IU Vitamin D3 Research Articles

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration

BackgroundCystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. ObjectiveWe used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. DesignTwenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. ResultsSeveral amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways—predominantly representing amino acid pathways—differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. ConclusionsNumerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting.

The bioavailability of vitamin D3, a model hydrophobic nutraceutical, in casein micelles, as model protein nanoparticles: Human clinical trial results

The use of protective protein-based nanovehicles to deliver hydrophobic nutraceuticals raises important questions regarding their consequent bioavailability compared to that inside fat, or in its presence. To answer that, vitamin-D3 was chosen as a model lipophilic-bioactive, re-assembled casein micelles (rCM) as a protein-based nanovehicle and 0% fat yoghurt as a model nonfat food. We performed a single-high-dose-ingestion clinical trial with 94 healthy human volunteers, each receiving 150g yoghurt containing 50,000IU of vitamin-D3. Vitamin-D3 was either in rCM in the absence or presence of fat, or dissolved in milk fat. Un-enriched nonfat yoghurt was the negative control. The bioavailability of vitamin-D3 was determined by measuring its status-indicator: serum 25-hydroxyvitamin D level. The bioavailability of vitamin-D3 within the protein nanoparticles in the absence of fat was found to be insignificantly different from its bioavailability within fat, suggesting that the bioavailability of lipophilic bioactives in protein nanovehicles is not lower than in fat.

Vitamin D Improves Selected Metabolic Parameters but Not Neuropsychological or Quality of Life Indices in OSA: A Pilot Study.

Our group and others have reported a high rate of vitamin D deficiency in obstructive sleep apnea (OSA), where vitamin D levels (25(OH) D) correlate negatively with OSA severity and some of its associated metabolic alterations. Data regarding vitamin D supplementation in OSA are lacking. We wanted to evaluate the effect of vitamin D3 supplementation on OSA symptoms and metabolic parameters. We conducted a pilot, double-blind, randomized, placebo-controlled trial of daily supplementation with 4,000 IU vitamin D3 (D3) or placebo (PL). We studied 19 Caucasian adults (14 male, mean age 55 y, mean body mass index [BMI] 30.4 kg/m2) with OSA. Fifteen patients were stable on continuous positive airways pressure (CPAP) therapy, whereas four were CPAP naïve. Assessments were completed at baseline and after 15 weeks of supplementation. Outcomes included sleepiness (Epworth Sleepiness Scale), quality of life (Sleep Apnea Quality of Life Inventory), fatigue (fatigue severity scale) and neuropsychological function (trail making test and Connor's Continuous Performance Test II). In addition, we assessed biochemical indices of vitamin D status (25(OH)D, calcium), inflammation (high sensitivity C-reactive protein, and lipoprotein-associated phospholipase A2), lipids (total cholesterol [low-density and high-density lipoprotein]) and glycemic indices (fasting glucose, oral glucose tolerance test). There was no change in BMI, medication, or CPAP usage. Although there was no change in neuropsychological or quality of life indices, we observed a significant increase in 25(OH)D (p = 0.00001) and significant decreases in both low-density lipoprotein (p = 0.04) and lipoprotein-associated phospholipase A2 (p = 0.037) as well as trends toward decreased fasting glucose (p = 0.09) and increased high-density lipoprotein (p = 0.07) in the D3 group compared to PL. Vitamin D3 supplementation increased vitamin D levels and decreased metabolic markers compared to placebo. Larger trials are required.

25(OH)D status: Effect of D3 supplement

SummaryBackgroundExcess adipose tissue may lead to sequestrating of vitamin D, making it less available for use in the body.ObjectiveThis study determined if overweight or obese individuals (BMI > 25 kg m−2) had insufficient (<30 ng mL−1) levels of 25‐hydroxyvitamin D [25(OH)D] and, if so, would serum levels respond to exogenous supplementation.MethodsSixty‐three women who were overweight/obese (BMI = 31.07 ± 5.00 kg m−2) were randomly assigned in a double‐blind manner to receive 5,000 IU of vitamin D3 (D3) (n = 31) or a placebo (PL) (n = 32) daily. Serum 25(OH)D concentrations were measured by finger‐stick analyses at baseline and after 8 weeks of supplementation. Data were analyzed by using a 2 × 2 (group × time) repeated measure multivariate analysis of variance to determine group differences for pre‐values and post‐values (p < 0.05).ResultsOn day one of the study, both D3 and PL groups had insufficient levels of vitamin D (mean ± SD) 24.03 ± 9.78 ng mL−1 and 23.62 ± 9.77 ng mL−1, respectively. After 8 weeks of supplementation, the D3 group 25(OH)D level rose to a mean of 43.57 ± 10.87 ng mL−1 (p < 0.001) versus the PL group whose 25(OH)D level remained statistically unchanged 24.31 ± 8.84 ng mL−1. Women who were overweight/obese had insufficient vitamin D levels prior to supplementation.ConclusionsFollowing supplementation with 5,000 IU of vitamin D3, all subjects' 25(OH)D levels rose to a sufficient level (≥30 ng mL−1). The findings of this study concur with the Institute of Medicine and Endocrine Society recommendations in that two to three times the daily requirement of vitamin D is required to improve serum vitamin D levels in individuals who are overweight or obese.

Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000IU vitamin D3 supplements (n=29) or placebo (n=29) every 2weeks for 6months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P=0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3±11.4 vs. -0.1±3.7ng/mL, P<0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3±7.3 vs. +2.4±5.9 μIU/mL, P<0.001), homeostasis model of assessment-insulin resistance (-1.2±1.6 vs. +0.5±1.2, P<0.001), homeostatic model assessment-Beta cell function (P=0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03±0.04 vs. -0.007±0.02, P<0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5±10.3 vs. +4.0±13.4μmol/L, P=0.001), total antioxidant capacity (TAC) (P=0.04), total glutathione (GSH) (+11.8±153.5 vs. -294.2±595.1μmol/L, P=0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8±1.0 vs. -0.03±1.4μmol/L, P=0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels. Clinical trial registration number www.irct.ir : IRCT201412065623N30.

Safety and Efficacy of Weekly 30,000 IU Vitamin D Supplementation as a Slower Loading Dose Administration Compared to a Daily Maintenance Schedule in Deficient Patients: A Randomized, Controlled Clinical Trial

Introduction: The primary objective of the study was to assess the safety and the efficacy of a “Slower Loading” dose of 30,000 IU vitamin D3 supplementation administered in a weekly schedule for 12 weeks in vitamin D deficient patients compared to the daily equivalent dose of 1000 IU/day regimens in a clinical trial. Methods: This open label, randomized, controlled, multicenter clinical trial was performed during the spring and summer period enrolling adult subjects with 25O HD levels <20 ng/ml. In a sub-study presented here, subjects were randomized into two treatment groups using 30,0000 IU Vitamin D3 film tablets either in weekly (WD30K group, daily dose equivalent of 4286 IU/day) or a standard dose for maintenance treatment in a daily administration (SDD1K group, 1000 IU/day). Subjects in a control group received a similar 30,0000 IU Vitamin D3 film tablets in a once-permonth schedule (MD30K), dosing schedule for 12 weeks, (an equivalent to 1000 IU/day). The assessment of efficacy made by the changes in 25O HD and PTH levels in a throughout 12 weeks. Routine laboratory tests, serum and urinary calcium served for laboratory-safety assessments in every 4 weeks throughout the duration of the study. Results: The baseline values of 25O HD at in group (WD30K, SDD1K and MD30K) were in similar range: 13.7 ± 3.7 ng/mL, 13.48 ± 3.9 ng/mL and 13.1 ± 4.3 ng/mL, respectively. A daily dose of 1000 IU for 12 weeks was effective in restoration of 25O HD values to above 20 ng/mL (50 nmol/L), however the median of the group failed to attain the 30 ng/mL (75 nmol/L) threshold. Dose-response was statistically different in the 4286 IU/day group compared to a 1000 IU/daily dose (p 30 ng/ml): 91% vs. 10% of subjects in after 8 weeks with 30,000 IU/wk and 1000 IU/d doses and 95% vs. 24% by end of the 12 weeks of treatment. The treatment-related increment potential was in a range of 2.26-2.92 ng/week for the weekly 30K dosing group compared to 1.32-1.70 ng/week for the 1000 IU/day standard maintenance dose group after 8 weeks. Treatment with 30,000 IU doses of Vitamin D3 in a weekly administration for 12 weeks did not abolish serum calcium levels. No difference in frequency of laboratory adverse events and other safety parameters was observed compared to lower maintenance doses or to control group. Conclusion: The safety of weekly loading oral doses of 30,000 IU vitamin D3 tablets was demonstrated and efficacy compared to the maintenance treatment with a daily dose equivalent of 1000 IU/d, in a daily or in monthly schedule in vitamin D deficient, adult population. Weekly administration of 30,000 IU loading dose for 12 weeks does not raise safety concern, but provides an effective tool for normalization of 25O HD levels to the desirable level of >30ng/mL in deficient patients.

Soluble TNF Receptors are Modulated by Vitamin D Status but not by Acute Perturbations in 25-Hydroxyvitamin D Following A Bolus of Supplemental Vitamin D

The first objective of this study was to identify if soluble tumor necrosis factor-receptor 1 (sTNFr1) and -receptor 2 (sTNFr2) are modulated by vitamin D status (insufficient vs. sufficient). The second objective was to reveal if soluble TNF receptors fluctuate with serum 25-hydroxyvitamin D (25(OH)D) concentrations following a bolus of supplemental vitamin D. Reportedly healthy male adults were randomly (double-blind) assigned to a placebo (n=15) or vitamin D (100,000 IU of cholecalciferol; n=14) supplement. Supplements were taken as a bolus immediately after and on the same day as providing the first blood sample (baseline (Bsl)). Fasting blood samples were also obtained at 1-, 3-, 7-, and 24-d after the bolus. Serum 25(OH)D, 1,25-dihyroxyvitamin D (1,25(OH)D), tumor necrosis factor (TNF)-α, sTNFr1, and sTNFr2 were measured in each blood sample. At Bsl, subjects were classified as vitamin D insufficient (serum 25(OH)D

Lower pain and higher muscular strength in immigrant women with vitamin D deficiency following vitamin D treatment

ABSTRACTBackground: Vitamin D deficiency is common among immigrants in the Nordic region. It may lead to osteomalacia with severe musculoskeletal pain. There are reports that vitamin D deficiency without osteomalacia may lead to pain but little is known of the effect of treatment.Objective: To investigate whether a moderate dose of cholecalciferol and calcium improves strength and pain in a group of vitamin D deficient women.Design: Twentyfive immigrant women with vitamin D deficiency diagnosed during pregnancy were treated postpartum with a daily dose of 1,600 IU cholecalciferol and 1,000 mg of calcium. They were examined at the start of treatment and again after 3 months of treatement and the results were statistically compared. Setting: Southern parts of Stockholm.Main outcome measures: Serum 25-hydroyvitamin D (25(OH)D), serum-parathyroid hormone (PTH), pain measured by a visual analogue scale (VAS), musculoskeletal strength by performance on a chair stand test (seconds), and bone tenderness by pressure algometer (kilo-Pascal).Results: Following the treatment, the 21 women attending had lowered cm in VAS, improved musculoskeletal strength, - and 25(OH)D levels were normalized.Conclusions: A moderate dose of vitamin D normalized l vitamin D levels, improved muscular strength and reduced pain in this group of vitamin D deficient immigrant women.

Vitamin D Toxicity in Young Breastfed Infants: Report of 2 Cases.

Vitamin D toxicity in infants is not uncommon, and has been reported as early as the 1930s, usually due to antirachitic treatment with very high doses of vitamin D. This usually involves administration of 600 000 IU vitamin D2 oral or intramuscularly (termed “stoss therapy”) resulting in vitamin D toxicity symptoms related to hypercalcemia.1-4 Most of these case reports occurred outside the United States. Recently, there are reports of vitamin D toxicity in very young breastfed infants, mostly in the United States, from inadvertent overdose with highly concentrated vitamin D formulation obtained over-the-counter or from free-standing stores (Table 1). Table 1. Case Reports of Breastfed Infants Who Had Vitamin D Toxicity.

Effect of Curcuma xanthorrhiza Supplementation on Systemic Lupus Erythematosus Patients with Hypovitamin D Which Were Given Vitamin D3 towards Disease Activity (SLEDAI), IL-6, and TGF-β1 Serum.

Background Curcumin contained in Curcuma xanthorrhiza is an immunomodulator that has similar biological effect as vitamin D. Combination of curcumin and vitamin D3 is expected to work synergistically. Objective To determine the effect of Curcuma xanthorrhiza supplementation on vitamin D3 administration to SLEDAI, IL-6, and TGF-β1 serum in SLE patients with hypovitamin D. Methods This was a double-blind RCT conducted in Saiful Anwar Hospital, Malang, in January 2016–March 2017. Subjects were SLE active (SLEDAI > 3) with levels of 25(OH)D3 ≤ 30 ng/ml and divided into two groups: those receiving cholecalciferol 3 × 400 IU and placebo 3 × 1 tablets (group I) and those receiving 3 × 400 IU cholecalciferol and Curcuma xanthorrhiza 3 × 20 mg for 3 months (group II). SLEDAI, levels of vitamin D, IL-6, and TGF-β1 in serum were evaluated before and after the treatment. Results There were no significant differences in SLEDAI reduction, decreased serum levels of IL-6, and increased levels of TGF-β1 serum among groups after the treatment. Decreased levels of serum IL-6 have a positive correlation with SLEDAI reduction. Conclusion. Curcuma xanthorrhiza supplementation on vitamin D3 had no effects on SLEDAI and serum levels of IL-6 and TGF-β1. This clinical trial is registered with NCT03155477.

Association of Vitamin D Repletion with Normalization of Elevated Serum 17-OH-Progesterone

Insulin resistance is associated with a number of conditions, such as non-classic 21-hydroxylase deficiency and allied disorders. Serum vitamin D is often deficient/ insufficient in insulin resistant individuals. Disorders associated with insulin resistance are often mitigated in association with vitamin D repletion. Here we report a patient with type 2 diabetes mellitus, lower extremity infection, vitamin D insufficiency, and elevated unstimulated serum 17-OH-progesterone (17-OHP), which normalized during vitamin D repletion. Serum 25-OHvitamin D (25-OHD) rose by 32% while serum 17-OHP fell by 87% over the course of four weeks receiving 50,000 IU ergocalciferol orally weekly. Vitamin D repletion in this setting restored normal serum 25-OHD levels and was associated with normalization of elevated serum 17-OHP. Serum 25-OHD levels should be determined before commencing glucocorticoids or mineralocorticoids for the treatment of elevated serum 17-OHP in disorders like non-classic adrenal hyperplasia (NCAH) and levels of 17- OHP, should be re-measured when vitamin D levels are replete to determine whether glucocorticoid/ mineralocorticoid replacement is actually necessary.

Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial.

Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production. A randomized controlled trial of daily vitamin D supplementation for 12weeks was performed with the aim to test the effects of 4000 versus 400IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children's hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring. A total of 34 subjects were randomized to either the intervention or control group, of whom 26.5% were female and 23.5% were African American. The mean age of the study cohort was 10.9 [standard deviation (SD) 5.8] years, the mean baseline glomerular filtration rate was 60 (SD 17.6) ml/min/1.73m2, and mean baseline 25D level was 29.7 (SD 11.5) ng/ml. At baseline, 50% of subjects were 25D deficient. There were no significant differences in baseline characteristics between the intervention and control groups. Treatment with 4000IU cholecalciferol was not associated with significant change in hepcidin level at 4 or 12weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. The median C-reactive protein level decreased significantly at 12weeks in the intervention group. These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis.

Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care

SummaryThis trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.IntroductionThe aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU (100 μg), 2000 IU (50 μg) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes.MethodsThis is a randomized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function.ResultsMean (SD) plasma 25(OH)D levels were 50 (18) nmol/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol/L after 12 months in those allocated 4000 IU, 2000 IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of >90 nmol/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function.ConclusionsAfter accounting for average 70% compliance in long-term trials, doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.

25 hydroxy vitamin D is higher when a renal multivitamin is given with cholecalciferol at hemodialysis.

Seventy six hemodialysis (HD) patients were used in a prospective randomized and clinical trial to determine if a multivitamin with vitamin D (cholecalciferol 12,000 IU/week) given during dialysis would improve the vitamin D status of hemodialysis subjects. Subjects were randomly assigned to two groups: 37 subjects were in the renal multivitamin without vitamin D (MV) group and 39 subjects were in a multivitamin route with vitamin D (MVD) group (12,000 IU of cholecalciferol per week). All subjects were given 2 multivitamin tablets at their 3 HD sessions each week for 20 weeks. Serum 25(OH)D, calcium (Ca), and phosphorus (P) levels were evaluated. At baseline, mean serum 25(OH)D were below adequate (<30 ng/mL) in the MV group (23.5±12.2 ng/mL) and in the MVD group (20.8±10.3 ng/mL). A significant increase was seen in serum 25(OH)D levels (37.7±11.4 ng/mL; p<0.001) in the MVD group after vitamin D supplementation with no rise in the MV group value (21.7±11.4 ng/mL; p=0.06). Prior to supplementation, 17.9% of patients in the MVD group had adequate serum 25(OH)D level and post supplementation 76.9% in the MVD group had adequate serum 25(OH)D. In the MV group, 18.9% subjects had adequate serum 25(OH)D levels at baseline with 18.9% having 25(OH)D >30 ng/mL at the end of the study. There were no significant differences in group values for serum Ca and P. The majority of HD subjects given a multivitamin with cholecalciferol at dialysis had improvement in their vitamin D status.

Long-term adherence and effects on grip strength and upper leg performance of prescribed supplemental vitamin D in pregnant and recently pregnant women of Somali and Swedish birth with 25-hydroxyvitamin D deficiency: a before-and-after treatment study

BackgroundMuscular weakness and severe vitamin D deficiency is prevalent in Somali (veiled) pregnant women, Sweden. The study aims here were to explore adherence to prescribed supplemental vitamin D in new mothers with vitamin D deficiency and its effects on grip strength and upper leg performance in Somali (target group TG) and Swedish women (reference group RG) from spring through winter.MethodsA before- and after study was designed. A cross-sectional sample of women in antenatal care with serum 25-OHD ≤50 nmol/L were prescribed one or two tablets daily (800 or 1600 IU vitamin D3 with calcium) for 10 months. Reminders were made by Somali nurses (TG) or Swedish doctors (RG). Baseline and 10 month measurements of plasma nmol/L 25-OHD, maximal grip strength held for 10 s (Newton, N) and ability to squat (yes;no) were done. Total tablet intake (n) was calculated. Outcome variables were changes from baseline in grip strength and ability to squat. Predicting variables for change in grip strength and ability to squat were calculated using linear and binary regression in final models. Undetectable 25-OHD values (<10 nmol/L) were replaced with ‘9’ in statistic calculations.ResultsSeventy-one women (46 TG, 1/3 with undetectable baseline 25-OHD; 25 RG) participated. At the 10-month follow up, 17% TG and 8% RG women reported having refrained from supplement. Mean 25-OHD increased 16 to 49 nmol/L (TG) and 39 nmol/L to 67 nmol/L (RG), (both p < 0.001). Grip strength had improved from 153 to 188 N (TG) (p < 0.001) and from 257 to 297 N (RG) (p = 0.003) and inability to squat had decreased in TG (35 to 9, p < 0.001). Intake of number of tablets predicted increased grip strength (B 0.067, 95%CI 0.008–0.127, p = 0.027). One tablet daily (>300 in total) predicted improved ability to squat (OR 16; 95% CI 1.8–144.6).ConclusionsAdherence to supplemental vitamin D and calcium should be encouraged as an even moderate intake was associated to improved grip strength and upper leg performance, which was particularly useful for the women with severe 25-OHD deficiency and poor physical performance at baseline.Trial registrationClinicalTrials.gov Identifier: NCT02922803. Date of registration: September 28, 2016.

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

Background: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation.Objective: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial.Methods: Eligible older adults who were not vitamin D–deficient [serum 25(OH)D ≥12 ng/mL] were randomly assigned in a modified 2 × 2 factorial design to 1 of 4 groups: daily 1000 IU cholecalciferol, 1200 mg Ca as carbonate, both, or placebo. Women could elect 2-group (calcium ± cholecalciferol) random assignment. In secondary analyses, we used multivariable models to assess factors associated with serum 25(OH)D concentrations in all enrollees (n = 2753) and with relative changes in serum 25(OH)D after 1 y cholecalciferol supplementation among those randomly assigned (n = 2187).Results: In multivariable models, 8 factors accounted for 50% of the variability of proportional change in serum 25(OH)D after cholecalciferol supplementation. Larger increases were associated with being female (34.5% compared with 20.5%; P < 0.001) and with lower baseline serum 25(OH)D (P < 0.0001), optimal adherence to study pill intake (P = 0.0002), wearing long pants and sleeves during sun exposure (P = 0.0002), moderate activity level (P = 0.01), use of extra vitamin D–containing supplements during the trial (P = 0.03), and seasons of blood draw (P ≤ 0.002). Several genetic polymorphisms were associated with baseline serum 25(OH)D and/or serum response, but these did not substantially increase the models’ R2 values. Other factors, including body mass index, were associated with serum 25(OH)D at baseline but not with its response to supplemental cholecalciferol.Conclusions: The factors that most affected changes in serum 25(OH)D concentrations in response to cholecalciferol supplementation included sex, baseline serum 25(OH)D, supplement intake adherence, skin-covering clothes, physical activity, and season. Genetic factors did not play a major role. This trial was registered at http://www.clinicaltrials.gov as NCT00153816.

Effect of vitamin D supplementation and isokinetic training on muscle strength, explosive strength, lean body mass and gait in severely burned children: A randomized controlled trial

ObjectiveTo determine the effects of vitamin D (VD) supplementation and isokinetic training on muscle strength, explosive strength (counter movement jump) (ES), lean body mass (LBM) and gait parameters in severe pediatric burn. MethodsForty-eight burned children with circumferential lower extremity burns covering 40–55% of the total body surface area (TBSA), aged 10–16 years (Mean±SD 13.01±1.75), were randomized into the standard of care (n=16), isokinetic (n=17) and VD (n=15) groups. Unburned children (n=20) served as matched controls. All burned children received 12 weeks of routine physical therapy program (RPTP). In addition, the isokinetic group received isokinetic training for the quadriceps dominant limb 3 times per week at angular velocity 150°/s, and the VD group received the isokinetic training plus an oral daily dose of vitamin D3 1000 IU (Cholecalciferol). The primary measures, assessed at baseline and 12 weeks, included quadriceps strength by isokinetic dynamometer, ES, LBM by dual-energy X-ray absorptiometry (DEXA) and gait parameters by GAITRite system. ResultsThe VD and isokinetic groups showed significant improvement in quadriceps strength, ES, LBM and gait parameters compared with the standard of care, and VD group show significant improvement in the VD level as compared with the other groups. The outcome measures (and percent of improvement where applicable) for the VD, isokinetic and standard of care are as follows: quadriceps strength, 85.25±0.93Nm (85%), 64.25±0.93 (36%) and 51.88±1.31Nm (12%); stride length, 94.00±2.69 (7%), 110.60±2.87 (25%) and 139.56±2.57 (60%); step length, 67.26±2.45 (72%), 55.25±2.49 (43%) and 43.76±1.34 (18%); velocity, 133.94±1.65 (82%), 99.94±1.65 (35%) and 80.11±1.91 (9%); and cadence, 140.63±1.36 (68%), 132.63±1.36 (58%) and 90.35±1.32 (9%), VD level 43.33±7.48 (75%), 24.77±7.38 (5%) and 25.63±8.39 (4%) respectively. ConclusionsVD supplementation combined with exercise training significantly increased muscle strength, ES, LBM, gait and VD level in severely burned children.

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial

BackgroundRecent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. ObjectivesWe evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DesignA multicenter, randomized, double-blinded, controlled clinical trial. ParticipantsMalnourished and sarcopenic men and women, 65 years and older (n = 330). InterventionA 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MeasurementsIsokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s−1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg−1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [<30 kg men; <20 kg women], low gait speed [<0.8 m·s−1]) and mild-moderate sarcopenia (low skeletal mass index, normal gait speed, or normal grip strength). ResultsBoth ONS groups (EONS and CONS) improved PT, MQ, grip strength, and gait speed from baseline with no treatment differences. Those with severe sarcopenia (44%) exhibited lower baseline PT and MQ, with no differences in strength improvements between treatments. However, participants with mild-moderate sarcopenia exhibited higher baseline PT and MQ, with differences in strength improvements at 12 weeks (EONS > CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. ConclusionONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS.

Rates of secondary hyperparathyroidism after bypass operation for super-morbid obesity: An overlooked phenomenon

With over 110,000 bariatric operations performed in the United States annually, it is important to understand the biochemical abnormalities causing endocrine dysfunction associated with these procedures. Here we compare 2 malabsorptive procedures, duodenal switch and Roux-en-Y gastric bypass, to determine the role malabsorption plays in secondary hyperparathyroidism in this population. Data from all super-obese patients undergoing duodenal switch or Roux-en-Y gastric bypass between August 2002 and October 2005 were prospectively collected. Postoperatively, all patients received 1,200mg of calcium citrate and 1,000 IU vitamin D3 per American Society for Metabolic and Bariatric Surgery guidelines. Beginning in 2007, duodenal switch patients were instructed to add daily vitamin D3 10,000 IU. Statistical analyses included Student t test, multivariate, and univariate logistic regression. Of 283 patients with a body mass index ≥50, 170 (60.1%) underwent duodenal switch, while 113 (39.9%) underwent Roux-en-Y gastric bypass. Of 132 (46.6%) patients with secondary hyperparathyroidism, 101 (59.4%) had undergone duodenal switch and 31 (27.4%) had undergone Roux-en-Y gastric bypass. Symptoms were more common in the duodenal switch group (33 patients [19.4%]) than Roux-en-Y gastric bypass (11 patients [9.7%]). Multivariate logistic regression demonstrated that the extent of bypass and duration of follow-up were the only 2 independent predictive risk factors for developing secondary hyperparathyroidism. Although vitamin D levels improved with increased vitamin D3 supplementation in 2007, rates of secondary hyperparathyroidism increased. Despite routine postoperative calcium and vitamin D3 supplementation, secondary hyperparathyroidism is common after Roux-en-Y gastric bypass and duodenal switch. The degree of iatrogenic malabsorption correlates with the incidence of secondary hyperparathyroidism. These rates suggest current supplementation guidelines are not sufficient in preventing secondary hyperparathyroidism. Further work is needed to better define the sequelae of long-term hyperparathyroidism.

Efficacy of high dose Vitamin D supplementation in improving serum 25(OH)D among migrant and non migrant population: a retrospective study.

BackgroundHigher dose of vitamin D supplementation 50000 IU is required for those whose serum 25(OH)D levels are 50 nmol/L and below. The increment in serum 25(OH)D though not significantly affected by race, sex or age it is negatively correlated to the baseline 25(OH)D concentration. This study investigated whether the mean increase in serum 25(OH)D will be higher among participants with lower baseline 25(OH)D levels and whether the duration of supplementation has an influence on the serum 25(OH)D achieved.MethodsA clinical audit of patients’ medical records from a community health centre in Melbourne for the period 01.01.2010 to 31–12.2012 was undertaken. Paired sample t test was used to determine difference in pre and post dose serum 25(OH)D. Simple and multiple linear regressions were used to examine the association between the difference in pre and post dose serum 25(OH)D and duration of supplementation and baseline serum 25(OH)D, adjusting for socio-demographic factors.ResultsA total of 205 patients were included in the study. Mean difference in serum 25(OH)D was highest 52.8 nmol/L (95 % CI: 46.63–58.92) among those whose serum 25(OH)D was below 25 nmol/L at baseline. Baseline 25(OH)D alone accounted for 13.7 % of variance in the effect size (F(2, 202) = 16.0. p < 0.001), with the effect size significantly higher among participants with a baseline 25(OH)D level of 25–49 nmol/L (β = 11.93, 95 % CI: 0.48, 23.40, p < 0.05). Mean serum 25(OH)D difference was highest, 47.53 nmol/L (95 % CI: 40.95–54.11) when measured within 3 months of supplementation. Duration of supplementation explained 2.9 % of the variance in the effect size (F (1, 203) = 6.11, p < 0.05) and there was an inverse relationship between the length of supplementation and mean pre and post supplementation serum 25(OH)D difference (β = −1.45, 95 % CI: −2.62, −0.29, p = 0.014).ConclusionFollowing 50000 IU vitamin D3 for 12 months mean serum 25(OH)D increase was highest among those whose baseline serum 25(OH)D was lower. Migrants especially dark-skinned are at a high risk for vitamin D deficiency in Australia. High dose vitamin D3 50000 IU (cholecalciferol) is effective in achieving sufficient serum 25(OH)D among these populations who tend to have lower baseline serum 25(OH)D.