Down Syndrome Abstract
of the Month:
Mar 2008
Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial.
Ellis, JM et al.
BMJ. 2008 Feb 22
Centre for Evidence-based Child Health, Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London
Abstract:
OBJECTIVES: To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down's syndrome. DESIGN: Randomised controlled trial with two by two factorial design. SETTING: Children living in the Midlands, Greater London, and the south west of England. PARTICIPANTS: 156 infants aged under 7 months with trisomy 21. INTERVENTION: Daily oral supplementation with antioxidants (selenium 10 mug, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo. MAIN OUTCOME MEASURES: Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months. RESULTS: Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval -2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, -1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results. CONCLUSIONS: This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down's syndrome.
My comments:
For some background on why this is important, see my page on vitamins here. Over the last several decades, many different supplements have been touted for children with DS, with claims including improving health, reducing infection, improving cognition and even "normalizing" the facial features. To date, the only studies showing positive results have been those studying selenium and zinc, resulting in mild immune and thyroid function.It has been noted for years that children with DS have increased oxidative activity in their cells. The end result of this activity isn't determined, but theories include premature aging and early brain cell death based on studies done on cells outside the body. Many parents have been told that using antioxidants such as vitamin E and selenium may help oxidative damage in the person with DS, including preventing mental retardation and Alzheimer's disease.
Research in the biochemistry of people with DS has shown changes in cellular enzymes that may prevent the cells from using folate correctly, causing a "functional" deficiency of folate, rather than a dietary deficiency. Parents have also been told that the use of folate supplements may also help prevent mental retardation and leukemia.
This study showed no effect with the use of these particular supplements. I don't expect any change in behavior to come from this study, however, as supplement proponents immediately claimed that the mixtures used in the present study didn't match the supplement they used (there are three major supplement mixtures currently promoted for children with DS).
I would be greatly surprised if any more research is done on a collection of nutritional supplements. With all the research to date, there's little evidence that would support spending any more money on such research. However, as we learn more about the function of specific genes on the 21st chromosome, we may see additional research looking at one or two specific nutrients and looking for specific clinical outcomes, similar to the folinic portion of the above study.
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