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Coenzyme Q10

Dr. Becky Lee
17 June 2016

Coenzyme Q10 - A Review Of Health Effects
by Dr. Becky Lee ND Naturopathic Doctor

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Concord, ON
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Coenzyme Q10 - A Review Of Health Effects




Coenzyme Q10 and Heart Health

Over 1.4 million Canadians suffer from heart disease, and it is one of the leading causes of deaths in Canada with more than 33,600 deaths per year.[1] Heart disease includes heart failure, angina, cardiomyopathy, coronary artery disease, valve disorders, and other conditions related to the heart. These staggering numbers call for the best possible treatments for heart disease, and coenzyme Q10 (CoQ10) was shown to be a promising therapy.


Heart Facts Heart Facts

The adult human heart weighs from 200 to 425 g and is able to convert chemical energy to mechanical energy extremely efficiently. To put it in numbers, it is capable of pumping out five litres of blood every minute, 7200 litres per day, and over 2.6 million litres every year.[2]

High blood pressure (BP) is one of the most important cardiovascular risk factors worldwide. Approximately two-thirds of patients do not achieve optimal BP control using drug therapy.[3] Other interventions are extremely important, as a reduction of 5 mmHg in systolic BP has been associated with a 7% reduction in all-cause mortality.[4]

The consequences of heart failure are concerning, and despite sophisticated diagnostic techniques and treatments, the risk of death within five years of diagnosis is greater than 50%.[5] CoQ10 levels in the blood have been found to be an independent predictor of mortality in congestive heart failure.[6]


About CoQ10

First isolated in 1957 from beef mitochondria, CoQ10 or ubiquinone is highly concentrated in heart-muscle cells due to their increased energy requirements.[7] In addition to its role in the formation of ATP, CoQ10 serves to delay or prevent lipid peroxidation and enhances cell-membrane stabilization.[8, 9] Due to the fact that mitochondria are particularly vulnerable to oxidative damage, mitochondria-targeted antioxidants like CoQ10 can be an effective therapeutic strategy in preventing or reducing the progression of cardiovascular and other disorders.[10]

CoQ10 is mostly found in active organs like the heart, where a substantial decline can be observed as people age.[11] An adult human body has approximately 2 g of CoQ10 and 0.5 g must be replaced daily, making the average turnover time in the body around four days.[11] In trials, supplemental CoQ10 has been found to be effective in cardiovascular disorders like cardiomyopathy, hypertension, angina pectoris, atherosclerosis, ischemic heart disease, cardiovascular surgery, hypertension, valvular heart diseases, and myocardial infarctions.[12, 13]


Sources

Common sources for CoQ10 are beef, poultry, broccoli, soya oil, fish oils, peanuts, sardines, and mackerel. However, the average dietary amount of CoQ10 is only 2–6 mg/d, which is insufficient to provide levels in the body required to be beneficial in disease states.[12, 13]


Metabolism and Excretion Biliary tract → Feces (60%) ↗ Oral → Small intestine → Blood → Liver ↘ Heart and other organs

CoQ10 is absorbed from the small intestine and transferred into the blood circulation. It is then carried to the liver, where it undergoes biotransformation, and is primarily excreted through the bile duct. In this process, only a fraction of the amount ingested is carried to other organs like the heart, adrenal glands, kidneys, and lungs.[14, 15]


Absorbability and Dosage Absorbability and Dosage

Due to its lipophilic (or “fat-loving”) nature, CoQ10 is best absorbed with meals or in emulsified form. Divided dosing also maximizes absorbability while minimizing potential side effects.[14]

What form of CoQ10 is best? Some sources report that ubiquinol, the reduced form of CoQ10, is two times more absorbable than ubiquinone.[16] Ubiquinol was seen to have dramatically improved absorption, and its use was correlated to improvements in CoQ10 levels and positive clinical outcomes that were not possible with the use of ubiquinone at even up to 900 mg/d.[17] However, it has also been reported that the form of CoQ10 ingested may not be so important. Ubiquinone appears to be reduced during or following absorption in the intestine, and as a result more than 95% of CoQ10 in circulation exists in the more active ubiquinol form after its ingestion.[11] Which form is best still remains unclear.

The recommended daily dose of CoQ10 ranges from 30 to 100 mg/d for healthy people,[11] or 60 to 300 mg/d in treating different conditions.[13] A maximum dosage of 1200 mg has been suggested for adult intake, as it has been found to be well-tolerated and safe.[18]

Normal blood levels range from 0.7 to 1.0 μg/mL; doses of 30–60 mg can be used to prevent CoQ10 deficiency and to maintain normal serum concentrations.[13] However, clinically useful levels necessitate above-normal CoQ10 blood levels that may be two to four times higher. In fact, 450 mg of CoQ10 a day was found to achieve a plasma level of 4 μg/mL and was much more successful in reversing the course of severe heart failure.[13]

These increased levels may take days or months to achieve. Oral administration of 100 mg/d of CoQ10 for two to eight months resulted in an increase of 20–85% in myocardial CoQ10 levels in patients with cardiomyopathy.[8, 19] Due to this slow plasma increase of CoQ10, clinical improvement is normally seen one to four weeks after initial start of treatment, and it may take months to reach maximal clinical benefit.[13]


Mechanism of Action

CoQ10 appears to work in several ways including targeting expression of multiple genes. This gene regulation and control of metabolism may explain many of the cardiovascular and other actions of CoQ10.[20] The beneficial effect of CoQ10 in hypertensive cases is a result of decreased resistance that is due to its direct action on the vascular wall. Free radicals inactivate nitric oxide (NO), preventing NO-mediated relaxation of the smoothmuscle layer of the vascular wall. By acting as a free radical scavenger, CoQ10 is able to prevent vasoconstriction and the resulting increase in blood pressure.[21] With regards to coronary heart failure and myocardial infarction, CoQ10 is thought to benefit these states through its direct impact on energy production by mitochondria, improving ATP availability for the failing heart.[13]


Side Effects Side Effects

In a long-term trial of 3500 patients with congestive heart failure, mild gastrointestinal upset was the only side effect reported.[22] CoQ10 supplementation has been found to be free of side effects at dosages up to 600 mg/d and well-tolerated and safe up to 1200 mg/d.[18] Aside from possible abdominal discomfort, nausea, vomiting, diarrhea, and anorexia, allergic rash and headache have also been reported in rare cases. It is reported that CoQ10’s antiplatelet effect may increase the risk of bleeding, especially in those on antiplatelet medication.[15] However, due to its vitamin K–like action, it may also act to oppose the anticoagulant effects of warfarin.[23]


What Does the Research Say?

In one trial of CoQ10, 424 patients with different types of myocardial diseases were studied.[24] Patients were treated with an average of 240 mg/d of CoQ10 and followed an average of approximately a year and a half. Significant improvement in New York Heart Association functional classification (Table 1) was seen: 58% of patients improved by one NYHA class, 28% improved by two classes, 1.2% by three NYHA classes. Within a month, myocardial function became measurably improved. By six months, maximal improvement was usually obtained, and this improvement was sustained in the majority of patients: 43% stopped between one and three drugs, and only 6% required the addition of one drug. The withdrawal of CoQ10 supplementation resulted in a measurable decline in myocardial function within one month, and a degression to pretreatment measurements within three to six months.[24, 25]

Table 1: New York Heart Association (NYHA) Classification of Functional Capacity (Chavey 2001)
ClassificationDescription
IAsymptomatic
IISymptoms with moderate exertion
IIISymptoms with minimal exertion
IVSymptoms at rest

The elderly population may benefit from the use of CoQ10, as using antihypertensive agents can be problematic because of the increased incidence of postural hypotension increasing the risk of falls and associated morbidity. Two large clinical trials in 1991 and 1997 confirmed that in adults over the age of 60 with isolated systolic hypertension (systolic blood pressure > 140, diastolic blood pressure < 90), reducing systolic blood pressure by 20 mmHg reduces the incidence of stroke, heart failure, and mortality.[26, 27] A few clinical trials of CoQ10 in hypertension, as well as trials of CoQ10 in cardiovascular pathologies, are summarized in Table 2.

Table 2: Clinical trials of CoQ10 in hypertension and cardiovascular pathologies
Study Design Heart Condition Tested CoQ10 Dosage Results
Double-blind, placebocontrolled, randomized n = 38 (28) Idiopathic dilated cardiomyopathy 2 mg/kg/d in two or three divided doses, increased to max dose of 10 mg/kg/d according to tolerance/ side effects After six months of supplementation, the children 8 months to 15 years of age showed significant improvements in the grading of diastolic function (p = 0.011) in comparison to the control group.[28] The mean cardiac failure index for this test group (5.8) was also lower than the control (9.0, p = 0.024).

CoQ10 appeared to improve diastolic function and ameliorate cardiac failure in children with dilated cardiomyopathy.
Meta-analysis (12 clinical trials) n = 352 (20) Hypertension 100– 120 mg/d for a period of 8–12 weeks This meta-analysis included four prospective randomized trials and eight before-and-after studies.[20] CoQ10 was found to reduce systolic blood pressure by as much as 17 mmHg and diastolic blood pressure by up to 10 mmHg.
Double-blind, placebo controlled, randomized n = 39 (29) Class II and III systolic heart failure 50 mg three times a day CoQ10 group showed 0.5‑class (p = 0.01) improvement in NYHA classification as well as significant increase in the six-minute walk test distance (p = 0.047) and an increase in exercise tolerance (p = 0.056) versus the control group.[29]
Double-blind, placebo controlled, randomized n = 42 (30) End stage heart failure 120 mg/d After 12 weeks, a lower incidence of dyspnea (14.3 v. 52.4%, p < 0.05), palpitation (9.5 v. 85.7%, p < 0.02), and weakness (19.0% v. 52.4%, p < 0.05) was seen in the test group versus the control.[30] As well, significant reductions in ejection fraction, left ventricular wall thickness and mass, as well as end systolic and end diastolic volumes were found in the CoQ10 group.
Double-blind, placebo controlled, randomized n = 76 (31) Isolated systolic hypertension 60 mg twice a day In elderly men and women 50–75 years of age, the average reduction in systolic BP of 17.8 ± 7.3 mmHg was seen after 12 weeks in the treatment group.[31] 55% of patients in this group achieved a ≥ 4 mmHg reduction in SBP. None of the patients exhibited orthostatic blood pressure changes.

Clinical Implications

The use of CoQ10 in patients with heart disease may not only be useful, but also critical in achieving clinical improvements in heart disease patients. While more research in this area is needed, there is enough research thus far that points to positive outcomes in its use. Its low side effect profile and nontoxic nature makes CoQ10 a treatment that can be used for all age groups and across a broad range of cardiovascular disease.

Following positive results outlined here and elsewhere, countries like Japan, Hungary, Italy, Norway, and Denmark now grant licensed prescription of CoQ10 for heart failure and ischemic heart disease,[32] a move that shows its valued acceptance and one that encourages a more prominent and widespread use of CoQ10.