ubiquinone and Diabetic-Neuropathies

We hypothesized that the addition of coenzyme Q10 (CoQ10) to pregabalin might be helpful in improving symptoms in patients suffering from painful diabetic neuropathy (PDN).. One hundred twelve patients with PDN were randomly allocated to receive CoQ10 + pregabalin (57 patients) or placebo + pregabalin (55 patients). Besides pregabalin (150 mg/day), the patients, upon their group assignment, received CoQ10 at a dosage of 100 mg every 8 h or matched placebo for 8 consecutive weeks. The primary efficacy measure was the changes in the pain intensity from baseline to endpoint measured on an 11-point NRS (numeric rating scale). Secondary efficacy measures included the changes in the pain-associated sleep interference score (SIS) as well as the patients' global improvement with treatment measured on the Clinicians' and Patients' Global Impression of Change (CGIC/PGIC).. On the intent‑to‑treat population (ITT) analysis, the CoQ10 + pregabalin regimen resulted in significantly greater pain relief than the placebo + pregabalin regimen. By the end of week 2, the decrease in the mean pain NRS score was similar in both groups, but at the end of weeks four and eight, the decrease in the mean pain NRS score was significantly greater in patients taking CoQ10 + pregabalin than in those taking placebo + pregabalin (p value = 0.01 and < 0.001, respectively). Likewise, at the end of week 8, the decrease in the pain-associated SIS was significantly greater in the patients supplemented with CoQ10 compared to placebo. Furthermore, the proportion of the responder patients (those having ≥ 50% decline in the mean pain NRS score) as well as the proportion of patients rated ''very much'' or ''much improved'' on the CGIC/PGIC scales were also significantly higher in the CoQ10 + pregabalin-treated patients than placebo + pregabalin-treated patients.. Our data support the idea that diabetic patients suffering from PDN may benefit from using antioxidant and anti-inflammatory supplements like CoQ10. However, further studies are required before supplementation with CoQ10 can be recommended for treating PDN.. The trial was registered at Iranian Registry of Clinical Trials (identifier code: IRCT20120215009014N385). Registration date: 2021-02-21.

Topics: Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Double-Blind Method; gamma-Aminobutyric Acid; Humans; Iran; Pain; Pregabalin; Treatment Outcome; Ubiquinone

This 12-week randomized placebo controlled clinical trial investigated the effect of Coenzyme Q10 (CoQ10) on diabetic neuropathy, oxidative stress, blood glucose and lipid profile of patients with type 2 diabetes.. Diabetic patients with neuropathic signs (n = 70) were randomly assigned to CoQ10 (200 mg/d) or placebo for 12 weeks. Blood samples were collected for biochemical analysis and neuropathy tests before and after the trial.. There were no significant differences between the two groups in terms of mean fasting blood glucose, HbA1c and the lipid profile after the trial. The mean insulin sensitivity and total antioxidant capacity (TAC) concentration significantly increased in the Q10 group compared to the placebo after the trial (P < 0.05). C-reactive protein (hsCRP) significantly decreased in the intervention group compared to placebo after the trial (P < 0.05). In the control group, insulin sensitivity decreased and HOMA-IR increased, which revealed a significant difference between groups after the trial. Neuropathic symptoms and electromyography measurements did not differ between two groups after the trial.. According to the present study, CoQ10, when given at a dose of 200 mg/d for 12 weeks to a group of neuropathic diabetic patients, did not improve the neuropathy signs compared to placebo, although it had some beneficial effects on TAC and hsCRP and probably a protective effect on insulin resistance.

Topics: Blood Glucose; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Ubiquinone

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Topics: Adult; C-Peptide; Coenzymes; Deafness; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; DNA, Mitochondrial; Family Health; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Hearing; Humans; Lactic Acid; Male; Middle Aged; Mothers; Point Mutation; Time Factors; Treatment Outcome; Ubiquinone

Diabetic neuropathy (DN) is the most common complication of diabetes. Neuroprotective effects of alpha lipoic acid (ALA) and coenzyme Q10 (CoQ10) has been previously shown in DN, but underlying mechanisms involved not been exactly found. The present study explored the neuroprotective effects of ALA and Q10 combination in experimental DN by ameliorating oxidative stress and apoptosis.. We investigated the effects of CoQ10 (10 mg/kg, orally, five weeks) and/or ALA (100 mg/kg, orally, five weeks) in STZ (45 mg/kg, i.p.)- induced DN in rats. After treatments motor function, oxidative stress biomarkers, ATP levels, expression of caspase 3 and UCP2 proteins were assessed by open-field, biochemical and ELISA methods and Western blot analysis. Dorsal root ganglion (DRG) neurons were histologically examined using H&E staining method.. ALA and/or CoQ10 treatment significantly (p < 0.05) attenuated DN - induced motor function deficiency by modulating distance moved and velocity. ALA and/or CoQ10 treatment dramatically suppressed DN - induced oxidative stress which was associated with decrease in LPO and ROS and increase in GSH and TAC in DRG neurons. ALA and/or CoQ10 was proved to prevent apoptosis and degeneration of DRG neurons, which appears to be mediated by regulating the expression of caspase 3 and UCP2 proteins, inducing ATP and improving DN-induced changes in DRG neurons. We found maximum effectiveness with ALA and CoQ10 combination on mentioned factors.. These results provide a possible basis of the underlying mechanism for application of ALA and CoQ10 combination in treatment of DN.

Topics: Administration, Oral; Animals; Apoptosis; Biomarkers; Blotting, Western; Caspase 3; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Ganglia, Spinal; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Thioctic Acid; Ubiquinone; Uncoupling Protein 2

The early onset of type 2 diabetes mellitus (DM), driven by increasing obesity, is associated with peripheral neuropathy. Here, we characterize diabetic neuropathic pain in New Zealand obese diabetic mice (NZO/HILtJ) as a polygenic model of obesity with type 2 diabetes and investigate the role of coenzyme Q10 (CoQ10) in the prevention and treatment of diabetic neuropathic pain. Since the overexpression of mitogen-activated protein kinase (MAPK), nuclear factor-κB proteins (NF-Kb), toll-like receptor 4 (TLR4) and downstream cytokines (such as CCL2, CXCL10) are considered important factors contributing to the development of neuropathic pain, the expression of these factors and the inhibitory effects of CoQ10 were evaluated. NZO/HILtJ mice spontaneously developed type 2 DM and increased body mass with diabetic neuropathic pain. CoQ10 treatment decreased pain hypersensitivity and long-term supplementation prevented the development of diabetic neuropathic pain but did not attenuate diabetes. Spinal cord, blood serum, liver tissue, and dorsal root ganglia (DRG) from diabetic mice demonstrated increased lipid peroxidation, which was decreased by CoQ10 treatment. The percentage of positive neurons of p65 (the activated marker of NF-KB) and MAPK in DRG were significantly higher in DM mice compared to controls. However, CoQ10 treatment significantly decreased p65 and MAPK positive neurons in the DRG of DM mice. RT-PCR demonstrated that elevated levels of mRNA of CCL2, CXCL10 or TLR4 in the spinal cord of DM mice decreased significantly when DM mice were treated with CoQ10.. This model may be useful in understanding the mechanisms of neuropathic pain in type 2 DM induced neuropathic pain and may facilitate preclinical testing of therapies. CoQ10 may decrease oxidative stress in the central and peripheral nervous system by acting as an anti-oxidant and free-radical scavenger. These results suggest that CoQ10 might be a reasonable preventative strategy for long-term use and using CoQ10 treatment may be a safe and effective long-term approach in the treatment of diabetic neuropathy.

Topics: Age Factors; Animals; Blood Glucose; Body Weight; Chemokine CCL2; Chemokine CXCL10; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Female; Gene Expression Regulation; Hyperalgesia; Lipid Peroxidation; Male; Mice; Pain Measurement; Pain Threshold; Recombinant Fusion Proteins; Toll-Like Receptor 4; Ubiquinone; Vitamins

Oxidative stress is a key factor implicated in the development of diabetic neuropathy. This study evaluates the prophylactic and antinociceptive effects of the antioxidant coenzyme Q10 (CoQ10) on diabetes-induced neuropathic pain in a diabetic mouse model.. Total 56 mice with type 1 diabetes induced by streptozotocin were used, 20 normal mice were used as control. Mechanical and thermal nociceptive behavioral assays were applied to evaluate diabetic neuropathic pain. Tissue lipid peroxidation, immunohistochemistry, reverse transcription, and polymerase chain reaction were used to evaluate the molecular mechanisms of CoQ10. Data are presented as mean ± SEM.. CoQ10 administration was associated with reduced loss of body weight compared with nontreated diabetic mice, without affecting blood glucose levels. Low dose and long-term administration of CoQ10 prevented the development of neuropathic pain. Treatment with CoQ10 produced a significant dose-dependent inhibition of mechanical allodynia and thermal hyperalgesia in diabetic mice. Dorsal root ganglia, sciatic nerve, and spinal cord tissues from diabetic mice demonstrated increased lipid peroxidation that was reduced by CoQ10 treatment. CoQ10 administration was also noted to reduce the proinflammatory factors in the peripheral and central nervous system.. The results of this study support the hypothesis that hyperglycemia induced neuronal oxidative damage and reactive inflammation may be pathogenic in diabetic neuropathic pain. CoQ10 may be protective by inhibiting oxidative stress and reducing inflammation by down-regulating proinflammatory factors. These results suggest that CoQ10 administration may represent a low-risk, high-reward strategy for preventing or treating diabetic neuropathy.

Topics: Analgesics; Animals; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Ubiquinone; Vitamins; Weight Loss

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Patients with diabetes can develop nerve problems at any time, but the longer a person has diabetes the greater the risk. This study aims to investigate diabetes- and coenzyme Q(10) (CoQ(10)) or alpha-lipoic acid (ALA) supplementation-induced changes in the conduction velocity (CV) distributions of rat sciatic nerve fibers. Sciatic nerve compound action potentials (CAPs) were recorded by suction electrode and CV distributions by the collision technique. Diabetes resulted in a significant increase in time to peak, rheobase and chronaxie values of these CAP waveforms, whereas the maximum depolarization, area, kinetics and CVs of both fast and slow nerve fiber groups were found to be decreased. Coenzyme Q(10) (CoQ(10)) supplementation was found to have some positive effect on the diabetes-induced alterations. CoQ(10) supplementation induced positive changes mainly in the area and fall-down phase of the kinetics of CAP waveforms, as well as rheobase, chronaxie and speed of the intermediately conducting groups ( approximately or equal to 40 m/s). alpha-Lipoic acid (ALA) supplementation did not produce statistically significant effects. This study has shown for the first time that diabetes induces a shift of actively contributing nerve fibers toward slower CVs, and supplementation with CoQ(10) not only stopped this shift but also tended to restore velocities toward those of the age-matched control group. In addition to its effects on mitochondrial alterations, these positive effects of CoQ10 on diabetic neuropathy can be attributed to its antioxidant activity.

Topics: Action Potentials; Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dietary Supplements; Injections, Intraperitoneal; Kinetics; Male; Neural Conduction; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Thioctic Acid; Ubiquinone

Topics: Adolescent; Adult; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Perception; Ubiquinone; Vibration