Objective: To determine whether vitamin D supplementation influences grip strength, explosive leg power, cardiorespiratory fitness and risk of exercise-induced bronchoconstriciton (EIB) in South African schoolchildren. Methods: Sub-study (n=450) in Cape Town schoolchildren aged 8-11 years, nested within a phase 3 randomised placebo-controlled trial (ViDiKids). The intervention was weekly oral doses of 10,000 IU vitamin D3 (n=228) or placebo (n=222) for 3 years. Outcome measures were serum 25-hydroxyvitamin D3 (25[OH]D3) concentrations, grip strength, standing long jump distance, peak oxygen uptake (VO2peak, determined using 20-metre multi-stage shuttle run tests) and the proportion of children with EIB, all measured at end-study. Results: 64.7% of participants had serum 25(OH)D3 concentrations <75 nmol/L at baseline. At 3-year follow-up, children randomised to vitamin D vs. placebo had higher mean serum 25(OH)D3 concentrations (97.6 vs. 58.8 nmol/L respectively; adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6) and long jump distance (128.3 vs. 122.1 cm; aMD 3.6 cm, 95% CI 0.0 to 7.2). No end-study differences in grip strength, VO2peak, or spirometric lung volumes were seen, but administration of vitamin D vs. placebo was associated with a borderline-significant increased risk of EIB (14.5% vs. 8.6%; adjusted odds ratio 1.92, 95% CI 0.99 to 3.73). Conclusion: A 3-year course of weekly oral supplementation with 10,000 IU vitamin D3 elevated serum 25(OH)D3 concentrations in South African schoolchildren and induced a small increase in long jump distance, but had no effect on grip strength or VO2 peak. Potential effects of vitamin D on risk of EIB require further research.

ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests.

NCT02880982

This research was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1, both awarded to ARM). RJW was supported by Wellcome (104803, 203135). He also received support from the Francis Crick Institute which is funded by Cancer Research UK (FC2112), the UK Medical Research Council (FC2112) and Wellcome (FC2112). NCH and CC are supported by the UK Medical Research Council [MC_PC_21003; MC_PC_21001].

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The trial was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2). Participants and their parents/guardians provided written informed assent and consent, respectively, to take part in the trial before any study procedures were conducted.

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