Coenzyme Q4 is a functional substitute for coenzyme Q10 and can be targeted to the mitochondria.

Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson's disease, and hypertension. Unfortunately, treatment with exogenous CoQ10 is often ineffective, likely due to its extreme hydrophobicity and high molecular weight. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium. Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.

Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment.

An organism's ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients.

CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model.

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

Protective effect of coenzyme Q10 against doxorubicin-induced cardiotoxicity: Scoping review article.

Introduction: Doxorubicin (dox) is classified as an antineoplastic antibiotic which is known as adriamycin from the anthracycline group. Due to the release of free radicals and lipid peroxidation which can cause acute cardiotoxicity. Coenzyme Q10 is found in many cells of the body, it is an antioxidant that reduces oxidative stress and lipid peroxidation. Aim: This scoping review aims to evaluate the cardioprotective effect of coenzyme Q10 in doxorubicin-induced cardiotoxicity in animals. Methods: This review was done based on Arksey and O'Malley's methodology, reviewing published articles from October 1978 and September 2023. Results: 14 out of 11,303 articles were included from the initial search, (10 out of 14 articles found that coenzyme Q10 protect has a protection effect against doxorubicin-induced cardiotoxicity). Conclusion: The results of this review found coenzyme Q10 protects against doxorubicin cardiotoxicity. It is a promising supplement that could be used to prevent cardiotoxicity induced by doxorubicin in cancer patients.

Coenzyme Q10 supplementation in burn patients: a double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Burn injuries are important medical problems that, aside from skin damage, cause a systemic response including inflammation, oxidative stress, endocrine disorders, immune response, and hypermetabolic and catabolic responses which affect all the organs in the body. The aim of this study was to determine the effect of coenzyme Q10 (CoQ10) supplementation on inflammation, oxidative stress, and clinical outcomes in burn patients. METHODS: In a double-blind placebo-controlled randomized clinical trial, 60 burn patients were randomly assigned to receive 100 mg CoQ10 three times a day (total 300 mg/day) or a placebo for 10 days. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), oxidative stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine, white blood cells (WBC), and body temperature were assessed as primary outcomes and albumin, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), other hematological parameters, blood pressure, O2 saturation, ICU duration, and 28-mortality rate were assessed as secondary outcomes. RESULTS: Fifty-two participants completed the trial. CRP and ESR levels were not significantly different between CoQ10 and placebo groups at the end of the study (P = 0.550 and P = 0.306, respectively). No significant differences between groups were observed for TAC (P = 0.865), MDA (P = 0.692), and SOD activity (P = 0.633) as well. Administration of CoQ10 resulted in a significant increase in albumin levels compared to placebo (P = 0.031). There was no statistically significant difference between the two groups in other measured outcomes (P > 0.05). CONCLUSION: Results showed that in patients with burn injury, CoQ10 administration had no effect on inflammatory markers and oxidative stress, although serum albumin levels were improved after supplementation. Further studies with albumin as the primary outcome are needed to confirm this finding.

Dantrolene and coenzyme Q10 as a suggested combination therapy to statin-induced myopathy in high fat diet rats: A possible interference with ROS/ TGF-ß / Smad4 signaling pathway.

One of the major hitches for statins' utilization is the development of myotoxicity. Versatile studies reported that the underlining molecular mechanisms including coenzyme Q10 (CoQ10)/ubiquinone depletion, as well as the disturbance in the cytoplasmic Ca2+ homeostasis. Therefore, we investigated the consequences of supplementing CoQ10 and dantrolene, a cytoplasmic Ca2+ reducing agent, in combination with simvastatin. This adjuvant therapy normalized the simvastatin-mediated elevation in serum ALT, AST, CK-MM, as well as tissue Ca2+ content, in addition to suppressing the simvastatin-mediated oxidative stress in simvastatin-treated rats, while having no effect upon statin-induced antihyperlipidemic effect. Additionally, the combination inhibited the simvastatin-induced TGF-ß/ Smad4 pathway activation. Collectively, the current study emphasizes on the potential utilization of dantrolene and CoQ10 as an adjuvant therapy to statins treatment for improving their side effect profile.

The effects of coenzyme Q10 supplementation on biomarkers of exercise-induced muscle damage, physical performance, and oxidative stress: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

PURPOSE: This study aims to elucidate the dose-dependent effect of coenzyme Q10 supplementation (CoQ10) on exercise-induced muscle damage (EIMD), physical performance, and oxidative stress in adults. METHODS: A systematic search was conducted through PubMed, Scopus, and ISI Web of Science databases up to August 2023, focusing on randomized control trials (RCTs) that investigated the effects of CoQ10 supplementation on EIMD recovery, physical performance and oxidative stress mitigation in adults. The weighted mean difference (WMD) and 95 % confidence interval (95 %CI) were estimated using the random-effects model. RESULTS: The meta-analysis incorporated 28 RCTs, encompassing 830 subjects. CoQ10 supplementation significantly decreased creatine kinase (CK) (WMD: -50.64 IU/L; 95 %CI: -74.75, -26.53, P < 0.001), lactate dehydrogenase (LDH) (WMD: -52.10 IU/L; 95 %CI: -74.01, -30.19, P < 0.001), myoglobin (Mb) (WMD: -21.77 ng/ml; 95 %CI: -32.59, -10.94, P < 0.001), and Malondialdehyde (MDA) (WMD: -0.73 µmol/l; 95 %CI: -1.26, -0.20, P = 0.007) levels. No significant alteration in total antioxidant capacity was observed post-CoQ10 treatment. Each 100 mg/day increase in CoQ10 supplementation was correlated with a significant reduction in CK (MD: -23.07 IU/L, 95 %CI: -34.27, -11.86), LDH (WMD: -27.21 IU/L, 95 %CI: -28.23, -14.32), Mb (MD: -7.09 ng/ml; 95 %CI: -11.35, -2.83) and MDA (WMD: -0.17 µmol/l, 95 %CI: -0.29, -0.05) serum levels. Using SMD analysis, "very large" effects on LDH and "moderate" effects on CK and MDA were noted, albeit nonsignificant for other outcomes. CONCLUSION: CoQ10 supplementation may be effective in reducing biomarkers of EIMD and oxidative stress in adults. Nevertheless, given the preponderance of studies conducted in Asia, the generalizability of these findings warrants caution. Further RCTs, particularly in non-Asian populations with large sample sizes and extended supplementation durations, are essential to substantiate these observations.

The role of coenzyme Q10 as a preventive and therapeutic agent for the treatment of cancers.

Currently, several options are available for the prevention and treatment of cancers; however, many limitations remain with these approaches. Recently, antioxidants have become important preventive and therapeutic alternatives with few adverse events and minimum cost. Coenzyme Q10 (CoQ10) is a naturally occurring component that performs an anticancer function by reducing oxidative stress. CoQ10 supplementation as an adjuvant therapy offers more progress in the elimination and development of cancers. This review aimed to critically assess and summarize the implication of CoQ10 in cancers, highlighting possible mechanisms, and future directions of research for the standardization of the current regimen for cancer prevention and treatment.

Efficacy of coenzyme Q10 and curcumin on antioxidant enzyme activity and hippocampal alteration following exposure to cyclophosphamide in male rat.

Coenzyme Q10 (KQ10) and curcumin (KUR) supplements are extensively used for their potential antioxidant, anticancer, and antiapoptotic properties. The present study investigated the neuroprotective potential of KQ10 and KUR against the side effect of cyclophosphamide (SF) (150 mg/kg) on the hippocampus of male Wistar albino rats. Forty-nine 10-12 weeks old rats were randomly divided into seven groups: control, olive oil (OL), SF, KQ10, KUR, SF+KQ10, and SF+KUR. Our biochemical finding showed a significant decrease in superoxide dismutase (SOD) level in the SF group compared to the control group (p < 0.05). There was also a significant reduction in the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions in the SF group compared to the control group (p < 0.05). In the SF+KQ10 group, we found a significant increase in serum SOD level and the total number of the hippocampal pyramidal neurons in the CA1, CA2, and CA1-3 regions compared to the SF group (p < 0.05). Immunohistochemical and histopathological examination exhibited noteworthy findings in the hippocampus tissues. Our findings showed that KQ10 administration significantly mitigated the hippocampal alteration caused by SF through enhancing antioxidant enzyme activity and reducing apoptosis. However, we found no protective activity of KUR on the hippocampus tissue, which may be due to its weak antioxidative activity.

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1ß pathway.

BACKGROUND: The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration. METHODS: To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1ß/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB). RESULTS: Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1ß) signaling pathway. CONCLUSIONS: These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1ß pathway in macrophages. TRIAL REGISTRATION: Date of registration 09/04/2021 (number: ChiCTR2100045256).

A Review of the Potential Role of CoQ10 in the Treatment of Hepatocellular Carcinoma.

The coenzyme ubiquinone-10 (CoQ10) is not only an important part of the electron transport chain of the mitochondrial inner membrane but also has complex biological functions beyond mitochondrial respiration. It is a natural nutrient that is not only produced by the body but is also found in foods, such as meat, eggs, fish, and vegetable oils. Because some types of cancer reduce CoQ10 blood levels, the use of CoQ10 supplements is recommended for the treatment of cancer patients. The anti-cancer effects of CoQ10 supplementation have been reported in several cancers, including colon and breast cancer. CoQ10 scavenges free radicals to reduce oxidative stress and minimize tissue damage. CoQ10 protects the body from damage caused by chemotherapy drugs by reducing the production of inflammatory cytokines and other inflammatory factors. Recent studies suggest that CoQ10 may be a supplement to pharmacotherapy for hepatocellular carcinoma. This article examines the effects of CoQ10 in hepatocellular carcinoma.

Exploring the impact of heat stress on oocyte maturation and embryo development in dairy cattle using a culture medium supplemented with vitamins E, C, and coenzyme Q10.

Heat stress is a significant factor affecting the fertility of dairy cattle due to the generation of free radicals. In assisted reproductive techniques, the inclusion of protective antioxidants becomes crucial to mitigate potential cellular damage. This study aimed to explore the impact of supplementing vitamins E, C, and coenzyme Q10 into the oocyte culture medium, with the goal of ameliorating the adverse effects of heat stress on oocyte maturation and embryo development in dairy cattle. A group of fifty Holstein dairy cows were synchronized, and their oocytes were harvested using the ovum pick-up method. High-quality oocytes were subjected to in vitro maturation (IVM) and in vitro fertilization (IVF) procedures, utilizing a culture medium containing, no supplements (Group 1), 100 µM of vitamins E (Group 2) and C (Group 3), along with 50 µM of coenzyme Q10 (Group 4). The ensuing zygotes were cultured, and the ensuing embryos were evaluated for blastocyst formation by the seventh day. An analysis of the blastocysts' inner cell mass (ICM) and trophectoderm (TE) cells was also conducted. The findings revealed that the group receiving supplementation of vitamin E and coenzyme Q10 exhibited significantly higher maturation and cleavage rates in comparison to both the control and the vitamin C groups. Furthermore, the count of ICM, TE, and blastocyst cells was notably elevated in the vitamin E supplemented group when compared to the control group. In summary, the effectiveness of vitamin E in enhancing IVM, IVF, and embryo development under conditions of heat stress surpassed that of vitamin C and coenzyme Q10.

Natural supplements in antiphospholipid syndrome: A case for further study.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL). Although long-term anticoagulation with vitamin K antagonists is considered standard of care, there is an unmet need for safe therapeutics as primary thromboprophylaxis or adjuncts to standard of care in APS. APS is driven by oxidative stress, procoagulant, proinflammatory and angiogenic pathways. For these reasons there has been an increased interest into the investigation of antithrombotic, anti-inflammatory and anti-oxidant properties of natural supplements in APS. The objective of this review is to summarize the mechanistic, epidemiologic and clinical evidence behind the use of natural supplements in APS, with a specific focus on vitamin D, omega-3 fatty acids, coenzyme Q10, gingerol, and isoquercetin. This review should serve as a compelling argument for the future study of natural supplements in APS.

The Association of Physical Activity Level with Micronutrient and Health Status of Austrian Bank Employees.

BACKGROUND: Favorable health benefits of an active lifestyle have been clearly documented within the context of occupational health. However, a knowledge gap exists regarding the monitoring and comparison of micronutrient status across varying levels of physical activity (PA). This study aimed to investigate the association of PA level with micronutrient status and the associated health biomarkers among a cohort of Austrian bank employees. METHODS: Using a cross-sectional design, this study involved the participation of bank employees (n = 123; average age: 43 years; 49% males) from the federal state of Tyrol, located in the western part of Austria. To assess PA levels and sedentary behavior, the Global Physical Activity Questionnaire (GPAQ; developed by the WHO) was administered. Accordingly, participants were categorized into three groups: low PA, moderate PA, and high PA. Participants' blood samples were obtained to measure blood levels of micronutrients, homocysteine, and CoQ10. The values of vitamins and minerals in whole-blood were compared to sex-specific reference ranges and grouped into three categories: below, within, or exceeding the reference range. RESULTS: The prevalence of a high PA level was 61%, while 18% of participants had a low PA level. Overweight/obesity was significantly less prevalent among participants with high PA levels (22%) compared to those with moderate (50%) and low (50%) PA levels (p = 0.045). No significant differences between PA levels were found for sex, age, diet type, homocysteine, or CoQ10 markers (p > 0.05). There was no significant PA-based difference in blood concentrations of most vitamins and minerals (p > 0.05), except for vitamin D (p = 0.001) among females, as well as selenium (p = 0.040) and vitamin B12 (p = 0.048) among males. CONCLUSION: The present findings offer initial insights into the link between PA behaviors, micronutrient status, and health, highlighting potential implications in occupational health and lifestyle, specifically in developing tailored approaches based on PA levels.

Comparison of Coenzyme Q10 (Ubiquinone) and Reduced Coenzyme Q10 (Ubiquinol) as Supplement to Prevent Cardiovascular Disease and Reduce Cardiovascular Mortality.

PURPOSE OF REVIEW: According to the World Health Organization (WHO), cardiovascular disease is the leading cause of death worldwide. Heart failure has been defined as a global pandemic leading to millions of deaths. Recent research clearly approved the beneficial effect of Coenzyme Q10 supplementation in treatment and prevention of cardiovascular disease in patients with heart failure in clinical trials but did not distinguish between the oxidised form CoQ10 and reduced form CoQH2 of Coenzyme Q10. The aim of this study is to determine differences in medical application of CoQ10 and CoQH2 supplementation and evaluate the efficacy of CoQ10 and CoQH2 supplementation to prevent cardiovascular disease in patients with heart failure. RECENT FINDINGS: A PubMed search for the terms "ubiquinone" and "ubiquinol" was conducted, and 28 clinical trials were included. Our findings go along with the biochemical description of CoQ10 and CoQH2, recording cardiovascular benefits for CoQ10 and antioxidative and anti-inflammatory properties for CoQH2. Our main outcomes are the following: (I) CoQ10 supplementation reduced cardiovascular death in patients with heart failure. This is not reported for CoQH2. (II) Test concentrations leading to cardiovascular benefits are much lower in CoQ10 studies than in CoQH2 studies. (III) Positive long-term effects reducing cardiovascular mortality are only observed in CoQ10 studies. Based on the existing literature, the authors recommend CoQ10 instead of CoQH2 to treat and prevent cardiovascular disease in patients with heart failure.

Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects.

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

Epilepsy and Coenzyme Q10 deficiency with COQ4 variants.

Coenzyme Q10 (CoQ10) is one of the essential substances for mitochondrial energy synthesis and extra-mitochondrial vital function. Primary CoQ10 deficiency is a rare disease resulting from interruption of CoQ10 biosynthetic pathway and biallelic COQ4 variants are one of the genetic etiologies recognized in this hereditary disorder. The clinical heterogenicity is broad with wide onset age from prenatal period to adulthood. The typical manifestations include early pharmacoresistant seizure, severe cognition and/or developmental delay, dystonia, ataxia, and spasticity. Patients may also have multisystemic involvements such as cardiomyopathy, lactic acidosis or gastro-esophageal regurgitation disease. Oral CoQ10 supplement is the major therapeutic medication currently. Among those patients, c.370G > A variant is the most common pathogenic variant detected, especially in Asian population. This phenomenon also suggests that this specific allele may be the founder variants in Asia. In this article, we report two siblings with infantile onset seizures, developmental delay, cardiomyopathy, and diffuse brain atrophy. Genetic analysis of both two cases revealed homozygous COQ4 c.370G > A (p.Gly124Ser) variants. We also review the clinical manifestations of primary CoQ10 deficiency patients and possible treatment categories, which are still under survey. As oral CoQ10 supplement may improve or stabilize disease severity, early precise diagnosis of primary CoQ10 deficiency and early treatment are the most important issues. This review article helps to further understand clinical spectrum and treatment categories of primary CoQ10 deficiency with COQ4 variant.

The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease.

Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.

Hyperbaric oxygen therapy and coenzyme Q10 synergistically attenuates damage progression in spinal cord injury in a rat model.

BACKGROUND: Identifying effective spinal cord injury (SCI) treatments remains a major challenge, and current approaches are still unable to effectively improve its. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with coenzyme Q10 (CoQ10) in the recovery of SCI in rats. MATERIAL AND METHODS: Ninety female mature Sprague-Dawley rats were allocated into five equal groups, including; sham group, SCI group, HBO group (underwent SCI and received HBO), CoQ10 group (underwent SCI and received CoQ10), and HBO+CoQ10 group (underwent SCI and received HBO plus CoQ10). Tissue samples at the lesion site were obtained for evaluation of stereological, immunohistochemical, biochemical, molecular. Also, functional tests were performed to evaluate of behavioral properties. RESULTS: We found that a significant increase in stereological parameters, biochemical factors (GSH, SOD and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells, as well as expression of inflammatory genes (TNF-α and IL-1ß) were considerably reduced in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. CONCLUSION: We conclude that co-administration of HBO and HBO+CoQ10 has a synergistic neuroprotective effects in animals undergoing SCI.