Template:Short description Template:Cs1 config Template:Use American English Template:Use dmy dates Template:Chembox
Coenzyme Q10 (CoQ10 Template:IPAc-en), also known as ubiquinone, is a naturally occurring biochemical cofactor (coenzyme) and an antioxidant produced by the human body.<ref name="lpi">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="sood">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="nccih">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, and dietary supplements.<ref name=lpi/><ref name=sood/> CoQ10 is found in many organisms, including animals and bacteria.
CoQ10 plays a role in mitochondrial oxidative phosphorylation, aiding in the production of adenosine triphosphate (ATP), which is involved in energy transfer within cells.<ref name=lpi/> The structure of CoQ10 consists of a benzoquinone moiety and an isoprenoid side chain, with the "10" referring to the number of isoprenyl chemical subunits in its tail.<ref name="pmid36768907">Template:Cite journalTemplate:Creative Commons text attribution notice</ref><ref name="Kadian-2022">Template:Cite journal</ref><ref name="pmid34064686">Template:Cite journalTemplate:Creative Commons text attribution notice</ref>
Although a ubiquitous molecule in human tissues, CoQ10 is not a dietary nutrient and does not have a recommended intake level, and its use as a supplement is not approved in the United States for any health or anti-disease effect.<ref name=lpi/><ref name=sood/>
Biological functionsEdit
Template:See also CoQ10 is a component of the mitochondrial electron transport chain (ETC), where it plays a role in oxidative phosphorylation, a process required for the biosynthesis of adenosine triphosphate, the primary energy source of cells.<ref name=lpi/><ref name="pmid34064686"/><ref name="pmid34596729">Template:Cite journal</ref>
CoQ10 is a lipophilic molecule that is located in all biological membranes of human body and serves as a component for the synthesis of ATP and is a life-sustaining cofactor for the three complexes (complex I, complex II, and complex III) of the ETC in the mitochondria.<ref name=lpi/><ref name="Kadian-2022"/> CoQ10 has a role in the transport of protons across lysosomal membranes to regulate pH in lysosome functions.<ref name=lpi/>
The mitochondrial oxidative phosphorylation process occurs in the inner mitochondrial membrane of eukaryotic cells.<ref name=lpi/> This membrane is highly folded into structures called cristae, which increase the surface area available for oxidative phosphorylation. CoQ10 plays a role in this process as an essential cofactor of the ETC located in the inner mitochondrial membrane and serves the following functions:<ref name=lpi/><ref name="pmid34596729"/>
- electron transport in the mitochondrial ETC, by shuttling electrons from mitochondrial complexes like nicotinamide adenine dinucleotide (NADH), ubiquinone reductase (complex I), and succinate ubiquinone reductase (complex II), the fatty acids and branched-chain amino acids oxidation (through flavin-linked dehydrogenases) to ubiquinol–cytochrome-c reductase (complex III) of the ETC:<ref name=lpi/><ref name="pmid34596729"/> CoQ10 participates in fatty acid and glucose metabolism by transferring electrons generated from the reduction of fatty acids and glucose to electron acceptors;<ref name="pmid33291255">Template:Cite journalTemplate:Creative Commons text attribution notice</ref>
- antioxidant activity as a lipid-soluble antioxidant together with vitamin E, scavenging reactive oxygen species and protecting cells against oxidative stress,<ref name=lpi/><ref name="pmid34064686"/> inhibiting the oxidation of proteins, DNA, and use of vitamin E.<ref name=lpi/><ref name="pmid32349341">Template:Cite journalTemplate:Creative Commons text attribution notice</ref>
BiochemistryEdit
Template:Expert needed Coenzymes Q is a coenzyme family that is ubiquitous in animals and many Pseudomonadota,<ref name="pmid20599680">Template:Cite journal</ref> a group of gram-negative bacteria. The fact that the coenzyme is ubiquitous gives the origin of its other name, ubiquinone.<ref name=lpi/><ref name=sood/><ref name="pubchem-Ubidecarenone">Template:Include-USGov</ref> In humans, the most common form of coenzymes Q is coenzyme Q10, also called CoQ10 (Template:IPAc-en) or ubiquinone-10.<ref name=lpi/>
Coenzyme Q10 is a 1,4-benzoquinone, in which "Q" refers to the quinone chemical group and "10" refers to the number of isoprenyl chemical subunits (shown enclosed in brackets in the diagram) in its tail.<ref name=lpi/> In natural ubiquinones, there are from six to ten subunits in the tail, with humans having a tail of 10 isoprene units (50 carbon atoms) connected to its benzoquinone "head".<ref name=lpi/>
This family of fat-soluble substances is present in all respiring eukaryotic cells, primarily in the mitochondria.<ref name=lpi/> Ninety-five percent of the human body's energy is generated this way.<ref name="pmid7599208">Template:Cite journal</ref> Organs with the highest energy requirements—such as the heart, liver, and kidney—have the highest CoQ10 concentrations.<ref name="pmid2599795">Template:Cite journal</ref><ref name="pmid1586151">Template:Cite journal</ref><ref name="pmid8288904">Template:Cite journal</ref><ref name="Žmitek-2008">Template:Cite journal</ref>
There are three redox states of CoQ: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol).<ref name=lpi/> The capacity of this molecule to act as a two-electron carrier (moving between the quinone and quinol form) and a one-electron carrier (moving between the semiquinone and one of these other forms) is central to its role in the electron transport chain due to the iron–sulfur clusters that can only accept one electron at a time and as a free radical–scavenging antioxidant.<ref name=lpi/><ref name="pubchem-Ubidecarenone"/>
DeficiencyEdit
There are two major pathways of deficiency of CoQ10 in humans: reduced biosynthesis, and increased use by the body.<ref name="pmid25091424">Template:Cite journal</ref> Biosynthesis is the major source of CoQ10. Biosynthesis requires at least 15 genes, and mutations in any of them can cause CoQ deficiency.<ref name="pmid25091424"/> CoQ10 levels also may be affected by other genetic defects (such as mutations of mitochondrial DNA, ETFDH, APTX, FXN, and BRAF, genes that are not directly related to the CoQ10 biosynthetic process).<ref name="pmid25091424"/> Some of these, such as mutations in COQ6, can lead to serious diseases such as steroid-resistant nephrotic syndrome with sensorineural deafness.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
AssessmentEdit
Although CoQ10 may be measured in blood 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.<ref name="pmid21844807">Template:Cite journal</ref> Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of 14C-labeled p-hydroxybenzoate.<ref name="pmid18387363">Template:Cite journal</ref>
CoQ10 is studied as an adjunctive therapy to reduce inflammation in periodontitis.<ref name="pmid37592831">Template:Cite journal</ref>
StatinsEdit
Although statins may reduce CoQ10 in the blood it is unclear if they reduce CoQ10 in muscle.<ref name="pmid28546301"/> Evidence does not support that supplementation improves statin side effects.<ref name="pmid28546301">Template:Cite journal</ref><ref>Template:Cite journal</ref>
Chemical propertiesEdit
The oxidized structure of CoQ10 is shown below. The various kinds of coenzyme Q may be distinguished by the number of isoprenoid subunits in their side-chains. The most common coenzyme Q in human mitochondria is CoQ10.<ref name=lpi/> Q refers to the quinone head and "10" refers to the number of isoprene repeats in the tail. The molecule below has three isoprenoid units and would be called Q3.
In its pure state, it is an orange-colored lipophile powder and has no taste or odor.<ref name="pubchem-Ubidecarenone"/>
BiosynthesisEdit
Biosynthesis occurs in most human tissue. There are three major steps:
- Creation of the benzoquinone structure (using phenylalanine or tyrosine, via 4-hydroxybenzoate)
- Creation of the isoprene side chain (using acetyl-CoA)
- The joining or condensation of the above two structures
The initial two reactions occur in mitochondria, the endoplasmic reticulum, and peroxisomes, indicating multiple sites of synthesis in animal cells.<ref name="pmid20494114">Template:Cite journal</ref>
An important enzyme in this pathway is HMG-CoA reductase, usually a target for intervention in cardiovascular complications. The "statin" family of cholesterol-reducing medications inhibits HMG-CoA reductase. One possible side effect of statins is decreased production of CoQ10, which may be connected to the development of myopathy and rhabdomyolysis. However, the role statins play in CoQ deficiency is controversial. Although statins reduce blood levels of CoQ, studies on the effects of muscle levels of CoQ are yet to come. CoQ supplementation also does not reduce side effects of statin medications.<ref name="pmid21844807"/><ref name="pmid28546301"/>
Genes involved include PDSS1, PDSS2, COQ2, and ADCK3 (COQ8, CABC1).<ref name="Espinós-2009">Template:Cite book</ref>
Organisms other than humans produce the benzoquinone and isoprene structures from somewhat different source chemicals. For example, the bacteria E. coli produces the former from chorismate and the latter from a non-mevalonate source. The common yeast S. cerevisiae, however, derives the former from either chorismate or tyrosine and the latter from mevalonate. Most organisms share the common 4-hydroxybenzoate intermediate, yet again uses different steps to arrive at the "Q" structure.<ref name="pmid11583838">Template:Cite journal</ref>
Dietary supplementEdit
Although neither a prescription drug nor an essential nutrient, CoQ10 is commonly used as a dietary supplement with the intent to prevent or improve disease conditions, such as cardiovascular disorders.<ref name=sood/><ref name="arenas">Template:Cite journal</ref> CoQ10 is naturally produced by the body and plays a crucial role in cell growth and protection.<ref name="pmid34064686"/> Despite its significant role in the body, it is not used as a drug to treat any specific disease.<ref name=lpi/><ref name=sood/><ref name=nccih/>
Nevertheless, CoQ10 is widely available as an over-the-counter dietary supplement and is recommended by some healthcare professionals, despite a lack of definitive scientific evidence supporting these recommendations,<ref name=lpi/><ref name=nccih/> especially when it comes to cardiovascular diseases.<ref name="pmid36852817">Template:Cite journal</ref>
Regulation and compositionEdit
CoQ10 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition.<ref name="canter-patient">Template:Include-USGov</ref><ref name="pmid26389329">Template:Cite book</ref><ref name="White-2014">Template:Include-USGov</ref><ref name="nice.org.uk-2017">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> However, it is sold as a dietary supplement not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics.<ref name="pmid10953455">Template:Cite journal</ref> The manufacture of CoQ10 is not regulated, and different batches and brands may vary significantly.<ref name="White-2014"/>
ResearchEdit
A 2014 Cochrane review found insufficient evidence to make a conclusion about its use for the prevention of heart disease.<ref name="pmid25474484">Template:Cite journal</ref> A 2016 Cochrane review concluded that CoQ10 had no effect on blood pressure.<ref name="pmid26935713">Template:Cite journal</ref> A 2021 Cochrane review found "no convincing evidence to support or refute" the use of CoQ10 for the treatment of heart failure.<ref name="pmid35608922">Template:Cite journal</ref>
A 2017 meta-analysis of people with heart failure taking 30–100 mg/d of CoQ10 found a 31% lower mortality and increased exercise capacity, with no significant difference in the endpoints of left heart ejection fraction.<ref name="pmid28738783">Template:Cite journalTemplate:Creative Commons text attribution notice</ref> A 2021 meta-analysis found that coenzyme Q10 was associated with a 31% lower all-cause mortality in HF patients.<ref>Template:Cite journal</ref> In a 2023 meta-analysis of older people, ubiquinone had evidence of a cardiovascular effect, but ubiquinol did not.<ref name="pmid37971634">Template:Cite journal</ref>
Although CoQ10 has been studied as a potential remedy to treat purported muscle-related side effects of statin medications, the results were mixed. Although a 2018 meta-analysis concluded that there was preliminary evidence for oral CoQ10 reducing statin-associated muscle symptoms, including muscle pain, muscle weakness, muscle cramps, and muscle tiredness,<ref name="pmid30371340">Template:Cite journalTemplate:Creative Commons text attribution notice</ref> 2015<ref name="pmid25440725"/> and 2024<ref name="pmid36852817"/> meta-analysis found that CoQ10 had no effect on statin myopathy.<ref name="pmid25440725">Template:Cite journal</ref><ref name="pmid36852817"/>
CoQ10 is studied as an adjunctive therapy to reduce inflammation in periodontitis.<ref name="pmid37592831"/>
PharmacologyEdit
AbsorptionEdit
CoQ10 in the pure form is a crystalline powder insoluble in water. Absorption as a pharmacological substance follows the same process as that of lipids; the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient.<ref name="Žmitek-2008"/> This process in the human body involves secretion into the small intestine of pancreatic enzymes and bile, which facilitates emulsification and micelle formation required for absorption of lipophilic substances.<ref name="pmid16551570">Template:Cite journal</ref> Food intake (and the presence of lipids) stimulates bodily biliary excretion of bile acids and greatly enhances absorption of CoQ10. Exogenous CoQ10 is absorbed from the small intestine and is best absorbed if taken with a meal. Serum concentration of CoQ10 in fed condition is higher than in fasting conditions.<ref name="Bogentoft-1991">Template:Cite book</ref><ref name="pmid17666877">Template:Cite journalTemplate:Verify source</ref>
MetabolismEdit
CoQ10 is metabolized in all tissues, with the metabolites phosphorylated in cells.<ref name=sood/> CoQ10 is reduced to ubiquinol during or after absorption in the small intestine.<ref name=sood/> It is absorbed by chylomicrons, and redistributed in the blood within lipoproteins.<ref name=sood/> Its elimination occurs via biliary and fecal excretion.<ref name=sood/>
PharmacokineticsEdit
Some reports have been published on the pharmacokinetics of CoQ10. The plasma peak can be observed 6–8 hours after oral administration when taken as a pharmacological substance.<ref name=sood/> In some studies, a second plasma peak was observed approximately 24 hours after administration, probably due to enterohepatic recycling and redistribution from the liver to circulation.<ref name="pmid16551570" />
Deuterium-labeled crystalline CoQ10 was used to investigate pharmacokinetics in humans to determine an elimination half-time of 33 hours.<ref name="pmid3781673">Template:Cite journal</ref>
BioavailabilityEdit
In contrast to the intake of CoQ10 as a constituent of food, such as nuts or meat, from which CoQ10 is normally absorbed, there is a concern about CoQ10 bioavailability when it is taken as a dietary supplement.<ref name="mantle">Template:Cite journal</ref><ref>Template:Cite journal</ref> Bioavailability of CoQ10 supplements may be reduced due to the lipophilic nature of its molecule and large molecular weight.<ref name=mantle/>
Reduction of particle sizeEdit
Nanoparticles have been explored as a delivery system for various drugs, such as improving the oral bioavailability of drugs with poor absorption characteristics.<ref name="pmid9121559">Template:Cite journal</ref> However, this has not proved successful with CoQ10, although reports have differed widely.<ref name="pmid14621964">Template:Cite journalTemplate:Verify source</ref><ref name="pmid12564745">Template:Cite journalTemplate:Verify source</ref> The use of aqueous suspension of finely powdered CoQ10 in pure water also reveals only a minor effect.<ref name="pmid3718593">Template:Cite journal</ref>
Water-solubilityEdit
Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and also is 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 despite the many attempts to optimize their composition.<ref name="Žmitek-2008" /> Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with the polymer tyloxapol,<ref name="USP619">Template:Cite patent</ref> formulations based on various solubilising agents, such as hydrogenated lecithin,<ref name="US 4483873">Template:Cite patent</ref> and complexation with cyclodextrins; among the latter, the complex with β-cyclodextrin has been found to have highly increased bioavailability<ref name="pmid18645245">Template:Cite journal</ref><ref name="Kagan-2010">Template:Cite journal</ref> and also is used in pharmaceutical and food industries for CoQ10-fortification.<ref name="Žmitek-2008" />
Adverse effects and precautionsEdit
Generally, oral CoQ10 supplementation is well tolerated.<ref name=lpi/> The most common side effects are gastrointestinal symptoms (nausea, vomiting, appetite suppression, and abdominal pain), rashes, and headaches.<ref name="pmid20601617">Template:Cite journal</ref> Some adverse effects, largely gastrointestinal, are reported with intakes.<ref name=sood/> Doses of 100–300 mg per day may induce insomnia or elevate liver enzymes.<ref name=sood/> The observed safe level risk assessment method indicated that the evidence of safety is acceptable at intakes up to 1200 mg per day.<ref name="pmid16814438">Template:Cite journal</ref>
Caution should be observed in the use of CoQ10 supplementation in people with bile duct obstruction and during pregnancy or breastfeeding.<ref name=sood/>
Potential drug interactionsEdit
CoQ10 taken as a pharmacological substance has potential to inhibit the effects of theophylline as well as the anticoagulant warfarin; CoQ10 may interfere with warfarin's actions by interacting with cytochrome p450 enzymes thereby reducing the INR, a measure of blood clotting.<ref name="pmid27012265">Template:Cite journal</ref> The structure of CoQ10 is similar to that of vitamin K, which competes with and counteracts warfarin's anticoagulation effects. CoQ10 is not recommended in people taking warfarin due to the increased risk of clotting.<ref name="pmid20601617"/>
Dietary concentrationsEdit
Detailed reviews on occurrence of CoQ10 and dietary intake were published in 2010.<ref name="pmid20301015">Template:Cite journal</ref> Besides the endogenous synthesis within organisms, CoQ10 also is supplied by various foods.<ref name=lpi/> CoQ10 concentrations in various foods are:<ref name=lpi/>
| Food | CoQ10 concentration (mg/kg) | |
|---|---|---|
| Vegetable oils | soybean oil | 54–280 |
| olive oil | 40–160 | |
| grapeseed oil | 64–73 | |
| sunflower oil | 4–15 | |
| canola oil | 64–73 | |
| Beef | heart | 113 |
| liver | 39–50 | |
| muscle | 26–40 | |
| Pork | heart | 12–128 |
| liver | 23–54 | |
| muscle | 14–45 | |
| Chicken | breast | 8–17 |
| thigh | 24–25 | |
| wing | 11 | |
| Fish | sardine | 5–64 |
| mackerel – red flesh | 43–67 | |
| mackerel – white flesh | 11–16 | |
| salmon | 4–8 | |
| tuna | 5 | |
| Nuts | peanut | 27 |
| walnut | 19 | |
| sesame seed | 18–23 | |
| pistachio | 20 | |
| hazelnut | 17 | |
| almond | 5–14 | |
| Vegetables | parsley | 8–26 |
| broccoli | 6–9 | |
| cauliflower | 2–7 | |
| spinach | up to 10 | |
| Chinese cabbage | 2–5 | |
| Fruit | avocado | 10 |
| blackcurrant | 3 | |
| grape | 6–7 | |
| strawberry | 1 | |
| orange | 1–2 | |
| grapefruit | 1 | |
| apple | 1 | |
| banana | 1 | |
Vegetable oils, meat, and fish are rich in CoQ10.<ref name=lpi/> Dairy products are much poorer sources of CoQ10 than animal tissues. Among vegetables, broccoli and cauliflower are good sources of CoQ10.<ref name=lpi/> Most fruits and berries are poor sources of CoQ10, except avocados, which have relatively high oil and CoQ10 content.<ref name="pmid20301015" />
IntakeEdit
In the developed world, the estimated daily intake of CoQ10 has been determined at 3–6 mg per day, derived primarily from meat.<ref name="pmid20301015" />
South Koreans have an estimated average daily CoQ (Q9 + Q10) intake of 11.6 mg/d, derived primarily from kimchi.<ref name="doijfca">Template:Cite journal</ref>
Effect of heat and processingEdit
Cooking by frying reduces CoQ10 content by 14–32%.<ref name="pmid9129255">Template:Cite journal</ref>
HistoryEdit
In 1950, a small amount of CoQ10 was isolated from the lining of a horse's gut, a compound initially called substance SA, but later deemed to be quinone found in many animal tissues.<ref name="pmid13622652">Template:Cite journal</ref> In 1957, the same compound was isolated from mitochondrial membranes of beef heart, with research showing that it transported electrons within mitochondria. It was called Q-275 as a quinone.<ref name="pmid13622652"/><ref name="pmid13445756">Template:Cite journal</ref> The Q-275/substance SA was later renamed ubiquinone as it was a ubiquitous quinone found in all animal tissues.<ref name="pmid13622652"/> In 1958, its full chemical structure was reported.<ref name="pmid13622652"/><ref name="Wolf-1958">Template:Cite journal</ref> Ubiquinone was later called either mitoquinone or coenzyme Q due to its participation to the mitochondrial electron transport chain.<ref name="pmid13622652"/> In 1966, a study reported that reduced CoQ6 was an effective antioxidant in cells.<ref name="pmid17805631">Template:Cite journal</ref>
See alsoEdit
- Idebenone – synthetic analog with reduced oxidant-generating properties
- Mitoquinone mesylate – synthetic analog with improved mitochondrial permeability
ReferencesEdit
Template:Electron transport chain Template:Enzyme cofactors Template:Antioxidants