Increase In Serum 25-hydroxyvitamin Research Articles

Accumulated LPS induced by colitis altered the activities of vitamin D-metabolizing hydroxylases and decreased the generation of 25-hydroxyvitamin D

It is generally accepted that low vitamin D (VD) levels are associated with a high prevalence factor for Inflammatory bowel disease (IBD). IBD patients have observed higher levels of lipopolysaccharide (LPS), ALT, and AST than healthy people. Gut-derived LPS causes inflammatory injury in the liver and kidney. The VD-metabolizing mechanism is involved in the liver and kidney, which means IBD might impact VD metabolism. However, whether IBD affects VD metabolism has not been studied. In vitro LPS resulted in decreased CYP2R1 in liver cells as well as decreased CYP27B1 and increased CYP24A1 in kidney cells, revealing that LPS changed the activities of several hydroxylases. Mice with acute colitis had an increased LPS in serum and liver with mild hepatic injuries, while mice with chronic colitis had a significant elevation of LPS in serum, liver, and kidney with hepatorenal injuries. Thus, the liver hydroxylase for VD metabolism would be the first to be affected in IBD. Consequently, serum 25-hydroxyvitamin D declined dramatically with a significant elevation of 24,25-dihydroxyvitamin D and 1,24,25-trihydroxyvitamin D. Unchanged serum levels of 1,25-dihydroxyvitamin D might be the result of other factors in vivo. In acute colitis, a small dosage (4 IU/day) of cholecalciferol could protect the colon, decrease the serum level of LPS, and finally increase serum 25-hydroxyvitamin D. However, this improvement of cholecalciferol was fading in chronic colitis. These results suggested that VD supplementations for preventing and curing IBD in the clinic should consider hepatorenal hydroxylases and be employed as soon as possible for a better outcome.

Combined Oral Contraceptives: Association with Serum 25-Hydroxyvitamin D and Calcium and Bone Homeostasis.

Background: Use of combined oral contraceptives (COCs) has been found to increase serum 25-hydroxyvitamin D [25(OH)D] but effects on calcium and bone homeostasis are unclear. Materials and Methods: Serum 25(OH)D, parathyroid hormone (PTH), alkaline phosphatase (ALK) and estradiol, dietary intake of bone-related nutrients and foods, bone mineral density (BMD), and body fat were compared in adult women (20-35 years; body mass index 21.5 ± 2.3 kg/m2) users (+COC, n = 32) and nonusers (-COC, n = 20) of COC. Biochemical markers were measured by automated assays. BMD at total body (TB), lumbar spine (LS), femoral neck (FN) and trochanter (TR), and body fat, were measured by dual-energy X-ray absorptiometry. Dietary intake was assessed by a food frequency questionnaire. Results: Intake of calcium, dairy foods, and fruits and vegetables, were adequate and did not differ by COC. Mean 25(OH)D was 35% higher in +COC (110.4 ± 27.3 nmol/L, 44.2 ± 1.8 ng/mL) compared with -COC (81.7 ± 22.8 nmol/L, 32.7 ± 2.3 ng/mL; p < 0.001). Mean PTH, ALK, and estradiol were 28%, 12%, and 62% lower, respectively, in +COC compared with -COC (p ≤ 0.05). Mean BMD z-scores (all sites) were adequate and did not differ by COC. There were no correlations between 25(OH)D and dietary, biochemical, and body composition variables. PTH was inversely correlated with TR-BMD z-score in -COC (r = -0.47; p = 0.04), and ALK was inversely correlated with TB-, TR-, and LS-BMD z-scores in -COC (r ≤ -0.43; p ≤ 0.04), but not in +COC. Conclusions: Increased serum 25(OH)D with COC use was paralleled by expected physiologic adjustments in calcium and bone homeostasis, and adequate bone mass status, in nonobese young adult women consuming bone-healthy diets.

Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study.

Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR). A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy. The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP). The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

Vitamin D level regulates serum lipids discrepantly in adults with and without dyslipidemia.

Vitamin D deficiency is associated with hyperlipidemia, but it remains unclear whether vitamin D supplementation reduces serum lipid levels. The aims of this study were to investigate the associations between increased serum 25-hydroxyvitamin D (25(OH)D) concentrations and lipid levels, and identify the characteristics of people with or without lipid reduction associated with increased 25(OH)D levels. The medical records of 118 individuals (53 men; mean age, 54.4 ± 10.6 years) whose serum 25(OH)D levels increased between two consecutive measurements were retrospectively reviewed. People with increased 25(OH)D levels (from 22.7 (17.6-29.2) to 32.1 (25.6-36.8) mg/dL; P < 0.01) had a significant reduction in serum levels of triglycerides (TG) (from 111.0 (80-164) to 104.5 (73-142) mg/dL; P < 0.01) and total cholesterol (TC) (from 187.5 (155-213) to 181.0 (150-210) mg/dL; P < 0.05). The individuals who responded to vitamin D (≥10% reduction in TG or TC levels) exhibited significantly higher baseline TG and TC levels than did those who did not. Only patients with hyperlipidemia (not those without hyperlipidemia) at baseline exhibited significantly reduced TG and TC levels at follow-up. However, increasing serum 25(OH)D concentrations were significantly correlated with decreasing lipid levels in individuals with baseline 25(OH)D levels less than 30 ng/mL, and in individuals aged 50-65 years (not in patients younger than 50 years or older than 65 years). In conclusion, increasing serum 25(OH)D concentrations may be potentially helpful for the treatment of hyperlipidemia in people with vitamin D deficiency.

Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study

AimsNon-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD. MethodsCross-sectional associations of indices of NAFLD with glycemia and vitamin D status were assessed in 3972 individuals screened for the D2d study. In those with prediabetes randomized to vitamin D or placebo (n = 2423), we examined longitudinal associations of NAFLD indices with incident T2D. We used validated non-invasive scores to assess steatosis [(hepatic steatosis index (HSI); NAFLD-liver fat score (NAFLD-LFS)] and advanced fibrosis [fibrosis-4 (FIB-4) index; AST to Platelet Ratio Index (APRI)]. ResultsEighty-five percent of screened participants had likely steatosis by HSI and 71 % by NAFLD-LFS; 3 % were likely to have advanced fibrosis by FIB-4 and 1.2 % by APRI. FIB-4 indicated that 20.4 % of individuals require further follow up to assess liver health. Steatosis and fibrosis scores were higher among participants with worse glycemia. The NAFLD-LFS and APRI predicted development of diabetes (hazard ratios [95%CI] 1.35 [1.07, 1.70]; P = 0.012) and 2.36 (1.23, 4.54; P = 0.010), respectively). The effect of vitamin D on diabetes risk was not modified by baseline NAFLD indices. Individuals with likely steatosis had a smaller increase in serum 25-hydroxyvitamin D level in response to vitamin D than those without steatosis. ConclusionsThe predicted high prevalence of steatosis, the need for further fibrosis workup, and the relationship between liver health and incident T2D suggest that routine screening with clinically accessible scores may be an important strategy to reduce disease burden.

Effect of vitamin D supplementation on various parameters in patients with non-alcoholic fatty liver disease: An updated meta-analysis.

The current updated meta-analysis aimed to explore the effects of vitamin D supplementation on various parameters in patients with non-alcoholic fatty liver disease (NAFLD), using the latest trials available. PubMed, Embase, and the Cochrane Library were screened for the collection of randomized controlled trials (RCTs) that compared the efficacy of additional vitamin D vs. the placebo group on NAFLD patients in the last 5 years. Trials included were focused on the assessment of anthropometric and biochemical indices. Our results revealed that additional vitamin D greatly increased serum 25-hydroxyvitamin D (25(OH)D), and decreased the low-density lipoprotein-cholesterol (LDL-C) levels. However, no significant differences were found in terms of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), c-glutamyltransferase, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR) and Ca2+ levels between the supplementation of vitamin D and placebo. The present study demonstrated the advantageous impact of supplementary vitamin D on the levels of 25(OH)D and LDL-C in NAFLD patients. However, the results failed to provide evidence for the superiority of additional vitamin D in relation to the concentrations of serum ALP, AST, TC, Ca, γ-glutamyl transferase (GGT), TC, FBG, IR and HDL-C.

Combined vitamin D and magnesium supplementation does not influence markers of bone turnover or glycemic control: A randomized controlled clinical trial

High-dose vitamin D supplementation can increase total osteocalcin concentrations that may reduce insulin resistance in individuals at risk for prediabetes or diabetes mellitus. Magnesium is a cofactor in vitamin D metabolism and activation. The purpose of this study was to determine the combined effect of vitamin D and magnesium supplementation on total osteocalcin concentrations, glycemic indices, and other bone turnover markers after a 12-week intervention in individuals who were overweight and obese, but otherwise healthy. We hypothesized that combined supplementation would improve serum total osteocalcin concentrations and glycemic indices more than vitamin D supplementation alone or a placebo. A total of 78 women and men completed this intervention in 3 groups: a vitamin D and magnesium group (1000 IU vitamin D3 and 360 mg magnesium glycinate), a vitamin D group (1000 IU vitamin D3), and a placebo group. Despite a significant increase in serum 25-hydroxyvitamin D concentrations in the vitamin D and magnesium group compared with the placebo group (difference=5.63; CI, -10.0 to -1.21; P=.001) post-intervention, there were no differences in serum concentrations of total osteocalcin, glucose, insulin, and adiponectin or the homeostatic model assessment of insulin resistance (HOMA-IR) among groups (P > .05 for all). Additionally, total osteocalcin (β=-0.310, P=.081), bone-specific alkaline phosphatase (β=0.004, P=.986), and C-terminal cross-linked telopeptide (β=0.426, P=.057), were not significant predictors of HOMA-IR after the intervention. Combined supplementation was not associated with short-term improvements in glycemic indices or bone turnover markers in participants who were overweight and obese in our study. This trial was registered at clinicaltrials.gov (NCT03134417).

Effect of vitamin D source and amount on vitamin D status and response to endotoxin challenge

The objectives were to test the effects of dietary vitamin D3 [cholecalciferol (CHOL)] compared with 25-hydroxyvitamin D3 [calcidiol (CAL)] on vitamin D status and response to an endotoxin challenge. Forty-five Holstein bull calves (5 ± 2 d of age) were blocked into weekly cohorts, fed a basal diet that provided 0.25 µg/kg body weight (BW) CHOL, and assigned randomly to 1 of 5 treatments: control [(CON) no additional vitamin D], 1.5 µg/kg BW CHOL (CHOL1.5), 3 µg/kg BW CHOL (CHOL3), 1.5 µg/kg BW CAL (CAL1.5), or 3 µg/kg BW CAL (CAL3). Calves were fed milk replacer until weaning at 56 d of age and had ad libitum access to water and starter grain throughout the experiment. Treatments were added daily to the diet of milk replacer until weaning and starter grain after weaning. Measures of growth, dry matter intake, and serum concentrations of vitamin D, Ca, Mg, and P were collected from 0 to 91 d of the experiment. At 91 d of the experiment, calves received an intravenous injection of 0.1 µg/kg BW lipopolysaccharide (LPS). Clinical and physiological responses were measured from 0 to 72 h relative to LPS injection. Data were analyzed with mixed models that included fixed effects of treatment and time, and random effect of block. Orthogonal contrasts evaluated the effects of (1) source (CAL vs. CHOL), (2) dose (1.5 vs. 3.0 µg/kg BW), (3) interaction between source and dose, and (4) supplementation (CON vs. all other treatments) of vitamin D. From 21 to 91 d of the experiment, mean BW of supplemented calves was less compared with CON calves, but the effect was predominantly a result of the CHOL calves, which tended to weigh less than the CAL calves. Supplementing vitamin D increased concentrations of 25-hydroxyvitamin D in serum compared with CON, but the increment from increasing the dose from 1.5 to 3.0 µg/kg BW was greater for CAL compared with CHOL (CON = 18.9, CHOL = 24.7 and 29.6, CAL = 35.6 and 65.7 ± 3.2 ng/mL, respectively). Feeding CAL also increased serum Ca and P compared with CHOL. An interaction between source and dose of treatment was observed for rectal temperature and derivatives of reactive metabolites after LPS challenge because calves receiving CHOL3 and CAL1.5 had lower rectal temperatures and plasma derivatives of reactive metabolites compared with calves receiving CHOL1.5 and CAL3. Supplementing vitamin D increased plasma P concentrations post-LPS challenge compared with CON, but plasma concentrations of Ca, Mg, fatty acids, glucose, β-hydroxybutyrate, haptoglobin, tumor necrosis factor-α, and antioxidant potential did not differ among treatments post-LPS challenge. Last, supplementing vitamin D increased granulocytes as a percentage of blood leukocytes post-LPS challenge compared with CON. Supplementing CAL as a source of vitamin D to dairy calves was more effective at increasing serum 25-hydroxyvitamin D, Ca, and P concentrations compared with feeding CHOL. Supplemental source and dose of vitamin D also influenced responses to the LPS challenge.

Effect of source and amount of vitamin D on serum concentrations and retention of calcium, magnesium, and phosphorus in dairy cows

The objectives of the experiment were to determine the effects of supplementing 2 amounts of 25-hydroxyvitamin D3 (calcidiol; CAL) compared with equal amounts of vitamin D3 (cholecalciferol; CHOL) on serum concentrations, absorptions, and retentions of Ca, Mg, and P in periparturient dairy cows. One hundred seventy-seven (133 parous and 44 nulliparous) pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit for energy-corrected milk yield (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments. Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d gestation until parturition. The prepartum diet had a dietary cation-anion difference of -128 mEq/kg of dry matter. All cows were fed a common postpartum diet containing 46 μg of vitamin D3/kg of dry matter without further supplementation of treatments. Concentrations of vitamin D metabolites, Ca, Mg, and P in serum were measured pre- and postpartum, in addition to total-tract digestibility and urinary excretion of Ca, Mg, and P in the prepartum period. Feeding 3 mg compared with 1 mg of CAL increased serum 25-hydroxyvitamin D3 (CAL1 = 94 vs. CAL3 = 173 ± 3 ng/mL). In comparison, the increment in serum 25-hydroxyvitamin D3 from feeding 3 mg compared with 1 mg of CHOL was small (CHOL1 = 58 vs. CHOL3 = 64 ± 3 ng/mL). Feeding CAL increased prepartum concentration of P in serum compared with CHOL (CHOL = 1.87 vs. CAL = 2.01 ± 0.02 mM), regardless of the amount fed, but neither source nor amount affected prepartum Ca or Mg in serum. Feeding CAL increased serum Ca and P for the first 11 d postpartum compared with CHOL (CHOL = 2.12 vs. CAL = 2.16 ± 0.01 mM serum Ca; CHOL = 1.70 vs. CAL = 1.78 ± 0.02 mM serum P) but the amount of vitamin D did not affect postpartum concentrations of Ca, Mg, and P in serum. Feeding CAL increased prepartum apparent digestibility of Ca compared with CHOL (CHOL = 26.6 vs. CAL = 33.5 ± 2.8%) but treatments did not affect Ca retention prepartum. Neither source nor amount of vitamin D affected Mg and P apparent digestibility, but CAL decreased the concentration of P excreted in urine during the prepartum period (CHOL = 1.8 vs. CAL = 0.8 ± 0.3 g/d). Calcidiol tended to increase the amount of Ca secreted in colostrum (CHOL = 9.1 vs. CAL = 11.2 ± 0.9 g/d) and Ca excreted in urine postpartum (CHOL = 0.4 vs. CAL = 0.6 ± 0.1 g/d) compared with CHOL. Collectively, feeding CAL at 1 or 3 mg/d compared with CHOL in the last 24 d of gestation is an effective way to increase periparturient serum P concentration and postpartum serum Ca of dairy cows fed a prepartum diet with negative DCAD.

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Sun Bathing Affects Overweight-Obese Subjects Vitamin D Deficiency

Background: There are increasing number of studies that discuss the effect of sun exposure to overweight and obese individuals with vitamin D deficiency (which is UVB exposure can increase serum 25-Hydroxyvitamin D levels). However, until now there is no a literature review about these studies. This shows a weak correlation between sun bathing and serum 25-Hydroxyvitamin D elevation in overweight and obese people. Aim: Describe the effect of the sun bathing for overweight-obese patient with vitamin D deficiency. Material and Methods: Electronic searching tools (ScienceDirect, Pubmed, and Google Scholar) were conducted from the 1990s until the recent literature. A sensitive search strategy uses specific terms. Studies were included if the population with BMI &gt; 25 Kg/m2; Sun Exposure intervention, the studies provided the comparison of implementation method, the studies provided 25-Hydroxyvitamin D status as the outcome. For the exclusion criteria: studies that included subjects metabolics syndrome. MMAT was used for eliminating biased research. Results: Two studies were fulfilled our inclusion criteria. The studies, were excluded, mainly because they lacked data, biased reseach, and failure to answer any authors questions. Conclusion: The sun exposure method has a positive corellation for increasing serum 25-Hydroxyvitamin D level in overweight and obese subjects with vitamin D deficiency, but internal factors (age and skin color) and external factors (season, temperature, dose, and duration) need to be considered to get effective result. Keywords: Obese, Overweight, Sun bathing, Vitamin D deficiency, 25-Hydroxyvitamin D.

Effects of narrowband ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations: A pilot study.

It is known that ultraviolet B exposure increases serum 25-hydroxyvitamin D(25(OH)D) concentrations. However, little is known about the influence of narrowband ultraviolet B exposure from a light-emitting diode (NBUVB-LED) on serum 25(OH)D levels. Thus, the purpose of this study was to investigate the effect of NBUVB-LED exposure on serum 25(OH)D concentrations.Two healthy adults were enrolled in this pilot study. Their skin was exposed to ultraviolet B light (60 mJ/cm2) 3 times a week for 4 weeks in the first intervention and every day for 4 weeks in the second intervention. Serum levels of 25(OH)D were measured every 2 weeks.Serum 25(OH)D levels were decreased in both subjects at the end of the first intervention (32.1 → 21.4 ng/mL, 33.9 → 21.4 ng/mL, respectively), whereas serum 25(OH)D levels were increased in the 2 weeks of the second intervention (29.5 and 28.0 ng/mL, respectively). At the end of the second intervention, the 25(OH)D concentrations were 19.0 and 20.4 ng/mL, respectively.NBUVB-LED exposure might increase serum 25(OH)D concentrations. Future studies should expand the number of participants and adjust for confounding factors.

The effect of combined magnesium and vitamin D supplementation on vitamin D status, systemic inflammation, and blood pressure: A randomized double-blinded controlled trial

ObjectivePoor vitamin D and magnesium status is observed in individuals who are overweight and obese (Owt/Ob) and is often associated with a heightened risk of cardiovascular disease. Magnesium is a cofactor that assists vitamin D metabolism. We aimed to determine the efficacy of a combined magnesium and vitamin D regimen compared with vitamin D only on increasing serum 25-hydroxyvitamin D (25OHD) concentrations and the effects of these supplements on cardiometabolic outcomes. MethodsThis 12-week double-blinded randomized controlled trial had three treatment arms: magnesium + vitamin D (MagD; 360 mg magnesium glycinate + 1000 IU vitamin D 3 × daily), vitamin D only (VitD; 1000 IU vitamin D 3 × daily), and placebo. A total of 95 Owt/Ob participants were randomized into one of these three study arms. Anthropometry, dietary intake, concentrations of serum 25OHD, serum parathyroid hormone (PTH), serum inflammatory markers, and blood pressure were obtained at baseline and week 12. ResultsThe MagD group experienced the greatest increase in serum 25OHD concentrations (6.3 ± 8.36 ng/mL; P < 0.05). There was a decrease in systolic blood pressure (7.5 ± 8.26 mmHg; P < 0.05) for individuals who had a baseline systolic blood pressure of >132 mmHg in the MagD group. There were no statistically significant treatment effects on serum PTH concentrations and markers of inflammation. ConclusionsA combined MagD treatment may be more effective in increasing serum 25OHD concentrations compared with VitD supplementation alone in Owt/Ob individuals.

UVB-exposed wheat germ oil increases serum 25-hydroxyvitamin D2 without improving overall vitamin D status: a randomized controlled trial

PurposeThis study investigated whether UVB-exposed wheat germ oil (WGO) is capable to improving the vitamin D status in healthy volunteers.MethodsA randomized controlled human-intervention trial in parallel design was conducted in Jena (Germany) between February and April. Ultimately, 46 healthy males and females with low mean 25-hydroxyvitamin D (25(OH)D) levels (34.9 ± 10.6 nmol/L) were randomized into three groups receiving either no WGO oil (control, n = 14), 10 g non-exposed WGO per day (– UVB WGO, n = 16) or 10 g WGO, which was exposed for 10 min to ultraviolet B-light (UVB, intensity 500–630 µW/cm2) and provided 23.7 µg vitamin D (22.9 µg vitamin D2 and 0.89 µg vitamin D3) (+ UVB WGO, n = 16) for 6 weeks. Blood was obtained at baseline, after 3 and 6 weeks and analyzed for serum vitamin D-metabolite concentrations via LC–MS/MS.ResultsParticipants who received the UVB-exposed WGO were characterized by an increase of circulating 25(OH)D2 after 3 and 6 weeks of intervention. However, the 25(OH)D3 concentrations decreased in the + UVB WGO group, while they increased in the control groups. Finally, the total 25(OH)D concentration (25(OH)D2 + 25(OH)D3) in the + UVB WGO group was lower than that of the non-WGO receiving control group after 6 weeks of treatment. In contrast, circulating vitamin D (vitamin D2 + vitamin D3) was higher in the + UVB WGO group than in the control group receiving no WGO.ConclusionUVB-exposed WGO containing 23.7 µg vitamin D can increase 25(OH)D2 levels but do no improve total serum levels of 25(OH)D of vitamin D-insufficient subjects.Trial registrationClinicalTrials.gov: NCT03499327 (registered, April 13, 2018).

Comparison of Two Strategies to Increase Serum Vitamin D Levels in a Real-World Setting: Sunlight Exposure and Oral Supplementation.

Sunlight exposure and oral supplementation are the key strategies to increase serum 25-hydroxyvitamin D [25(OH)D] concentration. We aimed to determine elevation in serum 25(OH)D levels by comparing sunlight exposure and oral vitamin D supplementation in vitamin D-deficient participants who chose the treatment strategy by shared decision-making. We enrolled 197 participants aged ≥19 y who had vitamin D deficiency (serum 25(OH)D<20 ng/mL). Participants selected their treatment method through shared decision-making by preference: sunlight exposure or 1,000 IU oral vitamin D3 supplementation daily. Changes in serum 25(OH)D concentration and duration of sunlight exposure were evaluated after 3 mo. Among 197 participants, 26 (13%) selected sunlight exposure and 171 (87%) selected oral vitamin D supplementation. Seasonal distribution of participants and follow-up rate after 3 mo were not significantly different. There was no significant increase in mean serum 25(OH)D levels in the sunlight exposure group. Conversely, the mean serum 25(OH)D level increased by 11 ng/mL after 3 mo in the oral vitamin D supplementation group. The duration of mean sunlight exposure per day during the study period was not significantly different between the groups. Oral supplementation with 1,000 IU vitamin D3 daily significantly increased serum 25(OH)D levels in vitamin D-deficient participants after 3 mo, while sunlight exposure did not. This study suggests that oral supplementation is more effective than sun exposure in increasing vitamin D levels in the Korean population. Therefore, new recommendations on maintaining adequate vitamin D levels are needed in the Korean population.

Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol

Introduction: The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee^®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC’s efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. Materials and Methods: Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. Results: The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels. Discussion/Conclusion: Analysis of postlaunch data confirmed ERC’s effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Vitamin D and bone minerals in neonates

Osteopenia and rickets remain a problem for high-risk infants, especially preterm infants <1500 g birthweight (very low birth weight, VLBW). The primary cause of osteopenia in VLBW infants is a low intake of calcium and phosphorus compared to requirements for the rapidly growing skeleton. Human milk is a relatively low mineral containing substance and cannot meet the bone mineral needs of very low birth weight infants. As such, most VLBW infants need additional bone minerals and in many neonatal care units these are provided as part of human milk fortificants or specialized infant formulas. In some nurseries, these are given to all infants < 1800–2000 g birthweight. Management of full-term infants who are small for gestational age at birth is less clear, but in general bone mineral content is associated more with body size than gestational age and supplementation is often provided to these infants. Although all infants, including preterm ones need a source of vitamin D, the benefits of providing high doses of vitamin D to healthy preterm neonates is unproven. Some evidence indicates that most calcium absorption is non-vitamin D dependent in the first weeks of life in both preterm and term infants. However, after achieving full feeds in the preterm infant, it is prudent to provide vitamin D at amounts comparable to that used in full-term infants. Higher doses increase serum 25-hydroxyvitamin D levels more rapidly, but evidence is inconclusive as to the relative benefits vs possible risks of higher doses. In healthy full-term infants, although vitamin D provision via supplement drops to the breastfed infant, high dose maternal supplementation to the lactating mother or infant formula is generally recommended, the current evidence only strongly supports its use in identified at-risk infants.

A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption

Obese and malabsorptive patients have difficulty increasing serum 25-hydroxyvitamin D [25(OH)D] after taking vitamin D supplementation. Since 25(OH)D is more hydrophilic than vitamin D, we hypothesized that oral 25(OH)D supplementation is more effective in increasing serum 25(OH)D concentrations in these patients. We aimed to investigate the pharmacokinetics of oral 25-hydroxyvitamin D3 [25(OH)D3] and oral vitamin D3 in healthy participants with differing BMI and malabsorptive patients. A randomized, double-blind crossover trial was performed in 6 malabsorptive patients and 10 healthy participants who were given 900 µg of either vitamin D3 or 25(OH)D3 orally followed by a pharmacokinetic study (PKS). After ≥28 d from the first dosing, each participant returned to receive the other form of vitamin D and undergo another PKS. For each PKS, serum vitamin D3 and 25(OH)D3 were measured at baseline and at 2, 4, 6, 8, and 12 h and days 1, 2, 3, 7, and 14. Pharmacokinetic parameters were calculated. Data were expressed as means±SEMs. The PKS of 900 µg vitamin D3 revealed that malabsorptive patients had 64% lower AUC than healthy participants (1177±425 vs. 3258±496 ng · h/mL; P<0.05). AUCs of 900 µg 25(OH)D3 were not significantly different between the 2 groups (P=0.540). The 10 healthy participants were ranked by BMI and categorized into higher/lower BMI groups (5/group). The PKS of 900 µg vitamin D3 showed that the higher BMI group had 53% lower AUC than the lower BMI group (2089±490 vs. 4427±313 ng · h/mL; P<0.05), whereas AUCs of 900 µg 25(OH)D3 were not significantly different between the 2 groups (P=0.500). Oral 25(OH)D3 may be a good choice for managing vitamin D deficiency in malabsorption and obesity. This trial was registered at clinicaltrials.gov as (NCT03401541.

Vitamin D Food Fortification and Biofortification Increases Serum 25-Hydroxyvitamin D Concentrations in Adults and Children: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundLow vitamin D status is a global public health issue that vitamin D food fortification and biofortification may help to alleviate. ObjectivesWe investigated the effect of vitamin D food fortification and biofortification on circulating 25-hydroxyvitamin D (25(OH)D) concentrations. We expanded the scope of earlier reviews to include adults and children, to evaluate effects by vitamin D vitamer, and investigate linear and nonlinear dose-response relations. MethodsWe conducted a systematic review and meta-analysis. We searched CINAHL, MEDLINE, PubMed, Embase, the Cochrane Library, and gray and unpublished literature sites for randomized controlled trials, including people of all ages, with the criteria: absence of illness affecting vitamin D absorption, duration ≥4 wk, equivalent placebo food control, dose quantification, dose ≥5 μg/d, baseline and endpoint or absolute change in 25(OH)D concentrations reported, random allocation, and participant blinding. Quality was assessed using the Jadad Scale. ResultsData from 34 publications (2398 adults: 1345 intervention, 1053 controls; 1532 children: 970 intervention, 562 controls) were included. Random-effects meta-analysis of all studies combined (mean dose 16.2 μg/d) indicated a pooled treatment effect of 21.2 nmol/L (95% CI: 16.2, 26.2), with a greater effect for studies using cholecalciferol than ergocalciferol. Heterogeneity was high (I2> 75%). Metaregression analyses for all studies combined suggested positive effect differences for baseline circulating 25(OH)D concentrations <50 nmol/L, dose ≥10 μg/d and a negative effect difference when the intervention arm included a calcium dose ≥500 mg/d greater than the control arm. Dose-response rates were found to be nonlinear (Wald test for nonlinearity P < 0.001). For all studies combined, a threshold occurred at ∼26 nmol/L for a dose of ∼21 μg/d. ConclusionsThese results support use of vitamin D food fortification to improve circulating 25(OH)D circulations in populations. This work was registered with PROSPERO as CRD42020145497.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18–70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.