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Development of a novel dietary assessment tool for vitamin D and the in vivo and in vitro effects of supplementation on asthma

Watkins, Stephanie
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2023-09
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Vitamin D is a secosteroid hormone with the essential role of maintaining calcium and phosphorus homeostasis to support bone metabolism. Furthermore, vitamin D has also been shown to have important immunomodulatory functions, which have been linked to inflammatory diseases such as asthma. In the UK, 18.8% of the general population are vitamin D deficient during the winter. In 2016, SACN proposed recommendations that adults in the UK consume 400 IU (10 μg) vitamin D day-1. Health and disease are linked to diet and nutrition therefore, assessing food intake is crucial. A food frequency questionnaire (FFQ) captures habitual food intake with a lower participant burden compared to alternative methods. Validation of a FFQ requires comparison of nutrient biomarkers with another method of dietary assessment. The first study in this thesis recruited 50 healthy volunteers to assess the agreement between a four-day food diary and a newly designed vitamin FFQ to measure dietary intake of vitamin D. Participants provided a blood sample for plasma analysis of 25(OH)D concentrations. Results of this study showed a strong correlation between vitamin D intake recorded by the FFQ and the food diary (r = 0.609, p < 0.0001) within 95% limits of agreement. Our analysis suggested that this FFQ is a useful and rapid tool for researchers and health professionals to assess vitamin D dietary intakes in UK adults. Vitamin D deficiency is linked to asthma in adults and associated with reduced lung function. Clinical trials investigating the effect of vitamin D supplementation have mainly focussed on asthmatic children and trials carried out in adults have used bolus dosing. The aim of chapter 3 was to conduct a 12-week randomised placebo-controlled trial investigating the effect of daily 5000 IU vitamin D supplementation on lung function and inflammation in 32 adults with mild to moderate asthma. The intervention resulted in a significant increase in the mean (± SD) ratio of FEV1: FVC from baseline (week 0) to post-intervention (week 12) in the vitamin D group (+ 0.05 ± 0.06) compared to the placebo group (+ 0.006 ± 0.04, p = 0.04). This dosing strategy at a level above current UK recommendations may be a useful adjunct to existing asthma control strategies. The Calu-3 cell line has been used as a model of asthma and the aim of chapter 4 was to investigate the effect of calcitriol and 25(OH)D treatment of Calu-3 cell cultures on cell proliferation and secretion of inflammatory biomarkers. Incubation of cultures for 24 and 72 hours respectively, with 50nM (p = 0.002; p < 0.0001), 100nM (p = 0.004; p = 0.007) and 200nM (p = 0.002; p < 0.0001) 25(OH)D resulted in significantly decreased proliferation compared to an untreated control. No effect was observed with calcitriol treatment. To our knowledge, this is the first in vitro study using the Calu-3 cell line to show differing effects of vitamin D metabolites. The findings from this thesis are clinically relevant in the UK in a population that is at increased risk of vitamin D deficiency during the winter months. The new tool designed and validated will facilitate easier measurement of vitamin D dietary intakes and the clinical trial and in vitro work have provided novel insights to patient outcomes and underlying mechanisms of the benefit of vitamin D supplementation to asthma patients.
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Watkins, S. (2023). Development of a novel dietary assessment tool for vitamin D and the in vivo and in vitro effects of supplementation on asthma [Unpublished doctoral thesis]. University of Chester.
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University of Chester
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Thesis or dissertation
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en
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