Coenzyme Q10: ubiquinone or ubiquinol?

Formulation of the Coenzyme Q10 supplements is very important. How do we know which producers of Coenzyme Q10 supplements can take the raw material, pictured here, and dissolve it in lipids and seal it in capsules so that it gives good health effects?

Recently, some readers have written in asking what my problem with the ubiquinol version of Coenzyme Q10 supplements is.  Let me try to answer that question.  I don’t think that I have a problem with ubiquinol itself.  I have great respect for ubiquinol’s utility as a lipid-soluble antioxidant.  The problem that I have tried to address on q10facts.com is the misleading nature of the marketing claims and the stretching of scientific facts in many of the marketing claims for the ubiquinol products.

Misleading claims about ubiquinol supplements
Let’s take a look.  It seems that the promoters of the ubiquinol supplements have made some claims that are misleading:

• Calling ubiquinol the only active form of Coenzyme Q10.  In fact, both forms of Coenzyme Q10 are active. Ubiquinone is active in the process of cellular energy production, and ubiquinol is active in the process of antioxidant protection.
• Saying that ubiquinol is responsible for energy production.  In fact, it is ubiquinone that is the first co-factor in the process of cellular energy production. Without ubiquinone, there is no energy production. Ubiquinol is formed as a by-product of ubiquinone’s role in energy production, and then the resulting ubiquinol plays a role in complex III in the inner membrane of the mitochondria where the energy substrate in the form of ATP (adenosine triphosophate) is produced.
• Representing ubiquinol as much better absorbed than ubiquinone. In fact, these claims were based not on head-to-head comparison studies but on comparisons of studies done at different times, under differing conditions, with different participant groups, and analyzed by different laboratories.  In the one small head-to-head comparison study that I have seen, the researchers pulled the data from one-third of the participants. The reason given was lack of compliance.
• Stating that ubiquinol is synthesized in a multi-step process in the body.  In fact, the body synthesizes ubiquinone in a complicated 17-step process. As far as I know, there is only one step in the conversion from the ubiquinone form to the ubiquinol form in the body, and that is the intermediate formation of the semi-ubiquinone molecule.  The promoters of the ubiquinol supplements have not made any attempt in the past ten years to explain that it is the action of reductase enzymes that facilitates the conversion of ubiquinone to ubiquinol or to explain what happens if the action of these enzymes is disturbed by harmful free radicals.
• Saying that the producers of the ubiquinol products have found a way to make the ubiquinol stable.  In fact, ubiquinol as an antioxidant is very unstable.  That is its nature.  It is only stable in a gelatin capsule filled with nitrogen.  Once it has been exposed to room air or to the acid and the enzymes in the stomach, ubiquinol is rapidly converted to ubiquinone.
• Claiming that everyone over the age of 45 years should be taking a ubiquinol supplement.  In fact, this claim needs much more documentation and clarification before it can be made.  Yes, there does seem to be an age-related decline in the ubiquinol-ubiquinone ratio.  The reduction in ubiquinol concentration may be caused in part by accumulating oxidative stress in older adults. There are some undocumented claims that it may be caused in part by a reduced ability to convert ubiquinone to ubiquinol in some older adults.  But, the best evidence so far seems to show that this reduced ability to convert ubiquinone to ubiquinol occurs in only 4 percent of members of the Caucasian population and in no more than 20 percent of other populations around the world. Much more research is needed.  It is the lack of documentation that is disturbing.

The best evidence of a good formulation of the Coenzyme Q10 supplement comes from the results of randomized controlled studies like the Q-Symbio study, the KiSel-10 study, and the Gulf War Veterans study.

Documented research results with Coenzyme Q10
Promoters of ubiquinone Coenzyme Q10 products, on the other hand, do not need to make dubious marketing claims.  They can report the results of clinical studies that have been published in peer-reviewed journals like the Journal of the American College of Cardiology and The International Journal of Cardiology.

Please remember, the idea behind q10facts.com was and is to get out the facts about the clinical research results of using Coenzyme Q10 supplements.  The audience I have wanted to reach is, more or less in order of priority:

• Heart failure patients and ischemic heart disease patients
• Low energy syndrome patients
• Patients taking statin medications
• Patients taking blood pressure medications
• Healthy middle-aged and older adults
• Individuals engaging in strenuous exercise

Documented health benefits with the ubiquinone form of Coenzyme Q10
I have wanted to look at gold standard studies of supplementation with Coenzyme Q10:

• Studies in which the participants have been randomly assigned to an active Coenzyme Q10 treatment group or to a placebo group
• Studies in which neither the doctors nor the participants have known whether any one participant is getting the active treatment or the placebo treatment (until the study is completed)

Published clinical research results with ubiquinone Coenzyme Q10
The supplements used in the clinical studies that have met the standard of randomized controlled trials have contained the ubiquinone form of Coenzyme Q10.  There have been no major randomized controlled trials of the ubiquinol products to date.

• Mortensen study: ubiquinone Coenzyme Q10 improves symptoms and survival of heart failure patients (2014)
• Alehagen study: ubiquinone Coenzyme Q10 combined with an organic selenium yeast reduces cardiovascular death and improves heart function in healthy elderly citizens (2013)
• Golomb study: ubiquinone Coenzyme Q10 improved general self-rated health scores and physical function in veterans of the 1990-1991 Gulf War (2014)
• Rosenfeldt study: pre-operative ubiquinone Coenzyme Q10 improved post-operative mitochondrial respiration efficiency and reduced oxidative stress in cardiac surgery patients (2005)
• Rosenfeldt meta-analysis: ubiquinone Coenzyme Q10 could lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects (2007)
• Morisco study: ubiquinone Coenzyme Q10 reduced hospitalizations and serious complications in patients with chronic congestive heart failure (1993)
• Henriksen study: ubiquinone Coenzyme Q10 can be taken by patients with Type 1 Diabetes mellitus without risk of hypoglycemia (1999)
• Eriksson study: ubiquinone Coenzyme Q10 was well tolerated and did not interfere with the glycemic control of Type 2 Diabetes mellitus patients, indicating that ubiquinone Coenzyme Q10 can be used safely for diabetes patients with cardiovascular diseases (1999)
• Engelsen study: ubiquinone Coenzyme Q10 did not influence the clinical effect of the anti-coagulant medication warfarin (2003)
• Judy study: ubiquinone Coenzyme Q10 preserved heart function and shortened the recovery time and reduced the number of complications for heart surgery patients (1993)

Formulation of the supplement most important
Before we get too hung up on the form of the Coenzyme Q10 supplement — ubiquinone or ubiquinol — we need to remember that it is the formulation of the supplement that is most important.  How the raw material Coenzyme Q10 is processed and dissolved in lipids and sealed in the capsules, that is the big factor.

Evidence of a good formulation
And the evidence that a formulation is good?  That must surely be the demonstrated health effects shown in randomized controlled studies like the Q-Symbio study, the KiSel-10 study, and the Gulf War Veterans study.

Sources:

Alehagen, U., Johansson, P., Björnstedt, M., Rosén, A., & Dahlström, U. (2013). Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. International Journal Of Cardiology, 167(5), 1860-1866.

Engelsen, J., Nielsen, J. D., & Winther, K. (2002). Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thrombosis And Haemostasis, 87(6), 1075-1076.

Eriksson JG, Forsen TJ, Mortensen SA, & Rohde M. (1999). The effect of Coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors. 1999;9(2-4):315-318.

Golomb, B. A., Allison, M., Koperski, S., Koslik, H. J., Devaraj, S., & Ritchie, J. B. (2014). Coenzyme Q10 benefits symptoms in Gulf War veterans: results of a randomized double-blind study. Neural Computation, 26(11), 2594-2651.

Henriksen JE, Andersen CB, Hother-Nielsen O, Vaag A, Mortensen SA, & Beck-Nielsen H. (1999). Impact of ubiquinone (Coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being in patients with Type 1 diabetes mellitus. Diabet Med, 16(4):312-318.

Judy, W. V., Stogsdill, W. W., & Folkers, K. (1993). Myocardial preservation by therapy with coenzyme Q10 during heart surgery. The Clinical Investigator, 71(8 Suppl), S155-S161.

Morisco, C., Trimarco, B., & Condorelli, M. (1993). Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. The Clinical Investigator, 71(8 Suppl), S134-S136.

Mortensen, S. A., Rosenfeldt, F., Kumar, A., Dolliner, P., Filipiak, K. J., Pella, D., & … Littarru, G. P. (2014). The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC. Heart Failure, 2(6), 641-649.

Rosenfeldt, F. L., Haas, S. J., Krum, H., Hadj, A., Ng, K., Leong, J., & Watts, G. F. (2007). Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal Of Human Hypertension, 21(4), 297-306.

Rosenfeldt, F., Marasco, S., Lyon, W., Wowk, M., Sheeran, F., Bailey, M., & … Pepe, S. (2005). Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue. The Journal Of Thoracic And Cardiovascular Surgery, 129(1), 25-32.