Biomarkers of oxidative stress and mitochondrial activity as predictors of response to a metabolic support therapy in Autism Spectrum Disorder: a randomized, placebo-controlled, cross-over trial of coenzyme Q10, vitamin E and polyvitamin B

Mitochodrial dysfunction, enhanced oxidative stress, and neuroinflammation have been consistently described in Autism Spectrum Disorder (ASD) by us and by other groups, since 2008. These abnormalities do not generally cause ASD, but seemingly represent consequences of primary anomalies affecting the neural, metabolic and immunological domains. They do, however, confer an additional dysfunctional burden which, if treated, may produce sizable improvement also at the behavioral level. In our retrospective study [Cucinotta et al., Front Psychiatry. 2022; 13: 829516], 45/59 (76.3%) autistic individuals treated with coenzyme Q10 (CoQ10), vitamin E and polyvitamin B displayed significant clinical improvement and excellent tolerability for up to two years of continued therapy. We then published the first exploratory randomized, placebo-controlled, cross-over trial (RCT) involving 31 patients with Phelan-McDermid syndrome, one of the best known syndromic forms of autism [Persico et al. Rare Dis Orphan Drugs J 2023;2:13]. This study provided statistical evidence of efficacy for CoQ10 and of an additional synergistic contribution by Vit.E+Vit.B, together with valuable methodological indications. Thanks to these two recent studies, we can now propose a conclusive RCT with a highly targeted experimental design: [CoQ10+VitE+VitB] vs [inactive placebo], each administered for 3 months in cross-over to 30 children and adolescents with ASD aged 3-17 years, with a one week wash-out period in between; CGI-I is the primary measure of efficacy; VAS, VABS, and WHOQOL are secondary measures; biomaterials (blood and urines) will be collected at 0-3-6 months (T0-T1-T2) to measure biomarkers of oxidative stress (8-oxo-dG, and advanced glycation end-products), the activity of mitochondrial complexes, proinflammatory cytokines (IL-1β, IL-6, IFN-γ, and IL-4), urinary selenium and heavy metals This study will close a 15-year long investigation “from bench to bedside”, hopefully translating basic science into better clinical management and improved quality of life for autistic individuals and their families.