Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial

Abstract

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3-500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

Key Vitamin D Target Genes with Functions in the Immune System

“…It acts as a negative regulator of the signaling pathways of NF-kB [56] and interferon [57], i.e., it suppresses the production of inflammatory cytokines and modulates the response to viral infections. The latter is a long overlooked effect of vitamin D on the immune system [58,59] and a reason why vitamin D deficiency may lead to high vulnerability against viral infections in the elderly, but also in school children [15,60,61].…”

The Role of Micronutrients in Support of the Immune Response against Viral Infections

“…From the early 2000s, various studies were conducted, mainly in children from lower socio-economic settings, to establish whether daily or weekly zinc supplementation could help in preventing respiratory tract infections ( Table 9 ) [ 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 ].…”

“…In 2007, Sazawal et al reported a slight reduction in the relative risk of all-cause mortality in children supplemented with zinc in Zanzibar [ 277 ]. Other studies found instead that zinc supplementation had no significant effect on the frequency of respiratory infections [ 274 , 275 , 276 , 278 , 279 , 281 ]. Some of these trials used a lower daily dose of zinc, which might be one of the reasons why the supplementation was less effective; however, both negative and positive results were reported with different zinc dosages, from 5 up to 30 mg/day.…”

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials

“…30 Since the date of the final literature search in this previous meta-analysis (Dec 31, 2015), 21 RCTs involving 64 220 participants who fulfilled the same eligibility criteria have been done (including four with unpublished data [NCT02404623, NCT02046577, NCT01875757, and NCT01758081]). [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] We therefore sought data from these more recent studies for inclusion in an updated metaanalysis of stratified aggregate (ie, trial-level) data to establish whether vitamin D supple mentation reduced overall ARI risk, and to evaluate whether the effects of vitamin D supplementation on ARI risk varied according to baseline 25(OH)D concentration, dosing regimen (frequency, dose, and trial duration), or age at enrolment.…”