November 2018 Issue

CPE Monthly: CoQ10 and Heart Health
By Ana Gabriela Reisdorf, MS, RD, CDE
Today's Dietitian
Vol. 20, No. 11, P. 48

Suggested CDR Learning Codes: 3100, 5090, 5160, 5420
Suggested CDR Performance Indicators: 8.3.6, 10.4.4
CPE Level 2

Take this course and earn 2 CEUs on our Continuing Education Learning Library

Heart disease remains the No. 1 cause of death in the United States, accounting for an estimated one in three deaths. According to the American Heart Association, one person dies every 40 seconds from heart disease. Heart disease costs more than $200 billion annually in health care expenses and lost productivity.1,2 The prevalence of heart disease in the United States makes prevention and management of this disease a primary concern for all health care practitioners.

Although many may think heart disease is synonymous with a heart attack, several different illnesses affect the heart and blood vessels. Some diseases of the heart are related to atherosclerosis, or hardening of the arteries due to a buildup of plaque, which causes a narrowing of the arteries and makes the heart work harder to pump blood. If a blood clot forms in the area where the plaque has built up, the blood won't flow through to the heart, causing muscle death in the heart and resulting in a heart attack.3

An ischemic stroke occurs when a blood clot blocks an already narrow blood vessel in the brain instead of the heart. This prevents the brain cells from receiving enough blood or oxygen and they begin to die, which can result in the individual being unable to perform basic functions such as walking or talking. The loss of function is sometimes permanent, but in other cases, some basic functions can be restored with proper treatment. A stroke also can occur due to high blood pressure that causes a blood vessel in the brain to burst.3

Another type of heart disease is congestive heart failure, a condition in which the heart doesn't pump blood effectively. The body can't meet its needs for nutrients and oxygen when the heart isn't working at its full capacity. Heart failure results in fatigue, shortness of breath, and pooling of blood in the extremities.3

An arrhythmia is an abnormal heartbeat— it could be too fast, too slow, or simply irregular—that affects the heart's ability to pump blood efficiently and effectively. The valves of the heart can't function properly, preventing blood from flowing through the heart or causing blood to leak.3

With the different types of heart disease and the association of these conditions with lifestyle factors, RDs, as integral members of health care teams, can have a significant impact on patients' ability to manage heart disease. They can help improve patient outcomes through the use of MNT, via lifestyle education, and by recommending appropriate supportive supplement regimens. The use of coenzyme Q10 (CoQ10) may be among the latter.

This continuing education course examines the benefit of CoQ10 for heart health. It reviews the current research on CoQ10 for improvement of symptoms related to various types of heart disease, including heart failure, heart attacks, and stroke. It also evaluates the use of CoQ10 before and after heart surgery. It's designed to help dietitians provide recommendations for appropriate dosing, safety, and efficacy in the treatment and management of heart disease.

What Is CoQ10?
CoQ10 is a naturally occurring quinone found in almost every cell membrane in the human body. It was discovered in 1957 by Frederick Crane, PhD, a researcher at the University of Wisconsin. He noticed an unidentified yellow substance in the mitochondria of cows and determined that the substance must be a type of quinone; at the time, quinones were believed to exist only in plants, as they'd never been identified in the human body. The unknown substance was named ubiquinone, meaning "ubiquitous quinone," as it was later discovered to be in almost every cell of the human body. The more common name for the compound, CoQ10, refers to the compound's chemical structure.4

Its highest concentrations are in the heart, liver, and kidneys. Plasma levels of CoQ10 naturally decrease as individuals age. People with diabetes, heart failure, and cancer, as well as those taking statin medications, also tend to have lower levels of this compound.5,6

Its primary function is to help mitochondria convert food into energy via oxidative phosphorylation. It also has antioxidant properties, protecting the body's cells by neutralizing damage by free radicals and reducing oxidative stress.

CoQ10 is a fat-soluble compound found primarily in fatty foods. Sources of CoQ10 include fatty fish such as salmon and tuna, organ meats, and whole grains. There's no Recommended Dietary Allowance for CoQ10, and it's not considered a vitamin because the body can make the quinones it needs. It's believed that diet contributes only about 25% of the CoQ10 found in the body's tissues. There have been no documented deficiency symptoms reported in the general population, although a rare genetic CoQ10 deficiency disrupts CoQ10 production.6

Since its discovery, CoQ10 has been extensively evaluated for its potential to help treat a variety of heart-related conditions. It may reduce risk of subsequent heart attacks for people who already have had one. It's been shown to reduce the severity of symptoms related to heart failure, improve heart function, and lower exercise intolerance. It also has the potential to lower blood pressure, improve cholesterol levels, and decrease some of the side effects of statin medications. Finally, it can help improve outcomes after heart surgery by reducing free radicals and strengthening the heart.

Heart Failure
Congestive heart failure is a disease related to an impairment of the heart's ability to pump blood, which leads to shortness of breath, fatigue, difficulty exercising, and pooling of blood in the extremities. Causes of heart failure include heart attack, diabetes, coronary artery disease, and high blood pressure. It's most common in men older than 65, blacks, and those who are overweight.7

An initial finding that CoQ10 levels were lower in patients with heart failure led to extensive research on the use of the compound as a supplemental treatment for the condition. Supplementation with CoQ10 has been shown in several studies to help manage symptoms of heart failure, reduce hospitalization rates, and possibly slow disease progression. A meta-analysis of 16 studies on CoQ10 supplementation and heart failure by Trongtorsak and colleagues published in the March 2017 issue of Journal of the American College oc Cardiology found that, in conjunction with standard treatment, the addition of CoQ10 significantly reduced all-cause mortality.

Heart failure generally results in low exercise tolerance, which is used as a marker to determine the severity and progress of the disease. A 2003 study by Keogh and colleagues evaluated the use of CoQ10 in subjects with heart failure. Researchers gave one-half the subjects a 150-mg CoQ10 supplement daily while others received a placebo for a three-month period. Those who received the CoQ10 supplement demonstrated significant improvements in heart function, measured by several exercise tolerance activities, compared with the placebo group. Subjects could significantly increase the distance they walked in a period of time as well as the amount of exercise they could perform based on the Naughton exercise scale. In addition, researchers found that those who received the CoQ10 supplements had a three times greater serum CoQ10 level than did those who received a placebo. It was concluded that the CoQ10 must have influenced the improvement in the subjects' ability to perform the exercise.8 Other studies have shown similar results, with CoQ10 helping to improve functional ability of those diagnosed with heart failure.9

CoQ10 supplementation has been shown to improve heart function directly by increasing ejection fraction, or the percentage of blood that leaves the heart each time it contracts. One of the primary symptoms of advanced heart failure is low ejection fraction, meaning the heart can't fully pump the necessary amount of blood during each contraction. A 2005 study by Belardinelli and colleagues found that those receiving 100 mg supplemental CoQ10 daily for four weeks experienced an increase in ejection fraction compared with a group that received a placebo. The study also found that CoQ10 increased contractility in the subjects, resulting in improved heart function.10

Other studies, however, haven't shown such significant improvement with CoQ10 supplementation. A 2000 study by Khatta and colleagues used CoQ10 in addition to conventional medical therapy for heart failure. Although supplementation with 200 mg per day of CoQ10 raised serum levels of the compound in the intervention group, it had no effect on ejection fraction, nor did it increase exercise duration.11

The variation in research results from CoQ10 supplementation may be related to whether the subjects were receiving traditional medical treatment for heart failure. A 2006 meta-analysis of 10 studies found that CoQ10 did improve ejection fraction across all studies by 3.7%, but the effect of the supplement was much weaker in patients taking angiotensin-converting enzyme, or ACE, inhibitors, a common treatment for the condition.12

The studies discussed above provide evidence that supplementation with CoQ10 may help improve symptoms of heart failure. There have been no reports of adverse effects associated with the use of CoQ10 by patients with heart failure, particularly when used alongside conventional treatment. CoQ10 supplementation likely can be recommended to safely help improve heart function in patients with heart failure. But a large-scale study is needed to determine an ideal dosage and the appropriate treatment regimen.

Coronary Heart Disease
Coronary heart disease (CHD), the leading cause of death in men and women in the United States, is related to a buildup of plaque inside the arteries of the heart. The plaque, as it builds up over time, can harden and block the passage of blood to the heart. The plaque also can rupture, leading to a blood clot, which can completely block the passage of blood. If the blood can't flow to the heart, a heart attack results. The section of the heart cut off from the flow of blood begins to die, which can lead to serious health problems and death.13

CoQ10 supplementation has been shown to be effective in helping to improve one of the underlying causes of CHD by reducing oxidative stress through its activity as an antioxidant. Elevated levels of reactive oxygen species (ROS) have been linked to an increase in cardiovascular events, although the exact pathophysiology of how this occurs remains unclear. ROS is a naturally occurring and useful molecule in the body, but an excessive production of this molecule can lead to cellular damage. Too much ROS has been implicated as one of the main causes of several chronic diseases, including heart disease. The primary function of antioxidants, including CoQ10, is to scavenge and reduce ROS, preventing cellular damage and possibly reversing disease.14 Research on CoQ10 and CHD has focused on the antioxidant ability of this nutrient and its potential for helping reverse one of the underlying causes of disease.

A 2012 intervention study investigated the effects of CoQ10 supplementation on 51 patients with CHD to determine whether it would affect antioxidant activity and oxidative stress in participants with at least 50% stenosis, or blockage, of a major artery. The participants were randomly assigned into one of three groups to receive a placebo, 60 mg/day of CoQ10, or 150 mg/day of CoQ10 over a 12-week period. Blood samples were taken every four weeks to determine CoQ10 concentrations, antioxidant activity, and oxidative stress. After the 12-week study period, plasma CoQ10 concentrations increased, as did antioxidant activity. A marker of oxidative stress, malondialdehyde, decreased significantly during the trial period. The group that received 150 mg/day had the most significant change in antioxidant activity and decreased oxidative stress.15

The precise pathophysiology of the connection between oxidative stress and CHD has yet to be determined, but it's clear that there's a connection. Due to the antioxidant function of CoQ10, there seems to be some promise in reducing incidences of CHD with proper utilization of the compound, but ideal dosages have yet to be determined.

Statins are widely used to treat coronary artery disease and help prevent stroke through their ability to lower blood cholesterol levels. Statin use has been associated with low levels of CoQ10. A 2004 study by Rundek and colleagues found that after treatment with 80 mg of atorvastatin for 30 days, subjects had significantly lower plasma levels of CoQ10.16 Similar results have been shown with other statin medications.17 But it has been difficult to compare results between studies to determine the exact effect of statins on CoQ10 because of variations in the type of statin, dosage, and study length.

Statin medications work by inhibiting cholesterol synthesis, which impedes the shared pathway that produces CoQ10. The depletion of CoQ10 by statins has been theorized to be an underlying cause of one of the primary side effects of statin use, muscle pain and breakdown, or statin-induced myopathy, which affects approximately 10% to 25% of people taking the medication.18 It's important to note that research hasn't found that statins reduce CoQ10 in muscle tissue; only serum levels have shown depletion. Therefore, studies that have evaluated CoQ10 supplementation have shown mixed results with improving muscle pain.19

A 2015 meta-analysis evaluated six studies with a total of 302 patients who were receiving statin therapy. Although CoQ10 supplementation decreased muscle pain in some studies, once the data were averaged among the six studies, the effect was no longer statistically significant. There also was no dose effect found between the evaluated studies.20

Other studies have shown different results. A small 2007 study by Caso and colleagues found that participants who were receiving statin treatment and were treated with 100 mg/day of CoQ10 for 30 days experienced a 40% decrease in muscle pain and a 38% decrease in pain interference with daily activities.21

It's understood that statins reduce serum levels of CoQ10, but the exact effect of the decrease of CoQ10 is unclear. It's hypothesized that statin-induced myopathy is caused by the depletion of CoQ10, but supplementation has shown mixed results. Although patients receiving statin therapy may benefit from a CoQ10 supplement in other ways due to the antioxidant properties of the compound, it doesn't seem to help alleviate this common side effect of statin treatment.

High blood pressure, or hypertension, is a risk factor for stroke and heart attacks. CoQ10 has been studied for its potential to lower blood pressure, but results are inconclusive.

A 2001 randomized, double-blinded, placebo-controlled study evaluated the effect of 60 mg CoQ10 supplementation in 46 men and 37 women with hypertension over a 12-week period. The group treated with CoQ10 had a systolic blood pressure of 17.8 mm Hg lower than that of those who received a placebo. There were no side effects noted with the administration of CoQ10 during the 12-week intervention.22

A 2003 systematic review identified eight studies of CoQ10 and high blood pressure. This review found supplementation with CoQ10 resulted in a decrease of 16 mm Hg in systolic blood pressure and 10 mm Hg in diastolic blood pressure. The authors concluded that CoQ10 is a safe addition or alternative to traditional blood pressure treatment, as no adverse effects were reported.23 Other reviews have shown similar results, with CoQ10 supplementation lowering systolic blood pressure by up to 17 mm Hg and diastolic by up to 10 mm Hg.24

A 2016 meta-analysis of all double-blinded, randomized, placebo-controlled trials found no evidence that CoQ10 helps lower blood pressure. However, due to the stringent selection criteria of this meta-analysis, only two studies were included with a total of 50 participants.25

The effect of CoQ10 on blood pressure may be related to its antioxidant capabilities and ability to decrease oxidative stress, which in turn lowers blood pressure. There's also some indication that CoQ10 may help reduce mitochondrial dysfunction, improving the production of adenosine triphosphate (ATP), which also may be associated with the improvement seen in blood pressure.26 In addition, CoQ10 has a vasodilation effect that helps decrease blood pressure. Supplementation with CoQ10 for patients with hypertension doesn't seem to have any adverse effects and may help lower blood pressure. Dosages between 60 and 200 mg per day seem to be safe and may be used in addition to traditional treatments.27 Patients, especially those taking blood pressure medication, should consult with their doctors before initiating therapy with CoQ10 to ensure safety and proper dosing so blood pressure doesn't drop too low.

Heart Surgery
Because CVD is the leading cause of death in the United States, cardiac surgery is becoming increasingly common. Those undergoing heart surgery are particularly at risk of increased mortality and postoperative complications. Research has shown that supplementation with CoQ10 before and during surgery improves outcomes and promotes recovery.

A 2005 study of 62 patients undergoing cardiac surgery examined the effect of 300 mg/day of CoQ10 supplementation. Subjects were given either a placebo or CoQ10 for two weeks preoperatively. Researchers evaluated plasma CoQ10 levels and excised samples of heart muscle and mitochondria from the patients before surgery. Postoperatively, measurements and samples were taken again. Researchers found that those who received CoQ10 supplements had more efficient mitochondria and decreased levels of ROS, and their heart muscles were able to recover faster. Based on these results, researchers concluded that CoQ10 supplementation might help patients recover more rapidly from cardiovascular surgery.28

A small study published in 1993 evaluated the effect of supplementation with 100 mg/day of CoQ10 on 10 high-risk patients over a 14-day preoperative period. During the two weeks before surgery, CoQ10 and ATP levels increased in those receiving the supplement. Cardiac function improved, but the results weren't significant. Postsurgery, heart function was significantly improved in patients who received CoQ10, and their recovery was shorter and without complications. Those in the control group experienced a longer recovery after surgery and cardiac function didn't improve to the same degree as those in the experimental group.29

But not all studies have shown such positive results. A 1996 study evaluated the use of short-term oral supplementation of CoQ10 for its effect on heart muscle damage that can occur after heart surgery. Twenty patients who were undergoing coronary surgery received either 600 mg of CoQ10 or placebo over a 12-hour period before surgery. Postoperatively, there were no significant differences found in plasma CoQ10 levels or cardiac function between the two groups.30

Based on available research, it seems that CoQ10 supplementation may be beneficial to recovery after cardiovascular surgery if it's initiated a few weeks before surgery. Dosages between 100 and 300 mg/day seem optimal to help lower the risk of postsurgery complications and speed recovery, as adverse effects haven't been reported at this level.

Dosing and Safety
Safety is always a concern for patients, especially when it comes to dietary supplements, which are unregulated by the FDA. There have been no reports of adverse effects associated with taking CoQ10, even at doses as high as 1,200 mg/day. It's even been suggested that 1,200 mg/day be set as the observed safe level for CoQ10, although further research is needed to determine the safety of megadosing. Levels higher than 1,200 mg have been tested for conditions such as Parkinson's disease and amyotrophic lateral sclerosis, but there isn't adequate evidence to determine whether those higher levels are safe or beneficial.31

Although higher dosages are considered safe, some people may experience gastrointestinal discomfort at these levels.31 Usually this can be minimized if the supplement is spread out into two or three doses throughout the day.

CoQ10 supplementation isn't recommended during pregnancy or breast-feeding due to lack of evidence relating to safety. But there's been some research suggesting that supplementation with CoQ10 may reduce the risk of preeclampsia or hypertension during pregnancy.32

Intake of CoQ10 from food is approximately 3 to 5 mg per day, coming primarily from oily fish (eg, salmon and tuna), organ meats (eg, liver), and whole grains. The recommended dosage of CoQ10 via supplements is between 30 and 200 mg/day. Ideal therapeutic dosages may be higher, depending on the condition for which they're being used.33

CoQ10 supplements come in two forms: tablets and gel caps with a bit of oil. Since CoQ10 is fat soluble, it's best absorbed with a little bit of fat; therefore the gel caps are likely to be better absorbed.33 If only tablets are available, taking the supplement with a meal containing fat may help with absorption.

There's been only one drug-nutrient interaction identified with the use of CoQ10 supplements. CoQ10 decreases the efficacy of warfarin when taken concomitantly.34 But this effect isn't seen in 100% of cases, so patients need to be monitored via lab tests to determine the effect of the supplement on the efficacy of this medication.

Final Thoughts
Based on current available research, CoQ10 appears to be a safe and effective treatment for several cardiovascular conditions. Overall, evidence suggests it has a protective effect for a variety of heart-related conditions with few side effects, even at high doses. Its efficacy may be related to its antioxidant function, its ability to reduce oxidative stress, and the role it plays in the energy pathway of the mitochondria.

RDs should consider recommending CoQ10 supplements for patients undergoing heart surgery or for those who have high blood pressure. CoQ10 supplements haven't been proven consistently effective in reducing statin-related myopathy, although patients receiving statin treatment do tend to have low serum CoQ10 levels. It's yet to be determined whether low CoQ10 levels should be addressed with supplementation.

As always, RDs should work as integral members of the health care team and communicate with team members about dietary patterns and supplements patients use. RDs always should inform the patients' doctors if any supplements are recommended or used to ensure patient safety and avoid unfavorable outcomes.

Click here for "CoQ10 Patient Handout/Fact Sheet."

— Ana Gabriela Reisdorf, MS, RD, CDE, is a nutrition consultant and writer based in Franklin, Tennessee.

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Describe the function of coenzyme Q10 (CoQ10) for heart health.
2. Recommend appropriate dietary or supplement sources of CoQ10.
3. Provide recommendations for appropriate dosing of CoQ10 as a complementary therapy for heart disease.
4. Assess drug/nutrient interactions and other safety concerns with use of CoQ10.

CPE Monthly Examination

1. What causes a heart attack?
a. Plaque build-up and a blood clot
b. Elevated blood pressure
c. Uncontrolled stress
d. Heart failure

2. Common symptoms of congestive heart failure include which of the following?
a. Heart attack
b. Fatigue and shortness of breath
c. High blood pressure
d. Elevated cholesterol levels

3. What's the primary function of coenzyme Q10 (CoQ10) in the body?
a. To maintain intact cellular membranes
b. To transport lipids
c. To help mitochondria convert food into energy
d. To keep cholesterol levels in check

4. Why is there no Recommended Dietary Allowance (RDA) for CoQ10?
a. RDAs are only for vitamins.
b. The body can make all the CoQ10 it needs.
c. We consume too much CoQ10 through diet.
d. There's inadequate evidence to determine the RDA.

5. How does CoQ10 supplementation appear to benefit patients with heart failure?
a. By reversing the effects of the disease
b. By improving exercise tolerance
c. By reducing swelling and edema
d. By eliminating the need for medication

6. Which of the following is true about reactive oxygen species (ROS)?
a. They're harmless and have no effect on health.
b. They lower risk of heart attacks.
c. They're neutralized by CoQ10 supplements.
d. They're necessary for maintaining heart health.

7. Taking CoQ10 supplements while taking statins may do which of the following?
a. Result in a dangerous drug-nutrient interaction
b. Have no effect on statin treatment
c. Help reduce muscle pain associated with statins
d. Reduce the efficacy of the medication

8. Why might a CoQ10 supplement help lower blood pressure?
a. It's a vasodilator.
b. It helps manage emotional stress.
c. It reduces the formation of ROS.
d. It addresses a deficiency of CoQ10.

9. How should CoQ10 be administered to improve postoperative outcomes for heart surgery?
a. At least two weeks before surgery
b. In high doses immediately before surgery
c. It can't be used before heart surgery.
d. After surgery within 12 hours

10. Which has been suggested to be the observed safe upper limit dose for CoQ10?
a. 10 mg/day
b. 100 mg/day
c. 1,200 mg/day
d. 2,500 mg/day

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