Beneficial Effects of Nutraceutical Cofactor Therapy in Patients with Mitochondrial Disorders

Abstract

Mitochondrial diseases are a group of heterogenous disorders that share common cellular consequences resulting from mitochondrial dysfunction: (i) decreased ATP production; (ii) increased reliance on alternative anaerobic energy sources; and (iii) increased production of reactive oxygen species. Objective: We evaluated the effect of a combination (COMB) therapy comprising creatine monohydrate, coenzyme Q1 and lipoic acid to target the above mentioned consequences using a randomized, double-blind, placebo-controlled, crossover study design in patients with mitochondrial cytopathies. Results: Compared with placebo, the COMB therapy resulted in lower resting plasma lactate concentrations, lower urinary 8-isoprostane excretion and attenuated the decline of peak dorsiflexion strength in all patient groups. Improved body composition was only observed in patients in the MELAS group. Interpretation: These results suggest that combination therapies targeting multiple final common pathways of mitochondrial dysfunction favorably influence surrogate markers of cellular energy dysfunction. Future therapies should be designed to target specific mitochondrial diseases to provide the greatest therapeutic benefits for those patients. In addition, future studies employing larger sample sizes in homogeneous groups of patients will be required to determine whether such combination therapies will influence function and quality of life.