Coenzyme Q10 Supplementation in Aging and Disease

Abstract

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ₁₀ deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ₁₀ are detected in tissues and organs providing the hypothesis that CoQ₁₀ supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ₁₀ biosynthesis and primary CoQ₁₀ deficiency syndrome, and have collected published results from clinical trials based on CoQ₁₀ supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ₁₀. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ₁₀ treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility.

Keywords: CoQ deficiency; Coenzyme Q; aging; antioxidant; disease; mitochondria.

Figure 1

The multiple functions of CoQ₁₀. (A) Mitochondria. (1) The main function of CoQ₁₀ in mitochondria is to transfer electrons to complex III (CIII). By transferring two electrons to CIII, the reduced form of CoQ₁₀ (ubiquinol) is oxidized to ubiquinone. The pool of ubiquinol can be restored by accepting electrons either from members of the electron transport chain (CI and CII), glycerol-3-phosphate dehydrogenase (GPDH) and dihydroorotate dehydrogenase (DHODH) that use cytosolic electron donors, or from acyl-CoA dehydrogenases (ACADs); (2) CoQ₁₀ is also a structural component of both CI and CIII and is associated with respiratory supercomplexes, especially the depicted supercomplex I+III+IV; (3) CoQ₁₀ is an obligatory factor in proton transport by uncoupling proteins (UCPs) with concomitant regulation of mitochondrial activity (López-Lluch et al., 2010). (B) Cell membrane activities of CoQ₁₀. Present in nearly all cellular membranes, CoQ₁₀ offers antioxidant protection, in part, by maintaining the reduced state of α-tocopherol (α-TOC) and ascorbic acid (ASC). Furthermore, CoQ₁₀ also regulates apoptosis by preventing lipid peroxidation. Other functions of CoQ₁₀ in cell membrane include metabolic regulation, cell signaling, and cell growth through local regulation of cytosolic redox intermediates such as NAD(P)H (López-Lluch et al., 2010).

Figure 2

Effects of CoQ₁₀ in human diseases. The positive effect of CoQ₁₀ has been already demonstrated in mitochondrial syndromes associated with CoQ₁₀ deficiency, inflammation, and cardiovascular diseases as well as in the delay of some age-related processes. Dashed lines depict other positive effects of CoQ₁₀ with regard to kidney disease, fertility, metabolic syndrome, diabetes, and neurodegenerative diseases. However, more research is needed to validate these observations.