Biomarkers of Inflammation and Oxidation: Coenzyme Q10

Optimal Takeaways

Coenzyme Q10 (CoQ10) is a versatile compound with potent antioxidant and anti-inflammatory effects. It is crucial to energy generation at the cellular level, and its depletion leads to fatigue, muscle weakness, neuroinflammation, and increased cardiometabolic risk.

CoQ10 production in the body declines with age and the use of statin drugs, which interfere with its synthesis. Genetic factors can interfere with its production as well. Low CoQ10 levels are associated with atherosclerosis, cardiovascular disease, heart failure, neurodegeneration, muscle pain and weakness, inflammation, and oxidation. High CoQ10 levels are associated with high-dose supplementation.  

Standard Range: Above 0.35 ug/mL

The ODX Range: Above 2.5 ug/mL

Low CoQ10 is associated with fatigue (Tsai 2022), energy depletion (Rabanal-Ruiz 2021), fibromyalgia, cancer, mitochondrial disorders, headaches, migraines (Sood 2024), oxidative stress, inflammation, aging, statin use, cardiovascular and cerebrovascular disease, heart failure, myocardial infarction, chronic kidney disease, hypertension, neuroinflammation, neurodegeneration, Alzheimer’s disease, Parkinson’s diseases, muscular dystrophy (Testai 2021), statin‐associated muscle symptoms (SAMSs), cardiac and skeletal muscle CoQ10 depletion (Qu 2018), mitochondrial deficiency syndrome, lipid peroxidation, LDL oxidation, atherosclerosis, lower cholesterol levels, compromised skeletal muscle function, and reduced physical activity (Hernandez-Camacho 2018).

Low CoQ10 is also associated with multiple system atrophy (MSA) (Mitsui 2023), liver disease, type 2 diabetes, chronic kidney disease, critical illness, cerebellar ataxia, primary deficiency due to genetic factors, and secondary deficiency due to chronic disease or pharmaceutical intervention (Hargreaves 2020).

High CoQ10 may be associated with excessive supplementation. Supplementation with 1,200 – 1,500 mg/day of CoQ10 is generally considered safe and well-tolerated. Higher doses may be used under medical supervision.

Overview

Coenzyme Q10 (CoQ10) is a naturally occurring lipid-soluble antioxidant produced in the body and consumed in small amounts in food. It is essential for energy metabolism and antioxidant protection. CoQ10 is found throughout the body with the highest concentrations in the mitochondria, particularly in the heart, liver, and kidney, which are highly metabolic organs. CoQ10 levels decrease with age and shift to a more oxidized state, decreasing CoQ10’s antioxidant capacity, especially in the heart and pancreas. Declining CoQ10 levels contribute to cardiovascular disease and impaired blood vessel function. Statin drugs deplete CoQ10 by inhibiting the HMG-CoA reductase enzyme that produces both cholesterol and CoQ10. Statin-induced depletion contributes to oxidative stress, arterial stiffness, and other adverse effects (Rabanal-Ruiz 2021).

Small amounts of CoQ10 are found in food, including fatty fish, soy, and spinach. A Mediterranean-style diet can provide 5 mg/day (Testai 2021). CoQ10 is also found in meat, dairy, eggs, oils, and legumes. It is best absorbed with a source of fat. CoQ10 is consumed in its oxidized ubiquinone CoQ10 form and converted to its fully reduced ubiquinol form in the small intestine; 95% of circulating CoQ10 is in the ubiquinol form (Sood 2024). However, normal CoQ10 metabolism depends on continual inter-conversion between ubiquinone and ubiquinol. In general, CoQ10 production peaks at age 25 and decreases by 50% by age 65. It can be depleted earlier by chronic disease, genetic factors, and pharmaceutical drugs. Low-density lipoprotein (LDL) is the primary carrier of circulating CoQ10, and LDL depletion can reduce CoQ10 levels (Hargreaves 2020).

The ubiquinol form of CoQ10 participates in energy generation via the mitochondrial electron transfer chain and is a potent antioxidant, scavenging cell membrane free radicals. Ubiquinol inhibits LDL oxidation more effectively than other antioxidants like beta-carotene or vitamin E. It can also regenerate other antioxidants, including vitamin C and E. Prolonged CoQ10 supplementation is considered safe and well-tolerated and can effectively increase plasma levels to 3-5 ug/mL with 300 mg/day doses. Benefits of supplementation include (Rabanal-Ruiz 2021):

• Support of mitochondrial energy generation
• Reduction of reactive oxygen species, oxidative stress, and endothelial dysfunction
• Increased nitric oxide levels and enhanced vasodilation
• Prevention of oxidized LDL accumulation in the arteries.
• Reduced vascular stiffness and hypertension
• Decreased cardiovascular mortality
• Improved clinical outcomes in coronary artery disease and CABG surgery
• Improved outcomes in heart failure, a condition associated with CoQ10 depletion
• Divided doses throughout the day may be more effective than one large daily dose.

Repletion of CoQ10 usually requires supplementation to reach therapeutic levels. 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 of CoQ10 daily. CoQ10 extracted from living tissues is more expensive than that produced in the laboratory by fermentation, which yields consistent quality and cheaper supplements (Sood 2024):

• 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 indicates that 100 to 600 mg of CoQ10 daily 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.
• A 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.
• Early treatment with high-dose supplementation (ranging from 5 to 50 mg/kg/day) can limit disease progression In patients with primary CoQ10 deficiency.
• A recent study of CoQ10 supplementation showed promising results in patients with primary CoQ10 deficiency with nephrotic syndrome and steroid-resistant nephrotic syndrome (SNHL) at a dose of 20 mg/kg/day.
• Typical CoQ10 dosing is 100-300 mg/day or 5 mg/kg/day.
• Toxicity is unlikely up to 1,200 mg/day.

CoQ10 levels may need to reach at least 2.5 ug/mL to be of benefit in heart failure (Mantle 2023). A dose of 200 mg taken twice daily may be needed to achieve a therapeutic blood level above 2.5 ug/mL. Cardiac trials often use a dose of 100-400 mg/day, while studies of neurodegenerative diseases, including Parkinson’s and amyotrophic lateral sclerosis, may use much higher doses of 600-3,000 per day (Raizner 2019). Supplementation with 100-200 mg/day of CoQ10 significantly reduced systolic blood pressure and increased circulating CoQ10 by 1.62 ug/mL, according to a meta-analysis of 26 studies (Zhao 2022).

The Q-SYMBIO study investigating adjunct CoQ10 supplementation in heart failure found that 100 mg of CoQ10 thrice daily for two years significantly reduced cardiac-related deaths and all-cause mortality. Better patient compliance with supplementation and achieving a blood level of CoQ10 of 3.4 ug/mL at three months and 3.6 ug/mL at two years resulted in significant reductions in major adverse cardiovascular events (MACE). It significantly improved left ventricular ejection fraction, compared to lower compliance and achieving a level of 3 ug/mL at three months and 2.1 ug/mL at two years. CoQ10 supplementation is effective in other metabolic disorders as well. A dose of 150-200 mg/day can significantly improve hemoglobin A1C and fasting glucose in type 2 diabetics; 100 mg thrice daily significantly improved creatinine in chronic kidney disease patients; and 100 mg/day significantly decreased biomarkers of systemic inflammation and oxidative stress in non-alcoholic fatty liver disease patients (Hargreaves 2020).

A meta-analysis of randomized controlled trials found that a CoQ10 dose of 300-400 mg/day effectively inhibits inflammatory mediators CRP, IL-6, and TNF-alpha and increases circulating CoQ10 in the general population (Hou 2023).

Fatigue is a common symptom in healthy individuals and those with chronic disease. A meta-analysis and systematic review found that CoQ10 can significantly reduce fatigue, an effect that increases with the dose and duration of supplementation. It may take up to three months for CoQ10 supplementation to be effective in the chronically ill with fatigue (Tsai 2022).

Extending 150 mg/day supplementation to three months improved sleep quality, autonomic nervous dysfunction, and math-related task performance in individuals with chronic fatigue syndrome (CSF). The positive effects were directly associated with improvements in circulating CoQ10. Supplementation with 400 mg/day of CoQ10 for three months had significant prophylactic effects and reduced migraine severity, duration, and frequency in a randomized, double-blind, placebo-controlled study. Researchers attribute the benefits to CoQ10’s anti-inflammatory effects. Combining 400 mg/day of CoQ10 with other nutraceuticals, such as magnesium, riboflavin, curcumin, and feverfew may enhance anti-migraine benefits (Testai 2021).

Doses of CoQ10 above 100 mg/day can significantly improve oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity, according to a meta-analysis of 19 research studies (Sangsefidi 2020).

Statin drugs can significantly reduce circulating CoQ10 by up to 54% regardless of statin duration or dose. Statins also deplete intramuscular CoQ10, including in cardiac and skeletal muscle, which is highly energy dependent. A meta-analysis of 12 randomized controlled studies found that CoQ10 supplementation effectively counteracts statin‐associated muscle symptoms (SAMSs), including muscle pain, weakness, cramping, and fatigue. Positive effects were independent of the dose or duration of CoQ10 supplementation, i.e., 100-600 mg/day and 30-90 days (Qu 2018).

The bioavailability of supplemental CoQ10 can be enhanced with the use of oily suspensions, emulsions, liposomes, nanostructured lipid carriers, micelles, particle size reduction (e.g., nanoparticles), and consuming it with a source of fat (Testai 2021). The ubiquinol (reduced) form is more bioavailable than the ubiquinone (oxidized) form, which is converted to ubiquinol in the body. A 1,500 mg/day dose of ubiquinol significantly improved unified multiple system atrophy rating scale (UMSARS) scores and secondary outcomes in a double-blind, placebo-controlled trial of 131 multiple system atrophy (MSA) patients. Low circulating CoQ10 is commonly seen in MSA, a progressive neurodegenerative disease with Parkinsonian, cerebellar ataxic, and pyramidal dysfunction characteristics. The 1,500 mg/day dose was associated with a blood CoQ10 level of 6.03 ug/mL after 48 weeks. Similar levels were reached in previous studies, e.g., 6.38-7.49 ug/mL with an 8-12 week dose of 2,400-3,600 mg/day of ubiquinone in Huntington’s patients. However, researchers note that blood levels as high as 10.23 ug/mL were reached in healthy adult males when supplemented with 1,500 mg/day of ubiquinol for two weeks. They suggest a maximum dose of 1,500 mg/day of ubiquinol is likely safe and well-tolerated (Mitsui 2023).

References

Hargreaves, Iain et al. “Disorders of Human Coenzyme Q10 Metabolism: An Overview.” International journal of molecular sciences vol. 21,18 6695. 13 Sep. 2020, doi:10.3390/ijms21186695

Hernandez-Camacho, Juan D et al. “Coenzyme Q10 Supplementation in Aging and Disease.” Frontiers in physiology vol. 9 44. 5 Feb. 2018, doi:10.3389/fphys.2018.00044

Hou, Shanshan et al. “Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.” Molecular nutrition & food research vol. 67,13 (2023): e2200800. doi:10.1002/mnfr.202200800

Mantle, David et al. “Coenzyme Q10 Metabolism: A Review of Unresolved Issues.” International journal of molecular sciences vol. 24,3 2585. 30 Jan. 2023, doi:10.3390/ijms24032585

Mitsui, Jun et al. “High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial.” EClinicalMedicine vol. 59 101920. 14 Apr. 2023, doi:10.1016/j.eclinm.2023.101920    

Qu, Hua et al. “Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials.” Journal of the American Heart Association vol. 7,19 (2018): e009835. doi:10.1161/JAHA.118.009835

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

Raizner, Albert E. “Coenzyme Q10.” Methodist DeBakey cardiovascular journal vol. 15,3 (2019): 185-191. doi:10.14797/mdcj-15-3-185

Sangsefidi, Zohreh Sadat et al. “The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials.” Food science & nutrition vol. 8,4 1766-1776. 19 Mar. 2020, doi:10.1002/fsn3.1492

Sood, Brittany, et al. “Coenzyme Q10.” StatPearls, StatPearls Publishing, 30 January 2024.

Testai, Lara et al. “Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases.” Nutrients vol. 13,5 1697. 17 May. 2021, doi:10.3390/nu13051697

Tsai, I-Chen et al. “Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Frontiers in pharmacology vol. 13 883251. 24 Aug. 2022, doi:10.3389/fphar.2022.883251

Zhao, Dan et al. “Dose-Response Effect of Coenzyme Q10 Supplementation on Blood Pressure among Patients with Cardiometabolic Disorders: A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Advances in nutrition (Bethesda, Md.) vol. 13,6 (2022): 2180-2194. doi:10.1093/advances/nmac100