Ubiquinol
Encyclopedia
Ubiquinol is an electron-rich (reduced) form of coenzyme Q10.
The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side chain is 9-10 units long in mammal
s. Coenzyme Q10 (CoQ10) exists in three redox
states, fully oxidized (ubiquinone), partially reduced
(semiquinone
or ubisemiquinone), and fully reduced (ubiquinol). The redox functions of ubiquinol in cellular energy production
and antioxidant
protection are based on the ability to exchange two electron
s in a redox cycle between ubiquinol (reduced) and the ubiquinone (oxidized) form.
Ubiquinol is a lipid
-soluble benzoquinol that is found in all cellular systems and in nearly every cell
, tissue
and organ in mammals. Ubiquinol is acquired through biosynthesis
, supplementation and in small amounts from diet
. Ubiquinol has an established role as an essential component of the electron transport chain
transferring electrons resulting in ATP synthesis. In mammals ATP production takes place predominantly in mitochondria and to a lesser extent in other organelle
s such as the Golgi apparatus
or endoplasmic reticulum
. The mitochondria typically produce nearly 95% of the energy required for cellular growth, development and healthy metabolism
. The antioxidant action of ubiquinol is now considered to be one of the most important functions in cellular systems. Ubiquinol is a potent lipophilic
antioxidant capable of regenerating other antioxidants such as tocopherol (Vitamin E
) and ascorbate (Vitamin C
). Recent studies also reveal function in gene expression
involved in human cell signaling
, metabolism and transport.
increased nearly twofold from 24% to 45%. The ejection fraction is a an assessment method that measures the ability of the heart’s ventricles to pump blood. While many factors can impact the ejection fraction including gender and method utilized for calculation, the typical healthy adult exhibits an ejection fraction of 60-65%. Additionally, beneficial effects in heart function could be demonstrated clinically, as subjects had an average improvement from NYHA Class IV to Class II. Based upon the recent clinical experience by Dr. Langsjoen, the therapeutic plasma CoQ10 levels are now considered to be >3.5 μg/ml, which is a significantly higher blood value than the >2.5μg/ml target in the past. In this study, there were no adverse effects of ubiquinone or ubiquinol, nor any drug interaction including patients on coumadin.
In 2010, researchers from Germany’s University of Kiel and Japan’s Shinshu University published a study examining genome-expression effects of ubiquinol and ubiquinone in an experimental model utilizing SAMP1 (Senescence Accelerated Mice Prone 1) mice. After 14 months of supplementation, the mice liver tissue was analyzed for a variety of gene expressions via microarray testing. The gene expression profiling demonstrated a functional connection between ubiquinol and the following signaling pathways: PPAR-α, LXR/RXR, and FXR/RXR. In all, eleven different ubiquinol-dependent genes related to cholesterol and lipid/lipoprotein metabolism were identified. With the exception of one gene, ubiquinone did not have any effect on these genes.
Some preliminary information indicates that ubiquinol may be involved in the aging process, as scientists have evaluated the ubiquinone and ubiquinol blood levels in subjects of different age groups. Not only do aged subjects have reduced CoQ10 biosynthesis, their ability to convert ubiquinone to ubiquinol is also diminished. The specific alignment of ubiquinol was recently investigated by creating unilamellar vesicles containing ubiquinol to probe the antioxidant’s position in cellular membranes. Based on the fluorescence exposure to the vesicles, the scientists concluded that ubiquinol distributes closer to the cell membrane surface rather than the interior hydrophobic region of the membranes.
A collaborative study between Waseda University and Tsukuba University demonstrated beneficial effects of ubiquinol on middle-aged and elderly women (average of 63.7 years of age). Following an eight week period of supplementation with 150 mg ubiquinol per day, subjects displayed significant improvements in physical activity and mental health scores (as measured by daily step count and SF-36 health survey).
Parkinson’s disease. MPTP is selectively toxic to cells of the substantia nigra, which are specialized cells in the brain stem involved in motor control and dopamine neurotransmitter synthesis. While both forms offered protection again MTPT-induced toxicity, ubiquinol exerted a stronger effect.
Researchers from the University of Sevilla in Spain identified that subjects with periodontitis had elevated mitochondrial ROS and significantly reduced coenzyme Q10 levels than subjects without periodontitis (60.2 pmol /mg protein versus 150.4 pmol Q, indicating a decline of 56%). A primary pathogenic factor giving rise to periodontal inflammation is the excess generation of reactive oxygen species (ROS). These ROS are leaked by the mitochondria as a by-product of the energy synthesis process.
While coenzyme Q10 is essential for mitochondrial synthesis of energy, it can also counter ROS formation, provided the coenzyme Q10 is in the ubiquinol form. Ubiquinol has specifically been shown to exert potent anti-inflammatory effects as seen in a genoexpression study involving human immune cells (monocytic cells known as THP-1). In that research model, the human immune cells were exposed to bacterial cell wall lipopolysaccharide (LPS) to induce expression and secretion of proinflammatory cytokines. Ubiquinol caused a reduction in the cellular release of various proinflammatory substances, specifically cytokine TNF-α and two chemokines.
The ubiquinol form of coenzyme Q10 has been studied specifically for its impact on oral health. Results were presented in June 2011 at the 63rd Meeting of the Vitamin Society of Japan by Nihon University School of Dentistry by researchers evaluating the effects of 150 mg of ubiquinol per day over a two month period in a double-blind, placebo-controlled clinical trial. The scientists measured various indicators of periodontal health including plaque adhesion, pocket depth, bleeding and gingival recession. Ubiquinol demonstrated significant benefits in plaque adhesion and an increase in the salivary antioxidant status, which are essential for the maintenance of oral health. A possible mechanism of these oral benefits maybe based on the antioxidant effect of ubiquinol, which could counteract periodontal inflammatory processes.
One factor that affects oral health is the amount of salivary secretion. Insufficient salivary secretion, also known as xerostomia, is associated with several negative effects including increased susceptibility to dental caries and periodontal disease. A comparative study by Japanese researchers examined the effects of ubiquinol and ubiquinone on salivary secretion. Sixty six patients were given either ubiquinol or ubiquinone at a dosage of 100 mg per day, or a placebo over a one month period. While both forms of orally administered coenzyme Q10 significantly enhanced salivary coenzyme Q10 levels, the ubiquinol form provided the greater rise in concentration: ubiquinone levels elevated from 60 to 87 ng/mL while ubiquinol elevated from 54.6 to 117.7 ng/mL. In addition, ubiquinol stimulated greater salivary secretion thus solidifying its position as the optimum form of coenzyme Q10 for oral health.
Further research along these lines demonstrate some of these genes related to the inflammation process to be redox-sensitive. An in vivo study was conducted utilizing both ubiquinone or ubiquinol on an accelerated aging rodent model strain called SAMP1. A variety of different tissues (liver, heart, brain, and kidney) were analyzed through microarray-based whole genomic expression profile. One of the findings was that ubiquinol was more effective than ubiquinone in raising CoQ10 levels in the liver (this effect of greater bioavailability has also been observed in humans). A review of the genome expression profiles on the liver samples revealed a ubiquinol-specific effect for genes in the PPAR-α (peroxisome proliferator activated receptor alpha) signaling pathway. Interestingly, these ubiquinol-sensitive genes are primarily involved in cholesterol synthesis (for example, 3-hydroxy-3-methylglutaryl-coenzyme A), lipid metabolism (FABP5), and lipoprotein metabolism (PLTP). These effects were specific for ubiquinol, as the regulation of PPAR-α genes was not observed with ubiquinone.
The reduction of ubiquinone to ubiquinol occurs in Complexes I & II in the electron transfer chain. The Q cycle is a process that occurs in cytochrome b
, a component of Complex III in the electron transport chain
,and that converts ubiquinol to ubiquinone in a cyclic fashion. When ubiquinol binds to cytochrome b, the pKa of the phenolic group decreases so that the proton ionizes and the phenoxide anion is formed.
If the phenoxide oxygen is oxidized, the semiquinone is formed with the unpaired electron being located on the ring.
A page on Proteopedia, Complex III of Electron Transport Chain, contains rotatable 3D structures of Complex III which can be used to study the peptide structures of Complex III and the mechanism of the Q cycle.
The natural ubiquinol form of coenzyme Q10 is 2,3-dimethoxy-5-methyl-6-poly prenyl-1,4-benzoquinol, where the polyprenylated side chain is 9-10 units long in mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s. Coenzyme Q10 (CoQ10) exists in three redox
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
states, fully oxidized (ubiquinone), partially reduced
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
(semiquinone
Semiquinone
Semiquinone is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone to quinone or alternatively the addition of a single H atom to a quinone....
or ubisemiquinone), and fully reduced (ubiquinol). The redox functions of ubiquinol in cellular energy production
Bioenergetics
Bioenergetics is the subject of a field of biochemistry that concerns energy flow through living systems. This is an active area of biological research that includes the study of thousands of different cellular processes such as cellular respiration and the many other metabolic processes that can...
and antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
protection are based on the ability to exchange two electron
Electron
The electron is a subatomic particle with a negative elementary electric charge. It has no known components or substructure; in other words, it is generally thought to be an elementary particle. An electron has a mass that is approximately 1/1836 that of the proton...
s in a redox cycle between ubiquinol (reduced) and the ubiquinone (oxidized) form.
Ubiquinol is a lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
-soluble benzoquinol that is found in all cellular systems and in nearly every cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
and organ in mammals. Ubiquinol is acquired through biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
, supplementation and in small amounts from diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
. Ubiquinol has an established role as an essential component of the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
transferring electrons resulting in ATP synthesis. In mammals ATP production takes place predominantly in mitochondria and to a lesser extent in other organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s such as the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
or endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
. The mitochondria typically produce nearly 95% of the energy required for cellular growth, development and healthy metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. The antioxidant action of ubiquinol is now considered to be one of the most important functions in cellular systems. Ubiquinol is a potent lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
antioxidant capable of regenerating other antioxidants such as tocopherol (Vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
) and ascorbate (Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
). Recent studies also reveal function in gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
involved in human cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
, metabolism and transport.
Nutrient function summary
Ubiquinol is the antioxidant form of CoQ10 and is essential for mitochondrial synthesis of energy. It is the only known lipid soluble antioxidant that is endogenously synthesized, protecting biological membranes against lipid peroxidation as well as regenerating other antioxidants such as Vitamin C and Vitamin E. Published clinical and experimental research shows that ubiquinol impacts cardiovascular health, neuronal metabolism, renal health, and genes related to lipid/lipoprotein metabolism and inflammation.Energy synthesis
In terms of its functions, ubiquinol's primary roles are in the synthesis of mitochondrial energy and as a protective antioxidant. The vitamin-like nutrient is found concentrated in the inner mitochondrial membrane where it serves as a carrier of reducing equivalents in the mitochondrial electron transport chain’s I and II complexes towards complex III. In this process, ubiquinol serves to produce ATP (adenosine triphosphate), the main energy intermediate in living organisms.Cardiovascular effects
Dr. Peter Langsjoen, a leading CoQ10 scientist and cardiologist based out of Tyler, Texas, has published research comparing effects of ubiquinone (oxidized, spent form) and ubiquinol (antioxidant form) on heart failure patients. The subjects in the study were classified as NYHA Class IV congestive heart failure and on maximal medical therapy. The patients were being administered a mean amount of 450 mg ubiquinone per day. Their blood levels of CoQ10 ranged from 0.9 to 2.0 mcg/mL plasma (mean value of 1.4 mcg/mL), an amount that the researcher considered subtherapeutic. Subjects were then switched over to 450 mg ubiquinol per day, and the follow up data from six of the subjects showed mean blood values of CoQ10 rose from 1.4 mcg/mL to 4.1 mcg/mL. In addition to the significant increase in plasma CoQ10, ejection fractionEjection fraction
In cardiovascular physiology, ejection fraction is the fraction of Blood pumped out of the Right Ventricle of the heart to the Pulmonary Circulation and Left Ventricle of the heart to the Systemic Circulation with each Heart beat or Cardiac cycle...
increased nearly twofold from 24% to 45%. The ejection fraction is a an assessment method that measures the ability of the heart’s ventricles to pump blood. While many factors can impact the ejection fraction including gender and method utilized for calculation, the typical healthy adult exhibits an ejection fraction of 60-65%. Additionally, beneficial effects in heart function could be demonstrated clinically, as subjects had an average improvement from NYHA Class IV to Class II. Based upon the recent clinical experience by Dr. Langsjoen, the therapeutic plasma CoQ10 levels are now considered to be >3.5 μg/ml, which is a significantly higher blood value than the >2.5μg/ml target in the past. In this study, there were no adverse effects of ubiquinone or ubiquinol, nor any drug interaction including patients on coumadin.
In 2010, researchers from Germany’s University of Kiel and Japan’s Shinshu University published a study examining genome-expression effects of ubiquinol and ubiquinone in an experimental model utilizing SAMP1 (Senescence Accelerated Mice Prone 1) mice. After 14 months of supplementation, the mice liver tissue was analyzed for a variety of gene expressions via microarray testing. The gene expression profiling demonstrated a functional connection between ubiquinol and the following signaling pathways: PPAR-α, LXR/RXR, and FXR/RXR. In all, eleven different ubiquinol-dependent genes related to cholesterol and lipid/lipoprotein metabolism were identified. With the exception of one gene, ubiquinone did not have any effect on these genes.
Antioxidant effects and aging
Ubiquinol is a potent lipid-soluble antioxidant capable of regenerating alpha tocopherol. It is important because it is the only lipid soluble antioxidant synthesized in the body. CoQ10 scientists have been investigating the relationship between suboptimal states marked by high levels of oxidative stress and the relative levels of ubiquinone and ubiquinol in the body - - both of which combined comprise a value called "total CoQ10". Disorders marked by elevated oxidative stress can cause major changes to the amounts of ubiquinol and ubiquinone in the body, a factor that is referred to by scientists as the ratio of ubiquinol to ubiquinone (ubiquinol:ubiquinone). Another way to describe this is through ubiquinol ratio, which is the percentage of ubiquinol in the total amount of CoQ10. A profound change was noted in the CoQ10 profile of type II diabetic subjects. Specifically, there was a decrease in the plasma ubiquinol ratio, suggesting a surge in oxidative stress. Another study also showed loss of ubiquinol in conditions marked by elevated oxidative stress. Subjects with hepatitis, cirrhosis, and hepatoma all exhibited a decrease in the ubiquinol concentrations, while the levels of total CoQ10 (ubiquinol + ubiquinone) was not reduced.Some preliminary information indicates that ubiquinol may be involved in the aging process, as scientists have evaluated the ubiquinone and ubiquinol blood levels in subjects of different age groups. Not only do aged subjects have reduced CoQ10 biosynthesis, their ability to convert ubiquinone to ubiquinol is also diminished. The specific alignment of ubiquinol was recently investigated by creating unilamellar vesicles containing ubiquinol to probe the antioxidant’s position in cellular membranes. Based on the fluorescence exposure to the vesicles, the scientists concluded that ubiquinol distributes closer to the cell membrane surface rather than the interior hydrophobic region of the membranes.
A collaborative study between Waseda University and Tsukuba University demonstrated beneficial effects of ubiquinol on middle-aged and elderly women (average of 63.7 years of age). Following an eight week period of supplementation with 150 mg ubiquinol per day, subjects displayed significant improvements in physical activity and mental health scores (as measured by daily step count and SF-36 health survey).
Neuronal health
A number of small studies have shown CoQ10 to benefit the neurological system, which includes the brain. In 2002, a study was published which examined the effects of CoQ10 (ubiquinone) in patients with early Parkinson’s disease. The scientists in that multi-center effort (Phase II study, funded by the National Institute of Neurological Disorders and Stroke [NINDS]) found that ubiquinone reduced the functional decline in Parkinson's disease. In light of the favorable results, a large, multi-center FDA NIH-approved Phase III study is currently underway. Another study took a comparative look at the protective effects of ubiquinone and ubiquinol in rodents administered MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin that induces changes similar to those found in idiopathicIdiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
Parkinson’s disease. MPTP is selectively toxic to cells of the substantia nigra, which are specialized cells in the brain stem involved in motor control and dopamine neurotransmitter synthesis. While both forms offered protection again MTPT-induced toxicity, ubiquinol exerted a stronger effect.
Oral health
Oral health comprises all aspects of the mouth, including the teeth and gums (gingiva) and their connective tissue, lips, tongue, and salivary glands. Emerging scientific information continues to establish a relationship between oral health status and a variety of systemic conditions, ranging from diabetes, respiratory diseases, osteoporosis, arthritis, and cardiovascular diseases. Oral health and systemic health are part of a bidirectional interface (each capable of exerting an effect on the other), and the link between the two is inflammation. Orally, inflammation can be commonly found in the condition known as periodontitis, which can result in the destruction of tooth-supporting collagen, alveolar bone, and the teeth. Periodontitis is known to elevate systemic markers of inflammation, such as C-reactive protein (an acute phase protein synthesized in the liver) and serum neutrophil elastase.Researchers from the University of Sevilla in Spain identified that subjects with periodontitis had elevated mitochondrial ROS and significantly reduced coenzyme Q10 levels than subjects without periodontitis (60.2 pmol /mg protein versus 150.4 pmol Q, indicating a decline of 56%). A primary pathogenic factor giving rise to periodontal inflammation is the excess generation of reactive oxygen species (ROS). These ROS are leaked by the mitochondria as a by-product of the energy synthesis process.
While coenzyme Q10 is essential for mitochondrial synthesis of energy, it can also counter ROS formation, provided the coenzyme Q10 is in the ubiquinol form. Ubiquinol has specifically been shown to exert potent anti-inflammatory effects as seen in a genoexpression study involving human immune cells (monocytic cells known as THP-1). In that research model, the human immune cells were exposed to bacterial cell wall lipopolysaccharide (LPS) to induce expression and secretion of proinflammatory cytokines. Ubiquinol caused a reduction in the cellular release of various proinflammatory substances, specifically cytokine TNF-α and two chemokines.
The ubiquinol form of coenzyme Q10 has been studied specifically for its impact on oral health. Results were presented in June 2011 at the 63rd Meeting of the Vitamin Society of Japan by Nihon University School of Dentistry by researchers evaluating the effects of 150 mg of ubiquinol per day over a two month period in a double-blind, placebo-controlled clinical trial. The scientists measured various indicators of periodontal health including plaque adhesion, pocket depth, bleeding and gingival recession. Ubiquinol demonstrated significant benefits in plaque adhesion and an increase in the salivary antioxidant status, which are essential for the maintenance of oral health. A possible mechanism of these oral benefits maybe based on the antioxidant effect of ubiquinol, which could counteract periodontal inflammatory processes.
One factor that affects oral health is the amount of salivary secretion. Insufficient salivary secretion, also known as xerostomia, is associated with several negative effects including increased susceptibility to dental caries and periodontal disease. A comparative study by Japanese researchers examined the effects of ubiquinol and ubiquinone on salivary secretion. Sixty six patients were given either ubiquinol or ubiquinone at a dosage of 100 mg per day, or a placebo over a one month period. While both forms of orally administered coenzyme Q10 significantly enhanced salivary coenzyme Q10 levels, the ubiquinol form provided the greater rise in concentration: ubiquinone levels elevated from 60 to 87 ng/mL while ubiquinol elevated from 54.6 to 117.7 ng/mL. In addition, ubiquinol stimulated greater salivary secretion thus solidifying its position as the optimum form of coenzyme Q10 for oral health.
Renal health
Researchers from the University of Tokyo have been examining the role of antioxidants in Chronic Kidney Disease. As a preliminary study, an animal model of chronic kidney disease was developed. Three experimental groups were created: a control group, a high salt diet group, and a high salt diet plus ubiquinol group. In comparison to the control group, the high salt diet increased oxidative stress (measured by the generation of superoxide anion in kidney tissue), increased hypertension, and induced albuminuria. However, the high salt diet plus ubiquinol group exhibited results indicating significant renoprotection by ubiquinol, including decreased generation of superoxide anion (antioxidant effect), decreased urinary albumin, and amelioration of hypertension. This study marks the first experimental research with the antioxidant ubiquinol in an animal model of chronic kidney disease.Inflammation and gene expression
Scientists have initiated a series of studies to examine the effects of CoQ10 on gene expression. In silico analysis of hundreds of genes have revealed CoQ10 to affect 17 different genes, which are functionally connected by four different cellular signalling pathways: G-protein coupled receptors, KAK/STAT, integrin, and beta-arrestin. Researchers involved in that study subsequently performed detailed investigations with the ubiquinol form. An in vitro investigation utilizing a human monocyte cell line (THP-1) exposed to a stimulator of inflammation called lipopolysaccharide (LPS) showed ubiquinol inhibited the release of proinflammatory substances, specifically cytokine TNF-α pro-inflammatory chemokines RANTES (normal T-call expressed and secreted) and MIP1-α (macrophage inflammatory protein). The scientists observed ubiquinol to exert a stronger effect on these inflammation-mediators than ubiquinone.Further research along these lines demonstrate some of these genes related to the inflammation process to be redox-sensitive. An in vivo study was conducted utilizing both ubiquinone or ubiquinol on an accelerated aging rodent model strain called SAMP1. A variety of different tissues (liver, heart, brain, and kidney) were analyzed through microarray-based whole genomic expression profile. One of the findings was that ubiquinol was more effective than ubiquinone in raising CoQ10 levels in the liver (this effect of greater bioavailability has also been observed in humans). A review of the genome expression profiles on the liver samples revealed a ubiquinol-specific effect for genes in the PPAR-α (peroxisome proliferator activated receptor alpha) signaling pathway. Interestingly, these ubiquinol-sensitive genes are primarily involved in cholesterol synthesis (for example, 3-hydroxy-3-methylglutaryl-coenzyme A), lipid metabolism (FABP5), and lipoprotein metabolism (PLTP). These effects were specific for ubiquinol, as the regulation of PPAR-α genes was not observed with ubiquinone.
Other findings
One study examined the relationship between ubiquinol and blood lipids in patients with Coronary Artery Disease. Specifically, the scientists sought to determine if a relationship exists between the extent of stenosis (narrowing of blood vessels) and the concentrations of ubiquinol and blood lipids. Often, CoQ10 is studied in relation to blood lipids, since in the blood it is almost entirely found in lipoproteins (in particular low density lipoprotein cholesterol LDL-C). In turn, lipoproteins package lipid soluble cholesterol for circulation in the water soluble blood (cholesterol is not found free), and hence the association between CoQ10, cholesterol, and lipoproteins. The subjects were not administered any ubiquinol or statins, thus providing a point of differentiation from other studies where supplementation took place. In order to quantify the extent of stenosis, the subjects underwent coronary angiography. Of the 36 total subjects, 20 were qualified as negative (less than 50% stenosis) while 16 subjects were positive (greater than 70% stenosis). The findings revealed the ubiquinol/lipids ratio was significantly higher in the low-stenosis group; conversely, the high-stenosis group had significantly lower values of the ubiquinol/lipids ratio. The scientists remarked that the ubiquinol/lipid ratio appears to be a sensitive factor for marking the progress of atherosclerotic changes. While this was not an intervention trial, an association did emerge between the ubiquinol/lipids ratio and the extent of stenosis.Bioavailability
It is well established that CoQ10 is not well absorbed into the body, as has been published in many peer-reviewed scientific journals. Since the ubiquinol form has two additional hydrogens, it results in the conversion of two ketone groups into hydroxyl groups on the active portion of the molecule. This causes an increase in the polarity of the CoQ10 molecule and may be a significant factor behind the observed enhanced bioavailability of ubiquinol. Orally, ubiquinol exhibits greater bioavailability than ubiquinone: 150 mg per day of ubiquinol in a softgel resulted in peak blood values of 3.84 mcg/ml within 28 days.Content in foods
In foods, there are varying amounts of ubiquinol. An analysis of a range of foods found ubiquinol to be present in 66 out of 70 items and accounted for 46% of the total coenzyme Q10 intake. The following chart is a sample of the results.| Food | Ubiquinol (mcg/gm) | Ubiquinone (mcg/gm) |
|---|---|---|
| Beef (shoulder) | 5.36 | 25 |
| Beef (liver) | 40.1 | 0.4 |
| Pork (shoulder) | 25.4 | 19.6 |
| Pork (thigh) | 2.63 | 11.2 |
| Chicken (breast) | 13.8 | 3.24 |
| Mackerel | 0.52 | 10.1 |
| Tuna (canned) | 14.6 | 0.29 |
| Yellowtail | 20.9 | 12.5 |
| Broccoli | 3.83 | 3.17 |
| Parsley | 5.91 | 1.57 |
| Orange | 0.88 | 0.14 |
Molecular aspects
Ubiquinol is a benzoquinol and is the reduced product of ubiquinone also called coenzyme Q10.The reduction of ubiquinone to ubiquinol occurs in Complexes I & II in the electron transfer chain. The Q cycle is a process that occurs in cytochrome b
Cytochrome b
Cytochrome b/b6 is the main subunit of transmembrane cytochrome bc1 and b6f complexes. In addition, it commonly refers to a region of mtDNA used for population genetics and phylogenetics.- Function :...
, a component of Complex III in the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
,and that converts ubiquinol to ubiquinone in a cyclic fashion. When ubiquinol binds to cytochrome b, the pKa of the phenolic group decreases so that the proton ionizes and the phenoxide anion is formed.
If the phenoxide oxygen is oxidized, the semiquinone is formed with the unpaired electron being located on the ring.
A page on Proteopedia, Complex III of Electron Transport Chain, contains rotatable 3D structures of Complex III which can be used to study the peptide structures of Complex III and the mechanism of the Q cycle.