Letters to the Editor

Provocation-Neutralization in the Treatment of Food Allergy


Am Fam Physician. 1999 Aug 1;60(2):392-402.

to the editor: I would like to thank Dr. Sicherer for his recent article on the evaluation and management of food “allergy.”1 The article's emphasis on life-threatening emergencies is timely in light of the recently publicized allergic reactions to foods such as peanut butter in Seattle-area schools.

However, I would take issue with the statement on page 419 of the article, which reads, “Unfortunately, unreliable information in the lay press and the use of unconventional and unproven methods, such as ‘provocation-neutralization,’ for diagnosing and treating behavior disorders can divert the patient's family from more useful treatments.”1

First, in my experience in family practice and environmental health, a distinct subset of patients does indeed have reproducible, physical changes in behavior, as well as asthma, headaches, arthritis, rhinitis and so on triggered by a particular food or additive. For such patients, the treatments that are usually helpful, such as conventional allergy care, psychotherapy and the use of medication, may, in fact, divert patients from the real issues. Provocation-neutralization really can be a helpful diagnostic and therapeutic technique to demonstrate sensitivity to foods and other agents. Sadly, those who criticize the technique have rarely seen it in operation.

Second, the expression “bona fide allergies” is misleading. The expression fails to recognize the existence of two distinct schools of thought in American allergy and clinical immunology: both a narrow and a broad definition of “allergy” exist. Unfortunately, many allergic reactions to foods, which happen to be non-IgE and even non-antibody, immune-mediated events, are ignored by many physicians to the patient's detriment.

Finally, Dr. Sicherer cited an article by Dr. Jewett, which was published in the New England Journal of Medicine, to support the above contention regarding provocation-neutralization.2 This reference is decidedly weak for several reasons. It does not use the standard definition of “neutralizing dose.” Also, several double-blind articles36 showing data that support the effective use of provocation-neutralization had been published by 1990, but were not cited by Dr. Jewett or by the editor of New England Journal of Medicine.

Thank you for allowing another viewpoint about this important, albeit controversial subject.


show all references

1. Sicherer SH. Manifestations of food allergy: evaluation and management. Am Fam Physician. 1999;59:415–24....

2. Jewett D, Fein G, Greenberg MH. A double-blind study of symptom provocation to determine food sensitivity. N Engl J Med. 1990;323:429–33.

3. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin Allergy. 1986;16:483–91.

4. Boris M, Schiff M, Weindorf S. Injection of low-dose antigen attenuates the response to subsequent bronchoprovocative challenge. Otolaryngol Head Neck Surg. 1988;98:539–45.

5. King WP, Rubin WA, Fadal RG, Ward WA, Trevino RJ, Pierce WB, et al. Provocation-neutralization: a two-part study. Part I. The intracutaneous provocative food test: a multi-center comparison study. Otolaryngol Head Neck Surg. 1988;99:263–71.

6. King WP, Fadal RG, Ward WA, Trevino RJ, Pierce WB, Stewart JA, et al. Provocation-neutralization: a two-part study. Part II. Subcutaneous neutralization therapy: a multi-center study. Otolaryngol Head Neck Surg. 1988;99:272–7.

in reply: I would like to thank Dr. Ranheim for his comments on my article.

I am not aware of “narrow” and “broad” definitions of allergy.1 A food allergy is a specific immunologic response to a food protein that may or may not be mediated by a specific IgE antibody. Indeed, a number of well-described, non–IgE-mediated food allergy reactions exist, mediated, for example, by T-cell elaboration of cytokines such as tumor necrosis factor alpha, as detailed in my article. Additionally, many disorders or symptoms that are caused by food or food products are not mediated by the immune system (intolerance, reactions to toxins or pharmacologic agents in foods), but have a defined pathophysiologic basis and are also described in my article.

A number of diagnostic and treatment modalities for food allergy are considered controversial and unproven.2,3 These include provocation-neutralization, IgG4 antibody testing, cytotoxic testing, electrodermal diagnosis, applied kinesiology, the “reaginic” pulse test and body chemical analysis. Generally, these tests are used to diagnose a wide variety of complaints that do not necessarily share a common pathophysiology. These tests and treatments also lack a rational basis in immunology. Restrictive diets that are based on results of these or any tests carry the risk of nutritional deficits and social and emotional stresses, so it is important to be sure that dietary changes are being advised on solid ground.

Dr. Ranheim has found provocation-neutralization to be a helpful diagnostic and therapeutic technique for his patients, as did the seven experienced clinical ecologists who participated in Dr. Jewett's study,4 before their techniques were shown to be unreliable in a carefully executed double-blind, placebo-controlled study. I am not aware of any subsequent studies that were so carefully controlled showing benefit to provocation-neutralization (in fact, no effect has been re-confirmed5), although the technique is still practiced and may not be a benign modality, especially if misused.6

When a question concerning true reactivity to a food arises, even in the face of positive tests for food-specific IgE antibody, the only way to determine a cause and effect relationship is through physician-supervised, double-blind, placebo-controlled oral food challenges. This diagnostic method is considered the “gold standard” since physician and patient bias is removed. I suggest that any diagnostic or therapeutic modality be held to this standard and studied systematically.


show all references

1. Bruijnzeel-Koomen C, Ortolani C, Aas K, Bindslev-Jensen C, Bjorksten B, Moneret-Vautrin D, et al. Adverse reactions to food. Allergy. 1995;50:623–35....

2. Bernstein IL, Storms WW. Practice parameters for allergy diagnostic testing. Joint Task Force on Practice Parameters for the Diagnosis and Treatment of Asthma. The American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1995;75(6 Pt 2):543–625.

3. Jenkins M, Vickers A. Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance. Clin Exp Allergy. 1998;28:1526–9.

4. Jewett D, Fein G, Greenberg MH. A double-blind study of symptom provocation to determine food sensitivity. N Engl J Med. 1990;323:429–33.

5. Fox RA, Sabo BM, Williams TP, Joffres MR. Intradermal testing for food and chemical sensitivities: a double-blind controlled study. J Allergy Clin Immunol. 1999;103(5 Pt 1):907–11.

6. Teuber SS, Vogt PJ. An unproven technique with potentially fatal outcome: provocation/neutralization in a patient with systemic mastocytosis. Ann Allergy Asthma Immunol. 1999;82:61–5.

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This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.



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