CoQ10 Reduces Cardiovascular Disease Risk and More

Coenzyme Q10 (CoQ10), a naturally occurring antioxidant produced in the body, is essential for energy metabolism and antioxidant protection. It is found in the highest concentrations in the mitochondria, particularly in the heart, liver, and kidney, which are highly metabolic organs.

Declining CoQ10 levels contribute to cardiovascular disease and impaired blood vessel function. Statin drugs interfere with endogenous CoQ10 production by inhibiting the HMG-CoA reductase enzyme that produces both cholesterol and CoQ10. In this manner, statins reduce circulating CoQ10 and contribute to oxidative stress, arterial stiffness, and other adverse effects.

CoQ10 levels decrease with age, especially in the heart and pancreas, and shift to a more oxidized state, reducing its antioxidant capacity.

Small amounts of CoQ10 are found naturally in foods. It is absorbed in the GI tract by the same process as lipids, though uptake of CoQ10 in the body ranges from only 2-3% of the dose consumed. Ingested CoQ10 is reduced to ubiquinol during or following absorption and is absorbed best with a source of fat. CoQ10 is insoluble in water, and supplemental formulations should optimize solubility and bioavailability by providing nanoparticulated CoQ10 (highest bioavailability), followed by solubilized, oil-emulsions, and finally, powder forms.

CoQ10 supplementation is safe, raises plasma CoQ10 levels, reduces oxidative stress, and improves cardiovascular health by supporting mitochondrial energy production, reducing vascular stiffness, and enhancing blood vessel dilation.

CoQ10 exists in three forms: ubiquinone (fully oxidized), ubisemiquinone (partially reduced free radical form), and ubiquinol (fully reduced). The ubiquinol form participates in energy generation via the mitochondrial electron transfer chain as well as a potent antioxidant, scavenging free radicals in cell membranes. It is more effective in inhibiting LDL oxidation than other antioxidants like beta-carotene or vitamin E. Ubiquinol can also regenerate other antioxidants such as vitamin C and E. [95% of circulating CoQ10 is in the ubiquinol form].

Prolonged CoQ10 supplementation is considered safe, well-tolerated, and can effectively increase plasma levels to 3-5 ug/mL.

Supplementation can:

• Reduce reactive oxygen species, oxidative stress, and endothelial dysfunction
• Increase nitric oxide levels and vasodilation
• Prevent arterial accumulation of oxidized LDL
• Decrease vascular stiffness and hypertension
• Decrease cardiovascular mortality
• Improve clinical outcomes in CABG surgery
• Note that divided doses throughout the day may be more effective than one large daily dose.

Mechanisms of action of CoQ10 in cardiovascular disease

ATP: adenosine triphosphate; ROS: reactive oxygen species; NO: nitric oxide; LDL: low-density lipoprotein; NT-proBNP: N-terminal prohormone BNP; FMD: flow-mediated dilation; CAD: coronary artery disease.

Source:  Rabanal-Ruiz, Yoana et al. “The Use of Coenzyme Q10 in Cardiovascular Diseases.” Antioxidants (Basel, Switzerland) vol. 10,5 755. 10 May. 2021, doi:10.3390/antiox10050755 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

CoQ10 in Heart failure (HF)

• HF is characterized by loss of contractile function due to energy depletion and low CoQ10.
• HF patients demonstrate plasma and myocardial CoQ10 deficiency.
• Plasma CoQ10 concentration is an independent predictor of mortality in chronic heart failure.
• HF severity can be reduced with CoQ10 90 mg/day.
• 200 mg/day of CoQ10 can reduce fatigue, dyspnea, and interventricular septal thickness in severe hypertrophic cardiomyopathy.
• Supplementation with 300 mg/day significantly increased serum CoQ10 to 3-5 ug/mL and significantly increased CoQ10 levels in mitochondria and cardiac ventricles.
• CoQ10 100 mg/day for 16 weeks tripled baseline CoQ10 (from 1.14 ug/mL to ~3.4 ug/mL), reduced CVD mortality by 43%, all-cause mortality by 42%, and hospital stays by 8% compared to placebo.
• Supplementation with 300 mg/day of CoQ10 for eight weeks significantly increased plasma CoQ10 from 1.08 to 3.24 ug/mL, a change that significantly correlated with improved brachial flow-mediated dilation. Improvements were most pronounced in subjects with more severe endothelial and mitochondrial dysfunction (measured by lactate/pyruvate ratios in the plasma).
• Over three months, a dose of 400 mg/day of CoQ10 as ubiquinol led to significant improvement of peripheral endothelial function in heart failure patients with reduced ejection fraction.
• Combining CoQ10 with selenium supplementation significantly reduced CVD and all-cause mortality in healthy subjects over five years. Fructosamine levels were also reduced. Cardioprotective effects were most pronounced in those with serum selenium below 85 ug/L (1.08 umol/L). Selenium is required for the thioredoxin reductase enzyme that reduces CoQ10 to its bioactive ubiquinol form.
• Combining CoQ10 with aged garlic extract can preserve arterial elasticity and significantly improve endothelial function. CoQ10 also improves function in those taking red yeast rice monacolin.

CoQ10 in Cardiac Surgery and Coronary Arterial Disease (CAD)

• Coronary artery disease (CAD) is associated with a low plasma CoQ10.
• A 150 mg dose of CoQ10 can decrease oxidative stress and increase antioxidant enzyme activities in patients with CAD.
• Presurgical treatment with 100 mg/day of CoQ10 significantly improves the cardiac concentration of CoQ10, myocardial ATP, cardiac pumping, and left ventricular ejection fraction.
• A two-week presurgical treatment with antioxidants, including 300 mg/day of CoQ10, significantly increased plasma CoQ10, atria, and mitochondria in elective cardiac surgery patients.
• A 7-10 day presurgical treatment with 150-180 mg/day of CoQ10 resulted in significantly fewer common complications, fewer repercussion arrythmias, and shorter hospital stays.
• A single 300 mg dose of CoQ10 given 12 hours before percutaneous coronary intervention significantly reduced hs-CRP, but a reduction in myocardial injury following the procedure was not observed. Researchers surmise there was insufficient time for plasma CoQ10 to reach therapeutic levels.
• Higher plasma CoQ10 30 days after primary angioplasty is associated with more favorable LV remodeling and systolic function, even six months after segment elevation myocardial infarction (STEMI). Preoperative CoQ10 administration also reduces perioperative NT-proBNP, a validated predictor of post-vascular surgery adverse events.
• General guidelines recommend 200-300 mg/day of CoQ10 for 7-14 days before cardiac surgery to improve mitochondrial function and increase myocardial tolerance to oxidative stress.

CoQ10 Hypercholesterolemia and Atherosclerosis

• CoQ10 levels can be significantly depleted during statin therapy due to their interference with CoQ10 production in the body, independent of statin use duration.
• CoQ10 may help relieve the myalgia associated with statin use, especially when combined with lower statin doses in those with previous statin intolerance. Higher CoQ10 levels correlate with lower creatine kinase levels, a marker of muscle breakdown, and vice versa.
• 100 mg of CoQ10 twice daily for one week increased CoQ10 serum levels and correlated with increased cholesterol efflux to HDL carriers.
• CoQ10 supplementation combined with aged garlic extract reduces the progression of coronary artery calcium, a marker of atherosclerosis.
• Hypercholesterolemia, oxidized LDL cholesterol, hypertension, and hyperglycemia promote atherosclerosis, which is associated with ischemic heart disease, cerebrovascular disease, and peripheral artery disease.
• A two-week CoQ10 supplementation combined with red yeast rice rich in monacolin significantly reduced total cholesterol, LDL cholesterol, triglycerides, serum glucose, and blood pressure.
• The combination of CoQ10 with metformin reduced fasting glucose, fasting insulin, and hemoglobin A1C and significantly improved insulin sensitivity better than metformin alone.
• CoQ10 supplementation can reduce CVD risk in diabetes and metabolic syndrome by lowering total and LDL cholesterol, enhancing nitric oxide bioavailability, and increasing antioxidant protection of LDL.

CoQ10, Endothelial Dysfunction and Hypertension

• A daily dose of 200 mg of CoQ10 and 200 ug of selenium can downregulate xanthine oxidase and NADPH oxidase, reducing uric acid, reactive oxygen species, and oxidative stress.
• Increased oxidative stress can disrupt the metabolism of nitric oxide, a compound that improves vascular tone, reduces platelet aggression and adhesion, inhibits white blood cell interactions with blood vessel walls, neutralizes LDL cholesterol oxidation, and supports endothelial function.
• CoQ10 supplementation can prevent endothelial dysfunction, inflammatory cytokine release, and disruption of nitric oxide metabolism induced by oxidized LDL.

Optimal Takeaways

• CoQ10 supplementation (200 mg/day or higher) is safe and well-tolerated over prolonged periods.
• Supplementation increases plasma CoQ10 levels and reduces oxidative stress, lowering cardiovascular mortality.
• Benefits heart health by improving heart failure symptoms, enhancing mitochondrial function, and increasing myocardial tolerance to oxidative stress.
• CoQ10 has anti-atherogenic effects, preventing arterial LDL oxidation and accumulation and reducing vascular stiffness and hypertension.
• Improves endothelial function by reducing reactive oxygen species (ROS) and boosting nitric oxide (NO) for vasodilation.

Reference

Rabanal-Ruiz, Yoana et al. “The Use of Coenzyme Q10 in Cardiovascular Diseases.” Antioxidants (Basel, Switzerland) vol. 10,5 755. 10 May. 2021, doi:10.3390/antiox10050755 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Wait, there’s more!

Meat has the highest amount of CoQ10, followed by dairy, eggs, and plant-based food sources (oils and legumes). However, repletion of CoQ10 usually requires levels higher than those found naturally in foods. CoQ10 is consumed in its oxidized CoQ10 form and reduced to its fully reduced ubiquinol form in the small intestine. 95% of CoQ10 is in the ubiquinol form.

The normal blood level of CoQ10 is 1 ug/mL, which can be increased to a potentially therapeutic level of 2 ug/mL with at least 100 mg/day of CoQ10 intake.

CoQ10 extracted from living tissues is more expensive than that produced in the laboratory by fermentation, yielding consistent quality and cheaper supplements.

• Supplementation with 50 mg twice daily decreases statin-related mild-to-moderate myalgias, resulting in an increased ability to perform daily activities. 
• A meta-analysis of RCTs indicated that CoQ10 supplementation of 100 to 600 mg/day decreases Statin-Associated Muscle Symptoms (SAMS).
• A double-blind, randomized controlled trial showed 300 mg daily to be safe and superior to a placebo for migraine prevention. 
• Another randomized, double-blind, placebo-controlled trial in adult women showed that 400 mg of supplementation decreased migraine frequency, severity, and duration. One study showed that 100 mg daily reduced the severity and number of headaches per month in migraine sufferers.
• In patients with primary CoQ10 deficiency, early treatment with high-dose supplementation (ranging from 5 to 50 mg/kg/day) can limit disease progression.
• A recent study of CoQ10 supplementation (20 mg/kg) demonstrated promising results in patients with primary CoQ10 deficiency with nephrotic syndrome and steroid-resistant nephrotic syndrome (SNHL).
• Typical CoQ10 dosing is 100-300 mg/day or 5 mg/kg/day.
• Toxicity is unlikely up to 1,200 mg/day.

CoQ10 Efficacy Evidence

Potential Level 1: This evidence for CoQ10 includes adjunctive treatment for patients with moderate-to-severe congestive heart failure.

Potential Level 2: This evidence includes CoQ10 supplementation for the below-mentioned indications.

• To improve endothelial function in patients with ischemic left ventricular systolic dysfunction heart failure.
• To improve endothelial function in the peripheral circulation of patients with type-2 diabetes mellitus with hyperlipidemia.
• To decrease pain, fatigue, and morning tiredness in patients with fibromyalgia.
• To improve aerobic capacity in patients with mitochondrial disorders.
• To decrease statin-related mild-to-moderate myalgias.
• To improve subjective fatigue and physical performance during bicycling exercise routines in healthy patients.
• To lessen symptoms of depression in patients with bipolar disorder alongside conventional pharmacologic therapy.
• To improve fasting blood glucose, insulin levels, and total testosterone levels in patients with polycystic ovary syndrome.
• To decrease migraine frequency in adult migraine sufferers.

Potential Level 3: This evidence for the use of CoQ10 includes the below-mentioned indications.

• To reduce cardiovascular mortality risk along with selenium administration in healthy older patients.
• To decrease the severity and number of headaches per month in adult and pediatric migraine sufferers.
• To attenuate disease progression in patients with primary CoQ10 deficiency.

Reference

Sood, Brittany, et al. “Coenzyme Q10.” StatPearls, StatPearls Publishing, 30 January 2024. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ),

The Quest Diagnostics standard range for serum CoQ10 is >0.35 ug/mL. However, optimal levels above 2 ug/mL should be achieved for therapeutic value.