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.


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