CoQ10, Hair, Nail, and Skin, Arterial Protection, Macular Degeneration, and ToxinsFebruary 2016
By Life Extension
Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and reversal of ATP synthase activity: implications for pathogenesis and treatment.
Disorders of coenzyme Q(10) (CoQ(10)) biosynthesis represent the most treatable subgroup of mitochondrial diseases. Neurological involvement is frequently observed in CoQ(10) deficiency, typically presenting as cerebellar ataxia and/or seizures. The aetiology of the neurological presentation of CoQ(10) deficiency has yet to be fully elucidated and therefore in order to investigate these phenomena we have established a neuronal cell model of CoQ(10) deficiency by treatment of neuronal SH-SY5Y cell line with para-aminobenzoic acid (PABA). PABA is a competitive inhibitor of the CoQ(10) biosynthetic pathway enzyme, COQ2. PABA treatment (1 mM) resulted in a 54 % decrease (46 % residual CoQ(10)) decrease in neuronal CoQ(10) status (p < 0.01). Reduction of neuronal CoQ(10) status was accompanied by a progressive decrease in mitochondrial respiratory chain enzyme activities, with a 67.5% decrease in cellular ATP production at 46 % residual CoQ(10). Mitochondrial oxidative stress increased four-fold at 77% and 46% residual CoQ(10). A 40% increase in mitochondrial membrane potential was detected at 46 % residual CoQ(10) with depolarisation following oligomycin treatment suggesting a reversal of complex V activity. This neuronal cell model provides insights into the effects of CoQ(10) deficiency on neuronal mitochondrial function and oxidative stress, and will be an important tool to evaluate candidate therapies for neurological conditions associated with CoQ(10) deficiency.
J Inherit Metab Dis. 2013 Jan;36(1):63-73
Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient.
Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that mitochondrial dysfunction and oxidative stress may have a role in the pathophysiology of FM. Coenzyme Q10 (CoQ10) is an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant. Low CoQ10 levels have been detected in patients with FM, and a significant decrease of clinical symptoms has been reported after oral CoQ10 supplementation. In this report, we show the effect of CoQ10 treatment on clinical symptoms, blood mononuclear cells, and mitochondrial and oxidative stress markers from a woman with FM. After CoQ10 treatment, the patient reported a significant improvement of clinical symptoms. At the cellular level, CoQ10 treatment restored mitochondrial dysfunction and the mtDNA copy number, decreased oxidative stress, and increased mitochondrial biogenesis. Our results suggest that CoQ10 could be an alternative therapeutic approach for FM.
Nutrition. 2012 Nov-Dec;28(11-12):1200-3
Effect of lifelong coenzyme Q10 supplementation on age-related oxidative stress and mitochondrial function in liver and skeletal muscle of rats fed on a polyunsaturated fatty acid (PUFA)-rich diet.
This study investigates aging-related changes in lipid peroxidation and functionality in liver and skeletal-muscle mitochondria in rats fed a diet rich in polyunsaturated fatty acids (PUFA), depending on supplementation or not with coenzyme Q(10) (CoQ(10)). Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with CoQ(10). At 6 and 24 months mitochondria were analyzed for fatty acid profile; hydroperoxides; alpha-tocopherol; CoQ(9;) CoQ(10;) cytochromes b, c+c(1), and a+a(3) contents; cytochrome c oxidase activity; and catalase activity in cytosol. Results of this study showed for the supplemented group an age-associated decrease in the peroxidizability index, an increase in catalase activity in skeletal muscle, and modulation of the aging-related changes in different mitochondrial electron-transport-chain components in skeletal muscle. These findings provide mechanisms to explain the effect of CoQ(10) in extending the life span of animals fed a PUFA-rich diet.
J Gerontol A Biol Sci Med Sci. 2007 Nov;62(11):1211-8
Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure.
There are obviously several causes of myocardial dysfunction but energy deficiency of the myocytes may play a significant role and probably is a common mechanism during the progression of myocardial failure. Theoretically, a poor utilization efficiency of oxygen may be due to exhaustion of the myocardial stores of bioenergetics. In this report the authors review their biochemical results from measurements of coenzyme Q10 (CoQ10) levels in blood and human endomyocardial biopsies using an HPLC method from patients with suspected myocardial disease (n = 45). The levels of CoQ10, which has a key role in the respiratory chain and the synthesis of ATP, was found to be significantly decreased in various groups of patients with myocardial failure (dilated and restrictive cardiomyopathy and alcoholic heart disease) as compared to “normal” myocardium (0.42 +/- 0.04 micrograms/mg dry weight). The deficiency of CoQ10 was more pronounced with increasing symptoms; e.g. patients with dilated cardiomyopathy in NYHA Classes III and IV had lower tissue CoQ10 content than those of Classes I and II (0.28 +/- 0.04 vs. 0.37 +/- 0.06 micrograms/mg, p less than 0.001). Nearly two thirds of a series of 40 patients in severe heart failure (Classes III and IV) treated with CoQ10, 100 mg daily, in an open, controlled design showed subjective and objective improvement. Clinical responders were 69% and 43% of patients with cardiomyopathy and ischaemic heart disease, respectively. The results suggest that CoQ10 is a novel and effective breakthrough in heart-failure therapy and it appears safe, as no adverse reactions were registered. The through in heart-failure therapy and it appears safe, as no adverse reactions were registered.
Int J Tissue React. 1990;12(3):155-62
Coenzyme Q, oxidative stress, and aging.
Coenzyme Q (CoQ) has three well-characterized functions in mitochondria, namely (i) transfer of reducing equivalents in the electron transport chain, (ii) generation of superoxide anion radical, O2*-, and (iii) quenching of free radicals. The main purpose of this review is to discuss the effects of CoQ10 intake for relatively prolonged periods on mitochondrial respiratory capacity, indicators of oxidative stress, and life span of animals, in context of the broader issue of whether or not the overall progression of the aging process can be modified by CoQ10 administration. Comparative studies on different mammalian species have indicated that the rate of mitochondrial superoxide anion radical generation is directly correlated with mitochondrial CoQ9 content and inversely related to amounts of CoQ10, particularly the CoQ10 bound to mitochondrial membrane proteins. Contrary to the historical view, dietary supplementation of mice and rats with CoQ10 has been demonstrated to augment the endogenous CoQ content (CoQ9 + CoQ10) in mitochondria and homogenates of various tissues, albeit to varying extent. Ingestion of CoQ10 results in the elevation of endogenous CoQ9, the predominant homologue in mice and rats. In our studies, there was no indication of a discernable effect of CoQ10 intake reflecting enhancement of mitochondrial respiratory activity, antioxidant capacity and pro-oxidant potentiation or prolongation of life span. The possibility that CoQ10 intake affects certain other biological functions by as yet unelucidated mechanisms cannot be ruled out as CoQ has been shown to broadly alter gene expression in mice.
Mitochondrion. 2007 Jun;7 Suppl:S103-11
Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.
BACKGROUND: Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking. METHODS: A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention. The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan-Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied. RESULTS: During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P=0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P=0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P=0.03). CONCLUSION: Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.
Int J Cardiol. 2013 Sep 1;167(5):1860-6
Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet.
This study investigates the usefulness of a long-term supplementation with coenzyme Q(10) in rats from the point of view of lifespan, DNA double-strand breaks and to assess whether this supplementation might attenuate oxidative alterations related to PUFA-rich diets, which would allow to preserve beneficial aspects of PUFA on health avoiding their deleterious aspects. Supplemented animals showed higher concentration of coenzyme Q(10) in liver mitochondria, lower levels of DNA double-strand breaks in peripheral blood lymphocytes. Animals supplemented on coenzyme Q reached a significantly higher mean life span (11,7% higher, i.e. 2,5 months) and a significantly higher maximum life span (24% higher, i.e. 6 months) than non-supplemented animals. These results suggest that a long-term supplementation with a small dosage of coenzyme Q(10) might represent a good anti-aging therapy in rats fed on a PUFA-based diet.
Exp Gerontol. 2004 Feb;39(2):189-94