| Ubiquinol, the reduced form of Coenzyme Q10 | | | | No discussion of CoQ10 would be complete without a |
| (CoQ10), is a recent addition to the supplement | | | | brief mention of its documented health benefits. |
| offerings of several companies, and one which has | | | | Supplemental CoQ10 (especially at therapeutic doses) |
| generated as much confusion as it has excitement. | | | | has been the subject of numerous studies over the |
| As a supplement, ubiquinol is fairly new. As a critical | | | | last half century, particularly in applications for |
| part of human metabolism, our knowledge of | | | | cardiovascular health. Several studies have shown |
| ubiquinol dates back nearly as far as the discovery of | | | | benefits of CoQ10 in patients diagnosed with chronic |
| CoQ10. While CoQ10 is often thought of as a "static" | | | | heart failure, exercise-induced angina, hypertension, or |
| nutrient within the context of nutrition, it is actually | | | | those who have recently experienced infarction. |
| one which dynamically interconverts between two | | | | There is also early evidence that CoQ10 may protect |
| useful states (the oxidized "ubiquinone", and the | | | | the heart from damage during chemotherapy, bypass |
| reduced "ubiquinol"). In this article, we will discuss | | | | surgery, or in diabetes. Aside from cardiovascular |
| ubiquinol as part of the CoQ10 "cycle", and how this | | | | applications, CoQ10 has also been studied for its |
| cycle has important consequences in human | | | | potential benefits for other conditions which involve |
| metabolism. Additionally, we will discuss how ubiquinol | | | | dysfunctions in cellular energetics , neurological |
| as a supplement may take advantage of this cycle | | | | degeneration, or oxidative damage (including |
| to exhibit increased assimilation into the body. | | | | Parkinson's and Huntington's disease, ALS and |
| What is CoQ10? | | | | periodontal disease). |
| Coenzyme Q10 or CoQ10 is a member of a family of | | | | While the clinical evidence for the potential benefit of |
| important biological compounds called ubiquinones. It is | | | | CoQ10 in many of these applications shows promise, |
| a lipophilic, water-insoluble substance which | | | | variability in study outcomes necessitates further |
| participates in a variety of biochemical oxidation and | | | | research in these areas before definitive |
| reduction reactions (redox reactions). First identified in | | | | recommendations can be made. Results of more |
| 1957 as an essential component of the energy | | | | recent studies have revealed that CoQ10 dosages |
| production system in cells, CoQ10 and other | | | | (particularly in terms of circulating plasma levels) may |
| members of the ubiquinone family have since been | | | | have been too low in earlier trials to demonstrate |
| identified as critical metabolic compounds in a range | | | | positive clinical benefits. Particularly in terms of |
| of aerobic organisms. Indeed, ubiquinones are | | | | cardiovascular health, CoQ10 blood levels of greater |
| ubiquitous. | | | | than 2.5 mcg/ml appear to have more consistent |
| Because of its critical role in metabolism, humans | | | | results in improving cardiovascular function. To put |
| have the ability to synthesize their own CoQ10 (eg. it | | | | this in perspective, a recent study of CoQ10 |
| is nutritionally non-essential), although modest | | | | supplementation in heart failure patients required a |
| amounts can be obtained through diet or as | | | | dosage of 300 mg of ubiquinone per day (in a |
| supplements. In humans, CoQ10 is found in each cell | | | | high-absorption delivery system) for one month to |
| in the body, but is particularly concentrated in tissues | | | | exceed this threshold and exhibit improvements in |
| which have large energy requirements (like the heart, | | | | cardiovascular parameters. Future clinical studies of |
| liver, kidneys, and skeletal muscles), with smaller | | | | CoQ10, designed with this threshold in mind, should |
| amounts in the brain, lungs, and intestines. There are | | | | continue to add to the growing body of evidence of |
| also substantial amounts of CoQ10 in circulation, most | | | | CoQ10's positive role in preserving proper |
| often associated with lipoprotein (LDL or HDL) | | | | cardiovascular function. And as we shall see in the |
| particles. The total CoQ10 pool in a normal adult has | | | | next section, the development of supplemental |
| been estimated to be between 0.5 and 1.5 grams. | | | | ubiquinol may facilitate our ability to deliver CoQ10 at |
| Within cells, about half of the cellular CoQ10 is found | | | | therapeutically-relevent levels. |
| within the mitochondria (the energy-producing centers | | | | Ubiquinol as a Supplement: Additional Benefits? |
| of cells), and this is where the final steps of CoQ10 | | | | As we have seen previously, CoQ10 functions by |
| synthesis occur. Extramitochondrial CoQ10 (that is, | | | | cycling between two stable forms, ubiquinol and |
| CoQ10 which is located in areas of the cell which are | | | | ubiquinone. The outcomes of this cycle are the |
| NOT charged with producing cellular energy) can | | | | generation of cellular energy, and the protection of |
| amount to 50-60% of the total CoQ10 pool. CoQ10 is | | | | membranes and lipids from oxidation. Dietary or |
| found throughout cell membranes, as well as in other | | | | supplemental CoQ10 also participates in this cycle. |
| cellular structures (organelles) such as nucleus, | | | | Dietary ubiquinone (oxidized CoQ10; the form most |
| cytoplasm, and endoplasmic reticulum. | | | | commonly found in foodstuffs and until recently, |
| Experimentation has also revealed that while the final | | | | supplements) can be reduced to ubiquinol during its |
| steps of CoQ10 production occur in the mitochondria, | | | | transit from the gut to the bloodstream. |
| it can be exported to other subcellular locations. | | | | If CoQ10, regardless of form or source, is still able to |
| Similar studies have shown that exogenous (obtained | | | | participate in the redox cycle, then what benefit |
| from the diet) CoQ10 incorporates not only into the | | | | would supplemental ubiquinol possibly have? The |
| mitochondria, but into the plasma (outer) membrane | | | | answer to this question requires an understanding of |
| of cells as well as other intracellular membranes. | | | | CoQ10 pharmacokinetics (the particulars of CoQ10's |
| One Role, Two Forms, Many Consequences | | | | absorption, utilization, and elimination). As it turns out, |
| In the course of participating in various oxidation and | | | | dietary or supplemental ubiquinol may have a distinct |
| reduction reactions, CoQ10 itself is cycled between | | | | advantage over ubiquinone in its facility of absorption. |
| two stable states (called a "redox pair"): a fully | | | | Like many fats and lipophilic nutrients, CoQ10 |
| oxidized form ("ubiquinone"), and a fully reduced form | | | | (regardless of form) is usually taken up by the |
| (called "ubiquinol"). CoQ10 cycles through these | | | | intestinal enterocytes (cells which line the intestines), |
| oxidated/reduced forms in order to achieve its | | | | packaged into lipid particles, and released into the |
| metabolic goals. The CoQ10 cycle is simple: Ubiquinone | | | | lymphatic system. From the lymphatic system, these |
| picks up electrons and becomes ubiquinol. Ubiquinol | | | | particles are shuttled into circulation, where they are |
| release its electrons and becomes ubiquinone again. | | | | free to be transported throughout the body to |
| And the cycle repeats. | | | | where they may be needed. The absorption of |
| It would appear, therefore, that CoQ10 has a very | | | | dietary CoQ10 is quite poor. It has limited solubility in |
| simple function - to move electrons. Why is the | | | | lipids, and its highly variable absorption depends on |
| movement of electrons important? This seemingly | | | | the other contents of the gut (for example, |
| trivial feat has important consequences in metabolism; | | | | absorption is lower on an empty stomach and |
| the transfer of electrons is a fundamental step in the | | | | greater when taken with food of high lipid content). |
| production of energy, in the regeneration of | | | | Some studies have measured absorption as low as |
| antioxidants in cell membranes, and in the | | | | 2-3% of the total dosage. |
| construction of other important biological molecules. | | | | One of the most exciting consequences of the |
| Each cell in the body needs a source of energy to | | | | development of a stabilized dosage form of ubiquinol |
| survive, so cells break down sugars, fats, and amino | | | | is its innate ability to be absorbed more efficiently |
| acids to make energy. In the mitochondria of our | | | | than ubiquinone. There is experimental evidence that |
| cells, CoQ10 is abundant, carrying electrons to aid in | | | | CoQ10 must be reduced (to ubiquinol) in intestinal |
| the chemical reactions that "burn" (oxidize) cellular fuel | | | | enterocytes prior to release into the lymphatic |
| to produce chemical energy in the form of adenosine | | | | system; this coupled absorption/reduction may be a |
| triphosphate (ATP). Since adequate amounts of ATP | | | | rate limiting step in CoQ10 assimilation. Dietary |
| are essential for powering our cellular machinery, it is | | | | ubiquinol (which is already reduced) avoids this |
| easy to understand the importance of CoQ10 in | | | | reduction reaction, and may be directly available for |
| human metabolism. Both forms of CoQ10 are | | | | absorption. This may explain why ubiquinol-based |
| necessary to shuttle electrons between | | | | CoQ10 supplements exhibit enhanced bioavailability |
| energy-producing reactions (ubiquinone picks them up, | | | | over ubiquinone supplements. Preliminary testing in |
| and ubiquinol drops them off). | | | | humans indicates at least double the absorption of |
| Outside of the mitochondria, CoQ10 performs a | | | | ubiquinol over ubiquinone. Comparisions of blood levels |
| slightly different role as a membrane and | | | | between trials, while less accurate, estimates the |
| lipid-associated antioxidant. About half of the human | | | | improvement in absorption to be significantly higher. |
| body's total CoQ10 pool may be functioning in this | | | | Future clinical studies (designed specifically to |
| capacity. CoQ10 is one of the major antioxidant | | | | compare the absorption of these forms) are required |
| constituents of the LDL particle. In its reduced form | | | | to more accurately quantify ubiquinol's enhanced |
| (ubiquinol), CoQ10 can be found alongside alpha- and | | | | absorption, and what effect patient age or medical |
| gamma-tocopherol, lycopene, and beta-carotene in | | | | condition may have on this value. |
| LDL particles as resident antioxidants to prevent LDL | | | | Summary |
| oxidation. Coenzyme Q10 is one of the first | | | | CoQ10, a critical biological molecule in the metabolism |
| antioxidants to be depleted when LDL is subjected to | | | | of aerobic organisms, owes its utility to its ability to |
| oxidation. Studies have implicated ubiquinol as a | | | | cycle between two relevent forms, ubiquinone and |
| regenerator of oxidized tocopherol within the LDL | | | | ubiquinol. This cycle takes a central role in several |
| particle; studies of hypercholesterolemic elderly | | | | metabolic reactions, notably the production of cellular |
| patients have equated highly oxidized LDL particles | | | | energy and the protection of membranes and lipids |
| with low ubiquinol levels. In its role as an antioxidant, | | | | from oxidative damage. Sufficient levels of CoQ10 |
| the reduced form of CoQ10 (ubiquinol) functions as | | | | are an important factor in human metabolism |
| the active antioxidant, giving up its electrons to other | | | | (particularly in the maintenance of cardiovascular |
| oxidized molecules (like oxidized tocopherol) to | | | | health) and clinical research in this area continues to |
| regenerate them. This process converts ubiquinol to | | | | strengthen this observation. Ubiquinol (the reduced |
| ubiquinone. The newly formed ubiquinone must then | | | | form of CoQ10) as a supplement or therapeutic may |
| be converted back into ubiquinol in order to become | | | | be an advantageous development. Its advantage |
| reengaged in the antioxidation process, although the | | | | may not have a direct effect on the well-regulated |
| mechanism by which this occurs within LDL particles is | | | | CoQ10 redox cycle in healthy people, but rather its |
| not yet known. | | | | ability to circumvent one of the possible limitations of |
| Health Benefits of CoQ10 | | | | CoQ10 absorption. |