By Sid Shastri M.Sc.,
Director of Research, Kaneka Nutrients
Since our successful NDI filing to the FDA in 2007, Ubiquinol has become an elite cardiovascular nutrient, and its ensemble of benefits continue to grow. Did you know that CoQ10 exists as a family of molecules with three redox states? Those three states are the oxidized form, “Ubiquinone,”, the semi-reduced state, “Semiquinone,” and the fully reduced/antioxidant state, known as “Ubiquinol.”
How do Ubiquinol and Ubiquinone differ? The Ubiquinol molecule has a molecular weight of 865 versus 863 for Ubiquinone—the only difference being two additional hydrogens (with their two electrons) on Ubiquinol. However, those hydrogens change the structure of the benzoquinone functional groups from ketones to hydroxyl groups, impacting the structure, solubility, and absorption of the molecule. In several published studies, Ubiquinol achieved better uptake into the plasma. Its superior absorption was demonstrated in a 2014 study in which 200 mg per day of Ubiquinol or CoQ10 in identical, oil-based dosage forms were administered in a cross-over fashion to healthy subjects for 4 weeks.1 Ubiquinol increased total plasma CoQ10 by 3.4 µg/ml (p<0.001; 0.9 to 4.3 µg/ml), while CoQ10 increased it by 1.6 µg/ml (p<0.001; 0.9 to 2.5 µg/mL), making Ubiquinol absorbed over 2 times as well as CoQ10 in a direct comparison (p<0.005).
When you think of the multiple redox states of CoQ10, you may be inclined to think there is balanced distribution of the form. Quite the contrary: published data clearly shows that young healthy subjects maintain their CoQ10 predominantly in the Ubiquinol form.2 Ubiquinol is not only the preferred form in plasma; scientists have also determined that the predominant form of CoQ10 in healthy tissue (including liver, pancreas, intestine, colon) is Ubiquinol.
CoQ10—especially the Ubiquinol form—is found concentrated in metabolically active cells and tissues. This is because its primary role is to facilitate electron transfer between redox components of the electron transport chain, with the ultimate goal of generating ATP (energy) formation.3 Its primary role relates to bioenergetics, ensuring constant synthesis of energy.
This is a process known as oxidative phosphorylation which takes place in the inner mitochondrial membrane.
During aging, it is important to protect macromolecules (RNA, DNA, proteins, and lipids) from attack by reactive oxygen species. Protecting the mitochondria from oxidative damage can protect their overall function and the integrity of mitochondrial DNA. Excess mitochondrial oxidation is thought to be one of many complex factors involved in the aging process. Another molecule prone to oxidation is LDL cholesterol; oxidized LDL is the first step to formation of plaque in the arteries. Ubiquinol’s antioxidant umbrella protects mitochondrial membrane proteins, DNA and LDL cholesterol from free radical-induced oxidative damage.7 However, not all antioxidants are as thorough and powerful as Ubiquinol. Its activity allows regeneration of other antioxidants such as vitamin C and vitamin E. Ubiquinol is the most protective antioxidant in the early stages of LDL-cholesterol oxidation.
CoQ10’s importance to the aging process has been known for decades as scientists have shown its decreased values in the brain, heart, and lung of elderly. More recently, scientists at Japan’s Kyorin University evaluated the percentage of CoQ10 vs. Ubiquinol in subjects of different ages and found that aged subjects had a higher percentage of CoQ10 vs. Ubiquinol, indicating greater oxidative stress.8 The impact of aging can be seen in a value called %CoQ10, which equals CoQ10 divided by (Ubiquinol+CoQ10). The %CoQ10 is an indicator of systemic oxidative stress. Research demonstrates the ratio of CoQ10 to Ubiquinol rises with aging. Wada, et al. reported the %CoQ10 in 25-year-olds was 2.8 while the %CoQ10 of 70-year-olds was 4.6 These and other data, including a 2020 8-week parallel group study demonstrating Ubiquinol reduced LDL oxidation and improved endothelial function point to a very important role of Ubiquinol in antioxidant protection and healthy aging.9
2. Okamoto T, et al. Matsuya T, Fukunaga Y, et al. Human serum ubiquinol-10 levels and relationship to serum lipids. Int J Vitam Nutr Res. 1989;59(3):288-292
3. Lenaz, G, et al. The Role of Coenzyme Q in Mitochondrial Electron Transport. Mitochondrion. 7S 2007 S8 - S33
4. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998 Apr;78(2):547-81
5. Sies H., Jones D. In: 2nd ed. Fink G., editor. Vol. 3. Elsevier; Amsterdam: 2007. Oxidative stress; pp. 45–48. (Encyclopedia of Stress)
6. Liquori I, et al. Oxidative stress, aging, and diseases. Cllin Interv Aging. 2018; 12:757-772
7. Fiorini, R, et al. Flourescence studies of the interactions of ubiquinol-10 with liposomes. Photochemistry and Photobiology. 2008, 84: 209–214
8. Wada, H, et al. Redox status of coenzyme Q10 is associated with chronological age. Journal of the American Geriatrics Society. 2007; 55(7): 1142-1144
9. Sabbatinelli J, et al. Ubiquinol ameliorates endothelial dysfunction in subjects with mild-to-moderate dyslipidemia: A Randomized Clinical Trial. Nutrients. 2020 Apr 15;12(4):1098
Director of Research, Kaneka Nutrients
Since our successful NDI filing to the FDA in 2007, Ubiquinol has become an elite cardiovascular nutrient, and its ensemble of benefits continue to grow. Did you know that CoQ10 exists as a family of molecules with three redox states? Those three states are the oxidized form, “Ubiquinone,”, the semi-reduced state, “Semiquinone,” and the fully reduced/antioxidant state, known as “Ubiquinol.”
How do Ubiquinol and Ubiquinone differ? The Ubiquinol molecule has a molecular weight of 865 versus 863 for Ubiquinone—the only difference being two additional hydrogens (with their two electrons) on Ubiquinol. However, those hydrogens change the structure of the benzoquinone functional groups from ketones to hydroxyl groups, impacting the structure, solubility, and absorption of the molecule. In several published studies, Ubiquinol achieved better uptake into the plasma. Its superior absorption was demonstrated in a 2014 study in which 200 mg per day of Ubiquinol or CoQ10 in identical, oil-based dosage forms were administered in a cross-over fashion to healthy subjects for 4 weeks.1 Ubiquinol increased total plasma CoQ10 by 3.4 µg/ml (p<0.001; 0.9 to 4.3 µg/ml), while CoQ10 increased it by 1.6 µg/ml (p<0.001; 0.9 to 2.5 µg/mL), making Ubiquinol absorbed over 2 times as well as CoQ10 in a direct comparison (p<0.005).
When you think of the multiple redox states of CoQ10, you may be inclined to think there is balanced distribution of the form. Quite the contrary: published data clearly shows that young healthy subjects maintain their CoQ10 predominantly in the Ubiquinol form.2 Ubiquinol is not only the preferred form in plasma; scientists have also determined that the predominant form of CoQ10 in healthy tissue (including liver, pancreas, intestine, colon) is Ubiquinol.
CoQ10—especially the Ubiquinol form—is found concentrated in metabolically active cells and tissues. This is because its primary role is to facilitate electron transfer between redox components of the electron transport chain, with the ultimate goal of generating ATP (energy) formation.3 Its primary role relates to bioenergetics, ensuring constant synthesis of energy.
This is a process known as oxidative phosphorylation which takes place in the inner mitochondrial membrane.
Ubiquinol and Aging
The Oxidative Stress Theory of Aging calls out the consistent and cumulative damage done by reactive oxygen species (ROS) inside the body as one of the main perpetrators of the normal changes seen in aging.4,5 The accumulation of oxidative damage to macromolecules (lipids, DNA, and proteins) by ROS constitutes the foundation of aging.6During aging, it is important to protect macromolecules (RNA, DNA, proteins, and lipids) from attack by reactive oxygen species. Protecting the mitochondria from oxidative damage can protect their overall function and the integrity of mitochondrial DNA. Excess mitochondrial oxidation is thought to be one of many complex factors involved in the aging process. Another molecule prone to oxidation is LDL cholesterol; oxidized LDL is the first step to formation of plaque in the arteries. Ubiquinol’s antioxidant umbrella protects mitochondrial membrane proteins, DNA and LDL cholesterol from free radical-induced oxidative damage.7 However, not all antioxidants are as thorough and powerful as Ubiquinol. Its activity allows regeneration of other antioxidants such as vitamin C and vitamin E. Ubiquinol is the most protective antioxidant in the early stages of LDL-cholesterol oxidation.
CoQ10’s importance to the aging process has been known for decades as scientists have shown its decreased values in the brain, heart, and lung of elderly. More recently, scientists at Japan’s Kyorin University evaluated the percentage of CoQ10 vs. Ubiquinol in subjects of different ages and found that aged subjects had a higher percentage of CoQ10 vs. Ubiquinol, indicating greater oxidative stress.8 The impact of aging can be seen in a value called %CoQ10, which equals CoQ10 divided by (Ubiquinol+CoQ10). The %CoQ10 is an indicator of systemic oxidative stress. Research demonstrates the ratio of CoQ10 to Ubiquinol rises with aging. Wada, et al. reported the %CoQ10 in 25-year-olds was 2.8 while the %CoQ10 of 70-year-olds was 4.6 These and other data, including a 2020 8-week parallel group study demonstrating Ubiquinol reduced LDL oxidation and improved endothelial function point to a very important role of Ubiquinol in antioxidant protection and healthy aging.9
Ubiquinol Q30™: Venturing Beyond Softgels
New technologies have given us the chance to offer Ubiquinol that is not constrained to softgel formats. We have created an innovative, stabilized form that is protected by a carbohydrate shell that provides an excellent oxygen barrier (Q30™). This formulation opens the door to including Ubiquinol in many innovations, including preconception health products, cognition formulations, and more. Please contact us at NutrientsSales@kaneka.com so we can assist your product development needs.References
1. Langsjoen PH and Langsjoen AM. Comparison study of plasma CoQ10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone. Clinical Pharmacol Drug Dev. 2014;3(1):13-172. Okamoto T, et al. Matsuya T, Fukunaga Y, et al. Human serum ubiquinol-10 levels and relationship to serum lipids. Int J Vitam Nutr Res. 1989;59(3):288-292
3. Lenaz, G, et al. The Role of Coenzyme Q in Mitochondrial Electron Transport. Mitochondrion. 7S 2007 S8 - S33
4. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998 Apr;78(2):547-81
5. Sies H., Jones D. In: 2nd ed. Fink G., editor. Vol. 3. Elsevier; Amsterdam: 2007. Oxidative stress; pp. 45–48. (Encyclopedia of Stress)
6. Liquori I, et al. Oxidative stress, aging, and diseases. Cllin Interv Aging. 2018; 12:757-772
7. Fiorini, R, et al. Flourescence studies of the interactions of ubiquinol-10 with liposomes. Photochemistry and Photobiology. 2008, 84: 209–214
8. Wada, H, et al. Redox status of coenzyme Q10 is associated with chronological age. Journal of the American Geriatrics Society. 2007; 55(7): 1142-1144
9. Sabbatinelli J, et al. Ubiquinol ameliorates endothelial dysfunction in subjects with mild-to-moderate dyslipidemia: A Randomized Clinical Trial. Nutrients. 2020 Apr 15;12(4):1098