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Scientific support broadens for this form of CoQ10.
Learning is the process of acquiring new knowledge or modifying existing knowledge. When working optimally, it can lead to the development of breakthrough technologies. It’s amazing to consider that 300,000 tons can be lifted 10,000 meters above ground for travel from continent to continent. But not all of our learning is sequential, or correct. According to Joseph T. Hallinan, the author of Why We Make Mistakes, most people think (incorrectly) that Reno is east of San Diego.
Similarly, a common but fundamental misconception is that ubiquinone is the only form of CoQ10. In fact, CoQ10 exists as ubiquinone (oxidized CoQ10, spent form) and ubiquinol (reduced CoQ10, antioxidant form). In order for CoQ10 to exhibit an antioxidant effect, the body must metabolize ubiquinone into its antioxidant form ubiquinol. The two, ubiquinone and ubiquinol, comprise a pair which can undergo chemical reactions called oxidation-reduction reaction (redox reactions).
Both ubiquinol and ubiquinone can be referred to as CoQ10; however, there are subtle molecular differences between the two forms. Ubiquinol has two hydrogen atoms and two electrons more than ubiquinone. Recent publications offer a better understanding of ubiquinol’s activity, including studies demonstrating effects on neuronal metabolism, renal health, and nutrient-gene interactions-all part of the broadening scientific foundation of ubiquinol.
Scientists have theorized that mitochondrial dysfunction may be a major pathophysiology behind Parkinson’s disease and Huntington’s disease. In 2002, a landmark study was published which examined the effects of CoQ10 (ubiquinone) in patients with early Parkinson’s disease.(1) The scientists in this multicenter effort (a Phase II study funded by the National Institute of Neurological Disorders and Stroke) found that ubiquinone reduced the functional decline associated with Parkinson’s disease. This finding helped ignite a new sensation in the industry. In the years following, CoQ10 sales have grown rapidly into the $400 million range, and CoQ10 stands today as one of the top three products in the dietary supplements industry.
Research along these lines continues to evolve and now involves the ubiquinol form of CoQ10. A recently published study by investigators from Cornell University utilized an experimental model of Parkinson’s disease. The 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), which is 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.
The scientists created multiple experimental groups in the study, including semi-chronic, chronic (via osmotic minipump), and acute MPTP administrations. These different MPTP administrations all exerted a massive loss of dopamine, while CoQ10 protected significantly against these toxic effects.
A unique aspect of this MPTP study was that it offered a direct comparison of conventional CoQ10 and ubiquinol. Not only did the scientists show protection by CoQ10 against neurotoxic MPTP, they demonstrated that the efficacy of ubiquinol was greater than that of ubiquinone.(2) It is clear that ubiquinol results in improved plasma concentrations, as well as an increase in efficacy.
Another study, conducted by researchers from Iwate Medical University in Japan, has shed some light on the influence of CoQ10 on neurological function. These scientists examined both ubiquinone and ubiquinol levels in the cerebrospinal fluid from a small number of untreated Parkinson’s disease patients, in order to ascertain the oxidative balance. These two forms of CoQ10 can be numerically added to create a value called Total CoQ10, and their relative values could provide a glimpse of antioxidant status within the body.
There was no correlation between the content of ubiquinone (oxidized CoQ10) and the age of the patients. However, the Parkinson’s disease patients did have higher concentrations of ubiquinone relative to the control group, and the %CoQ10 (which is the percentage of ubiquinone to Total CoQ10) was also higher.(3) This shift from reduced (ubiquinol) to oxidized (ubiquinone) in those with the disease may mark the extent of oxidative stress and, conversely, the level of antioxidant protection.
Researchers from Japan’s Kyorin University also evaluated the form of CoQ10 in subjects of different age groups. They found that aged subjects not only have reduced CoQ10 biosynthesis, but that their ability to reduce CoQ10 (convert ubiquinone to ubiquinol) also decreases.(4) Consequently, older subjects displayed a higher oxidative state (even if healthy), and the scientists noted the redox state may be a useful biomarker of aging. Possibly, the optimal ratio may be replenished with ubiquinol supplementation, but not necessarily with ubiquinone supplementation because aging deteriorates the ability to convert ubiquinone to ubiquinol. Studies such as these will continue to add interest to the role of ubiquinol in neurological function.
Genes Involving Lipid Metabolism and Inflammation
A recently published study by researchers from Germany’s University of Kiel and Japan’s Shinshu University may offer a mechanism for ubiquinol’s role in lipid and cardiovascular health.(5) In this study, a particular mice strain called SAMP1 (Senescence Accelerated Mice Prone 1) was studied because it is characterized by high oxidative stress status and therefore is a good model in which to study the potential effects of antioxidants.
Based on previous in vitro findings of differences between ubiquinone and ubiquinol, the researchers hypothesized about the presence of redox-dependent genes. After 14 months of ubiquinone or ubiquinol 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-alpha (PPAR-alpha is strongly involved in lipid metabolism), LXR/RXR, and FXR/RXR. Specifically, the researchers identified eleven different ubiquinol-dependent genes related to cholesterol and lipid/lipoprotein metabolism.
With the exception of one gene, ubiquinone did not have any effect on these genes. The single exception was the gene CYP51, which, interestingly, was down-regulated by ubiquinol but was up-regulated by ubiquinone. The CYP51 gene encodes for the cytochrome P450 enzyme lanosterol 14-demethylase, which is involved in the post-squalene part of cholesterol biosynthesis in mammals. Additionally, it was also seen that the ubiquinol experimental group was more effective in increasing Total CoQ10 concentrations than the ubiquinone-administered group.
Another genoexpression study examined the effects of ubiquinol on specific genes involved in inflammation. Previously, researchers from the University of Kiel demonstrated ubiquinol’s anti-inflammatory effect at concentrations of 10 micromoles (calculated to be 8.65 mcg/mL). That research model utilized a human monocyte cell line called THP-1 and exposed it to bacterial cell wall lipopolysaccharide (LPS), a substance known to induce expression and secretion of proinflammatory cytokines.
Specifically, ubiquinol caused a reduction in the cellular release of various proinflammatory substances, specifically cytokine TNF-alpha and two chemokines.(6) Utilizing the same experimental model of inflammation (human monocytic THP-1 stimulated with LPS), the researchers sought to determine ubiquinol’s transcriptional effects on LPS-inducible gene expression. In other words, what effect would ubiquinol have on gene expression in cells exposed to an inflammatory substance?
A total of 14 LPS-inducible genes were significantly down-regulated by the presence of ubiquinol. The strongest down-regulation was found to be the nuclear receptor coactivator 2 (NCOA2) gene. (A summary of these results can be seen in the table on page 80.) These genes may impact a variety of biological processes, including lipid metabolism and phospholipid transport (ABCB4), oxidation-reduction reactions and structural molecule synthesis (PLOD2), signal transduction processes, transcriptional regulation, and cell proliferation pathways.(7) These genes are connected indirectly to the inflammation cascade through the TNF (tumor necrosis factor) and IL-2 (interleukin-2) signaling pathways.
Worldwide, there is a growing population of people suffering from chronic kidney disease, which is a gradual loss of kidney function. Not only can chronic kidney disease lead to end-stage kidney failure, but it can also increase the risk of cardiovascular disease.
One of the primary functions of these super-processing organs is to filtrate waste from circulation. Based on observations that antioxidants mitigate renal dysfunction, researchers from the University of Tokyo investigated the role of ubiquinol in an animal model of chronic kidney disease. The study utilized three experimental groups: a control group, a high-salt diet group, and a high-salt diet plus ubiquinol group.
The high-salt diet increased oxidative stress (measured by the generation of superoxide anion in kidney tissue), increased hypertension, and induced albuminuria. On the other hand, the high-salt diet plus ubiquinol group demonstrated significant renoprotection by ubiquinol, including decreased generation of superoxide anion (antioxidant effect), decreased urinary albumin, and amelioration of hypertension.(8) While the mechanism of this action was not made clear, the scientists stated that in this experimental model, ubiquinol exerted renoprotective effects directly by antioxidant action and indirectly by antihypertensive effect. This study marks the first experimental research with the antioxidant ubiquinol in an animal model of chronic kidney disease.
These studies demonstrate that ubiquinol impacts neuronal metabolism, renal health, and genes related to lipid/lipoprotein metabolism and inflammation. As scientists map the multiple benefits of ubiquinol, the view unfolding is one of many opportunities.