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Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation

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Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation

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Ubiquinol-10 (CoQH2, the reduced form of coenzyme Q10) is a potent antioxidant present in human low-density lipoprotein (LDL). Supplementation of humans with ubiquinone-10 (CoQ, the oxidized coenzyme) increased the concentrations of CoQH2 in plasma and in all of its lipoproteins. Intake of a single oral dose of 100 or 200 mg CoQ increased the total plasma coenzyme content by 80 or 150%, respectively, within 6 h. Long-term supplementation (three times 100 mg CoQ/day) resulted in 4-fold enrichment of CoQH2 in plasma and LDL with the latter containing 2.8 CoQH2 molecules per LDL particle (on day 11). Approx. 80% of the coenzyme was present as CoQH2 and the CoQH2/CoQ ratio was unaffected by supplementation, indicating that the redox state of coenzyme Q10 is tightly controlled in the blood. Oxidation of LDL containing various [CoQH2] by a mild, steady flux of aqueous peroxyl radicals resulted immediately in very slow formation of lipid hydroperoxides. However, in each case the rate of lipid oxidation increased markedly with the disappearance of 80-90% CoQH2. Moreover, the cumulative radical dose required to reach this 'break point' in lipid oxidation was proportional to the amount of CoQH2 incorporated in vivo into the LDL. Thus, oral supplementation with CoQ increases CoQH2 in the plasma and all lipoproteins thereby increasing the resistance of LDL to radical oxidation.
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... α-TOH, like other fat-soluble vitamins, is transported in the body as part of the hydrophobic lipid core of LDL particles [96]. However, it is not α-TOH that protects circulating LDL particles from free radical peroxidation in the bloodstream, but the reduced (phenolic) form of coenzyme Q [6, [97][98][99][100][101]. Based on the fact that in one particle of LDL, there are no more than 1-2 coenzyme Q molecules per 800 molecules of free radical peroxidation substrate, unsaturated phospholipids [102,103] effective inhibition of free radical reactions in LDL by this antioxidant is impossible without its bioregeneration, possibly by mechanism with the participation of α-TOH and ascorbate [103][104][105][106][107]. At the same time, it has been shown that administration of α-TOH at high doses has no effect on LDL oxidizability in CHD patients in vivo [101]. ...
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... Second, Mohr, et al 5 demonstrated that supplementation with ubiquinone results in significantly increased concentrations of ubiquinol in the blood plasma and the circulating lipoproteins and leads to a significantly increased resistance of human low-density lipoproteins to lipid peroxidation. 5 Human biosynthesis of CoQ10 generally reaches a peak in a person's 20s and then gradually but steadily declines with increasing age. 6 The decline in the endogenous production of CoQ10 is associated with the ageing process and the development of ageing-related diseases. ...
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Background: Coenzyme Q10 (CoQ10) is a popular nutritional supplement that is available in both the oxidized and reduced form. The marketing of CoQ10 to physicians often asserts that one form is superior to the other. This study was designed to compare and contrast the stability, absorption and claims made for the reduced form of CoQ10 (ubiquinol) compared with the oxidized form (ubiquinone). There is a need for studies that examine the contents of commercially available ubiquinol products microscopically at room, body and 50°C temperatures. There is also a need for studies of the state of the ubiquinol contents when exposed to a 2.2 pH solution that simulates stomach acidity and an 8.2 pH solution that simulates acidity in the duodenum. Methods: An investigation of the instability of ubiquinol supplements was conducted via an in vitro study of 13 ubiquinol products marketed in the United States that measured the extent of the conversion of the ubiquinol content to ubiquinone, when the ubiquinol was squeezed out of the capsule at room temperature and when the ubiquinol contents were exposed to a 2.2 pH solution and an 8.2 pH solution. Results: In the in vitro study, the percentage of ubiquinol converted to ubiquinone at body temperature was greatest in the 8.2 pH simulated small intestinal juice: 76%. The percentage of ubiquinol converted to ubiquinone at body temperature in the 2.2 pH gastric juice that simulated conditions in the stomach was 54%. Conclusions: Ubiquinol in commercial nutritional supplements is fairly stable inside the gelatin capsule but unstable in gastric and small intestine digestive fluids. Based on the data from the lab studies, most of the ubiquinol from the capsule will be converted to ubiquinone prior to reaching the absorption cells in the small intestines. Animal studies are needed to test this hypothesis.
... If left untreated, the patient is at risk of suffering from coronary artery diseases such as myocardial infarction and stroke caused by acute thrombosis and plaque build-up [11]. Oxidative modification of LDL in the arterial wall is believed to contribute toward the development of atherosclerosis and is one of the major contributors of heart disease [12]. In addition, high level of LDL is well known to result in plaque build-up in the heart arteries, resulting in narrowing of the arteries which reduces the efficiency of oxygen-rich blood transport, a condition known as ischaemia [13]. ...
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Background: Coenzyme Q10 is one of the most widely sold nutritional supplements in the United States. Coenzyme Q10 is available in both its oxidized form (ubiquinone) and its reduced form (ubiquinol). The predominant marketing of Coenzyme Q10 to physicians and patients asserts that the ubiquinol form of Coenzyme Q10 has superior absorption to the ubiquinone form. This study has been designed to compare and contrast the stability and absorption of ubiquinol supplements, as well as the claims made for ubiquinol compared with ubiquinone.Ubiquinol, the reduced state of Coenzyme Q10, is commercially available as a nutritional supplement; however, ubiquinol, by its nature as an electron donor, is much less stable than ubiquinone, the oxidized state of Coenzyme Q10. The absorption, bioavailability and efficacy of ubiquinol products has been much less often tested in clinical trials. Consequently, insufficiently documented marketing claims are being made for ubiquinol supplements. Methods: In Part 1 of this report on the instability of the lipid-soluble antioxidant ubiquinol, SIBR Research presented data from lab studies showing that oral ubiquinol is likely to be oxidized to ubiquinone and absorbed as ubiquinone. In this Part 2, SIBR Research conducted a study of the transfer and absorption of orally ingested ubiquinol in large dogs. Results: In the dog studies, the percentage of ubiquinol converted to ubiquinone increased as the capsule contents passed through the stomach and small intestines and into the lymph system. Conclusions: The dog studies demonstrate that oral ubiquinol in commercial nutritional supplements is not stable in the gastrointestinal tract of large dogs. Based on these results, it seems likely that in humans also, most of the ubiquinol from capsules will be oxidized to ubiquinone in the acid profile between the stomach and the small intestines, where there is a wide range of acidity. The ubiquinol from the supplement will be absorbed in the ubiquinone state and will pass into the lymph system as ubiquinone, where it will be reduced back to ubiquinol. It will pass from the lymph system into the blood circulation as ubiquinol.
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A fast single-step lipid extraction procedure and high-performance liquid chromatography with in-line uv and electrochemical detection are used for the simultaneous quantitative determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions. The compounds of interest can be quantitatively extracted into hexane from a sodium dodecyl sulfate-treated aqueous homogenate after precipitation of protein by addition of an equal volume of ethanol. α-, γ-, and δ-Tocopherol, ubiquinol 9, ubiquinol 10, and ubiquinones 9 and 10 can be well separated on a reversed phase column. Ubiquinones are detected at 275 nm by the uv detector, and ubiquinols and tocopherols by the electrochemical detector in the oxidative mode. Quantitation is done by comparing chromatographic peak heights to those of a standard solution containing known amounts of tocopherols, ubiquinols 9 and 10, and ubiquinones 9 and 10, analyzed under identical conditions. The high sensitivity of the electrochemical detection allows operation at low potentials (+0.5 V) with low detector response, but high selectivity for the easily oxidizable tocopherols and ubiquinols and decreased baseline noise. The uv detection limits the overall sensitivity of the procedure to 2 pmol ubiquinone, corresponding to 0.1 μm ubiquinone in the lipid extract. The ranges of values obtained for rat and guinea pig tissues, for rat liver mitochondria, and for blood and plasma from rats and humans are given.