Bioavailability of CoQ10

Bioavailability of CoQ10
by DimitriPapadimitriou, Ph.D.

Ubiquinones, including coenzyme Q10 (CoQ10), arehighly insoluble in aqueous media. This may be attributed to the hydrocarbonisoprenoid side chain that provides the molecule with its lipophiliccharacteristics. Furthermore, the quinone portion of the molecule offers somehydrophilic tendencies, resulting in a situation where CoQ10, while exhibitingstrong lipophilic affinity, is also not very soluble in oils. This ambivalentsolubility is particularly suitable for its localization in the middle region ofthe phospholipid bilayer in cellular membranes.¹ Because of this ambivalentsolubility, the absorption of CoQ10 when administered orally tends to be slowand ineffective, extending only 5 percent to 10 percent of the administered dose and exhibiting appreciable variability.²

Most of the CoQ10 in plasma is associated with lipoproteins,particularly low density lipoprotein (LDL) in its reduced form, exerting apotent antioxidant action. Enrichment of CoQ10 levels by exogenoussupplementation results in significant increase of its plasma levels. Clinical studies conducted over a period of two monthsdemonstrate a dose-dependent effect in serum CoQ10 levels when administeredorally with the minimum effective dosage of 30 mg/d.³ Tissue distribution ofCoQ10 is primarily in the plasma and the liver; other tissues are marginally affected unless significantly higher doses aredelivered.⁴

During gastrointestinal uptake, dietary CoQ10 is efficientlyreduced to the antioxidant active ubiquinol with a very low redox potentialafter its oxidation; the respiratory chain recycles CoQ10 back to itsreduced form.⁵ This allows CoQ10 to act as a reducing agent of vitamin Eradical thus regenerating vitamin E.

Pharmacokinetic studies demonstrate after a single 100 mg doseof CoQ10, plasma levels increase slightly, reaching a peak after six hours and aterminal elimination half life of 33 hours while showing an additional peak at24 hours after dosing.⁶ Upon oral administration of CoQ10, a lag time of aboutone hour exists before increase of plasma levels can be detected; approximatelyseven days of administration is required to achieve maximum steady state plasmalevels. What significantly affects CoQ10 absorption is food. When CoQ10 isadministered in a capsule along with food or incorporated in a meal at a singledose of 30 mg, serum levels increase appreciably for both preparations.⁷ Thisdemonstrates how the bodys efficiency in bile secretion in the digestivetract impacts CoQ10 absorption, as well as how it may impact the release ofsustained release CoQ10 products. The time course of releasing CoQ10 from suchproducts will invariably coincide with the time of meal digestion, exhibitingperiods of enhanced absorbability. This has been shown in clinical studies wherehigher plasma levels were achieved for a time release preparation, at 50mg/d for15 days.⁸ The limitation of oral administration of CoQ10 is that high levels arerequired to reach tissues other than the liver. Therefore, CoQ10 has beenadministered intravenously in emulsion form either by incorporation incommercial intravenous food preparations or when emulsified with eggyolk.⁹

The efficacy of increasing CoQ10 serum levels whenadministered orally depends on the delivery form administered. Efficacy studiesconducted on dogs show both powder-filled capsules and oil base formulationsexhibited poor and slow absorption when administered orally.¹⁰ Numerousapproaches to improve the solubility of CoQ10 have been explored. Many of theseattempts have used various forms of lecithin,¹¹ liposomes,^12,13,14 aqueousdispersions,¹⁵ co-precipitate,¹⁶ and co-melt preparations. Formulators have alsotried complexation with a soluble adjuvant,¹⁷ or the co-administration of a thermonutrient such as piperine.¹⁸ In most instances, these approaches involve multiplestep processes and often resolve in using organic solvents that at acertain stage of the manufacturing need be removed. In addition, the potency ofCoQ10 in such preparations has been relatively low.

The key parameter in oral delivery products is the ease ofCoQ10 dispersion when in contact with water. Self-emulsifying systems have beenshown to provide an effective and rapid dispersability of CoQ10 and offer stableemulsions that are rapidly formed once in contact with water.¹⁹ A two-foldincrease in the bioavailability is observed with such systems when compared topowder-filled formulations. It is important to recognize in this instance thebodys ability to digest such emulsions.

Earlier findings showed when CoQ10 is emulsified in lipidmicrospheres it exhibits an enhanced bioavailability.²⁰ Emulsification of CoQ10appears to be a determinant factor for effective absorption when orally dosed;this also can have a limiting effect when not properly designed during productformulation development. Human studies demonstrate emulsified CoQ10 preparationsmade into complex micelles show no difference in efficacy from suspensions ofCoQ10 powder in oil, although both could increase CoQ10 serum levels.²¹ In thisinstance, size exclusion effects become more dominant than solubility effects;therefore, to obtain micelle solubility, the surfactant system needs to be of arelatively small molecular size or easily biodegradable by the digestionprocess. The proper use of surfactants to solubilize CoQ10 is critical in thatsolubilization must be followed by absorption.

Dimitri Papadimitriou, Ph.D., is with Arevno Consultants. Hemay be contacted at [email protected].

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