Biofactors 32(1-4): 161-7 (2008 Jan 1)
Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical aspects
L Tiano, L Padella, P Carnevali, O Gabrielli, F Bruge, F Principi, and GP Littarru
Institute of Biochemistry, Polytechnic University of the Marche, Ancona, Italy
Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with mental retardation and Alzheimer-like dementia, characteristic change of the individual's phenotype and premature ageing. Oxidative stress is known to play a major role in this pathology since a gene dose effect leads to elevated ratio of superoxide dismutase to catalase/glutathione peroxidase compared to controls in all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of DS. Hyperuricemia is another feature of DS that has an interesting relationship with oxidative stress since uric acid represents an important free radical scavenger. However its formation is connected to the conversion of Xanthine dehydrogenase (XDH) to Xanthine oxidase (XO) which leads to concomitant production of free radicals. Here we report that plasma samples from DS patients in pediatric age, despite an increased total antioxidant capacity, largely due to elevated Uric acid content (UA), present significantly elevated markers of oxidative damage such as increased allantoin levels. Moreover DS plasma samples do not differ from healthy control ones in terms of Coenzyme Q10 and susceptibility to peroxidative stimuli. On the contrary, lymphocyte and platelet CoQ10 content was significantly lower in DS patients, a fact that might underlie oxidative imbalance at a cellular level.
Pediatr Neurol 37(6): 398-403 (2007 Dec)
Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21
Miles MV, Patterson BJ, Chalfonte-Evans M, Hickey FJ, Schapiro MB, Steele PE, Tang PH, Hotze SL
Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center and University of Cincinnati Medical Center, Cincinnati, OH 45229-3039, USA
Endogenous coenzyme Q10 is an essential cofactor in the mitochondrial respiratory chain, a potent antioxidant, and a potential biomarker for systemic oxidative status. Evidence of oxidative stress was reported in individuals with trisomy 21. In this study, 14 children with trisomy 21 had significantly increased (P > 0.0001) plasma ubiquinone-10 (the oxidized component of coenzyme Q10) compared with 12 age- and sex-matched healthy children (historical controls). Also, the mean ratio of ubiquinol-10 (the biochemically reduced component):total coenzyme Q10 was significantly decreased (P < 0.0001). After 3 months of ubiquinol-10 supplementation (10 mg/kg/day) to 10 patients with trisomy 21, the mean ubiquinol-10:total coenzyme Q10 ratio increased significantly (P < 0.0001) above baseline values, and 80% of individual ratios were within normal range. No significant or unexpected adverse effects were reported by participants. To our knowledge, this is the first study to indicate that the pro-oxidant state in plasma of children with trisomy 21, as assessed by ubiquinol-10:total coenzyme Q10 ratio, may be normalized with ubiquinol-10 supplementation. Further studies are needed to determine whether correction of this oxidant imbalance improves clinical outcomes of children with trisomy 21.
Pediatr Neurol 35(1): 30-7 (2006 Jul)
Coenzyme Q10 absorption and tolerance in children with Down syndrome: A dose-ranging trial
Miles MV, Patterson BJ, Schapiro MB, Hickey FJ, Chalfonte-Evans M, Horn PS, Hotze SL
Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Ohio 45229, USA
Controlled studies of coenzyme Q(10) dosing and tolerance have been reported in adults, but not in pediatric patients. This study compares low- and high-dose coenzyme Q(10) (LiQ-NOL syrup) absorption and tolerance in children with Down syndrome. After a 1-month low-dose (1.0 mg/kg/day) run-in period, all participants received high-dose coenzyme Q(10) (10.0 mg/kg/day) for two additional months (in randomized sequence as one daily dose or split into two daily doses). Chemistry profiles and complete blood counts were determined just before and at the study completion. Plasma coenzyme Q(10) concentrations were determined initially and at each study visit. Parents reported adverse events and study drug evaluations using standardized forms. Most of the 16 children who completed this study tolerated high-dose coenzyme Q(10) well. Uncooperative behavior resulted in premature withdrawal of two participants, and may have been treatment-related. Pre- and posttreatment laboratory test changes were considered to be clinically nonsignificant. Study results indicate that high-dose coenzyme Q(10) (10 mg/kg/day) is well-absorbed and well-tolerated by most children with Down syndrome, and appears to provide plasma concentrations which are comparable to previous adult studies administering much higher coenzyme Q(10) dosages.