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Friday, July 30, 2010

Nudging forward a new paradigm for food allergies

Characterization of food allergies has produced abundant data on their clinical presentation, but the biological construct driving the pathology is a ghost in the machine. In this month’s issue, Vassallo and Camargo make an intrepid, but logical, gesture at a syncretic hypothesis of food allergy evolution.

The authors start with the epidemiologic observation that societal decreases in exposure to sunshine have led to a rise in vitamin D deficiency (VDD) and that these two changes are coeval with the increase in food allergies. They offer a hypothesis linking evidence of VDD to atopic progression, i.e., eczema, respiratory compromise, and food allergy. Specifically, they propose that VDD results in increased infection susceptibility and altered microbiota in the gut, which in turn, cause higher levels of mucosal barrier damage, permitting excessive exposure to food allergens through the “leaky gut.”

Vassallo and Camargo mention known associations between VDD, childhood obesity, and food allergy. Physiologic support for their hypothesis comes from recent evidence that vitamin D is critical to induction of tolerance, as well as antimicrobial peptide (AMP) production in the epithelium, and suppression of inflammatory responses.

It is the AMP factor that the authors use to tie VDD to the effector mechanism. In addition to increased susceptibility to infection, VDD causes dysregulation of AMPs in the intestine, supporting an abnormal intestinal flora. They also point to recent data that suggest VDD has a primary role in mucosal barrier compromise.

Wrapping up, Vassallo and Camargo note several incongruities, including that VDD prevalence is higher than food allergy prevalence and genetic atopic predispositions may act independently to increase food allergy risk, from which they suggest that multiple “hits” are required to result in food allergy. They urge future, cross-disciplinary research designed to examine their hypothesis that correction of VDD during pregnancy and early childhood will lead to improved tolerance, mucosal immunity, and balanced intestinal flora.

We asked the authors whether their hypothesis could be applied to adults as well as children:
JACI: You make the distinction between failure to develop tolerance as seen in childhood and loss of tolerance associated with adult onset of food allergy. Is there reason to believe that vitamin D supplementation might mitigate loss of tolerance as well?

Carlos Camargo: We have chosen to focus on children because that’s when most food allergy begins -- and where we have found supportive epidemiologic data (eg, our recent publication on season of birth and food allergy -- citation below). In brief, we found increased risk of food allergy among children born in fall/winter, as compared to spring/summer. We found no association between season of birth and food allergy in older patients. (Vassallo MF, Banerji A, Rudders SA, Clark S, Mullins RJ, Camargo CA Jr. Season of birth and food allergy in children. Ann Allergy Asthma Immunol 2010; 104: 307-313.)

While it’s theoretically possible that vitamin D supplementation might mitigate loss of tolerance in adults, we will continue to focus our research efforts on childhood food allergy.

Do you have any questions for the authors, or comments about this study? We want to hear from you. Please feel free to post your own questions or comments. All questions and comments will be forwarded to the authors for a response.


  1. I am of Asian Indian origin and have a child with food allergies. We live in the Boston area. From anecdotal evidence it appears that food allergies are very high among the 2nd generation Indian children and much higher than the general population. Have the authors or anybody else done any research on dark skin and food allergies?

  2. The authors respond: Although we also have the impression that food allergy is more common among darkly pigmented children in the northeastern US, such as children of Southeast Asian origin, we are not aware of studies on this issue. In a recent paper by Branum and Lukacs (Pediatrics 2009; 124: 1549-1555), the authors report a higher proportion of children with detectable food-specific IgE in the minority children (non-hispanic blacks > hispanics > non-hispanic whites), a finding that would support your observation. However, data on food allergy (identified with diagnostic codes) did not support this ranking; non-hispanic white children had the highest rates of recognized food allergy. We suspect, however, that there is substantial under-diagnosis of food allergy in US minority populations. We anticipate that broadening the racial/ethnic mix of research studies will expand our understanding of the health effects of sunlight and vitamin D, and clarify their possible contributions to the development and prevention of food allergy.

  3. Thank you for your response. I give my children a multivitamin everyday. Would you recommend giving them additional vitamin D supplements? I know the FDA recommendation is 400 IU. Is that enough for kids with dark skin living in the Northeast?

  4. The authors respond: Yes, we believe that most children in the Northeastern US (especially those with darkly pigmented skin) should take >400 IU daily during winter. The optimal amount will differ by child but many children will require 1000 IU daily to reach serum 25(OH)D of ~40 ng/ml. We encourage you to discuss this with your child's doctor.

  5. GRAS ingredients... the FDA gave pharmaceutical companies the right to "self-affirm" ingredients as Generally Recognized as Safe". What this means is the company has an independent company test an ingredient and they decide that it is GRAS. Nothing is submitted to the FDA. Nothing appears on the package insert. The ingredient is also a protected trade secret. All highly refined food oils are GRAS because they don't cause allergic reactions from a skin prick test. But that is not the same as injecting it with an adjuvant. Food allergies are directly caused by vaccinations. The increase in food allergies matches the vaccination schedule.

  6. What role do you think the hygiene hypothesis has in the increase in food allergy? Specifically, the increase of antibiotics, loss of intestinal helminths due to sanitation, and increase in time spent indoors with loss of contact with soil. Lost of contact with soil (CpG DNA) could account for a seasonal difference in rates of food allergies.