Reactions to Food and Drug Additives
A. Wesley Burks MD, in Middleton's Allergy: Principles and Practice, 2020
Prevalence of Reactions to Additives
Many food and drug additives have been reported to cause adverse reactions ranging from lethargy to severe asthma and anaphylaxis. Many of the food and drug additives listed inBoxes 80.1 and80.2 have been reported to cause adverse reactions. However, many of these adverse reactions have not been verified by appropriate diagnostic challenge procedures. Several food and drug additives have been extensively studied, including synthetic colorants, sulfites, monosodium glutamate (MSG), aspartame, and benzoates. The prevalence of food allergies and food additive-induced sensitivities has been assessed in several large studies. In a Dutch study that started with a survey of 1483 Dutch adults and proceeded through clinical challenge trials, only three individuals were identified with food additive sensitivities,2 amounting to 0.2% of the population. In a large Danish study of food additive-induced sensitivities that started with a survey of 4274 Danish school children, an intolerance to food additives confirmed by double-blind challenge occurred in 2% of the children selected from the survey on basis of atopic history but only 0.13% of the entire surveyed population.3 Young et al.4 evaluated the prevalence of sensitivities to food additives among a British population using a combination of a survey questionnaire given to 18,582 individuals and a series of mixed additive challenges conducted at home with self-reporting of symptoms. The researchers estimated the prevalence of adverse reactions to food additives as 0.01% to 0.23%.4 A study of the prevalence of adverse reactions to foods was conducted in Berlin, Germany, in which a questionnaire was answered by 4093 persons, and those with self-reported food reactions were followed up by telephone and clinical investigation including double-blind, placebo-controlled food challenges. The prevalence of adverse reactions to food additives (a mixture of various colors, preservatives, antioxidants, and flavor enhancers) was estimated at 0.18%.5 Although this estimate is somewhat higher than in the earlier Dutch and Danish studies, the German study included more food additives and higher doses.
The assessment of the prevalence of adverse reactions to food additives is difficult because the reactions are often linked to chronic disorders such as asthma, chronic urticaria, and atopic dermatitis. Because the disorders are chronic, placebo reactions can occur. In a study of 54 Koreans (ages 1-44 years) with a variety of allergic diseases (asthma, rhinitis, atopic dermatitis, chronic urticaria) challenged with a mixture of seven common additives versus placebo, five (9.3%) responded to the food additives, two (3.7%) reacted to both placebo and the additives, and three (5.5%) reacted to the placebo.6 The authors concluded that there were no statistically significant differences between placebo and food additives. Similarly, in a study of 100 patients with chronic urticaria including 43 patients who reported possible history of reactions to food and drug additives, only two patients had a positive urticarial response on single-blind challenge, and neither of those patients were reactive on double-blind, placebo-controlled challenge.7