ascorbic-acid and Down-Syndrome

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.

Topics: alpha-Tocopherol; Alzheimer Disease; Antioxidants; Ascorbic Acid; Down Syndrome; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Pilot Projects; Thioctic Acid; Treatment Outcome

The aim of this study was to investigate enzymatic and non-enzymatic antioxidant systems and levels of biomarker levels of oxidative damage in the saliva of patients with Down's syndrome (DS).. Saliva samples were collected from 30 patients with DS and control group (age: 14-24 years). Subsequently, the concentrations of superoxide dismutase, concentration of malondialdehyde, carbonylated proteins, uric acid, vitamin C and total protein, peroxidase activity and total antioxidant capacity were analyzed.. Patients with DS presented significantly higher concentrations of superoxide dismutase, higher levels of malondialdehyde and salivary total protein content than controls (p<0.05). Conversely, no difference in carbonylated proteins or antioxidants (uric acid, vitamin C, peroxidase, and total antioxidant capacity) was observed between DS patients and controls (p>0.05).. Patients with DS are more vulnerable to oxidative stress in saliva as indicated by the significant increase in malondialdehyde and superoxide dismutase concentrations found in this study.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; Case-Control Studies; Down Syndrome; Female; Humans; Male; Malondialdehyde; Oxidative Stress; Protein Carbonylation; Saliva; Salivary Proteins and Peptides; Superoxide Dismutase; Uric Acid; Young Adult

We previously demonstrated that systemic oxidative stress is present in Down syndrome (DS) patients. In the present study we investigated the antioxidant status in the peripheral blood of DS children and teenagers comparing such status before and after an antioxidant supplementation. Oxidative stress biomarkers were evaluated in the blood of DS patients (n=21) before and after a daily antioxidant intervention (vitamin E 400mg, C 500 mg) during 6 months. Healthy children (n=18) without DS were recruited as control group. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), gamma-glutamyltransferase (GGT), glucose-6-phosphate dehydrogenase (G6PD) and myeloperoxidase (MPO), as well as the contents of reduced glutathione (GSH), uric acid, vitamin E, thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC) were measured. Before the antioxidant therapy, DS patients presented decreased GST activity and GSH depletion; elevated SOD, CAT, GR, GGT and MPO activities; increased uric acid levels; while GPx and G6PD activities as well as vitamin E and TBARS levels were unaltered. After the antioxidant supplementation, SOD, CAT, GPx, GR, GGT and MPO activities were downregulated, while TBARS contents were strongly decreased in DS. Also, the antioxidant therapy did not change G6PD and GST activities as well as uric acid and PC levels, while it significantly increased GSH and vitamin E levels in DS patients. Our results clearly demonstrate that the antioxidant intervention with vitamins E and C attenuated the systemic oxidative damage present in DS patients.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; Case-Control Studies; Catalase; Child; Child, Preschool; Dietary Supplements; Down Syndrome; Female; gamma-Glutamyltransferase; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Humans; Male; Oxidative Stress; Peroxidase; Protein Carbonylation; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uric Acid; Vitamin E

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Autistic Disorder; Child; Down Syndrome; Humans; Male; Purpura; Scurvy

To assess homocysteine, folic acid and vitamin B12, trace element levels and oxidant/antioxidant status in Down syndrome (DS) mothers and children.. 42 mothers with previous history of bearing DS baby with karyotypically confirmed full trisomy 21 were included. 48 healthy mothers with their healthy children were considered as control. Serum B12, folic acid, total homocysteine (tHcy), vitamins E and C, TBARS and trace elements were estimated.. DS mothers showed higher levels of tHCy, lower levels of folic acid and vitamin B12 than controls. tHCy and folic acid concentrations were significantly decreased, while vitamin B12 exhibited a slight decrease in DS children versus control. Vitamins E and C, zinc and copper levels were markedly reduced in DS mothers. By contrast, TBARS showed significant elevation in them. Furthermore, DS children had severe reduction of vitamin C and zinc levels relative to healthy children. However, vitamin E showed slight reduction and TBARS displayed a slight rise in DS children.. Abnormal folic acid-homocysteine metabolism is a potent marker to identify women at risk for having DS child and it also exposes them to oxidant/antioxidant imbalance.

Topics: Adult; Ascorbic Acid; Child; Child, Preschool; Copper; Down Syndrome; Female; Folic Acid; Homocysteine; Humans; Male; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Tocopherols; Zinc

We report three cases of scurvy, with differing musculoskeletal presentations, from a tertiary teaching hospital in Sydney, Australia. Case 1 was a man with cerebral palsy who presented with knee swelling following a minor injury. In Case 2, a patient with thalassaemia major presented with purpuric rash, difficulty walking and distal thigh swelling and ecchymosis. Case 3 was a man with Down's syndrome who presented with acute ankle arthritis. Scurvy in Cases 1 and 3 were related to abnormal dietary preferences, whereas in Case 2, scurvy was thought to be related to thalassaemia. All three cases responded rapidly to vitamin C replacement. The subjects did not appear malnourished as they had adequate carbohydrate and protein intake.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Cerebral Palsy; Down Syndrome; Feeding Behavior; Hospitals, Teaching; Humans; Male; Scurvy; Treatment Outcome

Patients with Down's syndrome show an increased pulmonary vascular reactivity that could be due to an impaired vascular endothelial function, which is possibly related to increased oxidative stress. In 8 patients with Down's syndrome and 9 euploid patients of similar age, endothelium-dependent and -independent vasodilation was studied, measuring brachial flow velocity with an intravascular Doppler flow wire. Patients with Down's syndrome showed a significant impairment of endothelial function versus controls. In presence of the antioxidant vitamin C, endothelium-dependent vasodilation in the patients with Down's syndrome was only slightly, but not significantly, improved.

Topics: Acetylcholine; Analysis of Variance; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; Case-Control Studies; Child; Child, Preschool; Down Syndrome; Endothelial Cells; Endothelium, Vascular; Female; Humans; Male; Nitroglycerin; Oxidative Stress; Probability; Reference Values; Risk Assessment; Ultrasonography, Doppler, Pulsed; Vasodilation

The present study revealed ascorbic acid deficiency in the blood of many children with Down's syndrome. It also revealed a fairly definite connection between Vitamin C deficiency and diet in these patients and a similar link between ascorbic acid deficiency and this incidence of infections. Where necessary the prescription of Vitamin C for the prevention and treatment of recurring infection is therefore recommended, bearing in mind the valuable antioxidant properties of ascorbic acid that can be exploited in combating cell deterioration.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Diet; Down Syndrome; Female; Humans; Infant; Male

Previous studies have suggested that free radicals and related species play a role in lens damage. The molecules involved may include proteins, lipids and DNA. Focal cortical changes and cortical liquefaction have been reported in patients with Down's syndrome over the age of 15 years. There is evidence supporting the hypothesis that trisomy 21 patients have an increase in free radical reactions and lipoperoxidation susceptibility. This could be due to an increase in the H2O2 generation catalysed by CuZn SOD although the activity of other gene products coded for on chromosome 21 cannot be excluded. Thiobarbituric acid reactive products were measured in human erythrocytes of nine DS patients and nine age-matched controls. There was a significant increase in the first group (21.0 +/- 2.3 nmol MDA/g Hb vs 16.4 +/- 2.9 nmol MDA/g Hb; p less than or equal to 0.01). In plasma, however, TBA products and antioxidant levels (ascorbic acid, tocopherol and uric acid) were not significantly different. Further studies should be carried out, namely through the use of more specific and sensitive methods, to assess the possible association between oxidative stress and cortical lens damage in DS patients.

Topics: Adolescent; Adult; Ascorbic Acid; Cataract; Child; Child, Preschool; Down Syndrome; Erythrocytes; Free Radicals; Humans; Infant; Lipid Peroxidation; Oxygen; Superoxide Dismutase; Thiobarbiturates; Uric Acid; Vitamin E

Topics: Adult; Ascorbic Acid; Down Syndrome; Female; Humans; Middle Aged; Nicotinic Acids; Skin Diseases; Thiamine; Vitamin A; Vitamin E; Vitamins; Zinc