Coenzyme Q10: Difference between revisions

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==Overview==
==Overview==
[[Image:Ubiquinone.png|left|thumb|250px|Ubiquinone]]
'''Coenzyme Q<sub>10</sub>''' (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ<sub>10</sub>, CoQ, Q10, or Q) is a [[benzoquinone]], where Q refers to the [[quinone]] chemical group, and 10 refers to the [[isoprene|isoprenyl]] chemical subunits.  
'''Coenzyme Q<sub>10</sub>''' (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ<sub>10</sub>, CoQ, Q10, or Q) is a [[benzoquinone]], where '''Q''' refers to the [[quinone]] chemical group, and '''10''' refers to the [[isoprene|isoprenyl]] chemical subunits.  


This [[vitamin]]-like substance is, by nature, present in most human cells except red blood cells and eye lens cells (no mitochondria) and are responsible for the production of the body’s own energy. In each human cell, food energy is converted into energy in the [[mitochondria]] with the aid of CoQ<sub>10</sub>. Ninety-five percent of all the human body’s energy requirements ([[adenosine triphosphate|ATP]]) is converted with the aid of CoQ<sub>10</sub>.<ref>Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim  Biophys Acta 1271: 195-204, 1995</ref><ref>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</ref> Therefore, those organs with the highest energy requirements – such as the heart and the liver – have the highest CoQ<sub>10</sub> concentrations.<ref>Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292</ref><ref>Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234</ref><ref>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.</ref>  
This [[vitamin]]-like substance is, by nature, present in most human cells except red blood cells and eye lens cells (no mitochondria) and are responsible for the production of the body’s own energy. In each human cell, food energy is converted into energy in the [[mitochondria]] with the aid of CoQ<sub>10</sub>. Ninety-five percent of all the human body’s energy requirements ([[adenosine triphosphate|ATP]]) is converted with the aid of CoQ<sub>10</sub>.<ref>Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim  Biophys Acta 1271: 195-204, 1995</ref><ref>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</ref> Therefore, those organs with the highest energy requirements – such as the heart and the liver – have the highest CoQ<sub>10</sub> concentrations.<ref>Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292</ref><ref>Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234</ref><ref>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.</ref>


==History==
CoQ<sub>10</sub> was first discovered by Crane et al. in 1957 within beef heart mitochondria.<ref name="CRANE-1957">{{Cite journal  | last1 = CRANE | first1 = FL. | last2 = HATEFI | first2 = Y. | last3 = LESTER | first3 = RL. | last4 = WIDMER | first4 = C. | title = Isolation of a quinone from beef heart mitochondria. | journal = Biochim Biophys Acta | volume = 25 | issue = 1 | pages = 220-1 | month = Jul | year = 1957 | doi =  | PMID = 13445756 }}</ref> This vitamin-like nutrient has since been implicated in three major biological processes, imparting its alternate name of “ubiquinone”. Floating within the inner membrane of mitochrodria, CoQ<sub>10</sub> plays an important role in oxidative phosphorylation where it is responsible for the two electron oxidation of NADH.<ref name="Lenaz-1988">{{Cite journal  | last1 = Lenaz | first1 = G. | title = Role of mobility of redox components in the inner mitochondrial membrane. | journal = J Membr Biol | volume = 104 | issue = 3 | pages = 193-209 | month = Sep | year = 1988 | doi =  | PMID = 2850362 }}</ref><ref name="Mitchell-1976">{{Cite journal  | last1 = Mitchell | first1 = P. | title = Possible molecular mechanisms of the protonmotive function of cytochrome systems. | journal = J Theor Biol | volume = 62 | issue = 2 | pages = 327-67 | month = Oct | year = 1976 | doi =  | PMID = 186667 }}</ref> Second, CoQ<sub>10</sub> serves as a free radical scavenger that is the only lipid-soluble antioxidant that can be enzymatically regenerated to a reduced, active form.<ref>{{Cite web  | last =  | first =  | title = Highlights in ubiquinone research: proceedings of the International ... - Giorgio Lenaz, Universit di Bologna - Google Books | url = http://books.google.ca/books?id=GrXwAAAAMAAJ&q=HighlightsinUbiquinoneResearch+the+role+of+coenzyme+Q+in+as+antioxidant&dq=HighlightsinUbiquinoneResearch+the+role+of+coenzyme+Q+in+as+antioxidant&hl=&cd=3&source=gbs_api | publisher =  | date =  | accessdate = 28 May 2013 }}</ref><ref name="Ernster-1993">{{Cite journal  | last1 = Ernster | first1 = L. | last2 = Forsmark-Andrée | first2 = P. | title = Ubiquinol: an endogenous antioxidant in aerobic organisms. | journal = Clin Investig | volume = 71 | issue = 8 Suppl | pages = S60-5 | month =  | year = 1993 | doi =  | PMID = 8241707 }}</ref><ref name="Villalba-1997">{{Cite journal  | last1 = Villalba | first1 = JM. | last2 = Navarro | first2 = F. | last3 = Gómez-Díaz | first3 = C. | last4 = Arroyo | first4 = A. | last5 = Bello | first5 = RI. | last6 = Navas | first6 = P. | title = Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane. | journal = Mol Aspects Med | volume = 18 Suppl | issue =  | pages = S7-13 | month =  | year = 1997 | doi =  | PMID = 9266501 }}</ref> In this capacity it plays an important role in decreasing the amount of  superoxide radical (O2-). This radical is produced by physiological stress, such as  that caused by disease, and reacts rapidly with endothelial nitric oxide (NO) which is important for endothelial health and NO-mediated vasodilation. Lastly, CoQ<sub>10</sub> has more recently been identified as a potent gene regulator, significantly impacting the expression of genes encoding proteins involved in cell signaling, intermediate metabolism, transport, transcriptional control, disease mutation, phosphorylation, embryonal development, and binding.<ref name="Groneberg-2005">{{Cite journal  | last1 = Groneberg | first1 = DA. | last2 = Kindermann | first2 = B. | last3 = Althammer | first3 = M. | last4 = Klapper | first4 = M. | last5 = Vormann | first5 = J. | last6 = Littarru | first6 = GP. | last7 = Döring | first7 = F. | title = Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. | journal = Int J Biochem Cell Biol | volume = 37 | issue = 6 | pages = 1208-18 | month = Jun | year = 2005 | doi = 10.1016/j.biocel.2004.11.017 | PMID = 15778085 }}</ref>


==History==
==Occurrence in nature==  
Coenzyme Q was first discovered by professor [[Fred L. Crane]] and colleagues at the [[University of Wisconsin-Madison]] Enzyme Institute in [[1957]].<ref>{{cite journal |author=Crane F, Hatefi Y, Lester R, Widmer C |title=Isolation of a quinone from beef heart mitochondria |journal=Biochim Biophys Acta |volume=25 |issue=1 |pages=220-1 |year=1957 |pmid=13445756}}</ref><ref name="washington">Peter H. Langsjoen, "[http://faculty.washington.edu/~ely/coenzq10.html Introduction of Coezyme Q10]"</ref> In [[1958]], its chemical structure was reported by Professor [[Karl Folkers]] and coworkers at [[Merck & Co.|Merck]].<ref>Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K.
CoQ<sub>10</sub> occurs in [[mackerel]] and [[herring]] fresh heart tissue in concentrations of 105-148 μg/g. In fresh mackerel "red and white tissue," CoQ<sub>10</sub> concentrations of 67 and 15 μg/g, respectively, have been reported.  In fresh herring tissue, an amount of 15–24 μg/g of CoQ<sub>10</sub> has been reported.<ref>[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WJH-4MNHY1G-1&_user=10&_coverDate=08%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9d3ef3c2d1b8980a4bf544770f19a9e4 Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec]</ref>
Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.</ref><ref name="washington"> </ref>
 
CoQ10 Content of various foods:<ref>[http://www.thefactsaboutfitness.com/research/coq10.htm www.thefactsaboutfitness.com]</ref>
{| class="wikitable sortable"
! Food
! CoQ10 <br>[μg/g]
! Portion of Food <br>[g]
! CoQ10 Amount in Portion <br>[mg]
|- align="center"
| [[Pork]] heart
| 203
| 120
| 24
|- align="center"
| [[Chicken]] leg
| 17
| 120
| 2.0
|- align="center"
| [[Beef]] heart
| 41
| 120
| 4.8
|}
==Chemical properties==
==Chemical properties==
   
   
  The oxidized structure of '''CoQ''', or '''Q''', is given here. The various kinds of Coenzyme Q can be distinguished by the number of [[isoprene|isoprenoid]] [[side-chain]]s they have. The most common CoQ in human [[mitochondria]] is Q<sub>10</sub>. The image to the right has three [[isoprene|isoprenoid]] units and would be called Q<sub>3</sub>.  [[image:Ubiquinone3.png|center|300px]]
  The oxidized structure of CoQ is given here. The various kinds of CoQ can be distinguished by the number of [[isoprene|isoprenoid]] [[side-chain]]s they have. The most common CoQ in human [[mitochondria]] is CoQ<sub>10</sub>. The image to the right has three [[isoprene|isoprenoid]] units and would be called Q<sub>3</sub>.  [[image:Ubiquinone3.png|center|300px]]


  If Coenzyme Q is reduced by one equivalent, the following structure results, a '''ubisemiquinone''', and is denoted '''QH'''. Note the [[free-radical]] on one of the ring oxygens (either oxygen may become a free-radical, in this case the top oxygen is shown as such).  [[image:Ubisemiquinone3.png|center|300px]]
  If CoQ is reduced by one equivalent, the following structure results, a ubisemiquinone, and is denoted QH. Note the [[free-radical]] on one of the ring oxygens (either oxygen may become a free-radical, in this case the top oxygen is shown as such).  [[image:Ubisemiquinone3.png|center|300px]]
   
   
  If Coenzyme Q is reduced by two equivalents, the compound becomes a '''ubiquinol''', denoted '''QH<sub>2</sub>''':  [[image:ubiquinol3.png|center|300px]]
  If CoQ is reduced by two equivalents, the compound becomes a ubiquinol, denoted QH<sub>2</sub>:  [[image:ubiquinol3.png|center|300px]]


==Biochemical role==
==Biochemical role==
[[Image:ETC.PNG|left|thumb|300px|[[Electron transport chain]] ("UQ" visible in green near center.)]]
CoQ is found in the [[biological membrane|membranes]] of [[endoplasmic reticulum]], [[peroxisome]]s, [[lysosome]]s, [[vesicle (biology)|vesicle]]s, and the inner membrane of the [[mitochondrion]], where it is an important part of the [[electron transport chain]]; there it passes reducing equivalents to acceptors such as [[Coenzyme Q - cytochrome c reductase|Coenzyme Q: cytochrome c - oxidoreductase]]:  
CoQ is found in the [[biological membrane|membranes]] of [[endoplasmic reticulum]], [[peroxisome]]s, [[lysosome]]s, [[vesicle (biology)|vesicle]]s, and the inner membrane of the [[mitochondrion]], where it is an important part of the [[electron transport chain]]; there it passes reducing equivalents to acceptors such as [[Coenzyme Q - cytochrome c reductase|Coenzyme Q: cytochrome c - oxidoreductase]]:  


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CoQ is also essential in the formation of the [[apoptosome]], along with other adapter proteins. The loss of trophic factors activates pro-[[apoptosis|apoptotic]] enzymes, causing the breakdown of mitochondria.
CoQ is also essential in the formation of the [[apoptosome]], along with other adapter proteins. The loss of trophic factors activates pro-[[apoptosis|apoptotic]] enzymes, causing the breakdown of mitochondria.


==Biosynthesis==


 
The [[1,4-Benzoquinone|benzoquinone]] portion of CoQ<sub>10</sub> is synthesized from [[tyrosine]], whereas the [[isoprene]] sidechain is synthesized from [[acetyl-CoA]] through the [[mevalonate pathway]]. The mevalonate pathway is used for the first steps of cholesterol biosynthesis.


==Supplementation==
==Supplementation==
Because of its ability to transfer electrons and therefore act as an [[antioxidant]], Coenzyme Q is also used as a [[dietary supplement]]. When you are younger the body can synthesize Q<sub>10</sub> from the lower-numbered ubiquinones such as Q<sub>6</sub> or Q<sub>8</sub>. The sick and elderly may not be able to make enough, thus Q<sub>10</sub> becomes a [[vitamin]] later in life and in illness.
Because of its ability to transfer electrons and therefore act as an [[antioxidant]], CoQ<sub>10</sub> is also used as a [[dietary supplement]]. When you are younger the body can synthesize Q<sub>10</sub> from the lower-numbered ubiquinones such as Q<sub>6</sub> or Q<sub>8</sub>. The sick and elderly may not be able to make enough, thus Q<sub>10</sub> becomes a [[vitamin]] later in life and in illness.


===Mitochondrial disorders===
===Mitochondrial disorders===
Supplementation of Coenzyme Q<sub>10</sub> is a treatment for some of the very rare and serious [[mitochondrial disease|mitochondrial disorder]]s and other [[metabolic disorder]]s, where patients are not capable of producing enough coenzyme Q<sub>10</sub> because of their disorder. Coenzyme Q<sub>10</sub> is then prescribed by a physician.<ref>{{cite journal | last = Berbel-Garcia | first = A. | coauthors = ''et al.'' | title = Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS | journal = Clinical Neuropharmacology | volume = 27 | year = 2004 | month = July | pages = 187-191 | id = PMID 15319706 | accessdate = 2006-12-01 }}</ref>
Supplementation of CoQ<sub>10</sub> is a treatment for some of the very rare and serious [[mitochondrial disease|mitochondrial disorder]]s and other [[metabolic disorder]]s, where patients are not capable of producing enough CoQ<sub>10</sub> because of their disorder. CoQ<sub>10</sub> is then prescribed by a physician.<ref>{{cite journal | last = Berbel-Garcia | first = A. | coauthors = ''et al.'' | title = Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS | journal = Clinical Neuropharmacology | volume = 27 | year = 2004 | month = July | pages = 187-191 | id = PMID 15319706 | accessdate = 2006-12-01 }}</ref>
 
==Cardiac and Vascular Disease==
In 1970 Folkers et al. demonstrated that between 70-75% of patients with [[heart disease]] have low levels of CoQ<sub>10</sub>.<ref name="Folkers-1970">{{Cite journal  | last1 = Folkers | first1 = K. | last2 = Littarru | first2 = GP. | last3 = Ho | first3 = L. | last4 = Runge | first4 = TM. | last5 = Havanonda | first5 = S. | last6 = Cooley | first6 = D. | title = Evidence for a deficiency of coenzyme Q10 in human heart disease. | journal = Int Z Vitaminforsch | volume = 40 | issue = 3 | pages = 380-90 | month =  | year = 1970 | doi =  | PMID = 5450999 }}</ref> The increasing severity of heart disease was correlated with progressively declining blood and myocardial tissue levels of CoQ<sub>10</sub> in 1972.<ref name="Littaru-1972">{{Cite journal  | last1 = Littaru | first1 = GP. | last2 = Ho | first2 = L. | last3 = Folkers | first3 = K. | title = Deficiency of coenzyme Q 10 in human heart disease. I. | journal = Int J Vitam Nutr Res | volume = 42 | issue = 2 | pages = 291-305 | month =  | year = 1972 | doi =  | PMID = 5053855 }}</ref> Though it is thought that normal CoQ<sub>10</sub> [[serum]] levels can be maintained by doses of 30-60mg/day (per 1kg), clinical benefit may not actually be obtained until serum CoQ<sub>10</sub> levels reach 2-4 times their normal level. In patients with [[cardiomyopathy]] and low levels of myocardial CoQ<sub>10</sub>, the addition of 100mg/day of oral CoQ10 over a 2-8 month period has been shown to increase myocardial CoQ<sub>10</sub> levels between 20 and 85%.<ref name="Folkers-1985">{{Cite journal  | last1 = Folkers | first1 = K. | last2 = Vadhanavikit | first2 = S. | last3 = Mortensen | first3 = SA. | title = Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. | journal = Proc Natl Acad Sci U S A | volume = 82 | issue = 3 | pages = 901-4 | month = Feb | year = 1985 | doi =  | PMID = 3856239 }}</ref> Though these studies have correlated a CoQ10 deficit with cardiovascular disease and demonstrate that CoQ<sub>10</sub> serum and myocardial levels can be elevated with CoQ10 supplementation, the true efficacy of CoQ<sub>10</sub> supplementation in cardiovascular disease remains unclear.
 
===Hypertension===
A 2007 [[meta-analysis]] of all published trials of the use of CoQ<sub>10</sub> in the treating [[hypertension]] acts as the most comprehensive and current assessment of the efficacy and consistency of its therapeutic effect as well the incidence of side effects.<ref name="Rosenfeldt-2007">{{Cite journal  |last1 = Rosenfeldt | first1 = FL. | last2 = Haas | first2 = SJ. | last3 = Krum | first3 = H. | last4 = Hadj | first4 = A. | last5 = Ng | first5 = K.|last6 = Leong | first6 = JY. | last7 = Watts | first7 = GF. | title = Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. | journal = J Hum Hypertens | volume = 21 | issue = 4 | pages = 297-306 | month = Apr | year = 2007 | doi = 10.1038/sj.jhh.1002138 | PMID = 17287847 }}</ref> The analysis included 12 clinical trials, including three randomized controlled trials, one crossover study, and eight open label studies. Combined, the trials enrolled 326 patients, 120 as part of randomized trials and 214 as part of open label studies. Within the randomized controlled trials, the treatment groups experienced  a significant average drop in [[blood pressure|systolic]] and [[blood pressure|diastolic blood pressure]] compared to control groups (16.6 mm Hg and 8.2 mm Hg decrease, respectively; P<0.001). During the treatment phase of the lone 18 patient cross-over study systolic and diastolic pressures were on average also significantly decreased (11 mm Hg and 8 mm Hg decrease, respectively; P<0.001). Likewise, the weighted mean systolic and diastolic blood pressures of patients enrolled in open label observational studies were significantly lower after patients began taking CoQ<sub>10</sub> (13.5 mm Hg and 10.3 mm Hg decrease, respectively, P<0.001). Overall, CoQ<sub>10</sub> treatment resulted in systolic blood pressure decreases between 11 and 17 mm Hg and diastolic blood pressure decreases between 8 and 10 mm Hg. Among all the studies CoQ<sub>10</sub> treatment produced minimal side effects, the most common being gastrointestinal effects.
 
The most likely physiological explanation for the the [[hypotension|hypotensive]] effect of CoQ<sub>10</sub> observed in this meta-analysis is [[oxidative stress]] relief. CoQ10 indirectly increases the amount of free [[nitric oxide|NO]] by neutralizing destructive [[radical|free radicals]]. Indeed, this explanation supports the finding that CoQ<sub>10</sub> does not have a hypotensive or [[vasodilator|vasodilating]] effect in patients who are healthy and do not have NO activity suppressed by oxidative stress.
 
===Coronary Artery Disease===
CoQ<sub>10</sub> treatment has also proven beneficial in the treatment of [[coronary artery disease|coronary artery disease]] (CAD). A placebo-controlled study of 19 patients with CAD was conducted to evaluate the effect of 100 mg CoQ<sub>10</sub> tid for one month on vascular function as evaluated by extracellular [[superoxide dismutase]] (ecSOD) activity and brachial artery vasomotility measured by flow-dependent endothelial-mediated dilation (FMD). A secondary endpoint was to determine the effect of CoQ<sub>10</sub> on the cardiopulmonary test.<ref name="Tiano-2007">{{Cite journal  | last1 = Tiano | first1 = L. | last2 = Belardinelli | first2 = R. | last3 = Carnevali | first3 = P. | last4 = Principi | first4 = F. | last5 = Seddaiu | first5 = G. | last6 = Littarru | first6 = GP. | title = Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study. | journal = Eur Heart J | volume = 28 | issue = 18 | pages = 2249-55 | month = Sep | year = 2007 |doi = 10.1093/eurheartj/ehm267 | PMID = 17644511 }}</ref> A four-fold increase in serum CoQ<sub>10</sub> levels was reported within the treatment group and was significantly correlated with endothelium-dependent (ED)  relaxation. ecSOD activation, [[VO2 max|peak VO2]], and O2 pulse increases were also significantly greater in the treatment group compared to the placebo group. The effect of CoQ10 treatment was greatest on patients with the lowest levels of ecSOD and hence most vulnerable to oxidative stress.


===Migraine headaches===
ecSOD is an enzyme highly expressed in the heart that has been examined for its role in several diseases, including vascular-related diseases such as CAD. These results build upon and confirm a 2000 study demonstrating that ecSOD activity is substantially reduced in patients with CAD and that endothelium-bound ecSOD activity level strongly correlates with endothelial-mediated dilation (FMD), a biomarker of vascular function.<ref name="Landmesser-2000">{{Cite journal | last1 = Landmesser | first1 = U. | last2 = Merten | first2 = R. | last3 = Spiekermann | first3 = S. | last4 = Büttner | first4 = K. |last5 = Drexler | first5 = H. | last6 = Hornig | first6 = B. | title = Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. | journal = Circulation | volume = 101 | issue = 19 | pages = 2264-70 | month = May | year = 2000 | doi = | PMID = 10811593 }}</ref> It it also known that NO can induce ecSOD [[gene expression|expression]]. Therefore, likely physiological explanation for the benefit of CoQ<sub>10</sub> for vascular health in CAD stems in part from the ability of CoQ10 to relieve oxidative stress on NO, resulting increased ecSOD activity. The effect of CoQ<sub>10</sub> on peak VO2 and O2 pulse is most likely attributable to its bioenergetic properties.
Supplementation of Coenzyme Q<sub>10</sub> 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 trial|open-label]],<ref>{{cite journal |author=Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S |title=Open label trial of coenzyme Q10 as a migraine preventive |journal=Cephalalgia |volume=22 |issue=2 |pages=137-41 |year=2002 |pmid=11972582 |url = http://www.blackwell-synergy.com/doi/full/10.1046/j.1468-2982.2002.00335.x}}</ref> and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.<ref>{{cite journal |author=Sándor PS, et al.|title=Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial |journal=Neurology |volume=64 |pages=713-715 |year=2005 |url = http://www.neurology.org/cgi/content/abstract/64/4/713}}</ref> Dosages were 150 to 300 mg/day.
 
===Congestive Heart Failure===
Slides about the role of mitochondria in heart failure: [[File:Mitochondrial_Dysfunction_and_CHF_for_wikidoc.pdf]]


===Cancer===
CoQ<sub>10</sub> levels  are decreased in the setting of [[heart failure]] (HF), and progressive heart failure leads to lower and lower levels of CoQ<sub>10</sub>.  There have been modest sized [[double blind]] [[randomized controlled trials]] that have demonstrated CoQ<sub>10</sub> is associated with improved symptoms, functional capacity and quality of life in patients with heart failure.  The drug is generally well tolerated, with few side effects.
It is also being investigated as a treatment for [[cancer]], and as relief from cancer treatment side-effects.<ref>


Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
Congestive heart failure (CHF) is the third most common cause of cardiovascular disease, the leading cause of [[morbidity]] and [[mortality rate|mortality]] in the U.S. and around the world.<ref>{{Cite web  | last =  | first =  | title = related:mdvAhRE800UJ:scholar.google.com/ - Google Scholar | url =http://scholar.google.com/scholar?q=related:mdvAhRE800UJ:scholar.google.com/&hl=en&num=20&as_sdt=0,5 | publisher =  | date =  | accessdate = 28 May 2013}}</ref> A 2006 double-blind, placebo-controlled cross-over design study of 23 patients divided into three groups treated with a differing orders and combinations of exercise, 100 mg tid CoQ<sub>10</sub>, and placebo demonstrated that both peak VO2 and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ<sub>10</sub> and after exercise treatment.<ref name="Belardinelli-2006">{{Cite journal  | last1 = Belardinelli | first1 = R. | last2 = Muçaj | first2 = A. | last3 = Lacalaprice | first3 = F. | last4 = Solenghi | first4 = M. | last5 = Seddaiu | first5 = G. | last6 = Principi | first6 = F. | last7 = Tiano | first7 = L. | last8 = Littarru | first8 = GP. | title = Coenzyme Q10 and exercise training in chronic heart failure. | journal = Eur Heart J | volume = 27 | issue = 22 | pages = 2675-81 | month = Nov | year = 2006 | doi = 10.1093/eurheartj/ehl158 |PMID = 16882678 }}</ref> As in other studies, CoQ<sub>10</sub> supplementation resulted in a four-fold increase in plasma CoQ<sub>10</sub> levels. This study showed additionally that  exercise further increased plasma CoQ10 levels. While CoQ10 demonstrated a main effect on peak V02 (+ 9%), EDDBA (+38%), and the systolic wall thickening score index (SWTI) (-12%), exercise was also demonstrated to have comparable effects. While the combination of CoQ<sub>10</sub> supplementation and exercise resulted in the greatest benefit in these categories, the only significant synergistic effect observed between the two treatments was for peak SWTI.


</ref>
A 2013 meta-analysis serves as the most recent and comprehensive review of the effects of CoQ<sub>10</sub> supplementation on HF, specifically its impact on the [[ejection fraction]] (EF) and New York Heart Association (NYHA) functional classification in patients with CHF.<ref name="Fotino-2013">{{Cite journal  | last1 = Fotino | first1 = AD. | last2 = Thompson-Paul | first2 = AM. | last3 = Bazzano | first3 = LA. | title = Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis. | journal = Am J Clin Nutr | volume = 97 | issue = 2 | pages = 268-75 | month = Feb | year = 2013 | doi = 10.3945/ajcn.112.040741 | PMID = 23221577 }}</ref> The study found 120 potentially relevant studies during a literature review and selected 13 for the analysis, of which 7 were crossover and 6 were parallel-arm studies, with 12 double-blinded studies and 1 single-blind study. The enrollment of the analyzed studies was  395. A confounder in the analysis was the wide range in study duration (4 to 28 weeks) and variable CoQ<sub>10</sub> daily dosing (60 to 300mg). Supplementation with CoQ<sub>10</sub> resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and a 0.30 decrease (95% CI: -0.66, 0.06) in the NYHA functional class. Significant improvement in EF was seen in crossover trials, trials twelve weeks long or longer, studies published before 1994, studies with a daily  CoQ<sub>10</sub> dose >=100 mg, and in patients with less severe CHF. The study cautiously suggests that CoQ<sub>10</sub> supplementation may improve EF in patients with CHF.


===Brain health and neurodegenerative diseases===
===== Q-SYMBIO Trial=====
Recent studies have shown that the antioxidant properties of Coenzyme Q<sub>10</sub> benefit the body and the [[brain]] in animal models.<ref>{{cite journal | last = Matthews | first = R. T. | coauthors = ''et al.'' | title = Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects | journal = PNAS | volume = 95 | year = 1998 | month = July | pages = 8892-8897 | url = http://intl.pnas.org/cgi/content/abstract/95/15/8892 | accessdate = 2006-12-01 }}
In a modest sized, multicenter, [[double blind]],[[randomized controlled trial]], 420 patients with [[New York Heart Association]] ([[NYHA]]) Class III or IV heart failure who were receiving standard therapy, were randomized to either CoQ<sub>10</sub> or placebo.  The patients were followed for two years. <ref>http://www.escardio.org/about/press/press-releases/pr-13/Pages/first-drug-in-decade-improves-heart-failure-mortality.aspx</ref>.  The primary endpoint (MACE=unplanned hospitalization due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support) was reduced from 29 events (14%) in patients randomized to CoQ<sub>10</sub> compared to 55 (25%) in patients randomized to placebo (hazard ratio=2; p=0.003 by time to event analysis).  Randomization to CoQ<sub>10</sub> was associated with a halving of all cause mortality: there were 18 (9%) deaths among patients in the CoQ10 group versus 36 (17%) deaths among patients in the placebo group (hazard ratio=2.1; p=0.01).  Cardiovascular mortality was also reduced (p-0.02) as was the risk of rehospitalisations for heart failure (p=0.05). There tended to be fewer adverse events among patients randomized to CoQ<sub>10</sub> compared to the placebo (p=0.073).  It is unclear if there were greater benefits among patients treated with statins, drugs that lower CoQ<sub>10</sub>.


</ref> Some of these studies indicate that Coenzyme Q<sub>10</sub> protects the brain from neurodegenerative disease such as [[Parkinson's]],<ref>''Biol Signals Recept. 2001 May-Aug;10(3-4):224-53''</ref> although it does not relieve the symptoms.<ref name='NCT00180037'> {{cite web|url=http://tools.wikimedia.de/~magnus/makeref.php |title=Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease |last=Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group |date=May 14, 2007 |work=Archives of Neurologu }}</ref> Dosage was 300 mg per day.
===Treatment of Statin Intolerance===
CoQ<sub>10</sub> shares a common biosynthetic pathway with [[cholesterol]]. The synthesis of an intermediary precursor of CoQ<sub>10</sub>, [[mevalonate]], is inhibited by some [[beta blockers]], blood pressure-lowering medication,<ref>{{cite journal |author=Kishi T, Watanabe T, Folkers K |title=Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors |journal=Res Commun Chem Pathol Pharmacol |volume=17 |issue=1 |pages=157-64 |year=1977 |pmid=17892}}</ref> and [[statins]], a class of cholesterol-lowering drugs.<ref>[http://www.cholesterol-and-health.com/Synthesis-Of-Cholesterol.html The Synthesis of Cholesterol<!-- Bot generated title -->]</ref>  Statins can reduce serum levels of CoQ<sub>10</sub> by up to 40%.<ref>{{cite journal |author=Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G |title=Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study |journal=J Clin Pharmacol |volume=33 |issue=3 |pages=226-9 |year=1993 |pmid=8463436}}</ref> Some research suggests the logical option of supplementation with CoQ<sub>10</sub> as a routine adjunct to any treatment that may reduce endogenous production of CoQ<sub>10</sub>, based on a balance of likely benefit against very small risk.<ref>{{cite journal |author=Sarter B |title=Coenzyme Q10 and cardiovascular disease: a review |journal=J Cardiovasc Nurs |volume=16 |issue=4 |pages=9-20 |year=2002 |pmid=12597259}}</ref><ref>{{cite journal |author=Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C |title=Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer |journal=Clin Cancer Res |volume=2 |issue=3 |pages=483-91 |year=1996 |pmid=9816194}}</ref>


===Cardiac arrest===
===Cardiac arrest===
Another recent study shows a survival benefit after cardiac arrest if coenzyme Q<sub>10</sub> is administered in addition to commencing active cooling (to 32&ndash;34 degrees Celsius).<ref>
Another recent study shows a survival benefit after cardiac arrest if CoQ<sub>10</sub> is administered in addition to commencing active cooling (to 32&ndash;34 degrees Celsius).<ref>


{{cite journal | last = Damian | first = M. S. | coauthors = ''et al.'' | title = Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest | journal = Circulation, American Heart Foundation | volume = 110 | year = 2004 | month = July | pages = 3011-3016 | url = http://www.circ.ahajournals.org/cgi/content/abstract/110/19/3011 | accessdate = 2006-12-01 }}
{{cite journal | last = Damian | first = M. S. | coauthors = ''et al.'' | title = Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest | journal = Circulation, American Heart Foundation | volume = 110 | year = 2004 | month = July | pages = 3011-3016 | url = http://www.circ.ahajournals.org/cgi/content/abstract/110/19/3011 | accessdate = 2006-12-01 }}
Line 60: Line 95:
</ref>
</ref>


===Blood pressure===
===Migraine headaches===
There are several reports concerning the effect of CoQ<sub>10</sub> on blood pressure in human studies.<ref> 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) </ref>
Supplementation of CoQ<sub>10</sub> 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 trial|open-label]],<ref>{{cite journal |author=Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S |title=Open label trial of coenzyme Q10 as a migraine preventive |journal=Cephalalgia |volume=22 |issue=2 |pages=137-41 |year=2002 |pmid=11972582 |url = http://www.blackwell-synergy.com/doi/full/10.1046/j.1468-2982.2002.00335.x}}</ref> and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.<ref>{{cite journal |author=Sándor PS, et al.|title=Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial |journal=Neurology |volume=64 |pages=713-715 |year=2005 |url = http://www.neurology.org/cgi/content/abstract/64/4/713}}</ref> Dosages were 150 to 300 mg/day.
In a recent meta-analysis of the clinical trials of CoQ<sub>10</sub> for hypertension, a research group led by Professor FL Rosenfeldt (from the Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q<sub>10</sub> for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies.  
The research group concluded that coenzyme Q<sub>10</sub> 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.<ref> Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q<sub>10</sub> in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007</ref>


===Lifespan===
==Cancer==
Studies have shown that low dosages of Coenzyme Q<sub>10</sub> reduce [[oxidation]] and [[DNA]] double-strand breaks, and a combination of a diet rich in [[polyunsaturated fatty acids]] and Coenzyme Q<sub>10</sub> supplementation leads to a longer lifespan in rats<ref name=pmid_15036411>{{cite journal |author=Quiles JL, Ochoa JJ, Huertas JR, Mataix J |title=Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. |journal=Exp Gerontol. |volume=39 |issue=2 |pages=189-94 |year=2004 |pmid=15036411 |doi=}}</ref>
It is also being investigated as a treatment for [[cancer]], and as relief from cancer treatment side-effects.<ref>


==Biosynthesis==
Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006


The [[1,4-Benzoquinone|benzoquinone]] portion of Coenzyme Q<sub>10</sub> is synthesized from [[tyrosine]], whereas the [[isoprene]] sidechain is synthesized from [[acetyl-CoA]] through the [[mevalonate pathway]]. The mevalonate pathway is used for the first steps of cholesterol biosynthesis.
</ref>


==Inhibition by statins and beta blockers==
==Brain health and neurodegenerative diseases==
Coenzyme Q<sub>10</sub> shares a common biosynthetic pathway with [[cholesterol]]. The synthesis of an intermediary precursor of Coenzyme Q<sub>10</sub>, [[mevalonate]], is inhibited by some [[beta blockers]], blood pressure-lowering medication,<ref>{{cite journal |author=Kishi T, Watanabe T, Folkers K |title=Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors |journal=Res Commun Chem Pathol Pharmacol |volume=17 |issue=1 |pages=157-64 |year=1977 |pmid=17892}}</ref> and [[statins]], a class of cholesterol-lowering drugs.<ref>[http://www.cholesterol-and-health.com/Synthesis-Of-Cholesterol.html The Synthesis of Cholesterol<!-- Bot generated title -->]</ref>  Statins can reduce serum levels of coenzyme Q<sub>10</sub> by up to 40%.<ref>{{cite journal |author=Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G |title=Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study |journal=J Clin Pharmacol |volume=33 |issue=3 |pages=226-9 |year=1993 |pmid=8463436}}</ref> Some research suggests the logical option of supplementation with coenzyme Q<sub>10</sub> as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q<sub>10</sub>, based on a balance of likely benefit against very small risk.<ref>{{cite journal |author=Sarter B |title=Coenzyme Q10 and cardiovascular disease: a review |journal=J Cardiovasc Nurs |volume=16 |issue=4 |pages=9-20 |year=2002 |pmid=12597259}}</ref><ref>{{cite journal |author=Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C |title=Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer |journal=Clin Cancer Res |volume=2 |issue=3 |pages=483-91 |year=1996 |pmid=9816194}}</ref>
Recent studies have shown that the antioxidant properties of CoQ<sub>10</sub> benefit the body and the [[brain]] in animal models.<ref>{{cite journal | last = Matthews | first = R. T. | coauthors = ''et al.'' | title = Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects | journal = PNAS | volume = 95 | year = 1998 | month = July | pages = 8892-8897 | url = http://intl.pnas.org/cgi/content/abstract/95/15/8892 | accessdate = 2006-12-01 }}


==Occurrence in nature==
</ref>  Some of these studies indicate that CoQ<sub>10</sub> protects the brain from neurodegenerative disease such as [[Parkinson's]],<ref>''Biol Signals Recept. 2001 May-Aug;10(3-4):224-53''</ref> although it does not relieve the symptoms.<ref name='NCT00180037'> {{cite web|url=http://tools.wikimedia.de/~magnus/makeref.php |title=Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease |last=Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group |date=May 14, 2007 |work=Archives of Neurologu }}</ref> Dosage was 300 mg per day.
CoQ10 occurs in [[mackerel]] and [[herring]] fresh heart tissue in concentrations of 105-148 μg/g. In fresh mackerel "red and white tissue," CoQ10 concentrations of 67 and 15 μg/g, respectively, have been reported. In fresh herring tissue, an amount of 15–24 μg/g of CoQ10 has been reported.<ref>[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WJH-4MNHY1G-1&_user=10&_coverDate=08%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9d3ef3c2d1b8980a4bf544770f19a9e4 Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec]</ref>


CoQ10 Content of various foods:<ref>[http://www.thefactsaboutfitness.com/research/coq10.htm www.thefactsaboutfitness.com]</ref>
==Lifespan==
{| class="wikitable sortable"
Studies have shown that low dosages of CoQ<sub>10</sub> reduce [[oxidation]] and [[DNA]] double-strand breaks, and a combination of a diet rich in [[polyunsaturated fatty acids]] and CoQ<sub>10</sub>supplementation leads to a longer lifespan in rats<ref name=pmid_15036411>{{cite journal |author=Quiles JL, Ochoa JJ, Huertas JR, Mataix J |title=Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. |journal=Exp Gerontol. |volume=39 |issue=2 |pages=189-94 |year=2004 |pmid=15036411 |doi=}}</ref>
! Food
! CoQ10 <br>[μg/g]
! Portion of Food <br>[g]
! CoQ10 Amount in Portion <br>[mg]
|- align="center"
| [[Pork]] heart
| 203
| 120
| 24
|- align="center"
| [[Chicken]] leg
| 17
| 120
| 2.0
|- align="center"
| [[Beef]] heart
| 41
| 120
| 4.8
|}


==See Also==
==See Also==
Line 116: Line 128:
{{Electron transport chain}}
{{Electron transport chain}}
{{Enzyme cofactors}}
{{Enzyme cofactors}}
{{SIB}}
 


[[Category:Cellular respiration]]
[[Category:Cellular respiration]]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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

This vitamin-like substance is, by nature, present in most human cells except red blood cells and eye lens cells (no mitochondria) and are responsible for the production of the body’s own energy. In each human cell, food energy is converted into energy in the mitochondria with the aid of CoQ10. Ninety-five percent of all the human body’s energy requirements (ATP) is converted with the aid of CoQ10.[1][2] Therefore, those organs with the highest energy requirements – such as the heart and the liver – have the highest CoQ10 concentrations.[3][4][5]

History

CoQ10 was first discovered by Crane et al. in 1957 within beef heart mitochondria.[6] This vitamin-like nutrient has since been implicated in three major biological processes, imparting its alternate name of “ubiquinone”. Floating within the inner membrane of mitochrodria, CoQ10 plays an important role in oxidative phosphorylation where it is responsible for the two electron oxidation of NADH.[7][8] Second, CoQ10 serves as a free radical scavenger that is the only lipid-soluble antioxidant that can be enzymatically regenerated to a reduced, active form.[9][10][11] In this capacity it plays an important role in decreasing the amount of superoxide radical (O2-). This radical is produced by physiological stress, such as that caused by disease, and reacts rapidly with endothelial nitric oxide (NO) which is important for endothelial health and NO-mediated vasodilation. Lastly, CoQ10 has more recently been identified as a potent gene regulator, significantly impacting the expression of genes encoding proteins involved in cell signaling, intermediate metabolism, transport, transcriptional control, disease mutation, phosphorylation, embryonal development, and binding.[12]

Occurrence in nature

CoQ10 occurs in mackerel and herring fresh heart tissue in concentrations of 105-148 μg/g. In fresh mackerel "red and white tissue," CoQ10 concentrations of 67 and 15 μg/g, respectively, have been reported. In fresh herring tissue, an amount of 15–24 μg/g of CoQ10 has been reported.[13]

CoQ10 Content of various foods:[14]

Food CoQ10
[μg/g] 		Portion of Food
[g] 		CoQ10 Amount in Portion
[mg]
Pork heart 203 120 24
Chicken leg 17 120 2.0
Beef heart 41 120 4.8

Chemical properties

The oxidized structure of CoQ is given here. The various kinds of CoQ can be distinguished by the number of isoprenoid side-chains they have. The most common CoQ in human mitochondria is CoQ10. The image to the right has three isoprenoid units and would be called Q3.

If CoQ is reduced by one equivalent, the following structure results, a ubisemiquinone, and is denoted QH. Note the free-radical on one of the ring oxygens (either oxygen may become a free-radical, in this case the top oxygen is shown as such).

If CoQ is reduced by two equivalents, the compound becomes a ubiquinol, denoted QH2:

Biochemical role

CoQ is found in the membranes of endoplasmic reticulum, peroxisomes, lysosomes, vesicles, and the inner membrane of the mitochondrion, where it is an important part of the electron transport chain; there it passes reducing equivalents to acceptors such as Coenzyme Q: cytochrome c - oxidoreductase:

CoQH2+ 2 FeIII-cytochrome c → CoQ + 2 FeII-cytochrome c

CoQ is also essential in the formation of the apoptosome, along with other adapter proteins. The loss of trophic factors activates pro-apoptotic enzymes, causing the breakdown of mitochondria.

Biosynthesis

The benzoquinone portion of CoQ10 is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is used for the first steps of cholesterol biosynthesis.

Supplementation

Because of its ability to transfer electrons and therefore act as an antioxidant, CoQ10 is also used as a dietary supplement. When you are younger the body can synthesize Q10 from the lower-numbered ubiquinones such as Q6 or Q8. The sick and elderly may not be able to make enough, thus Q10 becomes a vitamin later in life and in illness.

Mitochondrial disorders

Supplementation of CoQ10 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 CoQ10 because of their disorder. CoQ10 is then prescribed by a physician.[15]

Cardiac and Vascular Disease

In 1970 Folkers et al. demonstrated that between 70-75% of patients with heart disease have low levels of CoQ10.[16] The increasing severity of heart disease was correlated with progressively declining blood and myocardial tissue levels of CoQ10 in 1972.[17] Though it is thought that normal CoQ10 serum levels can be maintained by doses of 30-60mg/day (per 1kg), clinical benefit may not actually be obtained until serum CoQ10 levels reach 2-4 times their normal level. In patients with cardiomyopathy and low levels of myocardial CoQ10, the addition of 100mg/day of oral CoQ10 over a 2-8 month period has been shown to increase myocardial CoQ10 levels between 20 and 85%.[18] Though these studies have correlated a CoQ10 deficit with cardiovascular disease and demonstrate that CoQ10 serum and myocardial levels can be elevated with CoQ10 supplementation, the true efficacy of CoQ10 supplementation in cardiovascular disease remains unclear.

Hypertension

A 2007 meta-analysis of all published trials of the use of CoQ10 in the treating hypertension acts as the most comprehensive and current assessment of the efficacy and consistency of its therapeutic effect as well the incidence of side effects.[19] The analysis included 12 clinical trials, including three randomized controlled trials, one crossover study, and eight open label studies. Combined, the trials enrolled 326 patients, 120 as part of randomized trials and 214 as part of open label studies. Within the randomized controlled trials, the treatment groups experienced a significant average drop in systolic and diastolic blood pressure compared to control groups (16.6 mm Hg and 8.2 mm Hg decrease, respectively; P<0.001). During the treatment phase of the lone 18 patient cross-over study systolic and diastolic pressures were on average also significantly decreased (11 mm Hg and 8 mm Hg decrease, respectively; P<0.001). Likewise, the weighted mean systolic and diastolic blood pressures of patients enrolled in open label observational studies were significantly lower after patients began taking CoQ10 (13.5 mm Hg and 10.3 mm Hg decrease, respectively, P<0.001). Overall, CoQ10 treatment resulted in systolic blood pressure decreases between 11 and 17 mm Hg and diastolic blood pressure decreases between 8 and 10 mm Hg. Among all the studies CoQ10 treatment produced minimal side effects, the most common being gastrointestinal effects.

The most likely physiological explanation for the the hypotensive effect of CoQ10 observed in this meta-analysis is oxidative stress relief. CoQ10 indirectly increases the amount of free NO by neutralizing destructive free radicals. Indeed, this explanation supports the finding that CoQ10 does not have a hypotensive or vasodilating effect in patients who are healthy and do not have NO activity suppressed by oxidative stress.

Coronary Artery Disease

CoQ10 treatment has also proven beneficial in the treatment of coronary artery disease (CAD). A placebo-controlled study of 19 patients with CAD was conducted to evaluate the effect of 100 mg CoQ10 tid for one month on vascular function as evaluated by extracellular superoxide dismutase (ecSOD) activity and brachial artery vasomotility measured by flow-dependent endothelial-mediated dilation (FMD). A secondary endpoint was to determine the effect of CoQ10 on the cardiopulmonary test.[20] A four-fold increase in serum CoQ10 levels was reported within the treatment group and was significantly correlated with endothelium-dependent (ED) relaxation. ecSOD activation, peak VO2, and O2 pulse increases were also significantly greater in the treatment group compared to the placebo group. The effect of CoQ10 treatment was greatest on patients with the lowest levels of ecSOD and hence most vulnerable to oxidative stress.

ecSOD is an enzyme highly expressed in the heart that has been examined for its role in several diseases, including vascular-related diseases such as CAD. These results build upon and confirm a 2000 study demonstrating that ecSOD activity is substantially reduced in patients with CAD and that endothelium-bound ecSOD activity level strongly correlates with endothelial-mediated dilation (FMD), a biomarker of vascular function.[21] It it also known that NO can induce ecSOD expression. Therefore, likely physiological explanation for the benefit of CoQ10 for vascular health in CAD stems in part from the ability of CoQ10 to relieve oxidative stress on NO, resulting increased ecSOD activity. The effect of CoQ10 on peak VO2 and O2 pulse is most likely attributable to its bioenergetic properties.

Congestive Heart Failure

Slides about the role of mitochondria in heart failure: File:Mitochondrial Dysfunction and CHF for wikidoc.pdf

CoQ10 levels are decreased in the setting of heart failure (HF), and progressive heart failure leads to lower and lower levels of CoQ10. There have been modest sized double blind randomized controlled trials that have demonstrated CoQ10 is associated with improved symptoms, functional capacity and quality of life in patients with heart failure. The drug is generally well tolerated, with few side effects.

Congestive heart failure (CHF) is the third most common cause of cardiovascular disease, the leading cause of morbidity and mortality in the U.S. and around the world.[22] A 2006 double-blind, placebo-controlled cross-over design study of 23 patients divided into three groups treated with a differing orders and combinations of exercise, 100 mg tid CoQ10, and placebo demonstrated that both peak VO2 and endothelium-dependent dilation of the brachial artery (EDDBA) improved significantly after CoQ10 and after exercise treatment.[23] As in other studies, CoQ10 supplementation resulted in a four-fold increase in plasma CoQ10 levels. This study showed additionally that exercise further increased plasma CoQ10 levels. While CoQ10 demonstrated a main effect on peak V02 (+ 9%), EDDBA (+38%), and the systolic wall thickening score index (SWTI) (-12%), exercise was also demonstrated to have comparable effects. While the combination of CoQ10 supplementation and exercise resulted in the greatest benefit in these categories, the only significant synergistic effect observed between the two treatments was for peak SWTI.

A 2013 meta-analysis serves as the most recent and comprehensive review of the effects of CoQ10 supplementation on HF, specifically its impact on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF.[24] The study found 120 potentially relevant studies during a literature review and selected 13 for the analysis, of which 7 were crossover and 6 were parallel-arm studies, with 12 double-blinded studies and 1 single-blind study. The enrollment of the analyzed studies was 395. A confounder in the analysis was the wide range in study duration (4 to 28 weeks) and variable CoQ10 daily dosing (60 to 300mg). Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and a 0.30 decrease (95% CI: -0.66, 0.06) in the NYHA functional class. Significant improvement in EF was seen in crossover trials, trials twelve weeks long or longer, studies published before 1994, studies with a daily CoQ10 dose >=100 mg, and in patients with less severe CHF. The study cautiously suggests that CoQ10 supplementation may improve EF in patients with CHF.

Q-SYMBIO Trial

In a modest sized, multicenter, double blind,randomized controlled trial, 420 patients with New York Heart Association (NYHA) Class III or IV heart failure who were receiving standard therapy, were randomized to either CoQ10 or placebo. The patients were followed for two years. [25]. The primary endpoint (MACE=unplanned hospitalization due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support) was reduced from 29 events (14%) in patients randomized to CoQ10 compared to 55 (25%) in patients randomized to placebo (hazard ratio=2; p=0.003 by time to event analysis). Randomization to CoQ10 was associated with a halving of all cause mortality: there were 18 (9%) deaths among patients in the CoQ10 group versus 36 (17%) deaths among patients in the placebo group (hazard ratio=2.1; p=0.01). Cardiovascular mortality was also reduced (p-0.02) as was the risk of rehospitalisations for heart failure (p=0.05). There tended to be fewer adverse events among patients randomized to CoQ10 compared to the placebo (p=0.073). It is unclear if there were greater benefits among patients treated with statins, drugs that lower CoQ10.

Treatment of Statin Intolerance

CoQ10 shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of CoQ10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[26] and statins, a class of cholesterol-lowering drugs.[27] Statins can reduce serum levels of CoQ10 by up to 40%.[28] 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.[29][30]

Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if CoQ10 is administered in addition to commencing active cooling (to 32–34 degrees Celsius).[31]

Migraine headaches

Supplementation of CoQ10 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,[32] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.[33] Dosages were 150 to 300 mg/day.

Cancer

It is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.[34]

Brain health and neurodegenerative diseases

Recent studies have shown that the antioxidant properties of CoQ10 benefit the body and the brain in animal models.[35] Some of these studies indicate that CoQ10 protects the brain from neurodegenerative disease such as Parkinson's,[36] although it does not relieve the symptoms.[37] Dosage was 300 mg per day.

Lifespan

Studies have shown that low dosages of CoQ10 reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and CoQ10supplementation leads to a longer lifespan in rats[38]

See Also

  • Idebenone - synthetic analog with reduced oxidant generating properties

External links

References

  1. ↑ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
  2. ↑ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
  3. ↑ Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292
  4. ↑ Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234
  5. ↑ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
  6. ↑ CRANE, FL.; HATEFI, Y.; LESTER, RL.; WIDMER, C. (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta. 25 (1): 220–1. PMID 13445756. Unknown parameter |month= ignored (help)
  7. ↑ Lenaz, G. (1988). "Role of mobility of redox components in the inner mitochondrial membrane". J Membr Biol. 104 (3): 193–209. PMID 2850362. Unknown parameter |month= ignored (help)
  8. ↑ Mitchell, P. (1976). "Possible molecular mechanisms of the protonmotive function of cytochrome systems". J Theor Biol. 62 (2): 327–67. PMID 186667. Unknown parameter |month= ignored (help)
  9. ↑ "Highlights in ubiquinone research: proceedings of the International ... - Giorgio Lenaz, Universit di Bologna - Google Books". Retrieved 28 May 2013.
  10. ↑ Ernster, L.; Forsmark-Andrée, P. (1993). "Ubiquinol: an endogenous antioxidant in aerobic organisms". Clin Investig. 71 (8 Suppl): S60–5. PMID 8241707.
  11. ↑ Villalba, JM.; Navarro, F.; Gómez-Díaz, C.; Arroyo, A.; Bello, RI.; Navas, P. (1997). "Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane". Mol Aspects Med. 18 Suppl: S7–13. PMID 9266501.
  12. ↑ Groneberg, DA.; Kindermann, B.; Althammer, M.; Klapper, M.; Vormann, J.; Littarru, GP.; Döring, F. (2005). "Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells". Int J Biochem Cell Biol. 37 (6): 1208–18. doi:10.1016/j.biocel.2004.11.017. PMID 15778085. Unknown parameter |month= ignored (help)
  13. ↑ Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec
  14. ↑ www.thefactsaboutfitness.com
  15. ↑ Berbel-Garcia, A. (2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology. 27: 187–191. PMID 15319706. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  16. ↑ Folkers, K.; Littarru, GP.; Ho, L.; Runge, TM.; Havanonda, S.; Cooley, D. (1970). "Evidence for a deficiency of coenzyme Q10 in human heart disease". Int Z Vitaminforsch. 40 (3): 380–90. PMID 5450999.
  17. ↑ Littaru, GP.; Ho, L.; Folkers, K. (1972). "Deficiency of coenzyme Q 10 in human heart disease. I.". Int J Vitam Nutr Res. 42 (2): 291–305. PMID 5053855.
  18. ↑ Folkers, K.; Vadhanavikit, S.; Mortensen, SA. (1985). "Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10". Proc Natl Acad Sci U S A. 82 (3): 901–4. PMID 3856239. Unknown parameter |month= ignored (help)
  19. ↑ Rosenfeldt, FL.; Haas, SJ.; Krum, H.; Hadj, A.; Ng, K.; Leong, JY.; Watts, GF. (2007). "Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials". J Hum Hypertens. 21 (4): 297–306. doi:10.1038/sj.jhh.1002138. PMID 17287847. Unknown parameter |month= ignored (help)
  20. ↑ Tiano, L.; Belardinelli, R.; Carnevali, P.; Principi, F.; Seddaiu, G.; Littarru, GP. (2007). "Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study". Eur Heart J. 28 (18): 2249–55. doi:10.1093/eurheartj/ehm267. PMID 17644511. Unknown parameter |month= ignored (help)
  21. ↑ Landmesser, U.; Merten, R.; Spiekermann, S.; Büttner, K.; Drexler, H.; Hornig, B. (2000). "Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation". Circulation. 101 (19): 2264–70. PMID 10811593. Unknown parameter |month= ignored (help)
  22. ↑ "related:mdvAhRE800UJ:scholar.google.com/ - Google Scholar". Retrieved 28 May 2013. External link in |title= (help)
  23. ↑ Belardinelli, R.; Muçaj, A.; Lacalaprice, F.; Solenghi, M.; Seddaiu, G.; Principi, F.; Tiano, L.; Littarru, GP. (2006). "Coenzyme Q10 and exercise training in chronic heart failure". Eur Heart J. 27 (22): 2675–81. doi:10.1093/eurheartj/ehl158. PMID 16882678. Unknown parameter |month= ignored (help)
  24. ↑ Fotino, AD.; Thompson-Paul, AM.; Bazzano, LA. (2013). "Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis". Am J Clin Nutr. 97 (2): 268–75. doi:10.3945/ajcn.112.040741. PMID 23221577. Unknown parameter |month= ignored (help)
  25. ↑ http://www.escardio.org/about/press/press-releases/pr-13/Pages/first-drug-in-decade-improves-heart-failure-mortality.aspx
  26. ↑ 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.
  27. ↑ The Synthesis of Cholesterol
  28. ↑ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol. 33 (3): 226–9. PMID 8463436.
  29. ↑ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs. 16 (4): 9–20. PMID 12597259.
  30. ↑ 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.
  31. ↑ Damian, M. S. (2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation. 110: 3011–3016. Retrieved 2006-12-01. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  32. ↑ 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. PMID 11972582.
  33. ↑ Sándor PS; et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology. 64: 713–715.
  34. ↑ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
  35. ↑ Matthews, R. T. (1998). "Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects". PNAS. 95: 8892–8897. Retrieved 2006-12-01. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  36. ↑ Biol Signals Recept. 2001 May-Aug;10(3-4):224-53
  37. ↑ Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group (May 14, 2007). "Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease". Archives of Neurologu.
  38. ↑ 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. PMID 15036411.


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