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.

Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

Risks of using mitoquinone during in vitro maturation and its potential protective effects against lipotoxicity-induced oocyte mitochondrial stress.

PURPOSE: Oxidative stress and mitochondrial dysfunction play central roles in reduced oocyte quality and infertility in obese patients. Mitochondria-targeted treatments containing co-enzyme Q10 such as mitoquinone (MitoQ) can increase mitochondrial antioxidative capacity; however, their safety and efficiency when supplemented to oocytes under lipotoxic conditions have not been described. METHODS: We tested the effect of different concentrations of MitoQ or its cationic carrier (TPP) (0, 0.1, 0.5, 1.0 µM each) during bovine oocyte IVM. Then, we tested the protective capacity of MitoQ (0.1 µM) against palmitic acid (PA)-induced lipotoxicity and mitochondrial dysfunction in oocytes. RESULTS: Exposure to MitoQ, or TPP only, at 1 µM significantly (P<0.05) reduced oocyte mitochondrial inner membrane potential (JC-1 staining) and resulted in reduced cleavage and blastocyst rates compared with solvent control. Lower concentrations of MitoQ or TPP had no effects on embryo development under control (PA-free) conditions. As expected, PA increased the levels of MMP and ROS in oocytes (CellROX staining) and reduced cleavage and blastocyst rates compared with the controls (P<0.05). These negative effects were ameliorated by 0.1 µM MitoQ. In contrast, 0.1 µM TPP alone had no protective effects. MitoQ also normalized the expression of HSP10 and TFAM, and partially normalized HSP60 in the produced blastocysts, indicating at least a partial alleviation of PA-induced mitochondrial stress. CONCLUSION: Oocyte exposure to MitoQ may disturb mitochondrial bioenergetic functions and developmental capacity due to a TPP-induced cationic overload. A fine-tuned concentration of MitoQ can protect against lipotoxicity-induced mitochondrial stress during IVM and restore developmental competence and embryo quality.

Neuronal Plasticity and Age-Related Functional Decline in the Motor Cortex.

Physiological aging causes a decline of motor function due to impairment of motor cortex function, losses of motor neurons and neuromuscular junctions, sarcopenia, and frailty. There is increasing evidence suggesting that the changes in motor function start earlier in the middle-aged stage. The mechanism underlining the middle-aged decline in motor function seems to relate to the central nervous system rather than the peripheral neuromuscular system. The motor cortex is one of the responsible central nervous systems for coordinating and learning motor functions. The neuronal circuits in the motor cortex show plasticity in response to motor learning, including LTP. This motor cortex plasticity seems important for the intervention method mechanisms that revert the age-related decline of motor function. This review will focus on recent findings on the role of plasticity in the motor cortex for motor function and age-related changes. The review will also introduce our recent identification of an age-related decline of neuronal activity in the primary motor cortex of middle-aged mice using electrophysiological recordings of brain slices.

Phenotypic, molecular, and functional characterization of COQ7-related primary CoQ10 deficiency: Hypomorphic variants and two distinct disease entities.

Primary coenzyme Q10 (CoQ10) deficiency is a group of inborn errors of metabolism caused by defects in CoQ10 biosynthesis. Biallelic pathogenic variants in COQ7, encoding mitochondrial 5-demethoxyubiquinone hydroxylase, have been reported in nine patients from seven families. We identified five new patients with COQ7-related primary CoQ10 deficiency, performed clinical assessment of the patients, and studied the functional effects of current and previously reported COQ7 variants and potential treatment options. The main clinical features included a neonatal-onset presentation with severe neuromuscular, cardiorespiratory and renal involvement and a late-onset disease presenting with progressive neuropathy, lower extremity weakness, abnormal gait, and variable developmental delay. Baker's yeast orthologue of COQ7, CAT5, is required for growth on oxidative carbon sources and cat5Δ strain demonstrates oxidative growth defect. Expression of wild-type CAT5 could completely rescue the defect; however, yeast CAT5 harboring equivalent human pathogenic variants could not. Interestingly, cat5Δ yeast harboring p.Arg57Gln (equivalent to human p.Arg54Gln), p.Arg112Trp (equivalent to p.Arg107Trp), p.Ile69Asn (equivalent to p.Ile66Asn) and combination of p.Lys108Met and p.Leu116Pro (equivalent to the complex allele p.[Thr103Met;Leu111Pro]) partially rescued the growth defects, indicating these variants are hypomorphic alleles. Supplementation with 2,4 dihydroxybenzoic acid (2,4-diHB) rescued the growth defect of both the leaky and severe mutants. Overexpression of COQ8 and 2,4-diHB supplementation synergistically restored oxidative growth and respiratory defect. Overall, we define two distinct disease presentations of COQ7-related disorder with emerging genotype-phenotype correlation and validate the use of the yeast model for functional studies of COQ7 variants.

Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs.

COQ7 encodes a hydroxylase responsible for the penultimate step of coenzyme Q10 (CoQ10) biosynthesis in mitochondria. CoQ10 is essential for multiple cellular functions, including mitochondrial oxidative phosphorylation, lipid metabolism, and reactive oxygen species homeostasis. Mutations in COQ7 have been previously associated with primary CoQ10 deficiency, a clinically heterogeneous multisystemic mitochondrial disorder. We identified COQ7 biallelic variants in nine families diagnosed with distal hereditary motor neuropathy with upper neuron involvement, expending the clinical phenotype associated with defects in this gene. A recurrent p.Met1? change was identified in five families from Brazil with evidence of a founder effect. Fibroblasts isolated from patients revealed a substantial depletion of COQ7 protein levels, indicating protein instability leading to loss of enzyme function. High-performance liquid chromatography assay showed that fibroblasts from patients had reduced levels of CoQ10, and abnormal accumulation of the biosynthetic precursor DMQ10. Accordingly, fibroblasts from patients displayed significantly decreased oxygen consumption rates in patients, suggesting mitochondrial respiration deficiency. Induced pluripotent stem cell-derived motor neurons from patient fibroblasts showed significantly increased levels of extracellular neurofilament light protein, indicating axonal degeneration. Our findings indicate a molecular pathway involving CoQ10 biosynthesis deficiency and mitochondrial dysfunction in patients with distal hereditary motor neuropathy. Further studies will be important to evaluate the potential benefits of CoQ10 supplementation in the clinical outcome of the disease.

A Glutamate Scavenging Protocol Combined with Deanna Protocol in SOD1-G93A Mouse Model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive disease of neuronal degeneration in the motor cortex, brainstem, and spinal cord, resulting in impaired motor function and premature demise as a result of insufficient respiratory drive. ALS is associated with dysfunctions in neurons, neuroglia, muscle cells, energy metabolism, and glutamate balance. Currently, there is not a widely accepted, effective treatment for this condition. Prior work from our lab has demonstrated the efficacy of supplemental nutrition with the Deanna Protocol (DP). In the present study, we tested the effects of three different treatments in a mouse model of ALS. These treatments were the DP alone, a glutamate scavenging protocol (GSP) alone, and a combination of the two treatments. Outcome measures included body weight, food intake, behavioral assessments, neurological score, and lifespan. Compared to the control group, DP had a significantly slower decline in neurological score, strength, endurance, and coordination, with a trend toward increased lifespan despite a greater loss of weight. GSP had a significantly slower decline in neurological score, strength, endurance, and coordination, with a trend toward increased lifespan. DP+GSP had a significantly slower decline in neurological score with a trend toward increased lifespan, despite a greater loss of weight. While each of the treatment groups fared better than the control group, the combination of the DP+GSP was not better than either of the individual treatments. We conclude that the beneficial effects of the DP and the GSP in this ALS mouse model are distinct, and appear to offer no additional benefit when combined.

CoQ10Phytosomes Improve Cellular Ubiquinone Uptake in Skeletal Muscle Cells: An Ex Vivo Study Using CoQ10-Enriched Low-Density Lipoproteins Obtained in a Randomized Crossover Study.

Coenzyme Q10 (CoQ10) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ10 uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ10 content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ10 following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ10 for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ10 crystalline form. After supplementation, plasma was collected for CoQ10 determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ10 content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ10-enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ10 to skin and muscle tissues.

Effect of dietary antioxidant supplements (selenium forms, alpha-tocopherol, and coenzyme Q10) on growth performance, immunity, and physiological responses in rainbow trout (Oncorhynchus mykiss) using orthogonal array design.

Dietary supplements containing antioxidants play an important role in reducing the risk of peroxidative attack in aquatic animals. In this work, an orthogonal array design (L9: 34) was used to evaluate the effect of four dietary antioxidant supplements on the physiological responses of rainbow trout at three levels. The supplements included different (A) selenium (Se) forms (inorganic, organic, and nanoparticle), (B) Se content (0, 0.3, & 0.5 mg/kg feed), (C) vitamin E (VE) content (0, 100, & 150 mg/kg feed), and (D) coenzyme Q10 (CoQ10) content (0, 10, & 20 mg/kg feed). Fish with an average body weight of 8.35 ± 0.33 g were randomly allocated to different experimental groups. According to the results, the antioxidant supplements included in the diet had no significant effects on the growth performance of fish (P > 0.05). Immunological and antioxidant parameters were mainly improved by the Se form (Nano-Se) and dietary CoQ10 supplementation. In addition, Se form and VE were more effective in digestive enzyme activities and hematology indices in comparison to other dietary antioxidants. Additionally, diets supplemented with nano-Se along with CoQ10 and VE improved fish resistance/stamina against stress. In conclusion, a more effective combination of the four antioxidant supplements was A2/3B2/3C3D3 (i.e., 0.5 mg/kg organic/nano-Se, 150 mg/kg VE, and 20 mg/kg CoQ10), which could mainly improve the physiological responses of rainbow trout.

The effect of dietary supplementation of coenzyme Q10 on reproductive variables of cadmium-challenged male Japanese quails (Coturnix Japonica).

BACKGROUND: In recent decades, efforts to produce more efficient poultry products have increased due to its high demand. Meanwhile, some stressors have a negative impact on poultry efficiency and reproduction. Cadmium (Cd) is a toxic heavy metal with a high potential for inducing reactive oxygen species. On the other hand, coenzyme Q10 (CoQ10), with antioxidant properties, exerts a free radical-neutralizing effect on biological systems under stressful conditions. OBJECTIVES: This study aimed to determine the effect of dietary CoQ10 supplementation on reproductive variables of Cd-challenged male quails. METHODS: Two hundred and sixteen 42-day-old Japanese quails with a male-to-female ratio of 1:3 were randomly divided into three experimental groups (n = 72) and fed by experimental diets from 9 to 13 weeks of age (woa). Treatments included a negative control (NC): feeding basal diet; positive control (PC): feeding basal diet and Cd administration (1 mg per 100 g body weight at 10 and 11 woa); and CdQ10: dietary supplementation of CoQ10 (900 mg per kg diet) and Cd administration. At 10 and 13 woa, liver and testis, cloacal gland index, sera concentration of malondialdehyde (MDA) and testosterone, total antioxidant capacity (TAC), alanine aminotransferase (ALT), testicular histology, mRNA abundance of Hsp70 and fatty acid profile of testis, as well as hatchability and fertility, were measured. RESULTS: Liver and testis weights, cloacal gland index, serum concentration of testosterone, ALT, MDA, TAC, mRNA abundance of HSP70, hatchability, and fertility were not affected by the treatments. However, Cd administration decreased seminiferous tubule diameter and seminiferous epithelium thickness (SET) in the PC group compared to the NC group (p < 0.05). The proportion of saturated fatty acids (SFA) in testis tissue was increased, and the proportion of PUFA and n-3 to n-6 PUFA ratio was decreased in the PC group compared to the NC group (p < 0.05). In addition, CoQ10 supplementation ameliorated the effect of Cd on decreasing SFA and increasing n-3 to n-6 PUFA ratio proportions. CONCLUSIONS: In conclusion, Cd exerts several adverse effects on reproductive-associated variables; some, but not all, of them are mitigated by CoQ10 supplementation.

Coenzyme Q10 for Diabetes and Cardiovascular Disease: Useful or Useless?

INTRODUCTION: Diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) have become some of the most urgent and prevalent health problems in recent decades, side by side with the growing obesity crisis. The close relationship between T2DM and CVD has become clear: endothelial dysfunction caused by oxidative stress and inflammation resulting from hyperglycaemia are the key factors in the development of vascular complications of T2DM, leading to CVD. Coenzyme Q10 (CoQ10) is a great candidate for the treatment of these diseases, acting precisely at the intersection between T2DM and CVD that is oxidative stress, due to its strong antioxidant activity and fundamental physiological role in mitochondrial bioenergetics. CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is synthesized endogenously in the body from tyrosine and mevalonic acid. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP). As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 supplementation has been used as an intensifier of mitochondrial function and an antioxidant with the aim of palliating or reducing oxidative damage that can worsen the physiological outcome of a wide range of diseases including T2DM and CVDs. CONCLUSION: Although there is not enough evidence to conclude it is effective for different therapeutic indications, CoQ10 supplementation is probably safe and well-tolerated, with few drug interactions and minor side effects. Many valuable advances have been made in the use of CoQ10 in clinical practice for patients with T2DM and a high risk of CVD. However, further research is needed to assess the real safety and benefit to indicate CoQ10 supplementation in patients with T2DM.

Dietary supplements for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most prevalent female endocrine reproductive disorders, affecting between 4 to 18% of the women in their reproductive age. It is generally characterized by several clinical aspects, among which anovulation, inflammation and infertility. Moreover, PCOS has several health implications, including increased metabolic, reproductive, and psychological risks. Previously, metformin and to some extent thiazolidinediones were considered as drug of choice for PCOS management, but they had several side-effects, and controversial results were obtained about their efficiency, especially in non-insulin-resistant non-obese patients. Thus, alternative treatment options are now being studied for PCOS, including different natural molecules and complementary medicines (CM) for the improvement of their health, wellbeing and fertility. Recently, treatment of PCOS patients with different natural molecules, coming from nutritional supplements and herbal medicines, has attained satisfactory results with the absence of any side effects. In this review, four natural molecules, curcumin, vitamin D, inositol and CoQ10 are discussed for their therapeutic ability. These molecules proved to decrease insulin sensitivity and inflammation, to improve the restoration of ovarian function, and they could restore hormonal balance and regulate the menstrual cycle, all of which are the main features and major concerns for women suffering from PCOS.

Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.

CONTEXT: 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. OBJECTIVE: This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose-response relationships in adults. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Hepatoprotective Effect of Coenzyme Q10 in Rats with Diclofenac Toxicity.

The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in metabolisms, detoxifications, storage, elimination of medications, and their metabolites. The present study aimed to examine the role of the natural and free radical scavenger "CoQ10" against diclofenac-induced hepatic and renal tissue injury. In total, 36 adult Wistar rats were randomly divided into three equal groups (n=12). The animals in the control group did not receive any medication or treatments, and the second group included animals that received intramuscular (IM) injection of Diclofenac (DF) (at a dose of 10 mg/kg once daily for 14 days). Moreover, the third group was given the IM injection of DF (at a dose of 10 mg/kg once daily for 14 days) +CoQ10. After 14 days, DF prompted signified hepatic and renal injury indicated by elevated biochemical parameters, such as total serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, and uric acid, compared to the control and the third group. However, the group that received Diclofenac+CoQ10 had significantly lower hepatic and renal dysfunctions, compared to the second treated group. DF toxic effects could be the consequences of mitochondrial dysfunction and free radical effects. Remarkably, therapeutic supplementation of CoQ10 diminished the DF-induced toxic oxidative injury and apoptotic cell death. The protective effects of CoQ10 were attributed to its antioxidants and free radical scavenger activity.

The Use of the Coenzyme Q10 as a Food Supplement in the Management of Fibromyalgia: A Critical Review.

The coenzyme Q10 is a naturally occurring benzoquinone derivative widely prescribed as a food supplement for different physical conditions and pathologies. This review aims to sum up the key structural and functional characteristics of Q10, taking stock of its use in people affected by fibromyalgia. A thorough survey has been conducted, using Pubmed, Scifinder, and ClinicalTrials.gov as the reference research applications and registry database, respectively. Original articles, reviews, and editorials published within the last 15 years, as well as open clinical investigations in the field, if any, were analyzed to point out the lights and shadows of this kind of supplementation as they emerge from the literature.

Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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.

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

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.

A novel COQ7 mutation causing primarily neuromuscular pathology and its treatment options.

Coenzyme Q10 (CoQ10) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ10 is synthesized by all cells and defects in the synthesis pathway result in primary CoQ10 deficiency that frequently leads to severe mitochondrial disease syndrome. CoQ10 is exceedingly hydrophobic, insoluble, and poorly bioavailable, with the result that dietary CoQ10 supplementation produces no or only minimal relief for patients. We studied a patient from Turkey and identified and characterized a new mutation in the CoQ10 biosynthetic gene COQ7 (c.161G > A; p.Arg54Gln). We find that unexpected neuromuscular pathology can accompany CoQ10 deficiency caused by a COQ7 mutation. We also show that by-passing the need for COQ7 by providing the unnatural precursor 2,4-dihydroxybenzoic acid, as has been proposed, is unlikely to be an effective and safe therapeutic option. In contrast, we show for the first time in human patient cells that the respiratory defect resulting from CoQ10 deficiency is rescued by providing CoQ10 formulated with caspofungin (CF/CoQ). Caspofungin is a clinically approved intravenous fungicide whose surfactant properties lead to CoQ10 micellization, complete water solubilization, and efficient uptake by cells and organs in animal studies. These findings reinforce the possibility of using CF/CoQ in the clinical treatment of CoQ10-deficient patients.

Effect of CoQ10 Administration to Psoriatic Iraqi Patients on Biological Therapy Upon Severity Index (PASI) and Quality of Life Index (DLQI) Before and After Therapy.

Psoriasis is a medical condition in which the skin of the body is affected at a multisytemic level. Patients with moderate to severe psoriasis have a considerably reduced quality of life as a result of their disease. For morphological indicators, the Psoriasis Area Severity Index (PASI) test is one of the methods for indicating the severity of the illness. An imbalance between pro-oxidants and antioxidants in our bodies causes oxidative stress and plays a crucial role in the pathophysiology of chronic inflammatory diseases like psoriasis(1). It has been considered that antioxidant treatment can be an effective therapeutic option. The goal of this clinical investigation was to see if there was a link between the percentage change in quality of life and the clinical severity of psoriasis during a 12-week period among Iraqi psoriatic patients. Over the course of 3 months, 24 psoriatic patients (9 females and 15 males) ranging in age from 17 to 72 years participated in a prospective double-blinded clinical experiment. Two groups of participants were formed. A biological medicine (adalimumab) and a placebo was given to group A (n = 11), whereas group B (n = 13) received 100 mg CoQ10 adjuvant therapy in addition to the biological medication already provided. The Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) were used to examine patients (DLQI). Treatment with both biological and adjuvant CoQ10 therapy showed a substantial association between the PASI and the DLQI (p = 0.000132). After 3 months of therapy, the mean (SD) of the PASI score for all patients was 20.88 7.15, with a 67.48% ± 22.25% improvement change. The mean SD of the DLQI score at baseline was 12.5 ± 4.71, with a change of 56.13% ± 20.15% following treatment. After therapy with a biological medication, there was a favorable association between the PASI and the DLQI (p > 0.05). This indicates that therapy with a biological medication with daily administration of 100 mg CoQ10 supplements to psoriatic patients for 12 weeks improved the correlation between PASI and DLQI.