Vitamin D3 Supplementation In Children Research Articles

Safety and efficacy of monthly high-dose vitamin D3 supplementation in children and adolescents with sickle cell disease.

Little is known about the impact of vitamin D supplementation on hand grip strength (HGS) and health-related quality of life (HRQoL) in children and adolescents with sickle cell disease (SCD). We aimed to evaluate the safety and efficacy of monthly high-dose vitamin D3 supplementation and its implications on bone mineral density (BMD), HGS, and HRQoL in patients with SCD and healthy controls. The study included 42 children with SCD and 42 healthy matched controls. The study participants were supplemented with high-dose monthly oral vitamin D3. Changes in the serum level of 25(OH) vitamin D3, maximum HGS, and BMD from baseline to 6months were assessed, and the HRQoL questionnaire and Childhood Health Assessment Questionnaire (CHAQ) were used to evaluate the functional capacity. At baseline, SCD subjects had poorer growth status indicated by negative Z scores. Suboptimal BMD was detected by significantly lower Z score, and lower HGS and worse HRQL parameters were found compared to the controls (P < 0.001). Median 25(OH) vitamin D3 was significantly lower in SCD patients compared to controls (16.5 vs. 28ng/mL, respectively (P < 0.001)). After 6months of vitamin D supplementation, there was significant improvement in the DEXA Z-score (P < 0.001), limitation of physical health (P = 0.02), pain scores (P < 0.001), and CHAQ grades (P = 0.01) in SCD patients. A significant improvement in HGS (P < 0.001 and P = 0.005) as well as the CHAQ score (P < 0.001 and P = 0.003) was detected in the SCD group and controls, respectively. There were no reported clinical adverse events (AEs) or new concomitant medications (CMs) during the study duration, and safe levels of Ca and 25 (OH) D3 were observed at 3 and 6months for both groups. There was a significant positive correlation between HGS and total physical score (r = 0.831, P < 0.001) and a negative correlation with CHAQ score (r = - 0.685, P < 0.001). We also detected a significant positive correlation between vitamin D levels at 6months and HGS (r = 0.584, P < 0.001), pain score (r = 0.446, P < 0.001), and a negative correlation with CHAQ score (r = - 0.399, P < 0.001). Conclusion: Monthly oral high-dose vitamin D supplementation was safe and effective in improving vitamin D levels, HGS, and HRQoL in SCD children and healthy subjects, and BMD scores in SCD patients. Further randomized controlled trials are warranted to assess an optimal dosing strategy and to investigate the impact on clinically significant outcomes in children and adolescents with SCD and their healthy counterparts. Trial registration: ClinicalTrials.gov , identifier NCT06274203, date of registration: 23/02/2024, retrospectively registered. What is known: • Several studies have reported a high prevalence of vitamin D deficiency and suboptimal bone mineral density (BMD) in sickle cell disease (SCD) patients. • Musculoskeletal dysfunction is reported in SCD patients with a negative impact on physical activity and health-related quality of life (HRQL). • Little is known regarding the impact of vitamin D3 supplementation in children and adolescents with SCD. What is new: • We found that monthly oral high-dose vitamin D3 supplementation was safe, tolerated, and effective in improving serum vitamin D levels, HGS, BMD scores, and HRQL in SCD patients.

TRAJECTORIES OF SERUM 25(OH)D IN CHILDREN WITH PARALYTIC SYNDROMES WHEN USING VITAMIN D FROM DIFFERENT MANUFACTURERS AND IN DIFFERENT DOSES

The prevalence of vitamin D deficiency and insufficiency varies significantly in different subpopulations of children depending on age and diseases, and recommendations for their correction in children with paralytic syndromes are limited.Aim. Empirical determination of blood 25(OH)D trajectory in children with paralytic syndromes when using vitamin D from different manufacturers and in different doses.Material and methods. The 25(OH)D (ng/ml) of blood serum was analyzed by immune-enzymatic method "Labline-90" (Austria) with the test system "Monobind Inc." (ELISA, USA) in 77 children with paralytic syndromes aged 1-18 years, a repeat study after vitamin D3 supplementation was conducted in 36 children. The rate of increase in 25(OH)D concentration per month was calculated. Methods of descriptive statistics, non-parametric correlation analysis and Kaplan-Meier survival analysis were used with MedCalc Statistical Software (Belgium).This study was approved by the Ethics Committee (protocol No. 5, October 2021), which was conducted with the involvement of minor patients and did not contain measures that could harm their health.The research was carried out within the framework of the Department of Pediatrics of Kharkiv National Medical University "Medical and social aspects of adaptation of children with somatic pathology in modern conditions" (state registration number 0120U102471, 2020).Results. Vitamin D insufficiency was diagnosed in 17% of children with paralytic syndromes, and vitamin D deficiency in 73%, so daily doses of 2000-4000 IU of vitamin D3 from different manufacturers were recommended at the discretion of the parents for 6 months. In reality, children received doses from 500 to 5000 IU randomly, from 2 to 7 months. Doses were stratified as greater than 2000 IU and less than 2000 IU. If the child received a dose of 2000 IU or more, the rate of increase of 25(OH)D in the blood in children was 3.6 ng/ml per month, if the dose was less than 2000 IU - 1.6 ng/ml per month.Conclusions. Children with paralytic syndromes should be screened and monitored for serum 25(OH)D levels. With a serum 25(OH)D level of less than 20 ng/ml, daily administration of vitamin D3 in a dose of at least 2000 IU for at least 6 months allows reaching a 25(OH)D level of 30 ng/ml in most of them. Further large-scale studies are needed to supplement current recommendations for vitamin D3 supplementation in children with paralytic syndromes.

Effect of Vitamin D3 Supplementation on Severe Asthma Exacerbations in Children With Asthma and Low Vitamin D Levels: The VDKA Randomized Clinical Trial

To investigate if supplementation with vitamin D3 would improve the time to a severe exacerbation in children at high risk with vitamin D insufficiency and taking low-dose inhaled corticosteroids (ICSs) for persistent asthma.The participants were recruited from 7 children’s hospitals across the United States. Participants, 6 to 16 years of age, had to have physician-diagnosed asthma for at least 1 year, being treated with low-dose ICSs, and have a serum 25-hydroxyvitamin D level less than 30 ng/mL. They also had to have at least 1 severe asthma exacerbation in the last year (defined as systemic steroids for at least 3 days or an emergency department visit or hospitalization requiring systemic corticosteroids). All participants had to show bronchodilator responsiveness or airway responsiveness to methacholine inhalation. The mean age of the participants was 9.8 years (40% girls). A total of 219 subjects passed screening and entered run-in. A total of 192 subjects were randomly assigned to active drug or placebo capsules.This was a randomized, double-blind, parallel, placebo-controlled clinical trial. Participants initially all received placebo capsules and were maintained on inhaled fluticasone propionate, 176 μg per day (6–11 years) or 220 μg per day (12–16 years) during run-in. They continued the ICSs and then were randomly assigned to daily vitamin D3 4000 IU or continuing placebo for 48 weeks. After 24 weeks, participants dose of fluticasone was reduced by 50%, if asthma was well controlled and spirometry was normal. Serum vitamin D levels and parameters of asthma control were measured every 16 weeks. The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of ICS was reduced halfway through the trial, and the cumulative fluticasone dose during the trial.A total of 94% of randomly assigned subjects completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had ≥1 severe exacerbations. Compared with the placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation. The mean time to exacerbation was 240 days in the vitamin D3 group versus 253 days in the placebo group (mean group difference: −13.1 days; adjusted hazard ratio: 1.13; P = .63). Vitamin D3 supplementation, compared with the placebo, did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of ICSs was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group: n = 11; placebo group: n = 9).In children 6 to 16 years old with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with a placebo, did not significantly improve the time to a severe asthma exacerbation or ICS dosing.As the authors note, in several observational studies, researchers have linked low serum vitamin D levels to severe asthma exacerbations, lower lung function, and reduced response to corticosteroids. Yet meta-analyses and reviews of vitamin D3 supplementation for severe asthma exacerbations have found insufficient evidence to recommend vitamin D3 supplementation in children. In this study, the authors, looking at a high-risk population for asthma exacerbations, add to that negative body of literature.

Clinical improvement following vitamin D3 supplementation in children with chronic tic disorders.

PurposeVitamin D deficiency has been found in children with chronic tic disorders (CTDs). Our previous data showed that serum 25-hydroxyvitamin D [25(OH)D] level in children with CTDs was lower than that of the healthy controls and lower serum 25(OH)D level was associated with increased severity of the tic disorder. Thus, we intend to further verify this phenomenon and examine the effect of vitamin D3 on CTDs.Patients and methodsIn total, 120 children with CTDs and 140 normal controls were enrolled in this study, with 36/120 of those in the CTD group receiving vitamin D3 treatment for 3 months. The Yale Global Tic Severity Scale (YGTSS) and Clinical Global Impression of Severity of Illness (CGI-SI) were, respectively, used to evaluate the tic severity. High-performance liquid chromatography and tandem mass spectrometry were used to measure serum 25(OH)D level.ResultsThose children with CTDs exhibited significantly lower 25(OH)D levels than did healthy controls, and these reduced 25(OH)D levels were linked to increasing severity of tic symptoms. After treatment with supplemental vitamin D3, serum 25(OH)D level and scores of YGTSS total, motor tics, phonic tics, total tic, impairment, and CGI-SI improved significantly in children with CTDs without any adverse reactions.ConclusionSupplementation vitamin D3, given its low cost and excellent safety, may be an effective means of improving symptoms in certain children with CTDs.

Comparison of the effects of perceptual-motor exercises, vitamin D supplementation and the combination of these interventions on decreasing stereotypical behavior in children with autism disorder

Objectives: The aim of this study was to examine the combined effects of perceptual-motor exercises and vitamin D3 supplementation on the reduction of stereotypical behavior in children with autism spectrum disorder (ASD).Methods: In this study, 100 eligible children with age ranging from 6 to 9 years were randomly selected and divided into four groups: Group A—perceptual-motor exercises (n = 25); Group B—25-hydroxycholecalciferol (25 (OH) D) (n = 25); Group C—perceptual-motor exercises and 25 (OH) D (n = 25); and Group D—control (n = 25).Results: The stereotypes decreased from elementary level, 17% in Group A, 13% in Group B and 28% in Group C among the participants. There was no change in the stereotypical in the control group during the interventions. Also, the stereotypes in Group C showed the highest decrease, compared to the other three groups.Conclusions: We concluded that combination of perceptual-motor exercises and vitamin D3 supplementation in children with ASD leads to significant reduction in their stereotypic behaviors.

Blunted serum 25(OH)D response to vitamin D3 supplementation in children with autism

Introduction: Data suggest a potential role for vitamin D in autism spectrum disorder (ASD) prevention and treatment. It is likely that the serum response to vitamin D supplementation contributes to its effectiveness. Multiple factors affect serum vitamin D 25(OH)D response to supplementation. Methods: We conducted post-hoc analysis of two double-blind, randomized, placebo-controlled trials (RCT) of vitamin D3 supplementation, one RCT involving children with ASD and another involving children with asthma. Both trials were conducted in the same geographic location (Dublin, Ireland, 53°N), conducted over Winter season and utilized the same vitamin D3 dose (2000 IU/day). Results: We included 18 children with ASD and 17 children with asthma. There was no significant difference in 25(OH)D or age at baseline, however, BMI was significantly lower in ASD (P = 0.03). Compliance with vitamin D supplementation was high in both trials. Despite a significantly longer intervention period (20w vs. 15w; P < 0.0001), ASD children had a significantly lower absolute increase (+26 vs. +45 nmol/l) in 25(OH)D (P = 0.04). Conclusions: Despite similar demographics, children with ASD had a lower increase in 25(OH)D levels with supplementation. Potential mechanisms include altered absorption/metabolism as well as well genetic factors. Clinical and research work relating to vitamin D is ASD should measure 25(OHO)D response to supplementation to assess therapeutic doses.

Short-Term Vitamin D3 Supplementation in Children with Neurodisabilities: Comparison of Two Delivery Methods

Background/Aims: Vitamin D deficiency is common in children with neurodisabilities. Oral vitamin D₃ may not be absorbed appropriately due to dysphagia and tube feeding. The aim of this study was to compare efficacy of vitamin D₃ buccal spray with that of oral drops. Methods: Twenty-four children with neurodisabilities (5–17 years) and vitamin D deficiency (25(OH)D ≤20 ng/mL) were randomized to receive vitamin D₃ buccal spray 800 IU/daily (n = 12) or oral drops 750 IU/daily (n = 12) for 3 months during winter. Results: Both groups had a significant increase in 25(OH)D (z = 150; p < 0.0001). The differences between baseline and final parathyroid hormone measurements did not reach significance in both groups. Markers of bone formation and resorption did not change significantly in both groups. The satisfaction with the formulation was significantly higher in the patients using spray. Conclusion: Vitamin D₃ supplementation with buccal spray and oral drops are equally effective in short-term treatment of vitamin D deficiency in children with neurodisabilities. Buccal spray may be more acceptable by the patients.

Open-Label Trial of Vitamin D3 Supplementation in Children with Autism Spectrum Disorder

JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume X, Number x, 2016 a Mary Ann Liebert, Inc. Pp. 1–10 DOI: 10.1089/cap.2015.0159 Original Article Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism Robert L. Hendren, DO, 1 S. Jill James, PhD, 2 Felicia Widjaja, MPH, 1 Brittany Lawton, BS, 1 Abram Rosenblatt, PhD, 1 and Stephen Bent, MD 1 Abstract Objective: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 lg/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome mea- sures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. Results: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure – the clinician rated CGI-I score – was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2–0.2, p = 0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine ( p = 0.05), decreases in S-adenosyl-l- homocysteine (SAH) ( p = 0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH ( p = 0.007), indi- cating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. Conclusions: Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry: Efficacy Study of Subcutaneous Methyl B12 in Children with Autism: NCT01039792 (clinical trials.gov1). Introduction with autism had significantly lower plasma methionine, S- adenosylmethionine (SAM), homocysteine, cystathionine, cysteine, and total glutathione as well as significantly higher levels of S-adenosyl-l-homocysteine (SAH), adenosine, and oxidized gluta- thione. These laboratory changes were consistent with increased oxidative stress and impaired methylation capacity in children with ASD ( James et al. 2004). As shown in Figure 1, these abnormalities are related to three interconnected metabolic pathways known col- lectively as methionine transmethylation/transsulfuration metabo- lism (Hirsch et al. 2008; Kalinina et al. 2014; Watson et al. 2014). A second study in 2006 of 80 children with ASD and 73 controls again demonstrated the same pattern of methylation deficit and oxidative stress ( James et al. 2006). A more recent study in 2012 examined 68 children with ASD, 40 unaffected siblings, and 54 age- matched unaffected, unrelated control children. Reduced methyla- tion capacity was associated with DNA hypomethylation and reduced glutathione antioxidant defense in the children with ASD but not in their unaffected siblings or control children (Melnyk et al. A utism spectrum disorder (ASD) is a complex neurodeve- lopmental disorder characterized by deficits in social inter- action and restricted, repetitive patterns of behavior that now affects 1 in 68 children (Developmental Disabilities Monitoring Network Surveillance Year Principal and Centers for Disease Control and Prevention 2014). ASD has a significant genetic component, with up to 25% of cases being caused by an identifiable genetic defect (Huguet et al. 2013). However, two recent epide- miologic studies have concluded that environmental influences have a greater contribution than genetic factors in the etiology of autism (Hallmayer et al. 2011; Sandin et al. 2014). Many metabolic processes have shown specific deficits in children with ASD, including both cellular methylation and glutathione- mediated antioxidant defense (Rossignol and Frye 2012). In 2004, James et al. reported findings of a small study of 20 children with autism compared with 33 healthy controls, and found that children Department of Psychiatry, University of California, San Francisco, California. Arkansas Children’s Hospital Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Funding: This study was supported by a grant from Autism Speaks (grant #3031 to Dr. Hendren).

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.

Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 (vitD3) versus placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. This was a double-blind trial of perinatally acquired HIV (PHIV)-infected subjects or behaviorally acquired HIV (BHIV)-infected subjects (5.0-24.9 years). Safety, 25(OH)D-related parameters and immune status were assessed at baseline, 3, 6 and 12 months. Fifty-eight subjects enrolled (67% male, 85% African American and 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6 and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P < 0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P < 0.001). Percentage of naive T-helper cells (Th naive%) were significantly (P < 0.01) and T-helper cells (CD4%) marginally (P < 0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P < 0.05). Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation.

Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus.

Suboptimal vitamin D (vitD) status is common in children and young adults infected with human immunodeficiency virus (HIV). The vitD supplemental dose needed to normalize vitD status in this population is unknown. In this double-blind trial, subjects infected with HIV ages 8.3 to 24.9 years were randomized to vitD3 supplementation of 4000 IU/day or 7000 IU/day and evaluated at 6 and 12 week for changes in vitD status and HIV indicators. A dose was considered unsafe if serum calcium was elevated (above age and sex-specific range) associated with elevated serum 25 hydroxyvitamin D (25(OH)D); >160 ng/mL). At baseline, 95% of subjects (n = 44; 43% with perinatally acquired HIV, 57% with behaviorally acquired HIV) had a suboptimal serum 25(OH)D concentration of <32 ng/mL (mean ± standard deviation, 19.3 ± 7.4; range, 4.4-33.6 ng/mL). After 12 weeks (main outcome) of D3 supplementation, both D3 doses were safe and well tolerated, with no evidence of elevation of serum calcium concentrations or deterioration in HIV immunologic or virologic status. Sufficient vitD status, defined as serum 25(OH)D ≥32 ng/mL, was achieved in 81% of all subjects, and only the 7000 IU/day group (86%) achieved this a priori efficacy criterion in >80% of subjects. Change in serum 25(OH)D did not differ between HIV acquisition groups. A 7000 IU/day D3 supplementation was safe and effective in children and young adults infected with HIV.

Blood Lead Concentration Is Not Altered by High‐Dose Vitamin D Supplementation in Children and Young Adults With HIV

Optimal vitamin D status is known to have beneficial health effects and vitamin D supplements are commonly used. It has been suggested that vitamin D supplementation may increase blood lead in children and adults with previous lead exposure. The objective was to determine the safety regarding lead toxicity during 12 weeks of high-dose vitamin D3 supplementation in children and young adults with human immunodeficiency virus (HIV). Subjects with HIV (8-24 years) were randomized to vitamin D3 supplementation of 4000 or 7000 IU/day and followed at 6 and 12 weeks for changes in serum 25-hydroxy vitamin D (25D) and whole-blood lead concentration. This was a secondary analysis of a larger study of vitamin D3 supplementation in children and adolescents with HIV. In 44 subjects (75% African American), the baseline mean ± standard deviation serum 25D was 48.3±18.6 nmol/L. Fifty percent of subjects had baseline serum 25D <50.0 nmol/L. Serum 25D increased significantly with D3 supplementation during the 12 weeks. No subject had a whole-blood lead >5.0 μg/dL at baseline or during subsequent visits. Whole-blood lead and 25D were not correlated at baseline, and were negatively correlated after 12 weeks of supplementation (P=0.014). Whole-blood lead did not differ between those receiving 4000 and 7000 IU of vitamin D3. High-dose vitamin D3 supplementation and the concomitant increased serum 25D did not result in increased whole-blood lead concentration in this sample of children and young adults living in a northeastern urban city.