Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia

Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
PEDIATRICS (Impact Factor: 5.47). 08/2012; 130(3):e561-7. DOI: 10.1542/peds.2011-3029
Source: PubMed


Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs.
By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January-March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D(3) (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months.
At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5-10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P < .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31-0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28-0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; P(interaction) = .27).
Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency.

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    • "Several RCTs showing a better effect of vitamin D supplementation compared to placebo on these diseases or their complications exist to-date (see for example [72–79]). The results of these positive RCTs are however generally not applicable to the general population as they were targeted to specific groups [76–78], or were the results of secondary objectives of studies that had been designed to study another function [72], or concerned intermediate parameters and not “hard” (clinical) end-points [73–75, 79]. Furthermore, numerous RCTs have been “null” in that they showed no benefit, but also no disadvantage compared to placebo. "
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    ABSTRACT: Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case-control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.
    09/2014; 72(1):32. DOI:10.1186/2049-3258-72-32
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    • "Evidence from double-blinded randomized clinical trials (RCTs) for vitamin D interventional studies is warranted to confirm the clinically relevant effect of vitamin D in RTIs. Camargo et al43 investigated whether vitamin D supplementation in children with vitamin D deficiency would lower the risk of ARI. Compared with controls, children receiving vitamin D (300 IU/daily) have been reported to have significantly fewer ARIs during the study period. "
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    ABSTRACT: Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed.
    Journal of Inflammation Research 05/2014; 7(1):69-87. DOI:10.2147/JIR.S63898
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    • "Urashima et al. reported that children, ages 6–15, receiving daily supplementation with 1200 IU vitamin D3 had a 42% lower risk of influenza A infection [17]. Camargo et al., reported a 50% risk reduction in parent-reported URTI among children, ages 9–11, receiving daily supplementation with 300 IU of vitamin D3[18]. "
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    ABSTRACT: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. We randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2) placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI95:0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI95:0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI95:0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log10 viral copies/mL (mean difference: -0.89, CI95: -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI95:0.53-1.26, p = 0.36). These results suggest that vitamin D3 is a promising intervention for the prevention of URTI. Vitamin D3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. Trial registration Clinical Trials Registration: NCT01158560.
    BMC Infectious Diseases 05/2014; 14(1):273. DOI:10.1186/1471-2334-14-273 · 2.61 Impact Factor
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