This week, Dr. Sydney Spiesel discusses whether food additives cause ADHD, the hurdles to effective scarring treatments, and the hazards of a new cause for concern, plasticizers.
Do food additives cause ADHD?
History: More than 30 years ago, Dr. Ben Feingold, a pediatric allergist, developed a diet free of food additives (artificial colors, flavors, and certain preservatives) as a treatment for some childhood allergies. To his surprise, some of the children placed on the diet experienced a striking change in behavior. Earlier, they’d been troublesome because of their dreaminess, lack of focus, or hyperactivity—the traits of attention deficit hyperactivity disorder. Afterward, some (though by no means all) seemed to show a remarkable decrease in these behaviors. Their parents became passionate advocates for this treatment, as did Dr. Feingold.
Caveat: But because the results were not uniform, and in many doctors’ hands ineffective, many health professionals were skeptical. Studies (many, many studies) were done to establish the validity of Feingold’s belief that food additives caused ADHD. But they were often poorly done, and their results were conflicting and not very impressive. Sometimes, sharp doctors working in special circumstances would catch a whiff of the result Feingold noted, but that was it.
New research: And then last week, an acceptably rigorous study of the idea behind the Feingold diet—that food additives might contribute to ADHD—appeared. Donna McCann, Jim Stevenson, and a number of their colleagues, mostly at the School of Psychology of the University of Southampton, studied the question in the way that medical science likes best: the double-blind placebo-controlled trial. They tested two groups of a total of 300 children: one set of 3-year-olds and a set of 8- to 9-year-olds, all living in a small English city. The children’s behavior was closely observed while they drank either plain dark-colored fruit juice (the placebo) or the same juice spiked with one of two food-coloring mixes also containing the common preservative sodium benzoate. (The amount and kind of food coloring wasn’t a lot—actually, it was the same as could be found in one or two 2-ounce bags of sweets.) The drinks, plain and spiked, looked and tasted the same. On different weeks, the kids were switched back and forth between the plain juice and the spiked juice without anyone knowing which was which. Their behavior was scored using some standard scales for ADHD.
Findings: Sure enough, there was, on average, a clear increase in hyperactive behavior from the scores measured when the kids took the additive-laden juice to the scores when the same kids took the plain juice. And, confirming the private observations of sharp rheumatologists, some children were strongly affected and others were not affected. It is unclear whether the change in behavior is caused by a true allergy (as Feingold surmised) or an effect on the chemistry of the brain. But for some kids, it’s real enough.
Remaining questions: Which of the six dyes and the preservative used to make the two test mixtures was the important one? All of them? One or two? Are the effects only due to artificial products, or are there natural products capable of producing the same results? Can we identify genetic differences that make some children susceptible? Until we unravel the answers to these questions, it certainly looks as if we should rethink the additives we put in food and drink
Tough scars
Problem: Scar tissue is nature’s overenthusiastic way of protecting us after injury. The body deploys it to plug up breaches in our skin to prevent infection and also strengthen the injured area. (Here’s more about how it works.) Normally, as time passes, the scarring diminishes. But sometimes it becomes what’s called hypertrophic, resulting in stiff, thick tissue. This extreme scarring can permanently immobilize body structures—fingers, hands, and wrists, for instance—and it can also be very disfiguring. Treatment costs in the United States for hypertrophic scars are estimated at about $4 billion every year.
History: In the last 60 or so years, medicine has learned a lot about how to prevent early death following serious burns or trauma. To stave off serious scar formation in these patients, we’ve learned to replace burned skin with healthy skin harvested from other parts of the body, or artificial skin substitutes. But the existing methods aren’t as effective as we’d like.
New research: A recent paper by Shahram Aarabi, Michael Longaker, and Geoffrey Gurtner, all of the Department of Surgery at Stanford University School of Medicine, explains why we’re still far from solving this difficult problem. First, as yet there are no really good animal models for the hypertrophic scarring that occurs in humans, limiting the possible research. Second, hypertrophic scarring almost certainly results from the complex interplay of three different forces and, until now, researchers have tended to focus only on one aspect at a time. Aarabi and colleagues point out that all three pieces of the puzzle need to be addressed to prevent hypertrophic scarring. These key elements are:
Findings: 1) Inflammation. After an injury, cells are drawn in to clean up the mess. These cells release many active chemicals that promote inflammation, causing swelling, increased blood flow, leakage of fluid into tissues, and irritation. Research on medications that reduce scarring by calming local inflammation (sometimes by blocking the activity of the released chemicals) is pointing at helpful treatments.
2) Regeneration. The extensive destruction of skin eliminates the stem cells normally scattered in it. If skin-forming stem cells are missing, a new, thin layer of healthy skin that would help to suppress scar development cannot form. Grafting sheets of undamaged skin helps somewhat. But what is really needed is a way to collect and purify adult skin stem cells from other sites in the injured patient, and then spread them evenly at the site of injury. This has been difficult, but there is finally some progress.
3) Physical forces. For reasons we don’t yet understand, certain physical forces—stretching, movement, and mechanical stress—contribute to the generation of excessive scars. This puts doctors in a treatment quandary: How can we keep joints moving after injury to prevent them from stiffening and losing mobility without adding to scarring? The answer will probably involve blocking the signaling mechanism that tells the scar to increase in response to movement, but so far little progress has been made at understanding the nature of this signaling.
Conclusion: Addressing severe scarring is different than many problems medical science confronts in that it depends on complex treatments which simultaneously address multiple causes. Understanding the three elements is a first step, at least.
Leaching plasticizers
Problem: In the 1967 movie The Graduate, the future was imagined in a single word— plastics. Well, we’re there now. Vast amounts of plastics are used to generate most of the objects we take for granted in our lives. And so are plasticizers, which add flexibility to plastics. (Here’s how.) The most common plasticizers, chemicals called phthalates, are incorporated into plastics at a rate of more than 18 billion pounds every year, worldwide. They’re also used to hold fragrance and color in cosmetics and to control the rate of release of some medications. And now, we’ve got problems. Unfortunately, phthalates don’t remain fixed in place forever. They slowly leach out of the plastic and become part of the water we drink and the food we eat. They are so heavily used that exposure to them cannot be avoided. They do accumulate in human beings. And increasing evidence suggests that these materials are not inert and benign, but rather active and sometimes harmful.
Effects: Phthalates (and bisphenol A, another important plasticizer) have profound effects on the reproductive system. These chemicals can cause damage to normal testicle development with inadequate male-hormone production. They can also block male hormone activity and mimic female hormone activity. These are the known effects in animals, and there is a strong suspicion that they may act similarly in humans. In animals, they can also cause cancer and fetal death and malformation.
Implications: So, now what? The search is on for affordable, nontoxic replacements for these plasticizers, but none have been found yet. Until then, I suppose all we can do is get rid of the worst of them and be careful about what we use them for. For instance, since premature infants are likely to be exceptionally sensitive to their effects, perhaps we should exclude them from materials intended for use in neonatal intensive care units. In a way, however, these chemical additives are like diesel trucks. We know their emissions are polluting and harmful but we can’t do without the stuff they carry.
