CoQ10 Levels Research Articles

Impaired mitochondrial quality control in fibromyalgia: Mechanisms involved in skeletal muscle alteration

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague–Dawley rats were injected with reserpine to induce FMS.These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells.

COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction

COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ10 levels, and reduced basal and maximal respiration in patients’ fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ10 (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

Idebenone ameliorates statin-induced myotoxicity in atherosclerotic ApoE−/− mice by reducing oxidative stress and improving mitochondrial function

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE−/− mice and whether idebenone could counteract it. After administering simvastatin to ApoE−/− mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

Health Patterns across Adulthood: An Age-Based Investigation of the Nutritional Status, Homocysteine, and CoQ10 of Bank Staff.

This study aimed to evaluate age-specific variations in the blood levels of micronutrients, homocysteine, and CoQ10, along with physical activity (PA) patterns, among 123 Austrian adult bankers in operational and frontline roles (mean age: 43 years; 50% female). Blood analysis was conducted to assess micronutrients and the serum concentrations of homocysteine and CoQ10. The micronutrient values in whole blood were compared to sex-specific reference ranges and categorized as below, within, or above them. The Global Physical Activity Questionnaire was utilized to assess PA patterns. Participants were classified as young adults (18-34 years), middle-aged adults (35-49 years), and older adults (50-64 years). Significant age-based differences were found in participants' mean homocysteine levels (p = 0.039) and homocysteine categories (p = 0.034), indicating an increasing prevalence of hyperhomocysteinemia with age. No significant difference between age categories was observed for sex, BMI, diet types, PA levels, sedentary behavior, and CoQ10 (p > 0.05). There was no significant age-based difference in the blood concentrations of most minerals and vitamins (p > 0.05), except for magnesium among females (p = 0.008) and copper among males (p = 0.042). The findings offer initial evidence of the age-related differences in the health status of adult bankers, providing insights for customized approaches to occupational health that support the importance of metabolic health and overall well-being across adulthood.

Gender Disparities in Health Biomarkers, Lifestyle Patterns, and Nutritional Status among Bank Staff: A Cross-Sectional Study.

Background and Objectives: Despite the importance of nutritional status and a healthy lifestyle in shaping overall well-being, little is known about examining gender-specific differences and trends in health, lifestyle, and nutritional status. The present study aimed to evaluate blood levels of micronutrients, homocysteine, and CoQ10, as well as physical activity (PA) levels and sedentary behavior, among a cohort of Austrian bank staff, with a particular focus on identifying gender differences as well as gender-specific nutritional deficiencies compared to the reference ranges. Materials and Methods: Following a cross-sectional study design, 123 Austrian bank staff (mean age: 43 years; 51% females) participated in this study. Blood samples were collected to evaluate participants' micronutrient status and serum levels of homocysteine and CoQ10. Whole-blood values of macronutrients were compared to gender-specific reference ranges and categorized into three groups: below, within, or over the range. The WHO's Global Physical Activity Questionnaire was used to assess PA levels and sedentary behaviors. Results: No significant difference between males and females was found for diet types, PA levels, sedentary time, homocysteine levels, or CoQ10 values (p > 0.05). A high PA level was reported by 64% of males and 58% of females. 71% of females and 56% of males were found to have a vitamin D deficiency. 63-98% of females and 72-97% of males showed normal blood levels for the remaining micronutrients, including potassium, calcium, magnesium, copper, iron, zinc, selenium, manganese, molybdenum, B6, B9, and B12. Conclusions: The findings highlight the necessity of implementing tailored strategies to foster healthy lifestyle behaviors, thereby enhancing the overall state of health, particularly in the context of occupational health.

The role of mitochondrial bioenergy and system glutathione in deficiency of Coenzyme Q and Complex I

Cytokine Coenzyme Q10 (CoQ10) is an insoluble coenzyme that is a component of the electron transport chain and is involved in oxidative phosphorylation in mitochondria. By a decrease in CoQ10, the energy requirements of the cell are not fully covered: cell division slows down, and the processes of tissue renewal and regeneration are disrupted. In our work, we used a model of mice CoQ9 Knockin (R239X). In homozygous mutant mice, a strong decrease in CoQ7 protein and the accumulation of dimethoxyubiquinone are observed. An impairment of hydrogen sulfide metabolism was previously identified as a significant pathomechanism of primary Coenzyme Q deficiency. The experimental results showed that the disruption of sulfide and glutathione metabolism in Coq9R239X mice is directly dependent on CoQ levels. Therefore, changes in dietary sulfur-containing amino acids do not alter sulfide metabolism and the glutathione system in Coq9R239X mice. As our experiments have shown, an increase in total glutathione is observed only in symptomatic brain tissue. It can be assumed that this is due to oxidative stress in the symptomatic brain tissue, which is often found with mitochondrial dysfunction.

Biallelic variants in the COQ4 gene caused hereditary spastic paraplegia predominant phenotype.

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in COQ4 have been reported to cause primary CoQ10 deficiency-7 (COQ10D7), which is a mitochondrial disease. We aimed to screened COQ4 variants in a cohort of HSP patients. A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants. In this study, five different COQ4 variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early-onset pure HSP caused by COQ4 variants. Functional studies in patient-derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure. Our findings revealed that bilateral variants in the COQ4 gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4-related disorders.

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.

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene

AbstractRecent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol in this process remains incompletely understood. In this work, we show that modulating cholesterol levels changes vulnerability of cells to ferroptosis. Cholesterol alters metabolic flux of the mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step in cholesterol biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation of Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), the branch point of cholesterol biosynthesis pathway, exhibits minimal effect on ferroptosis, simultaneous inhibition of both CoQ10 and squalene biosynthesis completely abrogates the effect of cholesterol. Mouse models of ischemia-reperfusion and doxorubicin induced hepatoxicity confirm the protective role of cholesterol in ferroptosis. Our study elucidates a potential role of ferroptosis in diseases related to dysregulation of cholesterol metabolism and suggests a possible therapeutic target that involves ferroptotic cell death.

Borderline hyperlipidemia preventive management with Berberine PL in asymptomatic prevention of early atherosclerosis.

The aim of this pilot, efficacy supplement registry was to use a supplementary management with berberine to control hyperlipidemia. The supplement Berberine (Berbevis™ as Sophy® tablets) was used to control lipids and to evaluate (as a natural, preventive management) the early evolution of subclinical atherosclerosis in subjects (otherwise healthy, not using drugs) with borderline hyperlipidemia. The registry involved two groups of subjects not using drugs for a total of 50 subjects and three months of supplementation. The registry groups using standard management (SM) or SM and supplement were resulted comparable. No side effects were observed during the three months of berberine supplementation. No tolerability problems were reported. All subjects managed with berberine completed the three-month registry. Compliance was >97% (% of correctly used tablets). Total cholesterol was significantly decreased with berberine (P<0.05) and HDL was significantly improved (P<0.5) with supplementation. Triglycerides decreased in the berberine groups (P<0.05) and the levels of CoQ10 remained within normal values in supplemented subjects. Oxidative stress - measured in Carr units - was significantly decreased with berberine (P<0.05). Routine blood tests remained within normal values during the registry. Body weight was significantly more decreased (P<0.05) with berberine in comparison with standard management. The fat proportion also decreased (P<0.05) with berberine supplementation and the abdominal fat thickness (in the peri-umbilical area) was significantly decreased after berberine supplementation (P<0.05). This pilot registry indicates that berberine administration is effective in reducing lipids (decreasing weight, fat percentage and abdominal fat) in otherwise healthy subjects not using drugs. A longer study, with more advanced hyperlipidemic subjects is suggested. Predictive analytics according to Siegel suggests that a six-month study with 60 patients, in more advanced hyperlipidemic, also evaluating the intima-media thickness for the analysis of vascular benefits, may produce a stronger evaluation for this product.

The influence of atorvastatin, amlodipine and ethoxidol on ubiquinol and ubiquinone endogenous plasma concentrations in patients with chronic heart failure.

Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain almost uninvestigated. The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF. The study included 62 patients with CHF divided into four groups depending on the prescribed therapy. For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLC-MS/MS was used. It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10 (+20.2Δ%). Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing pharmacotherapy.

Biosynthesis, Deficiency, and Supplementation of Coenzyme Q.

Originally identified as a key component of the mitochondrial respiratory chain, Coenzyme Q (CoQ or CoQ10 for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane types. Cells rely on endogenous CoQ biosynthesis, and defects in this still-not-completely understood pathway result in primary CoQ deficiencies, a group of conditions biochemically characterised by decreased tissue CoQ levels, which in turn are linked to functional defects. Secondary CoQ deficiencies may result from a wide variety of cellular dysfunctions not directly linked to primary synthesis. In this article, we review the current knowledge on CoQ biosynthesis, the defects leading to diminished CoQ10 levels in human tissues and their associated clinical manifestations.

Higher levels of the lipophilic antioxidants coenzyme Q10 and vitamin E in long-lived termite queens than in short-lived workers.

Termite queens and kings live longer than nonreproductive workers. Several molecular mechanisms contributing to their long lifespan have been investigated; however, the underlying biochemical explanation remains unclear. Coenzyme Q (CoQ), a component of the mitochondrial electron transport chain, plays an essential role in the lipophilic antioxidant defense system. Its beneficial effects on health and longevity have been well studied in several organisms. Herein, we demonstrated that long-lived termite queens have significantly higher levels of the lipophilic antioxidant CoQ10 than workers. Liquid chromatography analysis revealed that the levels of the reduced form of CoQ10 were 4 fold higher in the queen's body than in the worker's body. In addition, queens showed 7 fold higher levels of vitamin E, which plays a role in antilipid peroxidation along with CoQ, than workers. Furthermore, the oral administration of CoQ10 to termites increased the CoQ10 redox state in the body and their survival rate under oxidative stress. These findings suggest that CoQ10 acts as an efficient lipophilic antioxidant along with vitamin E in long-lived termite queens. This study provides essential biochemical and evolutionary insights into the relationship between CoQ10 concentrations and termite lifespan extension.

Traumatic Brain Injury Alters Cerebral Concentrations and Redox States of Coenzymes Q9 and Q10 in the Rat.

To date, there is no information on the effect of TBI on the changes in brain CoQ levels and possible variations in its redox state. In this study, we induced graded TBIs (mild TBI, mTBI and severe TBI, sTBI) in male rats, using the weight-drop closed-head impact acceleration model of trauma. At 7 days post-injury, CoQ9, CoQ10 and α-tocopherol were measured by HPLC in brain extracts of the injured rats, as well as in those of a group of control sham-operated rats. In the controls, about the 69% of total CoQ was in the form of CoQ9 and the oxidized/reduced ratios of CoQ9 and CoQ10 were, respectively, 1.05 ± 0.07 and 1.42 ± 0.17. No significant changes in these values were observed in rats experiencing mTBI. Conversely, in the brains of sTBI-injured animals, an increase in reduced and a decrease in oxidized CoQ9 produced an oxidized/reduced ratio of 0.81 ± 0.1 (p < 0.001 compared with both controls and mTBI). A concomitant decrease in both reduced and oxidized CoQ10 generated a corresponding oxidized/reduced ratio of 1.38 ± 0.23 (p < 0.001 compared with both controls and mTBI). An overall decrease in the concentration of the total CoQ pool was also found in sTBI-injured rats (p < 0.001 compared with both controls and mTBI). Concerning α-tocopherol, whilst no differences compared with the controls were found in mTBI animals, a significant decrease was observed in rats experiencing sTBI (p < 0.01 compared with both controls and mTBI). Besides suggesting potentially different functions and intracellular distributions of CoQ9 and CoQ10 in rat brain mitochondria, these results demonstrate, for the first time to the best of knowledge, that sTBI alters the levels and redox states of CoQ9 and CoQ10, thus adding a new explanation to the mitochondrial impairment affecting ETC, OXPHOS, energy supply and antioxidant defenses following sTBI.

L-shaped association between dietary coenzyme Q10 intake and high-sensitivity C-reactive protein in Chinese adults: a national cross-sectional study.

Background: Chronic inflammation contributes to the occurrence and progression of many diseases. Most previous clinical studies have explored the effect of high-dose CoQ10 supplements on inflammation. Food is another important source of CoQ10, but the relationship between the intake of CoQ10 from dietary sources and inflammation was unknown. We aimed to explore the dose-response association between the intake of dietary-derived CoQ10 and inflammation-related biomarkers. Methods: Seven thousand nine hundred and fifty-three Chinese adults from the China Health and Nutrition Survey (CHNS) were the subjects of this cross-sectional investigation. Dietary CoQ10 intake was assessed using dietary information from three days. High-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBC) were assessed using fasting venous blood. Results: In an adjusted linear regression model, CoQ10 consumption from dietary sources was inversely associated with hsCRP, with effect sizes in each group: Q2 (β = -0.85 mg L-1, 95% CI: -1.43 to -0.28 mg L-1, P = 0.004), Q3 (β = -0.70 mg L-1, 95% CI: -1.28 to -0.12 mg L-1, P = 0.017), and Q4 (β = -0.79 mg L-1, 95% CI: -1.39 to -0.19 mg L-1, P = 0.010). Moreover, restricted cubic splines (RCS) revealed a non-linear L-shaped association between dietary-derived CoQ10 consumption and hsCRP (Pnonlinear < 0.001). According to subgroup analyses, these relationships were more significant in males, or >45 years old (Ptrend < 0.05). Nevertheless, no significant relationship was found between dietary-derived CoQ10 intake and WBC. Conclusions: These findings suggested a significant negative association between dietary-derived CoQ10 and hsCRP levels.

The effect of squalene on cellular energy and inflammation in type 2 diabetes patients

Background: Squalene is a 30-carbon ring hydrocarbon in the triterpene class. Squalene as a bioactive compound has been shown to have several health benefits specifically in the reduction of diabetic symptoms, including anti-inflammatory effects.Objective: The purpose of the study was to examine effect of squalene on specific parameters regarding energy production and inflammation in those with type 2 diabetes mellitus. These parameters included ATP, NAD/NADH, CoQ10, NFκB, IκB-alpha, IκK-alpha, and IκK-beta.Methods: 150 volunteers were selected for this study split into 5 groups. Group 1 contained 30 healthy participants and served as the control. The remaining 120 participants were split into 4 groups containing 30 volunteers each. All the participants in groups 2, 3, 4, and 5 have type 2 diabetes mellitus. Group 2 did not receive any squalene while group 3, group 4, and group 5 all received an oral supplementation of squalene at 200 mg/day, 400 mg/day and 600 mg/day respectively. Participants were prescribed to take the oral supplementation of squalene for a total of 84 days. Blood samples were taken on days 1, 14, 28, 56, and 84 in five time periods. For all participants ATP, NAD/NADH, CoQ10, NFκB, IκB-α, IκK-α and IκK-β levels of all groups were evaluated.Results: Throughout the 84 days there was a statistically significant difference when comparing the healthy group and the diabetic groups in reducing ATP, NAD/NADH and CoQ10 (P &lt; 0.05) and increasing NFκB, IκB-α, IκK-α and IκK-β (P &lt; 0.05). When compared, participants in groups 3, 4, and 5 also showed a statistically significant in the changes of ATP, NFκB, IκB-α, IκK-α and IκK-β levels.Conclusions: Squalene as a bioactive compound can play an important role in reducing inflammatory mediators and increases energy production.Keywords: squalene, diabetes mellitus, ATP production, NAD/NADH, Reactive oxygen species (ROS), CoQ10, NFκB, IkB-α, IκK-α, IκK-β

The effect of squalene on cellular energy and inflammation in type 2 diabetes patients

Background: Squalene is a 30-carbon ring hydrocarbon in the triterpene class. Squalene as a bioactive compound has been shown to have several health benefits specifically in the reduction of diabetic symptoms, including anti-inflammatory effects.Objective: The purpose of the study was to examine effect of squalene on specific parameters regarding energy production and inflammation in those with type 2 diabetes mellitus. These parameters included ATP, NAD/NADH, CoQ10, NFκB, IκB-alpha, IκK-alpha, and IκK-beta.Methods: 150 volunteers were selected for this study split into 5 groups. Group 1 contained 30 healthy participants and served as the control. The remaining 120 participants were split into 4 groups containing 30 volunteers each. All the participants in groups 2, 3, 4, and 5 have type 2 diabetes mellitus. Group 2 did not receive any squalene while group 3, group 4, and group 5 all received an oral supplementation of squalene at 200 mg/day, 400 mg/day and 600 mg/day respectively. Participants were prescribed to take the oral supplementation of squalene for a total of 84 days. Blood samples were taken on days 1, 14, 28, 56, and 84 in five time periods. For all participants ATP, NAD/NADH, CoQ10, NFκB, IκB-α, IκK-α and IκK-β levels of all groups were evaluated.Results: Throughout the 84 days there was a statistically significant difference when comparing the healthy group and the diabetic groups in reducing ATP, NAD/NADH and CoQ10 (P &lt; 0.05) and increasing NFκB, IκB-α, IκK-α and IκK-β (P &lt; 0.05). When compared, participants in groups 3, 4, and 5 also showed a statistically significant in the changes of ATP, NFκB, IκB-α, IκK-α and IκK-β levels.Conclusions: Squalene as a bioactive compound can play an important role in reducing inflammatory mediators and increases energy production.Keywords: squalene, diabetes mellitus, ATP production, NAD/NADH, Reactive oxygen species (ROS), CoQ10, NFκB, IkB-α, IκK-α, IκK-β

Reduced platelet mitochondrial respiration and oxidative phosphorylation in patients with post COVID-19 syndrome are regenerated after spa rehabilitation and targeted ubiquinol therapy.

European Association of Spa Rehabilitation recommend spa rehabilitation for patients with post COVID-19 syndrome (post C-19). We studied effects of special mountain spa rehabilitation program and its combination with ubiquinol (reduced form of coenzyme Q10-CoQ10) supplementation on pulmonary function, clinical symptoms, endogenous CoQ10 levels, and platelet mitochondrial bioenergetics of patients with post C-19. 36 patients with post C-19 enrolled for rehabilitation in mountain spa resort and 15 healthy volunteers representing the control group were included in this study. 14 patients with post C-19 (MR group) were on mountain spa rehabilitation lasting 16-18days, 22 patients (MRQ group) were supplemented with ubiquinol (2 × 100mg/day) during the rehabilitation and additional 12-14 days at home. Clinical symptoms and functional capacity of the lungs were determined in the patients before and after the spa rehabilitation program. Platelet bioenergetics by high-resolution respirometry, plasma TBARS concentration, and CoQ10 concentration in blood, plasma and platelets were evaluated before and after the spa rehabilitation program, and in 8 patients of MRQ group also after additional 12-14 days of CoQ10 supplementation. Pulmonary function and clinical symptoms improved after the rehabilitation program in both groups, 51.8% of symptoms disappeared in the MR group and 62.8% in the MRQ group. Platelet mitochondrial Complex I (CI)-linked oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity were markedly reduced in both groups of patients. After the rehabilitation program the improvement of these parameters was significant in the MRQ group and moderate in the MR group. CI-linked OXPHOS and ET capacity increased further after additional 12-14 days of CoQ10 supplementation. CoQ10 concentration in platelets, blood and plasma markedly raised after the spa rehabilitation with ubiquinol supplementation, not in non-supplemented group. In the MRQ group all parameters of platelet mitochondrial respiration correlated with CoQ10 concentration in platelets, and the increase in CI-linked OXPHOS and ET capacity correlated with the increase of CoQ10 concentration in platelets. Our data show a significant role of supplemented ubiquinol in accelerating the recovery of mitochondrial health in patients with post C-19. Mountain spa rehabilitation with coenzyme Q10 supplementation could be recommended to patients with post C-19. This study was registered as a clinical trial: ClinicalTrials.gov ID: NCT05178225.

CoQ10 and Resveratrol Effects to Ameliorate Aged-Related Mitochondrial Dysfunctions.

Mitochondria participate in the maintenance of cellular homeostasis. Firstly, mitochondria regulate energy metabolism through oxidative phosphorylation. In addition, they are involved in cell fate decisions by activating the apoptotic intrinsic pathway. Finally, they work as intracellular signaling hubs as a result of their tight regulation of ion and metabolite concentrations and other critical signaling molecules such as ROS. Aging is a multifactorial process triggered by impairments in different cellular components. Among the various molecular pathways involved, mitochondria are key regulators of longevity. Indeed, mitochondrial deterioration is a critical signature of the aging process. In this scenario, we will focus specifically on the age-related decrease in CoQ levels, an essential component of the electron transport chain (ETC) and an antioxidant, and how CoQ supplementation could benefit the aging process. Generally, any treatment that improves and sustains mitochondrial functionality is a good candidate to counteract age-related mitochondrial dysfunctions. In recent years, heightened attention has been given to natural compounds that modulate mitochondrial function. One of the most famous is resveratrol due to its ability to increase mitochondrial biogenesis and work as an antioxidant agent. This review will discuss recent clinical trials and meta-analyses based on resveratrol and CoQ supplementation, focusing on how these compounds could improve mitochondrial functionality during aging.

The Effect of Coenzyme Q10 as a Part of Standard Therapy on Plasma Concentrations of Ubiquinol, Ubiquinone, Total CoQ10 and its Redox State in Patients with Ischemic Heart Disease.

Despite CoQ10 being a powerful antioxidant and its redox state that may characterize the body's antioxidant system, the latter remains unstudied in patients with cardiovascular diseases. This prospective case-control study aimed to investigate the concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with ischemic heart disease (IHD) and arterial hypertension (AH) during standard therapy and with the additional prescription of CoQ10. The study included 54 healthy individuals and 26 patients, who were divided into a control group receiving standard therapy and a test group receiving CoQ10 in addition to standard therapy. Quantitative determination of COQ10, ubiquinone and ubiquinol was carried out by HPLC-MS/MS. It was found that the CoQ10 level in patients was significantly lower than in healthy individuals (on average -32Δ%). In the test group, after treatment, the concentrations of ubiquinol (+53 Δ%), ubiquinone (-28 Δ%), total CoQ10 (+27 Δ%) and redox state (+112 Δ%) were significantly different from the baseline, while in the control group no significant differences were noticed. In the test group after treatment, the levels of total CoQ10 (+25 Δ%), ubiquinol (+43 Δ%), and redox state (+86 Δ%) were statistically significantly higher than in the control group and total CoQ10 concentration did not significantly differ from that in healthy individuals (-12 Δ%). The additional prescription of CoQ10 for patients with IHD significantly increases the level of total CoQ10, which leads to the increase of body antioxidant potential.