Environmental Toxicology and Pharmacology 4 (1997) 111114

Prevalence of intolerance to food additives

E. Young *

Department of Dermatology, Amersham General Hospital, Amersham, Bucks WHP7 0JB, UK

Abstract

Food additives have been implicated as aetiological factors in many different disease states. Concern arose from a suggested linkwith food additives and hyperactivity in children. They have also been implicated in many other disease states. This perception,often made by parents on behalf of their children, is not confirmed by double-blind placebo-controlled challenge studies. Thediscrepancy between public perception and the true prevalence of food additive reactions is great and this discrepancy betweenperception and confirmed reactions also exists with food-related symptoms. The discrepancy is much greater in the case of foodadditives than in foods. The mechanism of food additive reactions is not immunological and there is no in vivo or in vitroconfirmatory test. 1997 Elsevier Science B.V.

Keywords: Food additives; Intolerance; Prevalence

1. Introduction

In the late 1970s and early 1980s a wave of feelingarose in the UK concerning the safety and use of foodadditives in the nations diet. This had been precededby concern shown in the USA at Feingolds suggestionthat salicylates and food additives, particularly colours,could alter childrens behaviour and development(Feingold, 1973). Fuelled by the media, many pressuregroups arose, public interest increased and concernabout food in general and food additives in particular,as a potential cause of ill-health became more common.

Against this background, a joint report by the RoyalCollege of Physicians and the British Nutrition Foun-dation was published in 1984. This excellent and com-prehensive review concluded that no estimate could bemade of the prevalence of food intolerance because of alack of information and further recommended thatefforts should be made to obtain support for researchinto the epidemiological and scientific aspects of foodintolerance and to define the mechanisms by whichfoods and food additives cause reactions in susceptibleindividuals (Royal College of Physicians and TheBritish Nutrition Foundation, 1984).

As a consequence of the joint report, the Ministry ofAgriculture, Fisheries and Food commissioned work toidentify the prevalence of food additive intolerance inthe population of the UK and to identify the mecha-nisms involved. This work has been published as agroup of research papers (Medical Aspects of FoodIntolerance, 1987) and indicated that there was a greatdiscrepancy between the public perception of reactionsto food additives stated as affecting 7.4% of the popula-tion and reactions confirmed by double-blind placebo-controlled testing giving prevalence figures of between0.01 and 0.23% (Young et al., 1987).

The UK definition of food intolerance and foodaversion, as considered by the joint committee, indi-cates that food intolerance encompasses enzyme de-fects, pharmacological effects such as that of caffeine,irritant and toxic effects resulting in histamine release,an indirect effect caused by fermentation in the lowerbowel, irritant effects of substances such as curry spicesand other mechanisms as yet unknown. Food intoler-ance also encompasses true food allergy where there isevidence of an abnormal immunological reaction tofood. All these examples of food intolerance are repro-ducible even when the food is disguised and has nopsychological connection. In contrast, food aversion isdefined as psychological avoidance, when the food is* Tel.: 44 149 4734610; fax: 44 149 4734620.

1382-6689:97:$17.00 1997 Elsevier Science B.V. All rights reserved.PII S 1 382 -6689 (97 )10050 -3

E. Young : En6ironmental Toxicology and Pharmacology 4 (1997) 111114112

avoided for psychological reasons or psychological in-tolerance in which there is a reaction to the food forpsychological reasons, but when the food is given in adisguised fashion, no similar reaction occurs. This is incontrast to food intolerance where all reactions arereproducible on ingestion of the specific food, even ifthe food is disguised and unrecognised.

These definitions helped us to design a study wherebythe use of a double-blind placebo-controlled challengewould enable us to identify true reactions to foodadditives. All other methods of study are open toquestion yet much of the literature relates to history,diet diaries, elimination diets and open challenge stud-ies. Although difficult to pursue, the double-blindplacebo-controlled challenge remains the gold stan-dard in investigations of this type. Effectively, thismethod of study should rule out all psychological as-pects involved in the perception of food intolerance.

2. Results

Symptoms reported in the literature as most com-monly related to food additives are shown in Table 1and the most common food additives implicated appearin Table 2, together with the dosages used in the study.A questionnaire survey of approximately 30 000 peoplein 10 000 households in the Wycombe Health Authorityarea was carried out. This resulted in a 62% responserate with 7.4% of those responding claiming a reactionto food additives. All those responding positively andindicating willingness to participate further were invitedfor interview. As a result, 649 people attended theclinics for interview and 132 were selected for entry intoa double-blind placebo-controlled challenge study. Ofthe 132 selected, 62% completed the trial and in onlythree was the challenge positive (Table 3).

The results of the questionnaire survey revealed that7.4% of the positive respondents claimed they had hada problem with food additives, but they had rarelyconsidered this a symptom in isolation as 78% of them

Table 2Additives and dosages

Substance Dosea (mg)

Low High

Amaranth1. 0.5 2.5Sunset yellow 0.5 2.5

0.5 2.5Carmoisine2.50.5Tartrazine

Green S2. 0.5 1.0Quinoline yellow 1.0 2.5

2.51.0Indigo carmine

Annatto3. 1.0 10.0

1.04. 50BHA1.0 50BHT

5. 10010Sodium benzoate50 300Aspirin

a Low and high refer to doses used in challenge.

also claimed a reaction to foods. The only significantdifference was in the group that reported abnormalbehaviour. This group was more likely to perceive it asa response to food additives only.

Of the positive respondents, 50% had symptoms ofatopic disease which compared with a 28% incidence ofatopy in the total respondent population. An attemptwas made to assess the non-respondent population bytelephone and housecall and a sample of 280 of theseprovided detailed answers. In this non-respondentgroup only 1.1% perceived a problem with food addi-tives. Therefore, the problem of food additive intoler-ance has not been overestimated. The only possibility isthat some of the population do have reactions to foodadditives, but are unaware of it.

Of the 649 people interviewed as a result of thequestionnaire response, 10% had either no problem, butfelt that additives were harmful, or complained ofvague, mild, non-specific symptoms. At interview it wasfelt that 7% of those interviewed, equivalent to 1:200 ofthe population, reported symptoms which might havebeen attributable to monosodium glutamate sensitivity

Table 1Symptoms reported to food additives

ItchingFlushingEczemaUrticaria:angio-oedema

AsthmaRhinitisConjunctivitis

Gastro-intestinalHeadachesBehavioural:mood changesMusculo-skeletal symptomsOthers

Table 3Food additive study results

Total number surveyed 30000 approx.Positive respondents 18582 (62%)Called for interview 1223 (7.4%)Came to interview 649Entered into trial 132Completed trial 81Withdrew from trial 23Pending 32, lostPositive to challenge ?

E. Young : En6ironmental Toxicology and Pharmacology 4 (1997) 111114 113

and a further 6%, equivalent to 1:250 of the population,reported symptoms which was thought to be related tosulphites. Sulphites and MSG were excluded from theadditive challenge, however, because of the uncertaintyas to whether capsule challenge would give accurateresults.

A total of 132 subjects were submitted to additivechallenge, going through a double sequence (as shownin Table 2) with a low dose challenge designed toobviate severe reactions and a high dose challengechosen to equate with the maximum daily intake asestimated from figures provided by the Ministry ofAgriculture, Fisheries and Food. The additives weremixed in combinations which took chemical compati-bility into account. The capsules were of opaquegelatine tinted with iron oxide and titanium dioxide(neither of which has been reported as causing adversereactions). Placebo capsules contained lactose powder,lactose intolerance being uncommon in the community.Two weeks prior to study and during the period ofcapsule challenge, patients remained on an additive-freediet. Many who did not complete the study failedbecause of their inability to remain on this diet, and afurther 33 subjects remain lost to us. Of the positiverespondents, two reacted to annatto, and one atopicchild with behavioural symptoms reacted to azo dyes atlow and high doses, but his parents refused furtherstudy on his behalf. Statistical analysis by three meth-ods gave an estimated figure for prevalence of foodadditive intolerance in our population of 0.010.23%.This figure matches well with other studies and indi-cates that the problem is much less than perceived bythe study population.

3. Discussion

Many studies of the prevalence of food and foodadditive intolerance have been conducted on limitednumbers of selected groups of patients. The difficulty ofselecting a random population and the preparation ofproper controlled double-blind challenge study materialis considerable. Two recent studies from Denmarkdemonstrate these problems. In the first study usingselected children with atopic symptoms, open challengeshowed a 7% food additive intolerance rate as com-pared to a 2% rate when double-blind challenge wasused (Fuglsang et al., 1994). A similar study done on agroup of unselected schoolchildren showed again amuch higher rate of reaction to open challenge than todouble-blind challenge (Fuglsang et al., 1993). Madsenhas conducted a thorough review of existing prevalenceestimates (Madsen, 1994). Various studies show preva-lence estimates from 0.01% of a randomly selectedpopulation to 2% of atopic children. In all studies, therate of perception far exceeds the calculated prevalence

rate. The consequences of this mistaken perception areconsiderable in terms of health and finance and haveconsiderable social implications.

Despite the results of properly controlled challengetesting, many parents resist the suggestion that there isno problem with food additives, particularly as regardstheir children. Nutritionally, an additive-free dietshould cause no problems and additives can often bere-introduced at a later date as shown by Dr IanPollock, in a follow-up study of childhood food addi-tive intolerance (Pollock and Warner, 1987). Workdone by the study group to define mechanisms involvedhere revealed some interesting facts. Normal subjectswill release histamine in vivo when challenged with acumulative dose of 200 mg of tartrazine (Murdoch etal., 1987a). It is thought that the maximum daily intakeof tartrazine probably never exceeds 100 mg, althoughprevious investigators have used dosages in excess of150 mg, and the value of diagnostic challenge tests withhigh doses must remain suspect. Nevertheless in twopatients with chronic urticaria, who had reacted to azodyes after double-blind placebo-controlled challenge,clinical symptoms correlating with a rise in plasma andurinary histamine have been demonstrated (Murdoch etal., 1987b), and it is now established that tartrazine cancause adverse reactions in a very small percentage ofpeople. Much further work needs to be directed to themechanisms of mediator release. Studies designed toinvestigate cumulative and cocktail effects are exceed-ingly difficult to design and the work has only been asmall start to further investigation. There is no evidenceof an immunological mechanism being involved in foodadditive reactions.

Subsequent to this study, the Ministry of Agriculture,Fisheries and Food commissioned a similar study toidentify the prevalence of food intolerance in the UKpopulation (Young et al., 1994). In this study, the localpopulation of the Wycombe Health Authority area wasvalidated as being representative of the UK as a wholeand the perception of reactions to food additives haddropped from 7.4% of the UK population to 5.5% inthe space of a few years.

Our calculated figures for the prevalence of foodadditive and true food intolerance show a discrepancybetween perception and calculated prevalence which ismuch greater in the case of food additives where 7.4%of the population perceived a problem, the challengestudy revealing a prevalence of 0.010.23% than in thecase of food intolerance to eight major foodstuffs whereperception indicated that 20.4% of the UK populationperceive a problem and challenge study confirmed theproblem in 1.41.8%.

In the study, the problem of sulphite sensitivity wasnot addressed because of doubts as to its suitability incapsule challenge study. Sulphite intolerance is thoughtto be more common when sulphite is present in solution

E. Young : En6ironmental Toxicology and Pharmacology 4 (1997) 111114114

resulting in sulphur dioxide being liberated causingbronchoconstriction. Less commonly, it has been sug-gested that sulphite released in the stomach from cap-sules can provoke a reaction by an unknownmechanism, and there have been documented caseswhere sulphite anaphylaxis with an IgE mechanismseems probable (David, 1993). The prevalence of sul-phite sensitivity in the US has been estimated as 0.05%of the population, occurring most often in asthmaticadult women (Lester, 1995).

Monosodium glutamate claimed as causing the Chi-nese restaurant syndrome blamed in provokingasthma, has been the subject of many unsatisfactorystudies. Flavours contain similar chemical constituentsto many fragrances. Dermatologists are aware that 10%of the eczema-prone population present with a contactallergic eczema to fragrance. There have been reports ofeczematous flares after ingestion of certain flavours inthe fragrance-sensitive group (Viein et al., 1985). Possi-ble flavour reactions have not been investigated and thehuge number of chemicals involved could lead to awhole new field of study. Until labelling of flavoursubstances becomes a reality, research in this field willbe limited.

The public perception that all that is natural is goodand artificial bad undoubtedly exists. Azo dyes, ben-zoate preservatives and the antioxidants BHA and BHThave been incriminated as the main culprits. Undoubt-edly, with the use of more and more chemicals, furtherreactions will be reported. The difficulty of identifyingthese reactions in the absence of any in vitro or in vivotest makes reliance upon the double-blind placebo-con-trolled challenge study the only effective way of estab-lishing reasonable answers. To design and implementthese studies is a considerable task, but necessary togive the right answers.

The concern raised by Feingold in 1973 on the effectof food additives on childrens behaviour has beenintensively studied (Feingold, 1973). The ideas of Fein-gold have generated controversy and a review of the

literature on the subject concludes that there indeed canbe an effect of some foods on behaviour, but only in aminority of subjects properly studied (Robinson andFerguson, 1992). There is more evidence to incriminatetrue food substances as causing adverse behaviour insusceptible children than the much maligned food addi-tives.

References

David, T.S., 1993. Sulphite in Food and Food Additive Intolerance inChildhood. Blackwell, Oxford, p. 198.

Feingold, B.F., 1973. Food additives and child development. Hosp.Pract. 21, 17.

Fuglsang, G., Madsen, C., Saval, P., Osterballe, O., 1993. Prevalenceof intolerance to food additives among Danish schoolchildren.Paediatr. Allergy Immunol. 4, 123.

Fuglsang, G., Madsen, C., Halken, S., Jorgensen, S., Ostergaard,P.A., Osterballe, O., 1994. Adverse reactions to food additives inchildren with atopic symptoms. Allergy 49, 31.

Lester, M.R., 1995. Sulfite sensitivity: significance in human health. J.Am. Coll. Nutr. 14, 229.

Madsen, C., 1994. Prevalance of food additive intolerance. Hum.Exp. Toxicol. 13, 393.

Medical Aspects of Food Intolerance, 1987. J. R. Coll. Phys. 21, 4.Murdoch, R.D., Pollock, I., Naeem, S., 1987a. Tartrazine induced

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Pollock, I., Warner, J.O., 1987. A follow-up study of childhood foodadditive intolerance. J. R. Coll. Phys. 21, 248.

Robinson, J., Ferguson, A., 1992. Food sensitivity and the nervoussystem. Nutr. Res. Rev. 5, 203.

Royal College of Physicians and The British Nutrition Foundation,1984. Food intolerance and food aversion. J. R. Coll. Phys., 18, 1.

Viein, N., et al., 1985. Oral challenge with Balsam of Peru. ContactDermatitis 12, 104.

Young, E., Stoneham, M.D., Petruckevitch, A., Barton, J., Rona, R.,1994. A population study of food intolerance. Lancet 343, 1127.

Young, E., Patel, S., Stoneham, M., Rona, R., Wilkinson, J.D., 1987.The prevalence of reaction to food additives in a survey popula-tion. J. R. Coll. Phys. 21, 241.

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