Continuing Education Activity

Coenzyme Q10 (CoQ10) is not FDA-approved to treat any medical condition, although it is widely available over-the-counter as a dietary supplement and recommended by primary care providers and specialists alike. Diseases such as neurodegenerative diseases, fibromyalgia, diabetes, cancer, mitochondrial diseases, muscular diseases, and heart failure are associated with decreased circulating levels of CoQ10. Statin drugs, of note, block the production of an intermediate in the mevalonate pathway, a biochemical pathway that leads to the production of CoQ10. Therefore, researchers hypothesize that statin drugs may deplete the body of CoQ10. As muscle pain and cramping are such a common adverse effect of statins, they believe this depletion of CoQ10 is the culprit. This activity will highlight the mechanism of action, adverse event profile, latest research, and relevant interactions pertinent to CoQ10 for members of the interprofessional team to treat patients with potentially relevant conditions.

Objectives:

• Identify the purported indications for supplementing with coenzyme Q10.
• Describe the mechanism of action of CoQ10.
• Outline the potential benefit of CoQ10 in patients receiving statin therapy.
• Explain the importance of improving care coordination among the interprofessional team to enhance care delivery for patients with CoQ10 use.

Indications

Coenzyme Q10 (CoQ10) is not FDA-approved to treat any medical condition. However, it is widely available over-the-counter as a dietary supplement and recommended by primary care physicians and specialists alike. Diseases such as neurodegenerative diseases, fibromyalgia, migraine, diabetes, cancer, mitochondrial diseases, muscular diseases, and heart failure are associated with decreased circulating levels of CoQ10.[1][2][3][4][5] Many studies have been performed on the premise that increasing systemic CoQ10 levels in such conditions would allow for the proper functioning of processes that require CoQ10.[1][2][3]

A recently published systematic review showed that supplementation with CoQ10, in addition to standard therapy in patients with moderate-to-severe heart failure, is associated with symptom reduction and reduction of major adverse cardiovascular events.[2][6] It may also improve functional capacity, endothelial function, and left ventricle contractility in congestive heart failure patients.[2][7]

Supplementation has shown promising results in improving endothelial function in several subsets of patients. CoQ10 can improve endothelial function in patients with ischemic left ventricular systolic dysfunction heart failure.[8][9] Likewise, when compared with placebo, CoQ10 appears to improve endothelial function in the peripheral circulation of patients with type-2 diabetes mellitus with hyperlipidemia.[10] Evidence of the routine use of CoQ10 in patients with coronary artery disease apart from congestive heart failure is still scanty.[11][8]

There is also some evidence that, when combined with selenium, CoQ10 supplementation in healthy elderly patients and elderly patients with diabetes, hypertension, and ischemic heart disease, may decrease cardiovascular mortality risk.[12] Data are conflicting on whether CoQ10 may play a role in treating high blood pressure.[13]

CoQ10 has shown the potential to decrease pain, fatigue, and morning tiredness compared to placebo in patients with fibromyalgia.[14][15]Some data suggest that supplementation with moderate-to-high dose CoQ10 in patients with mitochondrial disorders may influence bicycle exercise aerobic capacity.[16]

Supplementation with CoQ10 in men with Peyronie disease may decrease penile plaque size, reduce penile curvature, and improve erectile function.[17]

Statin drugs, of note, block the production of an intermediate in the mevalonate pathway, a biochemical pathway that leads to the production of CoQ10.[18] Therefore, many physicians hypothesize that statin drugs may deplete the body of CoQ10. As muscle pain and cramping are common adverse effects of statins, they believe this depletion is the culprit.[19]

Although most studies have used patients with preexisting medical conditions, one study of healthy participants did show that oral supplementation improved subjective fatigue and physical performance during bicycle exercise routines.[20]

CoQ10 has also shown promise in migraine prophylaxis. A cohort study of 1550 children and adolescents with headaches found that this population has low CoQ10 levels.[21] Supplementation appeared to decrease headache frequency.[21] 

Interestingly, CoQ10 levels may be decreased in those with acute influenza infection.[22] However, studies on supplementation in this subset of patients have yet to be done.

When supplemented alongside standard psychiatric medical therapy, CoQ10 appears to lessen symptoms of depression in patients with bipolar disorder.[23]

In patients with polycystic ovary syndrome, supplementation may improve fasting blood glucose, insulin levels, and total testosterone levels.[24]

Mechanism of Action

CoQ10 also referred to as ubiquinone, is a fat-soluble, vitamin-like molecule found naturally in every cellular membrane in our bodies. It is a normal part of our diet but is also endogenously synthesized. It is essential for the proper transfer of electrons within the mitochondrial oxidative respiratory chain and adenosine triphosphate (ATP) production.[25] CoQ10 can increase the production of key antioxidants such as superoxide dismutase, an enzyme capable of reducing vascular oxidative stress in hypertensive patients.[26] CoQ10 reduces levels of lipid peroxidation via the reduction of pro-oxidative compounds.[27] CoQ10 can enhance blood flow and protect blood vessels via the preservation of nitric oxide.

Supplements offer CoQ10 in either the oxidized form (ubiquinone) or the reduced form (ubiquinol). The bioavailability of a given CoQ10 supplement depends on the lipid carrier it is immersed in, and any preservatives added.[28]

Administration

The vast majority of studies done on CoQ10 in humans have only evaluated it as an oral supplement. There are tablets, capsules, soft gels, and liquid oral supplement formulations available in the markets.  Various oral formulations from 30 mg to 600 mg per unit dose are available over the counter. Topical over-the-counter preparations are also available, but studies on this route of administration are limited. One study investigated a topical preparation as a treatment for age-related skin oxidative damage.[29] Meat has the highest amount of CoQ10, followed by dairy, eggs, and plant-based food sources (oils and legumes). CoQ10 extracted from living tissues is expensive than produced in the laboratory by fermentation procedure which yields consistent quality and cheaper supplements.[30]

• Supplementation with 50 mg twice daily has shown to decrease statin-related mild-to-moderate myalgias, resulting in an increased ability to perform daily activities.[19]
• Supplementation with 300 mg daily for 24 weeks in men with Peyronie disease may decrease penile plaque size, reduce penile curvature, and improve erectile function.[17]
• A double-blind, randomized controlled trial showed 300 mg daily to be safe and superior to a placebo for migraine prevention.[31] Another randomized, double-blind placebo-controlled trial in a cohort of adult women showed that 400 mg per day supplementation decreased migraine frequency, severity, and duration.[5] One study showed that only 100 mg daily reduced the severity of headaches and the number of headaches per month in migraine sufferers.[32]

Adverse Effects

• Coenzyme Q10 is present naturally in the human body. CoQ10 supplements are generally well-tolerated with only minor and infrequent adverse effects, including stomach upset, nausea, vomiting, and diarrhea.[33][34] 
• Doses of 100 mg per day or higher have been associated with mild insomnia in some individuals.[35] 
• Liver enzyme elevation has been seen in some patients taking 300 mg or more per day, but no liver toxicity has been reported.[35] 
• Supplementation has been shown to be tolerated, even up to 1200 mg/day.[3] 
• Other rare adverse effects have included dizziness, photophobia, irritability, headache, heartburn, increased involuntary movements, and fatigue.[33][34][36]

The FDA does not strictly regulate dietary supplements such as coenzyme Q10, nor are manufacturers required to prove their safety and purity both before and after release to the markets. However, several independent agencies test supplements for purity, composition, and strength and issue certifications to manufacturers that meet their testing criteria. However, these agencies do not test every batch that is manufactured, and they do not guarantee therapeutic value. Manufacturers who have received these agencies’ seal of approval will often advertise so on their product packaging.

Contraindications

Studies are limited on CoQ10 use in patients with kidney and liver disease, and therefore, coadministration of CoQ10 supplements should be avoided in these patients. Patients using chemotherapeutic drugs should also avoid using CoQ10 since there is little data on the interaction of CoQ10 with these drugs. Since CoQ10 has been shown to lower fasting blood glucose in some patients, it should be used with caution in those with diabetes and/or patients who are prone to hypoglycemic episodes. CoQ10 use should be avoided in nursing mothers, children, and infants as studies in these populations are lacking.[33]

CoQ10 is chemically similar to Vitamin-K, and there are some reports available for potential warfarin and CoQ10 interaction in the literature. There are chances of warfarin treatment failure when patients are taking CoQ10 supplements along with warfarin therapy. This interaction is believed to be reversible.[37][38][39]

Monitoring

Many studies have monitored blood levels of CoQ10 to assess the efficacy of supplementation. Average plasma concentrations appear to be about 0.34 to 1.65 micrograms/mL.[3] A toxic blood CoQ10 level has not been determined, mostly because CoQ10 toxicity is absent, even at the highest oral supplementation levels.[3][40]

Toxicity

CoQ10 is safe as a dietary supplement. Toxicity is unlikely, even up to a daily intake of 1,200 mg/day, although typical dosages studied have been 100 to 200 mg/day.[40]

Enhancing Healthcare Team Outcomes

Coenzyme Q10 is a safe, popular dietary supplement continuously being studied as an adjunctive treatment for several medical conditions. With the broad commercial base of the supplement industry and widespread interest in complementary and alternative medicine in the United States, many healthcare professionals will inevitably encounter patients interested in using it and other dietary supplements. As data on this promising supplement continues to grow, physicians, nurses, pharmacists, and other interprofessional healthcare team members must continue to update themselves on its potential as an adjunctive treatment for various medical conditions. With proper education and open communication regarding the patient's condition and use of supplements, including CoQ10, the chances for better outcomes are enhanced and potential adverse events minimized. [Level 5]

Potential Level I evidence for the use of CoQ10 includes adjunctive treatment for patients with moderate-to-severe congestive heart failure.[2]

Potential Level II evidence includes CoQ10 supplementation for the following indications:

• To improve endothelial function in patients with ischemic left ventricular systolic dysfunction heart failure[8]
• To improve endothelial function in the peripheral circulation of patients with type-2 diabetes mellitus with hyperlipidemia[10]
• To decrease pain, fatigue, and morning tiredness in patients with fibromyalgia[14][15]
• To improve aerobic capacity in patients with mitochondrial disorders[16]
• To decrease penile plaque size, reduce penile curvature, and improve erectile function in patients with Peyronie disease[17]
• To decrease statin-related mild-to-moderate myalgias[19]
• To improve subjective fatigue and physical performance during bicycling exercise routines in healthy patients[20]
• To lessen symptoms of depression in patients with bipolar disorder alongside conventional pharmacologic therapy[23]
• To improve fasting blood glucose, insulin levels, and total testosterone levels in patients with polycystic ovary syndrome[24]
• To decrease migraine frequency in adult migraine sufferers[5][31]

Potential Level III evidence for the use of CoQ10 includes the following indications:

• To reduce cardiovascular mortality risk along with selenium administration in healthy elderly patients[12]
• To decrease the severity of headaches and the number of headaches per month in adult and pediatric migraine sufferers[21][32]