Role of Vitamin D in Allergy Dr. Elizabeth Kiragu Paediatric Allergy Specialist Aga Khan University Hospital, Nairobi KPA Conference 9th April 2019

Primary role in bone homeostasis

Acceptable normal values for vitamin D Deficiency : < 20 ng/ ml Insufficiency: 21-29 ng/ ml Sufficient : 30-50 ng/ ml

Extra renal production in the immune system Local production of Vitamin D 3 by cells that express the gene CYP27B1 Epithelial cell,s monocytes, macrophages, APC, B & T cells express the VDR Activation of the VDR leads to interaction with VDRE and transcription of target genes with various effects on the immune system Immunomodulatory effect thought be an environmental factor in the pathogenesis of various immune conditions

Decreases infection by microbial pathogens by increasing production of antimicrobial peptides Strengthens the skin barrier Promotes tolerance Decreases lymphocyte responses Influence on homing in of lymphocytes

Adapted from Vitamin D in allergic disease: Shedding light on a complex problem. Muehleisen and Gallo, (J Allergy Clin Immunol 2013;131:324-9.)

Role in asthma Mirzakhani et al, 2015 Vitamin D increases glucocorticoid effect – stimulation on MPK1 ( mitogen activated protein kinase phosphatase → anti infl, Also increases IL 10 - immunosuppressive Mirzakhani et al, 2015

Reduction from 0. 44 – 0. 28 per person per year Reduction from 0.44 – 0.28 per person per year. No effect on day to day asthma control, lung functions Martineau et al, 2017

This analysis had a larger presentation of adults vs children 4% vs 19% Martineau et al, 2017

Unable to do sub-analysis of doses Wide range of doses used < 400 > 2000 IU Bolus and daily versus daily doses Baseline Vitamin D level Some studies found exacerbation of COPD in patients with higher baseline vitamin D who received further doses Severity of asthma Excluded severe asthma

Kim et al 2016

Limitation Sample size too small to make definitive conclusions Issues noted in studies included: Different dosses used 800 IU/ day – 4000 IU/ day Different types of Vitamin D Different dosing intervals No baseline Vitamin D measured No control for confounders

Trend towards lower Vitamin D levels in CSU patients 12 studies 1 – no difference 1- opposite Vitamin D supplementation in CSU improves symptoms Better response with higher doses

5105 participants Pooled analysis – OR 1.35 95% CI (0.79- 2.29) p= 0.27 between Vitamin D and Food allergy 4 studies defined Vitamin D deficiency < 20 ng/ ml: OR 1.18 95% CI ( 0.62- 2.27) p= 0.62 1 study – defined Vitamin D deficiency as < 30 ng/ ml: OR 2.04 95% CI( 1.02- 4.04) P = 0.04 Hampered by definition of Vitamin D deficiency

Conclusion Vitamin D has various effects on the immune system These effects can be utilized in the management of allergic conditions Role in prevention require better designed long term studies Stick to current guidelines