Vitamin therapy and children with Down Syndrome: a review of research.
Orthomolecular therapy (Evaluation)
Mentally disabled children (Care and treatment)
Down syndrome (Care and treatment)
Vitamin therapy (Evaluation)
Pruess, James B.
Fewell, Rebecca R.
Bennett, Forrest C.
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Name: Exceptional Children Publisher: Council for Exceptional Children Audience: Academic; Professional Format: Magazine/Journal Subject: Education; Family and marriage Copyright: COPYRIGHT 1989 Council for Exceptional Children ISSN: 0014-4029
Date: Jan, 1989 Source Volume: v55 Source Issue: n4

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ABSTRACT: The claim that large doses of vitamin-mineral supplements benefit mentally retarded children has captured the attention of the general public and the medical profession. A study, by Harrell, Capp, Davis, Pearless, and Ravitz 1981) reported inreases in IQ and improvements in behavior among mentally, retarded subjects (one third of whom were children with Down syndrome) receiving nutritional supplementation. However, subsequent studies, focusing exclusively on children with Down syndrome and using less flawed research designs, have demonstrated that vitamin therapy is not useful for members of this population,


The current American obsession with personal fitness has renewed interest among the general public and the medical profession in the effects of nutritional supplements on individual behavior and intelligence. Not only are large doses of vitamins and minerals believed to increase health and longevity, but they also allegedly benefit those with psychiatric disorders or developmental disabilities, including children with Down syndrome.

By vitamin therapy" we mean the administration of vitamins and minerals in amounts that exceed the recommended daily dietary allowance, as determined by the Food and Nutrition Board of the National Research Council (1980), in order to promote positive changes in physical health, appearance, and functioning. Belief in the effectiveness of vitamin therapy finds its theoretical rationale in "orthomolecular medicine," which is based on the idea that augmented concentrations of nutrients normally present in the human body are important for the treatment of "mental disorders" Pauling, 1968). In short, the "orthomolecular hypothesis" assumes a direct relationship between chemistry and behavior, one that can be exploited by an increased supply of assorted vitamins and minerals in order to solve complex disorders of human development.

In this article, we review the research on vitamin therapy for children with Down syndrome in order to discover whether it is a useful method of treatment for these children. VITAMIN THERAPY AND ITS EFFECTS: INITIAL REPORTS Pauling stated the orthomolecular hypothesis with reference to mental illness, which he viewed as resulting from insufficient amounts of specific vitamins in the brain cells. These vitamins included thiamine (B1), nicotinamide (B3), pyridoxine (B6), cyanocobalamin (B 12), biotin (H), ascorbic acid (C), and folic acid. "Orthomolecular therapy" would remedy these deficiencies and thereby contribute to overall physical health and optimal functioning of the mind. Schizophrenia The orthomolecular approach was congenial to those psychiatrists who accepted the assumption that schizophrenia is a physical illness caused by a genetically determined adrenalin deficiency in the body (Hoffer, Osmond, & Smythies, 1954). For example, Cott (1969) treated children diagnosed as schizophrenic by administering doses of nicotinamide, ascorbic acid, pyridoxine, deanol, acetamidobenzoate, and other vitamins and minerals, in combination with a prescribed diet for hypoglycemia low blood sugar). He reported positive results from this treatment (mostly on the basis of parent testimonials), which included a reduction in hyperactivity, more appropriate interactions with others, improved speech and language skills, and increased concentration and attention span. There were no reported negative side effects from the vitamin therapy. Learning Disabilities In a later article (1971), Cott offered a similar prescription niacin, ascorbic acid, pyridoxine, and calcium) for children with learning disabilities, and reported the same positive outcomes, which he saw as contributing to improved capacities for learning. This rambling discussion, a summary of the effects of proper diet and vitamin intake on "the creation of an optimum molecular environment for the mind," shows the willingness of some practitioners to apply the orthomolecular hypothesis to developmental disabilities (including autism) in addition to psychiatric disorders. In addition, Rimland, Calloway, and Dreyfus (1978) reported that withholding the administration of vitamin B6 to children with autism who were receiving vitamin therapy led to a deterioration in their behavior and overall functioning. Down Syndrome Turning to Down syndrome, reports indicate that vitamin therapy is one of a number of drug treatments that have been recommended or promoted over the years (Rynders, 1987). These remedies include glutamic acid (Gadson, 195 1); pituitary extract (Goldstein, 1954); fetal cell therapy Griffel, 1957; Schmidt, 1978); 5-hydroxytryptophan (Bazelon, Paine, Cowie, Hunt, Houck, & Manhanad, 1967); and dimethyl sulfoxide (DMSO) Aspillage, Morizon, & Avendano, 1975). Some of these treatments (notably, fetal cell therapy) have occurred in conjunction with the administration of vitamin megadoses. However, other panaceas offered for treating Down syndrome have concentrated on a single vitamin or a combination of vitamins. Pyridoxine (vitamin B6) is an example of the former (Coleman, 1973), while Turkel's controversial "U" series, an agglomeration of 48 substances including vitamins, minerals, enzymes, and hormones, exemplifies the latter. Turkel (1975) claimed that his treatment led to improvements in the intellectual functioning and physical attributes of children with Down syndrome.

A study by Harrell, Capp, Davis, Peerless, and Ravitz (1981) attracted the attention of both professionals and parents because, in contrast to Turkel's report, its endorsement of vitamin therapy was cloaked in the language of a controlled research investigation. Harrell and her associates set up this study in order to illuminate the concept of genetotrophic disease," which refers to afflictions of genetic origin that can be ameliorated by doses of one or more specific nutrients Williams, 1956). The subjects were 22 retarded children, ages 5-15, one-third of whom were children with Down syndrome, the remainder "unclassified." the subjects were divided into two groups (10 in Group 1, 12 in Group 2) matched according to IQ (mean IQ for Group 1: 46.3; for Group 2: 48.5). During the first 4-month phase of treatment, Group I children received a nutritional supplement consisting of I I vitamins and 8 minerals, while Group 2 children received placebos in the same form, a daily dosage of 6 tablets. During the second 4-month phase, both groups reduced in size because of dropouts) received supplements.

At the end of both phases, the principal investigator used the Stanford-Binet intelligence Scale, Form L-M, to test all subjects except two mute children who were examined using the Cattell Infant Scale. In addition, one of six psychologists (chosen by the parents) tested each child using the Wechsler intelligence Scale. The subjects were also checked for height, weight, urine pH, protein, blood cells, and thyroid.

At the end of the first phase, the 5 children who had received the supplements increased their IQ by 5.0 to 9.6 points (depending upon the examiner), while I I subjects given placebos showed no significant increase (0.0 - 1. 1). At the end of the second period, the Group 2 children who received the supplements showed an average IQ increase of 10.2-11.2 points, and 3 of the 5 subjects who had received the supplements during both phases of the study had additional IQ gains during the second 4 months. For most of the children with Down syndrome, the investigators reported an increase in IQ from 10 to 25 points, improved eyesight, and positive changes in physical appearance (decreased facial puffiness). Even more remarkably, other children transferred from special to regular education programs, and one 5-year-old progressed from uttering single words "Mama," "bye-bye") to reciting the Pledge of Allegiance. VITAMIN THERAPY CHALLENGED: CRITICAL RESPONSES According to reviews of the literature by Share (1976) and Rynders (1987), none of the proposed medical treatments of Down syndrome have stood up to challenges by carefully monitored research studies. For example, dimethyl sulfoxide (Gabourie, Becker, & Bateman, 1975), fetal cell therapy Black, Kato, & Walker, 1966; Foreman & Ward, 1987), and 5-hydroxytryptophan (Pueschel, Reed, & Cronk, 1984) were all proven ineffective in studies that used control groups, blinded investigators, and standardized assessment measures, methodological features usually absent from the initial reports of treatment advocates. The status of vitamin therapy as a credible form of treatment for children with developmental delays came under similar scrutiny. Critics perceived that earlier reports on the effectiveness of megavitamins suffered from anecdotal reporting styles or glaring weaknesses in methodology (Hoffobin & Pueschel, 1982).

For example, in the article by Rimland, Callaway, & Dreyfus (1978) mentioned previously, the authors claimed that withdrawing 16 children with autism from the vitamin B6 megadoses they were receiving resulted in a worsening of the children's behavior. However, as the authors themselves admitted, they failed to account for possible vitamin B6 addiction and the effects of other vitamin megadoses that the subjects were receiving at the same time. In addition, the parents and teachers of the subjects rated subject behaviors by means of narrative summaries and checklists of questionable reliability. More recent studies of the effect of vitamin B6 on children with Down syndrome (Pueschel, 1987) reported no significant improvement in the intellectual functioning of children receiving treatment.

Similarly, Bumbalo, Morelewicz, and Berens (1964) refuted Turkel's claims about the effectiveness of his U" series in a controlled study in which Turkel himself participated, assigning 24 children with Down syndrome to two equal groups and administering the drugs and placebos at random. The authors administered the Stanford-Binet to subjects and gave them physical exams at the beginning of the study and again at its conclusion one year later. They found no significant differences between the two groups except for improved "socialization" on the part of the treatment group. This was attributed to the actions of teachers and not to the U" medications.

Even the study by Haffell et al. (1981), which appeared to be a controlled research investigation, was not without methodological problems. For example, of the 22 children initially enrolled in the study, only 16 children (5 in the treatment group, I I in the control group) actually completed it. In addition, the study was not completely "doubleblind": During the second phase of the study, the principal investigator who was testing subjects knew that all of them were receiving vitamin supplements. The researchers who undertook studies in response to the findings of Harrell and her colleagues took care to eliminate these shortcomings from their own work.

However, not all of these investigations were faithful replications of the Harrell study. For example, Coburn, Schaltenbrand, Mahuren, Clausman, and Townsend (1983), and Ellis and Tomporowski (1983) selected institutionalized mentally retarded young adults as subjects, less than half of whom were individuals with Down syndrome. Nevertheless, both studies used the same combination of vitamins and minerals that Harrell and her associates administered. Over a 7-month period, Ellis and Tomporowski observed no changes in IQ or in adaptive behavior (independent living skills in the institution) for subjects who received the vitamin supplement. Similarly, Coburn et al. found no improvement in Stanford-Binet scores over a 20week period for subjects receiving the supplement. As the authors themselves admitted, neither of these studies of institutionalized young adults could produce results that invalidated the findings of Harrell et al. in regard to children who were living at home and attending day programs.

The studies by Ellman, Silverstein, Zingarelli, Schafer, and Silverstein (1984) and Chanowitz, Ellman, Silverstein, Zingarelli, and Ganger (1985) also focused upon the effects of vitamin and mineral supplements on mentally retarded young adults, with negative results. However, the latter investigation (following up an issue raised by Ellman et al.) sought to determine whether the administration of thyroid medication was an essential component of the nutritional supplementation treatment. Ellman et al. and Chanowitz et al. argued that the test of thyroid deficiency used in the Harrell study (the Barnes test, a measure of basal auxillary temperature) was unreliable and that thyroid administration may have been a "confounding variable" in the research results (especially as some children in both treatment and control groups received thyroid supplements). In their study, Chanowitz et al. demonstrated no connection between thyroid administration and IQ for the profoundly retarded, institutionalized subjects.

In short, the results of these four studies, undertaken with institutionalized mentally retarded young adults (among whom individuals with Down syndrome were a minority) failed to show that vitamin therapy was successful. However, because Harrell et al. emphasized that the greatest gains occurred in the children with Down syndrome (even though only four participated in the full study), three additional studies were undertaken to confirm or refute this finding (Bennett, McClelland, Kriegsmann, Andrus, & Sells, 1983; Smith, Spiker, Peterson, Cicchetti, & Justice, 1984; Weathers, 1983).

Each of these studies replicated and expanded the Harrell research design by eliminating its methodological defects and focusing exclusively on home-reared children with Down syndrome between 5 and 17 years of age. In each study, these children were randomly assigned by matched pairs to either vitamin/mineral or placebo groups. Subjects in the vitamin/mineral groups received the same nutritional supplement used by Harrell; in the Smith study, this group (but not the placebo group) also received a thyroid supplement. In each study, the investigators who assessed the children were "blind" throughout the duration of the study period (8 months for Bennett et al., and Smith et al., 4 months for Weathers). Bennett et al. and Weathers, following Harrell, used the Stanford-Binet Intelligence Scale, Form L-M, augmented by academic achievement, behavioral, and language measures (Bennett et al.) or tests of visual acuity and motor integration Weathers). Smith et al., on the other hand, made use of the Wechsler Intelligence Scale for Children-Revised or (for younger children) the Wechsler Preschool and Primary Scale of Intelligence, along with the Peabody Picture Vocabulary Test-Revised (Form L), physical examinations, and blood tests.

in each study, there were no differences between children in the vitamin/mineral groups or placebo groups with regard to any tested areas of development or behavior, including IQ. (However, Weathers reported that the mean IQ for the placebo group at the end of the study was actually higher than that of the group receiving the supplement.) In response to the claims by Harrell et al. and Rimland (1983) that vitamin therapy is most effective with younger children, Weathers conducted a post hoc analysis of the results to see whether the younger subjects in the study (ages 6-9) made greater improvements than subjects in other age groupings (9-12, 13-17). Such was not the case. In short, none of these studies confirmed either the findings reported by Harrell or the overall effectiveness of vitamin therapy. DISCUSSION In some instances, physicians have successfully prescribed supplements of one specific vitamin to ameliorate certain problems of metabolism that may be linked with mental retardation, for example, thiamine for patients with vitamin-dependent maple syrup urine disease (Elsas & Danner, 1982). Researchers have reported similar specific nutrient or metabolic deficiencies in children' with Down syndrome (e.g., vitamin A, vitamin B6, vitamin C, vitamin D, zinc) (Bjorksten, et al., 1980; Matin, Sylvester, Edwards, & Dickerson, 1981; Palmer, 1978). However, these deficiencies have not been consistently confirmed or documented Pueschel, 1987). For example, a recent study in Spain indicated no differences in levels of vitamin D between children with Down syndrome and nonretarded children (Del Arco, Riancho, Luzuriaga, Gonzalez-Macias, & Florez, 1986). On the other hand, Palmer (1978) addressed vitamin A deficiency in children with Down syndrome and its remediation in terms of resistance to disease, reporting a decrease in rate of infection and an increase in plasma vitamin A levels in children who had received vitamin A treatment for 6 months. Yet the author made no claims about the vitamin's capacity for improving intellectual functioning and behavior.

in none of the studies designed to test the claims of vitamin therapy proponents did the subjects have any recognized nutritional deficiencies. This issue was irrelevant to the studies, whose findings showed that there was no improvement in appearance, growth, intellectual development, or health as a result of the vitamin/mineral supplement administered to the children with Down syndrome.

Nevertheless, in two of the studies, some of the parents of the participating children continued to believe in the efficacy of the vitamin treatment. Smith et al. (1984) discovered that 41% of the parents whose children received placebos guessed that the children were taking the supplements. Weathers (1983) requested parents of both treatment and control group children to look for changes in their child's behavior, physical appearance, and overall health. Many parents in both groups reported positive changes such as greater attention span and alertness, and improved skin and hair texture. Moreover, most parents of children in both groups chose to continue the vitamin supplementation, in spite of the failure of the study to demonstrate its efficacy. Such a response may reflect a stubborn optimism or an adherence to a willed "definition of the situation": If we believe that vitamin megadoses bring positive results, then positive results will occur. Smith et al. also noted that, in addition to the effect of positive expectations for improvement, parents may be observing normal developmental changes in their children, and attributing these changes to the magical power of vitamins.

On the other hand, the attitudes of parents whose children participated in the study by Bennett et al. (1983) were quite different, perhaps because of differences in education level and socioeconomic status. These parents were somewhat skeptical about the alleged value of vitamin therapy, but were nevertheless willing to give it a try, and hopeful that perhaps some gains might occur. At the conclusion of the study, when its negative results were revealed and discussed, parents were grateful "that, for them, this controversial and emotional issue had been clarified in a careful, believable manner" p. 713). Coifman (1980) also took parental attitudes into account by enlisting the participation of a parent in an unbiased, controlled study that demonstrated to the parent's satisfaction the ineffectiveness of vitamin E megadoses for her child with Down syndrome.

In conclusion, the results of the studies undertaken in response to Haffell et al. clearly indicate that vitamin therapy is not useful for young children with Down syndrome and, therefore, do not support the idea that increases in nutrients contribute to improved mental functioning. None of the studies reported negative side effects from the administration of large doses of vitamins and minerals. Yet the toxic effects of vitamin megadoses (both water-soluble vitamins such as B6 and the fat-soluble vitamins A, D, and E) are increasingly recognized by the medical profession and the unhappy victims of vitamin overdose (Rudman & Williams, 1983). In addition, when (as frequently happens) vitamin megadoses are part of a treatment package" that includes vitamins, minerals, enzymes, and/or fetal cell injections, the ingredients of the combined treatment may interact, with serious consequences for the child's health. According to the American Academy of Pediatrics, vitamin and mineral supplementation is unnecessary for most preschool children, whose nutritional needs can be satisfied by a well-rounded diet. This advice is equally apt for children with Down syndrome (Pueschel, 1987).

Future advances in gene mapping may enable scientists to discover what the extra genetic material on the 2]st chromosome actually represents. On the basis of this knowledge, they may be able to devise forms of medical therapy that effectively address problems of biochemical functioning in children with Down syndrome. Such methods will have to surpass current applications of vitamin therapy, which at best contribute nothing to the development of behavior and intelligence and at worst may be harmful to a child's health.
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