Scientists’ letters to the Department of Health and Human Services Letter from CSPI to HHS Secretary Shalala October 25, 1999 Hon. Donna Shalala, Secretary U.S. Department of Health and Human Services 200 Independence Ave. SW Room 615F Washington, DC 20201 Dear Secretary Shalala:      The Center for Science in the Public Interest has published a report, “Diet, ADHD, and Behavior”, that reviews studies on the effect of diet on behavior (including ADHD) and touches on side effects of the stimulant drugs that have been used to treat behavior disorders in millions of children. I have enclosed our report and letters from doctors and scientists that urge HHS to take a variety of actions. I hope that you will give our recommendations serious consideration.      CSPI’s report reviews more than 20 controlled studies of diet and behavior. Most of the studies found that food dyes and, in some cases, other additives and foods provoked symptoms of ADHD or other behavior problems in some children. In light of that evidence, HHS should inform parents, school officials, and health-care providers that some children are affected by diet and that dietary therapy should be considered as a first course of treatment. We further recommend a broad research agenda to better understand foods’ effects on behavior, several regulatory measures (including more routine testing for behavioral effects of food additives and consideration of a ban on food dyes in foods and other products widely consumed by children), and educational efforts (revising literature and web sites, including a pamphlet that FDA cosponsors with a food-industry association, that deny that diet affects behavior).      Maximizing the use of non-pharmacologic treatments is particularly important because the stimulant drugs commonly used to treat ADHD have side effects, including insomnia, loss of appetite (and failure to grow), stomachache, and, possibly, Tourette’s syndrome. Importantly, a 1995 study by the National Toxicology Program found that methylphenidate (Ritalin), the most commonly used drug, caused liver tumors in mice. The NTP categorized that drug as a “possible human carcinogen.” When that study was published, the FDA said it would sponsor additional research, but little such research has been done. The package insert for methylphenidate notes the cancer study, but many doctors are unaware of or belittle that information, and, of course, patients or their parents never see the package insert. It is critical that a potentially carcinogenic drug that is used by a large number of children over many months or even years be well tested and found to be appropriately safe and that doctors and patients be aware of possible risks. Amphetamines, increasingly used to treat ADHD, did not cause cancer in an NTP study, but also need to be tested for long-term effects, particularly because its usage appears to be skyrocketing: Until additional safety tests are done -- we recommend several kinds of studies -- it is all the more important for HHS to urge physicians to consider alternative approaches to treating patients.      Thank you for your attention to this important issue. I look forward to your response. Sincerely,   Letter from Experts on Diet and Behavior to HHS Secretary Shalala. October 25, 1999 Hon. Donna Shalala, Secretary U.S. Department of Health and Human Services 200 Independence Ave. SW Room 615F Washington, DC 20201 Dear Secretary Shalala:      Attention Deficit/Hyperactivity Disorder (ADHD) and other behavioral disorders affect millions of children and adults. Those disorders, which constitute tremendous problems for victims, their families, and the general community, impair health and happiness and need to be treated. Some behavioral disorders, particularly ADHD, are typically treated with stimulant drugs such as methylphenidate (Ritalin). Drug usage has increased dramatically in the past two decades and is remarkably widespread. While 3-5% of U.S. elementary-school children have ADHD, a recent study found that in two cities, 18-20% of 5th-grade white boys were being treated with stimulant drugs (Am J Pub Health 1999;89:1359-64).      Over the past quarter-century numerous controlled studies have demonstrated that some children clearly are affected adversely by artificial colorings and certain foods. Those studies are summarized in a recent report (enclosed) by the Center for Science in the Public Interest (CSPI). In food-sensitive children, a modified diet may mitigate the need for drugs, which sometimes cause side effects (including reduced appetite, stomachaches, and insomnia).      In 1982, a National Institutes of Health consensus conference concluded that controlled studies “did indicate a limited positive association between defined [Feingold-type] diets and a decrease in hyperactivity.” Currently, though, the National Institute of Mental Health and the Food and Drug Administration largely dismiss foods and food additives as agents that can trigger behavioral problems (see CSPI report). NIMH has said that restricted diets “have not been shown to be effective in treating the majority of children or adults with ADHD.... families risk spending time, money, and hope on fads and false promises.” The FDA has cosponsored with an industry trade association a booklet that stated that “well-controlled studies conducted since then have produced no evidence that food color additives cause hyperactivity or learning disabilities in children,” even though the FDA itself sponsored one study demonstrating that some children are affected by food dyes. Moreover, a 1998 NIH consensus conference on the treatment of ADHD virtually ignored the body of evidence concerning diet.      The undersigned scientists and physicians urge the Department of Health and Human Services to carry out a broad range of research, as recommended by the 1982 NIH consensus conference, to fully investigate the relationships between diet and behavior. Additional research should explore potential adverse effects of stimulant drugs. We further urge HHS to provide parents with accurate information about dietary changes that might benefit their children and reduce the need for stimulant drugs. Specifically: 1. NIH should sponsor research to: (a) determine which foods and food additives provoke behavioral problems and what fraction of children are susceptible; (b) develop methods for identifying children who are sensitive to foods and additives; (c) investigate the underlying biological mechanisms for how food affects behavior; (d) develop techniques (such as desensitization) to reduce adverse effects of dietary constituents on children’s behavior; (e) develop means of increasing the ease and effectiveness of dietary treatment; (f) investigate the potential efficacy of nutritional supplements (including fatty acids, minerals, and vitamins) in treating ADHD. (g) conduct long-term animal and human studies to identify any possible carcinogenic, behavioral/social, reproductive, teratogenic and other effects of stimulant drugs; 2. NIH should sponsor a new consensus conference to provide a full and fair review of studies on diet and ADHD, as well as other alternative treatments. 3. NIMH, FDA, and other units of HHS should inform parents, school officials, and health-care providers that studies have demonstrated that certain foods and additives provoke symptoms of ADHD or other behavioral problems in some children. They should suggest that dietary therapy be considered as a first course of treatment, especially for children who suffer from allergies, sleep disturbances, and irritability. They should revise publications that dismiss diet as a contributor to behavioral problems and should note that stimulant drugs sometimes have adverse side effects. 4. The FDA should: (a) require new, as well as certain existing, food additives to be tested for behavioral effects; (b) consider banning the use of synthetic dyes in foods and other products (such as cupcakes, candies, sugary breakfast cereals, vitamin pills, drugs, and toothpaste) widely consumed by children.      We appreciate your attention to this important matter. Sincerely,   Sidney MacDonald Baker, M.D., research director, Children’s Development Database; former faculty member, Yale Medical School; former director, Gesell Institute of New Haven Joseph Bellanti, M.D., professor of pediatrics and microbiology-immunology, Georgetown University Medical Center, Washington, DC Marvin Boris, M.D. pediatrics, allergy, and immunology, Woodbury, NY William G. Crook, M.D., director, International Health Foundation, Jackson, TN Donald R. Davis, Ph.D., Biochemical Institute, University of Texas Austin Leo Galland, M.D., director, Foundation for Integrated Medicine, New York, NY William T. Kniker, M.D., clinical professor of pediatrics and internal medicine, Univesrsity of Texas Health Science Center at San Antonio, TX Sheldon Margen, M.D., professor emeritus, Public Health Nutrition, University of California, Berkeley; Chairman, editorial board, U.C. Berkeley Wellness Letter Sidney Walker III, M.D., founder, Behavioral Neurology International, La Jolla, CA Letter from Cancer Experts to HHS Secretary Shalala October 25, 1999 Hon. Donna Shalala, Secretary U.S. Department of Health and Human Services 200 Independence Ave. SW Room 615F Washington, DC 20201 Dear Secretary Shalala:       Attention Deficit/Hyperactivity Disorder (ADHD) and other behavior disorders plague millions of children and adults. Those disorders, which constitute tremendous problems for those individuals, their families, and the general community, are typically treated with stimulant drugs, most commonly methylphenidate (Ritalin). Drug usage has increased dramatically in the past two decades. While 3-5% of U.S. elementary-school children have ADHD, a recent study found that in two cities, 18-20% of 5th-grade white boys were being treated with stimulant drugs. Those issues, and the effect of diet on behavior, are described in the enclosed report by the Center for Science in the Public Interest.       In 1995 the National Toxicology Program published a study that found that methylphenidate caused benign and malignant liver tumors in mice (but not rats) (Toxicol. 1995;103:77-84). That study was particularly noteworthy because the hepatoblastomas seen in male mice are extremely unusual and, unlike many animal studies that use extraordinarily high dosages, the dosage of methylphenidate that caused cancer in the NTP study was as little as 2.5 times higher than the maximum recommended dosage in humans. The NTP concluded that methylphenidate is a “possible human carcinogen” and recommended further research.(1) That study was limited, in part, because the mice were exposed to the drug only beginning when they were 7-8 weeks old. The most sensitive studies usually expose animals beginning in utero.       When the NTP’s study was released, the Food and Drug Administration required makers of drugs containing methylphenidate to include on the package insert information about it. That insert is not seen by patients. An FDA press release acknowledged that the NTP findings constitute a “weak signal of carcinogenic potential,” but said the agency still considered the drug to be safe. The FDA said that it would “initiate additional follow-up studies, including both animal tests and epidemiological studies in humans using Ritalin.” Apparently, the only subsequent study was a short-term study, conducted by the National Institute of Environmental Health Sciences, of p53-deficient mice; it did not detect evidence of carcinogenicity. That study, which used a strain of mouse resistant to liver tumors, does not provide reassurance of safety and certainly does not eliminate the concerns raised by the NTP’s chronic-feeding study.       Considering the enormous numbers of children and adults who take stimulant drugs for long periods of time, we urge the Department of Health and Human Services to conduct studies on methylphenidate and other stimulant drugs, including: * a full range of animal studies to investigate any possible carcinogenic, behavioral, reproductive, teratogenic and other effects; * testing to assess cytogenetic damage in children who have been taking stimulant drugs; * long-term studies on large numbers of users of stimulant drugs to identify any adverse effects, such as behavior disorders, social problems, cancer, reproductive problems, or other health problem.      We also urge HHS to sponsor research to identify environmental triggers (such as pollutants and dietary constituents) of behavior disorders so that preventive measures could be taken that would minimize the need for pharmacologic treatment.      Finally, we urge HHS to inform parents, school officials, and health-care providers that stimulant drugs may have adverse side effects, including, in the case of methylphenidate, possibly cancer.      We appreciate your attention to this important issue. Sincerely,   Richard Clapp, D.Sc., associate professor, Department of Environmental Health, Boston University Devra Davis, Ph.D., director, Health, Environment, and Development Program, World Resources Institute, Washington Samuel Epstein, M.D., professor of environmental medicine, School of Public Health, University of Illinois Medical Center, Chicago Emmanuel Farber, M.D., Ph.D., professor of pathology, University of South Carolina School of Medicine Donald A. Fox, Ph.D., professor of biochemical and biophysical sciences, University of Houston Marvin S. Legator, Ph.D., professor and director of division of environmental epidemiology, University of Texas Medical Branch, San Antonio William Lijinsky, Ph.D., former director, chemical carcinogenesis program, Frederick Cancer Research Center 1. Indeed, three out of the seven NTP reviewers believed that the study demonstrated that the studies showed “clear evidence of carcinogenic activity.” (NTP Technical Report Series No. 439, pp. 11-12)

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