Coenzyme Q and stroke prevention -
Although some CoQ10 is obtained from the diet, most is manufactured within the liver, the capacity for which declines with age. These data therefore provide a rationale for the importance of CoQ10 in cardiovascular function, and its dietary supplementation.
The objective of this article is therefore to provide a brief overview of the pharmacology of CoQ10, and its role in the prevention and treatment of cardiovascular disease. Coenzyme Q10 CoQ10 is a naturally occurring vitamin-like substance, first characterised in by Professor Fred Crane at the University of Wisconsin.
CoQ10 is also known as ubiquinone, because of its ubiquitous distribution in all body tissues. Coenzyme quinones occur in several chemical forms, with CoQ10 being the only form found in human tissues figure 1.
CoQ10 plays a vital role in the biochemical mechanism supplying cells with energy, acting in conjunction with enzymes hence the name CoQ10 to convert sugars and fat into energy. The action of CoQ10 is of particular importance in tissues with a high energy requirement, such as cardiac muscle.
CoQ10 is also important as an antioxidant within the body. The objective of this article is, therefore, to provide an overview of the pharmacology of CoQ10, and its role in the prevention and treatment of cardiovascular disease. CoQ10 is an essential cofactor of enzymes involved in the process that supplies all cells with energy cellular respiration.
Specifically, CoQ10 is an intermediate in the electron transport system that generates energy in the chemical form of adenosine triphosphate ATP , shuttling electrons from complexes I and II to complex III of the mitochondrial respiratory chain figure 2.
Tissues with a high energy requirement, especially the heart and skeletal muscles, contain higher numbers of mitochondria within their cells, and are particularly reliant on maintaining adequate tissue CoQ10 levels for normal functioning. CoQ10 occurs in cells in two closely related forms, oxidised ubiquinone and reduced ubiquinol figure 1.
The interconversion between these two forms is essential for the normal functioning of CoQ10 figure 2. CoQ10 is important within the body as a major fat-soluble antioxidant, protecting cell membranes particularly those of mitochondria from the damaging effects of free radicals.
CoQ10 is the only lipid soluble antioxidant produced within the body, and for which there is enzymatic ability for its continual regeneration. When ubiquinone acts as a coenzyme for mitochondrial ATP production, it is reduced to ubiquinol; this, in turn, is readily oxidised back to ubiquinone via its interaction with free radicals continually generated as by-products of oxidative phosphorylation figure 2.
Most recently, gene expression profiling has shown that CoQ10 influences the expression of several hundred genes. In particular, studies in cell culture, animal models and human subjects have shown that CoQ10 can directly regulate gene expression relevant to inflammation and fat metabolism.
Although some CoQ10 approx. It has been estimated that the population of Denmark, for example, obtain only 3—5 mg of CoQ10 per day from their normal dietary sources. It is of note that CoQ10 shares a common synthetic pathway with cholesterol figure 3.
As people age, the capacity of the body to produce CoQ10 decreases; optimal production occurs around the mid-twenties, with a continual decrease thereafter figure 4. CoQ10 levels can also be depleted by intense exercise, certain types of prescription medicines, and by illness.
Dietary supplementation with CoQ10, therefore, provides a mechanism to maintain adequate levels within the body. However, it is important to note that the pharmaceutical quality and bioavailability of CoQ10 supplements from different manufacturers may vary widely see following section.
Most cases of deficiency result from factors such as ageing or the effects of drugs such as statins secondary deficiency.
Bioavailability is defined as the proportion of an orally administered substance that reaches the systemic circulation. CoQ10 is a fat-soluble substance. Following emulsification and micelle formation, CoQ10 is absorbed by mucosal cells of the small intestine, as for any other dietary fat.
CoQ10 is then transported via chylomicrons by the lymphatic system to the liver, where it is released into the blood in association with lipoproteins very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], high-density lipoprotein [HDL].
For dietary supplements, oil-based formulations show enhanced bioavailability. Absorption of CoQ10 is non-linear, with increasing doses absorbed to a decreasing degree. Higher daily doses of CoQ10 are, therefore, best taken in mg split doses.
When first manufactured, CoQ10 is produced in a crystalline form that cannot be absorbed from the digestive tract. In CoQ10 supplements, this crystalline form must be further treated to break it down into individual molecules to enable absorption figure 5 , and most importantly, the crystals should not re-form within the capsule.
Supplement manufacturers vary in their ability to fulfil these requirements. For ubiquinone, maximum plasma concentration is reached after approximately six hours, and the half-life is approximately 33 hours, resulting in the time to pharmacological steady state being rather prolonged 1—2 weeks.
Normal plasma levels are in the range 0. Supplementation with mg CoQ10 twice daily has been reported to raise blood levels from 0. Early studies on cardiovascular disease were hampered by a shortage of supply of CoQ10, poor absorption of CoQ10 in its original crystalline form, and insufficient daily dosage 30—60 mg.
However, subsequent studies demonstrated supplementation with CoQ10 had significant benefits in cardiovascular disease, particularly heart failure, as detailed in the following sections.
CoQ10 is available as a licensed medicine within the EU as Myoqinon ® ; however, in the UK, Myoqinon ® is classified as an unlicensed medicine.
Work on CoQ10 and CHF was pioneered in the s by Per Langsjoen, Karl Folkers and Gian Paolo Littarru. They established that patients with CHF had reduced levels of CoQ10 in blood and cardiac tissue, with the degree of deficiency correlating with the severity of heart failure.
They further carried out the first clinical trial of CoQ10 in CHF, establishing long-term efficacy and safety in more than patients over a period of six years.
Most subsequent clinical studies of whichever type have described significant clinical benefit following supplementation with CoQ For example, 24 out of 28 randomised-controlled studies of CoQ10 supplementation in heart failure over a year period to reported positive outcomes.
Some of these studies have been criticised as being underpowered; however, such criticism cannot be applied, for example, to the study by Morisco et al. Some studies, such as that by Watson et al. To date there have been three meta-analyses relating to CoQ10 supplementation and CHF, all of which identified significant improvement in parameters such as ejection fraction.
Most clinical trial studies to determine the efficacy and safety of CoQ10 have used the ubiquinone form. The Q-SYMBIO study is the first randomised-controlled trial adequately powered and of sufficient duration to determine the efficacy of CoQ10 supplementation on morbidity and mortality risk in heart failure patients.
Q-SYMBIO was a long-term two-year , randomised, double-blind, placebo-controlled, multi-centre trial in patients with chronic heart failure NYHA class III or IV.
Assessment included clinical examination, echocardiography and pro-brain natriuretic peptide pro-BNP biochemical marker status. The primary long-term end point was time to first major adverse cardiovascular event MACE , which included unplanned hospitalisation due to worsening heart failure and cardiovascular death.
There was no significant difference in adverse events between the CoQ10 treated and placebo groups over the duration of the study. It should be noted that in short-term assessment at 16 weeks , there was no significant improvement in patient symptoms or functional status following CoQ10 supplementation compared with placebo.
It is of relevance to compare the outcome of the Q-SYMBIO study with that of the recently published PARADIGM Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial study.
CoQ10 may protect against atherosclerosis by inhibiting the oxidation of LDL-cholesterol. Despite a relatively low level of CoQ10 0. In addition to protecting LDL-cholesterol from oxidation, CoQ10 may also inhibit its synthesis.
Supplementation with CoQ10 induces characteristic gene expression patterns, which are translated into reduced LDL-cholesterol levels.
In a double-blind, randomised-controlled trial, Singh et al. This was an additional benefit to optimal lipid-lowering therapy provided by lovastatin administration. Similarly, Lee et al.
A meta-analysis carried out by Gao et al. The primary action of CoQ10 in hypertension is vasodilation, via direct effects on the endothelium and vascular smooth muscle.
Hypertension is associated with an increase in oxidative stress, manifest by increased production of superoxide radicals within blood vessels; these in turn react with endothelial nitric oxide to reduce the availability of this chemical messenger, thereby reducing the ability of the endothelium to induce nitric oxide-mediated relaxation of vascular smooth muscle, and hence vasoconstriction and increased blood pressure.
Several clinical studies have reported that supplementation with CoQ10 can significantly reduce blood pressure in hypertensive patients, without adverse effects.
Thus, a randomised-controlled, double-blind trial of 60 patients receiving conventional antihypertensive medication was carried out by Singh et al.
A randomised-controlled, double-blind trial of patients with isolated systolic hypertension was reported by Burke et al. A meta-analysis by Rosenfeldt et al. CoQ10 appeared effective as an antihypertensive agent either alone, or in combination with conventional antihypertensive drugs.
The KiSel study was carried out on the elderly population of the Kinda region of Stockholm, who were given supplemental selenium and CoQ10 hence KiSel A five-year, prospective, randomised, double-blind, placebo-controlled trial in individuals aged 70—88 years.
Participants were assigned µg selenium SelenoPrecise and mg CoQ10 Bio-Quinone Q10 daily, or placebo. Assessment included clinical examination, echocardiography and the biochemical marker of heart tissue stress, N-terminal pro-BNP NT-proBNP.
In addition, cardiac function assessed by electrocardiogram ECG and NT-proBNP levels were significantly improved in the treatment group compared with placebo. Statins are potent inhibitors of 3-hydroxymethylglutaryl coenzyme A HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis.
Adverse effects, particularly skeletal muscle pain and weakness, may occur in a significant number of patients; variation from mild myalgia to rhabdomyolysis has been rationalised in terms of genetic susceptibility.
The inhibitory effect of statins on cholesterol biosynthesis is not selective, resulting in the inhibition of several non-sterol isoprenoid end products, including CoQ Statins also inhibit the synthesis of vitamin K2, a cofactor for matrix Gla-protein activation, which, in turn, protects arteries from calcification.
Statins inhibit the synthesis of several selenoproteins, including thioreductase redoxin 1, which plays a key role in the interconversion of oxidised and reduced forms of CoQ In this regard, a randomised-controlled trial by Caso et al.
More recently, a number of randomised-controlled trials, each comprising approximately 50—60 patients receiving statin therapy, have similarly reported significant benefits following CoQ10 supplementation. Thus Fedacko et al. Pourmoghaddas et al.
Skarlovnik et al. However, not all studies have found significant symptomatic benefit following CoQ10 supplementation.
In contrast to the above studies, Bookstaver et al. Similarly, Bogsrud et al. This disparity in outcomes between different studies has been ascribed to differences in supplement bioavailability, and methodological differences in pain assessment.
The supply of CoQ10 via National Health Service NHS prescription for statin-related myalgia is currently not recommended.
In Canada, the packaging of statin drugs is required to include a so-called black box warning, recommending the drugs be taken in conjunction with CoQ The safety of CoQ10 has been assessed by Hidaka et al.
Very rarely, individuals may experience mild gastrointestinal disturbance. There are no known toxic effects, and CoQ10 cannot be overdosed.
In addition, Yamaguchi et al. CoQ10 is not recommended for pregnant or lactating women, in whom the effects of CoQ10 have not been extensively studied. The safety of CoQ10 has been confirmed in more than randomised-controlled trials, on a wide range of disorders. The product Myoqinon ® mg CoQ10 capsules has a marketing authorisation within the EU for the adjuvant treatment of CHF.
As part of the licensing procedure, periodic safety update reports PSURs have to be submitted every three years. In a sample PSUR, over a three-year period the supply of 1. CoQ10 has at least three functions of relevance to the cardiovascular system, namely its role in cellular energy production, its role as an antioxidant, and its role in gene expression.
These functions, in turn, provide the basis for the plausibility of action of CoQ10 in the management of CHF, atherosclerosis and hypertension, as outlined above. Because CoQ10 is classed as a nutritional supplement, there is a common misconception that there is little or no evidence to support its use in the management of cardiovascular disease.
To date there are more than articles published in the peer-reviewed medical literature listed on the Medline database, including more than 60 double-blind, randomised, placebo-controlled clinical trials.
Of course, not all of these articles have reported positive findings with regard to CoQ10 and cardiovascular disease, but the balance of published evidence supports a beneficial role for CoQ10 in the management of cardiovascular disease, as detailed in this review.
There are presently more than randomised-controlled, clinical trials listed on Medline, in which CoQ10 has been investigated in a wide range of disorders. None of these studies have reported significant adverse effects arising from CoQ10 supplementation.
To be effective, CoQ10 needs to be given in sufficient dosage and for sufficient duration. The author acts as a medical adviser to Pharma Nord UK Ltd, a manufacturer of CoQ10 products.
Schmelzer C, Lindner I, Rimbach G et al. Function of coenzyme Q10 in inflammation and gene expression. Biofactors ; 32 — Yubero-Serrano EM, Gonzalez-Guarelia L, Rangel O et al. Mediterranean diet supplemented with coenzyme Q10 modifies the expression of pro-inflammatory and endoplasmic reticulum stress-related genes in elderly men and women.
J Gerontol A Biol Sci Med Sci ; 67 :3— Lee BJ, Huang YC, Chen SJ et al. Effects of coenzyme Q10 supplementation on inflammatory markers C-reactive protein, IL-6, homocysteine in patients with coronary artery disease.
Nutrition ; 28 — Weber C, Bysted A, Hilmer G. The coenzyme Q10 content of the average Danish diet. Int J Vitam Nutr Res ; 67 —9.
Quinzii CM, DiMauro S, Hirano M. Human CoQ10 deficiency. Neurochem Res ; 32 —7. Weis M, Mortensen SA, Rassing MR et al. Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers. Mol Aspects Med ; 15 — Langsjoen PH, Langsjoen AM.
Overview of the use of CoQ10 in cardiovascular disease. Biofactors ; 9 — Langsjoen PH, Langsjoen PH, Folkers K. A six year clinical study of therapy of cardiomyopathy with coenzyme Q Int J Tissue React ; 12 — Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long term multicentre randomised study.
Clin Invest ; 71 —6. Watson PS, Scalia GM, Galbraith A et al. Lack of effect of CoQ10 on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol ; 33 — Langsjoen PH.
Lack of effect of Coq10 on left ventricular function in patients with congestive heart failure. There are two forms of CoQ ubiquinone and ubiquinol. Ubiquinol, the active antioxidant form of CoQ10, is made in the body from ubiquinone. As we age, the levels of both forms drop.
As early as age 20, the amount of ubiquinone our bodies produce begins to drop. Compounding the problem, the body also loses its ability to make ubiquinol from ubiquinone.
Most dietary supplements contain ubiquinone and are relatively cost effective, while ubiquinol supplements, which may be of most benefit as we age, can be harder to find and more expensive. A simple blood test is available to measure CoQ10 levels.
A shortage of this antioxidant may lead to oxidative stress, which increases the risk for a range of disorders, including CVD. Cholesterol-lowering statins may also reduce blood levels of CoQ Recent studies suggest that CoQ10, either alone or combined with other therapies, may be beneficial for the following conditions.
What is Coenzyme Q10? What are the different forms of CoQ10? How does CoQ10 affect heart health? Cardiovascular disease CVD. Recent studies show that CoQ10 supplements can significantly increase HDL-C and ApoA1 levels, even in people taking statins, and may help reduce risk for CVD.
CoQ10 supplementation also lowers levels of inflammatory biomarkers shown to be risk factors for CVD, such as high-sensitivity C-reactive protein. Finally, low CoQ10 levels have been associated with greater tissue damage to the heart during a heart attack and the brain during stroke.
Statin-related muscle symptoms. Although statin therapy can significantly reduce heart attack and stroke risk , up to 25 percent of patients quit treatment within six months due to side effects, such as muscle aches and weakness.
Objectives: Coenzyme Q10 Strokw, ubiquinone stands among antiviral immune support supplements safest Coenzyme Q and stroke prevention prevehtion the elderly Coenzyme Q and stroke prevention protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is pevention in many surviving stroke patients as strokee are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. Researchers Coenzyme Q and stroke prevention that CoQ10 may have significant benefits for people with cardiovascular disease CVDfrom reducing strokr for preventikn heart attacks Soy-free performance foods improving outcomes Prevenyion patients with heart failure to lowering strome pressure and helping combat side effects of cholesterol-lowering statins. Coenztme these are exciting findings, messaging Coenzyme Q and stroke prevention syroke about Ptevention, particularly in the popular media, is often confusing, leading to less than optimal results and poor supplement choice. Found in almost every cell of the body, CoQ10 is a fat-soluble, vitamin-like substance that helps convert food into energy. A powerful antioxidant that protects against damage from toxic free radicals, CoQ10 is produced by the body and is also found in many foodswith higher levels in organ meats, such as liver or kidneys; as well as sardines, mackerel, chicken, cauliflower, broccoli and asparagus. There are two forms of CoQ ubiquinone and ubiquinol. Ubiquinol, the active antioxidant form of CoQ10, is made in the body from ubiquinone. As we age, the levels of both forms drop.
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