Ubiquinol is an electron-rich (reduced) form of coenzyme Q10.
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 organelles 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 have also revealed its function in gene expression involved in human cell signaling, metabolism and transport.
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 affects cardiovascular health, neuronal metabolism, renal health, and genes related to lipid/lipoprotein metabolism and inflammation.
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 toward complex III. In this process, ubiquinol serves to produce ATP (adenosine triphosphate), the main energy intermediate in living organisms.
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 having congestive heart failure and being on maximal medical therapy. The patients were being administered a mean amount of 450 mg ubiquinone per day. 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 fraction increased nearly twofold from 24% to 45%. The ejection fraction is an assessment method that measures the ability of the heart's ventricles to pump blood.
Statin medication targets inhibition of the mevalonate pathway to decrease cholesterol biosynthesis, however a consequence of their utilization is a depletion of CoQ10. Statins do not block all cholesterol production in the body. Similarly CoQ10 levels are not lowered completely. Nevertheless even a slight drop in CoQ10 levels can have a host of effects, some of which are not evident for years or even decades. The most common adverse effect of statins is skeletal muscle toxicity (myopathy), and the clinical manifestation of myopathy varies widely ranging from mild myalgia to rhabdomyolysis. Researchers recently investigated the effects of ubiquinol in 28 patients with statin myopathy. Nine subjects received atorvastatin, six subjects received rosuvastatin, six subjects received simvastatin, three subjects received fluvastatin, two subjects received lovastatin, and one patient received pravastatin. After 6 months of supplementation with 60 mg of ubiquinol per day, there was a significant reduction in muscle pain and weakness: muscle pain declined by 53.8% and muscle weakness declined by 44%.
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).
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. 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 idiopathic 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 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 may commonly be found in the condition known as periodontitis, which may 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. 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 may 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 may be 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.
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.
A recent study published in 2012 in a peer-reviewed publication The Journal of Urology investigated the effects of the ubiquinol (reduced form of CoQ10 or CoQ10H2) in subjects with male infertility. The study results demonstrated that supplementation with 200 mg of ubiquinol per day significantly improved sperm density, sperm motility, and sperm strict morphology. The researchers pointed out that oxidative stress (OS) is one of the main factors that influence male infertility, and that OS is known to negatively affect the ubiquinol-to-ubiquinone ratio.
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.
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.
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.