Abstract
Context
The results for the absorption and bioavailability of different product formulations of Coenzyme Q10 (CoQ10) that are found in the literature are highly variable and confusing to CoQ10 researchers and consumers.
Objective
The study intended to measure and compare the single-dose absorption and steady-state bioavailability of three types of Crystal Free (CF) CoQ10 formulations—CF CoQ10, crystalline CQ10, and dry-powder CoQ10.
Design
The researcher designed a randomized double-blind laboratory study for the three formulations that was conducted by the same laboratory and investigators and used the same protocol, the same analytical laboratory, and the same methods of analysis
Participants
Participants were matched groups of normal males and females.
Outcome Measures
Single-dose absorption and steady-state bioavailability was determined for nine CoQ10 formulations: (1) three formulations of CF CoQ10 in lipid-based softgels, (2) three formulations of crystalline CoQ10 in lipid-based softgels, and (3) three formulations of dry-powder CoQ10 in two-piece, hard gelatin capsules. Plasma profiles were constructed and used to calculate the plasma level at Cmax and the percentage of the dose. From the steady-state bioavailability profiles, the plasma concentrations and the area under the curve (AUC) were determined. From that data, the relationship between the single-dose absorption and the steady-state bioavailability was derived using a linear regression analysis.
Results
The single-dose absorption was significantly greater for the CF group compared to that for the crystalline and dry-powder groups (P ≤ .001). The absorption and bioavailability of the crystalline group was significantly greater than that for the dry-powder group (P ≤ .001). For the CF group, the Δ Cmax was 1.83 ± 0.58 ug/ml, the % absorption was 7.03 ± 2.03, the steady-state CoQ10 level was 3.28 ±0.92 ug/ml, and the AUC was 32.80 ± 10.05 ug/ml x days. For the crystalline group, the Δ Cmax was 1.40 ±0.24, the % absorption 3.08 ± 0.53, the steady-state plasma level was 2.50 ± 0.54 ug/ml, and the AUC was 7.55 ± 1.87 ug/ml x days. For the dry powder group, the Δ Cmax was 0.33 ± 0.05 ug/ml, the % absorption was 1.28 ± 0.96 %, the steady-state plasma CoQ10 level was 1.55 ± 0.43 ug/ml, and the AUC was 5.34 ± 1.10 ug/ml x days. The CF formulation’s absorption and bioavailability were superior to that of the crystalline and the dry powder formulations. The relationship between the single-dose absorption and the steady-state bioavailability was described by the linear equation y = 1.26 x 1.60.
Conclusions
The CF formulation was superior in absorption and steady-state bioavailability compared to the crystalline and dry powder formulations. The linear relationship between the single-dose absorption and the steady-state bioavailability gives an estimate of the steady-state bioavailability in a 24-hour study compared to a longer and more expensive 30-day study.
Introduction
For any orally ingested substance to have an effect, it must be absorbed by the body. Absorption is the process of a substance’s movement from the site of administration, the gut, into the systemic circulation. Bioavailability is the measure of how much a substance is able to be absorbed into the systemic blood circulation. Substances that are formulated to have high bioavailability help the body to absorb more of that substance, without increasing the dose.
Coenzyme Q10’s (CoQ10’s) molecule size—redox forms: ubiquinone/ubiquinol—is fairly large: 863.3/865.4 Daltons. Both redox forms in lipid-soluble materials are sold commercially as dry crystalline powder. The crystals in CoQ10 formulations are man-made, having been formed in the purification of CoQ10 in the manufacturing process. The large crystals—crystalline dry powder—aren’t directly absorbable through the intestinal walls. The body can’t absorb a crystal of any molecule.1 Since absorption occurs on a single-molecule basis, the crystals must be broken down into smaller single units of CoQ10 by being dissolved or melted.
This process in the human body involves secretion into the small intestine of pancreatic enzymes and bile, which facilitates the emulsification and micelle formation required for absorption of lipophilic substances. CoQ10 in the lymph, plasma, and cells isn’t in a crystalline form. Normal human digestion is very slow at dissolving large lipid crystals, and they don’t always fully dissolve in the small intestine. The absorption rate of CoQ10, plain, dry crystalline powder is low, less than 1%, of the dose administered. For orally ingested CoQ10, improving bioavailability does matter because of its poor bioavailability.
The lipid carriers formulated in crystalline CoQ10 products and in crystal-free (CF) CoQ10 products are critical for the absorption and the resulting plasma bioavailability of the ingested CoQ10. Some commercial lipid-based formulations use various technologies to improve CoQ10 absorption by micronizing—particle size reduction, emulsification, liposomes, micelles, and nanoparticles—and other formulas either partially or fully solubilize the crystalline powder. In most cases, partial crystallization can be found in these formulations.
The best analytical way in which science tests for absorption or bioavailability of a substance is by performing in-vivo human studies: (1) absorption studies—primarily to find out whether some of the essential nutrients have been absorbed from the gut or not, and if they were, to determine how much was absorbed; (2) steady-state studies—after repeated, consistent (regular) oral administration of a substance, a steady-state level of the substance is reached in the blood circulation; the steady state is the point at which the amount of substance going in is the same as the amount of drug being taken out. The 14- to 28-day steady-state bioavailability study and the single-dose absorption study have been described by many investigators.2-6
The single-dose absorption and steady-state bioavailability of different CoQ10 formulations that have been reported in the literature have been highly variable.1,2 Moreover, some confusion exists in the naming of absorption and bioavailability studies. Many authors designate single-dose absorption as bioavailability studies, while other authors call studies of steady-state bioavailability absorption studies.2-7
Single-dose Absorption
The earliest single-dose absorption study in the literature evaluated the Bio-Quinone Q10 formulation (Pharma Nord) compared to three other formulations.2 The study measured the Cmax, which is a pharmacokinetic measure used to determine drug or substance dosing and is the highest concentration of a drug or substance in the blood after a dose is given. The Cmax for the Bio-Quinone Q10 occurred in six hours at a level of 1.25 ug/ml. The calculated total CoQ10 absorbed at Cmax was 2800 ug. The calculated percentage of the dose absorbed at Cmax was 2.8% of a 100-mg dose. The other three formulations’ percentages of dose absorbed at Cmax were 0.90 to 1.55%.
The Cmax in most published studies ranges from 0.34 to 0.91 ug/ml.2-7 In one study, the Cmax at 4 hours after ingestion of 120 mg of CoQ10 was 5.99 ug/ml.5 In that study, a colloidal CoQ10, solubilized CoQ10 and an oil based CoQ10 were evaluated. Twenty normal participants were divided into groups of five. Each group received a supplement of a different CoQ10 product. The product with a delta Cmax of 5.99 ug/ml was the colloidal formulation. In 6 hours, a calculated 25 460 ug were absorbed at Cmax. The percentage of the ingested dose absorbed at Cmax was 25.5%. Almost all of the absorbed CoQ10 was diffused out of the blood in 10 hours. The half-life was 8 hours. The half-life for the other three products was 6 hours. The between-subject variation around the group mean level for the colloidal formulation was 6.6 %. The variance for the other three products were in the 12%-14% range. These between-subject variations are low compared to those reported from other studies.1,8,10,11
In a more recent, double-blind crossover study, the Cmax of a well-formulated preparation with specific carrier lipids and with a specific heating-and-cooling encapsulating process was 0.84 ug/ml.4 The estimated amount of the 100-mg dose of CoQ10 absorbed at Cmax was 3024 ug. The percentage of the dose absorbed at Cmax was 3.0%. The between-subject variation around the group mean level was 25%. The half-life in the blood exceeded 34 hours.
Other single-dose absorption studies can be found in the literature.2-6 In most of those studies, the Cmax occurred in six hours and ranged from 0.092 to 1.07 ug/ml. The percentage of a 100-mg dose absorbed at Cmax ranged from a low of 0.35% to a high of 3.4%. The lowest values were found in dry-powder crystalline formulations, while the highest values were found in a crystalline CoQ10 in a lipid-based soft gel.
Steady-state Bioavailability
Steady-state bioavailability is a reflection of absorption and is actually the accumulation of absorbed CoQ10 in the plasma over an extended time interval. It’s the plasma CoQ10 that is available to the cellular compartments.
Measurement of steady-state bioavailability doesn’t measure the CoQ10 entering the blood during the intestinal absorption interval. It measures the accumulation of CoQ10 in the plasma in response to a daily dose of CoQ10. Bioavailability isn’t a measure of absorption, but absorption has to occur before any accumulation can take place from a daily exogenous source.
The lipid carriers formulated in crystalline and CF CoQ10 products are critical for the absorption and the resulting plasma bioavailability of the ingested CoQ10. Most products in studies have used carrier lipids consisting of triglycerides or diglycerides. These diglycerides and triglycerides have to be broken down to monoglycerides in the digestive process before absorption.
Bhagavan and Chopra1 have recommended CoQ10 added to yogurt with oil for digestive stability and micellarization. Langsjoen et al7 have shown that concurrent consumption of peanut butter with CoQ10 improves the absorption of CoQ10.
The steady-state, CoQ10 concentration in dry-powder studies has been found to change the plasma level only by 0.15 to 0.45 ug/ml.2,3,6 The lipid-based soft gel formulations have been found to increase the plasma concentration by 1.3 to 2.9 ug/ml.2-6
CF Formulations
The clinical effectiveness of supplemental CoQ10 in the management of age-related degenerative diseases, low energy syndromes, statin-associated myopathies, and other clinical conditions has grown immensely as new and more absorbable CoQ10 products have been developed.10-14
Because the body can’t absorb a crystal of any molecule and because the thermal dissolution point of the CoQ10 crystal (48-52° C) is 10° C to 13° C above body temperature (37° C), CF formulations may have superior single-dose absorption and steady-state bioavailability compared to the absorption and bioavailability of crystalline softgel and dry-powder formulations. Moreover, a linear relationship may exist between single-dose absorption and steady-state plasma bioavailability because no CoQ10 accumulation can occur in the plasma if no absorption takes place.
The current study intended to measure and compare the single-dose absorption and steady-state bioavailability of three types of CoQ10 formulations—CF CoQ10, crystalline CQ10, and dry-powder CoQ10.
Methods
Participants
The researcher designed a randomized double-blind laboratory study. Participants were matched heterogenous groups of normal males and females. Wash-out intervals of 30 days separated the three sets of three studies.
All studies were conducted in one laboratory by the same investigators using the same protocol and the same analytical laboratory. The studies were approved by an independent review board in Austin, Texas.
Procedures
CoQ10 formulations
Single-dose absorption and steady-state bioavailability was determined for nine CoQ10 formulations: (1) three formulations of CF CoQ10 in lipid-based softgels, (2) three formulations of crystalline CoQ10 in lipid-based softgels, and (3) three formulations of dry-powder CoQ10 in two-piece, hard gelatin capsules.
The three CF formulations were: (1) Q-Best from Best Formulations, CoQsol-CF from Softgel Technologies, and HiSorb from National Vitamin. The three crystalline formulations were: (1) CoQ-Sol from Softgel Technologies, Q-Gel from Tishcon, and Q-Sorb from Nature’s Bounty. The dry-powder formulations were generic; numerous brands exist of the crystalline-powder products.
Outcome measures
The single-dose absorption and the steady-state bioavailability were tested when the capsules were heated to 50° C, where no crystals occurred in the formulations. Plasma samples were collected in rested and fasting participants from their forearm veins by venipuncture. The samples were rapidly chilled and centrifuged to separate the plasma from the formed elements in the blood and were labeled and rapidly frozen at -82° C. Sample collection was blinded, and samples were sent overnight to the analytical laboratory. All samples were analyzed in one facility using the same extraction protocol and the same high-performance liquid chromatography (HPLC) detection system.
From these samples, the plasma profiles for single-dose absorption and steady-state bioavailability were constructed. For the single-dose studies, plasma was collected from participants at baseline and at 2, 4, 6, 8, 10, 12, and 24 hours after ingestion of a 100-mg CoQ10 dose, and their plasma CoQ10 concentration was measured. The plasma level at Cmax and the percentage of the ingested dose were calculated. From the steady-state bioavailability profiles, the plasma concentrations and the area under the curve (AUC) were determined. Those plasma samples were collected at baseline and at 7-, 14-, 21-, and 28-day intervals.
Outcome Measures
Calculation: Percentage of ingested dose
The percentage of the ingested CoQ10 dose absorbed at Cmax was calculated from the change in plasma CoQ10 (ug/ml) multiplied by the plasma volume (ml) divided by the CoQ10 ingested dose (ug) multiplied by 100.
 |
The plasma volume was derived from a nomogram using gender, weight, and age.8
Calculation: AUC for the 28-day, time-based plasma bioavailability
The AUC was calculated using the sum of the daily CoQ10 change (Δ) in the plasma Sum of the daily Δ in plasma CoQ10 (0-28 days).
The AUC was calculated only for the steady-state bioavailability curve. No long-term steady-state interval exists in the single-dose absorption curve.17
Statistical Analysis
After the analysis, the measured results were sent to a statistical group, where the code was broken, and descriptive statistics were determined. From the collected data, the relationship between the single-dose absorption and the steady-state bioavailability was derived using linear regression analysis. A P value of ≤.05 was accepted as a significant difference between the CoQ10 products.
Results
Micrographs of Crystals in CF Formulations
Figure 1 presents microphotographs showing the crystal formulations in the three CoQ10 CF products in the capsule: (1) at room temperature, 24° C; (2) when heated to body temperature 37°C; (3) when heated to 50° C; and (4) when cooled to room temperature, 24° C.
Figure 1.
Microphotographs of Crystal-free (CF) Products in the Capsule. The figure shows the products at room temperature, 24°C; when heated to body temperature, 37° C; (3) when heated to 50° C; and when cooled to room temperature, 24° C. Q-Best contains conjugated linoleic acid (CLA) and a monoglyceride; CoQsol-CF contains lime oil and a triglyceride; and HiSorb contains campul oil and a triglyceride. Q-Best had no crystals at any temperature, whereas crystals were found in the CoQsol-CF and HiSorb except at 50° C.
The formulation with no crystals was Q-Best. The other formulations had crystals except when heated to 50° C.
Single-dose Absorption Curve
Figure 2 shows the single-dose, time-based profiles of the plasma CoQ10 mean concentrations for each group of three Co10 products.
Figure 2.
Time-based Profile of the Single-dose Absorption for the Group Means of the Crystal-free (CF), Crystalline in Lipid-base, and Dry-powder CoQ10 Formulations. The CF formulation had significantly greater absorption than the crystalline or dry-powder formulations (P ≤. 001). The group mean for the crystal-free product was 7.03% of the 100-mg dose. The absorption of the Q-Best formulation was 8.48%.
CoQ10 appeared in the plasma at four hours after ingestion of the dose and peaked at 6 to 8 hours, the Cmax. After the Cmax, a rapid decrease occurred in the plasma CoQ10, possibly explained by the fact that the study’s participants were fasting. This rapid decrease in plasma CoQ10 was followed by a much slower reduction in the plasma level for the last 12 hours of the 24-hour period as the plasma CoQ10 was slowly distributed to the body’s cells.
The CF formulation had significantly greater absorption than the crystalline or dry-powder formulations (P ≤ .001). The group mean for the CF products was 7.03% of the 100-mg dose. The absorption of the Q-Best formulation was 8.48%.
Steady-state Bioavailability Time-based Curve
Figure 3 presents the steady-state bioavailability profiles for the plasma CoQ10 of the different product types. The profiles were similar in all nine studies, and the plasma curves were hyperbolic. The steady-state plasma level started after 14 days of supplementation and remained constant thereafter. The CF formulation had a significantly greater bioavailability than the crystalline or dry-powder formulations (P ≤ .001).
Figure 3.
Steady-state Bioavailability and Plasma Profile for the Crystal-free Crystalline in the Lipid and Dry-powder CoQ10 Formulations The crystal-free formulation had a significantly greater bioavailability than the crystalline or dry-powder formulations (P ≤ .001).
Pharmacokinetics
Table 1 presents the individual and group means for the different CoQ10 product types. The Q-Best formulation’s single-dose absorption and steady-state bioavailability significantly exceeded that of all other formulations (P = .001). It was the only formulation that was truly crystal-free. For the CF products compared to the crystalline and dry-powder formulations, the average relative % differences were 145.34 ± 38.3 and 446.25 ± 153.36 greater than the best crystalline or dry-powder formulation, respectively (data not shown).
Table 1.
Summary of the CoQ10 Formulations’ Pharmaceutical Kinetics. The delta Cmax percentage of the dose absorbed at Cmax, the steady-state plasma CoQ10 concentration, and the AUC were significantly greater for the crystal-free (CF) group than for the other formulations (P ≤ .001). The Q-Best formulation had the best kinetics.
| Product Type | CoQ10 Product | n | Plasma Volume (ml) Mean ± SD | Baseline Control (ug/ml) Mean ± SD | Change in Cmax (ug/ml) Mean ± SD | Percent Absorption Mean ± SD | 30-day Steady-state Plasma CoQ10 Level ug/ml Mean ± SD | AUC ug/ml/day Mean ± SD |
|---|---|---|---|---|---|---|---|---|
| CF | Q-Best | 20 | 3854 ± 987.02 | 0.78 ± 0.20 | 2.20 ± 0.76 | 8.47 ± 2.63 | 4.32 ± 1.30 | 54.74 ± 15.63 |
| CoQsol-CF | 12 | 3946 ±1004.23 | 0.82 ± 0.25 | 1.86 ± 0.52 | 7.34 ± 2.20 | 3.26 ± 0.89 | 26.36 ± 6.86 | |
| HiSorb | 10 | 3776 ± 956.28 | 0.86 ± 0.26 | 1.44 ± 0.46 | 5.28 ± 1.35 | 2.26 ± 0.59 | 15.67 ± 4.67 | |
| Group Mean ± SD | 3854.67 ± 983.67 | 0.82 ± 0.24 | 1.83 ± 0.58a | 7.03 ± 2.03a | 3.28 ± 0.92a | 32.80 ± 10.05a | ||
| Crystalline | CoQ-Sol | 20 | 3876 ± 921.23 | 0.87 ± 0.25 | 0.73 ± 0.20 | 2.85 ± 0.53 | 2.33 ± 0.56 | 8.79 ± 2.12 |
| Q-Gel | 12 | 3879 ± 944.46 | 0.79 ± 0.27 | 0.76 ± 0.22 | 2.95 ± 0.56 | 2.65 ± 0.62 | 7.32 ± 1.87 | |
| Q-Sorb | 10 | 3844 ± 987.65 | 0.90 ± 0.28 | 0.90 ± 0.29 | 3.46 ± 0.51 | 2.51 ± 0.45 | 6.54 ± 1.62 | |
| Group Mean ± SD | 3566.54 ± 962.11 | 0.85± 0.25 | 1.40 ± 0.24b | 3.08 ± 0.53b | 2.50 ± 0.54b | 7.55 ± 1.87b | ||
| Dry powder | Q-dry powder | 20 | 3948 ± 905.34 | 0.89 ± 0.26 | 0.35 ± 0.057 | 1.38 ± 0.44 | 1.56 ± 0.52 | 5.04 ± 1.31 |
| Q-dry powder | 12 | 3907 ± 886.83 | 0.84 ± 0.19 | 0.23 ± 0.054 | 0.90 ± 0.52 | 1.76 ± 0.48 | 6.60 ± 1.58 | |
| Q-dry powder | 10 | 3856 ± 1023.49 | 0.86 ± 0.25 | 0.40 ± 0.050 | 1.55 ± 0.43 | 1.48 ± 0.37 | 5.87 ± 1.05 | |
| Group Mean ± SD | 3908 ± 9.88.47 | 0.864 ± 0.25 | 0.33 ± 0.05 | 1.28 ± 0.96 | 1.55 ± 0.43 | 5.34 ± 1.10 |
aSignificantly greater result for the CF group as compared to the crytalline and dry powder groups (P ≤ .001)
bSignificantly greater result for the crystalline group as compared to the dry powder group (P ≤ .001)
CF formulations
For the single-dose absorption and steady-state bioavailability kinetics, the Q-Best CF product was the CoQ10 formulation with significantly greater means compared to all other products. The CF group’s mean was also significantly different from those of the other two types of products (P ≤ .001). For that group, the mean value for the Δ Cmax was 1.83 ± 0.58 ug/ml, the % absorbed was 7.03 ± 2.03, the steady-state plasma bioavailability was 3.28 ± 0.92, and the AUC was 32.80 ± 10.05 ug/ml x days.
For the Q-Best, the mean value for the Δ Cmax was 2.20 ± 0.76 ug/ml, the % absorption was 8.47 ± 2.63 %, the steady state bioavailability was 4.32 ± 1.30 ug/ml and the AUC was 54.74 ± 15.63 ug/ml x days. For the CoQsol-CF, the mean value for the Δ Cmax was 1.86 ± 0.52, the % absorption was 7.34 ± 2.20, the steady-state bioavailability level was 3.26 ± 0.89 ug/ml, and the AUC was 26.36 ± 6.86 ug/ml x days. For the HiSorb, the mean value for the Δ Cmax was 1.44 ± 0.46 ug/ml, the % absorption was 5.28 ± 1.35, the steady state bioavailability was 2.26 ± 0.59 ug/ml, and the AUC was 15.67 ± 4.67 ug/ml x days.
Crystalline formulations
CoQ-Sol, Q-Gel, and Q-Sorb were significantly better absorbed and more bioavailable than the dry-powder formulations (P ≤ .001). For the group, the mean value for the Δ Cmax was 1.40 ± 0.24 ug/ml, the % absorption was 3.08 ± 0.53, the steady-state bioavailability was 2.50 ± 0.54 ug/ml, and the AUC was 7.55 ± 1.87 ug/ml x Days.
The individual kinetics were fairly similar among the formulations. For the CoQ-Sol, the mean value for the Δ Cmax was 0.73 ± 0.20 ug/ml, the % absorption was 2.85 ± 0.53, the steady-state bioavailability was 2.33 ± 0.56 ug/ml, and the AUC was 8.79 ±2.12 ug/ml x days. For the Q-Gel, the mean value for the Δ Cmax was 0.76 ± 0.22 ug/ml, the % absorption was 2.95 ± 0.56 ug/ml, the steady-state plasma level was 2.65 ± 0.62 ug/ml, and the AUC was 7.32 ± 1.87 ug/ml x days. For the Q-Sorb, the Δ Cmax was 0.90 ± 0.28 ug/ml, the % absorption was 3.46 ± 0.51, the steady state bioavailability was 2.51 ± 0.45 ug/ml, and the AUC was 6.54 ± 1.62 ug/ml x days.
Dry-powder formulations
These formulations had much lower single-dose absorption and steady-state bioavailability than the others. The mean for the group of three dry-powder formulations was significantly lower than those of the CF or crystalline formulations (P<.001). For the group, the mean value for the Δ Cmax was 0.33 ± 0.05 ug/ml, the % absorption was 1.28 ± 0.96, the steady-state bioavailability was 1.55 ± 0.43 ug/ml, and the AUC was 5.34 ±1.10 ug/ml x Days. The variations among the dry powders were small. These formulations were poorly absorbed and less bioavailable.
Relationship Between Absorption and Bioavailability
The relationship between single-dose absorption and steady-state bioavailability was determined for the nine studies (Figure 4). This relationship can be described by the linear equation y = 1.26 x + 1.60; the single-dose absorption rate of a CoQ10 product can be used to estimate the likely steady-state plasma bioavailability rate of the product.
Figure 4.
Relationship Between Single-dose Absorption and Steady-state Bioavailability
Discussion
The current study has made it possible to describe a linear relationship between the single-dose absorption and steady-state bioavailability of CoQ10 products.
The significantly (P ≤ .001) greater Cmax of each of the crystal-free CoQ10 products compared to the crystalline CoQ10 and dry powder CoQ10 products clearly shows the superior absorption of the crystal-free products. The 8.47, 7.34, and 5.28% of 100-mg dose absorption for the Q-Best, CoQ-Sol-CF and the HiSorb formulations clearly shows that the body has difficulty absorbing a crystal. Only single molecules can be absorbed in the simple facilitated diffusion process of CoQ10 absorption.2
In one prior study,5 the between-subject variation in the Cmax around the group mean for a colloidal formulation was 6.6%, and the variance for three other products was in the 12-14% range. The between-subject variation in the current study were 25.4%.
In the steady-state bioavailability measurement in the current study, the steady-state plasma levels of the CF CoQ10 products were significantly greater than those found for the crystalline CoQ10 products in a lipid-based soft gel (P ≤ .001) and significantly greater than those published in other studies giving a 100 mg dose daily.2-6
Other studies have shown that lipid-based softgel formulations can increase the plasma concentration by 1.3 to 2.9 ug/ml.1,6,18 In the present study, a single-dose of 100 mg of the Q-Best CF formulation increased the steady-state bioavailability significantly (P ≤ .001). The Q-Best was the only CoQ10 product in the current study with a monoglyceride carrier to facilitate the absorption process.
In the current study, only the Q-Best formulation was devoid of CoQ10 crystals. The CoSol-CF and the HiSorb-CF formulations contained crystals at room temperature, at body temperature, and after cooling after being heated to 50° C. When heated to 50° C, none of the formulations had crystals. The CoQ10 crystal’s thermal dissociation level is 50° C, which is well above the 37° C body temperature. A 13-degree Fahrenheit increase in body temperature is incompatible with life.
The current researcher hasn’t seen a description of the relationship between single-dose absorption and steady-state plasma bioavailability in the CoQ10 literature. Obviously, no accumulation of an exogenous CoQ10 in plasma can occur without absorption.
In the current study, the relationship has been described by the linear regression equation y = 1.26 x + 1.60. Thus, an estimate of what the steady-state bioavailability should be in a normal population can be determined from a short 24-hour absorption study rather from than a 28-day bioavailability study.
Please note that the relationship between single-dose absorption and steady-state bioavailability could well change in clinical settings and in elderly patients with digestive abnormalities, absorption difficulties, or variable plasma lipid profiles.
The variability between the tested formulations was great for the CF products compared to that for the crystalline or dry powder formulations. The reason was the fact that CoQ10 crystals were found in the CoQsol-CF product and the HiSorb CF product. The CoQ-Sol formulation was evaluated after being shipped to the laboratory overnight in a 50° C thermos bottle. The steady-state absorption was 7.34% of the 100 mg dose. When the CoQ10 capsules cooled to room temperature, crystals formed in the softgel capsule.
When the single-dose absorption and the steady-state bioavailability were determined when the CoQsol-CF product capsules were at room temperature in a multicenter s tu dy, 18 the single dose absorption was 0.35% and the steady state bioavailability was 1.70 ug/ml. In the current study, the CF capsules were full of crystals. The only CoQ10 formulation in which the researcher found no CoQ10 crystals was Best Formulations’ CF product.
In the current study, the time to peak (Cmax) was 6 to 8 hours in the single-dose studies and 14 days in the steady-state studies. The percentage of the dose can’t be calculated for the steady-state studies, but the AUC can be calculated. Some investigators calculate the AUC for single-dose studies.2-6 This is a questionable practice in that there is no extended steady-state interval in the single-dose absorption study.17
Thus, for those CoQ10 products with crystals, when ingested, very little dissociation will occur to single CoQ10 molecules that can be absorbed.
Conclusions
The current study clearly shows that the CF CoQ10 formulations are superior in both single-dose absorption and steady-state bioavailability compared to the crystalline and the dry-powder CoQ10 formulations. This enhanced absorption and bioavailability results from the fact that the CF formulations contain single CoQ10 molecules in the lipid solution and no CoQ10 crystals. The character of the single-dose absorption study curves is clearly different in their magnitude and time course compared to those of the steady-state bioavailability studies.
This current study also presents, for the first time, an equation (y = 1.26 x + 1.60) that makes possible the approximate estimation of the steady-state bioavailability of a CoQ10 product from the single-dose absorption of the CoQ10 product.
Acknowledgments
The author thanks Richard Morrill, editor at Q10 facts.com, for assistance in the writing of this article.
Biography
William V. Judy, PhD, Founder and President, SIBR Research.
Footnotes
Author’s Disclosure Statement
The studies were funded, under contract, by Best Formulations, Soft Gel Technologies, National Vitamin, and Nature’s Bounty companies. The author has no conflicts of interest related to the study.
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