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by Mary Coleman, M.D.
Is television becoming so powerful in the United States that it is taking the place of medical science? A popular evening television program in the United States is Nightline which, in spite of the inevitable oversimplification of topics discussed on television, often has a factual basis. On December 20, 1996, Nightline aired a program with extravagant claims for the use of multivitamins and minerals in Down syndrome. Exuberant parents claimed that their children were healthier, taller, happier and more intelligent since taking the multivitamin/mineral supplements.
On the program, no professionals seriously challenged these claims or suggested that parents discuss the claims with their own physician who could have consulted textbooks discussing this subject of multivitamins in Down syndrome (Pueschel et al., 1987; Rogers & Coleman, 1992). The impression was left with the viewer that multivitamins were an exciting new treatment for Down syndrome.
Multivitamins and Multiminerals
If only it was so simple. Megavitamins, often combined with minerals, enzymes and hormones, have been advocated for more than a generation as a treatment for Down syndrome in parts of Europe, Japan and the United States. In 1963, Haubold et al. recommended such a mixture as a therapy; in 1975, Turkel published a series of nearly 50 different substances; in 1981, Harrell et al. recommended a high dosage vitamin and mineral preparation for every child.
Because of the claims of Haubold et al., Turkel and Harrell et al. and because physicians understood so little about metabolism in Down syndrome and hoped that children with Down syndrome perhaps could be helped, an enormous amount of time and energy was spent at university research centers checking these claims. Studies were undertaken, using placebo, double-blind and other scientific techniques comparing children receiving these therapies to untreated controls, by White and Kaplitz (1964), Bumbalo et al (1964), Bremer (1975), Hitzig (1975), Coburn et al. (1983), Ellman et al. (1984), Smith et al. (1984), Menolascino et al. (1989) and Bidder et al. (1989). The controlled studies were uniformly negative finding no difference between the treated and untreated children, except for the complex Bidder study which documented an actual decrease in developmental progress and various side-effects of the multivitamins and minerals. No study that adhered to even minimal scientific methods documented any definite improvement or even suggestive trends in intelligence, speech or language, neuromotor function, height or health. Preuss et al. reviewed the literature in 1989 and flatly stated that indiscriminate multivitamin therapy was not useful in Down syndrome.
An understanding of the basic cause of Down syndrome in a child, too much chromosomal material, leads to a far more cautious approach and a concern for the fate of children subjected to indiscriminate megadoses of vitamins. Biochemicals, including enzymes, measured in Down syndrome usually are elevated (Sinet et al., 1976; Tokuda et al., 1997). These elevations are probably because of direct or indirect effects of the triple gene dose from genes on the 21st chromosome (Tan et al., 1973) making the level of these proteins too high rather than too low.
The function of most water-soluble vitamins are to act as co-enzymes in metabolic pathways in the body. These co-enzymes have the job of speeding up an enzyme, making it work faster. In the case of a child with too high level of an enzyme, feeding the child extra co-enzymes (water-soluble vitamins) would make the already elevated enzyme even higher, that is, even farther out of the normal range. This, of course, is in direct contradiction to the general principle of medical therapy which is to normalize functional levels of anything abnormal in the body.
Moving beyond the approach of giving a shotgun of all vitamins, is there any evidence that any single one vitamin might be needed in a child with Down syndrome?
In my own clinic, I found one child with Down syndrome who was vitamin B1 deficient; I never found a second one. Regarding vitamin B6, investigators were particularly interested in this vitamin because oral pharmacological doses of vitamin B6 elevates Serotonin, a neurotransmitter, was one of those very few substances found below the normal range in the blood of children with Down syndrome. However, the two studies scientifically performed using this vitamin showed no improvement at all in the young children with Down syndrome receiving it (Pueschel et al., 1985; Coleman et al., 1985). In addition, side-effects were reported (Coleman et al., 1985). Regarding vitamin B12, a study of one patient with Down syndrome and a specific malabsorption of vitamin B12 has been published (Cartlidge & Curnock, 1986). However, in most children studied, levels of vitamin B12 are normal (Ibarra et al., 1990). Folic acid, another water-soluble vitamin, has been indicated to counteract the drug toxicity of methotrexate, an antifolate agent, in children with Down syndrome who are being treated for leukemia (Peters et al., 1995).
There are four known fat-soluble vitamins, vitamins A, D, E, and K. Vitamin A is of particular interest in Down syndrome because there have been studies from as long ago as 1955 suggesting a deficiency of vitamin A may exist in both institutionalized and home-reared patients (Hirsch & Fisher, 1955; Palmer, 1978; Martin et al., 1981). There also have been good studies showing no evidence of deficiency (Barden, 1977; Pueschel et al, 1990; Storm, 1990; Erics et al., 1996). However, because doctors running a Down syndrome clinic occasionally find depressed levels of vitamin A deficiency in individual patients, a test for serum vitamin A is part of the preventive medicine checklist (Rogers & Coleman, 1992; also see the Down Syndrome Medical Interest Group (DSMIG) in Down Syndrome Quarterly for updates). In the Bidder et al. (1989) study, the study that documented a decrease in developmental progress on multivitamins and multiminerals, there was one positive finding of parental reports of better appearance and skin freshness. This raises the question of whether, mixed in among all of the other vitamins with their negative effects, there happened to be some children who were vitamin A deficient and benefitted from the vitamin A in their multivitamin preparation. Vitamin E has been measured in the brains of fetuses with Down syndrome and no evidence of deficiency was found (Metcalfe, 1989). The level of other fat-soluble vitamins in Down syndrome awaits scientific study.
Zinc is of interest to researchers in Down syndrome because it has been reported to be decreased in the serum (Bjorksten et al., 1980; Anneren & Gebre-Medhin, 1987; Kanavin et al., 1988; Lockitch et al., 1987) plasma (Stablile et al., 1991) and whole blood (Colombo et al., 1989). There also is a study which failed to confirm this decrease (Nobel & Warren, 1988). Zinc is related both to pathways involving vitamin A and the immunological system. Most other studies of mineral levels in individuals with Down syndrome are based on hair studies, unfortunately an often inaccurate procedure.
In a syndrome such as Down syndrome, where so many enzyme levels are known to be elevated, the shotgun approach of giving young children extraordinary levels of vitamins should be approached with caution. Instead, these children need to have annual evaluations of the preventive medical type (Rogers & Coleman, 1992). It is important to remember that each of these children is a separate individual; each child has a unique set of genes besides the effects o the extra genes on the 21st chromosome and they need individualized medical evaluations.
Careful examination of any child can indicate evidence of vitamin or mineral deficiencies; such deficiencies have clinical symptoms to alert the examining physician. In addition, there are routine checks, the preventive medical checklist, that are made periodically in any child with Down syndrome. When deficiencies are found in a child, such as thyroid, vitamin A or zinc, then, and only then, would supplements be indicated for that child.
There is a great deal we do not know about Down syndrome in spite of many advances in recent decades. Everyone who cares about the special needs of these children welcomes advances in the field if they are based on solid evidence. Indeed, there may be malabsorption of vitamins or minerals in some children; there may be co-enzyme methods of curbing the elevations of so many biochemical products measured in these children. There may be a way to protect these children by altering their immune systems in a positive way. We look forward to future scientific research.
Until then, we must be careful not to interfere with the metabolism of children with Down syndrome until we understand what we are doing. Properly handled from birth with knowledgeable educational and medical care, the overwhelming majority of children with Down syndrome now have great potential for a good life and it is important not to experiment on them for the sake of an elusive, miracle cure.
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Comment on Editorial: Vitamins and Down Syndrome
In her "Editorial: Vitamins and Down Syndrome" (DSQ, 2: 11-13, 1997), Dr. Mary Coleman discusses some studies on vitamin A and E in Down syndrome, and concludes that the level of other fat-soluble vitamins in Down syndrome awaits scientific study. She omits the paper Del Arco et al. entitled "Vitamin D status in children with Down syndrome" (J. Intellect Disab Res, 1993; 36: 251-257). The authors studied the serum levels of the active D metabolites 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D in 21 children with Down syndrome in Cantabria, a northern region of Spain located at 44 degrees north latitude. Serum calcium, magnesium, phosphate, alkaline phosphatase, parathormone and osteocalcin were also determined. The average levels of Vitamin D metabolites were comparable to those of an age-matched group in both winter and summer times and no child with Down syndrome showed values below the normal range.
Correspondence: Professor Jesus Florez,
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Editorial: Vitamins and Down Syndrome is published in Down Syndrome Quarterly (Volume 2, Number 2, June 1997) and is reprinted, duplicated, and/or transmitted with permission of the Editor. Information concerning publication policy or subscriptions may be obtained by contacting Dr. Samuel J. Thios, Editor, Denison University, Granville, OH 43023 (email: firstname.lastname@example.org). Editorial: Vitamins and Down Syndrome as well as other information regarding Down Syndrome Quarterly may be accessed through the home page of Down Syndrome Quarterly at "http://denison.edu/dsq."