Down syndrome and dementia: A randomized, controlled trial of antioxidant supplementation

Abstract

Individuals with Down syndrome over age 40 years are at risk for developing dementia of the Alzheimer type and have evidence for chronic oxidative stress. There is a paucity of treatment trials for dementia in Down syndrome in comparison to Alzheimer disease in the general (non-Down syndrome) population. This 2-year randomized, double-blind, placebo-controlled trial assessed whether daily oral antioxidant supplementation (900 IU of alpha-tocopherol, 200 mg of ascorbic acid and 600 mg of alpha-lipoic acid) was effective, safe and tolerable for 53 individuals with Down syndrome and dementia. The outcome measures comprised a battery of neuropsychological assessments administered at baseline and every 6 months. Compared to the placebo group, those individuals receiving the antioxidant supplement showed neither an improvement in cognitive functioning nor a stabilization of cognitive decline. Mean plasma levels of alpha-tocopherol increased ~2-fold in the treatment group and were consistently higher than the placebo group over the treatment period. Pill counts indicated good compliance with the regimen. No serious adverse events attributed to the treatment were noted. We conclude that antioxidant supplementation is safe, though ineffective as a treatment for dementia in individuals with Down syndrome and Alzheimer type dementia. Our findings are similar to studies of antioxidant supplementation in Alzheimer disease in the general population. The feasibility of carrying out a clinical trial for dementia in Down syndrome is demonstrated.

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

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Oral Ascorbic Acid and Alpha-Tocopherol to Reduce Behavioural Problems in Young Patients Affected of Fragile X Syndrome: A Randomized, Double-Blind, Placebo-Controlled Phase II Pilot Trial

“…The FDA's recommended daily dose is 10 mg/day, but the tolerable upper intake level is considered 300 mg/day (102). In our trial, we decided to use a maximum dose of 600 mg/day as it was proven in many other previous studies to be safe and give a therapeutic dose (85).…”

Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers

“…However, the use of the ALA is hampered by its instability and its rapid metabolism, suggesting that formulations containing ALA, in a form ensuring its stability and improving its bioavailability, can have important applications as medicines, nutritional supplements or cosmeceuticals [76] . Also, ALA as a mitochondrial cofactor termed 'mitochondrial nutrient' has been tested in a number of clinical trials such as alcohol-related liver disease [77] , diabetes-associated neuropathy [78] , heart disease [79] , HIV-1-related lipoatrophy [80] and mitochondrial diseases disease [81] . Also, there are only two clinical trial papers.…”