Abstract
Vitamin D is widely known for its role in bone metabolism, but this sterol hormone also has important immunomodulatory properties. Vitamin D is produced by the conversion of D3 in the skin following UVB exposure, or after ingestion of D2 or D3. At the extremes of latitude, there is insufficient UVB intensity in the autumn and winter months for adequate synthesis of vitamin D to occur. Growing evidence implicates vitamin D deficiency in early life in the pathogenesis of nonskeletal disorders (e. g., type 1 diabetes and multiple sclerosis) and, more recently, atopic disorders. Several studies have reported higher rates of food allergy/anaphylaxis or proxy measures at higher absolute latitudes. Although causality remains to be determined, these studies suggest a possible role for sunlight and/or vitamin D in the pathogenesis of food allergy/anaphylaxis.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Australasian Society for Clinical Immunology and Allergy. The economic impact of allergic disease in Australia: not to be sneezed at. ASCIA/Access Economics Report. November 2007 (http://www.allergy.org.au/content/view/324/76/). Accessed May 2011.
Patel DA, Holdford DA, Edwards E, Carroll NV. Estimating the economic burden of food-induced allergic reactions and anaphylaxis in the United States. J Allergy Clin Immunol. 2011. doi:10.1016/j.jaci.2011.03.013.
Lieberman JA, Sicherer SH. Quality of life in food allergy. Curr Opin Allergy Clin Immunol. 2011;11:236–42.
Thyagarajan A, Varshney P, Jones SM, et al. Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol. 2010;126:31–2.
Lack G. Epidemiologic risks for food allergy. J Allergy Clin Immunol. 2008;121:1331–6.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
Holick MF. Vitamin D: a millennium perspective. J Cell Biochem. 2003;88:296–307.
Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med. 2009;169:626–32.
Mansbach JM, Ginde AA, Camargo CA Jr. Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D? Pediatrics. 2009;124:1404–10.
Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United States: review of cases reported between 1986 and 2003. Am J Clin Nutr. 2004;80(suppl):1697S–705S.
Ginde AA, Sullivan AF, Mansbach JM, Camargo CA Jr. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010;202:436.e1–8.
Camargo CA Jr, Ingham T, Wickens K, et al. The New Zealand asthma and allergy Cohort study group. Vitamin D status of newborns in New Zealand. Br J Nutr. 2010;50:259–61.
Eyles D, Anderson C, Ko P, et al. A sensitive LC/MS/MS assay of 25OH vitamin D3 and 25OH vitamin D2 in dried blood spots. Clin Chim Acta. 2009;403:145–51.
Teale GR, Cunningham CE. Vitamin D deficiency is common among pregnant women in rural Victoria. Aust N Z J Obstes Gynacecol. 2010;50:259–61.
•• Wang TJ, Zhang F, Richards JB et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376: 180–8. A genome-wide association study of almost 34,000 Europeans revealed that at least 4 major genes associated with cholesterol synthesis, hydroxylation, and vitamin D transport were associated with marked variation in vitamin D levels.
•• Merewood A, Mehta SD, Grossman X et al. Widespread vitamin D deficiency in urban Massachusetts newborns and their mothers. Pediatrics. 2010; 125: 640–7. Of 489 maternal–infant pairs, more than 58% of infants and 36% of their mothers were vitamin D deficient, defined as 25(OH)D less than 20 ng/mL, with risk factors being higher maternal body mass index, skin color, and winter birth. Vitamin D sufficiency in the last two trimesters was associated with neonatal sufficiency.
•• Perampalam S, Ganda K, Chow K et al. Vitamin D status and its predictive factors in pregnancy in 2 Australian populations. Aust N Z J Obstetr Gynaecol. 2011. doi:10.1111/j.1479-828X.2011.01313.x. Vitamin D deficiency (defined as 25[OH]D levels <25 nmol/L) was seen in approximately 30% of pregnant women in two Australian cohorts, with risk factors being high body mass index, skin color, and winter birth. Oral vitamin D supplements of 500 IU/d were provided inadequate protection against insufficiency.
Scragg R, Camargo CA Jr. Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2008;168:577–86.
Javaid MK, Crozier SR, Harvey NC, et al. Princess Anne Hospital Study Group. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006;367:36–43. Erratum in: Lancet. 2006; 367: 1486.
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86:50–60.
Vassallo MF, Camargo CA Jr. Potential mechanisms for the hypothesized link between sunshine, vitamin D and food allergy in children. J Allergy Clin Immunol. 2010;126:217–22.
Searing DA, Leung DY. Vitamin D in atopic dermatitis, asthma and allergic diseases. Immunol Allergy Clin North Am. 2010;30:397–409.
Clark S, Camargo CA Jr. Epidemiology of anaphylaxis. Immunol Allergy Clin North Am. 2007;27:145–63.
Lieberman P, Camargo CA Jr, Bohlke K, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. 2006;97:596–602.
Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001;161:15–21.
Simons FE, Peterson S, Black CD. Epinephrine dispensing patterns for an out-of-hospital population: a novel approach to studying the epidemiology of anaphylaxis. J Allergy Clin Immunol. 2002;110:647–51.
Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007;85:788–95.
Camargo CA Jr, Clark S, Kaplan MS, et al. Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D. J Allergy Clin Immunol. 2007;120:131–6.
Staples JA, Ponsonby AL, Lim LL, McMichael AJ. Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence. Environ Health Perspect. 2003;111:518–23.
Mullins RJ, Clark S, Camargo CA Jr. Regional variation in EpiPen prescriptions in Australia: more evidence for the vitamin D-anaphylaxis hypothesis. Annals Allergy Asthma Immunol. 2009;103:488–95.
Braganza SC, Acworth JP, Mckinnon DR, et al. Paediatric emergency department anaphylaxis: different patterns from adults. Arch Dis Child. 2006;91:159–63.
Sheehan WJ, Graham D, Ma L, et al. Higher incidence of pediatric anaphylaxis in northern areas of the United States. J Allergy Clin Immunol. 2009;124:850–2.
Sheehan WJ, Graham D, Ma L, et al. Higher incidence of pediatric anaphylaxis in southern areas of the United States. J Allergy Clin Immunol. 2009;123:S185.
Hughes AM, Lucas RM, Ponsonby AL, et al. The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study. Pediatr Allergy Immunol. 2011;22:327–33.
Mulla ZD, Lin RY, Simon MR. Perspectives on anaphylaxis epidemiology in the United States with new data and analyses. Curr Allergy Asthma Rep. 2011;11:37–44.
Gupta R, Sheikh A, Strachan DP, Anderson HR. Time trends in allergic disorders in the UK. Thorax. 2007;62:91–6.
Poulos LM, Waters AM, Correll PK, et al. Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993–1994 to 2004–2005. J Allergy Clin Immunol. 2007;120:878–84.
Rudders SA, Banerji A, Vassallo MF, et al. Trends in pediatric emergency department visits for food-induced anaphylaxis. J Allergy Clin Immunol. 2010;126:385–8.
Sheikh A, Hippisley-Cox J, Newton J, Fenty J. Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. J R Soc Med. 2008;101:139–43.
Decker WW, Campbell RL, Manivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008;122:1161–5.
Grundy J, Matthews S, Bateman B, et al. Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol. 2002;110:784–9.
Mullins RJ, Dear K, Tang ML. Characteristics of childhood peanut allergy in the Australian Capital Territory 1995–2007. J Allergy Clin Immunol. 2009;123:689–93.
Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol. 2010;125:1322–6.
Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126:807–13.
Prescott SL, Smith P, Tang M, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol. 2008;19:375–80.
Mullins RJ, Clark S, Camargo CA Jr. Socio-economic status, geographic remoteness and childhood food allergy and anaphylaxis in Australia. Clin Exp Allergy. 2010;40:1523–32.
Joseph CL, Ownby DR, Havstad SL, et al. Early complementary feeding and risk of food sensitization in a birth cohort. J Allergy Clin Immunol. 2011;127:1203–10.
Mullins RJ, Clark S, Camargo CA Jr. Regional variation in infant hypoallergenic formula prescriptions in Australia. Pediatr Allergy Immunol. 2010;21(2 Pt 2):e413–20.
Aalberse RC, Nieuwenhuys EJ, Hey M, Stapel SO. ‘Horoscope effect’ not only for seasonal but also for non-seasonal allergens. Clin Exp Allergy. 1992;22:1003–6.
Pyrhönen K, Läärä E, Hiltunen L, et al. Season of the first trimester of pregnancy predicts sensitisation to food allergens in childhood: a population-based cohort study from Finland. J Epidemiol Community Health. 2010. doi:10.1136/jech.2009.105411.
Vassallo MF, Banerji AS, Rudders SA, et al. Season of birth is associated with food allergy in children. Annals Allergy Asthma Immunol. 2010;104:307–13.
Mullins RJ, Clarke S, Katelaris CH, et al. Season of birth and childhood food allergy in Australia. Ped Allergy Immunol. 2011;22:583–9.
Nwaru BI, Ahonen S, Kaila M, et al. Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age: a prospective cohort study. Pediatr Allergy Immunol. 2010;21(1 Pt 1):29–37.
•• Sharief S, Jariwala S, Kumar J et al. Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol. 2011;127:1195–202. 25(OH)D deficiency (defined as <15 ng/mL) was associated with higher rates of sensitization to peanut and inhalant allergens in children and adolescents.
Sidbury R, Sullivan AF, Thadhani RI, Camargo CA Jr. Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot study. Br J Dermatol. 2008;159:245–7.
Miyake Y, Sasaki S, Tanaka K, Hirota Y. Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Respir J. 2010;35:1228–34.
Camargo CA Jr, Ginde AA, Mansbach JM. Vitamin D, respiratory infections, and obstructive airway diseases. In: Holick MF, editor. Vitamin D: Physiology, molecular biology, and clinical applications. 2nd ed. Totowa: Humana Press; 2010. p. 997–1021.
Sandhu MS, Casale TB. The role of vitamin D in asthma. Ann Allergy Asthma Immunol. 2010;105:191–9.
Brehm JM, Schuemann B, Fuhlbrigge AL, et al. Childhood Asthma Management Program Research Group. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010;126:52–8.
Erkkola M, Kailaw M, Nwaruz BI, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy. 2009;39:875–82.
•• Hollams EM, Hart PH, Holt BJ et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011; in press. Low 25(OH)D levels at age 6 and 14 years were associated with higher rates of sensitization to inhalant allergens in an unselected community birth cohort.
•• Majak P, Olszowiec-Chlebna M, Smejda K, Stelmach I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J Allergy Clin Immunol. 2011;127:1294–6. In a double-blind, randomized trial of budesonide alone or budesonide plus vitamin D supplements in 48 patients aged 5 to 18 years, vitamin D–supplemented patients had significant improvements in forced expiratory volume in 1 second and fewer infection-related exacerbations in asthma.
Urashima M, Segawa T, Okazaki M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91:1255–60.
Peroni DG, Piacentini GL, Cametti E, et al. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children. Br J Dermatol. 2011;164(5):1078–82. doi:10.1111/j.1365-2133.2010.10147.x.
Solé D, Wandalsen GF, Camelo-Nunes IC, Naspitz CK. ISAAC—Brazilian Group. Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC)—phase 3. J Pediatr (Rio J). 2006;82:341–6.
Fsadni P, Fsadni C, Fava S, Montefort S. Correlation of worldwide incidence of type 1 diabetes (Diamond) with prevalence of asthma and atopic eczema (ISAAC). Clin Respir J. 2011. doi:10.1111/j.1752-699X.2011.00239.x.
Weiland SK, Hüsing A, Strachan DP, et al. ISAAC Phase One Study Group. Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children. Occup Environ Med. 2004;61:609–15.
Wjst M, Dharmage S, André E, et al. Latitude, birth date, and allergy. PLoS Med. 2005;2(10):e294.
Wjst M. Introduction of oral vitamin D supplementation and the rise of the allergy pandemic. Allergy Asthma Clin Immunol. 2009;5:8.
Gale CR, Robinson SM, Harvey NC, et al. Princess Anne Hospital Study Group. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr. 2008;62:68–77.
Hyppönen E, Sovio U, Wjst M, et al. Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann N Y Acad Sci. 2004;1037:84–95.
Kull I, Bergström A, Melén E, et al. Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood. J Allergy Clin Immunol. 2006;118:1299–304.
de Montis G, Truong M, Toussaint B, et al. Peanut sensitization and oily solution vitamin preparations. Arch Pediatr. 1995;2:25–8.
Moro JR, Iwata M, von Andriano UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8:685–98.
Rothers J, Wright AL, Stern DA et al. Cord blood 25 hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona. J Allergy Clin. Immunol 2011 (in press).
Raby BA, Lazarus R, Silverman EK, et al. Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Respir Crit Care Med. 2004;170:1057–65.
Hyppönen E, Berry DJ, Wjst M, Power C. Serum 25-hydroxyvitamin D and IgE—a significant but nonlinear relationship. Allergy. 2009;64:613–20.
Zittermann A, Dembinski J, Stehle P. Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10. Pediatr Allergy Immunol. 2004;15:242–6.
Hartmann B, Heine G, Babina M, et al. Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response. Allergy. 2011. doi:10.1111/j.1398-9995.2010.02513.x.
Milovanovic M, Heine G, Hallatschek W, et al. Vitamin D receptor binds to the ε germline gene promoter and exhibits transrepressive activity. J Allergy Clin Immunol. 2010;126:1016–23.
•• van der Aar AM, Sibiryak DS, Bakdash G et al. Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells. J Allergy Clin Immunol. 2011. doi:10.1016/j.jaci.2011.01.068. In this in vitro study, vitamin D3–primed human dendritic cells induced tolerogenic regulatory T cells expressing interleukin-10.
•• Camargo CA Jr, Ingham T, Wickens K et al. New Zealand Asthma and Allergy Cohort Study Group. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011;127:e180–7. doi: 10.1542/peds.2010-0442. Low cord blood 25(OH)D levels were associated with increased risk of respiratory infection and wheezing in early life, but not incident asthma at age 5 years.
Devereux G, Litonjua AA, Turner SW, et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr. 2007;85:853–9.
Roth DE. Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials. J Perinatol. 2011;31(7):449–59. doi:10.1038/jp.2010.203.
•• Stalgis-Bilinski KL, Boyages J, Salisbury EL et al. Burning daylight: balancing vitamin D requirements with sensible sun exposure. Med J Aust. 2011;194:345–8. This examination of sun exposure and vitamin D production showed it would be difficult to obtain sufficient vitamin D without exposing the skin to levels of UVR at which sun protection is currently recommended.
Disclosure
Dr. Mullins has received unrestricted investigator-initiated grants from Commonwealth Serum Laboratories Australia and Alphapharm Australia, Abbott Nutrition Australia, and the Ilhan Food Allergy Foundation.
Dr. Camargo has received investigator-initiated research grants from and served as a consultant for Dey Pharma and Sanofi-Aventis. Study sponsors had no input into the contents of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mullins, R.J., Camargo, C.A. Latitude, Sunlight, Vitamin D, and Childhood Food Allergy/Anaphylaxis. Curr Allergy Asthma Rep 12, 64–71 (2012). https://doi.org/10.1007/s11882-011-0230-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11882-011-0230-7