Review Are vitamins A and D important in the development of food allergy and how are they best measured? Rosita Zakariaeeabkoo a,b , Katrina J. Allen c,d,e , Jennifer J. Koplin c , Peter Vuillermin c,f,g , Ronda F. Greaves a,c, ⁎ a School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia b Clinical Biochemistry, Austin Pathology, Heidelberg, Victoria, Australia c Murdoch Children's Research Institute, Parkville, Victoria, Australia d Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia e Department of Allergy and Clinical Immunology, Royal Children's Hospital, Parkville, Victoria, Australia f Deakin University, Geelong, Victoria, Australia g Child Health Research Unit, Barwon Health, Geelong, Australia abstract article info Article history: Received 31 October 2013 Received in revised form 23 January 2014 Accepted 25 January 2014 Available online xxxx Keywords: Allergy Retinol Cholecalciferol Analysis Mass spectrometry Food allergy has a dramatic impact on a child's (and their family's) quality of life and places a major financial bur- den on the community. It has been hypothesized that the increase in food allergy may relate to the concordant rise in prevalence of vitamin D insufficiency. More recently a second hypothesis has implicated vitamin A suffi- ciency in the development of immune tolerance. Together, these hypotheses have prompted investigation into the circulating levels of vitamins A and D in relation to food allergy prevalence. This review aims to examine the relationship between vitamins A and D and food allergy. The first part of this review presents the available epidemiological data which proposes a dramatic increase of food allergy and related anaphylaxis during the last two decades. There is some indirect evidence that variation in food allergy prevalence within countries might be linked with ambient ultra violet radiation exposure and thus potentially with vitamin D levels. Only a few studies to date have directly examined the relationship between measured serum vitamin D levels and either food sensitization or allergy. The significance of vitamin A in food allergy prevalence is only provided through a hypothetical association due to its role in the immune system. The second part of this review discusses the relevant aspects of the analytical methods to assess vitamin A and D levels in children. The primary methods utilized relate to measuring the main circulating forms of vitamins A and D in blood i.e. retinol and 25-hydroxy-vitamin-D 3 respectively. Chromatographic separation coupled with mass spectrometric detection is considered the gold standard method for both vitamins. These analytical methods should be fully validated for the use in pediatric populations to ensure they are fit for their clinical purpose. © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 What is the link between vitamins A & D and food allergy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Vitamin D: the indirect evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Vitamin D: the direct evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Vitamin A: is it worth studying as a potential risk factor? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 What is the biological plausibility of vitamin D in relation to food allergy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 How are these vitamins measured? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Vitamin A methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Vitamin D methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Combined vitamins A and D analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Alternative sample collection — Guthrie cards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Where to from here? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Clinical Biochemistry xxx (2014) xxx–xxx ⁎ Corresponding author at: School of Medical Sciences, RMIT University, PO Box 71, Bundoora, Victoria 3083, Australia. E-mail address: ronda.greaves@rmit.edu.au (R.F. Greaves). CLB-08635; No. of pages: 8; 4C: http://dx.doi.org/10.1016/j.clinbiochem.2014.01.033 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem Please cite this article as: Zakariaeeabkoo R, et al, Are vitamins A and D important in the development of food allergy and how are they best measured?, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.01.033