J. Orild Psychol. Psychiai., Vol. 20, pp. 357-363. Pergamon Press Ltd. 1979. Printed in Great Britain. Association for Ghild Psychology and Psychiatry.

ANNOTATION FOOD ADDITIVES, ALLERGY AND HYPERKINESIS ERIC TAYLOR*

a long history of speculation that behaviour disorders might be caused by allergy. Shannon (1922) argued that behaviour problems could be a primary allergic reaction; Schneider (1945) asserted that allergy was important in causing the "syndrome" of childhood hyperkinesis. Speer (1954) described an "allergic tension-fatigue syndrome", including behaviour changes in children. Kittler (1970) presented some case studies of children with "minimal brain dysfunction" whose difficult behaviour had improved when dietary allergens (such as chocolate and milk) were excluded. However, while the idea has aged, it has not become respectable. Indeed, there were virtually no empirical studies until the last few years. More recently, much attention has been given to a similar speculation by Feingold (1975a,b). He asserts that hyperactivity and learning disorders are frequently caused by an intolerance of food additives. In his theory this is not an allergy, but a toxic effect. The difference is worth emphasizing. A toxin causes damage to the body directly. An allergy, by contrast, is an alteration of the body's response to a substance. It is produced by the immunological defence mechanisms. It is not shown in the first encounter with the allergen, but only in later contacts. In Feingold's hypothesis, the toxic effect is supposed to be apparent only in predisposed individuals and so the notion of an idiosyncratic response is still present. In particular, he blames artificial colours and flavourings, antioxidant preservatives such as butylated hydroxytoluene and butylated hydroxyanisole, and salicylates which occur naturally in some fruits (Feingold, 1977). He hypothesizes that when these are withdrawn from the diet, many hyperactive children will improve dramatically in their behaviour. Unfortunately, he presents no data other than uncontrolled anecdotes and the response of researchers and clinicians has accordingly been sceptical. The hypothesis has, however, evoked much interest in the popular press. The resulting clamour—and the clash of vested interests—have provoked more scientific evaluations. Recent months have seen the publication of several important trials. Unhappily the question remains open. Indeed, two major groups of investigators, as will be seen, have come to diametrically opposite conclusions regarding the importance of food additives. What can be made of the controversy so far? The topic presents many difficulties to the researcher. Firstly, the diet includes many restrictions. It is necessary, for instance, to exclude most breakfast cereals; salicylate-containing foods such as apples, oranges, tomatoes, cucumbers, strawberries, apricots, and almonds; ham, salami, frozen fish, cakes, jellies, soft drinks, ice cream, sweets, toothpaste and anything with artificial colouring or flavouring.

THERE IS

•Requests for reprints to: Dr. E. Taylor, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, England. 357

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Strict compliance is required. It follows that a great effort is required from the family, and it may be expected that attitudes and interactions among family members will be profoundly changed. The importance of a placebo eifect will therefore be great and adequate controls become crucial. Secondly, the need for strict compliance also means that minor deviations by a child determined on his regular ice cream can be disastrous for the trial. Negative results have sometimes been explained away on the Feingold hypothesis by supposing that the children "cheated". Thirdly, the hypothesis does not require that all children with hyperactive behaviour should be intolerant of food additives. A subgroup of children might respond very favourably to dietary treatment, yet be overwhelmed in a statistical analysis by an unresponsive majority. It is sometimes assumed that the diagnosis of hyperactivity delineates a homogenous group of children who might be expected to react alike; but this is far from being the case (Werry, 1968; Langhorne et al., 1976). Fourthly, the diagnostic criteria for "hyperactivity" are unclear (Sandberg et al., 1978) and it is possible that different researchers are selecting different groups of children. The studies to be considered below have all used the very broad. North American concept of hyperactivity. They are therefore relevant to many of the children who are regarded in the U.K. as manifesting unsocialised conduct disorder, learning disorders, or mixed disorder of conduct and emotions. Finally, the concept of the brain showing intolerance for certain foods has as many difficulties as that of hyperactivity. Indeed, many writers (e.g. Sieben, 1977) find it too implausible to take seriously. Is it in fact impossible? Some people with allergic conditions, such as asthmatics, are indeed hypersensitive to salicylates, and to synthetic dyes such as tartrazine, which are very widely used by food manufacturers (Stenius and Lemola, 1976). Tartrazine produced unpleasant symptoms in 32 out of a series of 97 individuals with a variety of allergic conditions (Neuman et al., 1978). Exclusion of tartrazine from the diet is valuable for such patients. It is less clear whether or not the brain can take part in this kind of allergy, for lymphocytes do not enter the brain. There have, however, been reports of focal neurological illnesses attributable to food allergy (Kennedy, 1938). Therefore, the hypothesis is not, on the face of it, absurd. Published studies have now tackled most of these problems, in various ways. 1. UNCONTROLLED REPORTS OF DIETARY TREATMENT These are of small value in view of the critical problems of placebo effect. Accordingly, they need not be considered in detail. Many of the 50 cases reported by Crook et al. (1961) showed an improvement in behaviour. Cook and Woodhill (1976) described 10 children out of 15 to be improved in their behaviour. Salzman (1976) reported improvement in a series of 15 children, which was notable for having been selected on the basis that they showed independent evidence of allergy to food additives. This seems a sensible and rarely used method of selecting children for study, and deserves to be repeated. It is all the more unfortunate that he does not adequately give the criteria by which the children were determined to be allergic.

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2. COMPARISONS OF HYPERACTIVES WITH CONTROLS

Palmer, Rapoport and Quinn (1975) compared the diets taken by 56 hyperactive boys and by 23 matched controls. There was no evidence that the hyperactives' diet contained more additives. This does not, of course, contradict the hypothesis that hyperactives show an altered reaction to these substances. Salzman (1976), in a study already cited, reported that 18 out of 31 hyperactive children showed an altered reaction. Little can be concluded. Certainly there is no compelling evidence for an important allergic contribution. Nor has it been shown that allergic children are at increased risk for hyperactivity. For instance, Purcell et al. (1969) like Block et al. (1964) found that, within a group of asthmatic children, the less allergic actually showed more psychopathology—but this was in the direction of being more timid, anxious and introverted. In any event, there is no indication that this type of allergy is a potent cause of disorders of behaviour or of learning. It might, however, be argued that behaviour disturbance can be the only evidence of allergy. This leads to the danger of circularity in reasoning; only studies regulating the diet can give evidence for or against. 3. CONTROLLED COMPARISONS OF DIFFERENT DIETS Two major comparisons have been undertaken. Conners et al. (1976) make a guarded claim for a positive result of the diet; Harley et al. (1978) claim a negative result. As this is at the heart of the controversy, it is worth considering some of the complexities of the trials. Conners et al. (1976) treated 15 children, each of whom received two diets in succession. The experimental diet involved the exclusion of food additives and salicylates; the control diet required the exclusion of different foods. The children's overactive behaviour was rated by parents and teachers on the Conners questionnaires (Conners, 1969, 1970). The ratings by teachers were substantially more favourable during the experimental diet than during the control. On the other hand, the ratings by parents did not show a significant difference (and the authors suggest that parents' ratings are less reliable and that hyperactivity is most clearly observed in the classroom). Several reservations need to be made. Firstly, the two diets may not have been adequately matched. The experimental diet excluded more preferred foods, and may have involved different problems of selection and preparation for the mothers. Second, it must be very doubtful whether the parents were truly "blind" in view of the media concern with the danger of additives (Levine and Liden, 1976). We have already seen that it is essential that the effects of expectation and of adherence to a complex regime should be controlled for. Third, the effect may not have been large enough to be clinically worthwhile. For 10 of the 15 children, the clinician's global rating was that there had been minimal change, no change, or worsening. Only one child was rated as showing "marked improvement". Fourth, great reliance is placed on the subjective judgement of the teacher; and this could maximise the effects of expectation. Fifth, there was a marked order effect: the advantage of the experimental diet seems only to have been apparent when the control diet was given first and followed by the experimental diet. The questionnaire used does tend to

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produce an improvement in scores on repeated testing, even if no treatment is given (Werry, Sprague and Cohen, 1975). Perhaps this magnified the result of the experiment. For all these reasons—as well as the small number of children involved—this study cannot support the hypothesis with any strength. The finding by Harley et al. (1978) of no difference between experimental and control diets is based on a more satisfactory study. Thirty-six school-age children each received successively an experimental diet eliminating additives and a control diet eliminating other foods. Extraordinary measures were taken to ensure compliance: all family members went on to the diet, existing food was removed from the household and all food was provided, week by week, by the investigators. Extra food was supplied for parties, etc., and even for the classmates of the investigated children when any of them had a treat. The investigators also took steps to confuse parents as to which diet was in force by making changes in the food supplied that were irrelevant to the comparison. They used multiple outcome measures, including not only the Conners rating scales but also the direct observation of the children in their classrooms and in the laboratory, and a battery of neuropsychological tests. These measures unequivocally failed to show an advantage for the experimental diet. This study deserves respect, and constitutes the best available evidence on the general effect of the diet. Of course, one can never wholly prove a negative. Feingold has been reported (Kolata, 1978) as objecting on several counts: (a) that the study was financially supported by the food industry. But it is hard to see that the interest of the industry could be served by falsification of results. (b) that failure of compliance with the diet could account for the lack of response. But if the rigorous precautions of this study were not sufficient, it is unlikely that routine clinical use will be practicable. (c) a more serious reservation is that even if the diet does not have a general effect it could have a good effect for a subgroup of children. Indeed, the same study has found suggestive evidence that a smaller number of younger (preschool) children showed consistent improvement with the diet as indexed by the ratings of their parents. A powerful strategy of examining this possibility is the challenge studies considered below. 4. CHALLENCE STUDIES

So far, the sceptics have had the better of the argument. A recent paper, however, by Goyette et al. (1978) suggests grounds for supporting the argument that a fraction of hyperactive children is allergic. They chose 16 children for study on the basis that their hyperactivity had previously improved with the experimental diet. If this improvement was more than chance, then a challenge with the incriminated additives should, of course, worsen their behaviour. The responsive children were therefore retained on their diet and given, in addition, either chocolate cookies baked with large amounts of dyes or placebo cookies without the dyes. The results were not impressive nor statistically significant, but hinted that the younger children might be transiently impaired on a visuomotor tracking test. The investigators therefore examined a further 13 younger children (mean age 6 yr) whose hyperactivity had improved on the diet, and used ratings applied only to the 3 hours after ingestion of the cookie. With this method there was a statistically significant effect:

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the supposedly allergenic cookies caused an increase in hyperactivity by comparison with the placebo. Again, there must be reservations. The numbers are of course very small for so far-reaching a conclusion, and the measure of improvement is a subjective rating scale applied in a way for which it was neither designed nor standardised. Much depends on whether the cookies which contained a large amount of flavouring and colouring were truly indistinguishable from those which did not. But the design is a powerful one and deserves replication. Williams et al. (1978) have also published a recent account of a challenge study. They studied children aged 6-14, diagnosed as hyperactive and being treated with stimulant drugs; responsiveness to the diet was not a ground for selection. Each child was placed on the experimental diet and then received four one-week periods of treatment: with and without stimulant drugs and with and without food additives. The additives were given in cookies, or witheld from placebo cookies, in the same way as in the study by Goyette et al. (1978). Overall, the results indicated that the elimination of additives had a small but significant action in improving behaviour; stimulant drugs had a considerably larger effect. Once again, however, the only measures were the Conners rating scales. The interaction of treatments is rather hard to explain. For the parents' ratings, the diet effect was only significant when the children were also receiving active drug. This finding does not support an aetiological role for the additives. Could they have interacted with absorption or metabolism of the drug? For the teachers' ratings, on the other hand, the diet effect was only significant when the children were not receiving drugs. Any conclusion, like that from the Goyette et al. (1978) work, can only be suggestive. It is certainly puzzling that they should appear to find a more lasting effect than Goyette et al. in a group of children less likely to respond. Before any conclusions can be drawn, it is important to consider whether anything is known of the supposed mechanism and possible hazards. As to the mechanism, the suggestion was made by Kennedy (1938) and more recently by Moyer (1976) that localised areas of the brain developed angioneurotic oedema. This is entirely speculative, as is Feingold's (1975a) idea that there is a toxic effect on brain chemistry in predisposed individuals. It is also possible that additives such as tartrazine have the same effect of producing transient feelings of malaise as in the study by Neuman et al. (1978); and that bad behaviour is a reaction to this. POSSIBLE ADVERSE EFFECTS OF THE DIET Physical risks are few, but other nutritional changes are of course entailed. In particular, the vitamin C intake may be reduced to less than that required, and it is advisable to give supplements. While the carbohydrate requirement is likely to be reduced, the intake should not normally become inadequate. Many parents will find it hard to manage; many children will find it irksome. Clinicians will be well aware of the risks of introducing any regime of difficulty and complexity. While it may succeed in creating a beneficial atmosphere of involvement and positive expectation, it may also do the reverse. It may become a prolonged punishment. If expectations are inflated, relative failure may lead to pessimism and scapegoating. Some parents may feel more guilty, and some children more stigmatised. Other kinds of treatment may be wrongly neglected.

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ERIC TAYLOR CONCLUSIONS

There is still no persuasive evidence that intolerance of food additives is a major cause of hyperactivity. Eliminating additives from the diet is an arduous procedure, which will not help most children with behaviour disorders—not, at any rate, in ways large enough and lasting enough to be clinically important. Evidence from challenge studies and from clinical anecdotes suggests that the diet might prove to have helpful effects for a minority of children (especially those under 6 yr). This requires confirmation; no mechanism is known, and there is no reason to think that any effect is specific to hyperactive behaviour. What advice should be given to families containing a severely restless and impulsive child? On present evidence, the diet should not be recommended as a routine clinical procedure. Some families—probably an increasing number—will decide to try it nonetheless. The clinician's job then will often be that of supervising an experimental treatment. This implies a duty to monitor change with sufficient care to allow a sensible judgement. The use of a placebo control is probably the clearest way to make such a decision. The diet does seem to justify more experimental work; research should aim not only to replicate the design of existing studies, but also to include more objective measures of change, more independent evidence of allergy, and more attention to the possibility of predicting change. REFERENCES BLOCK, J., JENNINGS, P., HARVEY, E . and SIMPSON, E . (1964) Interaction between allergic potential

and psychopathology in childhood asthma. Psychosom. Med. 26, 307-320. CONNERS, C . K . (1969) A teacher rating scale for use in drug studies with children. Am. J. Psychiat. 126, 884-888. CONNERS, C . K . (1970) Symptom pattems in hyperkinetic, neurotic and normal children. Child Dev. 41, 667-682. CONNERS, C . K . , GOYETTE, C . H . , SOUTHV^^CK, D . A., LEES, J . M. and ANDRULONIS, P. (1976) Food

additives and hyperkinesis. Pediatrics 58, 154^166. COOK, P. S. and WOODHILL, J . M. (1976) The Feingold dietary treatment of the hyperkinetic syndrome. Med. J. Aus. 2, 85-90. CROOK, W . G . , HARRISON, W . W . , CRAWFORD, S. E . and EMERSON, B . S. (1961) Systemic manifesta-

tions due to allergy. Pediatrics 27, 790-799. FEINGOLD, B . F . (1975a) Adverse reactions to food additives with special reference to hyperkinesis and learning difficulty (H-LD). In The Man—Food Equation (Edited by STEELE, F . and BOURNE, A.). Academic Press, London. FEINGOLD, B . F . (1975b) Hyperkinesis and leaming disabilities linked to artifical food flavors and colors. Am. J. Mrs. 75, 797-803. FEINGOLD, B . F . (1977) A critique of'Controversial Medical Treatment of Leaming Disabilities'. Acad. Ther. 13, 173-185. GOYETTE, C . H . , CONNERS, C . K . , PETTI, T . A. and CURTIS, L . E . (1978) Effects of artificial colors

on hyperactive children: a double-blind challenge study. Psychopharm. Bull. 14, 39-40. HARLEY, J . P., RAY, R . S., TOMASI, L . , EICHMAN, P. L., MATTHEWS, C . G . , CHUN, R . , CLEBLAND,

C. S. and TRAISMAN, E . (1978) Hyperkinesis and food additives: testing the Feingold hypothesis. Pediatrics 61, 818-828. KENNEDY, F . (1938) Allergy and its effect on the central nervous system. Arch. Neurol. Psychiat. 39, I361-I366. KITTLER, F . J . (1970) The effect of allergy on children with minimal brain damage. In Allergy of the Nervous System (Edited by SPEER, F . ) . Charles C. Thomas, Springfield. KOLATA, G . B . (1978) Food additives and hyperactivity. Science 199, 516.

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LANGHORNE, J. E., LONEY, J., PATERNITE, C . E . and BECHTOLDT, H . P. (1976) Childhood hyper-

kinesis: a return to the source. J. abnorm. Psychol. 85, 201-209. LEVINE, M . D . and LIDEN, C . B. (1976) Food for inefficient thought. Pediatrics 58, 145. MOYER, K . E . (1976) The Psychobiogy of Aggression. Harper & Row, New York. NEUMAN, I., ELIAN, R . , NAHUM, H . , SHAKED, P. and CRETER, D . (1978) The danger of 'yellow dyes'

(tartrazine) to allergic subjects. Clin. Allerg. 8, 65-68. PALMER, S., RAPOPORT, J. L. and QUINN, P. O. (1975) Food additives and hyperactivity. Clin. Pediat. 14, 956-988. PURCELL, K . , MUSER, J., MIKLICH, D . and DIETIKER, K . E . (1969) A comparison of psychologic

findings in variously defined asthmatic subgroups. J. Psychosom. Res. 13, 67-75. SALZMAN, L . K . (1976) Allergy testing, psychological assessment and dietary treatment of the hyperactive child syndrome. Med. J. Aus. 2, 248-251. SANDBERG, S. T . , RUTTER, M . and TAYLOR, E . (1978) Hyperkinetic disorder in psychiatric clinic attenders. Dev. Med. Child Neurol. 20, 279-299. SCHNEIDER, W . F . (1945) Psychiatric evaluation of the hyperkinetic child. J. Pediat. 26, 559-570. SHANNON, W . R . (1922) Neuropathic manifestations in infants and children as a result of anaphylactic reactions to foods contained in their dietary. Am. J. dis. Child. 24, 89-94. SIEBEN, R . L . (1977) Controversial medical treatments of learning disabilities. Acad. Ther. 13, 133147. SPEER, F . (1954) The allergic tension-fatigue syndrome. Ped. Clin. N. Am. 1, 1029-1037. STENIUS, R . S . M . and LEMOLA, M . (1976) Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma. Clin. Allergy 6, 119-126. WERRY, J. S. (1968) Studies of the hyperactive child—IV. An empirical analysis of the minimal brain dysfunction syndrome. Archs gen. Psychiat. 19, 9-16. WERRY, J. S., SPRAGUE, R . L . and COHEN, M . N . (1975) Conners' Teacher Rating Scale for use in drug studies with children—an empirical study. J. abnorm. Child Psychol. 3, 217-229. WILLIAMS, J. I., CRAM, D . M . , TAUSIG, F . T . and WEBSTER, E . (1978) Relative effects of drugs and

diet on hyperactive behaviours: an experimental study. Pediatrics 61,811-817.