CoenzymeQ10: Questions and Answers--True or False?
Article by Arnie Gitomer
CoenzymeQ10: True or False?• Coenzyme Q10 is an important cofactor functioning in both energy metabolism and as an important lipophilic antioxidant.
Coenzyme Q10 (CoQ10) is a lipid soluble enzyme cofactor and naturally found in nearly every cell, tissue and organ in your body. CoQ10 is acquired through biosynthesis, supplementation and in small amounts from the diet. CoQ10 has an established role in cellular energy production. The antioxidant action of the reduced form of CoQ10 (ubiquinol) is now considered to be one of its most important functions in cellular systems. Ubiquinol is a potent lipophilic antioxidant capable of regenerating other antioxidants and provides important protection against oxidative damage to lipids, proteins and DNA. Recent studies also reveal function in gene expression involved in human cell signaling, metabolism and transport.
• Kaneka CoQ10 has Self Affirmed GRAS (Generally Regarded As Safe) status supported by extensive safety studies that have been published in scientific refereed journals.
Of all of the commercially available CoQ10 products on the market Kaneka CoQ10TM is supported by extensive safety studies and has obtained Self-Affirmed GRAS status.
• Commercial CoQ10 is manufactured by two different processes.
There are in fact three different processes employed to manufacture CoQ10: 1. The yeast fermentation method 2. A fermentation process using bacteria and 3. A synthetic method that uses solanesol derived from tobacco as starting material.
• Kaneka Corporation, the worlds largest CoQ10 manufacturer, has been manufacturing CoQ10 using the proven yeast fermentation method for over 30 years. Most other CoQ10 manufacturers have been in operation less than ten years.
Kaneka Q10™ is the worlds only yeast fermented CoQ10. It is the recognized industry standard, with the highest purity and it is the most bio-identical to what humans produce in vivo. Other producers of CoQ10 utilize bacterial fermentation or chemical synthesis using solanesol from tobacco.
• All CoQ10 products are manufactured by companies here in the US.
Kaneka Corporation is the only company that manufactures CoQ10 in the USA as well as in Takasago, Japan. International Food and Pharmaceutical GMPs are strictly adhered to at both locations.
• Of the thousands of scientific studies on the research and clinical study focusing on the biochemistry and health benefits of CoQ10 published worldwide over the past thirty years have been conducted using predominantly Kaneka CoQ10.
• In all of the critical large-scale NIH granted Phase I, II and now Phase III clinical studies evaluating the health benefits of CoQ10 for Huntington’s Disease, Parkinson’s Disease and ALS only Kaneka CoQ10 has been used in these studies conducted in major medial centers in the US.
Kaneka CoQ10TM has been used in the vast majority of clinical trials over the past three decades, including National Institutes of Health (NIH) funded studies.
• Coenzyme Q10 exists in only one functional form in the body.
Coenzyme Q10 exists in at least three functional forms in the body. Formally there are three active biological forms of CoQ10 of metabolic interest – CoQ ubiquinone – CoQH ubisemiquinone – CoQH2 ubiquinol. They are all metabolically active – see below.
• There is a very significant difference between the reduced form of CoQ10 (ubiquinol) and the oxidized CoQ10 form (ubiquinone) that has been commercially available from Kaneka for over thirty years.
There is a simple structural difference but a very significant functional metabolic difference between ubiquinone (the oxidized CoQ10 form) and ubiquinol (the reduced CoQ10 form). Ubiquinol has two additional hydrogens (with the addition of two electrons) as seen below on the left.
This enzymatically driven conversion (from ubiquinone to ubiquinol) in the mitochondria facilitates the critical transfer of electrons in the mitochondrial electron transport chain which is fundamental to subsequent ATP production. Additionally, it is the transfer of these reducing agents that confer the strong lipid soluble active antioxidant activity of the ubiquinol form in plasma and tissues. Over 90% of the CoQ10 in the plasma of a healthy young individual is in the reduced ubiquinol form. Ubiquinol is considered to be the strongest lipid soluble antioxidant, regenerating Vitamin E and providing an active defense against oxidative insult to lipids, proteins and DNA.
• Ubiquinone is lipid soluble and ubiquinol is water soluble.
Both ubiquinone and ubiquinol are lipid soluble.
• Ubiquinone is biosynthesized but ubiquinol is not.
Both are generated naturally in our bodies. Ubiquinone is biosynthesized as with most all redox active cofactors (FAD, NAD, etc) the oxidized form is biosynthesized and the reduced forms (ubiquinol, NADH, FADH, etc) are naturally derived (biosynthesized) via reversible cellular enzymatic systems.
• Only ubiquinone is required – not ubiquinol – for cellular ATP production.
All forms of CoQ10 are critical for ATP production. Without the reversible transfer of electrons (hydrogens) between ubiquinone and ubiquinol there would be no electron transport in the mitochondrial Electron Transport Chain – which means there would be sub-optimal production of cellular energy in the form of ATP.
• All forms of CoQ10 are metabolically important.
• All forms of CoQ10 are found at the same levels in the plasma of healthy individuals.
Over 90% of the CoQ10 in the plasma of a healthy young individual is in the reduced ubiquinol form. Ubiquinol is considered to be the strongest lipid soluble antioxidant that is biosynthesized, providing an active defense against oxidative insult to lipids, proteins and DNA.
• Ingested ubiquinone is effectively converted (reduced) to ubiquinol in young healthy individuals.
Normally, when you ingest CoQ10 either from food or a supplement, the ubiquinone form generally follows the digestive path of most lipids – it is first incorporated into chylomicrons, reduced in the small intestine and shuttled through the lymphatic system to the circulation. The supplemental ubiquinol form – Kaneka QH™ – is already reduced (has the added two electrons) and seems to be more readily absorbed as indicated by enhanced blood plasma levels – where it functions as a strong lipid soluble antioxidant and is further distributed to tissues.
• Ubiquinol seems to produce a higher level of bioavailability than ubiquinone.
Studies published in peer-reviewed scientific journals indicate that ubiquinol may provide greater absorption based on resulting plasma levels. Absorption seems to increase with age and/or in the presence of acute or chronic disease states.
• As we age are affected by increasing oxidative stress, our body is still capable of metabolizing and maintaining optimum Q10 levels and functional forms.
As we get older the ability of our bodies to produce and metabolize CoQ10 declines. We not only do not biosynthesize as much CoQ10 (ubiquinone) but in addition, the ability of our body to efficiently produce the reduced ubiquinol form also declines. The result is less cellular energy, slower conversion to the reduced form and subsequently diminished protection against oxidative insult and subsequent cellular damage.
Ubiquinol provides a strong first stage defense against cellular oxidative insult and needs to be replenished to maintain optimum health. Supplementation with the new Kaneka QH™ readily replenishes optimum levels of this important cellular antioxidant.
• Only one form of CoQ10 is redox active.
All forms of CoQ10 are redox active and play very important metabolic roles in conversion from one form to the other. All CoQ10 forms are essential for the maintenance of energy homeostasis, cell growth and development and viability.
• What does ‘redox active’ mean and why is it important?
A ‘redox active’ material is one that has the capability of accepting or donating one or more electrons. Coenzyme Q10 functional redox activity is reversible in cellular systems which means that it continuously and reversibly transfers electrons. This function is fundamental and critical to its role in cellular respiration (ATP production) which occurs primarily in the mitochondria, and this function is also fundamental to CoQ10 role as a strong lipid soluble antioxidant.
‘Redox’ is an abbreviation for Reduction – Oxidation reactions which are reversible reactions in biological systems. It is implied when we refer to CoQ10 as an electron carrier in mitochondria generated cellular respiration that CoQ10 can accept and release electrons. Formally there are three active biological forms of CoQ10 of metabolic interest – CoQ ubiquinone – CoQH ubisemiquinone – CoQH2 ubiquinol. They are all metabolically active. CoQ is the oxidized form and active ‘acceptor’, CoQH is both an active acceptor and ‘antioxidant’ as it can donate its lone H to reduce (antioxidize) and/or accept another H to generate the active antioxidant form CoQH2 (ubiquinol).
• Both Ubiquinone (oxidized form) and Ubiquinol (reduced form) are active lipid soluble antioxidants.
Of the two only Ubiquinol (CoQH2) is the active antioxidant form that is derived de novo via reduction of ubiquinone (CoQ) the active and critical coenzyme in mitochondrial electron transport (cellular respiration) and thus essential for the maintenance of energy homeostasis, cell growth and development and cell viability.
The point is that each of the metabolic forms of Q10 are active, important nutrients – CoQ10 has an important function & CoQ10H and CoQ10H2 have important metabolic functions. Current study indicates that they are of specific importance in targeted areas. Recent advertisements/articles, although fairly well balanced, imply (to the consumer) that CoQH2 (ubiquinol) is the only active form - almost disqualifying the importance of CoQ10 (ubiquinone) despite nearly 30 years of research and clinical evaluation demonstrating considerable health benefit.
• Ubiquinol is unstable in air. In order to make ubiquinol – Kaneka QHTM commercially available – has taken nearly ten years of development.
Since ubiquinol is easily oxidized in air, it is difficult to supply a commercially viable, stable, reduced form. Kaneka established the technology that enables the manufacture of ubiquinol in bulk and its encapsulated form with stability and has confirmed its safety in preclinical toxicity studies and published human clinical study.
• Only Kaneka Corporation has developed the technology to produce commercially stable Kaneka QHTM and is the only bulk manufacturer of Kaneka QHTM.
Kaneka researchers developed the commercially available ubiquinol – Kaneka QHTM conducting over a decade of research and development to provide a pure, stable form of ubiquinol and to conduct extensive safety and efficacy studies that have been published in scientific refereed journals.
• Safety Studies have been conducted on Kaneka QHTM.
Safety studies have been conducted and published exhibiting that this is safe and effective. This may be a new ‘reduced form’ – but it is still Coenzyme Q10 – fully recognizable metabolically whether in the oxidized ubiquinone form or the reduced ubiquinol form.
• Kaneka completed the formal FDA submission for ubiquinol as a New Dietary Ingredient.
The name for the FDA acknowleged NDI is “Kaneka QHTM”. Kaneka QHTM (ubiquinol) – the active antioxidant form of Coenzyme Q10 - is the first supplemental form of bio-identical ubiquinol ever developed. The scientists at Kaneka have created a process that manufactures this highly active antioxidant - and it is redefining the market!
• Kaneka QHTM is recommended for everyone.
If you are young and healthy you would probably want to consider the conventional oxidized ubiquinone form – Kaneka Q10™. If you are older, baby-boomers and beyond, and/or suffering from acute or chronic health conditions, or are compromised by excessive oxidative stress, then you may want to consider the reduced ubiquinol form – Kaneka QH™.
Of special note is the fact that many recent studies point out that plasma ubiquinol declines in response to age-related health conditions - as the ubiquinol acts as an important first-line defense against the oxidative insult associated with these disorders. The plasma ubiquinol ratio also changes with the aging process. Supplementation with Kaneka QHTM helps replenish effective CoQ plasma levels and optimized the ubiquinol-plasma ratio.
As a healthy twenty year old you readily biosynthesize/reduce all the CoQ10 you can use. In fact, in a healthy individual the predominant form of CoQ10 in the plasma and tissues is in the reduced ubiquinol form. This reduced form is a very powerful lipid-soluble antioxidant that is readily converted from the ubiquinone form in your body.
As we get older the ability of our bodies to produce and metabolize CoQ10 declines. There can be a number of reasons for this including increased metabolic demand, metabolic disorders, insufficient dietary CoQ10 intake, deficiency of factors required for biosynthesis, oxidative insult, or any combination. Some reports say this decline becomes apparent around 40 years of age, some as early as 20 with slow but continuous decline. The result is less cellular energy, slower conversion to the reduced form and subsequently diminished protection against oxidative insult.
The reduced form (ubiquinol) provides a strong first stage defense against cellular oxidative insult and needs to be replenished to maintain optimum health.
Not surprisingly more and more scientific reports indicate that dramatic decreases in CoQ10 concentrations, mitochondrial dysfunction and increased oxidative stress are associated with the aging process and many age related disorders.
• General recommended dosages for Kaneka QHTM have been established.
This could vary and you should always consult with your healthcare provider but a general rule of thumb may be as follows: If you fit the older and/or stress category mentioned earlier, and you are looking to maintain optimum health you may want to start at 200mg to 300mg per day - studies show that the CoQ10 plasma levels plateau at about two to three weeks at this dose, then 100mg per day is a good maintenance dose.
• Is it true that orally administered Kaneka QHTM, the reduced, ubiquinol form of CoQ10 survives the digestive tract resulting in higher plasma ubiquinol concentrations?
Published scientific studies provide evidence that ingested Kaneka QHTM results in significantly higher plasma ubiquinol concentrations in a dose dependant manner.
Following oral administration of a single dose, ubiquinol was gradually absorbed reaching a maximum at 6 hr.
Results of a 4-week multiple dose study is exhibited in Fig. 2 below – taken directly from the published paper (Regulatory Toxicology and Pharmacology 47 (2007) 19-28, K. Hosoe, et. al.) – measured plasma ubiquinol concentrations reached a markedly high value of 8.413 umol/L, an 11-fold increase over baseline.
[See Fig. 2 to the right]
• There are no published studies directly comparing ubiquinone (CoQ10) to ubiquinol (Kaneka QHTM) in human subjects.
Direct comparative studies between CoQ10 and Kaneka QHTM have consistently shown that an equivalent dose of Kaneka QHTM results in substantially higher plasma Q10 levels in older healthy individuals.
• Only people 40 or older benefit from Ubiquinol.
Study results show a significant increase in plasma CoQ10 levels with Ubiquinol in direct comparison to conventional CoQ10 in people in their mid-twenties and older.
• Published studies show that the Redox status of CoenzymeQ10 is associated with chronological age and age-related health conditions.
The redox status – the ratio of ubiquinol (reduced form) to the ubiquinone (oxidized form) declines resulting in higher levels of the oxidized form than the reduced ubiquinol form. Remember – in a healthy individual the predominant CoQ10 form is the reduced ubiquinol form in both the tissues and the plasma.
Since the ability of our bodies to regenerate the ubiquinol form declines, it becomes increasingly important to replenish the reduced ubiquinol form by supplementing with Kaneka QHTM.
• You can learn more about Kaneka QHTM, including a list of the Brands that sell Kaneka QHTM at KanekaQH.com.
It is very important to note that plasma and tissue concentrations of CoQ10 (especially the ubiquinol form) decrease as we age and this decrease in CoQ10 is associated with the aging process and many of the varied forms of age-related health conditions including fatigue and the decline in stamina and energy often associated with aging – and that supplementation with Coenzyme Q10, and especially Kaneka QH™, replenishes the diminished levels of Q10. Kaneka QH™ is especially effective in replenishing optimum levels of ubiquinol and fostering a strong protective defense against oxidative stress and age-related health conditions.
Both CoQ10 (Ubiquinone) and CoQ10H2 (Ubiquinol) are critically important nutrients that should be considered seriously for optimum health.
This article was submitted by Robert J. Barry, Ph.D., Director of Scientific Affairs, Kaneka Nutrients L.P.
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