suggests that the preservative sodium benzoate and commonly used artificial food colorings in fact may exacerbate hyperactive behavior in young children.

In the Lancet study, researchers led by Jim Stevenson, a professor of psychology at the University of Southampton, United Kingdom, built upon a previous double-blind placebo-controlled study of preschool children. In that study, published in the June 2004 Archives of Disease in Childhood, 3-year-old children on a diet free of artificial dyes and benzoate preservatives exhibited increased hyperactivity when challenged with a drink containing a mixture of the widely used sodium benzoate plus the dyes Sunset Yellow, carmoisine, tartrazine, and Ponceau 4R (in their later paper, Stevenson and colleagues termed this combination "mix A"). Again using a double-blind placebo-controlled design, the Southampton team expanded the study group to include 153 3-year-olds and 144 8- and 9-year-olds representative of the general population.

Children ate diets free of the elements in mix A and a second, more concentrated mixture of additives ("mix B," comprising sodium benzoate plus the dyes Sunset Yellow, carmoisine, Quinolone Yellow, and Allura Red AC) for six weeks. During that time, they drank a daily serving of plain juice (placebo) or juice containing one of the two mixes; the test drink changed weekly. To measure hyperactivity, the team calculated a global hyperactivity aggregate (GHA) based upon questionnaires completed by parents, teachers, and trained observers. Older children also completed a computer-based assessment of attention. Small but significant increases in GHA occurred with mix A in both age groups, with 3-year-olds showing a greater effect. Mix B was associated with a small significant effect in 8- and 9-year-olds, but not in 3-year-olds, who had a wide range of individual responses.

"The outstanding feature of the results was the similar pattern of an adverse effect across both ages for both mixes—although this did not reach statistical significance in every case," says Stevenson. An unpublished study based on genetic samples from the children examines these individual differences in greater detail. "Our [forthcoming] data indicate that genetics rather than anything else accounts for these individual differences in response within an age group," Stevenson says.

Although the Southampton researchers conclude that their results strongly support a relationship between food additives and behavior, they do not claim that food additives cause clinically defined ADHD. "It is very important to clarify that the food additives and preservative studied only increased activity level modestly," says Andrew Adesman, chief of developmental and behavioral pediatrics at Schneider Children's Hospital in New Hyde Park, New York. "I think the reasonable lessons from this study are that there may be modest effects on activity level from additives or preservatives and that better, more precise studies are needed to determine whether it is the additives alone, the preservatives alone, or the combination that is responsible for these modest adverse effects." The authors describe these research needs with the additional requirement of considering the time elapsed between additive consumption and subsequent behavior.

Nevertheless, after reviewing the Southampton study, the British Committee on Toxicity concluded that the results could be clinically relevant for individual children, particularly those who already show a tendency toward hyperactivity. On the basis of this study the British Food Standards Agency, which funded the research, has advised parents to consider eliminating the colorings used in the study from the diets of children who exhibit hyperactive behaviors.

"It will be interesting to see how the [U.S.] Food and Drug Administration reacts to this study," says Adesman. "Hopefully, they will either encourage or mandate additional studies looking at food effects of additives on children and also adults."

The FDA is aware of the Southampton study but has not received the study data, according to administration spokesman Mike Herndon. "We will examine this recent report to see if the results suggest whether any action to modify our current regulations is appropriate," he says. "However, we have no reason at this time to change our conclusions that the ingredients that were tested in this study that currently are permitted for food use in the United States are safe for the general population."

Julia R. Barrett

Food Additives and Hyperactivity

Environ Health Perspect. doi:10.1289/ehp.11182 available via http://dx.doi.org [Online 27 May 2008]

Referencing: Hyperactive Ingredients?

In the December 2007 Forum article on the links between food additives and hyperactivity, Barrett (2007) offered a somewhat distorted perspective on the public health implications of these additives. Barrett described a clinical trial testing the proposition that consumption of a blend of artificial food flavors and sodium benzoate induces changes in children's behavior (McCann et al. 2007). The results of that study support such a claim.

Barrett (2007) fumbled the significance of the trial (McCann et al. 2007) for environmental health. The Forum article emphasized how food additives might contribute to the clinical diagnosis of attention deficit/hyperactivity disorder rather than on the more significant finding that food additives, particularly synthetic colors at levels prevailing in the diet, induce adverse behavioral responses. This is hardly a novel finding. In 1980, such effects were documented in two different groups of subjects with two different experimental designs (Swanson and Kinsbourne 1980; Weiss et al. 1980). Many later publications have confirmed their results. I briefly reviewed the data in Environmental Health Perspectives (Weiss 2000).

According to Barrett (2007), a Food and Drug Administration (FDA) official, Mike Herndon, maintains that the agency sees "… no reason at this time to change our conclusions that the ingredients that were tested in this study that currently are permitted for food use in the United States are safe for the general population." This is a rather baffling statement. In fact, our study (Weiss et al. 1980) was funded by the FDA, and its results, along with a number of others from that period, definitively demonstrated adverse behavioral effects of synthetic food colors (Weiss 1982). During the intervening years, with a plethora of confirmations, the FDA has remained blindly obstinate. It continues to shield food additives from testing for neurotoxicity and apparently believes that adverse behavioral responses are not an expression of toxicity.

Herndon and the FDA should seriously consider what the late Philip Handler said about balancing risks and benefits:

A sensible guide would surely be to reduce exposure to hazard whenever possible, to accept substantial hazard only for great benefit, minor hazard for modest benefit, and no hazard at all when the benefit seems relatively trivial. (Handler 1979)

The FDA has never clarified the health benefits of artificial food colors.

The author declares he has no competing financial interests.

References

Barrett JR. 2007. Hyperactive ingredients? Environ Health Perspect 115:A578.

Handler P. 1979. Some comments on risk. In: The National Research Council in 1979; Current Issues and Studies. Washington, DC:National Academy of Sciences, 3–24.

McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, et al. 2007. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567.

Swanson JM, Kinsbourne M. 1980. Food dyes impair performance of hyperactive children on a laboratory learning test. Science 207:1485–1487.

Weiss B. 1982. Food additives and environmental chemicals as sources of childhood behavior disorders. J Am Acad Child Psychiatry 21:144–152.

Weiss B. 2000. Vulnerability of children and the developing brain to neurotoxic hazards. Environ Health Perspect 108(suppl 3):375–381.

Weiss B, Williams JH, Margen S, Abrams B, Caan B, Citron LJ, et al. 1980. Behavioral responses to artificial food colors. Science 207:1487–1489.

Editor's Note

Weiss correctly points out that several investigators, including himself, have reported links between food additives and hyperactivity in children. He is also correct in stating that food additives appear to exacerbate existing hyperactive behavior in children, rather than contribute to the clinical diagnosis of attention deficit/hyperactivity disorder (ADHD). The study by McCann et al. [Lancet 370:1560–1567 (2007)] supports that conclusion, as described in Barrett's December 2007 Forum article [Environ Health Perspect 115:A578 (2007)].

We believe it was important to mention ADHD because hyperactivity and clinically defined ADHD are often conflated in the science news press. The point of referring to ADHD and therein clarifying the relationship between ADHD and hyperactivity was to put the import of the findings by McCann et al. (2007) into proper perspective. 118

Republished in verbatim from http://www.ehponline.org/docs/2008/11182/letter.html#resp