Coenzyme Q10

Coenzyme Q10
IUPAC name
2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-decamethyltetraconta-2,6,10,14,18,22,26,30,34,38-decaenyl]-5, 6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione
Identifiers
CAS number 303-98-0 YesY
PubChem 5281915
Properties
Molecular formula C59H90O4
Molar mass 863.34 g mol−1
Related compounds
Related compounds 1,4-Benzoquinone
Quinone
Plastoquinone
 YesY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 (pronounced "ko-cue-ten"), CoQ, Q10, or Q) is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.

This oil-soluble 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 body’s energy is generated this way.[1][2] Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney —have the highest CoQ10 concentrations.[3][4][5]

Contents

Coenzyme Q10 concentrations in foods and dietary intake

Detailed reviews on occurrence of CoQ10 and dietary intake were published recently.[6] Besides endogenous synthesis, CoQ10 is also supplied to the organism by various foods. However, despite the scientific community’s great interest in this compound, a very limited number of studies have been performed to determine the contents of CoQ10 in dietary components. The first reports on this issue were published in 1959, but the sensitivity and selectivity of the analytical methods at that time did not allow reliable analyses, especially for products with low concentrations. [6] Developments in analytical chemistry have since enabled a more reliable determination of CoQ10 concentrations in various foods (Table below).

Table: CoQ10 levels in selected foods [6]
Food Coenzyme Q10 concentration [mg/kg]
Meat
- beef
-- heart 113
-- liver 39-50
-- muscle 26-40
- pork
-- heart 11.8-128.2
-- liver 22.7-54.0
-- muscle 13.8-45.0
- chicken
-- heart 116.2-132.2
Fish
- sardine 5-64
- mackerel
-- red flesh 43-67
-- white flesh 11-16
- salmon 4-8
- tuna 5
Oils
- soybean 54-280
- olive 4-160
- grapeseed 64-73
- sunflower 4-15
- rice bran /
- coconut /
Nuts
- peanuts 27
- walnuts 19
- sesame seeds 18-23
- pistachio nuts 20
- hazelnuts 17
- almond 5-14
Vegetables
- parsley 8-26
- broccoli 6-9
- cauliflower 2-7
- spinach up to 10
- grape 6-7
- Chinese cabbage 2-5
Fruit
- avocado 10
- blackcurrant 3
- strawberry 1
- orange 1-2
- grapefruit 1
- apple 1

Meat and fish are the richest source of dietary CoQ10. The compound is non-equally distributed among different tissues of the same animal source, depending on their function. Different levels can be found in the heart, liver, muscle etc.. CoQ10 levels over 50 mg/kg can be found in beef, pork and chicken heart and chicken liver. [6]

Dairy products are much poorer sources of CoQ10 compared to animal tissues, while a modest amount can be found in butter – 7 mg/kg.[6]

Substantial differences in reported CoQ10 contents have been observed in fish, in particular mackerel and sardine. Mackerel and herring were recently studied in detail, and the highest CoQ10 level was also found in the heart tissue (105-148 μg/g).[7] while lower concentrations were found in the body tissue (mackerel: 67μg/g in the red tissue, 15μg/g in the white tissue; herring tissue: 15–24 μg/g).[7] Flat fish, eels and other bottom fish have lower contents of CoQ10. Low CoQ10 levels were also found in salmon (4-8 mg/kg), despite its significant fat content. Fish and shellfish represent an important dietary source of CoQ10 (estimated at 9%-22% in different countries).[6]

Vegetable oils are also quite rich in CoQ10. Very different results can be found in the literature for CoQ10 levels in soybean, corn and olive oil. Soybean, grapeseed and olive oil are also good sources of CoQ10. Some oils, particularly corn oil, are much richer in CoQ9 than in CoQ10.[6]

Peanuts, sesame seeds, and pistachio are the richest CoQ10 representatives within nuts and seeds, with levels over 20 mg/kg. Many other nuts are also good sources of this compound. [6]

Within vegetables, parsley, and perilla are the richest CoQ10 sources, but significant differences in their CoQ10 levels can be found in the literature. Broccoli, grape, and cauliflower are modest sources of CoQ10. Most fruit and berries represent a poor to very poor source of CoQ10, with the exception of avocado, with a relatively high CoQ10 content.[6]

Intake

In the developed world, the estimated daily intake of CoQ10 has been determined at 3-6 mg per day, derived primarily from meat.[6]

Effect of heat and processing

Cooking by frying reduces CoQ10 content by 14-32%.[8]

Discovery

Coenzyme Q10 was first discovered by Professor Fredrick L. Crane and colleagues at the University of Wisconsin–Madison Enzyme Institute in 1957.[9][10] 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.[10][11]

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 Coenzyme Q in human mitochondria is CoQ10. 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.)

CoQ10 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. In its reduced form (ubiquinol), Coenzyme Q10 acts as an important antioxidant in the body.

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.

Absorption and metabolism

Absorption

CoQ10 is a crystalline powder that is insoluble in water because of 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.[12],[13] 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 facilitated chiefly by secretions from the pancreas and bile salts in the small intestine.[14] A general rule is that the higher the dose orally administered the lower the percent of the dose absorbed.[14]

Metabolism

Data on the metabolism of CoQ10 in animals and humans are limited.[12] 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.[15] 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.[16]

Factors affecting CoQ10 levels

Various factors reduce the concentration of CoQ10 in different organs; the following are known:

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,[20] and statins, a class of cholesterol-lowering drugs.[21][22] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[23] 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.[24][25]

Pharmacokinetics

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.[26] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.[27]

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[12], such as Nano CoQ-10.[2]

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;[28] 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.[29],[30] The use of the aqueous suspension of finely powdered CoQ10 in pure water has also only revealed a minor effect.[16]

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.[16] 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,[31] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.[13]

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.[12] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,[32] formulations based on various solubilising agents, i.e., hydrogenated lecithin, [33] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.[34],[35] and is also used in pharmaceutical and food industry for CoQ10-fortification.[12] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc can be used to increase the bioavailability of Coenzyme Q10.

Supplementation benefits

Coenzyme Q10 is the 3rd most sold dietary ingredient in the United States after omega-3 and multivitamins.

According to the Mayo Clinic[36] "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 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.[37] Coenzyme Q10 is then prescribed by a physician.[38]

Heart failure

There is some clinical evidence[39] that supplementation with coenzyme Q10 is beneficial in 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.[40] 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.[36]

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,[41] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[42] Dosages were 150 to 300 mg/day.

Cancer

CoQ10 is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[43]

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).[44]

Blood pressure

There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[45] In a recent (2007) 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.[46]

Periodontal disease

Studies have shown that diseased gum tissue is deficient in CoQ10 compared to healthy gum tissue.[47],[48] Human clinical trials have suggested a link between oral administration of CoQ10 and improved gingival health,[49] immune response in gum tissues,[50] and a reversal of the diseased gum conditions.[51] In addition to oral supplementation, topical application of CoQ10 on gum tissues has been shown to improve periodontitis and gingivitis conditions.[52]

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.[53] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q10 supplementation.[54] But multiple studies have since found no increase in lifespan or decrease in aging in mice and rats supplemented with coenzyme Q10. [55] [56] [57] [58] Another study demonstrated that coenzyme Q10 extends the lifespan of C. elegans (nematode).[59]

Radiation injury

A 2002 study reported that, in rat experiments, coenzyme Q10 taken as dietary supplement reduced radiation damage to the animals' blood.[60]

Parkinson's disease

A 2002 study in 80 Parkinson's disease patients found 1200mg/day reduced the progression by 44%.[61] [62]

See also

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. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Pravst et al. (2010) Coenzyme Q10 Contents in Foods and Fortification Strategies Critical Reviews in Food Science and Nutrition, 50 (4) 269-280
  7. ↑ 7.0 7.1 Nathalie Soucheta and Serge Laplante, Seasonal variation of coenzyme Q10 content in pelagic fish tissues from Eastern Quebec
  8. ↑ The coenzyme Q10 content of the average Danish die...[Int J Vitam Nutr Res. 1997] - PubMed Result
  9. ↑ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta 25 (1): 220–1. doi:10.1016/0006-3002(57)90457-2. PMID 13445756. 
  10. ↑ 10.0 10.1 Peter H. Langsjoen, "Introduction of Coezyme Q10"
  11. ↑ 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.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Zmitek et al. (2008) Agro Food Ind. Hi Tec. 19, 4, 9. - Improving the bioavailability of CoQ10
  13. ↑ 13.0 13.1 H. N. Bhagavan and R. K. Chopra, Mitochondrion, 7: S78-S88 (2007).
  14. ↑ 14.0 14.1 H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006).
  15. ↑ 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.
  16. ↑ 16.0 16.1 16.2 Y. Ozawa, Y. Mizushima, I. Koyama, M. Akimoto, Y. Yamagata, H. Hayashi and H. Murayama, Drug Res., 36-1: 689-690 (1986).
  17. ↑ doi:10.1007/BF02535072
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  18. ↑ doi:10.1111/j.1471-4159.1990.tb01889.x
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  19. ↑ PMID 8151122 (PubMed)
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  20. ↑ 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. PMID 17892. 
  21. ↑ The Synthesis of Cholesterol
  22. ↑ Mortensen, S.A.; et al. (1997). "Dose-Related Decrease of Coenzyme Q10 During Treatment with HMG-CoA Reductase Inhibitors". Molecular Aspects of Medicine 18 Suppl.: 137–144. PMID 9266515. 
  23. ↑ 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. PMID 8463436. 
  24. ↑ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs 16 (4): 9–20. PMID 12597259. 
  25. ↑ 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. PMID 9816194. 
  26. ↑ H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006)
  27. ↑ Y. Tomono, J. Hasegawa, T. Seki, K. Motegi and N. Morishita, Int. J. Clin. Pharmacol. Ther., 24: 536-541 (1986).
  28. ↑ 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).
  29. ↑ C. H. Hsu, Z. Cui, R. J. Mumper and M. Jay, AAPS PharmSciTech., 4: E32 (2003).
  30. ↑ S. S. Joshi, S. V. Sawant, A. Shedge and A. D. Halpner, Int. J. Clin. Pharmacol. Ther., 41: 42-48 (2003).
  31. ↑ T. R. Kommuru, M. Ashraf, M. A. Khan and I. K. Reddy, Chemical & Pharmaceutical Bulletin, 47: 1024-1028 (1999).
  32. ↑ K. Westesen and B. Siekmann. Particles with modified physicochemical properties, their preparation and uses. US6197349. 2001.
  33. ↑ H. Ohashi, T. Takami, N. Koyama, Y. Kogure and K. Ida. Aqueous solution containing ubidecarenone. US4483873. 1984
  34. ↑ Zmitek, J. et all (2008) Relative bioavailability of two forms of a novel water soluble CoQ10 Ann. Nutri. Metab. 52:281-287 (2008)
  35. ↑ D. Madhavi, and D. Kagan. (2010) "A Study of the Bioavailability of a Sustained-release CoEnzyme Q10-β-cyclodextrin Complex" 9(1):20-25.
  36. ↑ 36.0 36.1 Mayo Clinic Drugs and Supplements: Coenzyme Q10 (accessed 13 November 2008)
  37. ↑ Genova, M.L.; et al. (May 2003). "Mitochondrial Production of Oxygen Radical Species and the Role of Coenzyme Q as an Antioxidant". Experimental Biology and Medicine 228 (5): 506–513. PMID 12709577.  [1]
  38. ↑ 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 (4): 187–191. doi:10.1097/01.wnf.0000137862.67131.bf. PMID 15319706. 
  39. ↑ Peter H. Langsjoen, University of Washington, INTRODUCTION TO COENZYME Q10 (accessed 13 November 2008)
  40. ↑ ROBERT ALAN BONAKDAR and ERMINIA GUARNERI, American Family Physician page on CoEnzyme Q10 (Sept 2005, accessed 13 November 2008)
  41. ↑ 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. doi:10.1046/j.1468-2982.2002.00335.x. PMID 11972582. http://www.blackwell-synergy.com/doi/full/10.1046/j.1468-2982.2002.00335.x. 
  42. ↑ Sándor PS, et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology 64 (4): 713–715. doi:10.1212/01.WNL.0000151975.03598.ED (inactive 2010-04-28). PMID 15728298. http://www.neurology.org/cgi/content/abstract/64/4/713. 
  43. ↑ 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
  44. ↑ Damian, M. S.; et al. (July 2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation 110 (19): 3011–3016. doi:10.1161/01.CIR.0000146894.45533.C2. PMID 15520321. http://www.circ.ahajournals.org/cgi/content/abstract/110/19/3011. Retrieved 2006-12-01. 
  45. ↑ 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)
  46. ↑ 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
  47. ↑ Littarru GP, Nakamura R, Ho L, Folkers K, Kuzell WC (1971). "Deficiency of coenzyme Q10 in gingival tissue from patients with periodontal disease". Proc Natl Acad Sci U S A 68 (10): 2332–2335. doi:10.1073/pnas.68.10.2332. PMID 5289867. 
  48. ↑ Nakamura R, Littarru GP, Folkers K, Wilkinson EG (1974). "Study of CoQ10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10". Proc Natl Acad Sci U S A 71 (4): 1456–60. doi:10.1073/pnas.71.4.1456. PMID 4151519. 
  49. ↑ McRee JT, Hanioka T, Shizukuishi S, Folkers K (1993). "Therapy with coenzyme Q10 for patients with periodontal disease". J Dent Health 43: 659–666. 
  50. ↑ Folkers K, Hanioka T, Xia LJ, McRee JT, Langsjoen P (1991). "Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex". Biochem Biophys Res Commun. 176 (2): 786–91. doi:10.1016/S0006-291X(05)80254-2. PMID 1673841. 
  51. ↑ Wilkinson EG, Arnold RM, Folkers K (1976). "Bioenergetics in clinical medicine. VI. adjunctive treatment of periodontal disease with coenzyme Q10". Res Commun Chem Pathol Pharmacol. 14 (4): 715–719. PMID 785563. 
  52. ↑ Hanioka T, Tanaka M, Ojima M, Shizukuishi S, Folkers K (1994). "Effect of topical application of coenzyme Q10 on adult periodontitis". Mol Aspects Med. 15 (Suppl:s): 241–248. doi:10.1016/0098-2997(94)90034-5. PMID 7752836. 
  53. ↑ 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. doi:10.1016/j.exger.2003.10.002. PMID 15036411. 
  54. ↑ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension.". Advances in Anti-Aging Medicine. 1 (1): 205–215. 
  55. ↑ Lonnrot K, Holm P, Lagerstedt A, Huhtala H, Alho H (1998). "The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentrations and life span of male rats and mice.". Biochem Mol Biol Int.. 44 (4): 727–37. PMID 9584986. 
  56. ↑ Lee C-K, Pugh TD, Klopp RG, Edwards J, Allison DB, Weindruch R,Prolla TA. (2004). "The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.". Free Radic Biol Med. 36 (8): 1043–57. doi:10.1016/j.freeradbiomed.2004.01.015. PMID 15059645. 
  57. ↑ Sohal RS, Kamzalov S, Sumien N, Ferguson M, Rebrin I, Heinrich KR,Forster MJ. (2006). "The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice.". Free Radic Biol Med. 40 (3): 480–7. doi:10.1016/j.freeradbiomed.2005.08.037. PMID 16443163. 
  58. ↑ Nathalie Sumien,Kevin R. Heinrich, Ritu A. Shetty, Rajindar S. Sohal, and Michael J. Forster. (2009). "Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice". J. Nutr. 139 (10): 1926–1932. doi:10.3945/jn.109.110437. PMID 19710165. 
  59. ↑ 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. doi:10.1016/j.mad.2003.10.002. PMID 14706236. 
  60. ↑ A. S. Koryagin, E. V. Krylova, and L. D. Luk'yanova (June 2002). "Effect of Ubiquinone-10 on the Blood System in Rats Exposed to Radiation". Bulletin of Experimental Biology and Medicine 133 (6): 562–564. doi:10.1023/A:1020225623808. ISSN 0007-4888. PMID 12447465. . Abstract: "The use of synthetic ubiquinone-10 (2 and 10 mg/kg) as a therapeutic food additive normalized the counts of erythrocytes, reticulocytes, and leukocytes and the content of hemoglobin in the blood and inhibited lipid peroxidation in erythrocytes in irradiated rats (3 Gy)."
  61. ↑ "Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease". 2002. http://www.ninds.nih.gov/news_and_events/press_releases/pressrelease_parkinsons_coenzymeq10_101402.htm. 
  62. ↑ Shults et al. (October 2002,). ""Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline."". Archives of Neurology, 59, No. 10, pp. 1541-1550. 

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Mitochondrial electron transport chain/oxidative phosphorylation
Primary
Complex I/NADH dehydrogenase - Complex II/Succinate dehydrogenase - Coenzyme Q - Complex III/Coenzyme Q - cytochrome c reductase - Cytochrome c - Complex IV/Cytochrome c oxidase
Other
Alternative oxidase - Electron-transferring-flavoprotein dehydrogenase
Enzyme cofactors
Active forms

vitamins: TPP / ThDP (B1) · FMN, FAD (B2) · NAD+, NADH, NADP+, NADPH (B3) · Coenzyme A (B5) · PLP / P5P (B6) · Biotin (B7) · THFA / H4FA, DHFA / H2FA, MTHF (B9) · AdoCbl, MeCbl (B12) · Ascorbic Acid (C) · Phylloquinone (K1, Menaquinone (K2) · Coenzyme F420
non-vitamins: ATP · CTP · SAMe · PAPS · GSH · Coenzyme B · Coenzyme F430 · Coenzyme M · Coenzyme Q · Heme / Haem (A, B, C, O) · Lipoic Acid · Methanofuran · Molybdopterin · PQQ · THB / BH4 · THMPT / H4MPT

minerals: Ca2+ · Cu2+ · Fe2+, Fe3+ · Mg2+ · Mn2+ · Mo · Ni2+ · Se · Zn2+
Base forms
vitamins: Thiamine (B1) · Riboflavin (B2) · Niacin, Niacinamide (B3) · Pantothenic Acid (B5) · Pyridoxine, Pyridoxamine, Pyridoxal (B6) · Cyanocobalamin, Hydroxocobalamin (B12)

: NUT

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noco, nuvi, sysi/, met

drug(A8/11/12)
Antioxidants
Acetyl-L-Carnitine (ALCAR) • Alpha-Lipoic Acid (ALA) • Ascorbic Acid (Vitamin C) • Carotenoids (Vitamin A) • Curcumin • Edaravone • Flavonoids (Quercetin, Kaempferol, Catechin, EGCG, etc) • Gallic Acid • Glutathione • Hydroxytyrosol • L-Carnitine • Ladostigil • Melatonin • N-Acetylcysteine (NAC) • N-Acetylserotonin (NAS) • Oleocanthal • Oleuropein • Rasagiline • Resveratrol • Selegiline • Selenium • Tocopherols (Vitamin E) • Tocotrienols (Vitamin E) • Tyrosol • Ubiquinone (Coenzyme Q) • Uric Acid