Effect of a Combination of Carnitine, Coenzyme Q10 and Alpha-Lipoic Acid (MitoCocktail) on Mitochondrial Function and Neurobehavioral Performance in Children with Autism Spectrum Disorder

Background: Emerging research has suggested that mitochondrial (mt) dysfunction, causing secondary bioenergetic deficit and increase in oxidative stress, may play a role in the etiology of some patients with autism spectrum disorder (ASD) (Legido A et al. Semin Pediatr Neurol 2013;20:163).

Objectives: The hypothesis of this FDA-IRB approved open-label pilot trial was that patients with ASD and indications of mt dysfunction would improve clinically and/or biochemically following treatment with a combination of carnitine, coenzyme Q10 and alpha-lipoic acid (MitoCocktail).

Methods: To be eligible, participants had to fulfill DSM V diagnostic criteria for ASD and have abnormal buccal swab mt RCC (respiratory chain complexes) I and IV test results. RCC I and IV were measured through immunocapture and spectrophotometric procedures with values normalized to citrate synthase activity. A total of 11 patients (10M, 1F), aged 5-12 years completed the protocol. They received MitoCocktail daily for a 3-month period. Behavioral outcome data was collected from the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the Autism Spectrum Rating Scale (ASRS) and the Aberrant Behavior Checklist (ABC), administered at baseline (Time 1), three months into treatment (Time 2), and three months after treatment was discontinued (Time 3). Three separate scores (subscales and total) from the ADOS-2, three from the ASRS (subscales and total), and five (subscales) from the ABC were contrasted at Time 1 vs. Time 2. Those showing significant change were then examined for return toward baseline at Time 2 vs. Time 3. RCC I and IV levels were also compared across these time points. Paired t-tests were used to evaluate differences.

Results: Mean buccal complex I/IV activity ratio was significantly (p<0.02) reduced during MitoCocktail treatment compared to baseline. All subjects showed at least one specific sign of metabolic improvement, which waned 3 months post-treatment in 7 of the 11 participants. Of the 11 total or subscale scores considered, all showed change in means from Time 1 to Time 2. Statistically significant changes were observed for the Unusual Behavior subscale from the ASRS (p<0.006), the Lethargy subscale from the ABC (p <0.01), and the Inappropriate Speech subscale from the ABC (p<0.02). From Time 2 to Time 3, scores worsened on each of these three subscales with statistically significant changes on Lethargy (p<0.01) and Inappropriate Speech subscales (p<0.007).

Conclusions: The findings of this small pilot study provide preliminary support for the hypothesis that the use of MitoCocktail has a therapeutic benefit, improving maladaptive behavior and speech that correlate with changes in mt function. Larger placebo-controlled trials are needed to demonstrate efficacy.