as well as foods such as corn, wheat, and milk regardless of additive content. After a preliminary trial, this type of defined diet was then modified by reintroducing individual food items one at a time and evaluating the effects of such additions upon the subject's behavior.
Is There Empirical Evidence for an Effect of These Diets on Hyperactivity?
Parents and other observers have frequently reported dramatic improvements in many hyperactive children during uncontrolled trials of various defined diets. However, such dramatic improvements were not observed in a number of controlled trials reported at the conference.
While differences and inadequacies in the design of the controlled trials make analysis difficult, these studies did indicate a limited positive association between "the defined diets" and a decrease in hyperactivity. Some hyperactive children demonstrated less evidence of hyperactivity on defined diets, or modifications thereof, than on an appropriate control diet. Such decreases involved only a small proportion of patients; furthermore, the decreases in hyperactivity were not observed consistently. Studies also indicated that some hyperactive children on a defined diet experienced an increase in hyperactivity when given moderate doses of artificial food dyes, and did not experience similar increases after receiving a placebo. This increase in hyperactivity was also experienced by only a small group of patients, and the increase was not consistently reported by teachers, parents, and other observers.
Clinical observations also indicated that children who were successfully managed on a defined diet experienced hyperactivity after dietary noncompliance. Controlled challenge studies have primarily involved the administration of food dyes to children, but have not included other food flavors or preservatives that are allegedly implicated in the causation of hyperactivity. Therefore, these controlled challenge studies do not appear to have addressed adequately the role of diet in hyperactivity.
Is There Any Biological Explanation to Support an Effect of Defined Diets on Hyperactivity?
Only one specific biological explanation has been proposed--that the food dye erythrosine (FDC Red No. 3) inhibits neurotransmitter uptake. Experimental studies first suggested that Red No. 3 could inhibit the uptake of dopamine and other neurotransmitters in vitro. If true, this observation presented a mechanism by which this food additive could affect behavior. However, more recent studies suggested that this effect of Red No. 3 was the result of nonspecific interactions, and these studies raised doubts about whether Red No. 3 would affect the behavior of the intact organism. In support of this latter idea, data from three groups using the laboratory rat found that Red No. 3 caused no increase in activity or had effects only at near-lethal doses. Additionally, one study in children found that the minor behavioral changes apparently caused by challenge with a mixture of food colors were a result of food colors other than Red No. 3.
Despite these negative preliminary data, it was recognized that further research, especially pharmacokinetic studies, were needed before these questions could be answered conclusively about Red No. 3 or other dietary agents. Moreover, other explanations of why a defined diet lacking food dyes, flavorings, preservatives, salicylates, and major food antigens may be beneficial can only be suggested. Direct toxic effects, idiosyncratic reactions to such agents, and hypersensitivity (allergic) responses (both IgE-mediated and non-IgE-mediated) to food antigens also could cause the observed findings. This might be by direct effects on the central nervous system or by indirect effects on other systems. However, no direct evidence for the operation of these mechanisms in treated patients is available at this time.
Placebo effects and observer bias inherent to any major therapeutic intervention (when not controlled by appropriate blinded procedures), may also account for some of the reported benefits.
If Defined 