What is CoQ10?Heart Energy Engine and More.

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Biochemistry of CoQ10(Co Q 10).

Coenzyme Q10 CAS 303-98-0 photo picture image CoQ10 is made up of a quinone ring, but also contains a side chain consisting of ten repeating 5-carbon isoprene units. Because of its structure, CoQ10 is highly lipophilic and practically insoluble in water. This lipophilic nature also affects bioavailability, making its absorption poor, highly variable, and strongly dependent on the stomach's contents (i.e. foods rich in fat). Another major factor in the bioavailability of CoQ10 is the large size of the molecule. Dietary supplement encapsulators try to develop delivery systems for CoQ10 to enhance bioavailability, and have utilized oil-based soft gel capsules containing microemulsions rather than powder-based forms of this nutrient. However, most CoQ10 dosage forms exhibit negligible dissolution,no more than 10%.

 It is clear that the dosage form of a supplement has a significant effect on nutrient bioavailability. Absorption into the general circulation is an important part of delivery. In general, the effect of dosage form on bioavailability depends on the rapidity with which the particular form releases the nutrient into the biological fluids or how rapidly the nutrient may permeate a cell membrane. Not surprisingly, absorption is most rapid from solutions and decreases in the order: solutions, suspensions, capsules, compressed tablets, coated tablets. Commercially available CoQ10 dosage forms include powder-based tablets (compressed), powder-filled capsules (2-piece hard shell), and soft gelatin capsules. Other forms, such as chewable wafers, intra-oral sprays, and intravenous solutions, are available, but are less common.

 As previously discussed, the dosage form of a supplement has a significant effect on bioavailability. A prerequisite to absorption is dissolution, and this is a disadvantage of the powder-forms of CoQ10. Better preparations appear to be soft gel capsules with CoQ10 in an oil base, but absorption is still dependent upon the number and size of CoQ10 crystals in the product.

 Solubility and Particle Size of Coenzyme Q10 in a Soft Gelatin Formulation:

 Coenzyme Q10 (CoQ10) has been characterized as a poorly-soluble, crystalline material. CoQ10 can be rendered soluble in vegetable oils or combinations of vegetable oils and detergent compounds, however re-crystallization has been identified as a challenge to these systems. A citrus-derived monoterpene, d-limonene, was observed to solubilize CoQ10 and this solution was analyzed to confirm solubility.

 The solvent:a mixture of d-limonene and tocopherol,was compared with the same solvent mixture plus the addition of CoQ10. These samples were analyzed using visual inspection with a phase contrast microscope at magnifications of 200x, 400x, and 1000x, a dark field microscope, and polarized light microscope. No particles were identified using any of the methods of microscopy.

 The samples were also analyzed using a Particle Sizing Systems Nicomp 380 ZLS photon correlation analyzer, a Microtrac UPA 150 Doppler Shift Photon Correlation Analyzer, and a Malvern Zetasizer Nano instrument. Again no particulate material could be detected in either of the samples. The lack of particulate material indicates that CoQ10 can be fully solubilized in a solvent comprised of d-limonene and tocopherol within the concentration limits used in this formulation.

 Peak Absorption Study Results:

 Starting with day 1 of the study, volunteers took 60 mg CoQsol-CF, followed by a breakfast consisting of orange juice or milk with a bagel or cereal, and serial blood samples were taken at 0, 4, 6, 8, and 12 hours. Within four hours after ingesting the CoQ10, the plasma levels for the group increased significantly to 1.36 ug/ml. Peak plasma levels occurred at six hours (Tmax) and the maximum plasma concentration (Cmax) was 2.28 ug/ml. Thereafter, plasma CoQ10 rapidly decreased over the next two hours to a mean level of 1.58 ug/ml.

 The amount of CoQ10 absorbed at Cmax was 4,769.5 ug based on the average plasma volume 3400 ml. When compared to the ingested dose (60,000 ug = 60 mg), the percent of the dose absorbed at Cmax is 7.95%. This percentage makes it a superior product in terms of absorption.
 Coenzyme Q10 CAS 303-98-0 photo picture image

 Steady State Plasma CoQ10 Bioavailability Results:

 Volunteers continued taking 60 mg CoQsol-CF? daily for 28 days. During this time, volunteers followed their regular diet and activity, and returned to the testing facility on days 7, 14, 21, and 28 at 6:00 a.m. in a rested and fasted condition,minimum eight hours for collecting blood samples. The mean plasma-level of CoQ10 were determined and data are shown in the graph. In seven days the mean plasma CoQ10 level increased significantly to 2.39 ug/ml. At the 28th day, the mean plasma CoQ10 was 2.75 ug/ml. This means that in this steady state study, the mean CoQ10 plasma level increased by 200% (calculated increase was 6,458.9 ug/ml at a constant daily dose of 60 mg/day for 28 days).

 The area under the plasma CoQ10 and time base curve between days 0 and 28 days (AUC) is used to determine the bioavailability of CoQsol-CF. The AUC for CoQsol-CF was 42.27ug/ml.day.

 Animal Study

  Soft Gel Technologies, Inc. also funded an animal study on CoQsol-CF whose main objective was to compare bioavailability and tissue distribution after supplementation with different preparations of CoQ10, including CoQsol-CF. Previous studies demonstrated that CoQ10 supplementation is associated with increased CoQ accumulation in serum and liver. The significant accumulation of CoQ in tissues other than the liver was also observed but only when high doses of CoQ was administered over longer periods of time. In order to establish whether CoQsol-CF is superior to powder CoQ10 in terms of enhancing tissue CoQ storage, high daily doses of both formulations are recommended.

 Protocol

  Young male mice were randomly assigned to 4 groups, 12 animals per group. After acclimation, treatment groups received CoQsol-CF, CoQsol, or powder CoQ10 product at the dose 300 mg/kg body weight (BW)/day, by gavage, for 10 weeks. The control group received CoQ10 vehicle (also by gavage) for the same period of time. At the end of the study, blood was collected by heart puncture and tissues were collected. Serum and tissue homogenates (liver, heart, skeletal muscle, spleen, brain and lung) were analyzed for CoQ10, CoQ9, total CoQ and reduced forms of CoQ10 and CoQ9 concentrations by HPLC (high performance liquid chromatography).

 Results

  It was observed that different preparations lead to accumulation of CoQ in different organs. The graphs depicted below illustrate that various CoQ10 delivery systems accumulate in different tissue types. CoQsol-CF demonstrated enhanced accumulation in blood serum, heart, and liver tissue, all of which are key storage and use locations for CoQ. Supplementation with our original CoQsol formula resulted in the accumulation of total CoQ in mitochondria isolated from heart, brain and spleen. Even the CoQ10 powder showed enhanced uptake in muscle and lung tissue. The results of the present study suggest that different preparations are metabolized in different ways leading to the differences observed in tissue accumulation.

 Limitations of Animal Study

  The mouse is a challenging model for CoQ10 research, because rodents' primary storage form of CoQ is CoQ9. Lipid metabolism differs from humans in that the major source of cholesterol in rodents is from HDL (85-90%), whereas humans obtain cholesterol from LDL. In addition, high serum levels of CoQ in mice may significantly reduce blood pressure, thereby causing a negative response. Despite these limitations, the mouse model provided useful insight for future work.

 Design:

  A randomized, multi-center, parallel study comparing the bioavailabilities of two coenzyme Q10 formulations (CoQsol-CF and CoQ10 powder in hard shell capsules) in 30 healthy, human subjects has been initiated. Steady state and acute dose bioavailability in plasma and tissues will be investigated. Antioxidant properties of the two coenzyme Q10 preparations will also be compared. The values studied will include: total antioxidant status, total plasma glutathione, and isoprostane lipid peroxide levels. Functional measures of cardiovascular health including homocysteine and CRP levels will also be measured. In addition, safety data will be gathered.

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citations1.What is CoQ10?Heart Energy Engine and More.

last edit date:13th,May.2009.