It was a hot, dry afternoon in the summer of 2019 in the middle of an herb farm in the North Okanagan. Acres of colorful herbs, including echinacea, chamomile and calendula, adorned the rolling landscape and swayed in the gentle wind. I was attending a seminar in a modified barn with one of the preeminent naturopathic lecturers in North America. The talk was on mitochondria and cellular aging. During the question-and-answer section of the presentation, the talk diverted to the subject of coenzyme Q10 or more specifically, what type of Q10 was preferred? Simply put, which was better ubiquinone or ubiquinol? The esteemed doctor gave an honest and forthright answer and said he simply wasn’t sure. The group of about fifty individuals included naturopaths, dentists, medical doctors, chiropractors, and other allied health professionals. Some opinions were offered and were loosely based on personal experience and conjecture. They seemed to lack scientific merit and the support of evidence-based medicine. One other doctor emphatically contested that ubiquinol was by far better and this was based on the idea that it had superior absorption. Still others said ubiquinone was just as good. The seminar concluded without a general consensus, and we all left without closure about whether ubiquinone or ubiquinol was better—or was there even a difference?

The answer to the question nagged the back of my brain when I had time to think about it. I ruminated about what I seemed to know about coenzyme Q10. Q10 was certainly one of my top ten most important supplements that I recommended. It was good for mitochondrial function and the generation of energy inside cells. It was supposed to be a good antioxidant. It appeared to very safe. I recommended it to almost every patient who took a statin medicine to lower cholesterol. I recommended it to improve brain function, skin support, chronic fatigue, periodontal disease, and maybe to help improve kidney function. I knew it was fat soluble and had a poor absorption profile. I knew that ubiquinol was a more expensive form of Q10 and was told that it was supposed to have superior absorption and perhaps worked better. I used both forms of Q10 at different, random times without much forethought. The major difference I knew for sure was that ubiquinone was a bright orange or yellow color and ubiquinol was milky white in appearance. Beyond that, I realized didn’t know much.

Coenzyme Q10 is a naturally occurring benzoquinone compound that is important in electron transport in mitochondrial membranes. Coenzyme Q10 has a ubiquinone ring structure and has a side chain of 10 isoprenoid units. The name Q10 is derived from its chemical structure. The Q refers to the quinone benzene ring group, and 10 is related to the number of isoprenoid subunits in its tail. The atomic weight of Q10 is 863.3 grams/mole. Its melting point is between 50 to 52 degrees Celsius. The active site of electron transfer and binding are two double-bonded oxygen molecules on the quinone ring structure. Uncoupling of one of the oxygen bonds to the ring structure creates a negative charge that attracts an unpaired positive hydrogen atom for binding. The oxidized form of Q10 is known as ubiquinone and is displayed by 2 opposite oxygen molecules with a double bound to the quinone ring structure. The reduced form of Q10 is known as ubiquinol and is displayed by two opposite OH or hydroxyl groups bound to the quinone ring structure. Ubiquinone and ubiquinol are inter-converted into each other depending on the redox reaction and the necessity to accept or donate electrons. Both are necessary and both are considered active, albeit with different redox states.¹

Mantle and Dybring provided an excellent overview of the absorption process and subsequent metabolism of coenzyme Q10. They acknowledged that some manufacturers made incorrect claims regarding the bioavailability of Q10 supplements based on the current research.

Contrary to some manufacturers claim, ubiquinol is not the active form of Q10. Both forms are continuously inter-converted from one type to the other. Most Q10 studies found on medical databases are with the ubiquinone form. Two landmark studies about Q10 in congestive heart failure (CHF) both used ubiquinone. The 2014 Q-Symbio study involved 420 CHF patients in a placebo-controlled trial who were administered the ubiquinone form of Q10. A significant improvement in heart function was observed in the Q10-treated group. The 2013 Kisel-10 study was conducted with 443 heart patients in Sweden and showed significant improvement with the group that received 200 milligrams of ubiquinone per day. Mantle and Dybring further stated that coenzyme Q10 is being constantly regenerated. Q10 influences several hundred genes in the human body. And at least five different enzymes are believed to be involved in the conversion of ubiquinone to ubiquinol. There appears to be a wide variability in individual absorption capacity.²

Ingested levels of coenzyme Q10 from daily food intake are estimated to be up to 5 milligrams per day. Total daily requirements of Q10 in the body are estimated to be 500 milligrams per day. Total body stores of Q10 are estimated to be 2 milligrams. Therefore, ingested sources and body stores of Q10 are being constantly regenerated to meet daily requirements and demands. These numbers seem to justify the recommended daily dose of 300 milligrams of Q10 in congestive heart failure patients to meet therapeutic plasma levels. Optimal biosynthesis of Q10 occurs in the mid-twenties and decreases with age. Q10 was originally purified from bovine heart tissue in the 1950s. Q10 exists in cis and trans isomeric forms based on the isoprenoid side chain stereochemistry. The trans form of Q10 was identified as the only active form utilized in the human body. It is only absorbed as an unbound molecule. It is transported as ubiquinol in the plasma bound LDL and VLDL molecules in the blood irrespective of what form that is initially ingested. Some manufacturers claim that ubiquinol is better absorbed.²

The concept of superior absorption promulgated on the internet originated from comparisons between bioavailability data take from earlier published studies that did not provide the form of Q10 used, provided no direct comparison between the different forms and did not use thermal dispersion techniques to enhance the absorption of ubiquinone. Newer research shows lipid carriers such as soy or palm oil seem to enhance the intestinal absorption of Q10. The transit time from stomach to duodenum is about 60 to 90 minutes. Most ingested ubiquinol will be oxidized to ubiquinone during this time. The transit time from stomach to intestines to lymph is between 5 to 8 hours. Q10 is generally acknowledged to have poor water solubility and is incorporated in fat micelles for transport and absorption. Absorption is via passive facilitated diffusion across enterocytes. Nashimoto and others discovered a mechanism of intestinal Q10 absorption involving Niemann-Pick C1 like (NPC1LI) transporter protein. This protein spans the cellular membrane of enterocytes and hepatocytes and is involved in absorption of fat soluble molecules and cholesterol. Transport of Q10 was dramatically increased by genetic over-expression of this protein transporter in animal experimental models. Singh and others showed that the administration of 2 capsules of 100 milligrams of Q10 at different times increased absorption better than the 2 capsules administered at the same time. They concluded that there was a limit to the intestinal absorption capacity of Q10.^2-4

Once inside enterocytes Q10 is incorporated into chylomicrons and released via exocytosis and then transferred to lymph and blood. Q10 in the blood is mainly in the reduced form as ubiquinol. Dietary or supplementary Q10 in the oxidized form as ubiquinone is rapidly converted to the reduced form as ubiquinol in the enterocytes and lymph. Q10 is mainly protein bound in the blood and very little is in free form. Chylomicrons containing Q10 in the form of LDL and VLDL then go to the liver for processing. Cmax or maximum concentration in the blood occurs 6 hours after initial ingestion of Q10. The half life of Q10 in the blood is about 33 hours. Plasma levels vary from person to person and can range from 0.5 to 1.5 micrograms/milliliter. Twice per day dosing resulted in increased plasma levels to 0.90 to 3.25 micrograms/milliliter.

Q10 is found in all cells and is dispersed to all tissues of the body. Generally, the higher the level of cellular metabolic activity, the higher the concentration of Q10 of intracellular Q10. Heart tissue has the highest concentration in the entire body. Q10 is not considered a vitamin per se, because all cells in the body can make it, except for red blood cells. Besides mitochondria, Q10 is also found in the endoplasmic reticulum, Golgi apparatus, lysosomes, and peroxisomes.²

Kaikkonen and others summarized the main determinants and absorption of plasma Q10 in the form of ubiquinone in a blinded, placebo-controlled trial. A dose of 30 milligrams had only a marginal effect on plasma Q10 levels in a group of non-Q10 deficient subjects. However, a dose of 200 milligrams increased plasma Q10 levels by 6.1 times.^2,5

Bhagavan and Chopra showed that both total and plasma Q10 levels increased above baseline in a gradual manner with increased doses of Q10. Plasma Q10 levels hit a plateau at 2,400 milligrams of Q10 per dose. Ninety-five percent of all circulating Q10 was in the form of ubiquinol in plasma and blood. Solubilized forms of Q10 have superior bioavailability as evidenced by the increased Q10 dose response.^2,6

Bhagavan and Chopra discussed Q10 absorption, tissue uptake, metabolism, and pharmacokinetics. They acknowledged that Q10 is hydrophobic, has large molecular weight, and has a rather slow and limited absorption profile. The time to reach maximum concentration in the blood is up to 6 hours after initial ingestion. The elimination half life is up to 33 hours. The accepted plasma reference range was between 0.40 to 1.91 micromoles/liter in healthy adults. There is a correlation between increased plasma Q10 levels and ingested dose to a certain point. Animal studies showed that Q10 in large doses is taken up by all tissues, including heart and brain. They also noted that Q10 has an excellent safety profile.^2,7

Barakat and others analyzed the fraction absorbed of different coenzyme Q10 formulations in human and animal models. The purpose of their review was to assess different drug delivery systems that might improve the problems of low solubility and low absorption of Q10. Different drug delivery systems that might enhance Q10 bioavailability ranged from simple oil dispersions to emulsions and nanotechnology. The results were given as fraction of the original amount absorbed and measured in the bloodstream. In humans the fraction absorbed of different formulations ranged from 1.53 to 12.48%. The highest fraction absorbed was measured in a formulation that had a self-emulsified drug delivery system or sedds. It was generally agreed upon that coenzyme Q10 has a poor absorption profile because of its hydrophobicity and large molecular weight size. And it was further agreed, that technological enhancements in formulations and delivery system are necessary to improve its profile and utility as a supplement in humans.⁸

Lopez-Lluch and others assessed the bioavailability of seven different forms of Q10 supplements administered as a single 100-milligram dose to 14 young, healthy volunteers. Bioavailability was measured 48 hours after consuming a single dose of different Q10 supplements followed by a washout period of four weeks, then followed with another measurement after consuming a different formulation. They analyzed the area under the curve (AUC) that represented the percentage of Q10 that entered blood circulation. They also analyzed Cmax or the peak plasma concentration of Q10 following intestinal absorption. The failure to subject crystalline Q10 in the ubiquinone form to thermal crystal dispersion resulted in a 75% decrease of absorption and a subsequent decrease in plasma levels. Ubiquinol is not bound in a crystal lattice and does not require crystal dispersion to enhance absorption. Different Q10 matrix affected different absorption rates. The two best responses were an oxidized Q10 in capsule and reduced Q10 in a soft gel.^2,9

In one crossover study by Vitetta and others, 150 milligrams of either ubiquinone, ubiquinol or ubiquinone liposome were administered to a group of subjects at different times. Significant intra-subject variability of Q10 absorption was observed and persisted throughout the duration of the study irrespective of what form of Q10 was used. They concluded that Q10 absorption rates varied significantly between individual subjects. No significant difference between the type of Q10 and absorption was noted.^2,10

A study by Miles and others looked at nine healthy subjects who were given 100 milligrams of Ubiquinone and 100 milligrams of ubiquinol at different times. No significant difference in plasma Q10 levels was observed. In contrast, some other studies showed a significant improvement in bioavailability of ubiquinol versus ubiquinone, particularly in older subjects.^2,11

In a 2009 study by Evans and others, a 100-milligram single dose of ubiquinone and ubiquinol was given to 10 healthy volunteers over the 60 years. The plasma level of Q10 was significantly higher when ubiquinol was consumed compared to ubiquinone.^2.12

In 2018 Zhang and others performed a double-blind randomized crossover trial involving 10 adult males who were 55 years or older. Respondents consumed a specific form of 200 milligrams of Q10 per day for two weeks, followed by a two-week washout period, then consumed 200 milligrams of a different form of Q10 for two weeks. Four different blood samples were taken at different times. Plasma Q10 levels were significantly higher when the subjects took ubiquinol. Ubiquinol significantly increased plasma ubiquinone levels from 0.2 to 0.6 micromoles/deciliter and total serum Q10 levels from 1.3 to 3.4 micromoles/deciliter. Ubiquinone did not significantly increase plasma levels. Of the 10 subjects, six responded better to ubiquinol and two responded better to ubiquinone supplementation.^2,13

In a 2014 study, Langsjoen and Langsjoen compared ubiquinol versus ubiquinone in a crossover study where 12 healthy volunteers consumed 200 milligrams of a form of Q10 for four weeks, followed by a four-week washout, then consumed 200 milligrams of the other form of Q10 for four weeks. The ubiquinol treated timeline resulted in significantly higher levels of plasma Q10. Plasma Q10 levels increased from 0.9 to 2.5 micrograms/milliliter after four weeks when ubiquinone was administered. Plasma Q10 levels increased from 0.9 to 4.3 micrograms/milliliter after four weeks when ubiquinol was administered. It was noted that the crystal ubiquinone was not subject to thermal dispersion before encapsulation. No side effects were observed and either Q10 was well tolerated.^2,14

Pravst and others assessed the bioavailability of different formulations of coenzyme Q10 in a randomized, three period, crossover study involving 21 older adults between the ages of 65 to 74 years. The treatment was a single dose of 100 milligrams of Q10 in the of ubiquinone, ubiquinol, and water-soluble Q10 syrup at separate times. Ubiquinol increased plasma levels 1.2 times above baseline compared to ubiquinone. The water-soluble syrup increased plasma levels 2.4 times above baseline compared to ubiquinone. No difference in redox status was observed between the different formulations. The absorbed Q10 observed in the blood was in the form of ubiquinol for all different formulations.¹⁵

Petrangolini and others revealed that the phytosomal form of Q10 improved absorption by three times. One capsule improved plasma Q10 levels to 0.864 +/- 0.120 micrograms/milliliter. This represented an increase of 41% above unbound Q10. Two capsules improved plasma Q10 levels to 1.321 +/- 0.400 micrograms/milliliter. This represented an increase of 116% above unbound Q10. This was compared to a baseline of one capsule of unbound Q10 giving a plasma level of 0.614 +/- 0.120 micrograms/milliliter and two capsules giving a level of 0.614 +/- 0.160 micrograms/milliliter.^2,16

Other studies use a variety of agents to improve Q10 absorption, including polyethylene, phosphorylate, tocopherols, poloxamer, polyvinyl, and hydrolyzed protein.²

Archie just showed up at my office one day. Archie was a rough-and-tumble logger and backwoodsman from the mountains above Christina Lake. He was a middle-aged man with a long beard, a paunch, and a plaid jacket. He had just come from the cardiologist’s office. He said he had a heart attack several years prior and was on cholesterol, blood pressure, and blood thinners. He was very fatigued, short of breath, and had trouble walking a block or more. He took no vitamins and ate a typical meat and potatoes diet. His vital signs and lab tests all appeared within normal limits. I gave him a vitamin B12 shot, recommended a multi-vitamin, and told him to take coenzyme Q10. He left and I didn’t see him for a year and a half.

A clean-shaven man in a plaid jacket showed up at my office one day. He asked if I remembered him. I said I didn’t. He told me that he came from the cardiologist’s office and his heart function improved by 40%. He was on the same medicine as before and the doctors didn’t know why. They told him to keep on doing whatever he is doing. And more importantly, Archie said he felt much better and could now walk much further without fatigue or shortness of breath. He liked Q10 and said he thought it really helped him.

Sharon was a long-time cancer patient who had an inquisitive mind and a keen interest in alternative medicine. One day she said she had a present for me. She said that one of her best friends was the manager of a vitamin company. She took out what looked like a sack of dark, black capsules. She said here were the Q10 capsules that fell on the floor during the manufacturing process at the vitamin factory. They couldn’t re-bottle them and just generally threw them away. She was allowed to collect some and was giving some as a sample for me. Now in my possession was several hundred or more 200 milligrams of high-quality encapsulated coenzyme Q10 for me to try. And so I tried them. Being a somewhat aggressive type A personality with a curious mind, I decided to see if more was better. I took upwards to 2600 milligrams of Q10 per day for about a month. My energy improved and I felt really good. As I was lap swimming at the time, I felt stronger and faster than before. I did not experience any side effects and I still slept well. I liked Q10.

Now to circumambulate the question, which is better ubiquinone or ubiquinol? The oxidized form of coenzyme Q10 as ubiquinone is interconverted to the reduced form as ubiquinol easily and rapidly in the body at many levels and then reconverted back again to its original form. Despite what some overzealous manufacturers suggest ubiquinol is not better or more active. The cumulative absorption data suggests that ubiquinol is probably better absorbed than ubiquinone. However, newer emulsions of ubiquinone have shown improved absorption profiles. If the extra cost of ubiquinol justifies taking a lesser dose to reach a therapeutic plasma Q10 level, then so be it. The current evidence suggests that both are fairly equally good.

References

1. Pubchem. National Library of Medicine. Coenzyme Q10. https://pubchem.ncbi.nlm.nih.gov/compound/Coenzyme-Q10. Accessed January 5, 2021.

2. 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.
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4. Singh RB et al. Randomized, double-blind placebo-controlled trial of coenzyme Q₁₀ in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998: 12;347–353.
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12. Evans M et al. A randomized, double blind-trial on the bioavailability of two CoQ10 formulations. J Funct Foods. 2009: 1;65-73.
13. Zhang Y et al. Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men. Food Funct. 2018 Nov 14: 9(11);5653-5659.
14. Langsjoen PH and Langsjoen AM. Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with uniquinol verus ubiquinone. Clin Pharmacol Drug Dev. 2014 Jan: 3(1);13-7.
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