coenzyme Q10

What is Coenzyme Q10

Coenzyme Q10 (CoQ10) also called ubiquinone or ubidecarenone, is a substance that is naturally present in the human body in most body tissues, with the highest levels in the heart, liver, kidneys, and pancreas. The lowest amounts are found in the lungs. CoQ10 decreases in the body as people get older. Your body uses Coenzyme Q10 for cell growth and to protect cells from damage. Coenzyme Q10 is a lipid-soluble benzoquinone that has 10 isoprenyl units in its side chain and is a key component of the mitochondrial respiratory chain for adenosine triphosphate (ATP) synthesis by acting as an electron carrier in mitochondria and as a co-enzyme for mitochondrial enzymes 1), 2). Studies has indicated that coenzyme Q10 is an intracellular antioxidant can protects membrane phospholipids, mitochondrial membrane protein, and low density lipoprotein-cholesterol (LDL-C) from free radical-induced oxidative damage 3). In vitro or in vivo studies have demonstrated that coenzyme Q10 not only plays an antioxidant, but also has anti-inflammation effects 4) by modulating the expression of cyclooxygenase-2 and nuclear factor-κB (NF-κB) in the liver tissue of rats with hepatocellular carcinoma 5).

A coenzyme helps an enzyme do its job. An enzyme is a protein that speeds up the rate at which chemical reactions take place in cells of the body. The body’s cells use coenzyme Q10 to make energy needed for the cells to grow and stay healthy. The body also uses coenzyme Q10 as an antioxidant. An antioxidant protects cells from chemicals called free radicals.

Figure 1. Coenzyme Q10

coenzyme Q10

A coenzyme Q10 deficiency occurs with age; however, certain drugs can cause depletion of coenzyme Q10 levels, particularly hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins 6). Statins are prescribed to reduce cholesterol levels and work by inhibiting HMG-CoA reductase and the mevalonate metabolic pathway 7). Mevalonate is used to synthesize cholesterol as well as coenzyme Q10 8), therefore, when statin drugs lower cholesterol levels they simultaneously lower coenzyme Q10 levels. Statins are known to block coenzyme Q10 biosynthesis and reduce serum concentrations of coenzyme Q10 by up to 40% 9). Furthermore, statin use is often associated with a variety of muscle-related symptoms or myopathies. Research has suggested that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment 10).

Coenzyme Q10 is sold in the United States as a dietary supplement. Supplementary oral administration of coenzyme Q10 has been shown to increase coenzyme Q10 levels in plasma, platelets, and white blood cells 11). Because CoQ10 has important functions in the body and because people with some diseases have reduced levels of this substance, researchers have been interested in finding out whether CoQ10 supplements might have health benefits. Studies suggest that CoQ10 deficiency may be associated with a multitude of diseases as diverse as coronary artery disease and congestive heart failure, Parkinson’s disease, diabetes, and breast cancer, as well as the risk factor, hypertension 12). It has been suggested that Coenzyme Q10 has the potential to lower blood pressure without significant adverse events in hypertensive patients 13).

There are also a number of ways that Coenzyme Q10 could act favorably to reduce blood pressure. Coenzyme Q10 could act directly on vascular endothelium and decrease total peripheral resistance by acting as an antagonist of vascular superoxide, by either scavenging it, or suppressing its synthesis 14). Further to this, a recent meta-analysis has associated CoQ10 supplementation with a significant improvement in arterial endothelial function in patients with and without cardiovascular disease 15). Coenzyme Q10’s antioxidant properties may also result in the quenching of free radicals that cause inactivation of endothelium-derived relaxing factor or fibrosis of arteriolar smooth muscle, or both 16). In addition, CoQ10 has been found to decrease blood viscosity and improve blood flow to cardiac muscle in patients with ischemic heart disease; therefore it may reduce blood pressure 17).

Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 (the reduced form of coenzyme Q10) within circulating lipoproteins. In its reduced form the coenzyme Q10 molecule acts as a powerful intracellular antioxidant due to its ability to hold electrons rather loosely, and will quite easily give up one or both electrons. The antioxidant and free radical scavenger effects of coenzyme Q10 can therefore help to prevent lipid peroxidation and thus the progression of atherosclerosis 18). Furthermore, coenzyme Q10 has also been found to modulate the amount of ß-integrin levels on the surface of blood monocytes, strongly suggesting that the anti-atherogenic effects of coenzyme Q10 are mediated by other mechanisms beside its antioxidant properties 19).

Coenzyme Q10 (CoQ10) key facts

  • Coenzyme Q10 (CoQ10) has not been shown to be of value in treating cancer, but it may reduce the risk of heart damage caused by one type of cancer chemotherapy drug.
  • Only a few studies have looked at whether CoQ10 might help prevent heart disease, and their results are inconclusive. Research on the effects of CoQ10 in heart failure is also inconclusive. However, there is evidence that CoQ10 may reduce the risk of some complications of heart surgery.
  • Although results of individual studies have varied, the overall scientific evidence does not support the idea that CoQ10 can reduce muscle pain caused by the cholesterol-lowering drugs known as statins.
  • The small amount of evidence currently available suggests that CoQ10 probably doesn’t have a meaningful effect on blood pressure.
  • Guidelines from the American Academy of Neurology and the American Headache Society say that coenzyme Q10 is “possibly effective” in preventing migraines, but this conclusion is based on limited evidence.
  • A major study showed that coenzyme Q10, even in higher-than-usual doses, didn’t improve symptoms in patients with early Parkinson’s disease. A 2017 evaluation of this study and several other, smaller studies concluded that coenzyme Q10 is not helpful for Parkinson’s symptoms.
  • Coenzyme Q10 (CoQ10) has also been studied for a variety of other conditions, including amyotrophic lateral sclerosis (Lou Gehrig’s disease), Down syndrome, Huntington’s disease, and male infertility, but the research is too limited for any conclusions to be drawn.

Coenzyme Q10 (CoQ10) supplement benefits

The U.S. Food and Drug Administration (FDA) does not approve dietary supplements as safe or effective. The company that makes the dietary supplements is responsible for making sure that they are safe and that the claims on the label are true and do not mislead the patient. The way that supplements are made is not regulated, so all batches and brands of coenzyme q10 supplements may not be the same.

Coenzyme Q10 for cancer

There have been few clinical trials that study the use of CoQ10 in patients with cancer. A trial of 236 breast cancer patients were randomized to receive either Coenzyme q10 or placebo, each combined with vitamin E, for 24 weeks. The study found that levels of fatigue and quality of life were not improved in patients who received Coenzyme q10 compared to patients who received the placebo.

A randomized trial of 20 children treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma looked at whether Coenzyme q10 would protect the heart from the damage caused by doxorubicin. The results reported that CoQ10 decreased the harmful effects of doxorubicin on the heart.

Clinical trials have been limited to small numbers of people, and it is not clear if the benefits reported were from the Coenzyme q10 therapy, other dietary supplements, or standard treatments used before or during the CoQ10 therapy.

Reversal of statin-induced myopathy

Statins (HMG-CoA reductase inhibitors) deplete circulating coenzyme Q10 levels by interfering with its biosynthesis 20). Most studies indicate a correlation between the decrease in serum coenzyme Q10 and decreases of total and low-density lipoprotein cholesterol levels. This effect may be particularly important in elderly patients, in whom coenzyme Q10 levels are already compromised, and is also associated with higher dosages (lower dosages do not seem to affect intramuscular levels of coenzyme Q10) 21). The use of ezetimibe alone or in combination with a statin does not offer protection against depletion of coenzyme Q10 22). No correlation has been established for decreased serum coenzyme Q10 and cardiovascular events 23). Supplemental coenzyme Q10 increased circulating levels of the compound. However, results from randomized clinical trials are inconsistent in showing an effect on statin-associated myopathy 24), 25).

Neurological disorders

The case for coenzyme Q10 as a treatment option in neurological (mitochondrial-related) disease is not as strong 26). The role of coenzyme Q10 in Parkinson, Alzheimer, and Huntington diseases; amyotrophic lateral sclerosis; and Friedreich ataxia is postulated but not established 27).

Studies in Friedreich and non-Friedreich ataxia have largely shown a continued worsening of disease, as measured by the International Cooperative Ataxia Group rating scale, irrespective of coenzyme q10 use (5 mg/kg/day) 28).

A link between mitochondrial dysfunction and Parkinson disease has been established, but the relationship with coenzyme Q10 has not 29). A multicenter clinical trial found a decrease in worsening of symptoms in patients with early Parkinson disease receiving coenzyme Q10 1,200 mg/day, but not at lower dosages 30). Effects were not apparent at 1 month, but were evident at 8 months. Changes in daily living factors were more pronounced than clinical disease progression changes 31). Increases in plasma coenzyme Q10 were recorded. A larger trial using higher dosages (coenzyme Q10 600 mg chewable wafers 4 times a day) found a mean change in total rating score high enough to warrant a phase 3 trial 32); however, the trial was not designed to evaluate efficacy 33). A multicenter trial of patients receiving anti-Parkinson medication found no difference in symptoms over placebo 34).

The role of mitochondrial stress in Alzheimer disease led to more studies of coenzyme Q10 35). Multicenter clinical trials using idebenone dosages of up to 360 mg 3 times a day found no effect on the rate of decline over placebo. Analyses using various rating scales showed some differences that were not considered clinically important, mirroring other older trials 36). Similarly, no slowing of decline was noted in Huntington disease 37).

Other uses

Coenzyme Q10 has been evaluated in migraine versus placebo in small trials. Decreases in attack frequency, days with headache, and days with nausea were found for a daily dose of 300 mg 38). The coadministration of ubiquinone with tamoxifen mitigated the hyperlipidemia associated with tamoxifen, and tumor marker levels indicated an antiangiogenesis effect 39). An Agency for Healthcare Research and Quality review of clinical trials reported no evidence to support the use of ubiquinone in the prevention or treatment of cancer 40).

Deficiencies of coenzyme Q10 have been described, predominantly affecting children, in a spectrum of diseases including infantile-onset, multisystem diseases, as well as adult-onset cerebellar ataxia and pure myopathies 41). Lymphocyte and platelet coenzyme Q10 levels were lower in Down syndrome 42), while lowered serum levels are associated with phenylketonuria and mevalonic aciduria 43).

In infants with Prader-Willi syndrome, coenzyme Q10 had no effect on lean mass versus growth hormone 44).

Coenzyme Q10 for blood pressure and cardiovascular disease

Considering the key role of coenzyme Q10 in cellular energy production, and the high energy requirements of cardiac cells, coenzyme Q10 has a potential role in the prevention and treatment of heart ailments by improving cardiac bioenergetics 45).

Studies have shown that a coenzyme Q10 deficiency is associated with cardiovascular disease 46); however, it is uncertain whether a coenzyme Q10 deficiency is the cause or the effect of disease, especially in observational studies 47). Patients with ischemic heart disease (coronary heart disease) and dilated cardiomyopathy have been found to have significantly lower levels of coenzyme Q10 compared to healthy controls 48). In addition, the concentrations of coenzyme Q10 in blood and heart tissue decline with increasing severity of heart disease 49). Coenzyme Q10 deficiency has also been observed in patients with hypertension; enzymatic deficiency of coenzyme Q10 has been reported in 39% of hypertensive patients compared with only 6% of healthy controls 50).

Congestive heart failure

Much of the research on coenzyme Q10 is related to the secondary prevention of cardiovascular disease and results of clinical trials support the use of coenzyme Q10 in the treatment of congestive heart failure 51). Several meta-analyses and systematic reviews of clinical trials in congestive heart failure have been published, with results generally being more consistent for congestive heart failure than with other disease states. The inclusion of 2 trials in which coenzyme Q10 failed to show an effect greater than placebo in these analyses, results in only a trend in favor of coenzyme Q10 in improving cardiac function (an increase in resting ejection fraction of 1.9% 52). In a meta-analysis that included trials with a crossover or parallel-arm design, a 3.7% absolute difference in resting ejection fraction was found for coenzyme Q10 53). In other trials, coenzyme Q10 has been used in combination with other micronutrients 54). The studies, however, either do not evaluate or are underpowered to evaluate mortality outcomes 55). Because differing Coenzyme Q10 preparations were used in the studies, both the bioavailability of the compound 56) and the adequacy of dosing to reach sufficient plasma coenzyme Q10 levels for effect have been questioned 57).

Hypertension

In primary prevention, a meta-analysis of observational studies and clinical trials (12 studies, total of 362 patients) has shown that coenzyme Q10 supplementation reduces blood pressure 58). Rosenfeldt et al. conducted a meta-analysis, comprising three randomized trials 59), 60), 61), one randomized crossover study 62) and eight open-label studies 63), 64), 65) in 362 hypertensive patients, most of whom had essential hypertension or isolated systolic hypertension 66). They reported that coenzyme Q10 therapy had the potential to reduce BP by up to 17/10 mm Hg 66). The meta-analysis was however, limited by the inclusion of studies which were open-labeled and not placebo-controlled. Furthermore, there were considerable differences in patient populations with respect to age, underlying disease and comorbidities, coenzyme Q10 dose and duration, and use of concomitant antihypertensive therapy between the trials. Finally, the meta-analysis did not make use of individual patient data from the component studies, which would have provided a more robust assessment of any effect of coenzyme Q10 on arterial pressure.

On the other hand, a recent 2016 Cochrane systematic review of randomized controlled trials in participants with primary hypertension dispute these findings 67). The 2016 Cochrane Review provides moderate-quality evidence that coenzyme Q10 does not have a clinically significant effect on blood pressure. Due to the small number of individuals and studies available for analysis, more well-conducted trials are needed 68).

The additional findings from Young et al. 69), showing no effect of coenzyme q10 on the 24-hour ambulatory monitoring systolic BP, diastolic BP, or heart rate compared to placebo provide supporting evidence for the conclusion that coenzyme Q10 has no clinically significant effect on BP (blood pressure). The 24-hour measurements are done using an automatic machine, and thus are free from observer bias that could occur with clinic measurements done by a physician or nurse.

These findings concur with another double-blind, placebo-controlled intervention trial by Mori et al. 70) who found 8 weeks of coenzyme Q10 administration had no effect on 24-h ambulatory BP in patients with chronic kidney disease. In that study, treated BP levels were 125/73 mm Hg before randomization. As noted above, however, any antihypertensive action of coenzyme Q10 is likely to be less obvious the lower the baseline level of BP. In this regard, it has been shown that coenzyme Q10 does not have vasodilatory effects in normotensive animals or humans 71).

In conclusion, randomized controlled studies demonstrated that compared with placebo, coenzyme Q10 does not result in clinically significant reductions in systolic or diastolic 24-h ambulatory BP or heart rate in patients with the metabolic syndrome and inadequately treated hypertension, although there was a significant reduction in daytime diastolic BP loads. Coenzyme Q10 was well tolerated and was not associated with any clinically relevant changes in safety parameters.

Cardiac surgery and cardiac arrest

The use of coenzyme Q10 in improving mitochondrial function has been evaluated in cardiac surgery. A review was published of 8 studies, in which improvements in contractility of the myocardial tissue were demonstrated in association with increases in serum coenzyme Q10 72). Doses of coenzyme Q10 300 mg daily for 2 weeks prior to surgery were evaluated versus placebo 73). A randomized, placebo-controlled trial evaluated coenzyme Q10 450 mg in divided doses in conjunction with hypothermia after cardiac arrest. Increased survival was shown for the coenzyme Q10 group 74).

Coenzyme Q10 dosage

Several dosage forms exist, including compressed and chewable tablets, powder-filled and gel-filled capsules, liquid syrups, and newer solubilized formulations. The reduced form of coenzyme Q10, ubiquinol, is also commercially available. It may also be given by injection into a vein (IV).

Pharmacokinetic studies suggest split dosing is superior to single daily dosing; for tissue uptake and crossing the blood-brain barrier, plasma coenzyme Q10 levels should be higher than normal 75).

Usual adult dose of Coenzyme-Q10 is 30 to 200 mg/day oral.

In observational studies and clinical trials (12 studies, total of 362 patients) has shown that coenzyme Q10 supplementation reduces blood pressure 76). Dose of coenzyme Q10 ranged between 34 and 225 mg/day and duration of individual studies from one to 56 weeks.

Cardiovascular and neurologic trials predominately use coenzyme Q10 dosages of 300 mg/day or coenzyme Q10 dosages of 5 mg/kg/day.

High-dose coenzyme Q10 (1,200 mg/day) was used in patients with early Parkinson disease 77), while dosages of 2,700 to 3,000 mg/day were used in amyotrophic lateral sclerosis trials 78). An open-label study that included children evaluated tolerability of high-dose coenzyme Q10. Daily dosages of 60 mg/kg given in 3 divided doses were used for 1 month 79).

Coenzyme Q10 side effects

No serious side effects of CoQ10 have been reported. Mild side effects such as insomnia or digestive upsets may occur.

Reported side effects from the use of Coenzyme-Q10 include the following:

  • High levels of liver enzymes.
  • Nausea.
  • Heartburn.
  • Headache.
  • Pain in the upper part of the abdomen.
  • Dizziness.
  • Rashes.
  • Unable to fall sleep or stay asleep.
  • Feeling very tired.
  • Feeling irritable.
  • Sensitive to light.

It is important to check with health care providers to find out if CoQ10 can be safely used with other drugs. Certain drugs, such as those that are used to lower cholesterol, blood pressure, or blood sugar levels, may decrease the effects of Coenzyme-Q10. CoQ10 may change the way the body uses warfarin (a drug that prevents the blood from clotting) and insulin.

Coenzyme-Q10 may interact with the anticoagulant (blood thinner) warfarin and the diabetes drug insulin, and it may not be compatible with some types of cancer treatment.

What other drugs will affect Coenzyme Q10?

Do not take Coenzyme Q10 without medical advice if you are using any of the following medications:

  • omega-3 fatty acids;
  • vitamins (especially A, C, E, or K);
  • blood pressure medicine;
  • cancer medicine; or
  • warfarin (Coumadin, Jantoven).

This list is not complete. Other drugs may affect Coenzyme Q10, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Toxicology

A review of animal experiments and clinical trials has estimated an acceptable daily intake for coenzyme Q10 to be 12 mg/kg (ie, 720 mg/day for a 60 kg person) based on a no-observed-adverse-effect level in rats of 1,200 mg/kg/day. An observed safety level based on clinical data is given as 1,200 mg/day. No accumulation in plasma or tissue following cessation of coenzyme Q10 consumption was noted and endogenous biosynthesis was not affected 80).

Coenzyme Q10 are a class of lipid-soluble benzoquinones that are involved in mitochondrial electron transport. They are found in the majority of aerobic organisms, from bacteria to mammals, hence the name ubiquinone (“ubiquitous quinone”).

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