Applied nutritional investigationPotential food allergens in wine: Double-blind, placebo-controlled trial and basophil activation analysis
Introduction
Known allergenic food proteins are traditionally used in wine-making. Milk, evaporated milk, casein, potassium caseinate, and isinglass are used in the fining process to remove phenolic and tannin compounds from white wine, and egg white is used to remove tannin compounds from red wine. Non–grape-derived tannins such as those from the bark and galls of trees are also used. The proteins are added to the wine and the precipitates removed.
The components of milk and egg white that may cause food allergy in humans are well characterized [1], [2], [3], [4], [5], [6], as is the allergenicity of tree nuts and cross-reacting peanuts [7], [8], [9], [10]. Isinglass is a collagen extracted from fish swim bladders with an as yet undefined allergenic importance, but several fish allergens are known [11]. For many years, wine labels have been mandated to identify added preservatives (such as sulfur dioxide and sorbic acid), antioxidants (such as ascorbic and erythorbic acids), and coloring materials (such as caramel). The requirement for labeling for sulfur dioxide is related to its potential to cause an adverse reaction in sulfite-sensitive asthmatic individuals [12].
New labeling legislation by Food Standards Australia New Zealand (FSANZ) requires that wine labels identify detectable potentially allergenic processing aids, additives, or other ingredients. Similar regulations are under consideration by Canada, the European Union, and the United States. From the wine-makers’ perspective, only minimal residual protein should remain after fining to avoid visible precipitates. There is no published literature on whether any proteins derived from fining agents are present in the finished wine, and whether these could provoke an allergic reaction. Commercial enzyme-linked immunosorbent assays (ELISAs) for some of these proteins are available, but it is not known whether the assays would detect concentrations that could provoke allergic reactions. The definitive test for whether proteins used in fining can provoke an allergic reaction is a double-blind clinical study with appropriate allergic individuals [13], [14].
Adult prevalence of food allergy is approximately 1% [15], with peanuts and other nuts, fish, and shellfish accounting for most anaphylactic reactions. Allergy to egg and milk proteins is common in infants but usually resolves by 4 y of age, rarely persisting to adulthood; this low adult prevalence is reflected in the small number of these subjects in the study. Although immunoglobulin E (IgE)-mediated reactions to grape proteins have been described, these are uncommon and generally observed only in Mediterranean countries [16], [17], [18]. Few case studies have reported adverse reactions to wine [17], [19], [20], [21], [22] and no systematic studies have distinguished reactions due to allergens from pharmacologic responses to biogenic amines, salicylates, or sulfites. Other adverse reactions have been attributed anecdotally to yeast [23]. In our clinical experience, we have no reports of anaphylactic reactions attributable to residual food allergen protein-fining agents in commercial wines. In particular, patients with known food allergies do not report anaphylactic reactions necessitating avoidance of fined wine.
We conducted a double-blind, placebo-controlled clinical trial of fined wines in subjects with confirmed allergy to fish, peanuts, eggs, or milk. Sensitive laboratory functional assays to detect blood basophil activation from these subjects using a large panel of protein-fined and control unfined wines were performed to determine whether this assay could be used as an in vitro predictor of adverse reactions.
Section snippets
Participants
Twenty-six food-allergic subjects (12 women and 14 men; age range, 19–63 y) were recruited from the Allergy Clinics, Alfred Hospital (Melbourne, Australia). The diagnosis of IgE-mediated food allergy was made by a clinical allergist, based on a history of anaphylaxis and corresponding demonstration of specific IgE to allergens of fish, peanut, egg, and/or milk using the ImmunoCAP fluoroenzyme system (CAP-FEIA, Pharmacia Diagnostics, Uppsala, Sweden) or by skin prick testing (wheal ≥4 mm in
Results
Seventy-six wine challenges (27 wines including 3 control wines) were performed on the 37 subjects (26 food allergic and 11 non-food allergic). All subjects had an FEV1 >80% predicted on study entry. No subject developed anaphylaxis (laryngeal edema) after wine challenge and no diary card abnormalities were noted during follow-up. Overall there was no statistically significant difference in any parameter measured between subject groups or between processing aids.
Five mild reactions occurred in
Discussion
We have demonstrated that wine made using the food allergen proteins named in the new FSANZ legislation and according to good manufacturing practice poses a negligible risk of clinically significant adverse food reaction (anaphylaxis) in adult subjects with confirmed food allergy to fish, nuts, or eggs. A double-blind, placebo-controlled challenge with 24 wines fined using egg white, non–grape-derived tannins, milk, casein, and isinglass was performed on a panel of 26 food-allergic and 11
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This work was funded by the Grape and Wine Research and Development Corporation of Australia, the National Health and Medical Research Council of Australia, and the Alfred Research Trusts.