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Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

A New Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers

Author(s): Giovanna Petrangolini, Massimo Ronchi, Elisabetta Frattini, Eric De Combarieu, Pietro Allegrini and Antonella Riva*

Volume 16, Issue 8, 2019

Page: [759 - 767] Pages: 9

DOI: 10.2174/1567201816666190902123147

open access plus


Background: Coenzyme Q10 is a fundamental endogenous factor involved in cell energy production that shows protective properties in oxidative stress, mainly in skeletal and heart muscle. Coenzyme Q10 supplementation appears to benefit athletes in strenuous training and in the elderly, demonstrating ant-inflammatory properties by reducing inflammatory cytokines. Improved absorption of coenzyme Q10 via a new delivery system would represent an important step forward in the use of coenzyme Q10 as a dietary supplement.

Objective: The aim of the study was to evaluate the solubility and oral absorption in human healthy volunteers of a new food grade coenzyme Q10 phytosome formulation.

Methods: Solubility studies were performed in vitro in simulated gastrointestinal fluids; human studies were conducted in healthy volunteers to evaluate oral absorption in a Single dose study, in comparison with the coenzyme Q10 capsules, and in a repeated study at two increasing doses.

Results: The highest solubility shown by coenzyme Q10 phytosome in simulated intestinal fluids results in an improvement in oral absorption of coenzyme Q10 in healthy volunteers, three times more than the coenzyme Q10 according to AUC (area under the time/concentration curve) values. When two increasing doses (one and two capsules) were administered to healthy volunteers within a two-week schedule, the plasmatic levels of coenzyme Q10 resulted in 0.864±0.200 μg/ml (Mean±S.D.+41%) and 1.321±0.400 μg/ml (+116%), respectively versus baseline (0.614±0.120 μg/ml one capsule, 0.614±0.160 μg/ml two capsules). This detected dose-related bioavailability of coenzyme Q10 phytosome was even observed with no alterations in vital signs, neither in the physical examination nor in ECG, and no changes of clinical and biochemical parameters were observed.

Conclusion: These findings, taken together, support the safety profile and significantly improved coenzyme Q10 oral absorption in humans with this new phytosome delivery formulation.

Keywords: Phytosome, CoQ10, pharmacokinetic, oral absorption, healthy volunteers, food-grade.

Graphical Abstract
Gutierrez-Mariscal, F.M.; Yubero-Serrano, E.M.; Villalba, J.M.; Lopez-Miranda, J.; Coenzyme, Q. Coenzyme Q10: From bench to clinic in aging diseases, a translational review. Crit. Rev. Food Sci. Nutr., 2019, 59(14), 2240-2257.
[] [PMID: 29451807]
Laredj, L.N.; Licitra, F.; Puccio, H.M. The molecular genetics of coenzyme Q biosynthesis in health and disease. Biochimie, 2014, 100, 78-87.
[] [PMID: 24355204]
Orlando, P.; Silvestri, S.; Galeazzi, R.; Antonicelli, R.; Marcheggiani, F.; Cirilli, I.; Bacchetti, T.; Tiano, L. Effect of ubiquinol supplementation on biochemical and oxidative stress indexes after intense exercise in young athletes. Redox Rep., 2018, 23(1), 136-145.
[] [PMID: 29734881]
Del Pozo-Cruz, J.; Rodríguez-Bies, E.; Navas-Enamorado, I.; Del Pozo-Cruz, B.; Navas, P.; López-Lluch, G. Relationship between functional capacity and body mass index with plasma coenzyme Q10 and oxidative damage in community-dwelling elderly-people. Exp. Gerontol., 2014, 52, 46-54.
[] [PMID: 24512763]
Qu, H.; Guo, M.; Chai, H.; Wang, W.T.; Gao, Z.Y.; Shi, D.Z. Effects of Coenzyme Q10 on statin-induced myopathy: An updated meta-analysis of randomized controlled trials. J. Am. Heart Assoc., 2018, 7(19)e009835
[] [PMID: 30371340]
Lee, B.J.; Tseng, Y.F.; Yen, C.H.; Lin, P.T. Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: A randomized, placebo-controlled trial. Nutr. J., 2013, 12(1), 142.
[] [PMID: 24192015]
Hernández-Camacho, J.D.; Bernier, M.; López-Lluch, G.; Navas, P.; Coenzyme, Q. Coenzyme Q10 supplementation in aging and disease. Front. Physiol., 2018, 9, 44.
[] [PMID: 29459830]
Zaki, N.M. Strategies for oral delivery and mitochondrial targeting of CoQ10. Drug Deliv., 2016, 23(6), 1868-1881.
[] [PMID: 25544601]
Riva, A.; Ronchi, M.; Petrangolini, G.; Bosisio, S.; Allegrini, P. Improved oral absorption of quercetin from quercetin phytosome®, a new delivery system based on food grade lecithin. Eur. J. Drug Metab. Pharmacokinet., 2019, 44(2), 169-177.
[] [PMID: 30328058]
Augustijns, P.; Wuyts, B.; Hens, B.; Annaert, P.; Butler, J.; Brouwers, J. A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption. Eur. J. Pharm. Sci., 2014, 57, 322-332.
[] [PMID: 23994640]
Ciceri, D.; Peterlongo, F.; Ronchi, M. Solid dispersions of Coenzyme Q10 patent Pubblication WO/2016/198576, December 15,, 2016.
López-Lluch, G.; Del Pozo-Cruz, J.; Sánchez-Cuesta, A.; Cortés-Rodríguez, A.B.; Navas, P. Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization. Nutrition, 2019, 57, 133-140.
[] [PMID: 30153575]
Miles, M.V. The uptake and distribution of coenzyme Q10. Mitochondrion, 2007, (7)(Suppl.), S72-S77.
[] [PMID: 17446143]
Tomono, Y.; Hasegawa, J.; Seki, T.; Motegi, K.; Morishita, N. Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man. Int. J. Clin. Pharmacol. Ther. Toxicol., 1986, 24(10), 536-541.
[PMID: 3781673]
Betteridge, D.J. What is oxidative stress? Metabolism, 2000, 49(2)(Suppl. 1), 3-8.
[] [PMID: 10693912]
Kreher, J.B.; Schwartz, J.B. Overtraining syndrome: A practical guide. Sports Health, 2012, 4(2), 128-138.
[] [PMID: 23016079]
Tanskanen, M.; Atalay, M.; Uusitalo, A. Altered oxidative stress in overtrained athletes. J. Sports Sci., 2010, 28(3), 309-317.
[] [PMID: 20077275]
He, F.; Li, J.; Liu, Z.; Chuang, C.C.; Yang, W.; Zuo, L. Redox mechanism of reactive oxygen species in exercise. Front. Physiol., 2016, 7, 486.
[] [PMID: 27872595]
Kemi, O.J.; Haram, P.M.; Loennechen, J.P.; Osnes, J.B.; Skomedal, T.; Wisløff, U.; Ellingsen, Ø. Moderate vs. high exercise intensity: Differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovasc. Res., 2005, 67(1), 161-172.
[] [PMID: 15949480]
Bełtowski, J.; Wójcicka, G.; Górny, D.; Marciniak, A. The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J. Physiol. Pharmacol., 2000, 51(4 Pt 2), 883-896.
[PMID: 11220496]
Huang, C.J.; McAllister, M.J.; Slusher, A.L.; Webb, H.E.; Mock, J.T.; Acevedo, E.O. Obesity-related oxidative stress: The impact of physical activity and diet manipulation. Sports Med. Open, 2015, 1(1), 32.
[] [PMID: 26435910]
Sarmiento, A.; Diaz-Castro, J.; Pulido-Moran, M.; Moreno-Fernandez, J.; Kajarabille, N.; Chirosa, I.; Guisado, I.M.; Javier Chirosa, L.; Guisado, R.; Ochoa, J.J. Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. Biofactors, 2016, 42(6), 612-622.
[] [PMID: 27193497]
Emami, A.; Tofighi, A.; Asri-Rezaei, S.; Bazargani-Gilani, B. The effect of short-term coenzyme Q10 supplementation and pre-cooling strategy on cardiac damage markers in elite swimmers. Br. J. Nutr., 2018, 119(4), 381-390.
[] [PMID: 29498347]
Mazidi, M.; Kengne, A.P.; Banach, M. Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res., 2018, 128, 130-136.
[] [PMID: 28847708]
Fan, L.; Feng, Y.; Chen, G.C.; Qin, L.Q.; Fu, C.L.; Chen, L.H. Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res., 2017, 119, 128-136.
[] [PMID: 28179205]
Fung, W.Y.; Liong, M.T.; Yuen, K.H. Preparation, in-vitro and in-vivo characterisation of CoQ10 microparticles: electrospraying-enhanced bioavailability. J. Pharm. Pharmacol., 2016, 68(2), 159-169.
[] [PMID: 26730452]
Lee, J.S.; Suh, J.W.; Kim, E.S.; Lee, H.G. Preparation and characterization of mucoadhesive nanoparticles for enhancing cellular uptake of coenzyme Q10. J. Agric. Food Chem., 2017, 65(40), 8930-8937.
[] [PMID: 28933847]
Muthukumaran, K.; Kanwar, A.; Vegh, C.; Marginean, A.; Elliott, A.; Guilbeault, N.; Badour, A.; Sikorska, M.; Cohen, J.; Pandey, S. Ubisol-Q10 (a Nanomicellar water-soluble formulation of CoQ10) treatment inhibits alzheimer-type behavioral and pathological symptoms in a double transgenic mouse (TgAPEswe, PSEN1dE9) model of Alzheimer’s disease. J. Alzheimers Dis., 2018, 61(1), 221-236.
[] [PMID: 29154270]
Verma, D.D.; Hartner, W.C.; Thakkar, V.; Levchenko, T.S.; Torchilin, V.P. Protective effect of coenzyme Q10-loaded liposomes on the myocardium in rabbits with an acute experimental myocardial infarction. Pharm. Res., 2007, 24(11), 2131-2137.
[] [PMID: 17657597]
Xia, S.; Xu, S.; Zhang, X.; Zhong, F.; Wang, Z. Nanoliposomes mediate coenzyme Q10 transport and accumulation across human intestinal Caco-2 cell monolayer. J. Agric. Food Chem., 2009, 57(17), 7989-7996.
[] [PMID: 19663384]
Riva, A.; Vitale, J.A.; Belcaro, G.; Hu, S.; Feragalli, B.; Vinciguerra, G.; Cacchio, M.; Bonanni, E.; Giacomelli, L.; Eggenhöffner, R.; Togni, S. Quercetin phytosome® in triathlon athletes: A pilot registry study. Minerva Med., 2018, 109(4), 285-289.
[] [PMID: 29947492]
Bank, G.; Kagan, D.; Madhavi, D. Coenzyme Q10. Clinical Update and Bioavailability Journal of Evidence-Based Complementary & Alternative Medicine, 2011, 16(2), 129-137.
Rodick, T.C.; Seibels, D.R.; Babu, J.R.; Hugging, K.W.; Ren, G.; Mathews, S.T. Potential role of coenzyme Q10 in health and disease conditions. Nutr. Diet. Suppl., 2018, 10, 1-11.
Bhagavan, H.N.; Chopra, R.K. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion, 2007, (7)(Suppl.), S78-S88.
Rosenfeldt, F.; Marasco, S.; Lyon, W.; Wowk, M.; Sheeran, F.; Bailey, M.; Esmore, D.; Davis, B.; Pick, A.; Rabinov, M.; Smith, J.; Nagley, P.; Pepe, S. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue. J. Thorac. Cardiovasc. Surg., 2005, 129(1), 25-32.
[] [PMID: 15632821]
Chopra, R.K.; Goldman, R.; Sinatra, S.T.; Bhagavan, H.N. Relative bioavailability of coenzyme Q10 formulations in human subjects. Int. J. Vitam. Nutr. Res., 1998, 68(2), 109-113.
[PMID: 9565826]
Martucci, A.; Reurean-Pintilei, D.; Manole, A. Bioavailability and sustained plasma concentrations of CoQ10 in healthy volunteers by a novel oral timed-release preparation. Nutrients, 2019, 11(3), 527.
[] [PMID: 30823449]

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