Depletion and Supplementation of Coenzyme Q10 in Secondary Deficiency Disorders

Abstract

Coenzyme Q10 (CoQ10) deficiency is broadly divided into two types, primary and secondary. Primary CoQ10 deficiencies are relatively rare disorders resulting from mutations in genes directly involved in the CoQ10 biosynthetic pathway, and are not a subject of this article. Secondary CoQ10 disorders are relatively common, and may occur for a variety of reasons; these include mutations in genes not directly related to the synthetic pathway, oxidative stress induced reduction of CoQ10, and the effects of pharmacological agents such as statins. CoQ10 is of key importance in cell metabolism; in addition to its role in mitochondrial oxidative phosphorylation, it is a major endogenous antioxidant, and has a role in the metabolism of sulphides, lipids and amino acids. Given its importance in cell metabolism, it is unsurprising that secondary CoQ10 deficiency has been linked with a wide range of disorders. In this article, we have reviewed evidence of secondary CoQ10 deficiency in both common and less common disorders, and highlighted those disorders in which CoQ10 supplementation has been shown to be of significant clinical benefit.

The Ubiquinone-Ubiquinol Redox Cycle and Its Clinical Consequences: An Overview

“…With regard to the deficiency of components directly involved in the redox cycle in more general terms, only two components (CoQ10 as ubiquinone/ubiquinol and NAD as NAD+/NADH) are commercially available in supplement form. Of these two substances, CoQ10 is by far the best characterised; the bioavailability is well established (Mantle & Dybring, 2020) [54], and the efficacy and safety of supplemental CoQ10 have been described in a considerable number of randomised controlled clinical trials (Mantle et al, 2022) [32]. The bioavailability of orally administered NAD+ or NADH is uncertain (She et al, 2021) [55], and intravenous infusion of NAD+ serves as an alternative method of administration by-passing the intestinal tract (Braidy et al, 2019) [56].…”

“…Depleted CoQ10 levels have been reported in several secondary deficiencies. Randomised controlled clinical trials have shown supplementation with CoQ10 to be of significant benefit, particularly in heart failure, chronic kidney disease, type II diabetes, reproductive disorders, and fibromyalgia (Mantle et al, 2022) [32].…”

Primary Coenzyme Q10 Deficiency: An Update

“…At least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status [ 3 ]. Many of the data relating to CoQ10 biosynthesis were initially obtained from studies in yeast, with deficiencies corresponding to the above genes denoted as CoQ1 to CoQ11 (numbering refers to date order of identification) [ 9 ].…”

“…Secondary CoQ10 disorders are relatively common and may occur for a variety of reasons; these include mutations in genes not directly related to the synthetic pathway, the oxidative-stress-induced reduction of CoQ10, and the effects of pharmacological agents such as statins. The role of CoQ10 deficiency and the benefits of supplementation in secondary CoQ10 disorders have been reviewed recently [ 3 ] and are not further considered in the present article.…”

Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

“…Illness: The levels of CoQ 10 in blood and other tissues are typically decreased in a number of disorders, including cardiovascular disease, neurological disorders, diabetes, liver disorders, pulmonary disorders, and reproductive disorders (reviewed by Mantle et al [127]). For example, in patients with heart failure, depletion of both circulatory and cardiac tissue levels of CoQ 10 have been reported; in cardiac biopsy samples, CoQ 10 levels in patients with NYHA Class III and IV heart failure were 0.28+/−0.04 µg/mg tissue dry weight, compared to the level in normal cardiac tissue of 0.42+/−0.04 µg/mg tissue dry weight [128].…”