The efficacy of coenzyme Q10 treatment in alleviating the symptoms of primary coenzyme Q10 deficiency: A systematic review

Abstract

Coenzyme Q₁₀ (CoQ₁₀ ) is necessary for mitochondrial electron transport. Mutations in CoQ₁₀ biosynthetic genes cause primary CoQ₁₀ deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ₁₀ supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ₁₀ treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ₁₀ treatment (27.0%). In five cases, the patient's condition was reported to deteriorate after halting of CoQ₁₀ treatment. 12 cases reported improvement in the severity of ataxia and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for 4 patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ₁₀ supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings, thus, suggest a need for caution when seeking to justify the widespread use of CoQ₁₀ for the treatment of any disease or as dietary supplement.

Keywords: CoQ biosynthesis; CoQ10 supplementation; coenzyme Q; mitochondrial disorders; primary CoQ10 deficiency; ubiquinone.

FIGURE 1

CoQ₁₀ in the mitochondria, pathology of CoQ₁₀ deficiency and oral supplementation. (A) The final steps of CoQ₁₀ biosynthesis are carried out in the inner mitochondrial membrane. The CoQ₁₀ biosynthetic pathway includes both enzymes (in blue) and structural or regulatory components (in purple). Only the numbers in their names are shown for COQ proteins (COQ2‐7, COQ8A, COQ8B and COQ9). They are known to form a large complex, the CoQ biosynthetic complex or CoQ‐synthome. COQ10A and COQ10B whose functions are uncertain and not known to be part of the complex are not shown. The most essential function of CoQ₁₀ is to transport electrons in the mitochondrial respiratory chain. Although CoQ₁₀ is found in the mitochondrial membrane, in the figure this is not shown for clarity. (B) Primary CoQ₁₀ deficiency predominantly manifests as mitochondrial disorder, with organs with high energy needs being most often affected. (C) Intestinal absorption of CoQ₁₀ is thought to occur through the formation of mixed micelles with other dietary lipids. Once inside the enterocytes, CoQ₁₀ is incorporated into chylomicrons (CM), which are transported via the lymphatics to the blood circulation. Because of its extreme hydrophobicity and its relatively large size, the absorption of orally administered CoQ₁₀ has been reported to be poor

FIGURE 2

Flow diagram for identification and selection of primary CoQ₁₀ deficiency patients

FIGURE 3

Violin plots of CoQ₁₀ treatment dose and duration. (A) Two graphs are shown for dosage comparisons because CoQ₁₀ treatment dosages were reported in 2 different units (mg/kg/day and mg/day). (B) Comparison of CoQ₁₀ treatment duration. (C) Disease durations before CoQ₁₀ treatment. ns: not significant (Student's t‐test). Sample sizes are indicated on the graphs. Note that the measures plotted in these graphs only include the patients for which the information was provided in the case reports, which is why the sample sizes are different