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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).
checkY verify (what is checkY☒N ?)

Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 /ˌkoʊ ˌkjuː ˈtɛn/, CoQ, or Q10 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 CoQ10: 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 the electron transport chain and as an antioxidant respectively.

Discovery and history

CoQ10 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 1961 Peter Mitchell 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 redox functions of CoQ in cellular energy production and antioxidant protection are based on the ability to exchange two electrons in a redox cycle between ubiquinol (reduced CoQ) and ubiquinone (oxidized CoQ).[8][9] 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

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 is fat-soluble and is therefore mobile in cellular membranes; it 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 oxygen, which is 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 (Note: recent research now establishes that Vitamin K2 co-performs this role with CoQ10[10]). 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 continuously goes through 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.[11] 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.[11] 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, which may provide benefit 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 "statin" family of cholesterol-reducing medications block HMG Co-A reductase, so taking CoQ10 may alleviate a statin side-effect of rhabdomyolysis. 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.[12] 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.[13] 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.[14]

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 into the small intestines of pancreatic enzymes and bile that facilitate emulsification and micelle formation that is required for the absorption of lipophilic substances.[15] 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.[16][17]

Metabolism

Data on the metabolism of CoQ10 in animals and humans are limited.[18] 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.[19] 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.[20]

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 be affected by other genetic defects (such as mutations of mitochondrial RNA, ETFDH, APTX and BRAF, genes that are not directly related to the CoQ10 biosynthetic process) while the role of statins is controversial.[21] 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 are 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.[22] 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.[23]

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 blood mononuclear cells.[21] Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of 14C-labelled p-hydroxybenzoate.[24]

Inhibition by statins and beta blockers

CoQ10 shares a biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of CoQ10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[25] and statins, a class of cholesterol-lowering drugs.[26] Statins can reduce serum levels of CoQ10 by up to 40%.[27] Some research suggests the logical option of supplementation with CoQ10 as a routine adjunct to any treatment that may reduce endogenous production of CoQ10, based on a balance of likely benefit against very small risk.[28][29] However, there are still no conclusive data that support the role of CoQ10 deficiency in the pathogenesis of statin-related myopathy. [citation needed]

Pharmacokinetics

Some reports have been published on the pharmacokinetics of CoQ10. The plasma peak can be observed 2–6 hours after oral administration, depending mainly 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.[15] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.[30]

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; different formulations and forms have been developed and tested on animals or humans.[18]

Reduction of particle size

An 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;[31] 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.[32][33] The use of the aqueous suspension of finely powdered CoQ10 in pure water has also revealed only a minor effect.[20]

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.[20] 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,[34] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.[35]

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 CoQ10. 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.[18] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,[36] formulations based on various solubilising agents, i.e., hydrogenated lecithin,[37] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.[38][39] and is also used in pharmaceutical and food industry for CoQ10-fortification.[18] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers, etc. can be used to increase the bioavailability of CoQ10.[citation needed]

Supplementation benefits

CoQ10 has been proposed as a treatment for numerous health conditions and there is good scientific evidence to support its use for the treatment of conditions such as heart failure and high blood pressure. Recommended adult doses of CoQ10 generally range between 22-400 milligrams daily although considerably higher dosages have been utilized for the treatment of particular diseases.[40] It is not approved by the FDA for the treatment of any condition, although it has been approved for further investigation (in its reduced form as solubilized ubiquinol) as an orphan product in the treatment of Huntington's disease[41] and pediatric congestive heart failure.[42]

Heart disease

CoQ10 levels have been found to be lower in the heart muscle of patients with chronic heart failure (CHF) and low blood plasma levels of CoQ10 are associated with increased mortality in heart failure. Low plasma total cholesterol (TC) concentrations have also been associated with higher mortality in heart failure and plasma CoQ10 is closely associated with low-density lipoprotein cholesterol (LDL-C). This association was investigated in one study of 236 patients with CHF which found that low levels of CoQ10 were an independent predictor of increased mortality.[43]

CoQ10 is available as medicine and food supplement in several European countries.[citation needed]

Studies in the 1990s concluded that dietary supplements with CoQ10 reduces oxidation of low-density lipoprotein cholesterol and this antioxidant effect has important implications for the treatment of heart disease.[44][45]

The Q-SYMBIO trial is a randomized, double-blind, placebo-controlled trial to determine the benefits of CoQ10, with an endpoint including survival, involving 422 patients with chronic heart failure.[46] Results have not yet been published, but investigators reported at the Heart Failure 2013 congress that after 2 years, among patients in the CoQ10 group the risk of a major adverse cardiovascular event (MACE) was reduced by one half; moreover CoQ10 also halved the risk of dying from all causes and there were fewer adverse events in the CoQ10 group than placebo group.[47][48]

Some cardiologists opined that the Q-SYMBIO study was well-done, but was relatively small and required confirmation. It was noted that previous recommendations on CoQ10 were that it appears to be safe, doesn't seem to have any side effects, but is probably not of huge benefit and is not inexpensive. Nonetheless, the Q-SYMBIO study was characterized as an "intriguing trial" that showed a decrease in heart failure related events warranting further research. [49]

Migraine headaches

Supplementation of CoQ10 has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. A double-blind, randomized, placebo-controlled trial found statistically significant results with a small sample size of 42 patients.[50] Dosages were 150 to 300 mg/day.

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

Cancer

CoQ10 is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[51][52][53][54]

Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if CoQ10 is administered in addition to commencing active cooling of the body to 90–93 degrees Fahrenheit (32–34 degrees Celsius).[55]

Blood pressure

There are several reports confirming the benefit of CoQ10 for treating high blood pressure in human subjects.[56]

A recent (2007) meta-analysis of the clinical trials of CoQ10 for hypertension reviewed all published trials of CoQ10 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 CoQ10 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.[57]

Periodontal disease

A review study has shown that there is no clinical benefit to the use of CoQ10 in the treatment of periodontal disease.[58] Most of the studies suggesting otherwise were outdated, focused on in-vitro tests,[59][60][61] had too few test subjects and/or erroneous statistical methodology and trial set-up,[62][63] or were sponsored by a manufacturer of the product.[64]

Dr. Bruno Loos, head of the periodontology department at Academisch Centrum Tandheelkunde Amsterdam (ACTA), states[citation needed] that the Pharma Nord website links to scientific articles that profess to prove the effectiveness of CoQ10 for periodontal disease, but all are of very poor quality.[citation needed][65] The Dutch Academy of Periodontics (NvvP) has issued numerous warnings against claims of any link between CoQ10 and periodontal disease.[66][67]

Lifespan

One study demonstrated that low dosages of CoQ10 reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and CoQ10 supplementation leads to a longer lifespan in rats.[68] Coles and Harris demonstrated an extension in the lifespan of rats when they were given CoQ10 supplementation.[69] But multiple studies have since found no increase in lifespan or decrease in aging in mice and rats supplemented with CoQ10.[70][71][72][73] Another study demonstrated that CoQ10 extends the lifespan of C. elegans (nematode).[74]

Anti-aging

A 2013 study that characterizes an aspect of aging due to a nucleic communication breakdown with mitochondria inherently postulates a novel approach for CoQ10 as an anti-aging factor, being that it facilitates mitochondria in energy production, thereby reversing the aging effect resulting from nutrient-deprived mitochondria, likened to the findings of non-functioning mitochondria as described in the study.[75]

Radiation injury

In 2002, a study reported that, in rat experiments, CoQ10 taken as dietary supplement reduced radiation damage to the animals' blood.[76]

Parkinson's disease

A phase III trial of 1200 mg/d and 2400 mg/d for Parkinson's disease was discontinued early for lack of effectiveness in August 2011, and concluded, "The investigational drug is unlikely to demonstrate efficacy over placebo for this indication. However, no safety issues were discovered."[77]

Cosmetics

CoQ10 may be of benefit as an ingredient for topical cosmetic products.[78]

CoQ10 concentrations in foods and dietary intake

Detailed reviews on occurrence of CoQ10 and dietary intake were published in 2010.[79] 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.[79] Developments in analytical chemistry have since enabled a more reliable determination of CoQ10 concentrations in various foods (Table below).

CoQ10 levels in selected foods[79]
Food CoQ10 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, 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.[79]

Intake

In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.[79]

Effect of heat and processing

Cooking by frying reduces CoQ10 content by 14–32%.[80]

See also

  • Idebenone – synthetic analog with reduced oxidant generating properties
  • MitoQ

References

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  44. ^ Mohr D, Bowry VW, Stocker R (June 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}}: CS1 maint: multiple names: authors list (link)[verification needed]
  45. ^ Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K (September 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}}: CS1 maint: multiple names: authors list (link)[verification needed]
  46. ^ Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIOmarker status (Brain-Natriuretic Peptide [BNP]), and long-term outcome (hospitalisations/mortality), Current Controlled Trials, ISRCTN94506234
  47. ^ First Drug to Significantly Improve Heart Failure Mortality in Over a Decade ScienceDaily, 25 May 2013. Web. 26 May 2013.
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  49. ^ Common Supplement May Help Patients Fight Heart Failure, Dennis Thompson, HealthDay, Reporter, 24 May 2013
  50. ^ 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.
  51. ^ 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.
  52. ^ Coenzyme Q10. NCI
  53. ^ Clinical trial number NCT00976131 for "Study of CoQ10 During One Cycle of Doxorubicin Treatment for Breast Cancer" at ClinicalTrials.gov
  54. ^ Clinical trial number NCT00096356 for "Coenzyme Q10 in Relieving Treatment-Related Fatigue in Women With Breast Cancer" at ClinicalTrials.gov
  55. ^ 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.
  56. ^ 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)
  57. ^ 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.
  58. ^ T.L.P. Watts, BDS, MDS, PhD, FDS, Department of Periodontology and Preventive Dentistry, UMDS, Guy's Hospital London (1995). "Coënzyme Q10 and periodontal treatment: is there any beneficial effect?". British Dental Journal. 178 (6): 209–213. doi:10.1038/sj.bdj.4808715. PMID 7718355.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  59. ^ Folkers, K; Hanioka, T; Xia, L; McRee Jr, 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.
  60. ^ Littarru GP, Nakamura R, Ho L, Folkers K, Kuzell WC (October 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}}: CS1 maint: multiple names: authors list (link)
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  62. ^ 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)
  63. ^ 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)
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  65. ^ Dr. Bruno Loos in several of his dissertations on the subject in the Dutch Dental Journal (Nederlands Tandartsenblad)- already quoted
  66. ^ Kees Karsten, Dennis Verhoeve, Bruno Loos en Sacha Eikenboom. (1997). "Fabrikant misleidt parodontitis patiënten met Q10. Wetenschappelijke onderbouwing van vermeend effect ontbreekt". Nederlands Tandartsenblad (7): 52.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  67. ^ Kees Karsten, Dennis Verhoeve, Bruno Loos en Sacha Eikenboom. Fabrikant Bio-Quinon Q10 veroordeeld. KAG, consumentenbond en NVvP tevreden over uitspraak rechter. Nederlands Tandartsenblad 52/21/1997
  68. ^ 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.
  69. ^ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension". Advances in Anti-Aging Medicine. 1 (1): 205–15.
  70. ^ 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.
  71. ^ 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.
  72. ^ 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.
  73. ^ 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.
  74. ^ 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.
  75. ^ Gomes, Ana P.; Price, Nathan L.; Ling, Alvin J. Y.; Moslehi, Javid J.; Montgomery, Magdalene K.; Rajman, Luis; White, James P.; Teodoro, João S.; Wrann, Christiane D.; Hubbard, Basil P.; Mercken, Evi M.; Palmeira, Carlos M.; de Cabo, Rafael; Rolo, Anabela P.; Turner, Nigel; Bell, Eric L.; Sinclair, David A. (2013). "Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging". Cell. 155 (7): 1624–1638. doi:10.1016/j.cell.2013.11.037. PMID 24360282.
  76. ^ 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.
  77. ^ Clinical trial number NCT00740714 for "Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (QE3)" at ClinicalTrials.gov
  78. ^ "Coenzyme Q10--its importance, properties and use in nutrition and cosmetics".
  79. ^ 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.
  80. ^ 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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