Iron, alpha-tocopherol, oxidative damage and micronucleus formation in rat splenocytes

The influence of low and high alpha-tocopherol diets in concert with a high polyunsaturated fat content and a modest increase in dietary iron has been studied. Iron supplementation at 5 times the recommended dietary level was not associated with any increased sensitivity of splenocytes to any of several oxidative challenges ex vivo. Despite the significantly higher alpha-tocopherol concentrations in plasma and liver in animals supplemented with this vitamin, there was no apparent protection against oxidative genotoxicity as judged by the formation of micronuclei in splenocytes subjected to oxidative stress ex vivo. These results add to the accumulating evidence that vitamin E supplementation has little effect against oxidative genomic damage, at least as demonstrated by an increase in micronucleus frequency.     

Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation.

Twelve clinically healthy subjects participated in a vitamin E supplementation study. Eight were given daily dosages of 150, 225, 800, or 1200 IU RRR-alpha-tocopherol for 21 days (two persons per dose) and four received placebo. Prior, during, and after the supplementation period, alpha-tocopherol, gamma-tocopherol, and carotenoids were determined in plasma and low density lipoprotein (LDL). The maximum levels of alpha-tocopherol were 1.7- to 2.5-times the baseline values in plasma and 1.7- to 3.1-times in LDL. A high correlation existed between alpha-tocopherol in plasma and LDL. gamma-Tocopherol significantly decreased in plasma and LDL during vitamin E supplementation. No significant influence on the lipoprotein and lipid status and carotenoid levels of the participants occurred throughout the supplementation. The resistance of LDL against copper-mediated oxidation was also measured. The oxidation resistance of LDL was significantly higher during vitamin E supplementation. However, the efficacy of vitamin E in protecting LDL varied from person to person. The statistical evaluation of all data gave a correlation of r2 = 0.51 between alpha-tocopherol in LDL and the oxidation resistance as measured by the length of the lag-phase preceding the oxidation of LDL. No association was seen between levels of carotenoids and vitamin E in plasma and LDL. The present study clearly shows that in humans the oxidation resistance of LDL can be increased by vitamin E supplementation.     

Serum ex vivo lipoprotein oxidizability in patients with ischemic heart disease supplemented with vitamin E

The decreased oxidizability of plasma lipoproteins is related to the increased vitamin E intake and its association with a relatively lower incidence of coronary heart disease has been proposed. We investigated the effect of the in vivo vitamin E supplementation on the oxidizability of serum lipids in patients with ischemic heart disease and a moderate hypercholesterolemia. Thirty-two patients (16 males and 16 postmenopausal women) participated in this placebo-controlled, randomized trial. They were treated with 400 mg vitamin E/day for 6 weeks. The copper-induced serum lipid oxidizability ex vivo was assessed by measuring conjugated diene formation at 245 nm. We also measured vitamin E, malondialdehyde (MDA) and uric acid concentrations in the plasma. Because of observed significant differences in parameters of serum lipid oxidizability (lag time and maximal rate of oxidation), plasma alpha-tocopherol and MDA levels between male patients and postmenopausal women supplemented with vitamin E, the results were compared between both genders. Six weeks of vitamin E supplementation significantly increased plasma vitamin E levels (by 87 %) in male patients but in postmenopausal women only by 34 %. Concomitantly with increased plasma levels of vitamin E the decrease in plasma MDA levels was observed in male patients (decrease by 20 %; p=0.008), but in postmenopausal women the decrease did not attain statistical significance. Plasma uric acid levels were not apparently changed in placebo or vitamin E supplemented groups of patients. The changes in ex vivo serum lipid oxidizability after vitamin E, supplementation have shown a significantly prolonged lag time (by 11 %; p=0.048) and lowered rate of lipid oxidation (by 21 %; p=0.004) in male patients in comparison with postmenopausal women. Linear regression analysis revealed a significant correlation between plasma vitamin E levels and the lag time (r=0.77; p=0.03) and the maximal rate of serum lipid oxidation (r=-0.70; p=0.05) in male patients. However, in postmenopausal women the correlations were not significant. We conclude that 400 mg vitamin E/day supplementation in patients with ischemic heart disease and a moderate hypercholesterolemia influenced favorably ex vivo serum lipid oxidation of male patients when compared with postmenopausal women. The observed differences between both genders could be useful in the selection of the effective vitamin E doses in the prevention of coronary heart disease.     

Vitamin E and heart disease: basic science to clinical intervention trials

A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.     

Fluvastatin depresses the enhanced lipid peroxidation in vitamin E-deficient hamsters.

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has recently been reported to have the antioxidative activity in vitro. However, it is still unclear whether chronic treatment with this drug actually leads to amelioration of the redox status in the body. In this study, we investigated the antioxidative effect of fluvastatin in vivo, using a vitamin E-deficient hamster model, an in vivo model of enhanced oxidative stress. After pre-treatment with a vitamin E-deficient diet for 2 months, fluvastatin, pravastatin or probucol was added to the diet for 1 month. Vitamin E deficiency caused a significant increase in the levels of plasma oxidative stress markers such as 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and hydroperoxides. Furthermore, there was a significant increase in the oxidizability of plasma lipids in the vitamin E-deficient animals, indicating that the oxidative stress was increased in the circulation. Fluvastatin markedly depressed the above oxidative stress markers in plasma, and significantly decreased the oxidizability of plasma lipids without affecting their levels. Probucol, a reference antioxidant, also showed a similar effect while pravastatin, another HMG-CoA reductase inhibitor, showed only a weak improvement. We suggest that the treatment with fluvastatin leads to a reduction of oxidative stress in vivo, which is mainly derived from its antioxidative property rather than its lipid-lowering activity.     

Oxidative stress and antioxidant status in mouse kidney: effects of dietary lipid and vitamin E plus iron

The purpose of this study was to determine the effects of dietary fat, vitamin E, and iron on oxidative damage and antioxidant status in kidneys of mice. Sixty 1-month-old male Swiss-Webster mice were fed a basal vitamin E-deficient diet that contained either 8% fish oil + 2% corn oil or 10% lard with or without 1 g all-rac-alpha-tocopherol acetate or 0.74 g ferric citrate per kilogram of diet for 4 weeks. Significantly (P < 0.05) higher levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), and conjugated dienes were found in the kidneys of mice fed with fish oil compared with mice fed lard irrespective of vitamin E status. Mice maintained on a vitamin E-deficient diet had significantly higher renal levels of TBAR, but not conjugated dienes, than the supplemented group. Fish oil fed mice receiving vitamin E supplementation had lower levels of alpha-tocopherol than did mice in the lard fed group. Significantly higher levels of ascorbic acid were also found in the kidneys of mice fed with fish oil than were found in mice fed lard. The levels of protein carbonyls and glutathione (GSH), and activities of catalase, superoxide dismutase, selenium (Se)-GSH peroxidase, and non-Se-GSH peroxidase were not significantly altered by dietary fat or vitamin E. Dietary iron had no significant effect on any of the oxidative stress and antioxidant indices measured. The results obtained provide experimental evidence for the pro-oxidant effect of high fish oil intake in mouse kidney and suggest that dietary lipids play a key role in determining cellular susceptibility to oxidative stress.     

Fat soluble antioxidants in brood‐rearing great tits Parus major: relations to health and appearance

The concept of parasite‐mediated sexual selection assumes that females may improve offspring fitness by selecting mates on the basis of sexual ornaments that honestly reveal the health state of a partner. Expression of such signals may be particularly sensitive to oxidative damage caused by excess production of oxidative metabolites and free radicals. To control and neutralise free radicals, animals rely heavily on dietary fat‐soluble antioxidants such as vitamin E and A, and carotenoids. However, the organism's need for free radical scavenging may interfere with the opposite need to generate oxidative stress for fighting parasitic infections. We investigated plasma concentrations of carotenoids and vitamin A and E in brood‐rearing great tits Parus major in relation to carotenoid‐based plumage coloration, sex, habitat, leukocyte hemoconcentrations and infection status with Haemoproteus blood parasites. Rural great tits differed from urban ones and males from females with respect to the hue of the yellow ventral feathers. However, plasma antioxidant concentrations were not related to sex, habitat or plumage coloration. Plasma carotenoid concentration correlated positively with indices of immune system activation as measured by blood counts of lymphocytes and eosinophils. Birds with gametocytes of Haemoproteus in their blood had higher plasma concentrations of carotenoids and vitamin E than unparasitized individuals. These results are consistent with the idea that maintenance of high blood antioxidant levels might conflict with individual needs to rely on oxidative stress for fighting infections.     

Oxidative stress does not influence carotenoid mobilization and plumage pigmentation

Oxidative stress has been suggested to create a link between 'good genes' and carotenoid coloration via an allocation conflict between external pigmentation and internal antioxidant functions. However, although carotenoid displays have been extensively investigated, there are no experimental tests of the antioxidant efficiency of carotenoids in vivo. We induced oxidative stress in a small passerine (the great tit, Parus major) under both carotenoid deprivation and supplementation, and investigated the effect on carotenoid mobilization (i.e. plasma) and allocation (i.e. deposition in feather incorporation and liver storage). We found no effects of the stressor on either mobilization or allocation of carotenoids. These results reject the previously suggested superior role of carotenoid's function as antioxidant in vivo with important implications for signal content and honesty.     

Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E

Vitamin E is a lipophilic anti-oxidant that can prevent the oxidative damage of atherogenic lipoproteins. However, human trials with vitamin E have been disappointing, perhaps related to ineffective levels of vitamin E in atherogenic apoB-containing lipoproteins. Phospholipid transfer protein (PLTP) promotes vitamin E removal from atherogenic lipoproteins in vitro, and PLTP deficiency has recently been recognized as an anti-atherogenic state. To determine whether PLTP regulates lipoprotein vitamin E content in vivo, we measured alpha-tocopherol content and oxidation parameters of lipoproteins from PLTP-deficient mice in wild type, apoE-deficient, low density lipoprotein (LDL) receptor-deficient, or apoB/cholesteryl ester transfer protein transgenic backgrounds. In all four backgrounds, the vitamin E content of very low density lipoprotein (VLDL) and/or LDL was significantly increased in PLTP-deficient mice, compared with controls with normal plasma PLTP activity. Moreover, PLTP deficiency produced a dramatic delay in generation of conjugated dienes in oxidized apoB-containing lipoproteins as well as markedly lower titers of plasma IgG autoantibodies to oxidized LDL. The addition of purified PLTP to deficient plasma lowered the vitamin E content of VLDL plus LDL and normalized the generation of conjugated dienes. The data show that PLTP regulates the bioavailability of vitamin E in atherogenic lipoproteins and suggest a novel strategy for achieving more effective concentrations of anti-oxidants in lipoproteins, independent of dietary supplementation.     

Fat soluble antioxidants in brood-rearing great tits Parus major: relations to health and appearance

The concept of parasite-mediated sexual selection assumes that females may improve offspring fitness by selecting mates on the basis of sexual ornaments that honestly reveal the health state of a partner. Expression of such signals may be particularly sensitive to oxidative damage caused by excess production of oxidative metabolites and free radicals. To control and neutralise free radicals, animals rely heavily on dietary fat-soluble antioxidants such as vitamin E and A, and carotenoids. However, the organism's need for free radical scavenging may interfere with the opposite need to generate oxidative stress for fighting parasitic infections. We investigated plasma concentrations of carotenoids and vitamin A and E in brood-rearing great tits Parus major in relation to carotenoid-based plumage coloration, sex, habitat, leukocyte hemoconcentrations and infection status with Haemoproteus blood parasites. Rural great tits differed from urban ones and males from females with respect to the hue of the yellow ventral feathers. However, plasma antioxidant concentrations were not related to sex, habitat or plumage coloration. Plasma carotenoid concentration correlated positively with indices of immune system activation as measured by blood counts of lymphocytes and eosinophils. Birds with gametocytes of Haemoproteus in their blood had higher plasma concentrations of carotenoids and vitamin E than unparasitized individuals. These results are consistent with the idea that maintenance of high blood antioxidant levels might conflict with individual needs to rely on oxidative stress for fighting infections.     

Vitamin E and oxidative stress

Oxidative stress can result from or be enhanced by a large variety of conditions, including nutritional imbalance, exposure to chemical and physical agents in the environment, strenuous physical activities, injury, and hereditary disorders. While many enzymes and compounds are involved in protecting cells from the adverse effects of oxidative stress, vitamin E occupies an important and unique position in the overall antioxidant defense. The antioxidant function of vitamin E is closely related to the status of many dietary components. Vitamin E-depleted animals are generally more susceptible to the adverse effects of environmental agents than supplemented animals. Also, vitamin E supplementation is beneficial to certain groups of the population. However, supplementing vitamin E in experimental subjects maintained on a nutritionally adequate diet does not always provide additional protection. Differential metabolic responses in various organs and differences in experimental conditions often contribute in the discrepancies in the literature. The lack of clear evidence for the occurrence of lipid peroxidation or antioxidant function of vitamin E in vivo can be attributed partly to the presence of active pathways for metabolizing hydroperoxides, aldehydes, and other oxidation products. Specific and sensitive techniques for measuring lipid peroxidation products in biological systems are essential for understanding the role of free radical-induced lipid peroxidation in tissue damage and antioxidant function of vitamin E in vivo.     

Effect of Vitamin E and Polyunsaturated Fatty Acids on Cryopreserved Sperm Quality in Bos taurus Bulls Under Testicular Heat Stress

Taurine bulls are highly susceptible to heat stress, leading to increased oxidative stress (OS) and impaired sperm viability. Polyunsaturated fatty acids (PUFAs) supplementation can be an alternative to improve semen quality, which also results in more sperm susceptibility to lipid peroxidation. Moreover, this deleterious effect can be exacerbated in animals affected by heat stress. Vitamin E is a key antioxidant that counteracts lipid peroxidation of sperm membrane caused by OS. Thus, combining PUFAs with vitamin E may improve sperm quality. In this context, this study aimed to evaluate the effect of interaction between PUFAs and vitamin E on sperm quality in Bos taurus bulls under testicular heat stress. Sixteen taurine bulls under testicular heat stress were randomly assigned in four groups: Control, Vitamin E, PUFA, and PUFA?+?Vitamin E. All groups lasted for 60 days. Samples were cryopreserved/thawed and analyzed for motility variables (CASA), membrane and acrosome integrity, mitochondrial activity, susceptibility to oxidative stress, DNA integrity, and sperm-binding capacity. Results showed that vitamin E had a beneficial effect on some sperm characteristics, whereas PUFA supplementation had an adverse effect when the two treatments were evaluated separately. Finally, the association between PUFAs and vitamin E did not improve sperm quality.     

Dietary supplementation with beta-carotene, but not with lycopene, inhibits endothelial cell-mediated oxidation of low-density lipoprotein.

Carotenoids may protect low-density lipoprotein from oxidation, a process implicated in the development of atherosclerosis. Our previous studies showed that in vitro enrichment of low-density lipoprotein (LDL) with beta-carotene protected it from cell-mediated oxidation. However, in vitro enrichment with either lutein or lycopene actually enhanced oxidation of the LDL. In the present studies we have examined the impact of LDL carotenoid content on its oxidation by human aortic endothelial cells (EaHy-1) in culture, comparing the effects of in vivo supplementation with in vitro enrichments. The beta-carotene content in human LDL was increased three- to sixfold by daily supplementation with 15 mg beta-carotene for 4 weeks, and the lycopene content of LDL in other individuals was increased two- to threefold by ingestion of one glass (12 ounce) of tomato juice daily for 3 weeks. LDL isolated from these healthy, normolipidemic donors not taking supplemental carotenoid was incubated at 0.25 mg protein/ml with EaHy-1 cells in Ham's F-10 medium for up to 48 h. Following dietary beta-carotene supplementation, LDL oxidation (as assessed by formation of lipid hydroperoxides) was markedly inhibited, to an even greater extent than was observed for LDL enriched in vitro with beta-carotene (that resulted in an 11- to 12-fold increase in LDL beta-carotene). No effect on cell-mediated oxidation was observed, however, for LDL enriched in vivo with lycopene. Thus, beta-carotene appears to function as an antioxidant in protecting LDL from cell-mediated oxidation although lycopene does not. The fact that the three- to sixfold enrichments of LDL with beta-carotene achieved by dietary supplementation were more effective in inhibiting oxidation than the 11- to 12-fold enrichments achieved by an in vitro method suggests that dietary supplementation is a more appropriate procedure for studies involving the enrichment of lipoprotein with carotenoids.     

Oxidative stress during ex vivo hemodialysis of blood is decreased by a novel hemolipodialysis procedure utilizing antioxidants

The high cardiovascular mortality in patients receiving hemodialysis (HD) has been attributed, in part, to oxidative stress. Here we examined the effectiveness of antioxidants introduced by means of a novel hemolipodialysis (HLD) procedure in terms of reducing oxidative stress during ex vivo blood circulation. Oxidative stress was studied in a model HD system resembling the extracorporeal circulation of blood during clinical HD. Blood circulation produced an increase of up to 280% in free hemoglobin levels and an increase of 320% in electronegative LDL (LDL(-)) subfraction. A significant correlation between LDL(-) and free hemoglobin levels confirmed previous findings that LDL(-) formation during ex vivo circulation of blood can be mediated by the oxidative activity of free hemoglobin. These effects were significantly attenuated during HLD using a dialysis circuit containing vitamin E with or without vitamin C. By contrast, HLD with vitamin C alone had a marked pro-oxidant effect. TBARS, lipid hydroperoxides, vitamin E and beta-carotene content in LDL were not significantly altered by the HD procedure. These findings demonstrate the occurrence of oxidative stress in human plasma where lipoproteins are a target and indicate antioxidant-HLD treatment as a specific new approach to decreasing the adverse oxidative stress frequently associated with cardiovascular complications in high-risk populations of uremic patients.     

Oxidative stress and serum paraoxonase activity in experimental hypothyroidism: effect of vitamin E supplementation

Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Since data on the oxidative status of hypothyroidism are limited and controversial, we investigated the oxidant and antioxidant status and serum paraoxonase/arylesterase activities in propylthiouracil-induced hypothyroidism and examined the effect of vitamin E supplementation on this experimental model. Forty male Sprague Dawley rats were randomly divided into four groups (group 1, control; group 2, control + vitamin E; group 3, propylthiouracil; group 4, propylthiouracil + vitamin E). Plasma, red blood cell, liver, heart and skeletal muscle malondialdehyde levels were increased in the propylthiouracil-treated group compared with the control rats and were decreased in propylthiouracil + vitamin E group compared with the propylthiouracil-treated group. Vitamin E supplementation also significantly increased liver and kidney reduced glutathione levels in propylthiouracil treated animals. Serum paraoxonase and arylesterase activities were decreased in propylthiouracil treated group and vitamin E supplementation caused significant increase in serum paraoxonase activity compared with the propylthiouracil-treated rats. These findings suggest that hypothyroidism is accompanied with increased oxidative stress and vitamin E supplementation exerts beneficial effects on this situation.     

Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: Improvement during vitamin E supplementation

Antioxidants such as vitamin E protect unsaturated fatty acids of LDL against oxidation. In the ex vivo model used, LDL was exposed to Cu²⁺ ions, a potent prooxidant capable of initiating the oxidation of LDL. The lag time, indicating the delay of conjugated diene formation in LDL due to antioxidant protection, was measured in 54 cystic fibrosis (CF) patients with plasma -tocopherol levels below (Group A, n = 30) or above (Group B, n = 24) 15.9 μmol/L (mean - 2 SD of Swiss population). Patients were reevaluated after 2 months on 400 IU/d of oral RRR--tocopherol. In group A, -tocopherol concentrations in LDL increased significantly from 3.2 ± 1.6 mol/mol LDL to 8.2 ± 2.8 mol/mol (P < 0.001) and lag times increased from 79 ± 33, min to 126 ± 48 min (P < 0.001), whereas in the vitamin E sufficient group B no further increase neither in LDL -tocopherol concentrations or in lag times was observed. LDL oleic acid concentrations were higher, and linoleic acid concentrations were lower in patients than in controls. After efficient vitamin E supplementation, lag times were positively related to LDL -tocopherol (P < 0.01) and negatively to LDL linoleic and arachidonic acid content (P < 0.001). The maximum rate of oxidation correlated positively with linoleic and arachidonic acid concentrations, as did the maximum conjugated diene absorbance. These results indicate that LDL resistance to oxidation is impaired in vitamin E deficient CF patients but can be normalized within 2 months when -tocopherol is given in sufficient amounts. Linoleic and arachidonic acid content exhibit a major influence on the LDL resistance to oxidation.     

Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation

To assess the effects of short-term and long-term vitamin C supplementation in humans on plasma antioxidant status and resistance to oxidative stress, plasma was obtained from 20 individuals before and 2h after oral administration of 2g of vitamin C, or from eight subjects enrolled in a vitamin C depletion-repletion study using increasing daily doses of vitamin C from 30 to 2500 mg. Plasma concentrations of ascorbate, but not other physiological antioxidants, increased significantly after short-term supplementation, and increased progressively in the long-term study with increasing vitamin C doses of up to 1000 mg/day. Upon incubation of plasma with a free radical initiator, ascorbate concentrations were positively correlated with the lag phase preceding detectable lipid peroxidation. We conclude that vitamin C supplementation in humans dose-dependently increases plasma ascorbate concentrations and, thus, the resistance of plasma to lipid peroxidation ex vivo. Plasma and body saturation with vitamin C in humans appears desirable to maximize antioxidant protection and lower risk of oxidative damage.     

Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized placebo-controlled clinical study

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in the change of plasma concentrations and in the antioxidative efficiency, we carried out a double-masked, double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), d-alpha-tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated the pharmacokinetics of Q10 in a separate one-week substudy. In the group that received both antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10 supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.     

Differential Indicators of Diabetes-Induced Oxidative Stress in New Zealand White Rabbits: Role of Dietary Vitamin E Supplementation

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. PlasmaLPOwas influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasmaLPOwas the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.     

The role of vitamin E in atherosclerosis

Epidemiological and biochemical studies infer that oxidative processes, including the oxidation of low-density lipoprotein (LDL), are involved in atherosclerosis. Vitamin E has been the focus of several large supplemental studies of cardiovascular disease, yet its potential to attenuate or even prevent atherosclerosis has not been realised. The scientific rationale for vitamin E supplements protecting against atherosclerosis is based primarily on the oxidation theory of atherosclerosis, the assumption that vitamin E becomes depleted as disease progresses, and the expectation that vitamin E prevents the oxidation of LDL in vivo and atherogenic events linked to such oxidation. However, it is increasingly clear that the balance between vitamin E and other antioxidants may be crucial for in vivo antioxidant protection, that vitamin E is only minimally oxidised and not deficient in atherosclerotic lesions, and that vitamin E is not effective against two-electron oxidants that are increasingly implicated in both early and later stages of the disease. It also remains unclear as to whether oxidation plays a bystander or a casual role in atherosclerosis. This lack of knowledge may explain the ambivalence of vitamin E and other antioxidant supplementation in atherosclerosis.