Coenzyme Q10

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Coenzyme Q10
File:Ubiquinone.png
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
style="background: #F8EABA; text-align: center;" colspan="2" | Identifiers
CAS number 303-98-0 YesY
PubChem 5281915
SMILES Script error: No such module "collapsible list".
style="background: #F8EABA; text-align: center;" colspan="2" | Properties
Molecular formula C59H90O4
Molar mass 863.34 g mol−1
style="background: #F8EABA; text-align: center;" colspan="2" | 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, 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 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] There are three redox states of Coenzyme Q10: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol).


Discovery

Coenzyme Q10 was first discovered by Professor Fredrick 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 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.
300px

Biochemical role

File:ETC.PNG
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 biosynthesis is a multistage process requiring at least eight vitamins and several trace elements. 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.[9],[10] 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.[11] A general rule is that the higher the dose orally administered the lower the percent of the dose absorbed.[11]

Metabolism

Data on the metabolism of CoQ10 in animals and humans are limited.[9] 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.[12] 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.[13]

Factors affecting CoQ10 levels

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

  • Use of statins reduce CoQ10 levels — see below.
  • Aging, in individuals older than 20 years, reduces CoQ10 levels in internal organs.[14][15]
  • UV exposure reduces CoQ10 levels in the skin.[16]

    • 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,[17] and statins, a class of cholesterol-lowering drugs.[18][19] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[20] 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.[21][22]

    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.[23] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.[24]

    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[9], such as Nano CoQ-10.[1]

    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;[25] 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.[26],[27] The use of the aqueous suspension of finely powdered CoQ10 in pure water has also only revealed a minor effect.[13]

    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.[13] 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,[28] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.[10]

    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.[9] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,[29] formulations based on various solubilising agents, i.e., hydrogenated lecithin, [30] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.[31],[32] and is also used in pharmaceutical and food industry for CoQ10-fortification.[9] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc can be used to increase the bioavailability of Coenzyme Q10.

    Ubiquinol form

    Since the ubiquinol form has two additional hydrogens, it results in the conversion of two ketone groups into hydroxyl groups on the active portion of the molecule. This causes an increase in the polarity of the CoQ10 molecule and maybe a significant factor behind the observed enhanced bioavailability of ubiquinol. Orally, ubiquinol exhibits greater bioavailability than ubiquinone: one study showed subjects ingesting 150 mg per day ubiquinol supplementation displayed peak values within 28 days of 3.84 mcg/ml of plasma.[33] Additionally, research in an animal model investigating the neuroprotective effects of both forms of CoQ10 showed greater blood levels and improved efficacy by ubiquinol in comparison to ubiquinone.[34]


    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[35] "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.[36] Coenzyme Q10 is then prescribed by a physician.[37]

    Heart failure

    There is some clinical evidence[38] 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.[39] 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.[35]

    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,[40] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[41] 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.[42] [43] [44] [45]

    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).[46]

    Blood pressure

    There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[47] A recent (2007) meta-analysis of the clinical trials of CoQ10 for hypertension 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 meta-analysis 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.[48]

    Periodontal disease

    Studies have shown that diseased gum tissue is deficient in CoQ10 compared to healthy gum tissue.[49],[50] Human clinical trials have suggested a link between oral administration of CoQ10 and improved gingival health,[51] immune response in gum tissues,[52] and a reversal of the diseased gum conditions.[53] In addition to oral supplementation, topical application of CoQ10 on gum tissues has been shown to improve periodontitis and gingivitis conditions.[54]

    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.[55] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q10 supplementation.[56] But multiple studies have since found no increase in lifespan or decrease in aging in mice and rats supplemented with coenzyme Q10. [57] [58] [59] [60] Another study demonstrated that coenzyme Q10 extends the lifespan of C. elegans (nematode).[61]

    Radiation injury

    A 2002 study reported that, in rat experiments, coenzyme Q10 taken as dietary supplement reduced radiation damage to the animals' blood.[62]

    Parkinson's disease

    A 2002 study in 80 Parkinson's disease patients found 1200mg/day reduced the progression by 44%.[63] [64] and a phase III trial of 1200mg/d and 2400mg/d should run until 2011.[65]

    Coenzyme Q10 concentrations in foods and dietary intake

    Detailed reviews on occurrence of CoQ10 and dietary intake were published recently.[66] 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. [66] 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 [66]
    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 and levels over 50 mg/kg can be found in beef, pork and chicken heart and chicken liver. Dairy products are much poorer sources of CoQ10 compared to animal tissues. Vegetable oils are also quite rich in CoQ10. 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.[66]

    Intake

    In the developed world, the estimated daily intake of CoQ10 has been determined at 3-6 mg per day, derived primarily from meat.[66]

    Effect of heat and processing

    Cooking by frying reduces CoQ10 content by 14-32%.[67]

    See also

    References

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    External links

    Primary
    Other
    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

    M: NUT

    cof, enz

    drug(A8/11/12)

    bg:Коензим Q

    ca:Coenzim Q10 cs:Koenzym Q10 de:Ubichinon-10 es:Coenzima Q fo:Q10 fr:Coenzyme Q10 it:Coenzima Q he:קו-אנזים Q10 nl:Co-enzym Q10 ja:ユビキノン oc:Coenzim Q10 pl:Ubichinon pt:Ubiquinona ro:Coenzima Q10 ru:Кофермент Q sl:Ubikinon fi:Ubikinoni uk:Убіхінон

    zh:泛醌
    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. doi:10.1016/0006-3002(57)90457-2. PMID 13445756. 
    7. ↑ 7.0 7.1 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. ↑ 9.0 9.1 9.2 9.3 9.4 Zmitek et al. (2008) Agro Food Ind. Hi Tec. 19, 4, 9. - Improving the bioavailability of CoQ10
    10. ↑ 10.0 10.1 H. N. Bhagavan and R. K. Chopra, Mitochondrion, 7: S78-S88 (2007).
    11. ↑ 11.0 11.1 H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006).
    12. ↑ 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.
    13. ↑ 13.0 13.1 13.2 Y. Ozawa, Y. Mizushima, I. Koyama, M. Akimoto, Y. Yamagata, H. Hayashi and H. Murayama, Drug Res., 36-1: 689-690 (1986).
    14. ↑ 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. doi:10.1007/BF02535072. PMID 2779364.  More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help) edit
    15. ↑ Söderberg, M.; Edlund, C.; Kristensson, K.; Dallner, G. (1990). "Lipid Compositions of Different Regions of the Human Brain During Aging". Journal of Neurochemistry. 54: 415–419. doi:10.1111/j.1471-4159.1990.tb01889.x.  edit
    16. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. edit
    17. ↑ 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. 
    18. ↑ The Synthesis of Cholesterol
    19. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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    21. ↑ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs. 16 (4): 9–20. PMID 12597259. 
    22. ↑ 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. 
    23. ↑ H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006)
    24. ↑ Y. Tomono, J. Hasegawa, T. Seki, K. Motegi and N. Morishita, Int. J. Clin. Pharmacol. Ther., 24: 536-541 (1986).
    25. ↑ 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).
    26. ↑ C. H. Hsu, Z. Cui, R. J. Mumper and M. Jay, AAPS PharmSciTech., 4: E32 (2003).
    27. ↑ S. S. Joshi, S. V. Sawant, A. Shedge and A. D. Halpner, Int. J. Clin. Pharmacol. Ther., 41: 42-48 (2003).
    28. ↑ T. R. Kommuru, M. Ashraf, M. A. Khan and I. K. Reddy, Chemical & Pharmaceutical Bulletin, 47: 1024-1028 (1999).
    29. ↑ K. Westesen and B. Siekmann. Particles with modified physicochemical properties, their preparation and uses. US6197349. 2001.
    30. ↑ H. Ohashi, T. Takami, N. Koyama, Y. Kogure and K. Ida. Aqueous solution containing ubidecarenone. US4483873. 1984
    31. ↑ Zmitek, J. et all (2008) Relative bioavailability of two forms of a novel water soluble CoQ10 Ann. Nutri. Metab. 52:281-287 (2008)
    32. ↑ D. Madhavi, and D. Kagan. (2010) "A Study of the Bioavailability of a Sustained-release CoEnzyme Q10-β-cyclodextrin Complex" 9(1):20-25.
    33. ↑ Hosoe K, et al. Study On Safety And bioavailability of ubiquinol (Kaneka QH™) after single and 4-week multiple oral administration to healthy volunteers. Regulatory Toxicology and Pharmacology. 2007, 47: 19-28
    34. ↑ Cleren, C, et al. Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. Journal of Neurochemistry. 2008, 104: 1613-1621
    35. ↑ 35.0 35.1 Mayo Clinic Drugs and Supplements: Coenzyme Q10 (accessed 13 November 2008)
    36. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. [2]
    37. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
    38. ↑ Peter H. Langsjoen, University of Washington, INTRODUCTION TO COENZYME Q10 (accessed 13 November 2008)
    39. ↑ ROBERT ALAN BONAKDAR and ERMINIA GUARNERI, American Family Physician page on CoEnzyme Q10 (Sept 2005, accessed 13 November 2008)
    40. ↑ 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. 
    41. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
    42. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
    43. ↑ http://www.cancer.gov/cancertopics/pdq/cam/coenzymeQ10/Patient/page2 Coenzyme Q10. NCI
    44. ↑ http://clinicaltrials.gov/ct2/show/NCT00976131 Study of CoQ10 During One Cycle of Doxorubicin Treatment for Breast Cancer
    45. ↑ http://clinicaltrials.gov/ct2/show/NCT00096356 Coenzyme Q10 in Relieving Treatment-Related Fatigue in Women With Breast Cancer
    46. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
    47. ↑ 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)
    48. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
    49. ↑ 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. PMC 389415 Freely accessible. PMID 5289867. 
    50. ↑ 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. PMC 388248 Freely accessible. PMID 4151519. 
    51. ↑ McRee JT, Hanioka T, Shizukuishi S, Folkers K (1993). "Therapy with coenzyme Q10 for patients with periodontal disease". J Dent Health. 43: 659–666. 
    52. ↑ 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. 
    53. ↑ 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. 
    54. ↑ 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. 
    55. ↑ 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. 
    56. ↑ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension". Advances in Anti-Aging Medicine. 1 (1): 205–215. 
    57. ↑ 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. 
    58. ↑ 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. 
    59. ↑ 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. PMC 2834650 Freely accessible. PMID 16443163. 
    60. ↑ 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. PMC 2744613 Freely accessible. PMID 19710165. 
    61. ↑ 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. 
    62. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.. 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)."
    63. ↑ "Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease". 2002. 
    64. ↑ 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.  Check date values in: |date= (help)
    65. ↑ http://clinicaltrials.gov/ct2/show/NCT00740714 Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (QE3)
    66. ↑ 66.0 66.1 66.2 66.3 66.4 Pravst et al. (2010) Coenzyme Q10 Contents in Foods and Fortification Strategies Critical Reviews in Food Science and Nutrition, 50 (4) 269-280
    67. ↑ The coenzyme Q10 content of the average Danish die...[Int J Vitam Nutr Res. 1997] - PubMed Result
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