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Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.

This oil-soluble vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human bodys energy is generated this way.[1][2] Therefore, those organs with the highest energy requirements—such as the heart and the liver—have the highest CoQ10 concentrations.[3][4][5]

History

Coenzyme Q was first discovered by professor Andrew L. Crane and colleagues at the University of Wisconsin–Madison Enzyme Institute in 1957.[6][7] In 1958, its chemical structure was reported by Dr. Karl Folkers and coworkers at Merck; in 1968, Folkers became a Professor in the Chemistry Department at the University of Texas at Austin.[7][8]

Chemical properties

The oxidized structure of CoQ10 is shown on the top right. The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid side-chains they have. The most common CoQ in human mitochondria is Q10. The 10 refers to the number of isoprene repeats. The image below has three isoprenoid units and would be called Q3.

Ubiquinone3.png

Biochemical role

Electron transport chain ("UQ" visible in green near center.)

CoQ is found in the membranes of many organelles. Since its primary function in cells is in generating energy, the highest concentration is found on the inner membrane of the mitochondrion. Some other organelles that contain CoQ10 include endoplasmic reticulum, peroxisomes, lysosomes, and vesicles.

Supplementation

Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q is used as a dietary supplement.

According to the Mayo Clinic[9] "CoQ10 has been used, recommended, or studied for numerous conditions, but remains controversial as a treatment in many areas." Further clinical results are needed to determine whether the supplementation with Coenzyme Q10 is beneficial for healthy people.

Mitochondrial disorders

Supplementation of Coenzyme Q10 is a treatment for some of the very rare and serious mitochondrial disorders and other metabolic disorders, where patients are not capable of producing enough coenzyme Q10 because of their disorder. Coenzyme Q10 is then prescribed by a physician.[10]

Heart failure

There is some clinical evidence[11] that supplementation with Coenzyme Q10 is beneficial treatment of patients with congestive heart failure. However, The American College of Cardiology published in 2005 an expert consensus document concluding that the value of coenzyme Q10 in cardiovascular disease has not been clearly established.[12] The Mayo clinic says that there is not enough scientific evidence to recommend for or against the use of CoQ10 in patients with coronary heart disease.[9]

Migraine headaches

Supplementation of Coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far, three studies have been done, of which two were small, did not have a placebo group, were not randomized, and were open-label,[13] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[14] Dosages were 150 to 300 mg/day.

Cancer

It is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[15]

Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if coenzyme Q10 is administered in addition to commencing active cooling of the body to 90–93 degrees Fahrenheit (32–34 degrees Celsius).[16]

Blood pressure

There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[17] In a recent meta-analysis of the clinical trials of CoQ10 for hypertension, a research group led by Professor Frank Rosenfeldt (Director, Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q10 for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies. The research group concluded that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side-effects.[18]

Lifespan

One study demonstrated that low dosages of coenzyme Q10 reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and coenzyme Q10 supplementation leads to a longer lifespan in rats.[19] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q10 supplementation.[20] Another study demonstrated that coenzyme Q10 extends the lifespan of c. elegans (nematode).[21]

Biosynthesis

The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is also used for the first steps of cholesterol biosynthesis.

Inhibition by statins and beta blockers

Coenzyme Q10 shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of Coenzyme Q10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[22] and statins, a class of cholesterol-lowering drugs.[23] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[24] Some research suggests the logical option of supplementation with coenzyme Q10 as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q10, based on a balance of likely benefit against very small risk.[25][26]

Absorption and metabolism

CoQ10 is a crystalline powder that is insoluble in water due to its low polarity. It has a relatively high molecular weight (863 g/mol) and its solubility in lipids is also limited so it is very poorly absorbed in the gastrointestinal tract.[27],[28] Absorption follows the same process as that of lipids and the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient. Emulsification and micelle formation is required for the absorption of fats. For CoQ10, this process is chiefly facilitated by secretions from the pancreas and bile salts in the small intestine.[29] A general rule is that the higher the dose orally administered, the lower the percent of the dose absorbed.[29]

Data on the metabolism of CoQ10 in animals and humans are limited.[27] A study with 14C-labeled CoQ10 in rats showed most of the radioactivity in the liver 2 hours after oral administration when the peak plasma radioactivity was observed, but it should be noted that CoQ9 is the predominant form of coenzyme Q in rats.[30] It appears that CoQ10 is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ10 supplementation, the levels return to their normal levels within a few days, irrespective of the type of formulation used.[31]

Factors affecting ubiquinone levels

Use of statins reduce ubiquinone levels.
Aging, in individuals older than 20 years, reduces ubiquinone levels in internal organs.[32][33]
UV exposure reduces ubiquinone levels in the skin.[34]

Pharmacokinetics and bioavailability

Some reports have been published on the pharmacokinetics of CoQ10. The plasma peak can be observed 2–6 hours after oral administration, mainly depending on the design of the study. In some studies, a second plasma peak was also observed at about 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.[35] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.[36]

Improving the bioavailability of CoQ10

The importance of how drugs are formulated for bioavailability is well known. In order to find a principle to boost the bioavailability of CoQ10 after oral administration, several new approaches have been taken and different formulations and forms have been developed and tested on animals or humans.[27]

Reduction of particle size

The obvious strategy is reduction of the particle size to as low as the micro- and nano-scale. Nanoparticles have been explored as a delivery system for various drugs and an improvement of the oral bioavailability of drugs with poor absorption characteristics has been reported;[37] the pathways of absorption and the efficiency were affected by reduction of particle size. This protocol has so far not proved to be very successful with CoQ10, although reports have differed widely.[38],[39] The use of the aqueous suspension of finely powdered CoQ10 in pure water has also only revealed a minor effect.[31]

Soft-gel capsules with CoQ10 in oil suspension

A successful approach was to use the emulsion system to facilitate absorption from the gastrointestinal tract and to improve bioavailability. Emulsions of soybean oil (lipid microspheres) could be stabilised very effectively by lecithin and were utilised in the preparation of soft gelatine capsules. In one of the first such attempts, Ozawa et al. performed a pharmacokinetic study on beagle dogs in which the emulsion of CoQ10 in soybean oil was investigated; about two times higher plasma CoQ10 level than that of the control tablet preparation was determined during administration of a lipid microsphere.[31] Although an almost negligible improvement of bioavailability was observed by Kommuru et al. with oil-based soft-gel capsules in a later study on dogs,[40] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.[28]

Novel forms of CoQ10 with increased water-solubility

Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and has also been shown to be successful for Coenzyme Q10. Various approaches have been developed to achieve this goal, with many of them producing significantly better results over oil-based soft-gel capsules in spite of the many attempts to optimize their composition.[27] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,[41] formulations based on various solubilising agents, i.e. hydrogenated lecithin, [42] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.[43] and is also used in pharmaceutical and food industry for CoQ10-fortification.[27] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc can be used to increase the bioavailability of Coenzyme Q10.

Occurrence in nature

Fresh tissue samples from both mackerel and herring found the concentration of Coenzyme Q10 to be higher in the heart tissue (105-148 μg/g) compared to concentrations found in the body tissue. The red tissue of mackerel contained a higher concentration (67μg/g) of CoQ10 than the white tissue (15μg/g) whilst in herring tissue the concentration was found to range between 1524 ug/g. A small seasonal variance in the concentrations of CoQ10 was observed in both fish [44].

References

  1. ^ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
  2. ^ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
  3. ^ Okamoto, T.et al. (1989) Interna.J.Vit.Nutr.Res.,59,288-292
  4. ^ Aberg,F.et al. (1992)Archives of Biochemistry and Biophysics, 295, 230-234
  5. ^ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
  6. ^ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta 25 (1): 220–1.
  7. ^ a b Peter H. Langsjoen, "Introduction of Coezyme Q10"
  8. ^ Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K. Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.
  9. ^ a b Mayo Clinic Drugs and Supplements: Coenzyme Q10 (accessed 13 November 2008)
  10. ^ Berbel-Garcia, A.; et al. (July 2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology 27: 187–191.
  11. ^ Peter H. Langsjoen, University of Washington, INTRODUCTION TO COENZYME Q10 (accessed 13 November 2008)
  12. ^ ROBERT ALAN BONAKDAR and ERMINIA GUARNERI, American Family Physician page on CoEnzyme Q10 (Sept 2005, accessed 13 November 2008)
  13. ^ Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia 22 (2): 137–41.:10.1046/j.1468-2982.2002.00335.x. 11972582. http://www.blackwell-synergy.com/doi/full/10.1046/j.1468-2982.2002.00335.x. 
  14. ^ Sándor PS, et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology 64: 713-715:10.1212/01.WNL.0000151975.03598.ED. 15728298. http://www.neurology.org/cgi/content/abstract/64/4/713. 
  15. ^ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
  16. ^ Damian, M. S.; et al. (July 2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation 110: 3011–3016.http://www.circ.ahajournals.org/cgi/content/abstract/110/19/3011. Retrieved 2006-12-01. 
  17. ^ Cupp MJ and Tracy TS. Chapter 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone), pp 53-85 in Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey (2003)
  18. ^ Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007
  19. ^ Quiles JL, Ochoa JJ, Huertas JR, Mataix J (2004). "Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet.". Exp Gerontol. 39 (2): 189–94.
  20. ^ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension.". Advances in Anti-Aging Medicine. 1 (1): 205-215. 
  21. ^ Ishii N, Senoo-Matsuda N, Miyake K, Yasuda K, Ishii T, Hartman PS, Furukawa S (2004). "Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress.". Mech Ageing Dev. 125 (1): 41-6.
  22. ^ Kishi T, Watanabe T, Folkers K (1977). "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Res Commun Chem Pathol Pharmacol 17 (1): 157–64.
  23. ^ The Synthesis of Cholesterol
  24. ^ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol 33 (3): 226–9.
  25. ^ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs 16 (4): 9-20. 10.1002/cncr.11242<hr><a (inactive 2008-06-26).
  26. ^ Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clin Cancer Res 2 (3): 483–91.
  27. ^ a b c d e Zmitek et al. (2008) Agro Food Ind. Hi Tec. 19, 4, 9. - Improving the bioavailability of CoQ10
  28. ^ a b H. N. Bhagavan and R. K. Chopra, Mitochondrion, 7: S78-S88 (2007).
  29. ^ a b H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006).
  30. ^ H. Kishi, N. Kanamori, S. Nisii, E. Hiraoka, T. Okamoto and T. Kishi, Metabolism and Exogenous Coenzyme Q10 in vivo and Bioavailability of Coenzyme Q10 Preparations in Japan. In Biomedical and Clinical Aspects of Coenzyme Q. pp. 131-142, Elsevier, Amsterdam 1964.
  31. ^ a b c Y. Ozawa, Y. Mizushima, I. Koyama, M. Akimoto, Y. Yamagata, H. Hayashi and H. Murayama, Drug Res., 36-1: 689-690 (1986).
  32. ^ Kalén, A.; Appelkvist, E. L.; Dallner, G. (1989). "Age-related changes in the lipid compositions of rat and human tissues". Lipids 24 (7): 579–584.
  33. ^ Söderberg, M. (1990). "Lipid Compositions of Different Regions of the Human Brain During Aging". Journal of Neurochemistry 54: 415–419.
  34. ^ Shindo, Y; Witt, E; Han, D; Packer, L (Apr 1994). "Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis". The Journal of investigative dermatology 102 (4): 470–5.
  35. ^ H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006)
  36. ^ Y. Tomono, J. Hasegawa, T. Seki, K. Motegi and N. Morishita, Int. J. Clin. Pharmacol. Ther., 24: 536-541 (1986).
  37. ^ E. Mathiowitz, J. S. Jacob, Y. S. Jong, G. P. Carino, D. E. Chickering, P. Chaturvedi, C. A. Santos, K. Vijayaraghavan, S. Montgomery, M. Bassett and C. Morrell, Nature, 386: 410-414 (1997).
  38. ^ C. H. Hsu, Z. Cui, R. J. Mumper and M. Jay, AAPS PharmSciTech., 4: E32 (2003).
  39. ^ S. S. Joshi, S. V. Sawant, A. Shedge and A. D. Halpner, Int. J. Clin. Pharmacol. Ther., 41: 42-48 (2003).
  40. ^ T. R. Kommuru, M. Ashraf, M. A. Khan and I. K. Reddy, Chemical & Pharmaceutical Bulletin, 47: 1024-1028 (1999).
  41. ^ K. Westesen and B. Siekmann. Particles with modified physicochemical properties, their preparation and uses. US6197349. 2001.
  42. ^ H. Ohashi, T. Takami, N. Koyama, Y. Kogure and K. Ida. Aqueous solution containing ubidecarenone. US4483873. 1984
  43. ^ Zmitek, J. et all (2008) Relative bioavailability of two forms of a novel water soluble CoQ10 Ann. Nutri. Metab. 52:281-287 (2008)
  44. ^ Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec
  45. ^ The coenzyme Q10 content of the average Danish die...[Int J Vitam Nutr Res. 1997] - PubMed Result

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