-44.57 ng/mL in our area in summer.

Vitamin D Supplementation on Carotid Remodeling and Stiffness in Obese Adolescents.

Obesity is associated with vitamin D (VD) deficiency and arterial stiffness. This randomized control trial assessed the effects of VD supplementation during a weight-loss program on carotid intima-media thickness (IMT) and carotid compliance in obese adolescents. Participants were randomly assigned to receive either a 12-week lifestyle program with VD supplementation (n = 13), a lifestyle program without VD supplementation (n = 13) or a control group composed of normal-weight adolescents (n = 18). Serum total and free 25-hydroxyvitamin D (25(OH)D), IMT and carotid compliance were measured before and after the trial. Insufficiency in 25(OH)D concentration was found in 73% of obese participants compared to 22% among controls. Obese adolescents had lower free 25(OH)D and displayed higher IMT but lower carotid compliance than controls. Free 25(OH)D and IMT were negatively correlated in adolescents displaying VD insufficiency at baseline. After three months, total and free 25(OH)D increased in both groups. The changes of IMT and carotid compliance were similar between groups. The changes in IMT were correlated with the changes in total 25(OH)D in obese adolescents with VD insufficiency at baseline (r = −0.59, p = 0.03). While the lifestyle program with VD supplementation did not affect carotid compliance, IMT reduction was improved in obese adolescents.

Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism

Introduction: Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol). Methods: Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo. Results: More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3–7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 μg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 μg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment. Conclusion: Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.

Effectiveness of three Vitamin D dosing protocols on raising and maintaining blood serum levels of 25-hydroxyvitamin D over a three-month period: a randomized, prospective study.

Vitamin D has gained attention in the medical community due to its critical role in calcium homeostasis and overall bone health. No standard vitamin D dosing protocol in fracture care has been established for patients deficient in 25-hydroxyvitamin D. This prospective and randomized study aimed to find a dosing regimen that would safely achieve and maintain a therapeutic level of 25-hydroxyvitamin D in deficient patients over three months. Between June 2016 and May 2017, 48 patients with baseline total 25-hydroxyvitamin D less than 30.0ng/mL were randomly assigned to either group one (one dose of 100,000 international units (IU) of Vitamin D2) or group 2 (100,000IU of Vitamin D2 once weekly for twelve weeks) or group 3 (50,000IU of Vitamin D2 daily for ten days followed by 2,000IU of Vitamin D3 daily for 74days). Baseline serum levels were drawn followed by interval levels at week 2, 6 and 12. The primary outcome was to determine which protocol could achieve and maintain therapeutic levels of total 25-hydroxyvitamin D over the course of three months. Our secondary outcome was to monitor for negative side effects. Group 1 did not show any statistically significant increase in serum levels and had no reported side effects. There was a statistically significant increase in serum total 25-hydroxyvitamin D in group 2 between all-time points except between weeks 6 and 12. Two (12.5%) participants in group 2 reported side effects. Group 3 had the greatest change in serum levels from weeks 0 to 2 but had a significant decrease between weeks 2 and 6. No change was seen between weeks 6 and 12. Three (17.5%) participants in group 3 reported side effects. Group 2 sustained and maintained a satisfactory level of total 25-hydroxyvitamin D over three months without any severe side effects.

The Association Between Active Transportation and Serum Total 25-Hydroxyvitamin D Levels Among US Childbearing-Aged Women.

Serum total 25-hydroxyvitamin D (25[OH]D) and physical activity (PA) both play important roles in maternal-fetal health. However, a high prevalence of vitamin D and PA insufficiency has been observed in women of childbearing age. Active transportation may increase overall PA levels and potentially boost serum 25(OH)D levels. Data from the National Health and Nutrition Examination Survey between 2007 and 2014 were used. A total of 5601 women aged 18-49 years were included. Transportation PA (TPA) was quantified as metabolic equivalents of task and serum 25(OH)D levels was measured. Multivariable logistic regression models adjusted for potential confounders were conducted. The corresponding adjusted odds ratios associated with vitamin D insufficiency (<50nmol/L) were 1.09 (95% confidence interval, 0.87-1.37) for 1 to 499 MET minutes per week of TPA, 0.69 (0.52-0.91) for 500 to 1000 MET minutes per week of TPA, and 0.95 (0.72-1.26) for >1000 MET minutes per week of TPA, respectively, compared with no TPA. Using vitamin D deficiency (<30nmol/L) as the outcome led to similar results. The association between TPA and serum 25(OH)D levels was more robust in high sedentary time. A moderate level of TPA is related to lower odds of suboptimal vitamin D status among women of childbearing age.