Blood CoQ_{10} levels and safety profile after singe-dose or chronic administration of PureSorb-Q™40: Animal and human studies

Issue title: The Fifth Conference of the International CoQ10 Association, Kobe 2007 – 50th anniversary of CoQ10 discovery

Article type: Research Article

Authors: Nukui, Kazuki | Yamagishi, Toshihiko | Miyawaki, Hiromi | Kettawan, Aikkarach | Okamoto, Tadashi | Belardinelli, Romualdo | Tiano, Luca | Littarru, Gian Paulo | Sato, Kiyoshi

Affiliations: Nisshin Pharma Inc., Tokyo, Japan | Miyawaki Orthopedic Clinic, Hokkaido, Japan | Institute of Nutrition, Mahidol University, Thailand | Department of Health Sciences and Social Pharmacy, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan | Lancisi Heart Institute, Department of Cardiology and Cardiac Surgery, Ancona, Italy | Institute of Biochemistry, Polytechnic University of the Marche, Ancona, Italy

Note: [] Address for correspondence: T. Yamagishi, 25, Kanda-Nishiki-cho 1chome, Chiyoda-ku, Tokyo 101-8441, Japan. Tel.: +81 3 5282 6533; Fax: +81 3 5282 6150; E-mail: [email protected]

Abstract: Coenzyme Q_{10} (CoQ_{10}) is known to be highly hydrophobic and, as such, insoluble in water: this leads to serious inconvenience when trying to incorporate it in food products. Its absorption is also known to be very limited. PureSorb-Q™40 (P40) (Water-soluble type CoQ_{10} powder, CoQ_{10} content 40 w/w % was developed in order to improve its use with food products and to enhance its absorption. In the present study the absorption of this novel formulation was compared to a conventional lipid soluble CoQ_{10} by administering both products to rats and humans. Acute, single-administration studies in rats showed that P40 has a higher absorption, compared to lipid soluble CoQ_{10}, both in prandial and fasting states. Similarly, single administration in humans revealed a higher absorption level for P40, taken in the fasting state or together with meals. In the rat study, no adverse effects were observed with P40 at doses up to 2,000 mg/kg in both sexes. In a double-blind, placebo controlled, comparative study conducted on 46 healthy volunteers and randomly divided into two groups, in the group receiving 900~mg of CoQ_{10} per day, for 4 consecutive weeks, the average level at two weeks was 8.79 ± 3.34 μg/mL, similar to the corresponding level after 4 weeks (8.33 ± 4.04 μg/mL). After 2 weeks of washout, serum CoQ_{10} level decreased to 1.30 ± 0.49 μg/mL. P40 intake did not cause any significant changes in symptoms and clinical laboratory tests as assessed by physical, hematological, blood biochemical or urinalysis. Clinical examinations also did not reveal any abnormalities. The above blood (serum) CoQ_{10} level at 2 weeks after start of intake was compared with other reported values. The same dose of CoQ_{10} (900mg/day), when administered by softgel capsules yielded a plasma CoQ_{10} concentration of 3.6 μg/mL, while P40 levels were 8.79 ± 3.34 mug/mL. These levels are remarkably high for instance when compared to the corresponding levels obtained, in patients affected by Parkinson's disease, with CoQ_{10} doses up to 2,400mg/day. A clinical study was conducted using doses of 300 mg/day and 600 mg/day, in patients affected by cardiovascular disease. Also in this case there was linearity in the response with the levels obtained by administering P40 at a dose of 100 and 900 mg/day.

Keywords: Coenzyme Q[TeX:] _{10}, PureSorb-™Q40, P40, absorption, uptake, rat, human, blood CoQ[TeX:] _{10} level

Journal: BioFactors, vol. 32, no. 1-4, pp. 209-219, 2008