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Coenzyme Q10

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Coenzyme Q10
Names
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
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.590 Edit this at Wikidata
UNII
  • InChI=1S/C59H90O4/c1-44(2)24-15-25-45(3)26-16-27-46(4)28-17-29-47(5)30-18-31-48(6)32-19-33-49(7)34-20-35-50(8)36-21-37-51(9)38-22-39-52(10)40-23-41-53(11)42-43-55-54(12)56(60)58(62-13)59(63-14)57(55)61/h24,26,28,30,32,34,36,38,40,42H,15-23,25,27,29,31,33,35,37,39,41,43H2,1-14H3/b45-26+,46-28+,47-30+,48-32+,49-34+,50-36+,51-38+,52-40+,53-42+ checkY
    Key: ACTIUHUUMQJHFO-UPTCCGCDSA-N checkY
  • InChI=1/C59H90O4/c1-44(2)24-15-25-45(3)26-16-27-46(4)28-17-29-47(5)30-18-31-48(6)32-19-33-49(7)34-20-35-50(8)36-21-37-51(9)38-22-39-52(10)40-23-41-53(11)42-43-55-54(12)56(60)58(62-13)59(63-14)57(55)61/h24,26,28,30,32,34,36,38,40,42H,15-23,25,27,29,31,33,35,37,39,41,43H2,1-14H3/b45-26+,46-28+,47-30+,48-32+,49-34+,50-36+,51-38+,52-40+,53-42+
    Key: ACTIUHUUMQJHFO-UPTCCGCDBK
  • O=C1/C(=C(\C(=O)C(\OC)=C1\OC)C)C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)C
Properties
C59H90O4
Molar mass 863.365 g·mol−1
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 /ˌkoʊ ˌkjuː ˈtɛn/, 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). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in electron transport chain and as an antioxidant respectively.

Discovery and history

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] In 1961 Peter Mitchel proposed the electron transport chain (which includes the vital protonmotive role of CoQ10) and he received a Nobel prize for the same in 1978. In 1972, Gian Paolo Littarru and Karl Folkers separately demonstrated a deficiency of CoQ10 in human heart disease. The 1980s witnessed a steep rise in the number of clinical trials due to the availability of large quantities of pure CoQ10 and methods to measure plasma and blood CoQ10 concentrations. The antioxidant role of the molecule as a free radical scavenger was widely studied by Lars Ernster. Numerous scientists around the globe started studies on this molecule since then in relation to various diseases including cardiovascular diseases and cancer.

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 subunits in their side-chains. The most common Coenzyme Q in human mitochondria is CoQ10. Q refers to the quinone head and 10 refers to the number of isoprene repeats in the tail. The image below has three isoprenoid units and would be called Q3.

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.

CoQ10 and electron transport chain

CoQ10, fat-soluble and therefore mobile in cellular membranes, plays a unique role in the electron transport chain (ETC). In the inner mitochondrial membrane electrons from NADH and succinate pass through the ETC to the oxygen, which is then reduced to water. The transfer of electrons through ETC results in the pumping of H+ across the membrane creating a proton gradient across the membrane, which is used by ATP synthase (located on the membrane) to generate ATP. CoQ10 functions as an electron carrier from enzyme complex I and enzyme complex II to complex III in this process. This is crucial in the process, since no other molecule can perform this function. Thus, CoQ10 functions in every cell of the body to synthesize energy.

Antioxidant function of CoQ10

The antioxidant nature of CoQ10 derives from its energy carrier function. As an energy carrier, the CoQ10 molecule is continually going through an oxidation-reduction cycle. As it accepts electrons, it becomes reduced. As it gives up electrons, it becomes oxidized. In its reduced form, the CoQ10 molecule holds electrons rather loosely, so this CoQ molecule will quite easily give up one or both electrons and, thus, act as an antioxidant.[9] CoQ10 inhibits lipid peroxidation by preventing the production of lipid peroxyl radicals (LOO). Moreover, CoQH2 reduces the initial perferryl radical and singlet oxygen, with concomitant formation of ubisemiquinone and H2O2. This quenching of the initiating perferryl radicals, which prevent propagation of lipid peroxidation, protects not only lipids, but also proteins from oxidation. In addition, the reduced form of CoQ effectively regenerates vitamin E from the a-tocopheroxyl radical, thereby interfering with the propagation step. Furthermore, during oxidative stress, interaction of H2O2 with metal ions bound to DNA generates hydroxyl radicals and CoQ efficiently prevents the oxidation of bases, in particular, in mitochondrial DNA.[9] In contrast to other antioxidants, this compound inhibits both the initiation and the propagation of lipid and protein oxidation. It also regenerates other antioxidants such as vitamin E. The circulating CoQ10 in LDL prevents oxidation of LDL, therefore, by providing its benefits in cardiovascular diseases.

Biosynthesis

Starting from acetyl-CoA, a multistep process of mevalonate pathway produces farnesyl-PP (FPP), the precursor for cholesterol, CoQ, dolichol, and isoprenylated proteins. An important enzyme in this pathway is HMG Co-A reductase, which is usually a target for intervention in cardiovascular complications. The long isoprenoid side-chain of CoQ is synthesized by trans-prenyltransferase, which condenses FPP with several molecules of isopentenyl-PP (IPP), all in the trans configuration.[10] The next step involves condensation of this polyisoprenoid side-chain with 4-hydroxybenzoate, catalyzed by polyprenyl-4-hydroxy benzoate transferase. Hydroxybenzoate is synthesized from tyrosine or phenylalanine. In addition to their presence in mitochondria, these initial two reactions also occur in the endoplasmic reticulum and peroxisomes, indicating multiple sites of synthesis in animal cells.[11] Increasing the endogenous biosynthesis of CoQ10 has attained attention in the recent years as a strategy to fight CoQ10 deficiency.

Genes involved include PDSS1, PDSS2, COQ2, and COQ8/CABC1.[12]

Absorption and metabolism

Absorption

CoQ10 is a crystalline powder that is insoluble in water. 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.This process in the human body involves the secretion of pancreatic enzymes and bile into the small intestines that facilitate emulsification and micelle formation that is required for the absorption of lipophilic substances.[13] Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances the absorption of CoQ10. Exogenous CoQ10 is absorbed from the small intestinal tract and is best absorbed if it is taken with a meal. Serum concentration of CoQ10 in fed condition is higher than in fasting conditions.[14][15]

Metabolism

Data on the metabolism of CoQ10 in animals and humans are limited.[16] 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.[17] 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 normal within a few days, irrespective of the type of formulation used.[18]

CoQ10 deficiency and toxicity

There are two major factors that lead to deficiency of CoQ10 in humans: reduced biosynthesis, and increased utilization by the body. Biosynthesis is the major source of CoQ10. Biosynthesis requires at least 12 genes, and mutations in many of them cause CoQ deficiency. CoQ10 levels can also can be affected by other genetic defects (such as mutations of mitochondrial DNA, ETFDH, APTX and BRAF, genes which are not directly related to the CoQ10 biosynthetic process) while the role of statins is controversial.[19] Some chronic disease conditions (cancer, heart disease, etc.) are also thought to reduce the biosynthesis and increase the demand for CoQ10 in the body, but there is no definite data to support these claims. Toxicity is not usually observed with high doses of CoQ10. A daily dosage up to 3600 mg was found to be tolerated by healthy as well as unhealthy persons.[20] However, some adverse effects, largely gastrointestinal, are reported with very high intakes. The observed safe level (OSL) risk assessment method indicated that the evidence of safety is strong at intakes up to 1200 mg/day, and this level is identified as the OSL.[21]

Clinical assessment techniques

Although CoQ10 can be measured in plasma, these measurements reflect dietary intake rather than tissue status. Currently most clinical centers measure CoQ10 levels in cultured skin fibroblasts, muscle biopsies, and in blood mononuclear cells.[19] Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of 14C-labelled p-hydroxybenzoate.[22]

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,[23] and statins, a class of cholesterol-lowering drugs.[24] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[25] 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.[26][27]. However, there are still no conclusive data that support the role of CoQ10 deficiency in the pathogenesis of statin-related myopathy.

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.[13] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.[28]

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.[16]

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;[29] 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.[30][31] The use of the aqueous suspension of finely powdered CoQ10 in pure water has also revealed only a minor effect.[18]

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.[18] 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,[32] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.[33]

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.[16] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,[34] formulations based on various solubilising agents, i.e., hydrogenated lecithin,[35] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.[36][37] and is also used in pharmaceutical and food industry for CoQ10-fortification.[16] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc. can be used to increase the bioavailability of Coenzyme Q10.[citation needed]

Supplementation benefits

Coenzyme Q10 is the 3rd most sold dietary ingredient in the United States after Omega-3 and multivitamins.[citation needed]

According to the Mayo Clinic, "CoQ10 has been used, recommended, or studied for numerous conditions, but remains controversial as a treatment in many areas."[38] Coenzyme Q-10 is approved for use as an orphan product in the treatment of Huntington's disease and mitochondrial cytopathies;[citation needed] other uses are still unproven, including in the treatment of congestive heart failure and athletic performance.[citation needed]

Heart health

Coenzyme Q10 helps to maintain a healthy cardiovascular system. There is evidence of CoQ10 deficiency in heart failure. Recently, CoQ10 plasma concentrations have been demonstrated as an independent predictor of mortality in chronic heart failure, CoQ10 deficiency being detrimental to the long-term prognosis of chronic heart failure.[39][citation needed] CoQ10 is available as medicine in several European countries, but is in these countries also available as a food supplement. Oxidation of the circulating LDL is thought to play a key role in the pathogenesis of atherosclerosis, which is the underlying disorder leading to heart attack and ischemic strokes[40][41][42] and CHD. Studies in the last decade have demonstrated that the content of Ubiquinol in human LDL affords protection against the oxidative modifications of LDL themselves, thus lowering their atherogenic potency.[43][44]

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,[45] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[46] Dosages were 150 to 300 mg/day.

It has been used effecitvely in the prophylaxis of migraines, especially in combination with a daily supplement of magnesium citrate 500 mg and riboflavin (vitamin B2) 400 mg.[47]

Cancer

CoQ10 is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[48][49][50][51]

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).[52]

Blood pressure

There are several reports concerning the effect of CoQ10 on blood pressure in human studies.[53]

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.[54]

Periodontal disease

Studies have shown that diseased gum tissue is deficient in CoQ10 compared to healthy gum tissue.[55][56] Human clinical trials have suggested a link between oral administration of CoQ10 and improved gingival health,[57] immune response in gum tissues,[58] and a reversal of the diseased gum conditions.[59] In addition to oral supplementation, topical application of CoQ10 on gum tissues has been shown to improve periodontitis and gingivitis conditions.[60]

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.[61] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q10 supplementation.[62] But multiple studies have since found no increase in lifespan or decrease in aging in mice and rats supplemented with coenzyme Q10.[63][64][65][66] Another study demonstrated that coenzyme Q10 extends the lifespan of C. elegans (nematode).[67]

Radiation injury

A 2002 study reported that, in rat experiments, coenzyme Q10 taken as dietary supplement reduced radiation damage to the animals' blood.[68]

Parkinson's disease

A 2002 study in 80 Parkinson's disease patients found 1200 mg/day reduced the progression by 44%.[69][70] and a phase III trial of 1200 mg/d and 2400 mg/d should run until 2011.[71]

Coenzyme Q10 concentrations in foods and dietary intake

Detailed reviews on occurrence of CoQ10 and dietary intake were published recently.[72] 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.[72] Developments in analytical chemistry have since enabled a more reliable determination of CoQ10 concentrations in various foods (Table below).

CoQ10 levels in selected foods[72]
Food Coenzyme Q10 concentration [mg/kg]
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.[72]

Intake

In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.[72]

Effect of heat and processing

Cooking by frying reduces CoQ10 content by 14–32%.[73]

See also

References

  1. ^ Ernster, L; Dallner, G (1995). "Biochemical, physiological and medical aspects of ubiquinone function". Biochimica et Biophysica Acta. 1271 (1): 195–204. PMID 7599208.
  2. ^ Dutton, PL; Ohnishi, T; Darrouzet, E; Leonard, MA; Sharp, RE; Cibney, BR; Daldal, F; Moser, CC (2000). "4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport". In Kagan, VE; Quinn, PJ (eds.). Coenzyme Q: Molecular mechanisms in health and disease. Boca Raton: CRC Press. pp. 65–82.
  3. ^ Okamoto, T; Matsuya, T; Fukunaga, Y; Kishi, T; Yamagami, T (1989). "Human serum ubiquinol-10 levels and relationship to serum lipids". International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 59 (3): 288–92. PMID 2599795.
  4. ^ Aberg, F; Appelkvist, EL; Dallner, G; Ernster, L (1992). "Distribution and redox state of ubiquinones in rat and human tissues". Archives of biochemistry and biophysics. 295 (2): 230–4. doi:10.1016/0003-9861(92)90511-T. PMID 1586151.
  5. ^ Shindo, Y; Witt, E; Han, D; Epstein, W; Packer, L (1994). "Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin". The Journal of investigative dermatology. 102 (1): 122–4. doi:10.1111/1523-1747.ep12371744. PMID 8288904.
  6. ^ Crane, F; Hatefi, Y; Lester, R; Widmer, C (1957). "Isolation of a quinone from beef heart mitochondria". Biochimica et Biophysica Acta. 25 (1): 220–1. doi:10.1016/0006-3002(57)90457-2. PMID 13445756.
  7. ^ a b Peter H. Langsjoen, "Introduction of Coezyme Q10"[self-published source?]
  8. ^ Wolf, Donald E.; Hoffman, Carl H.; Trenner, Nelson R.; Arison, Byron H.; Shunk, Clifford H.; Linn, Bruce O.; McPherson, James F.; Folkers, Karl (1958). Journal of the American Chemical Society. 80 (17): 4752. doi:10.1021/ja01550a096. {{cite journal}}: Missing or empty |title= (help)
  9. ^ a b http://www.mbschachter.com/coenzyme_q10.htm
  10. ^ Tran UC, Clarke CF (2007). "Endogenous Synthesis of Coenzyme Q in Eukaryotes". Mitochondrion. 7 (Suppl): S62–71. doi:10.1016/j.mito.2007.03.007. PMC 1974887. PMID 17482885. {{cite journal}}: Unknown parameter |month= ignored (help)
  11. ^ Bentinger M, Tekle M, Dallner G (2010). "Coenzyme Q—biosynthesis and functions". Biochem. Biophys. Res. Commun. 396 (1): 74–9. doi:10.1016/j.bbrc.2010.02.147. PMID 20494114. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Carmen Espinós; Vicente Felipo; Francesc Palau (1 August 2009). Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies. Springer. pp. 122–. ISBN 9789048128129. Retrieved 4 January 2011.
  13. ^ a b Bhagavan, Hemmi N.; Chopra, Raj K. (2006). "Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics". Free Radical Research. 40 (5): 445–53. doi:10.1080/10715760600617843. PMID 16551570.
  14. ^ Bogentoft 1991[verification needed]
  15. ^ Ochiai A, Itagaki S, Kurokawa T, Kobayashi M, Hirano T, Iseki K (2007). "Improvement in intestinal coenzyme q10 absorption by food intake". Yakugaku Zasshi. 127 (8): 1251–4. doi:10.1248/yakushi.127.1251. PMID 17666877. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)[verification needed]
  16. ^ a b c d Zmitek et al. (2008) Agro Food Ind. Hi Tec. 19, 4, 9. – Improving the bioavailability of CoQ10
  17. ^ Kishi, H.; Kanamori, N.; Nisii, S.; Hiraoka, E.; Okamoto, T.; Kishi, T. (1964). "Metabolism and Exogenous Coenzyme Q10 in vivo and Bioavailability of Coenzyme Q10 Preparations in Japan". Biomedical and Clinical Aspects of Coenzyme Q. Amsterdam: Elsevier. pp. 131–42.
  18. ^ a b c Ozawa, Y; Mizushima, Y; Koyama, I; Akimoto, M; Yamagata, Y; Hayashi, H; Murayama, H (1986). "Intestinal absorption enhancement of coenzyme Q10 with a lipid microsphere". Arzneimittel-Forschung. 36 (4): 689–90. PMID 3718593.
  19. ^ a b Trevisson E, Dimauro S, Navas P, Salviati L (2011). "Coenzyme Q deficiency in muscle". Curr. Opin. Neurol. 24 (5): 449–56. doi:10.1097/WCO.0b013e32834ab528. PMID 21844807. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Hyson HC, Kieburtz K, Shoulson I; et al. (2010). "Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects". Mov. Disord. 25 (12): 1924–8. doi:10.1002/mds.22408. PMID 20669312. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Hathcock JN, Shao A (2006). "Risk assessment for coenzyme Q10 (Ubiquinone)". Regul. Toxicol. Pharmacol. 45 (3): 282–8. doi:10.1016/j.yrtph.2006.05.006. PMID 16814438. {{cite journal}}: Unknown parameter |month= ignored (help)
  22. ^ Montero R, Sánchez-Alcázar JA, Briones P; et al. (2008). "Analysis of coenzyme Q10 in muscle and fibroblasts for the diagnosis of CoQ10 deficiency syndromes". Clin. Biochem. 41 (9): 697–700. doi:10.1016/j.clinbiochem.2008.03.007. PMID 18387363. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ 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". Research communications in chemical pathology and pharmacology. 17 (1): 157–64. PMID 17892.
  24. ^ Mortensen, SA; Leth, A; Agner, E; Rohde, M (1997). "Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors". Molecular aspects of medicine. 18 (Suppl): S137–44. PMID 9266515.
  25. ^ Ghirlanda, G; Oradei, A; Manto, A; Lippa, S; Uccioli, L; Caputo, S; Greco, AV; Littarru, GP (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". Journal of clinical pharmacology. 33 (3): 226–9. PMID 8463436.
  26. ^ Sarter, B (2002). "Coenzyme Q10 and cardiovascular disease: a review". The Journal of cardiovascular nursing. 16 (4): 9–20. PMID 12597259.
  27. ^ Thibault, A; Samid, D; Tompkins, AC; Figg, WD; Cooper, MR; Hohl, RJ; Trepel, J; Liang, B; Patronas, N (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clinical cancer research. 2 (3): 483–91. PMID 9816194.
  28. ^ Tomono, Y; Hasegawa, J; Seki, T; Motegi, K; Morishita, N (1986). "Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man". International journal of clinical pharmacology, therapy, and toxicology. 24 (10): 536–41. PMID 3781673.
  29. ^ Mathiowitz, Edith; Jacob, Jules S.; Jong, Yong S.; Carino, Gerardo P.; Chickering, Donald E.; Chaturvedi, Pravin; Santos, Camilla A.; Vijayaraghavan, Kavita; Montgomery, Sean (1997). "Biologically erodible microspheres as potential oral drug delivery systems". Nature. 386 (6623): 410–4. doi:10.1038/386410a0. PMID 9121559.
  30. ^ Hsu CH, Cui Z, Mumper RJ, Jay M (2003). "Preparation and characterization of novel coenzyme Q10 nanoparticles engineered from microemulsion precursors". AAPS PharmSciTech. 4 (3): E32. doi:10.1208/pt040332. PMC 2750625. PMID 14621964.{{cite journal}}: CS1 maint: multiple names: authors list (link)[verification needed]
  31. ^ Joshi SS, Sawant SV, Shedge A, Halpner AD (2003). "Comparative bioavailability of two novel coenzyme Q10 preparations in humans". Int J Clin Pharmacol Ther. 41 (1): 42–8. PMID 12564745. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)[verification needed]
  32. ^ Kommuru, TR; Ashraf, M; Khan, MA; Reddy, IK (1999). "Stability and bioequivalence studies of two marketed formulations of coenzyme Q10 in beagle dogs". Chemical & pharmaceutical bulletin. 47 (7): 1024–8. PMID 10434405.
  33. ^ Bhagavan HN, Chopra RK (2007). "Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations". Mitochondrion. 7 (Suppl): S78–88. doi:10.1016/j.mito.2007.03.003. PMID 17482886. {{cite journal}}: Unknown parameter |month= ignored (help)[verification needed]
  34. ^ K. Westesen and B. Siekmann. Particles with modified physicochemical properties, their preparation and uses. US6197349. 2001.
  35. ^ H. Ohashi, T. Takami, N. Koyama, Y. Kogure and K. Ida. Aqueous solution containing ubidecarenone. US4483873. 1984
  36. ^ Žmitek, Janko; Šmidovnik, Andrej; Fir, Maja; Prošek, Mirko; Žmitek, Katja; Walczak, Jaroslaw; Pravst, Igor (2008). "Relative Bioavailability of Two Forms of a Novel Water-Soluble Coenzyme Q10". Annals of Nutrition and Metabolism. 52 (4): 281–7. doi:10.1159/000129661. PMID 18645245.
  37. ^ Kagan, Daniel; Madhavi, Doddabele (2010). "A Study on the Bioavailability of a Novel Sustained-Release Coenzyme Q10-ß-Cyclodextrin Complex". Integrative Medicine. 9 (1).
  38. ^ Mayo Clinic Drugs and Supplements: Coenzyme Q10 . Retrieved 13 November 2008.
  39. ^ Molyneux SL, Florkowski CM, George PM; et al. (2008). "Coenzyme Q10: an independent predictor of mortality in chronic heart failure". J. Am. Coll. Cardiol. 52 (18): 1435–41. doi:10.1016/j.jacc.2008.07.044. PMID 19017509. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)[verification needed]
  40. ^ Witztum, JL (1994). "The oxidation hypothesis of atherosclerosis". Lancet. 344 (8925): 793–5. doi:10.1016/S0140-6736(94)92346-9. PMID 7916078.
  41. ^ Parthasarathy, S; Steinberg, D; Witztum, JL (1992). "The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis". Annual review of medicine. 43: 219–25. doi:10.1146/annurev.me.43.020192.001251. PMID 1580586.
  42. ^ Heller, FR; Descamps, O; Hondekijn, JC (1998). "LDL oxidation: therapeutic perspectives". Atherosclerosis. 137 Suppl: S25–31. PMID 9694538.
  43. ^ Mohr D, Bowry VW, Stocker R (1992). "Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation". Biochim. Biophys. Acta. 1126 (3): 247–54. doi:10.1016/0005-2760(92)90237-P. PMID 1637852. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)[verification needed]
  44. ^ Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K (1995). "The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions". Proc. Natl. Acad. Sci. U.S.A. 92 (20): 9388–91. doi:10.1073/pnas.92.20.9388. PMC 40990. PMID 7568138. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)[verification needed]
  45. ^ Rozen, TD; Oshinsky, ML; Gebeline, CA; Bradley, KC; Young, WB; Shechter, AL; Silberstein, SD (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.
  46. ^ Sándor, PS; Di Clemente, L; Coppola, G; Saenger, U; Fumal, A; Magis, D; Seidel, L; Agosti, RM; Schoenen, J (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial". Neurology. 64 (4): 713–5. doi:10.1212/01.WNL.0000151975.03598.ED. PMID 15728298.
  47. ^ Migraine Action UK
  48. ^ Sakano, K; Takahashi, M; Kitano, M; Sugimura, T; Wakabayashi, K (2006). "Suppression of azoxymethane-induced colonic premalignant lesion formation by coenzyme Q10 in rats". Asian Pacific journal of cancer prevention : APJCP. 7 (4): 599–603. PMID 17250435.
  49. ^ Coenzyme Q10. NCI
  50. ^ Clinical trial number NCT00976131 for "Study of CoQ10 During One Cycle of Doxorubicin Treatment for Breast Cancer" at ClinicalTrials.gov
  51. ^ Clinical trial number NCT00096356 for "Coenzyme Q10 in Relieving Treatment-Related Fatigue in Women With Breast Cancer" at ClinicalTrials.gov
  52. ^ Damian, M. S.; Ellenberg, D; Gildemeister, R; Lauermann, J; Simonis, G; Sauter, W; Georgi, C (2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest: A Preliminary Study". Circulation. 110 (19): 3011–6. doi:10.1161/01.CIR.0000146894.45533.C2. PMID 15520321.
  53. ^ Tracy, Melanie Johns (2003). "Ch. 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone)". Dietary supplements: toxicology and clinical pharmacology. Humana Press. pp. 53–85. ISBN 978-1-58829-014-4. {{cite book}}: |first2= missing |last2= (help); External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  54. ^ Rosenfeldt, F L; Haas, S J; Krum, H; Hadj, A; Ng, K; Leong, J-Y; Watts, G F (2007). "Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials". Journal of Human Hypertension. 21 (4): 297–306. doi:10.1038/sj.jhh.1002138. PMID 17287847.
  55. ^ 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): 2332–5. doi:10.1073/pnas.68.10.2332. PMC 389415. PMID 5289867. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ 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. PMID 4151519. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ McRee JT, Hanioka T, Shizukuishi S, Folkers K (1993). "Therapy with coenzyme Q10 for patients with periodontal disease". J Dent Health. 43 (5): 659–666. doi:10.5834/jdh.43.659.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  58. ^ Folkers, K; Hanioka, T; Xia, L; McReejr, J; Langsjoen, P (1991). "Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the aids related complex". Biochemical and Biophysical Research Communications. 176 (2): 786–91. doi:10.1016/S0006-291X(05)80254-2. PMID 1673841.
  59. ^ Wilkinson, EG; Arnold, RM; Folkers, K (1976). "Bioenergetics in clinical medicine. VI. adjunctive treatment of periodontal disease with coenzyme Q10". Research communications in chemical pathology and pharmacology. 14 (4): 715–9. PMID 785563.
  60. ^ 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): S241–8. doi:10.1016/0098-2997(94)90034-5. PMID 7752836.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  61. ^ Quiles, J; 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". Experimental Gerontology. 39 (2): 189–94. doi:10.1016/j.exger.2003.10.002. PMID 15036411.
  62. ^ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension". Advances in Anti-Aging Medicine. 1 (1): 205–15.
  63. ^ Lönnrot, 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". Biochemistry and molecular biology international. 44 (4): 727–37. PMID 9584986.
  64. ^ Lee, C; Pugh, TD; Klopp, RG; Edwards, J; Allison, DB; Weindruch, R; Prolla, TA (2004). "The impact of α-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice". Free Radical Biology and Medicine. 36 (8): 1043–57. doi:10.1016/j.freeradbiomed.2004.01.015. PMID 15059645.
  65. ^ Sohal, Rajindar S.; Kamzalov, Sergey; Sumien, Nathalie; Ferguson, Melissa; Rebrin, Igor; Heinrich, Kevin R.; Forster, Michael J. (2006). "Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice". Free Radical Biology and Medicine. 40 (3): 480–7. doi:10.1016/j.freeradbiomed.2005.08.037. PMC 2834650. PMID 16443163.
  66. ^ Sumien, N.; Heinrich, K. R.; Shetty, R. A.; Sohal, R. S.; Forster, M. J. (2009). "Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice". Journal of Nutrition. 139 (10): 1926–32. doi:10.3945/jn.109.110437. PMC 2744613. PMID 19710165.
  67. ^ 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". Mechanisms of Ageing and Development. 125 (1): 41–6. doi:10.1016/j.mad.2003.10.002. PMID 14706236.
  68. ^ Koryagin, A. S.; Krylova, E. V.; Luk'yanova, L. D. (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. PMID 12447465.
  69. ^ "Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease". 2002.
  70. ^ Shults, C. W.; Oakes, D; Kieburtz, K; Beal, MF; Haas, R; Plumb, S; Juncos, JL; Nutt, J; Shoulson, I (2002). "Effects of Coenzyme Q10 in Early Parkinson Disease: Evidence of Slowing of the Functional Decline". Archives of Neurology. 59 (10): 1541–50. doi:10.1001/archneur.59.10.1541. PMID 12374491.
  71. ^ Clinical trial number NCT00740714 for "Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (QE3)" at ClinicalTrials.gov
  72. ^ a b c d e Pravst, Igor; Zmitek, Katja; Zmitek, Janko (2010). "Coenzyme Q10 Contents in Foods and Fortification Strategies". Critical Reviews in Food Science and Nutrition. 50 (4): 269–80. doi:10.1080/10408390902773037. PMID 20301015.
  73. ^ Weber, C; Bysted, A; Hłlmer, G (1997). "The coenzyme Q10 content of the average Danish diet". Int J Vitam Nutr Res. 67 (2): 123–9. PMID 9129255.

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