Oxidative stress and oral tocotrienol supplementation: a novel approach to the complementary therapy of Friedreich ataxia

In this work, we investigated white blood cell gene expression of SOD-1, SOD-2, catalase, GPX-1, GSR and GSTM-1; plasma content of GSH and GSSG; plasma Oxygen Radical Absorbance Capacity; amount of plasma carbonylated proteins; urinary levels of Hexanoyl-Lysine adduct; lipid composition of erythrocyte membranes. Oxidative stress is always associated with Friedreich’s Ataxia (FRDA) also accompained by impaired mitochondrial functions. Patients are currently treated with idebenone, a CoQ10 analogue, believed effective in view of its ability to counteract free radical damages. Vit. E is known to be effective on oxidative stress related pathologies, taking into account our esperience in the field of the class of natural vitamin E “tocotrienol” we have started the present investigation in order to develop a model useful to investigate the efficacy of a tocotrienol based approaches on oxidative stress damage protection. A mixture (OXI-3 internal reference name) of enantiomerically pure tocotrienols (alpha, beta, gamma and delta) has been selected and tested in patients monitoring the above reported different biochemical parameters. The pilot investigation was conducted on five young FRDA patients who assumed OXI-3 (equivalent to 5 mg/kg/day), for two months. The wide array of different markers consistently pointed to the presence of oxidative stress in FRDA patients, despite the fact that the idebenone therapy had not been discontinued. However, even a two month low-dose tocotrienol supplementation led to the decrease of oxidative stress indexes and to parameter values that approached those of healthy controls. Moreover, there are evidences that a longer tocotrienol treatment may be more effective in reducing oxidative stress.