Rapid Normalization of Vitamin D Levels: A Meta-Analysis

Abstract

BACKGROUND: Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain. METHODS:We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose ($1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields. RESULTS:We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine's Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels .75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (.50 000 IU) achieved group 25(OH)D levels .75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses .400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses ,400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens .300 000 IU.CONCLUSIONS: Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses .300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit. Dr McNally conceptualized and designed the study, carried out the initial analysis, drafted the initial manuscript, and revised the manuscript for important intellectual content; Mr Iliriani, Dr Pojsupap, and Ms O'Hearn designed the data collection instrument, determined study eligibility, acquired data, and revised the article critically for important intellectual content; Dr Sampson conceptualized and designed the search strategy, acquired data, drafted the initial manuscript, and revised the manuscript for important intellectual content; Drs McIntyre, Fergusson, and Menon conceptualized and designed the study, interpreted the data, and critically revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted.The systematic review was registered with PROSPERO (identifier CRD42013006677). Normalization of vitamin D status has the potential to speed recovery and improve outcomes in multiple acutely unwell pediatric populations. Most of the guidelines and clinical practice surrounding vitamin D dosing involves a daily intake of ,1000 IU. 6,7 Because these standard dosing strategies target healthy children and require months to restore normal levels, they are not applicab...

Treatment of Vitamin D Deficiency in Predominantly Hispanic and Black Adolescents: A Randomized Clinical Trial

“…The highest post-treatment 25(OH)D level was 66.5ng/mL, well below toxic range (88–100ng/mL). 32 The mean baseline VDBP level was almost twice as high in the 66 Hispanic participants compared with the 34 black participants (p<0.001) and did not change with vitamin D3 treatment (Table II). The mean post-treatment serum 25(OH)D level in each of the high-dose arms was in the sufficient range, whereas, the mean post-treatment level in the low-dose arm remained in the deficient range (Figure 2, A).…”

“…A meta-analysis for rapid normalization of vitamin D levels (within one month) in pediatric trials found greater efficacy for single or intermittent high-dose loading regimens (≥50,000IU) compared to daily low-dose regimens (1,000–4,000IU) in children and called for more trials studying loading-dose regimens, especially in adolescent patients. 32 Further, they reported an adverse event analysis showing the safety of doses <400,000IU in adolescents.…”

“…32, 34 In this study, we further categorize severe and mild/moderate vitamin D deficiency to inform treatment decisions in clinical practice. Our study suggests that adolescents with severe deficiency do not necessarily need higher treatment doses than those with milder deficiency as they have better treatment responses.…”

Dosage of Vitamin D in Children and Adolescents

“…Установлено статистически значимое снижение риска обострения аст-мы (на 59%) при терапии витамином D по сравнению с контролем [28].…”

Prevention and Treatment of Vitamin D Deficiency: Current Look at the Issue

“…По данным боль-шого метаанализа, нагрузочные дозы до 300 000 МЕ (это соответствует, например, двум флаконам Аквадетрима, объем одного флакона -10 мл, в котором содержится 15 000 МЕ витамина D в 1 мл) безопасны в плане гипер-кальциемии или гиперкальциурии: риск этих побочных эффектов повышается при использовании доз более 400 000 МЕ [21].…”