UNASSIGNED: Infertility and the pathogenesis of polycystic ovarian syndrome (PCOS) are both influenced by insulin resistance and dyslipidemia. Presumably, adding coenzyme Q10 (CoQ10) to these patients\' diets will be beneficial. Therefore, this study aimed to examine the effects of CoQ10 supplementation on metabolic profiles in women candidates for in-vitro fertilization (IVF).
UNASSIGNED: For this randomized, double-blinded, parallel, placebo-controlled clinical experiment, 40 PCOS-positive infertile women who were IVF candidates were included. They ranged in age from 18 to 40. The 20 participants in the two intervention groups received either CoQ10 or a placebo for 8 weeks. The expression of glucose transporter 1 (GLUT-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), low-density lipoprotein receptor (LDLR), as well as metabolic profiles such as insulin metabolism and lipid profiles were evaluated. Quantitative RT-PCR determined the expression of GLUT-1, PPAR-γ, and LDLR on peripheral blood mononuclear cells. Lipid profiles and fasting glucose were assessed using enzymatic kits, and insulin was determined using Elisa kit.
UNASSIGNED: In comparison to the placebo, CoQ10 supplementation significantly reduced blood insulin levels (-0.3±1.0 vs. 0.5±0.7, P=0.01) and insulin resistance (-0.1±0.2 vs. 0.1±0.2, P=0.01), and increased PPAR-γ expression (P=0.01). In infertile PCOS patients\' candidates for IVF, CoQ10 supplementation showed no appreciable impact on other metabolic profiles. Also, CoQ10 supplementation revealed no significant impact on GLUT-1 (P=0.30), or LDLR (P=0.27) expression. Within-group changes in insulin levels (P=0.01) and insulin resistance (P=0.01) showed a significant elevation in the placebo group. When we adjusted the analysis for baseline BMI, baseline values of variables, and age, our findings were not affected.
UNASSIGNED: Eight weeks of CoQ10 supplementation demonstrated positive benefits on PPAR-γ expression, insulin resistance, and serum insulin in infertile PCOS women candidates for IVF.

Previous studies have shown beneficial effects of coenzyme Q10 (CoQ10) supplementation on blood pressure (BP). However, the optimal intake of CoQ10 for BP regulation in patients with cardiometabolic disorders is unknown, and its effect on circulating CoQ10 is also unclear. We aimed to assess the dose-response relation between CoQ10 and BP, and quantify the effect of CoQ10 supplementation on the concentration of circulating CoQ10 by synthesizing available evidence from randomized controlled trials (RCTs). A comprehensive literature search was performed in 3 databases (PubMed/MEDLINE, Embase, and Cochrane Library) to 21 March, 2022. A novel 1-stage restricted cubic spline regression model was used to evaluate the nonlinear dose-response relation between CoQ10 and BP. Twenty-six studies comprising 1831 subjects were included in our meta-analysis. CoQ10 supplementation significantly reduced systolic blood pressure (SBP) (-4.77 mmHg, 95% CI: -6.57, -2.97) in patients with cardiometabolic diseases; this reduction was accompanied by a 1.62 (95% CI: 1.26, 1.97) μg/mL elevation of circulating CoQ10 compared with the control group. Subgroup analyses revealed that the effects of reducing SBP were more pronounced in patients with diabetes and dyslipidemia and in studies with longer durations (>12 wk). Importantly, a U-shaped dose-response relation was observed between CoQ10 supplementation and SBP level, with an approximate dose of 100-200 mg/d largely reducing SBP (χ2 = 10.84, Pnonlinearity = 0.004). The quality of evidence was rated as moderate, low, and very low for SBP, diastolic blood pressure (DBP), and circulating CoQ10 according to the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE), respectively. The current finding demonstrated that the clinically beneficial effects of CoQ10 supplementation may be attributed to the reduction in SBP, and 100-200 mg/d of CoQ10 supplementation may achieve the greatest benefit on SBP in patients with cardiometabolic diseases. This study was registered on PROSPERO as CRD42021252933.

Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults.
This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose-response relationships in adults.
Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships.
Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD -5.53 mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoprotein cholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01).
CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatest effect on TC.

Previous studies have shown beneficial effects of coenzyme Q10 (CoQ10) supplementation on blood pressure (BP). However, the optimal intake of CoQ10 for BP regulation in patients with cardiometabolic disorders is unknown, and its effect on circulating CoQ10 is also unclear. We aimed to assess the dose-response relation between CoQ10 and BP, and quantify the effect of CoQ10 supplementation on the concentration of circulating CoQ10 by synthesizing available evidence from randomized controlled trials (RCTs). A comprehensive literature search was performed in 3 databases (PubMed/MEDLINE, Embase, and Cochrane Library) to 21 March, 2022. A novel 1-stage restricted cubic spline regression model was used to evaluate the nonlinear dose-response relation between CoQ10 and BP. Twenty-six studies comprising 1831 subjects were included in our meta-analysis. CoQ10 supplementation significantly reduced systolic blood pressure (SBP) (-4.77 mmHg, 95% CI: -6.57, -2.97) in patients with cardiometabolic diseases; this reduction was accompanied by a 1.62 (95% CI: 1.26, 1.97) μg/mL elevation of circulating CoQ10 compared with the control group. Subgroup analyses revealed that the effects of reducing SBP were more pronounced in patients with diabetes and dyslipidemia and in studies with longer durations (>12 wk). Importantly, a U-shaped dose-response relation was observed between CoQ10 supplementation and SBP level, with an approximate dose of 100-200 mg/d largely reducing SBP (χ2 = 10.84, Pnonlinearity = 0.004). The quality of evidence was rated as moderate, low, and very low for SBP, diastolic blood pressure (DBP), and circulating CoQ10 according to the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE), respectively. The current finding demonstrated that the clinically beneficial effects of CoQ10 supplementation may be attributed to the reduction in SBP, and 100-200 mg/d of CoQ10 supplementation may achieve the greatest benefit on SBP in patients with cardiometabolic diseases. This study was registered on PROSPERO as CRD42021252933.

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.

Coenzyme Q (CoQ) is an important component of the mitochondrial electron transport chain. The finding that multiple chronic diseases show lower levels of CoQ10 has led to the possibility that CoQ10 supplementation could be an effective approach to ameliorate or prevent disease progression. In this review, we discuss the state of the art regarding the role of CoQ10 in health and disease and describe the latest clinical studies which have tested the effects of CoQ10 supplementation in inflammatory diseases. The results of these studies indicate that individuals suffering from inflammation-related diseases show improvement under the CoQ10 supplementation protocol. However, these results have been inconsistent, leading to the need for additional studies at the preclinical and clinical levels, involving a greater number of subjects and different treatment regimes.

BACKGROUND: Primary coenzyme Q10 (CoQ10) deficiencies are clinically and genetically heterogeneous group of disorders associated with defects of genes involved in the CoQ10 biosynthesis pathway. COQ7-associated CoQ10 deficiency is very rare and only two cases have been reported.
RESULTS: We report a patient with encephalo-myo-nephro-cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Using whole exome sequencing, we identified compound heterozygous variants in the COQ7 gene consisting of a deletion insertion resulting in frameshift [c.599_600delinsTAATGCATC, p.(Lys200Ilefs*56)] and a missense substitution [c.319C>T, p.(Arg107Trp), NM_016138.4]. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level.
CONCLUSIONS: This third patient presenting with lethal encephalo-myo-nephro-cardiopathy represents the severe end of this ultra-rare mitochondrial disease caused by biallelic COQ7 mutations. The response to CoQ10 supplement is poor and alternative treatment strategies should be developed for a more effective management of this disorder.

COQ2 mutations cause a rare infantile multisystemic disease with heterogeneous clinical features. Promising results have been reported in response to Coenzyme Q10 treatment, especially for kidney involvement, but little is known about the long-term outcomes.
We report four new patients from two families with the c.437G→A (p.Ser146Asn) mutation in COQ2 and the outcomes of two patients after long-term coenzyme Q10 treatment.
Index cases from two families presented with vomiting, nephrotic range proteinuria, and diabetes in early infancy. These patients were diagnosed with coenzyme Q10 deficiency and died shortly after diagnosis. Siblings of the index cases later presented with neonatal diabetes and proteinuria and were diagnosed at the first day of life. Coenzyme Q10 treatment was started immediately. The siblings responded dramatically to coenzyme Q10 treatment with normalized glucose and proteinuria levels, but they developed refractory focal clonic seizures beginning at three months of life that progressed to encephalopathy.
In our cohort with CoQ10 deficiency, neurological involvement did not improve with oral coenzyme Q10 treatment despite the initial recovery from the diabetes and nephrotic syndrome.

Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol. There is a possible risk of new-onset diabetes mellitus with statin treatment but the mechanisms behind are unknown. Coenzyme Q10 (CoQ10) supplementation has been found to improve glucose homeostasis in various patient populations and may increase muscle glucose transporter type 4 content. Our aim was to investigate if 8 weeks of CoQ10 supplementation can improve glucose homeostasis in simvastatin-treated subjects. Thirty-five men and women in treatment with a minimum of 40 mg of simvastatin daily were randomized to receive either 2 × 200 mg/day of CoQ10 supplementation or placebo for 8 weeks. Glucose homeostasis was investigated with fasting blood samples, oral glucose tolerance test (OGTT) and intravenous glucose tolerance test. Insulin sensitivity was assessed with the hyperinsulinemic-euglycemic clamp. Different indices were calculated from fasting samples and OGTT as secondary measures of insulin sensitivity. A muscle biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes. There were no changes in body composition, fasting plasma insulin, fasting plasma glucose, or 3-h glucose with intervention, but glycated hemoglobin decreased with time. Glucose homeostasis measured as the area under the curve for glucose, insulin, and C-peptide during OGTT was unchanged after intervention. Insulin secretory capacity was also unaltered after CoQ10 supplementation. Insulin sensitivity was unchanged but hepatic insulin sensitivity increased. No changes in muscle GLUT4 content was observed after intervention. CoQ10 supplementation does not change muscle GLUT4 content, insulin sensitivity, or secretory capacity, but hepatic insulin sensitivity may improve.

BACKGROUND: ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration.
METHODS: A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation.
RESULTS: Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m2, proteinuria was 1,008 (IQR 281-1,567) mg/m2/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m2, P=0.61).
CONCLUSIONS: ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective.