Evidence that l-Carnitine and Selenium Supplementation Reduces Oxidative Stress in Phenylketonuric Patients

Abstract

It is well established that the involvement of reactive species in the pathophysiology of several neurological diseases, including phenylketonuria (PKU), a metabolic genetic disorder biochemically characterized by elevated levels of phenylalanine (Phe). In previous studies, we verified that PKU patients (treated with a protein-restricted diet supplemented with a special formula not containing L-carnitine and selenium) presented high lipid and protein oxidative damage as well as a reduction of antioxidants when compared to the healthy individuals. Our goal in the present study was to evaluate the effect of Phe-restricted diet supplemented with L-carnitine and selenium, two well-known antioxidant compounds, on oxidative damage in PKU patients. We investigated various oxidative stress parameters in blood of 18 treated PKU patients before and after 6 months of supplementation with a special formula containing L-carnitine and selenium. It was verified that treatment with L-carnitine and selenium was capable of reverting the lipid peroxidation, measured by thiobarbituric acid-reactive species, and the protein oxidative damage, measured by sulfhydryl oxidation, to the levels of controls. Additionally, the reduced activity of glutathione peroxidase was normalized by the antioxidant supplementation. It was also verified a significant inverse correlation between lipid peroxidation and L-carnitine blood levels as well as a significant positive correlation between glutathione peroxidase activity and blood selenium concentration. In conclusion, our results suggest that supplementation of L-carnitine and selenium is important for PKU patients since it could help to correct the oxidative stress process which possibly contributes, at least in part, to the neurological symptoms found in phenylketonuric patients.

Increased oxidative stress in patients with 3-hydroxy-3-methylglutaric aciduria

“…The reported mechanisms for the L-carnitine antiperoxidative role include inhibition of xanthine oxidase activity, scavenger action of free radicals, and chelation of the iron required for the generation of hydroxyl radicals [45,46] or by facilitating the fatty acids transport, thereby lowering the availability of lipids for peroxidation [47]. Reinforcing the hypothesis that L-carnitine could prevent lipid peroxidation in HMGA, this same protective effect was observed in other inborn errors of metabolism, such as in phenylketonuria [48], in maple syrup urine disease [24,31], and in disorders of propionate metabolism [28,33].…”

Evaluation of Plasma Trace Element and Mineral Status in Children and Adolescents with Phenylketonuria Using Data from Inductively-Coupled-Plasma Atomic Emission and Mass Spectrometric Analysis

“…Previous studies have reported Se and Zn deficiencies in children and adolescents with PKU [15] but also normal plasma Se and Zn levels [21]. Reduced antioxidant capacity was described in subjects with PKU, and Se supplements were considered in the light of oxidative stress parameters [22]. Moreover, omega-3 docosahexaenoic acid (DHA) can play a role in alleviating oxidative stress and DHA supplementation has been shown to have health benefits in children with PKU [23].…”

Oxidative Stress Parameters in Urine from Patients with Disorders of Propionate Metabolism: a Beneficial Effect of l-Carnitine Supplementation

“…Our results in this study are also in agreement with the data reported by Mc Guire et al (2009), showing a marked reduction of urinary AOx in patients with PA. Interestingly, we found that patients under therapy also presented deficiency of their urinary AOx. It is presumed that these alterations can occur because of the treatment with restricted diets (such as in phenylketonuric patients) which are poor in micronutrients necessary for the antioxidant status or, alternatively, by an unusual increase in metabolic by-products which will directly or indirectly deplete the cell's antioxidant capacity (Moyano et al 1997;Wajner et al 2004;Sitta et al 2011;Ribas et al 2011).…”