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Accepted Manuscript

Bioavailability of coenzyme Q10 supplements depends on carrier

lipids and solubilization

Guillermo López-Lluch , Jesús del Pozo-Cruz ,

Ana Sánchez-Cuesta , Ana Belén Cortés-Rodrı́guez ,
Plácido Navas

PII: S0899-9007(18)30488-X
DOI: 10.1016/j.nut.2018.05.020
Reference: NUT 10230

To appear in: The End-to-end Journal

Received date: 19 January 2018

Revised date: 17 April 2018
Accepted date: 22 May 2018

Please cite this article as: Guillermo López-Lluch , Jesús del Pozo-Cruz , Ana Sánchez-Cuesta ,
Ana Belén Cortés-Rodrı́guez , Plácido Navas , Bioavailability of coenzyme Q10 supplements depends
on carrier lipids and solubilization, The End-to-end Journal (2018), doi: 10.1016/j.nut.2018.05.020

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Highlights

 CoQ10 preparations show high differences in bioavailability in humans.

 Physiological unknown factors affect CoQ10 bioavailability in humans.
 Composition of vehicle in CoQ10 preparations affects bioavailability in

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humans.

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 Addition of antioxidants to CoQ10 preparations can decrease
bioavailability.

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 For each individual best CoQ10 preparation must be empirically
determined.

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For: Nutrition

Bioavailability of coenzyme Q10 supplements depends on

carrier lipids and solubilization

Guillermo López-Lluch1*, Jesús del Pozo-Cruz2, Ana Sánchez-Cuesta1, Ana

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Belén Cortés-Rodríguez1 and Plácido Navas1.

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1
Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo,

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CABD-CSIC, CIBERER, Instituto de Salud Carlos III, Carretera de Utrera

km. 1, 41013 Sevilla, Spain.

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Departamento de Educación Física y Deporte, Universidad de Sevilla, Spain.
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*Address correspondence:
Dept. Fisiología, Anatomía y Biología Celular, Centro Andaluz de Biología
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del Desarrollo, CABD-CSIC, Universidad Pablo de Olavide, CIBERER,

Instituto de Salud Carlos III, Carretera de Utrera km. 1, 41013 Sevilla,

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Spain.
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E-mail: glopllu@upo.es
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Abstract
Bioavailability of supplements with CoQ10 in humans seems to depend on the

excipients of formulations and on physiological characteristics of the individuals.

For this reason, the objective of this study was to test seven different

supplement formulations containing 100 mg of CoQ10 in 14 young, healthy

individuals. Bioavailability was measured as Area Under the Curve (AUC) of

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plasma CoQ10 levels over 48 hours after ingestion of a single dose.

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Measurements were repeated in the same group of 14 volunteers in a double-

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blind crossover design with a minimum of 4 weeks wash-out between intakes.

Bioavailability of the formulations showed large differences that were

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statistically significant. The two best absorbable formulations were soft-gel
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capsules containing ubiquinone (oxidized CoQ10) or ubiquinol (reduced CoQ10).

The matrix used to dissolve CoQ10 and the proportion and addition of
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preservatives such as vitamin C affected the bioavailability of CoQ 10. Although

control measurements documented that all formulations contained 100 mg of

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either CoQ10 or CoQ10H2, some of the participants showed high and others

lower capacity to reach high increase of CoQ10 in blood, indicating the

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participation of individual unknown physiological factors. This study highlights

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the importance of individual-adapted selection of best formulations in order to

reach the highest bioavailability of CoQ10 in humans.

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Keywords: ubiquinol; ubiquinone; bioavailability; human; coenzyme Q 10.

Running title: Coenzyme Q10 bioavailability in humans

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Introduction

Coenzyme Q10 (CoQ10) is an essential component of the human electron

transport chain in mitochondria, and also an important lipid-soluble antioxidant

that protects cell membranes and lipoproteins against oxidative damage [1-3].

CoQ10 (in its oxidized form, ubiquinone) can be reduced by many

oxidoreductases to maintain a redox cycle [3]. In its reduced form, CoQ10H2

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(ubiquinol) is able to transfer electrons to acceptors such as complex III in the

mitochondrial electron transport chain (ETC) or, for example, to α-tocopherol in

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other cellular membranes [3]. In this reaction, CoQ10H2 is oxidized back to

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CoQ10. In mitochondria, oxidoreductases that reduce CoQ10 are complex I and

complex II in the ETC, but also dihydro-orotate dehydrogenase, acyl-CoA

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dehydrogenase, sulfide:quinone oxidoreductase, choline and proline

dehydrogenases, whereas in other membranes, Cytochrome b 5 reductase and

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NQO1 are the main oxidoreductases that maintain CoQ10 in its reduced form [4-
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8].

In blood, CoQ10 is located in lipoproteins. Many studies have demonstrated

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that there is a clear relationship between the levels of total cholesterol or LDL

and CoQ10 in plasma [9]. In LDL, CoQ10 shows a clear antioxidant function
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since it is the first antioxidant to be depleted when these lipoproteins are

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exposed to oxidative stress [10]. The proportion of CoQ10H2 to total CoQ10 in

plasma varies from 97-98% to 90%, depending on the study and the age of the

individuals [11-13]. Older subjects show an impaired CoQ10 status with lower

serum CoQ10 concentration and higher proportion of the oxidized form [14].

Reduced levels of CoQ10 in plasma have been also recently associated with the

progression of sarcopenia [15]. In agreement with these findings, we have

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recently shown that higher physical capacity in older individuals shows a direct

relationship with CoQ10 levels in plasma, whereas higher BMI shows an inverse

relationship [16, 17]. In older individuals, higher CoQ10 levels in plasma were

associated with lower LDL oxidation [16]. All these results indicate that the

maintenance of CoQ10 levels in plasma is important in preventing LDL-

oxidation, thereby reducing cardiovascular disease risk and preventing muscle

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deterioration during aging.

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Dietary contribution of CoQ10 is minimal, with daily intakes around 3-5

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mg/day [18]. For this reason, supplementation with CoQ10 can be recommended

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in cases of deficiency to restore, at least, the antioxidant capacity and to avoid

LDL oxidation. However, studies of bioavailability show that response of

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individuals to CoQ10 supplementation is very variable. Further, the causes of the

low bioavailability of CoQ10 have been associated with its large molecular
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weight, high lipophilicity and poor aqueous solubility [19]. For this reason

considerable research has been carried out to increase its bioavailability

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including the use of different types of liposomes or new surfactants [20-24]. The
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different procedures carried out to manufacture CoQ10 to increase bioavailability

and stability has been revised recently [19]..

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In order to determine which factors presented in CoQ10 supplements affect

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the different response to CoQ10 in humans, we determined the bioavailability of

seven different CoQ10 formulations differing in the composition of matrix, crystal

structure and additives, in the same group of 14 healthy individuals.

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Material and Methods.

Subjects

This study comprised 14 healthy young (18-33 years) subjects, see

Supplementary Table 1 participant characteristics. All subjects participated after

signing an informed consent document and all procedures performed in this

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study were in accordance with the ethical standards of the Pablo de Olavide

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University research committee (approval number: 2_2015) and with the 1964

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Helsinki declaration and its later amendments or comparable ethical standards.

Study design US
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The investigation was performed as a double-blind crossover design, with a

washout period of at least 4 weeks between each test. Participants were

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selected between young volunteers that had not taken drugs to reduce fat or
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statins or vitamin supplements (including vitamin E) during the last month, and

maintained a normal lifestyle avoiding the intake of any drug or alcohol during
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the 48 h of each determination. Participants were required to fast for 8 hours

prior to donation of the first peripheral venous blood sample from the antecubital
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vein. Baseline CoQ10 level was measured at time -1h prior to supplementation.
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Immediately after the intake of any preparation the volunteers had a normal

Spanish breakfast including fruit juice, milk, yogurt and cakes; and

approximately 5 hours later a standard Spanish type lunch including vegetables

and meat. Voluntees were asked to maintain the same type of diet during the 48

h of the study. Blood extractions were performed at 2, 4, 6, 8, 24 and 48 h after

CoQ10 sample intake. Blood was placed in a test tube containing heparin (BD

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Vacutainer® LH PSTTM II). After each round of extractions, tubes were

immediately centrifuged at 3000 x g using an Eppendorf benchtop centrifuge

(Model 5810 R) for 10 minutes at room temperature, plasma fraction was

rapidly separated and stored at -80°C until to analysis.

Subjects remained in the CABD research facility from the baseline blood

sampling until the 8 hour blood sample collection. Collection of the 24h and 48h

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blood samples was performed at separate visits. No adverse events (subjective

symptoms) or any change in the concomitant medications were recorded at any

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visit.

Formulations tested
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The formulations, prepared by Pharma Nord using the same CoQ10 raw
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material, differed in matrix, crystal structure and additives and, in the case of

NYD formulation, in capsule type (Table 1). Actual CoQ10 (ubiquinone) /

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CoQ10H2 (ubiquinol) content was measured, as well as individual dose variation

of three capsules per preparation. The content of CoQ10 of the 100 mg capsules
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was determined against CoQ10 CRS Ph. Eur., standard using HPLC-UV normal
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phase chromatography. The CoQ10 was detected at a wavelength of 273 nm.

The HPLC system applied was qualified and the method was validated in
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accordance to ICH guideline Q2. The content of CoQ10H2 was measured by a

similar method, but with ubiquinol as reference standard. The dose variation in

all cases was less than 2 mg CoQ10 / CoQ10H2. Two formulations are indicated

by the trade name (Pharma Nord); the other five are identified by preparation

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codes since they are not commercialized and were prepared also by Pharma

Nord only for this study.

The researchers did not know any characteristics of the formulations until

the end of the study; samples were codified in origin and received by the

researchers without any indication of their composition including the already

commercialized formula. The nature of the formulations was only revealed after

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the final analysis of the data.

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Coenzyme Q determination in plasma

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Plasma CoQ10 levels were determined no later than 1 week after procedure
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from 100 μL plasma samples. CoQ6 was used as an internal standard at

approximately 100 pmol per sample as previously indicated [25]. A more

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detailed and adapted procedure is indicated in supplementary information.

CoQ10 levels were quantified via electrochemical detection, and expressed as

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mg/L.
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Pharmacokinetics parameters
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The Area Under the Curve (AUC0-48) corresponding to the 48 h investigation

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period was computed using the trapezoidal rule by using the Sigma Plot 12.5

software. Maximal concentration (Cmax) and time to maximal concentration

(Tmax) were determined for each of the CoQ10 samples.

Statistics

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Statistical analysis was performed using Sigma Plot 12.5 software.

Comparison between two groups was determined by using the paired t-test,

applying the Shapiro-Wilk normality test. Analysis of more than two groups was

performed by One Way ANOVA with Bonferroni post-hoc, applying the

Kolmogorov-Smirnov normality test. Statistical significance was determined at

p≤0.05.

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Results.

The profile of CoQ10 increase in plasma after the intake of 100 mg CoQ10 of

different formulations is shown in Figure 1. Clearly, the change in plasma CoQ10

levels was higher with Myoqinon when compared with all the other formulations.

This increase was apparent after 4 hours of CoQ10 intake, reaching a peak at 8

h and decreasing afterwards towards normal levels at 48 hours (Figure 1).

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Myoqinon and Ubiqinol QH induced similar plasma profiles (Figure 1). A

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significant incorporation with Ubiqinol QH was found 6 hours after intake, also

reaching a maximum at 8 hours. In the case of Ubiqinol QH, C max was around

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half of the Cmax seen with Myoqinon. In the five remaining formulations,

incorporation was very low. NYD, ICT and KOJ showed a similar pattern of
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incorporation, with a peak at 24-48 hours around 0.2-0.3 mg/L over the baseline

levels of CoQ10. In the case of these compounds Cmax was around 0.35 mg/L,
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very low compared to Myoqinon or Ubiqinol QH. In the case of SMF and ERG,
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the response was even lower (Figure 1, Table 2 and 3).

AUC0-48h was determined as mg/L/48h (Table 2). Clearly, Myoqinon showed

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the highest mean AUC0-48h of CoQ10 in plasma followed by Ubiqinol QH. As

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indicated in Figure 2, the relative presence of CoQ10 in the case of Ubiquinol

QH in plasma was around half of Myoqinon. With the other compounds, CoQ10
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incorporated less into plasma. With KOJ, ICR and NYD mean AUC0-48h was

about 30% of the levels reached with the best compound. ERG and SMF did

not show any meaningful incorporation (Table 2, Figure 2).

In general, the bioavailability of the different compounds indicated a great

variability among the different participants (Figure 3 and Supplementary Table

2). Among the different formulations tested, KOJ and ERG showed lesser
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variability whereas the best formulations, Myoqinon and Ubiqinol QH showed

the highest variability.

Among the two best formulations, Myoqinon and Ubiqinol QH presented a

similar incorporation profile, showing a peak at 8 hours after intake and a slow

decrease up to and beyond 48 h. Lag phase with Ubiqinol QH was longer than

with Myoqinon. Cmax obtained with Ubiqinol QH was significantly lower than in

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the case of Myoqinon (Figure 1, Supplementary Figure 1). A clear difference in

the mean and median AUC0-48h (Table 2) of the two formulations was found.

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However, Ubiqinol QH showed a lower rate of decrease after reaching Cmax

(Figure 1).
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Figure 4 provides a direct comparison of the individual AUC0-48h of the two
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best responding formulations Myoqinon and Ubiqinol QH. Participants showed a

significant 1.7-fold better absorption with Myoqinon in comparison with Ubiqinol

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QH (Table 3). The distribution of the AUC0-48h for different individuals (the
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difference between minimal and maximal values) was also more disperse with

Ubiqinol QH than with Myoqinon (Figure 4). Interestingly, some of the

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individuals that showed lower AUC0-48h with Myoqinon, presented similar or

higher uptake of Ubiqinol QH, whereas other individuals showing high

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bioavailability with Myoqinon showed low uptake with Ubiqinol QH. In general,
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most of the individuals showed lower uptake with Ubiqinol QH (Figure 4). These

results indicate that the response of each individual is independent of the redox

nature of CoQ10.

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Discussion

This study determined the bioavailability of seven different formulations of

CoQ10 from the same origin (in which matrix, oil suspensions, crystal structure

and additives varied) in an analysis lasting 48 h after the intake of one single

capsule containing 100 mg CoQ10. The same cohort tested all the seven

formulations. In order to avoid external factors, the CoQ10 used in this study was

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from the same source and prepared by the same company. Our results show a

great variability in CoQ10 absorption between individuals in agreement with

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many previous studies about acute bioavailability of CoQ10 indicating the

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participation of individual physiology factors [26-30].

The low bioavailability of CoQ10 has been associated with its large
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molecular weight, high lipophilicity and poor aqueous solubility [19]. Some

studies have demonstrated that modifications in excipient composition markedly

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affects CoQ10 bioavailability [31, 32]. In general, our results indicate that the
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nature of the oil used as matrix for solubilizing CoQ10 is essential for the

bioavailability of CoQ10. In our study, soy oil matrix was the best excipient, since
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other combinations such as olive oil and cocoa-butter in ICT and ERG

formulations or olive oil and soy oil in SMF formulation showed lower
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bioavailability besides showing the same content of CoQ10 than KOJ that only
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differed in the composition of the oil matrix.

Further, our results indicate that a higher surface to volume ratio in CoQ 10

crystals was very important to improve bioavailability. Myoqinon and KOJ only

differed by a specific heat/cooling procedure of recrystallization of CoQ10 which

gives a higher surface to volume ratio in Myoqinon as indicated in patent WO

2016038150 A1. AUC0-48h with KOJ was only a quarter of the mean AUC0-48h
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reached with Myoqinon and ΔCmax was around a third with a delay in the

incorporation of CoQ10 into plasma. Further, near all the participants showed a

clear decrease in the AUC0-48h with KOJ in comparison with Myoqinon with the

exception of three of the participants that showed low incorporation with both

formulations (Supplementary Fig 2).

CoQ10 is better absorbed from aqueous or emulsified vehicles than from

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powder filled formulations [28, 33, 34]. However, in our study NYD preparation

(the micronized CoQ10 preparation used in this study) showed a similar

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bioavailiability than KOJ, ICT, ERG and significantly higher than SMF. Only

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Myoqinon showed significant higher bioavailability than this micronized

preparation probably explaining the differences found in other studies [27].

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In this study, the most effective compositions were Myoqinon and Ubiqinol

QH. These compositions differ in the nature of the fat used to dissolve CoQ10
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and in the redox nature of CoQ10. Considering the importance of oil matrix and
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the presence of liposomes by the presence of soya been oil, the difference in oil

composition probably explains why the mean AUC0-48h of Myoqinon was higher
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than the mean of Ubiqinol QH (Table 1 and Supplementary Figure 1). Another

important factor could be the presence of vitamin C in the Ubiquinol QH

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preparation. When we compared the mean AUC0-48h of ICT with ERG

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formulations, which differs only in the presence of vitamin C as additive, the

mean AUC0-48h with ERG was 50% lower than with ICT, although both

formulations were prepared with the same procedure and oil matrix

(Supplementary Figure 3). Taken into consideration this effect of Vitamin C, the

presence of 12 mg of vitamin C in the formulation of Ubiqinol QH could have

also affected the net incorporation of CoQ10 into blood plasma. Other studies

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have also shown that the addition of antioxidants decrease the AUC of a

generic CoQ10 preparation, such as in the case of addition of vitamin E [35].

Furthermore, a previous study comparing a commercial solubilized preparation

containing 100 mg CoQ10 in soy oil with a solubilized preparation containing 100

mg CoQ10 with polysorbate 80, MCT and 300 mg of non-esterified soybean

phytosterols (Sterol CoQ10) in a soft gelatin capsule. In this case, a lower,

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although no significant, AUC was found with the Sterol CoQ10 formulation [30].

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To our knowledge, the only study that compared the bioavailability of the

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oxidized and the reduced form of CoQ10 in humans studied the chronic

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accumulation of CoQ10 in plasma after a daily intake of 200 mg/day of CoQ10 or

CoQ10H2 for 4 weeks [36]. In this study almost all CoQ10 found in plasma was in
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the reduced form, independently of the redox nature of the compound used as

supplement [37]. Langsjoen et al., used the same oil in both formulations
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(diglyceryl monooleate, bee wax, soy lecithin and canola oil), whereas in our

preparation soy oil was the matrix used to solubilize CoQ10 in Myoqinon, and
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medium chain triglycerides (MCT) with the addition of vitamin C for Ubiqinol QH;
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probably explaining our differences in bioavailability.

We cannot exclude the possibility that CoQ10H2 can reach the liver and be
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retained for a longer time than CoQ10. The longer lag phase found with Ubiqinol
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QH in comparison with Myoqinon could be explained by a higher retention time

in both enterocytes and hepatocytes. Furthermore, after reaching Cmax, plasma

CoQ10 level with Ubiqinol QH treatment showed a slower decrease than with

Myoqinon treatment (Supplementary Figure 1). In fact, a recent study performed

in diabetic rats, in which ubiquinol-10 was better absorbed in the liver and

pancreas, suggests a longer retention time in these organs that could explain

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the decrease found in the AUC in comparison with ubiquinone in our study [37].

In other study performed in mice showing CoQ synthesis deficiency by mutation

in the COQ9 gene, the use of water soluble formulations of ubiquinone-10 or

ubiquinol-10 showed a better incorporation of ubiquinol-10 in tissues [38].

These studies indicate the necessity to go in depth into the physiology of CoQ

bioavailability in order to improve its incorporation into tissues.

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We wanted to compare our results with previous acute bioavailability

studies using CoQ10, however this is a complex task since the different time

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periods and doses used in the literature make impossible a correct comparison.

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In our study, we found that there was a direct and very strong correlation

between AUC0-48h and ΔCmax with independence of the compound used

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(Supplementary Figure 3). Using this relationship we reviewed the literature

about the acute effect of CoQ10 supplementation in humans (Table 4). The
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results shown in our study agree with the previous study of Weis et al., [29] in

which modifications of the Myoqinon formulation impaired the bioavailability of

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CoQ10 in human plasma. Further, in both, our study and Weis’ study, Myoqinon
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showed the highest increase of CoQ10 in plasma after a single dose of 100 mg.

No other preparation reached such ΔCmax concentration with this dose; a similar
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variation of concentration was reached only with higher doses such as 150 mg

[39] or 300 mg [40].

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Our study also highlights the fact that the intake of CoQ10 strongly depends

on the individual. Explanations for this may be different microbiota, different

capacities to absorb fats from the gut, or even a different metabolic capacity of

the enterocytes. This observation has been confirmed in other studies with

many other formulations [27, 39, 40]. It seems clear that further studies are

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needed in order to clarify the physiological aspects in the different response of

high incorporating populations in comparison with low incorporating people.

This is very important in cases of CoQ10 deficiency such as in CoQ10-synthesis

deficiency [41], cardiovascular disease [42], aging [2] or sarcopenia [15].

Further, the trials performed to determine the therapeutic effect of CoQ10

supplementation in aging and different diseases use very different dosages in

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small population and with a short follow-up periods [42]. Most patients respond

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to the supplementation with oral CoQ10 [43], however, the different

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bioavailability of CoQ10 requires the use of the best formulation for each

individual in order to reach the highest CoQ10 incorporation into both plasma

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and tissues. We consider that more studies are needed in order to understand
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the mechanisms involved in the different bioavailability of CoQ10 preparations in

humans.
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Conclusion.
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Herein, we demonstrate that the bioavailability of CoQ10 formulations

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depends on the individual and on the type of excipients used for solubilisation of

CoQ10. In our study, the seven tested formulations showed large and significant
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differences in bioavailability. Although, our results are only applicable to the

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compositions used in this study, they highlight the complexity of CoQ10

bioavailability in humans. Even in highly effective compositions, humans show

different response depending on unknown physiological factors probably

including lifestyle, weight, BMI, gender and age of the individual. Special

attention must be paid to elderly people, one of the main target population for

CoQ10 supplementation. Therefore, our study strongly suggest the necessity of

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testing the efficacy of any CoQ10 supplementation in humans by the analysis of

CoQ10 levels in plasma in order to find the most effective preparation for each

patient.

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Acknowledgements

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The authors wish to thank Pharma Nord, Denmark for their generous support

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and for supplying the compounds and the different formulations used in this

study. We also want to thank the volunteers for their predisposition to

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participate in this study and their patience. We also want to thank the Cell

Physiopathology and Bioenergetics Laboratory and especially Juan Carlos

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Rodriguez-Aguilera for his help in the development of HPLC CoQ10 analysis.

The research group is also funded by the Andalusian Government grant BIO177
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(FEDER funds of European Commission).

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Conflict of interest

The authors declare that they have received funding and were supplied with the
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compounds used in this study by Pharma Nord, Denmark.

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Author Contributions: For this study, G.L-L. and P.N. conceived and designed

the experiments, analysed the data and wrote the paper. J.P-C, A.S-C, and

A.B.C-R., supervised extractions and performed the determinations in blood

plasma. All the authors revise and approve the manuscript.

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Figure legends.

Fig. 1. Absorption curves of the kinetics of plasma CoQ10. Changes in mean

plasma CoQ10 concentrations ± SEM over 48 hours after administration of a

single dose of one 100 mg capsule CoQ10 differing in matrix and crystal

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structure.

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Fig 2. Comparative relative absorption as the area under the curve (mean

AUC0-48h) between seven 100 mg coenzyme CoQ10 compositions. The

highest AUC was found with Myoqinon. Values of other compounds are

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indicated in relative to the mean AUC0-48h of Myoqinon. Error bars represent

SEM.

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Fig. 3. Comparative AUC0-48h in plasma CoQ10 levels in mg/L over 48 h for

all formulations. The data represent the maximum, minimum, median (solid
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line), average, (dotted line) with SD indications for each curve. Letters indicate
a
the statistical difference vs. Myoqinon. Significantly different p≤0.05 vs.
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Myoqinon; b Significantly different, p≤ 0.01 vs Myoqinon.

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Fig 4. AUC0-48h for each participant after a single oral 100 mg dose of

Myoqinon and Ubiqinol QH. Data represent the AUC0-48h of each participant
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with both formulations.

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[4] Luna-Sanchez M, Hidalgo-Gutierrez A, Hildebrandt TM, Chaves-Serrano J,

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Table 1. Preparation characteristics.

Preparation Type Matrix Measured

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CoQ10/CoQH10 content
Myoqinon Softgel Soy-oil matrix, drug specification 100.6 mg /
heat/cooling recrystallization
procedure; (1)
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KOJ, CoQ10 Softgel Same as Myoqinon but without 100.6 mg /

heat/cooling procedure
ICT, CoQ10 Softgel Olive oil, cocoa-butter produced 98.9 mg /
accordingly normal softgel filling
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technology
ERG, CoQ10 Softgel Olive oil, cocoa-butter, 25 mg vit 100.5 mg /
C produced accordingly normal
softgel filling technology
Ubiqinol QH Softgel MCT-oil, 12 mg Vit.C, patented; 0.5 mg / 102 mg
(2)
NYD, CoQ10 Hard Gel Fine grinded (micronized) CoQ10 98.3 mg /
powder
SMF, CoQ10 Softgel Olive-oil/soy-oil matrix produced 100.6 mg /
accordingly normal softgel filling
technology
Full manufacturing procedure: 1) Patented WO 2016038150 A1; 2) Patented DK 2008 00040
U3

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Table 2. Pharmacokinetic parameters after administration of a single 100 mg dose of CoQ10 of

7 different formulation.

Preparation AUC0-48
Mean Median Range ΔCmax (mg/L) Tmax (h)
Myoqinon 25.15 ± 4.07 24.54 (2.40 - 52.81) 0.95 ± 0.16 8

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b b
KOJ, CoQ10 6.89 ± 1.66 5.62 (-2.04 - 15.67) 0.33 ± 0.05 48

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b b
ICT, CoQ10 6.28 ± 3.07 2.47 (-5.28 - 35.52) 0.35 ± 0.10 24

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b b
ERG, CoQ10 2.45 ± 1.64 2.92 (-7.88 - 10.79) 0.26 ± 0.05 6
a a
Ubiqinol QH 14.75 ± 3.71 14.196 (-5.55 - 49.96) 0.49 ± 0.11 8
b b

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NYD, CoQ10 8.94 ± 3.33 5.15 (-3.38 - 41.58) 0.38 ± 0.09 24
b b
SMF, CoQ10 -0.73 ± 3.01 -2.78 (-11.78 - 26.02) 0.18 ± 0.10 48
AUC0-48 is indicated as mg/L/48h as the mean ± SEM. C max is indicated as mg/L above baseline
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a
as the mean ± SEM and Tmax as h. Significantly different p≤0.05 vs. Myoqinon; b Significantly
ns
different, p≤ 0.01 vs Myoqinon. No significant.
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Table 3. Magnitude of the difference in mean AUC for a single 100 mg dose of the 7
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formulations.

Factor X/Y
X↓ Y→ Myoqinon KOJ ICT ERG Ubiqinol NYD SMF
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b b b a a b
Myoqinon 1 0.275 0.251 0.098 0.590 0.357 0.029
b ns a a ns a
KOJ 3.630 1 1.097 0.371 2.141 1.297 0.106
b ns ns a ns ns
ICT 3.981 1.100 1 0.407 2.348 1.422 0.116
b a ns b ns ns
ERG 10.218 2.815 2.567 1 6.025 3.650 0.298
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a a a b ns b
Ubiqinol 1.696 0.467 0.426 0.173 1 0.606 0.049
b ns ns ns ns a
NYD 2.800 0.771 0.703 0.286 1.651 1 0.082
b a ns ns b a
SMF 34.340 9.459 8.626 3.509 20.25 12.266 1
a b
Difference significantly different p≤0.05; Significantly different, p≤ 0.01. ns Not significant.
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Table 4. Comparative study of ΔCmax obtained after a single dose experiment with different preparations of CoQ 10 in human studies.

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Study Subjects Preparation Dose ΔCmax SEM

Weber et al., 1997 [44] Male; age 22 ± 1,1. N=9 Capsule 30 mg 0.31
López-Lluch et al., 2017 (this study) Both gender; age 18-30 N=14 (10M/4F) Softgel. Myoqinon 100 mg 1.069 0.177

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ICT
ERG
Ubiqinol QH
NYD
100 mg
100 mg
100 mg
100 mg
100 mg
0.238
0.351
0.258
0.473
0.381
0.053
0.095
0.047
0.108
0.086
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SMF 100 mg 0.181 0.097
Weis et al., 1994 [29] Both gender, age 24-30. N=10 (5M/5F) Hardgel 100 mg 0.775 0.185
Softgel. Bioqinon 100 mg 1.454 0.285
Softgel 100 mg 0.837 0.186
Softgel 100 mg 0.883 0.186
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Wajda et al., 2007 [45] Both gender; (12M/12F) Capsule 100 mg 0.025
NanoSolve 100 mg 0.103
Young et al 2012 [30] Male; age 18-40. N=36 Softgel 100 mg 0.259 0.025
Softgel + sterols 100 mg 0.189 0.034
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Molyneux et al., 2004 [27] Male; age 21-28; N=10 Q-gel, Softgel 150 mg 0.506
Softgel 150 mg 0.277
Capsule-liquid 150 mg 0.197
Capsule-powder 150 mg 0.175
Capsule-liquid 150 mg 0.152
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Capsule-liquid 150 mg 0.149

Chewable tablets 150 mg 0.120
Molyneux et al., 2007 [40] Male; age 20-26; N=8 Q-gel (2 x 30 mg) 60mg 0.267
Q-gel (5 x 30 mg) 150 mg 0.802
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Q-gel (10 x 30 mg) 300 mg 1.010

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Q-gel (3 x 100 mg) 300 mg 0.518

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Martinefski et al. 2016 [46] Both gender, age 18-40. N=6 (3M/3F) Capsule 250 mg 0.490 0.129
Liquid 250 mg 0.980 0.103
Constantinescu et al. 2007 [35] Both gender; mature N=25 (15M/10F) Chewable Wafer 600 mg 0.770
Chewable Wafer + vit E 600 mg 0.660
Softgel 600 mg 0.690

Lucker et al., 1984 [47]

Hosoe et al., 2007 [39] US
Both gender; age 31,9; N=10 (5M/5F)
Male; age 34,2 ± 4,6 N=5
Hard capsule
Powder
Kaneka QH, softgel, ubiquinol
Kaneka QH, softgel, ubiquinol
600 mg
333 mg
150 mg
300 mg
0.660
0.980
1.061
2.506
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