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Coenzyme Q10 or CoQ10 is an organic molecule that is naturally synthesized in the liver. According to Dr. Karl Folkers and other experts, humans can biosynthesize coenzyme Q10 from tyrosine through a cascade of aromatic precursors which indispensably require certain vitamins: vitamins B2, B6, B12, folic acid, niacin, and pantothenic acid. CoQ10 is comprised of a quinone ring and a hydrocarbon side chain made up of 10 isoprene units. This side chain is synthesized from acetyl-CoA. The quinone ring is synthesized from the amino acids (tyrosine or phenylalanine) and is responsible for CoQ10 having such powerful antioxidant activity. The reduced form of CoQ10 is able to scavenge free radicals that may cause damage to the body’s DNA, proteins, and lipids, opening the door to a host of various diseases including cardiovascular disease, and neurodegerative diseases such as Alzheimer’s or Parkinson’s.

Because it is a vitamin-like substance located in virtually every cell, CoQ10 is also known as ubiquinone—from “ubiquitous” to signify its widespread distribution in the human body, and “quinone,” a chemical structure with a unique ability to be oxidized and reduced. Found in most living organisms, it is essential to the production of cellular energy and can be both synthesized in the body and derived from dietary sources. There are dietary sources of CoQ10, including meat, poultry and fish, but these sources contain a small amount of CoQ10. Daily intakes from food typically range between 3 to 5 mg/day, which cannot significantly raise blood and tissue levels.

Healthy humans who consume a well-balanced diet have the ability to synthesize coenzyme Q10. Unhealthy individuals and those on an inadequate diet may not synthesize CoQ10 in sufficient quantities. Thus, the biosynthesis of coenzyme Q10 in the human body requires a good diet—one that is high in vitamins, minerals, and other nutrient factors. The NHANES studies reveal that many Americans do not have an adequate diet. Rather, their intake of most water-soluble vitamins (B-complex vitamins and vitamin C), vitamin A and some minerals and trace elements is insufficient. As noted earlier, many of these nutrients are essential for the biosynthesis of coenzyme Q10. In addition, it has been shown that in disease states, nutrients from food sources may not necessarily be absorbed or available. According to some experts, coenzyme Q10 should be considered an essential nutrient, as it is well established that coenzyme Q10 is essential for the health of every cell in the human body.

Coenzyme Q10 resembles vitamin K in its chemical structure. Biochemically, reduced CoQ10 functions much like vitamin E in that it acts as an antioxidant by donating a hydrogen to free radicals. Like vitamins E and K, CoQ10 is also a lipophilic (fat-soluble) molecule. To better explain, it can only be absorbed in the presence of fat, because it is water insoluble. For better CoQ10 absorption, it either has to be introduced in a fat soluble medium or taken with fat in the diet. Many question why CoQ10 should be supplemented, especially since we produce it naturally in the body and obtain it in our food supply. It has been suggested by some clinical data that the body’s natural ability to synthesize CoQ10 may diminish as we age. In addition, those with heart disease seem to produce even less, and they are the ones that need it the most.

The most important role CoQ10 plays in the body is to support the production and function of adenosine triphosphate, or ATP, the metabolic energy on which the body runs. CoQ10 is found primarily within the membrane of a cell organelle called the mitochondrion, which is often referred to as the “power house” of the cell. Mitochondria are affectionately known as this because of their ability to drive the production of ATP. CoQ10 is an important rate-limiting nutrient that is a cofactor in the mitochondrial electron transport chain—the biochemical pathway in cellular respiration from which ATP is derived. It serves as an electron transport carrier during the processes of respiration and oxidative phosphorylation. Since nearly all cellular activities are dependent upon energy, coenzyme Q10 is essential for the health of all human tissues and organs.

The heart is one of the most metabolically active tissues in the body, thus it requires large amounts of uninterrupted energy. Heart muscle cells have the greatest concentration of mitochondria, and subsequently, more CoQ10 than any other type of cell. Each heart cell can have thousands of mitochondria (5,000 per cell) to meet these energy demands.

Numerous studies indicate coenzyme Q10 also plays an important role in the maintenance of the entire cardiovascular system. As previously mentioned, CoQ10, in its reduced form, plays an important role as an antioxidant nutrient. The antioxidant potential of CoQ10 helps our bodies prevent or delay cellular deterioration. It is this deterioration that is one of the predominant causes of heart disease. CoQ10 is essential for healthy heart function, as well as to protect the veins and arteries from free radical damage. Research has shown that CoQ10 supplementation exerts a sparing effect on vitamin E in healthy subjects. It also reduces levels of lipid peroxidation, the pivotal step in the cause of atherosclerosis, thereby decreasing the risk of cardiovascular diseases.

Several clinical trials have provided evidence supporting the use of supplementation with CoQ10 in the prevention and treatment of various disorders related to oxidative stress. It has been shown that CoQ10’s antioxidant properties and its central role in mitochondrial oxidative phosphorylation make it useful as adjunct therapy for cardiovascular diseases such as congestive heart failure (a disease in which the heart does not adequately maintain circulation), hypertension (high blood pressure), cardiomyopathy (heart muscle disease), angina pectoris (chest pain), drug-induced cardiotoxicity, and ventricular arrhythmia. A significant deficiency of CoQ10 was detected in patients with hypertension. A pilot study showed that CoQ10 supplementation at dosages that ranged from 30 to 360 mg/day to patients with hypertension led to an increase in CoQ10 levels and statistically significant decreases in systolic and diastolic blood pressure.

CoQ10 is also gaining notoriety as a helpful dietary supplement for non-cardiac conditions including diabetes, Parkinson’s disease, periodontal disease, compromised immune systems, cancer, muscular dystrophy, and chronic obstructive pulmonary disease (COPD). There is substantial evidence that oxidative damage may play a key role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. In a recent study, the percent content of the oxidized form of CoQ10 (a marker of oxidative stress) in total CoQ10 (both oxidized and reduced forms) was found to be slightly elevated in Parkinson’s disease patients, when compared with normal subjects, suggesting elevated oxidative stress in Parkinson’s disease patients.

CoQ10 supports a broad range of functions in the body leading many experts to suggest that CoQ10 should be an integral part of any dietary supplementation program.

Cholesterol biosynthesis is a complex metabolic process. At least 26 steps are involved in its production, and it shares a common pathway with CoQ10 synthesis. It is produced from acetyl-CoA, just like the isoprenoid side chain of CoQ10. Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is one of the next substrates down the synthesis chain, requiring the enzyme HMG-CoA reductase to form the mevalonate compound.

In the United States, millions of Americans are taking cholesterol-lowering prescription drugs known as “statins” (Pravachol®, Zocor®, Lipitor®, etc.). Statins are a class of pharmaceuticals that are used to lower cholesterol levels, primarily LDL cholesterol. They are sometimes referred to as “HMG-CoA reductase inhibitors,” because they block this key enzyme, which is responsible for the body’s production of cholesterol. Essentially, it inhibits the endogenous production of cholesterol.

Inhibition of HMG-CoA reductase by statin drugs at the mevalonate level will inevitably decrease the levels of both cholesterol and CoQ10. The cholesterol-lowering medications interfere with the body’s ability to produce CoQ10, because these drugs also block the manufacture of other substances necessary for body functions including CoQ10. Ironically, the drugs are taken to lower cholesterol, but at the same time CoQ10, which protects the heart, is produced on a much smaller scale. People taking statin drugs can develop CoQ10 deficiencies and may require supplementation. Several studies revealed a possible dose-related and significant decrease in CoQ10 serum levels as a result of HMG-CoA reductase inhibitor treatment (e.g., simvastatin, pravastatin, lovastatin) alone. In a double-blind, randomized clinical trial hypercholesterolemic patients received either lovastatin or pravastatin over a period of 18 weeks. At the end of the study period, the total serum level of CoQ10 declined by about 25 percent in the lovastatin and pravastatin groups.

Supplementing with CoQ10 is necessary to prevent its depletion in the body while on these drugs. Furthermore, the LDL cholesterol that is limited by statin drugs is one of the primary transport compounds for CoQ10 in humans. Clearly, statins deliver a double-threat to CoQ10 status through their limitation of production and transport of this important cofactor.

CoQ10’s safety has been evaluated. Doses of 30-60 mg/day are generally recommended to prevent CoQ10 deficiency and to maintain normal serum concentrations of 0.7-1.0 µg/mL (micrograms per milliliter). However, therapeutic doses of 100-200 mg/day are advocated for the treatment of chronic heart disease. These higher doses may achieve serum concentrations of 2.0-3.0 µg/mL, reported by some investigators to have a positive impact on cardiovascular health. The dosage in a Parkinson’s disease study ranged from 300-1200 mg/day, taken for 16 months. The group that received the largest dose of CoQ10 (1200 mg/day) displayed less of a decline in mental function, motor function, and ability to carry out activities of daily living.

If CoQ10 is going to be effective, adequate blood levels must be maintained for a prolonged period.

CoQ10 is absorbed slowly. Absorption is dependent on the presence of fat in the gastrointestinal (g.i.) tract. Peak plasma levels are attained within 5-10 hours following oral administration. CoQ10 is primarily excreted through the biliary tract, and over 60% of the oral dose is recovered in the feces.

With this very basic understanding of CoQ10, you’ll now be able to appreciate the superiority of CoQsol-CF™.

There are currently two different manufacturing techniques being used to commercially produce coenzyme Q10. Soft Gel Technologies, Inc.® has access to material from three different Japanese manufacturers. One manufacturer, Nisshin Pharma, uses the solanesol method and the other two manufacturers, Kaneka and Asahi, use the microbiological fermentation method. The following is a brief summary of the two manufacturing methods:

The Solanesol Method:

The first CoQ10 to be admitted as a pharmaceutical ingredient in Japan was produced by the solanesol method. Plants from the Solanaceae family contain a nine-isoprenoid long alcohol known as solanesol. Solanesol is first extracted from the plant and is then converted to a ten-isoprenoid compound called decaprenol. During the final step, the decaprenol is reacted with hydroquninone to produce CoQ10. The CoQ10 produced by the solanesol method has a long history of safety and efficacy. The compound actually extracted from the tobacco leaf is the solanesol. The process begins with a n-hexane extraction. The solvent is removed by molecular distillation.

With this method, both trans and cis forms of CoQ10 are formed but subsequent purification steps reduce the quantity of cis isomers to below 0.5%, generally below 0.2%. Nisshin Pharma’s specification is not more than 0.5%.

Microbiological Fermentation:

Coenzyme Q10 produced by microbiological fermentation was also admitted as a pharmaceutical ingredient in Japan and also has a long history of safety and efficacy. With the fermentation method, selected strains of microbes are placed in a fortified molasses-based carbohydrate medium where they produce CoQ10, as well as CoQ6, CoQ7, CoQ9 and CoQ11 during the fermentation process. The actual microbe used in the process is proprietary. The carbohydrate medium used is derived from sugar beets, but its exact composition is also proprietary.

Subsequent purification steps generally greatly reduce or eliminate the presence of other coenzyme homologues listed above. The USP specification for non-CoQ10 homologues is 1.0%. All of our material meets this requirement. Material produced in this manner is considered natural in the United States, Europe and Japan. The CoQ10 used is produced by microbiological fermentation, which is the all-trans isomer form.

Recently, there has been a great deal of controversy regarding differences in isomer (cis vs. trans) impurities contained commercially-available products. It is important to note that the compounds involved in the controversy are not hazardous. These impurities are compounds having positive health benefits but the health benefits are not as great as the benefits obtained from all-trans coenzyme Q10.

Coenzyme Q10 manufactured using the solanesol method has the potential to contain “cis” isomers in which the ten-isoprenoid unit tail is bent rather than straight. It is commonly believed that the bent tail limits the molecule’s ability to penetrate cellular and organelle membranes. It is also possible that material made using the solanesol method contains some CoQ9. Subsequent purification steps generally greatly reduce or nearly eliminate the presence of these isomers.

Coenzyme Q10 manufactured by microbiological fermentation is 100% in the all-trans isomeric form, identical in structure of the coenzyme Q10 made by the human body. However, material made by microbiological fermentation has the potential to contain other homologues, sometimes referred to “related substances” such as CoQ7, CoQ8, and/or CoQ9. Subsequent purification steps generally greatly reduce or eliminate the presence of the other forms of coenzymes listed above.

All the coenzyme Q10 material utilized by Soft Gel Technologies, Inc.® is guaranteed to be a minimum of 98% pure. This is considered a natural material and is in full compliance with the current United States Pharmacopeia/ National Formulary (USP/NF), European Pharmacopeia, and Japanese Pharmacopeia monographs and standards.

CoQ10 is a raw material and finished good that is important to our customers and is in short supply this year. Most people are aware that the availability of CoQ10 continues to be very scarce. Four factors contribute to this type of market condition. The first factor is attributed to an increased demand for CoQ10 when it was granted FOSHU (Foods for Specific Health Use) status in Japan. The second factor was the publication of research supporting higher dosages for therapeutic applications. Third, the planned expansion of production facilities and necessary closures during the construction process created a shortage of raw material. The fourth factor surfaced unexpectedly, because manufacturing difficulties lead to unplanned closure of facilities. These factors follow the basic supply and demand economic model, thereby driving prices up to record levels.

When raw material is scarce, the primary impact of the shortage is increased pricing. The market tends to ration material to those who exhibit the greatest demand. Secondary impacts include a slowed rate of product development and product introductions. Manufacturers will only introduce a new product if they feel strongly assured that their vendor can consistently maintain a supply of the necessary ingredients. Shortages can undermine confidence throughout the supply chain—from the end consumer to their retailer, and continues up through the manufacturer and their supplier.

At Soft Gel Technologies, Inc.®, we have leveraged our long term relationships with our suppliers and our capital in order to secure an adequate supply of key ingredients. We are still subject to market fluctuations, but we feel that this is preferable as opposed to not having material for our customers. Manufacturers that have cultivated relationships with suppliers tend to do well in a volatile market. On the other hand, companies that are opportunistic in their purchasing strategy and forego developing an alliance with vendors are more susceptible to the ebb and flow of the marketplace.

Finished product manufacturers can apply innovative strategies with key ingredients that are subject to scarcity, by capitalizing on synergistic combinations of ingredients or by utilizing delivery systems that enhance bioavailability. Soft Gel Technologies, Inc.® encompasses this methodology in its efforts to cope with a fluctuating market. As a result of research and development efforts, we have developed a CoQ10 product that is 100% solubilized. This formulation provides our customers with a high level of value and excellent results regarding CoQ10 bioavailability. This new product is called CoQsol-CF™, the “crystal-free” advantage.

CoQsol-CF™ is a unique, patent-pending formula comprised of CoQ10, d-limonene, tocopherols (vitamin E), and medium chain triglycerides (MCTs). This combination created a liquid (100% solubilized), crystal-free solution of CoQ10 that provides enhanced bioavailability. It contains all natural ingredients. Even the gelatin shell color is derived from turmeric. No synthetic dyes are utilized.

To fully understand the characteristics of this non-polar, organic solvent, some background information regarding volatile oils is provided below.

Volatile oils, also known as essential oils, are complex chemical substances, frequently having two or three hundred constituents. Most volatile oils are carbon-hydrogen compounds (hydrocarbons), and terpenes are the most common hydrocarbons. They are responsible for providing the scent to various parts of a plant. When exposed to air or steam, they evaporate, which explains why they are called “volatile” oils. In citrus fruits (orange, lemon, lime, etc.), these oils can be found in oil reservoirs from the fruit peel.

Methods of extraction for volatile oils vary, but most are extracted by distillation. Water distillation is used for the more robust oils, particularly those high in terpenes. Water and steam distillation is the method most commonly used, being powerful yet gentle for more sensitive constituents. The volatile oils thus distilled float on the surface of the distillate and can be separated easily. Direct steam distillation may be used where the plant is prepared very soon after picking.

Plants have the capacity to synthesize low molecular weight compounds that are called secondary metabolites, because their role in growth and development is unclear. The largest class of secondary metabolites in plants is the terpenoids (or terpenes). The structure of terpenes varies widely, as they can exhibit hundreds of different carbon skeletons. However, they do share a common feature: all terpenes have carbon atom isoprene units in multiples of 5. Terpenes are formed from acetyl-CoA via the mevalonic acid pathway, since mevalonic acid and isopentenyl pyrophosphate are involved in their biosynthesis.

The properties of a volatile oil are determined by the number of isoprene units and the various side groups (such as alcohols, esters, acids, nitrogen, and sulphur) that may be attached. If a terpene has no added side groups, it is called an unoxygenated terpene. The most common type of terpenes in volatile oils are monoterpenes—hydrocarbons consisting of two isoprene units. Limonene found in more than 30 species of fruits and vegetables, especially in citrus oils, is a specific monoterpene hydrocarbon that exists naturally as the dextrorotatory isomer, d-limonene.

There are several applications for d-limonene in the food and pharmaceutical industries. The Food and Drug Administration recognized d-limonene to be Generally Recognized As Safe (GRAS) in 1960 as a synthetic flavoring substance. In 1965 a Flavor and Extract Manufacturers’ Association (FEMA) expert panel determined d-limonene to be GRAS. It is widely used as a flavor additive in foods and beverages, as a fragrance in perfumes and a variety of household products, and as an industrial solvent and degreaser. Recently, d-limonene has become a potential candidate for a variety of medical applications because of its reported use as a chemoprotective agent in experimental animal models. Several dietary supplements have been introduced to the natural products industry that contain food-grade d-limonene with potencies up to 1000 mg per serving to address a variety of health concerns. There are two main grades of d-limonene obtained as a by-product of the citrus juice industry—food grade and technical grade. Food-grade d-limonene undergoes a distillation process, and is used for consumer products, while technical grade d-limonene is used for industrial products.

This monoterpene solvent was chosen to be in CoQsol-CF™ for its solubilizing properties. CoQ10, with its side chain of isoprenoid units, is highly soluble in hydrocarbon monoterpenes, including d-limonene (“Like dissolves like” chemistry principle). d-Limonene can be combined with CoQ10 without causing chemical interactions or degradation.

Tocopherols are added because they enhance the biological function of CoQ10, which in turn, helps maintain the antioxidant state of vitamin E. Vitamin E is important to the action of CoQ10, because it is used to convert CoQ10 to its most active reduced form. CoQ10 can work synergistically with vitamin E, regenerating its active form, tocopherol, in the same synergistic mechanism as with vitamin C. Preparations of CoQ10 that contain lipid vehicles, such as vitamin E, increase solubility and yield more efficient absorption rates than that of the purified coenzyme alone.

During supplementation with CoQ10, the level of lipid peroxidation decreased in healthy subjects, yet levels of another antioxidant, vitamin E, remained constant. It appears CoQ10 exerts a sparing effect on vitamin E and perhaps more efficiently prevents lipid peroxidation (by inhibiting both its initiation and propagation, whereas vitamin E inhibits only propagation).

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.

Crystals are formed when CoQ10 is produced commercially. CoQ10 crystals dissolve when they are mixed with certain solvents or if they are heated (CoQ10’s melting point is 118°F or 48°C). CoQ10 will recrystallize upon cooling to room temperature. This recrystallization frequently creates larger crystals than the finely-milled starting material, which are even more difficult for the body to assimilate. The size of CoQ10 crystals and degree of solubility of a CoQ10 mixture will likely affect the bioavailability of CoQ10.

With all of these factors in mind, CoQsol-CF™ was created—a unique formula of CoQ10, d-limonene, and vitamin E tocopherols. Tocopherols are added, because they interfere with the recrystallization of CoQ10. Food grade d-limonene is used, because it is a non-polar, organic solvent that is not water soluble. This lipid soluble monoterpene was chosen for its solubilizing properties. CoQ10, with its side chain of isoprenoid units, is fairly soluble in monoterpenes (also isoprene units), including d-limonene. Research has demonstrated that the solubilization of natural food supplements is enhanced with d-limonene microemulsions. This essential oil component can be used with CoQ10 without causing chemical interactions or degradation. The properties of d-limonene also prevent the degradation of the gelatin shell, as gelatin is insoluble in most organic solvents.

Upon microscopic examination at 200x, CoQsol-CF™ is devoid of crystals (photo on right), while a paste consisting of CoQ10 powder and soybean oil exhibits a crystalline structure (photo on left). Please note that the photos have not been retouched and were taken in our in-house laboratory. Also be aware that the first photo displaying the crystals is NOT our CoQsol® formula!

Overall absorption can be improved by manipulating the formulation/delivery system. A well-formulated suspension is second only to a solution in terms of bioavailability. Suspensions are rapidly absorbed, mainly because of the large surface area of the very small particles in the suspension. Reducing the particle size increases the surface area of the nutrient, thus increasing the rate and extent of g.i. absorption. The smaller the particle size the better!

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.

We, at Soft Gel Technologies, Inc.®, wanted to determine if our CoQsol-CF™ product had good absorption and bioavailability, so a study was funded to obtain this information in 2004.

In a pilot clinical trial involving five normal volunteers (3 men and 2 women), the peak absorption characteristics and steady state bioavailability of CoQsol-CF™ were determined. For the control sample, volunteers were in a rested and fasted condition—minimum eight hours. The mean control plasma level was established to be 0.88 μg/ml.

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 μg/ml. Peak plasma levels occurred at six hours (Tmax) and the maximum plasma concentration (Cmax) was 2.28 μg/ml. Thereafter, plasma CoQ10 rapidly decreased over the next two hours to a mean level of 1.58 μg/ml.

The amount of CoQ10 absorbed at Cmax was 4,769.5 μg based on the average plasma volume 3400 ml. When compared to the ingested dose (60,000 μg = 60 mg), the percent of the dose absorbed at Cmax is 7.95%. This percentage makes it a superior product in terms of absorption.

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 μg/ml. At the 28th day, the mean plasma CoQ10 was 2.75 μg/ml. This means that in this steady state study, the mean CoQ10 plasma level increased by 200% (calculated increase was 6,458.9 μg/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 42.27μg/ml.day.

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.

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).

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.

Click on image for full size

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.

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.

Soft Gel Technologies, Inc.® (SGTI®) is a leading contract manufacturer providing specialty soft gelatin encapsulation that exceeds the highest standards of quality, purity, and performance to the Natural Products industry. What rivals our drive to excel in supplying the finest soft gels, is our desire to provide our customers with the most comprehensive service possible. SGTI®’s leading product is a patented, highly-bioavailable CoQ10 soft gel marketed as CoQsol®. Other key products include GlucoTrim®, a banaba leaf extract for blood glucose management, and Injuv®, a low molecular weight hyaluronic acid for cosmeceutical and joint health applications. Soft Gel Technologies, Inc.® is a privately-held company based in Los Angeles, CA.

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