Ubiquinol or ubiquinone: which coenzyme Q10 to choose

Ubiquinol or ubiquinone: two labels, the same molecule, coenzyme Q10, in two different states. Ubiquinone is the oxidised form, the one the industry has been producing for decades. Ubiquinol is the reduced form, the one the body uses to donate electrons and which it continuously derives from the other.

The difference between the two is measured in the blood of those who have taken them for weeks, and three human studies have done this. Here we will look at what coenzyme Q10 does in cells and what those studies found, including why the difference disappears with a single dose. Then how the picture changes with age and with statins, how to take the molecule and how we have formulated our 100 mg softgel.

What is coenzyme Q10 and what does it do in cells

Coenzyme Q10 is in every cell of the body, and its name says as much: 'ubi' comes from the Latin ubique, everywhere. The body produces it itself along the mevalonate pathway, the same chain of reactions that gives rise to cholesterol, and it obtains a small amount from food. The molecule has a ring-shaped head, a quinone, and a tail of ten isoprene units, hence the '10': this tail makes it fat-soluble and keeps it anchored to the inner mitochondrial membrane, where it works.

Its job is a to-and-fro of electrons. Coenzyme Q10 collects them from the first complexes of the respiratory chain and delivers them to the third, and from this process the cell derives ATP, the energy currency for everything it does. When in its reduced form, the same molecule also protects membrane lipids from oxidation: it is one of the few fat-soluble antioxidants the body produces on its own.

In the blood of a healthy adult, it circulates at between 0.40 and 1.91 µmol/L. Taken orally, it reaches its peak in about six hours, with an elimination half-life of around 33 hours: levels build up over days with repeated doses [1].

In the European Union, coenzyme Q10 has no authorised health claims. In 2010, EFSA examined six proposals, from energy metabolism to blood pressure to protection from oxidative damage, and for none of them did it recognise a cause-and-effect relationship. What can be said with certainty is what the molecule does in the cell and what studies have measured in the blood.

Difference between ubiquinol and ubiquinone: reduced and oxidised form

Coenzyme Q10: two forms, one molecule

+ 2 electrons (→ ubiquinol)

UBIQUINONE oxidised form

UBIQUINOL reduced form

− 2 electrons (→ ubiquinone)

Ubiquinol and ubiquinone are the same molecule in two oxidation states. In ubiquinone, the ring has two ketone groups; in ubiquinol, those two groups have accepted two electrons and two protons and have become hydroxyl groups. The transition from one to the other is continuous and reversible, and passes through a one-electron intermediate, the semiquinone. This is exactly the job coenzyme Q10 does in the cell: it loads up with electrons, unloads them, and reloads. Ubichinolo and ubichinone are the same words with traditional Italian spelling.

The difference can also be seen with the naked eye. Ubiquinone is a stable, yellow-orange powder; ubiquinol is white and reoxidises on its own in the air, reverting to ubiquinone. The reduced form therefore requires more care in formulation and packaging, and we will come to our softgel shortly.

In the blood, the contest is already decided: about 95% of the coenzyme Q10 in circulation is ubiquinol, and the ratio between the two forms changes little after intake, whichever form is taken, because absorbed ubiquinone is reduced to ubiquinol [2]. Our Ubiquinol bears the wording 'active form of coenzyme Q10' on the front, and the reason is this: it is the form that donates electrons in the respiratory chain, and it is the one that prevails in the blood.

Ubiquinol or ubiquinone: what human studies have measured

The cleanest comparison was made by Langsjoen and Langsjoen in 2013 on twelve healthy volunteers [3]. Each person took 200 mg per day of ubiquinone for four weeks, then a four-week break, then 200 mg per day of ubiquinol for another four weeks, with the same excipients in the softgel: only the form changed.

Total plasma coenzyme Q10 rose from 0.9 to 2.5 µg/mL with ubiquinone and from 0.9 to 4.3 µg/mL with ubiquinol. The coenzyme Q10 to cholesterol ratio went from 0.2 to 0.7 with ubiquinone and from 0.2 to 1.2 µmol/mmol with ubiquinol. Both differences are significant. Ubiquinone also almost tripled the levels; ubiquinol took them higher. The study is small, open-label and with the two forms in a fixed sequence: these are its limitations.

Plasma CoQ10 after 4 weeks at 200 mg per day

012345

Ubiquinone

0.9 µg/mLbefore

2.5 µg/mLafter

Ubiquinol

0.9 µg/mLbefore

4.3 µg/mLafter

Ubiquinol after

Five years later, Zhang and colleagues repeated the comparison with a more rigorous, double-blind, crossover design in ten elderly men [4]: 200 mg per day with a main meal for two weeks, a washout period, then the other form. With ubiquinol, total plasma coenzyme Q10 rose from 1.3 to 3.4 µmol/L, a significant increase; with ubiquinone, the increase was small and not significant. Six out of ten participants responded better to ubiquinol, two to ubiquinone. In the same study, markers of oxidative stress measured in plasma and ATP in mononuclear cells remained unchanged with both forms.

The third study concerns the ingredient we use, mentioned by name. Hosoe and colleagues, researchers from the Kaneka Corporation, administered Kaneka QH to healthy volunteers in a single-blind, placebo-controlled study [5]: a single dose of 150 or 300 mg, then four weeks at 90, 150 or 300 mg per day. Trough concentrations reached a plateau around the fourteenth day, at 2.61 µg/mL with 90 mg, 3.66 with 150, and 6.53 with 300, and laboratory tests showed no safety issues up to 300 mg.

And then there is the study that generates the opposite numbers online. In 2020, Pravst and colleagues compared, in twenty-one healthy elderly people between 65 and 74 years of age, one ubiquinol capsule and one ubiquinone capsule at the same 100 mg dose, but as a single dose, monitoring their blood for 48 hours [6]. The bioavailability of ubiquinol was found to be 1.7 times that of ubiquinone, with a confidence interval so wide (from 0.9 to 3.1) as to make the difference non-significant. And the coenzyme Q10 appeared in the blood almost entirely as ubiquinol even when it had been taken as ubiquinone.

Lined up, the four studies tell a single story. Ubiquinol's advantage is a finding about the state of coenzyme Q10 after weeks of intake, once blood levels have stabilised. At a single dose, in the first 48 hours, the difference between the two capsules is not apparent: the two types of study measure different things. We covered the general criterion, the chemical form as the primary factor in bioavailability, in Bioavailability of supplements: what it really depends on. What matters here is the practical consequence: ubiquinol gives its best when taken every day, for weeks.

Our Ubiquinol with Kaneka QH® provides the reduced form from these studies in a 100 mg oil-based softgel: the daily dose is one softgel, with meals.

Coenzyme Q10 after 40: why levels decline with age and with statins

The body produces coenzyme Q10 throughout life, but in varying amounts. Kalén, Appelkvist and Dallner measured the ubiquinone content in human tissues from individuals aged one day to 81 years [7]: in most organs, the peak is reached around the age of twenty, after which the content continuously decreases with age; the pancreas and adrenal glands are exceptions, with the maximum level reached at one year old. This is physiological: less is produced with age, and the amount obtained from food remains small. The comparison between the two forms was conducted specifically on elderly men, and it was in this age group that Zhang measured the advantage of ubiquinol [4].

Then there is a second, pharmacological, cause of decline. Statins lower cholesterol by blocking the enzyme that governs the mevalonate pathway, and that pathway is the same one from which coenzyme Q10 is derived: blocking it reduces it as well. The systematic review by Marcoff and Thompson clearly documents this: statin treatment reduces circulating coenzyme Q10, and supplementation restores it [8]. Regarding the effects at the muscular level, the data remain scarce and contradictory.

People taking a statin are therefore among those who most often consider a coenzyme Q10 supplement, and for them, the reduced form – the one which, in studies lasting several weeks, brings blood levels higher – is the choice consistent with the data. When taking medication, the decision should be made with a doctor.

How to take coenzyme Q10: oil-based softgel with a meal containing fats

How to take coenzyme Q10

1. Fat-soluble
2. Already dissolved in the softgel
3. With a meal

Coenzyme Q10 is a large, fatty molecule, insoluble in water. For this reason, its intestinal absorption is slow and limited, and it improves in formulations where the molecule is already dissolved in an oil rather than in a dry powder [1][2]. This is the logic behind the softgel: the active ingredient arrives in the stomach already in solution, ready to be emulsified with the fats from the meal, which act as a carrier. In Zhang's study, the capsules were taken with one of the main meals [4], and this is how ours should also be taken: one softgel a day, with meals.

The same reasoning applies to another fat-soluble active ingredient in our catalogue, the Organic Astaxanthin Oil, an oil-based capsule to be taken with a meal. The general picture on morning, evening, and full or empty stomach is in Supplements in the morning or evening, on a full or empty stomach; the softgel as a dosage form, alongside capsules and tablets, is described in Capsules or tablets: how to choose the form of a supplement.

Ubiquinol with Kaneka QH®: how our 100 mg softgel is formulated

In formulating our Ubiquinol, we decided on three things. The form is ubiquinol, the reduced form, which studies lasting several weeks have measured at higher levels in the blood. The raw material is Kaneka QH®, ubiquinol obtained through bio-fermentation, the same ingredient used in the study by Hosoe and colleagues [5]. Each softgel contains 100 mg of it.

Then there is the carrier. The ubiquinol is in an oil-based softgel, a soft capsule with the active ingredient already dissolved: a fat-soluble molecule must be delivered to its destination already in solution. The shell, with each component and its function declared on the label, has been described item by item in the article Excipients in supplements: what they are for and which ones matter.

Finally, there is protection. We have seen that ubiquinol re-oxidises in the air: for this reason, the formula contains vitamin E, with the role of an antioxidant, which shields the reduced form inside the capsule. And it is present in an amount that also matters for the person taking it: 6.7 mg α-TE per softgel, 56% of the Nutrient Reference Value, for which the product is a source of vitamin E. Vitamin E contributes to the protection of cells from oxidative stress.

The jar is made of amber glass, which shields it from light, and should be kept in a cool, dry place, away from light and heat sources.

Two more things, stated openly. It contains soya, in the form of soya lecithin, a plant-based emulsifier declared as required by law. The beeswax acts as a coating agent and is of animal origin: the product is suitable for vegetarians, but not for those following a vegan diet. The pack contains 30 or 60 softgels, i.e., one or two months' supply at the daily dose of one.

Coenzyme Q10: dosage in studies and supplements

One 100 mg softgel per day, taken with a meal, is the daily dose of our product, and it is a full dose: in the Hosoe study, 90 mg per day is enough for blood levels to stabilise at 2.61 µg/mL, above the reference range for those who do not supplement [5]. For most people, this is the right dose.

For the maximum results measured in studies, you can go up to 200 mg per day, i.e. two softgels. This is the dose at which Langsjoen [3] and Zhang [4] measured the advantage of ubiquinol over ubiquinone, and it is the maximum daily intake that the Ministry of Health allows for coenzyme Q10 in supplements: two softgels remain within the legal limit.

Hosoe's curve shows what changes: with 150 mg, levels rise to 3.66 µg/mL, and with 300 mg to 6.53. Higher dose, higher plateau, although less than proportionally: the efficiency of absorption decreases as the amount taken at one time increases [2][5]. Those taking medication, including statins, should agree the dose with their doctor.

Coenzyme Q10: side effects and warnings reported in studies

The safety profile, in the studies cited, is reassuring. In the Hosoe study, laboratory tests, physical examinations, vital signs and electrocardiograms showed no significant changes up to 300 mg per day for four weeks [5]. Langsjoen recorded no side effects [3]. Marcoff and Thompson, in their review, write that there are no known risks for this supplement [8].

On the label of our Ubiquinol, the warnings are those required by law, stated verbatim: "Do not exceed the recommended daily dose. Food supplements should not be used as a substitute for a varied and balanced diet and a healthy lifestyle. Keep out of the reach of children under three years of age." The directions for use are "Adults and children aged ≥ 12: take 1 softgel per day with meals". During pregnancy, breastfeeding and if you are undergoing medical treatment, a doctor's advice should be sought before taking any supplement.

Frequently asked questions

What is the difference between ubiquinol and ubiquinone?

They are the two forms of coenzyme Q10, the same molecule in two oxidation states: ubiquinone is the oxidised form, and ubiquinol is the reduced form, which has accepted two electrons. In the body, they are continuously converted into one another, and it is precisely this exchange that is the work of coenzyme Q10 in the mitochondria. In the blood, about 95% of coenzyme Q10 circulates as ubiquinol.

Is ubiquinol better absorbed than ubiquinone?

In repeated-dose studies, yes: with 200 mg per day for four weeks and the same excipients, plasma coenzyme Q10 rose to 4.3 µg/mL with ubiquinol versus 2.5 with ubiquinone [3], and in two weeks in elderly men, the increase was significant only with ubiquinol [4]. At a single dose, in the first 48 hours, the difference between the two capsules was not significant [6]. The advantage relates to the levels that are built up over weeks.

Why is ubiquinol recommended after the age of 40?

Because the coenzyme Q10 content in tissues peaks at around twenty years of age and then continuously declines with age [7], and because the comparison that showed the advantage of ubiquinol on plasma levels was conducted specifically in elderly men [4]. It is the form that, for the same dose, brings coenzyme Q10 in the blood to a higher level after weeks of intake.

Should coenzyme Q10 be taken before or after meals?

With a meal. It is a fat-soluble molecule, and the fats in the meal aid its absorption; in studies, the capsules were taken with a main meal [4]. Our Ubiquinol is taken as follows: one softgel per day, with meals.

What is Kaneka QH®?

It is the brand of ubiquinol obtained through bio-fermentation that we use in our softgel. It was studied by name in a single-blind, placebo-controlled study conducted by researchers from the Kaneka Corporation, which measured its absorption and safety up to 300 mg per day for four weeks [5].

How many mg of ubiquinol per day?

One 100 mg softgel per day is the daily dose of our product, which is already sufficient to stabilise blood levels above those of people who do not supplement [5]. For the maximum results measured in studies, you can go up to 200 mg per day, two softgels: the dose used in the comparisons between the two forms [3][4] and the maximum intake allowed in supplements in Italy. Those taking medication should discuss it with their doctor.

Should people taking statins supplement with coenzyme Q10?

Statins block the mevalonate pathway, the same one from which coenzyme Q10 originates, and they lower its circulating levels; supplementation brings them back up, while regarding muscle effects, the data are scarce and contradictory [8]. Those taking statins are therefore among those who most often consider a coenzyme Q10 supplement, and the reduced form is the one that, in studies lasting several weeks, most increases blood levels. When taking a medication, the choice is made with a doctor.

Is ubiquinol suitable for vegans?

Our Ubiquinol with Kaneka QH® contains beeswax (E 901) as a coating agent, which is of animal origin. It is suitable for those who follow a vegetarian diet; those who follow a vegan diet should take this into account.

Further reading

• Bioavailability of supplements: what it really depends on
• Supplements morning or evening, on a full or empty stomach: a practical guide
• Capsules or tablets: how the form of a supplement is chosen

Regulatory references and sources

Studies

1. Bhagavan H.N., Chopra R.K., Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics, Free Radic Res 2006;40(5):445-53. PMID 16551570 — doi:10.1080/10715760600617843.
2. Bhagavan H.N., Chopra R.K., Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations, Mitochondrion 2007;7 Suppl:S78-88. PMID 17482886 — doi:10.1016/j.mito.2007.03.003.
3. Langsjoen P.H., Langsjoen A.M., Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone, Clin Pharmacol Drug Dev 2013;3(1):13-7. PMID 27128225 — doi:10.1002/cpdd.73 (12 healthy volunteers, 200 mg/day, 4 weeks per form).
4. Zhang Y., Liu J., Chen X.Q., Oliver Chen C.Y., Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men, Food Funct 2018;9(11):5653-9. PMID 30302465 — doi:10.1039/c8fo00971f (10 elderly men, 200 mg/day, 2 weeks per form).
5. Hosoe K. et al., Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and 4-week multiple oral administration to healthy volunteers, Regul Toxicol Pharmacol 2006;47(1):19-28. PMID 16919858 — doi:10.1016/j.yrtph.2006.07.001 (90, 150 or 300 mg/day, 4 weeks).
6. Pravst I. et al., Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals, Nutrients 2020;12(3):784. PMID 32188111 — doi:10.3390/nu12030784 (21 healthy elderly individuals, 100 mg single dose, 48 hours).
7. Kalén A., Appelkvist E.L., Dallner G., Age-related changes in the lipid compositions of rat and human tissues, Lipids 1989;24(7):579-84. PMID 2779364 — doi:10.1007/BF02535072.
8. Marcoff L., Thompson P.D., The role of coenzyme Q10 in statin-associated myopathy: a systematic review, J Am Coll Cardiol 2007;49(23):2231-7. PMID 17560286 — doi:10.1016/j.jacc.2007.02.049.

Regulatory references and opinions

1. EFSA NDA Panel, Scientific Opinion on the substantiation of health claims related to coenzyme Q10, EFSA Journal 2010;8(10):1793 — doi:10.2903/j.efsa.2010.1793.
2. Regulation (EU) No 432/2012 — list of permitted health claims (vitamin E: “contributes to the protection of cells from oxidative stress”).
3. Regulation (EC) No 1924/2006 — nutrition and health claims made on foods.
4. Legislative Decree of 21 May 2004, No 169 — implementation of Directive 2002/46/EC on food supplements.
5. Ministry of Health, Other nutrients and other substances with a nutritional or physiological effect — permitted daily intakes in food supplements (coenzyme Q10 and ubiquinol: 200 mg).