Dr. Judy: What Does the Evidence Show About Ubiquinone vs Ubiquinol?

Dr Judy's book
Dr. William V. Judy, president of SIBR Research and author of Coenzyme Q10: An Insider’s Guide, addresses the question of whether to buy a ubiquinone Coenzyme Q10 supplement or a ubiquinol supplement.

Here Dr. Judy writes about the question of Coenzyme Q10 supplements in the form of ubiquinone vs ubiquinol.

For some time now, I have been thinking about the data comparing the absorption and bioavailability of the two commercially available forms of Coenzyme Q10: ubiquinone and ubiquinol.

  • ubiquinone is the oxidized form of Coenzyme Q10, the form that is essential for ATP energy production in the cells. It is the most tested form. When it accepts two electrons, it is reduced and becomes ubiquinol.
  • Ubiquinol is the reduced form of Coenzyme Q10. In its reduced form, Coenzyme Q10 is an important lipid-soluble antioxidant. The Coenzyme Q10 in the lymph and blood is predominantly in the ubiquinol form. This makes sense, as there is more need for antioxidant protection in the blood than there is for bio-energetics.

Some of the numbers that have been presented in marketing claims for this newer and less tested form, ubiquinol, have seemed surprisingly high.

Analysis of the Steady-State Bioavailability of Ubiquinone and Ubiquinol

I have done an analysis of the steady-state bioavailability of ubiquinol compared to 1) dry powder ubiquinone, 2) dry-powder-in-oil-base ubiquinone, and 3) crystal-free oil-based ubiquinone formulations. Note that I am not talking about studies of single-dose absorption here.

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Dr. Judy Writes About Coenzyme Q10

Dr. William V. Judy
Dr. William V. Judy, founder and president of SIBR Research, writes as a guest columnist for Q10facts.com. Dr. Judy has done clinical research in the Coenzyme Q10 adjuvant treatment of patients with heart failure, chronic fatigue syndrome, and prostate cancer. He has supported Prader-Willi children with Coenzyme Q10 therapy. He is the author of the 2018 book Coenzyme Q10: An Insider’s Guide, which is available on amazon.com. ISBN 978-87-7776-186-7.

The question that I get asked about the most is whether there is any benefit from supplementing with Coenzyme Q10 if a person does not have a diagnosed CoQ10 deficiency?

Yes, I think there is a benefit. We should not be waiting until an obvious CoQ10 deficiency manifests itself. Instead, we should be giving people in their 40s and above the following advice:

  1. Your cells’ bio-synthesis of Coenzyme Q10 will decline with increasing age. Taking various medications, statin medications in particular, will also inhibit your body’s own production of Coenzyme Q10.
  2. The heart muscle cells need sufficient Coenzyme Q10 to produce enough ATP energy. To prevent the development and worsening of heart disease, you need to take daily CoQ10 supplements to get your plasma CoQ10 levels above 2.0 mcg/mL. If you already have symptoms of heart disease, you probably need to get your plasma CoQ10 levels above 2.5 mcg/mL [Langsjoen 2014].
  3. Taking 2 or 3 times 100 mg of Coenzyme Q10 daily, together with a meal, for 12 to 24 weeks, should get your plasma CoQ10 levels up to the target level. Firstly, taking more than 100 mg at a time will not bring much extra benefit. Secondly, taking the Coenzyme Q10 together with some fat in a meal will improve the absorption of the Coenzyme Q10.
  4. You must continue to take CoQ10 supplements even after you reach a plasma concentration of 2.0 mcg/mL. If you stop taking the CoQ10 supplement, your blood levels will decline. Moreover, the Coenzyme Q10 will not go from the blood into the tissue cells unless you have a higher concentration of CoQ10 in the blood.

What is a CoQ10 Deficiency?

In the USA, the normal level of plasma CoQ10 is quoted to be 0.45 to 1.50 mcg/mL. I feel that the 0.45 – 0.60 mcg/mL plasma levels are found in individuals with clinical conditions.

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CoQ10 Supplementation for MS Patients

Wheelchair in the park
MS patients may consider using a wheelchair to conserve strength and reduce fatigue or to prevent falls. Clinical trial evidence shows that high doses of CoQ10 daily can reduce the feeling of fatigue.

Daily supplementation of 60 multiple sclerosis patients with 200 milligrams of Coenzyme Q10 for three months showed beneficial clinical outcomes for the multiple sclerosis patients [Moccia 2019]:

The open-label crossover design study also had the following biological benefits [Moccia 2019]:

  • decreased the intracellular production of harmful free radicals
  • reduced the extent of oxidative damage in the peripheral blood
  • improved the anti-inflammatory environment in the peripheral blood
  • attenuated the extent of pro-inflammatory cytokines in the peripheral blood

CoQ10 and MS and Depression and Fatigue

In a randomized, double-blinded, placebo-controlled trial, daily CoQ10 supplementation of multiple sclerosis patients with 500 mg/day for 12 weeks was associated the following health benefits [Sanoobar 2016]:

  • a significant decrease in fatigue symptoms quantified using the fatigue severity scale
  • a significant improvement of depression symptoms as shown in Beck Depression Inventory scores

CoQ10 and MS and Inflammation and Oxidative Stress

In the same study, supplementation with 500 milligrams per day for 12 weeks significantly reduced the blood levels of known bio-markers for systemic inflammation compared to the placebo group [Sanoobar 2015]:

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Daily CoQ10 Supplementation for Senior Citizens

Dr. William Judy
Dr. William Judy, founder and president of SIBR Research, says that individuals vary in the extent to which their cells synthesize less CoQ10 with increasing age in the adult years. Generally, though, he is concerned if an individual has a blood CoQ10 concentration below 0.60 micrograms per milliliter.

As we get older – and more susceptible to aging-related diseases – the mitochondria and the endoplasmic reticula in our cells synthesize significantly less Coenzyme Q10. This seems to be especially true of CoQ10 bio-synthesis in the heart muscle cells, kidney cells, leg muscle cells, and abdominal wall muscle cells [Díaz-Casado 2019].

In some human tissues, the highest levels of CoQ10 are found in 20-year-olds. After the 20’s comes the ageing-related decline in CoQ10 levels in various human tissues [Kalén 1989].

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Low Coenzyme Q10 Status and Increased Heart Disease Risk

Dr. William Judy
Long-time Coenzyme Q10 researcher Dr. William Judy says that there is considerable individual variation in blood CoQ10 concentrations. Generally, though, he regards a plasma or serum CoQ10 level below 0.60 micrograms per milliliter as a warning sign.

Japanese cardiologists have reported a significant connection between low Coenzyme Q10 status and the risk of death from heart disease and other causes [Shimizu 2020].

  • The researchers collected and examined blood samples from 242 men and women admitted to Juntendo University Hospital’s coronary care unit in Tokyo.
  • They followed the heart disease patients for a three-year period.
  • 58 of the 242 patients (24%) died during the follow-up period from heart disease, cancer, infection, and other causes.
  • The patients who died had an average blood CoQ10 concentration of 0.48 micrograms per milliliter. The patients who survived had a higher average blood CoQ10 concentration of 0.58 micrograms per milliliter.
  • Overall, the researchers found that patients with a “higher” blood CoQ10 concentration of 0.46 or greater micrograms per milliliter had a 52% lesser likelihood of dying from all causes than did the patients with blood CoQ10 concentrations below 0.46 micrograms per milliliter.
  • Nota bene: The patients with the low CoQ10 blood levels were the patients with the higher dosages of statin medications.

Why Low CoQ10 Levels are Associated with Heart Disease Mortality

Book Insider's Guide to Coenzyme Q10
In his book Insider’s Guide to Coenzyme Q10, Dr. Judy discusses the effects of increasing age, malnutrition, and statin medications on blood Coenzyme Q10 levels and the consequent effect on heart function. Available from amazon.com. ISBN: 978-87-7776-186-7.

This research shows that heart disease patients with lower blood CoQ10 levels are at greater risk of dying sooner than heart disease patients with higher blood CoQ10 levels [Shimizu 2020].

  • Statin medications are known to inhibit the body’s endogenous production of Coenzyme Q10; logically, every heart patient taking a statin medication will need adjunctive Coenzyme Q10 treatment. Okuyama et al [2015] have explained the mechanisms by which statin medication may increase the risk of developing atherosclerosis and heart failure.
  • Lower blood CoQ10 levels are also associated with greater age [Shimizu 2017]. Malnutrition among senior citizens may be contributing to low CoQ10 status; this is another argument for supplementation.
  • Adequate levels of Coenzyme Q10 are associated with reduced levels of blood bio-markers for inflammation, in particular interleukin 6, C-reactive protein, and tumor necrosis factor alpha [Fan 2017].

Evidence from CoQ10 Supplementation and Heart Disease Studies

  • Professor Urban Alehagen’s KiSel-10 Study has shown that daily supplementation of senior citizens with Coenzyme Q10 and selenium-enriched yeast for four years cuts the risk of heart disease in half [Alehagen 2013].
  • Professor Svend Aage Mortensen’s Q-Symbio Study has shown that adjunctive treatment of chronic heart failure patients with Coenzyme Q10 for two years significantly reduces the risk of death from heart disease and of death from all causes [Mortensen 2014; Mortensen 2019].

Bottom Line: CoQ10 Status and Cardiovascular Disease risk

Adequate levels of Coenzyme Q10 are essential to the cells’ production of ATP energy; moreover, Coenzyme Q10 is an important lipid-soluble antioxidant that scavenges harmful free radicals [Shimizu 2017].

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CoQ10 for Dogs and Cats

King Charles Spaniel
Myxomatous mitral valve disease is the most common heart disease in dogs. It often leads to congestive heart failure. The Cavalier King Charles Spaniel is especially at risk of developing mitral valve disease at an early age. From the onset of congestive heart failure in dogs with mitral valve disease, the median survival time is less than a year even with medical therapy [Christiansen 2020]. Applied early enough, Coenzyme Q10 supplements may increase the life expectancy and quality of life for dogs at risk of heart disease.
Increasingly, people are feeding their dogs CoQ10 supplements. The CoQ10 supplementation is used provide dogs and cats the following health benefits [Gollakner 2020; Puotinen CJ 2019]:

  • improved cellular energy production
  • enhanced antioxidant protection against lipid peroxidation
  • anti-inflammatory effects
  • reduced endothelial dysfunction

Typically, the CoQ10 supplement is given by mouth as a capsule or as a liquid. It is possible, of course, to squeeze the CoQ10 filling out of a capsule onto the dog food.

Pharmacokinetics Study of Repeated Oral CoQ10 Dosing of Spaniels

Now, a research team in Denmark has investigated the pharmacokinetics of oral dosing of Cavalier King Charles Spaniels over a three-week period [Christiansen 2020].

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CoQ10 and Oxidative Stress: A 2020 Meta-analysis

Dr. Judy An Insider's Guide to Coenzyme Q10
Dr. William V. Judy, founder and president of SIBR Research, explains the differences between the ubiquinone form of Coenzyme Q10 and the ubiquinol form. The book is available from amazon.com. ISBN 978-87-7776-186-7.

First off, a few definitions:

Coenzyme Q10 is an essential bio-nutrient with vitamin-like properties. It is not considered a vitamin because our cells do synthesize Coenzyme Q10. However, once we reach adulthood, our bio-synthesis of Coenzyme Q10 begins to decline with increasing age [Kalén 1989]. Furthermore, statin medications are known to inhibit the bio-synthesis of Coenzyme Q10 [Okuyama 2015]. Supplementation is a must.

Oxidative stress is the result of an imbalance between the body’s production of harmful free radicals as a by-product of metabolic processes and the body’s supply of antioxidants to neutralize the free radicals. Oxidative stress, unchecked, results in damage to cell membranes, proteins, lipids, and DNA.

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Higher Plasma CoQ10 Levels, Lower Levels of Muscle Damage

Soccer stadium
The study participants were professional players of the Athletic Club Bilbao team that competed in the first division of the Spanish soccer league during the 2014/15 and 2015/16 seasons. Cumulative exhaustive exercise causes oxidative stress and damage to muscle cells; it also depletes the levels of Coenzyme Q10 in plasma, showing that the Coenzyme Q10 has been active as an antioxidant during the intense exercise. Higher CoQ10 levels can protect against the damage caused by strenuous exercise.

Data from a two-year observational study indicate that maintaining high levels of Coenzyme Q10 in plasma during the hardest part of the soccer season helps professional players [Sanchez-Cuesta 2020]:

  • prevent muscle damage (lower creatine kinase levels)
  • prevent kidney damage (lower uric acid levels)
  • reduce stress (lower cortisol levels)
  • achieve higher physical capacity (video analysis of distance run and running speed)

Based on the results of the observational study, the researchers speculated that CoQ10 can be safely used as a supplement for the prevention of accumulated muscle and kidney damage in elite athletes, possibly even for improving recovery time after intense competition [Sanchez-Cuesta 2020].

Coenzyme Q10 in Plasma is Predominantly in the Ubiquinol State

Coenzyme Q10 molecules are redox molecules with an oxidized state (ubiquinone) and a reduced state (ubiquinol). The Coenzyme Q10 in the plasma is predominantly in the reduced CoQ10 state, i.e. in the state that serves as an electron donor, making it the ideal state for antioxidant neutralization of harmful free radicals [Judy 2018].

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CoQ10 and Aging – A New Book

Professor Lopez-Lluch and Professor Littarru
Professor Guillermo López-Lluch (left), editor of the book Coenzyme Q and Aging, 2020, published by Springer Nature. ISBN: 978-3030456412.

Coenzyme Q10 is important to our understanding of the progression of the aging process and to our understanding of aging-related diseases such as cancer, cardiovascular disease, metabolic syndrome and diabetes, neurodegenerative disorders, and kidney diseases [López-Lluch 2020].

This is the message of a 369-page book entitled Coenzyme Q in Aging. The book is edited by Professor Guillermo López-Lluch, Pablo de Olavide University, Sevilla, Spain. It is dedicated to the memory of Professor Fred L. Crane (December 3, 1925 – August 11, 2016), who first discovered Coenzyme Q10, one of the most important molecules in humans [López-Lluch 2020].

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CoQ10 Supplementation to Improve Fertility in Women

Storch bringing baby
Three meta-analyses show beneficial effects of CoQ10 supplementation on semen quality, semen quantity, and semen mobility. Here, a meta-analysis of studies of CoQ10 supplementation of women with infertility shows a significant effect on clinical pregnancy rates.

A meta-analysis of five randomized controlled clinical studies (n=449 infertile women) has shown that CoQ10 supplementation increases clinical pregnancy rates compared with placebo treatment or no treatment. The CoQ10 supplementation significantly increases clinical pregnancy rates both overall and in infertility subgroups such as the poor ovarian response subgroup (n=286) and the polycystic ovarian syndrome subgroup (n=163) [Florou 2020].

All study participants were women of reproductive age (mean age 33 years) diagnosed with either poor ovarian response or polycystic ovary syndrome. All were attending an assisted reproductive technology clinic [Florou 2020].

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