Coenzyme Q10 FAQ
Q2. What are the best designed clinical trials of supplementary CoQ10?
A2. The following clinical trials are among the most-often cited studies of CoQ10 supplementation:
Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018 Apr 11;13(4):e0193120.
López-Lluch G et al. Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization. Nutrition. 2019 Jan;57:133-140.
Mortensen SA et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014 Dec;2(6):641-9.
Q3. How bioavailable is supplementary oral CoQ10?
A3. Generally, CoQ10 has poor absorption and bioavailability because of its crystalline nature, its very low water solubility, and its high melting point. Proper formulation of the CoQ10 supplement involves the selection of suitable carrier oils and the application of a crystal dispersion process. Proper formulation of the CoQ10 supplement will improve absorption and bioavailability significantly.
Source: Mantle D, Dybring A. Bioavailability of Coenzyme Q10: An overview of the absorption process and subsequent metabolism. Antioxidants (Basel). 2020 May 5;9(5):386.
Q4. How important is the redox form of CoQ10 to the absorption process?
A4. CoQ10 supplements are available in two oxidation/reduction (redox) states: the oxidized form called ubiquinone and the reduced form called ubiquinol. Differences in CoQ10 absorption and in plasma CoQ10 levels are associated much more with differences in supplement formulation quality than with differences in the redox state (ubiquinone or ubiquinol). Given a high-quality crystal dispersion formulation and equivalent dosages, the two CoQ10 redox forms can achieve comparable plasma levels.
Note that there are relatively big differences in the absorption of commercially available CoQ10 supplements. It is important to buy a supplement with documented absorption and bioavailability.
Source: López-Lluch G et al. Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization. Nutrition. 2019 Jan;57:133-140.
Q5. Are ubiquinol supplements better absorbed than ubiquinone supplements?
A5. Claims to this effect are mostly misleading. The differences reported in older studies resulted from comparisons of newer ubiquinol formulations with older formulations of ubiquinone, e.g., dry powder formulations or formulations containing many CoQ10 crystals.
In a 2020 review, Mantle & Dybring have rebutted the misleading claims for better absorption of ubiquinol. Moreover, they document the existence of numerous enzyme systems that catalyze the conversion of ubiquinone to ubiquinol in the body tissues as needed. There is no need to take a ubiquinol supplement in order to get enough ubiquinol.
Source: Mantle D, Dybring A. Bioavailability of Coenzyme Q10: An overview of the absorption process and subsequent metabolism. Antioxidants. 2020 May 5;9(5):386.
Q6. What is the optimal dose of supplementary CoQ10?
A6. Dose-response relationships are still poorly understood. For prevention of cardiovascular disease, including patients on statin medications and patients with hypertension, the commonly tested dose is 200-300 mg/day, taken at meal times in separate 100-mg doses.
For sufferers of migraine headaches, daily doses up to 400 mg have been tested. Typically, the tested dosage ranges from 100-300 mg/day.
Q7. How does supplementary CoQ10 improve cardiovascular outcomes?
A7. Several biological mechanisms may explain the improvement
of symptoms and survival of heart failure patients taking CoQ10 supplements:
• Improved ATP energy generation in the heart muscle
• Reduced levels of oxidative stress and inflammation
• Improved endothelial function
• Protection of the heart muscle tissue against ischemia
Q8. Can supplementary CoQ10 counteract statin-induced muscle pain and weakness?
A8. Statins are inhibitors of the action of the HMG-CoA reductase enzyme. Statins block the bio-synthesis of both cholesterol and CoQ10. CoQ10 depletion via statins is documented. Although clinical trials of CoQ10 in statin-induced muscle pain and weakness have yielded mixed results, the weight of the evidence supports the use of supplementary CoQ10 in patients on statin medications.
Source: Raizner AE, Quiñones MA. Coenzyme Q10 for patients with cardiovascular disease: JACC Focus Seminar. J Am Coll Cardiol. 2021 Feb 9;77(5):609-619.
Q9. What role does CoQ10 play in mitochondrial diseases?
A9. Secondary CoQ10 disorders are fairly common. They occur for various reasons: aging, gene mutations, oxidative stress, statin medication effects. CoQ10 is of major importance in mitochondrial ATP energy generation. Consequently, secondary CoQ10 deficiency has been linked to a wide range of disorders.
In a 2022 review, Mantle et al have reviewed the evidence for CoQ10 supplementation in several disorders associated with mitochondrial dysfunction. CoQ10 deficiency syndromes often respond well to supplementation.
Source: Mantle D, Turton N, Hargreaves IP. Depletion and supplementation of coenzyme Q10 in secondary deficiency disorders. Front Biosci (Landmark Ed). 2022 Dec 19;27(12):322.
Q10. How does supplementary CoQ10 affect aging and longevity?
A10. Plasma CoQ10 levels decline with age. In a man aged 80 years, the heart muscle tissue content of CoQ10 is less than half that of a 20-year-old man. The Q-Symbio Study has shown that CoQ10 supplementation can reduce cardiovascular and all-cause mortality and can reduce the need for hospitalization.
Source: Kalén A et al. Age-related changes in the lipid compositions of rat and human tissues. Lipids. 1989 Jul;24(7):579-84.
Mortensen SA et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014 Dec;2(6):641-9.
Q11. Are there clinically meaningful antioxidant effects of supplementary CoQ10 in humans?
A11. In a 2022 review of 34 RCTs comprising 2,012 study participants, Dai et al showed that taking a CoQ10 supplement 100−150 mg/day had significantly better benefits for the levels of total antioxidant capacity, of the antioxidant enzyme superoxide dismutase, and malondialdehyde (a biomarker for oxidative stress).
A. Dai S et al. Effects of coenzyme Q10 supplementation on biomarkers of oxidative stress in adults: A GRADE-assessed systematic review and updated meta-analysis of randomized controlled trials. Antioxidants (Basel). 2022 Jul 13;11(7):1360.
Q12. Who benefits most from supplementary CoQ10?
A. Individual who are likely to respond most to CoQ10 supplementation include the individuals in the following groups:
• Older adults
• Statin users
• Heart failure patients
• Individuals with secondary CoQ10 deficiency
Q12B. Are there any safety concerns with long-term use of supplementary CoQ10?
A. CoQ10 is well tolerated. The observed safety level for CoQ10 is 1200 mg/day/person. CoQ10 supplementation does not affect the biosynthesis of endogenous CoQ10. CoQ10 does not accumulate in plasma or tissues after the discontinuation of supplementation. Overall, CoQ10 has very low toxicity and does not induce serious adverse effects in humans.
Source: Hidaka T et al. Safety assessment of coenzyme Q10. Biofactors. 2008;32(1-4):199-208.
Q13. How should CoQ10 levels in humans be measured clinically?
A13. It is easy to measure the level of plasma CoQ10. However, it is not known to what extent plasma CoQ10 concentrations tissue or mitochondrial levels. well. Folkers et al compared blood CoQ10 levels with CoQ10 levels in heart muscle tissue biopsies. Their analysis of the blood CoQ10 levels in four classes of patients with heart muscle disease (cardiomyopathy) indicated that the blood CoQ10 levels can be lower in patients with more severe symptoms (New York Heart Association functional classes III and IV).
Source: Folkers K et al. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985 Feb;82(3):901-4.
Q14. How long does supplementary CoQ10 take to achieve a steady-state plasma CoQ10 concentration?
A14. Please note that the CoQ10 steady-state bioavailability can vary in accordance with differences in clinical settings and in study participants. For example, the time to plasma CoQ10 steady state can be different in healthy young volunteers, in patients with heart failure or with statin-induced muscle pain, in elderly patients, and in individuals with
digestive abnormalities, with absorption difficulties, or with different plasma lipid profiles. Other factors include the dosage and posology, the formulation, and clinical purpose.
In a 2022 study, Dr. William Judy indicated that the CoQ10 steady state in plasma is reached after approximately 14 days.
In a 2006 study, Bhagavan & Chopra reported a time to plasma CoQ10 steady state of 6 – 8 days.
Sources: Judy WV. The Single-dose absorption and steady-state bioavailability of different coenzyme Q10 formulations. Integr Med (Encinitas). 2022 Feb;21(1):28-34.
Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006 May;40(5):445-53.