Coenzyme Q10

Coenzyme Q, also known as ubiquinone, is a naturally occurring biochemical cofactor and an antioxidant produced by the human body. The human body mainly produces the form known as coenzyme Q₁₀, but other forms exist. CoQ is used by and found in many organisms, including animals and bacteria. As a result, it can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, and dietary supplements.
CoQ plays a role in mitochondrial oxidative phosphorylation, aiding in the production of adenosine triphosphate, which is involved in energy transfer within cells. 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.
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.

Biological functions

CoQ₁₀ is a component of the mitochondrial electron transport chain, where it plays a role in oxidative phosphorylation, a process required for the biosynthesis of adenosine triphosphate, the primary energy source of cells.
CoQ₁₀ is a lipophilic molecule that is located in all biological membranes of the human body and serves as a component for the synthesis of ATP and is a life-sustaining cofactor for the three complexes of the ETC in the mitochondria. CoQ₁₀ has a role in the transport of protons across lysosomal membranes to regulate pH in lysosome functions.
The mitochondrial oxidative phosphorylation process occurs in the inner mitochondrial membrane of eukaryotic cells. 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:

electron transport in the mitochondrial ETC, by shuttling electrons from mitochondrial complexes like nicotinamide adenine dinucleotide, ubiquinone reductase, and succinate ubiquinone reductase, the fatty acids and branched-chain amino acids oxidation to ubiquinol–cytochrome-c reductase of the ETC: CoQ₁₀ participates in fatty acid and glucose metabolism by transferring electrons generated from the reduction of fatty acids and glucose to electron acceptors;
antioxidant activity as a lipid-soluble antioxidant together with vitamin E, scavenging reactive oxygen species and protecting cells against oxidative stress, inhibiting the oxidation of proteins, DNA, and use of vitamin E.
Biochemistry

is a quinone and functions as an electron carrier in the mitochondrial electron transport chain of eukaryotes and many bacteria. The other name for CoQ is ubiquinone which was assigned by the IUPAC-IUB Commission on Biochemical Nomenclature in 1975 due to its ubiquitous presence from bacteria to humans. In humans the isoprene side chain has ten isoprene units, hence the abbreviation CoQ₁₀.
Coenzymes Q is a coenzyme family that is ubiquitous in animals and many Pseudomonadota, a group of gram-negative bacteria. The fact that the coenzyme is ubiquitous gives the origin of its other name, ubiquinone. In humans, the most common form of coenzymes Q is coenzyme Q₁₀, also called CoQ₁₀ or ubiquinone-10.
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 in its tail. In natural ubiquinones, there are from six to ten subunits in the tail, with humans having a tail of 10 isoprene units connected to its benzoquinone "head".
This family of fat-soluble substances is present in all respiring eukaryotic cells, primarily in the mitochondria. Ninety-five percent of the human body's energy is generated this way. Organs with the highest energy requirements—such as the heart, liver, and kidney—have the highest CoQ₁₀ concentrations.
There are three redox states of CoQ: fully oxidized, semiquinone, and fully reduced. The capacity of this molecule to act as a two-electron carrier and a one-electron carrier 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.

Deficiency

There are two major pathways of deficiency of CoQ₁₀ in humans: reduced biosynthesis, and increased use by the body. Biosynthesis is the major source of CoQ₁₀. Biosynthesis requires at least 15 genes, and mutations in any of them can cause CoQ deficiency. CoQ₁₀ levels also may be affected by other genetic defects. Some of these, such as mutations in COQ6, can lead to serious diseases such as steroid-resistant nephrotic syndrome with sensorineural deafness.

Assessment

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. Culture fibroblasts can be used also to evaluate the rate of endogenous CoQ₁₀ biosynthesis, by measuring the uptake of ¹⁴C-labeled p-hydroxybenzoate.
CoQ₁₀ is studied as an adjunctive therapy to reduce inflammation in periodontitis.

Statins

Although statins may reduce CoQ₁₀ in the blood it is unclear if they reduce CoQ₁₀ in muscle. Evidence does not support that supplementation improves statin side effects.

Chemical properties

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. 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.

Biosynthesis

Biosynthesis occurs in most human tissue. There are three major steps:

Creation of the benzoquinone structure
Creation of the isoprene side chain
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.
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.
Genes involved include PDSS1, PDSS2, COQ2, and ADCK3.
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.

Dietary supplement

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. Despite its significant role in the body, it is not used as a drug to treat any specific disease.
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, especially when it comes to cardiovascular diseases.

Regulation and composition

CoQ₁₀ is not approved by the U.S. Food and Drug Administration for the treatment of any medical condition. However, it is sold as a dietary supplement not subject to the same regulations as medicinal drugs, and is an ingredient in some cosmetics. The manufacture of CoQ₁₀ is not regulated, and different batches and brands may vary significantly.

Research

A 2014 Cochrane review found insufficient evidence to make a conclusion about its use for the prevention of heart disease. A 2016 Cochrane review concluded that CoQ₁₀ had no effect on blood pressure. A 2021 Cochrane review found "no convincing evidence to support or refute" the use of CoQ₁₀ for the treatment of heart failure.
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. A 2021 meta-analysis found that CoQ₁₀ was associated with a 31% lower all-cause mortality in HF patients. In a 2023 meta-analysis of older people, ubiquinone had evidence of a cardiovascular effect, but ubiquinol did not.
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, 2015 and 2024 meta-analysis found that CoQ₁₀ had no effect on statin myopathy.