Jan 8, 2002
Minerals, Vitamins and
Down Syndrome
by Len Leshin, MD, FAAP
Zinc
(Note: in all these articles, the dosage of zinc was 1 mg per kg of body weight per day, up to a maximum of 50 mg per day. The Recommended Daily Allowance for infants is 5 mg per day; for children 10 mg per day, and for adults 15 mg per day. The effects of high doses of zinc for long periods of time are not known.)
pro:Licastro, F et al. Neuroendocrine immune modulation induced by zinc in a progeroid disease -- Down syndrome. Ann NY Acad Sci 1994;299-306. 51 children with DS were given zinc. Researchers state thyroid function tests became normal and white blood cell function improved.
Stabile A et al. Immunodeficiency and plasma zinc levels in children with Down syndrome: A long-term follow-up of oral zinc supplementation. Clin Immuno Immunopath 58:207-216, 1991. Children with DS and low blood zinc levels showed improved lymphocyte function after zinc therapy. Children with DS who had normal zinc levels at the start of the study had no such response.
Licastro, F et al. Zinc affects the metabolism of thyroid hormones in children with Down syndrome. Intern J Neurosci 65:259-268, 1992. 25 children with DS were given zinc; after 4 months, improved thyroid function tests and increased thymulin were noted.
Chiricolo, M et al. Enhanced DNA repair in lymphocytes of Down syndrome patients: the influence of zinc supplementation. Mutation Res 295:105-111, 1993. 15 children were given zinc; after 4 months, improved DNA repair in response to radiation damage was noted.
Napolitano, G et al. Growth delay in Down syndrome and Zinc sulphate supplementation. Am J Med Genet Suppl 7:63-65, 1990. 22 children with DS were given zinc; 15 of those reached a higher centile on the growth chart.
Napolitano, G et al. Is Zinc deficiency a cause of subclinical hypothyroidism in Down syndrome? Ann Genet 33:9-15, 1990. 17 subjects with DS were given zinc; this improved the T3 hormone and had no effect on the T4 hormone.
Kadrabova J, Sustrova M et al. Changed serum trace element profile in Down's syndrome. Biol Trace Element Res 54:201-206, 1996. 16 subjects with DS ages 4 to 23 years had blood tests done. Serum zinc and selenium were lower than the control subjects, serum copper was higher in the subjects with DS, and magnesium levels were normal.
Trubiani O et al. Programmed cell death of peripheral myeloid precursor cells in Down patients: Effect of zinc therapy. Ultrastruct. Path. 20: 457-462, 1996. Children with DS have more circulating immature blood cells which do not function well to fight infection. In this study, zinc appeared to induce the death of these immature cells, causing the body to release more mature white blood cells.
Antonucci A et al. Detection of apoptosis in peripheral blood cells of 31 subjects affected by Down syndrome before and after zinc therapy. Ultrastruct. Path. 21:449-452, 1997. Zinc supplementation suppressed the enzyme gamma-endonuclease, leading to improved survival of white blood cells.
Bucci I, Napolitano G et al. Zinc sulfate supplementation improves thyroid function in hypozincemic Down children. Biol Trace Element Res 67:257-268, 1999. In children with DS and low blood zinc levels, zinc supplementation corrected abnormally high TSH blood levels.
anti:
Lockitch, G et al. Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc. J Peds 114(5):781-787, 1989. 64 children with DS between 1 and 19 years were given zinc in a double-blinded, controlled study for 1 year. No effect noted on serum immunoglobulins or complement, or on lymphocyte function. A trend toward fewer sick days was noted.
Brigino, EN et al. Normalization of cellular zinc levels in patients with Down's syndrome does not always correct low thymulin levels. Acta Paediatr 85:1370-1372, 1996. 5 children with DS were given zinc. The thymulin (a protein produced by the thymus to stimulate the function of certain lymphocytes) levels were low in 4 of 5 children and remained low despite normalized zinc levels.
Sustrova M, Strbak, V. Thyroid function and plasma immunoglobulins in subjects with Down's syndrome during ontogenesis and zinc therapy. J Endocrinol Invest 17:385-390, 1994. 110 subjects with DS were studied. Zinc therapy did not improve thryoid blood tests.
Zatta P. Letter to the editor, Biol Trace Element Res 73:93-94, 2000. In response to Bucci's 1999 study (above), warns about supplementing zinc due to the concern that zinc may be an etiological cofactor in the development of Alzheimer's disease. [Bucci et al replied to this concern in another Letter to the editor, Biol Trace Element Res 82:273-275, 2001, stating that the evidence regarding the role of zinc is very conflicting, and there is enough evidence for the benefits of supplementation of zinc in people with DS to encourage its use pending more evidence to the contrary.]
Selenium
(Note: selenium is a "cofactor" in the enzyme glutathione peroxidase, which helps turn hydrogen peroxide in cells into oxygen and water. The dose of selenium used by the majority of the studies below is 10 micrograms (mcg) per kilogram of body weight per day. The U.S. Recommended Daily Allowance for selenium for infants is 10 mcg per day, for children 20 mcg per day, for teens 40 to 50 mcg per day, adult males 70 mcg per day, and adult females 55 mcg per day. The effects of high doses of selenium for long periods of time aren't known.)
Anneren G et al. Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome. Acta Paediatr Scand 78:879-884, 1989. Besides the results noted in the title of this article, the authors also noted the parents of the children receiving selenium stated the children had fewer infections while taking the selenium.
Anneren G et al. Increase in serum concentrations of IgG2 and IgG4 by selenium supplementation in children with Down syndrome. Arch Dis Child, 65:1353-1355, 1990. Dr Anneran et al did this study to follow up the surprise findings in the above study; showing selenium may have an immunoregulatory function also.
Antila E et al. Selenium therapy in Down syndrome: a theory and clinical trial. Antioxidants in Therapy and Prev Med, ed. I. Emerit et al, 183-186, Plenum Press, 1990. Selenium supplementation increased red blood cell glutathione peroxidase activity.
Kanavin OJ et al. Thyroid hypofunction in Down's syndrome. Biol Trace Elem Res 78(1-3):35-42, 2000. Thirty-eight institutionalized adults with DS studied, and had lower levels of serum selenium and free thyroxin (T4), and higher Thyroid Stimulating Hormone levels. A positive correlation was found between the low selenium levels and free T4. The authors speculate that supplemental selenium may help thyroid function.
Vitamins
(My personal editorial comments are in parentheses.)
Abalan F et al. A study of digestive absorption in four cases of Down syndrome. Med Hypothesis 31:35-38, 1990. (Presence of undigested meat fibers in stools of 4 adults with DS; authors presume chronic malnutrition from this result.)
Ani C et al. Nutritional supplementation in Down syndrome: theoretical considerations and current status. Dev Med Child Neuro 42:207-213, 2000. (A short, good review of the research to date, concluding there is no good evidence yet for the use of supplements. The authors call for a well designed study on the use of antioxidants in DS to settle the question once and for all.)
Bennett, FC et al. Vitamin and mineral supplementation in Down's syndrome. Pediatrics 72(5):707-13, 1983. (Tried to duplicate Harrell's study, but concluded no differences between placebo and supplements.)
Bidder RT et al. The effects of Multivitamins and Minerals on children with Down syndrome. Dev Med Child Neuro 31:532-537, 1989. (Another attempt to duplicate Harrell's findings, and ends up arguing against using supplements.)
Blackston RD et al. Controlled studies comparing early intervention programs versus supplemental nutritional therapies in children with Down syndrome. Amer J Hum Genet 61(Supp):34, 1997 (abstract). (24 children with DS ages 6 to 17 were given GTC -- Dr. Harrell's formula -- for four months. In comparison with 23 children taking placebos, there was no difference in IQ, visual-motor integration, changes in height or weight, or changes in behavior.)
Cantor DS et al. A report on phosphatidylcholine therapy in a Down syndrome child. Psychol Rep 58(1):207-17, 1986. (Reports the trial of one child with DS on phophatidylcholine. This child did have some improvement of language skills. This study has not been replicated to date.)
Cartlidge PHT and Curnock DA. Specific malabsorption of vitamin B12 in Down's syndrome. Arch Dis Child 61(5):514-15, 1986. (This is a case study of one child with a malabsorption disease who happens to have DS.)
Coleman M et al. A double blind study of vitamin B6 in Down's syndrome infants. J Ment Defic Res 29:233-40, 1985. A study of evoked potentials (EEG patterns in response to stimulation) and cognitive function in children with DS given B6. (There was improvement in evoked potentials but had no clinical effect on cognition.)
Colombo ML, et al. Ascorbic acid in children with Down's syndrome. Minerva Pediatr 41(4):189-92, 1989. Ascorbic acid (vitamin C) deficiency found in the blood of children with DS, showing a definite link between diet and deficiency, and a link between vitamin C deficiency and incidence of infections. (A study by S. Pueschel in 1987 showed normal levels of vitamin C in children with DS.)
Del Arco C., et al. Vitamin D status in children with Down's syndrome. J Intel Disab Res 36:251-257, 1992. 21 children with DS in Spain were shown to have normal levels of active vitamin D metabolites, calcium, magnesium, phosphate, and parathormone levels. (Normal sun exposure is enough to provide needed levels of vitamin D.)
Harrell, RF et al. Can nutritional supplements help mentally retarded children? An exploratory study. Proc Natl Acad Sci 78 (1):574-578, 1981. (This study looked at 16 retarded children, 4 of whom had DS; the American Academy of Pediatrics is on record criticising this study, stating "scant and unconvincing experimental evidence." --AAP policy statement, Aug, 1981.)
Kleijnen J, Knipschild, P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Biol Psych 29:931-941, 1991. (review of 53 experimental trials, 10 of which used children with Down syndrome; no effects on those children in any of the reviewed studies.)
Menolascino FJ, et al. Vitamin supplements and purported learning enhancement in mentally retarded children. J Nutr Sci Vitaminol 35(3): 181-92, 1989. (An attempt to duplicate Harrell's study with children with DS and other causes for mental retardation, and found no differences between treated and untreated children.)
Metcalfe T et al. Vitamin E concentrations in human brain of patients with Alzheimer's Disease, Fetuses with Down's Syndrome, Centenarians, and controls. Neurochem Research, 14(12):1209-1212, 1989. (No differences in vitamin E concentrations in the brain between fetuses with DS and controls, and patients with AD and controls. The patients with AD did not have DS as well. Argues that the increased in-vitro lipid peroxidation seen in fetal DS brain tissue is not due to a lack of vitamin E, nor does the oxidation cause a depletion of vitamin E.)
Palmer S Influence of vitamin A nutrition on the immune response: findings in children with Down's syndrome. Int J Vitam Nutr Res 48(2):188-216, 1978. Concluded that vitamin A deficiency was common in children with DS and caused increased susceptibility to infection. (See Storm's article, listed below.)
Pincheira J et al. Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Down's syndrome. Clin Genet 55(3):192-7, 1999. Vitamin E given in vitro to white blood cells from patients with DS. The treated cells had less DNA damage suffered from caffeine than did the untreated cells. (Implies that vitamin E's antioxidant effects keep the white blood cells from harm.)
Pruess JB et al. Vitamin therapy and children with Down syndrome: a review of research. Exceptional Children 55(4): 336-341, 1989. (Intensive review of many articles advocating vitamin therapy. From the study: "In conclusion, the results of the studies undertaken in response to Harrell et al. clearly indicate that vitamin therapy is not useful for young children with DS, and therefore, do not support the idea that increases in micronutrients contribute to improved mental functioning.")
Pueschel SM et al. 5-hydroxytryptophan and pyridoxine: their effects in young children with Down's syndrome. Am J Dis Child 134(9):838-44, 1980. (No differences noted in motor, mental or social development.)
Pueschel SM et al. Vitamin A gastrointestinal absorption in persons with Down syndrome. J Mental Defic Res 34: 269-275, 1990. (Shows no abnormal vitamin A absorption in DS.)
>Smith GF et al. Use of megadoses of vitamins with minerals in Down syndrome. J Pediatr 105(2): 228-34. (Another study showing Harrell's supplement to be ineffective.)
Storm W. Hypercarotenaemia in children with Down syndrome. J Mental Defic Res 34:283-286, 1990. (44 fasting children with DS studied, none with vit. A deficiency, some with hypercarotenemia.)
Weathers C. Effects of nutritional supplementation on IQ and certain other variables associated with Down syndrome. Am J Ment Defic 88(2): 214-7, 1983. (Not only did this study refute Harrell's study, but at the end of the study, the group of children getting the placebo had a higher mean IQ than the treatment group!)
Weise P et al. The use of 5-hydroxytryptophan in the treatment of Down's syndrome. Pediatrics 54(2): 165-8, 1974. (No difference between treated and untreated children.)
Related links:
- The Effects of Vitamin Therapy on the Number of Parent-Reported Illnesses
in a Group of Children with Down Syndrome - Multi-nutrient Formulas and Other Substances as Therapies for Down Syndrome:
An Overview, by Ben Sacks and Frank Buckley - Dr. Mary Coleman's editorial from Down Syndrome Quarterly