High-dose Antioxidant Supplementation Research Articles

Glutathione for defense of your body’s natural antioxidant

Glutathione is a powerful antioxidant that has gained a lot of attention for its purported health benefits. But what is glutathione, and does it actually affect the body ?Some people swear by its anti-aging properties, while others say that it can treat autism, increase fat metabolism, and even prevent cancer. It is best to avoid high-dose antioxidant supplements unless a trusted healthcare provider prescribes or recommends them. The best way to take in antioxidants is through foods and beverages, such as vegetables, fruits, nuts, fish, spices, and tea. The levels of the antioxidant GSH, which can be increased through diet and lifestyle changes, may influence motivation levels. People often want to get more done in a day, but sometimes it’s hard to feel motivated to complete tasks. Several factors influence motivation, but there’s a lot about the physiology behind motivation that experts don’t completely understand. A​ recent study published in eLife found that levels of the antioxidant glutathione in a specific part of the brain likely play a key role in motivation levels. One can increase their glutathione levels through dietary sources, for example, by eating sulfur-rich foods such as meat, eggs, and grains, and consuming more dairy and whey protein.

Antioxidants for preventing and reducing muscle soreness after exercise.

Antioxidants for preventing and reducing muscle soreness after exercise.

Immunological aspects of sport nutrition.

Prolonged bouts of exercise and heavy training regimens are associated with depression of immune system functions that can increase the risk of picking up opportunistic infections such as the common cold and influenza. Some common sport nutrition practices including high-carbohydrate diets and carbohydrate ingestion during exercise, training with low-glycogen stores, intentional dieting for weight loss, ingestion of high-dose antioxidant supplements and protein ingestion post exercise may influence immune system status in athletes. In order to maintain robust immunity, athletes need to consume a well-balanced diet that is sufficient to meet their requirements for energy, carbohydrate, protein and micronutrients. Dietary deficiencies of protein and specific micronutrients are well known to be potential causes of immune dysfunction and an adequate intake of some essential minerals including iron and zinc and the vitamins A, D, E, B6 and B12 are important to maintain a healthy immune function. Vitamin D may be a particular concern as recent studies have emphasised its importance in limiting infection episode incidence and duration in both the general population and in athletes and many individuals exhibit inadequate vitamin D status during the winter months. There is only limited evidence that individual amino acids, β-glucans, herbal extracts and zinc are capable of boosting immunity or reducing infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotics, vitamin D3, bovine colostrum and plant polyphenol containing supplements or foodstuffs currently offer the best chance of success, particularly for those individuals who are prone to illness.

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Introduction: Antioxidant supplementation has been shown to decrease post-operative atrial fibrillation in cardiac surgery patients. A high-dose antioxidant supplementation protocol of ascorbic acid, selenium, and vitamin E for 7 days was implemented at our institution in October 2005 for patients admitted to the Trauma ICU. Previous studies in trauma patients demonstrated that antioxidant supplementation decreases mortality and hospital/ICU length of stay. The purpose of this study is to determine if the incidence of atrial arrhythmias is reduced in trauma patients receiving high-dose antioxidant supplementation. Hypothesis: We hypothesize that antioxidant supplementation decreases the incidence of atrial arrhythmias in trauma patients. Methods: In this single-center, retrospective cohort study at Vanderbilt University Medical Center, patients?18 years of age and admitted to the Trauma ICU for? 48 hours were eligible for inclusion. The antioxidant group consists of patients admitted from October 2005 to June 2011 who received the antioxidant protocol for? 48 hours. The control group consists of patients admitted from January 2000 to September 2005, prior to antioxidant supplementation. Patients experiencing arrhythmias were identified by ICD-9 codes. The primary outcome is the incidence of atrial arrhythmias in the first two weeks of hospitalization or prior to discharge. Results: There were 4,691 patients in this study (1,622 patients in the antioxidant group and 2,414 patients in the control group). The incidence of atrial arrhythmias was 3.02% in the antioxidant group versus 3.31% in the control group (P = 0.096; Adj OR[95% CI]: 1.64 [0.92, 2.93]). There was no difference in the average time to arrhythmia occurrence. The expected survival time of patients in the control group was decreased compared to those receiving antioxidant therapy (Adj TR[95% CI]: 0.65 [0.43, 0.97]). Conclusions: The high-dose antioxidant protocol did not significantly decrease the incidence of atrial arrhythmias in trauma patients. This study confirmed the benefit of decreased hospital mortality seen in previous studies of antioxidant supplementation at our institution.

Heart healthy=prostate healthy: SELECT, the symbolic end of preventing prostate cancer via heart unhealthy and over anti-oxidation mechanisms?

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized over 35 000 men into four groups: high-dose vitamin E (400 IU day−1), high-dose selenium (200 mcg day−1), combination of vitamin E and selenium, or placebo.1 The brief time period to reach full recruitment was unprecedented; thus, it seemed that participants and health-care professionals were equally eager to test the hypothesis that high-dose antioxidant supplementation could prevent prostate cancer. However, the trial was terminated early, after a median of 5.5 years due to a lack of efficacy, although at the time a non-significant (P=0.06) increased risk of prostate cancer in the vitamin E arm, and type 2 diabetes in the selenium group (P=0.16) were observed.

Abstract 1728: The Defect in HDL Function and Reverse Cholesterol Transport Found in Diabetic Mice with the Haptoglobin 2–2 Genotype Can Be Corrected with High Dose Antioxidant Therapy

Background. The primary function of the haptoglobin (Hp) protein is to clear free hemoglobin (Hb). Two common alleles exist at the Hp locus (1 and 2). We recently demonstrated that reverse cholesterol transport is impaired in individuals with Diabetes Mellitus (DM) and the Hp 2–2 genotype which may explain the increased incidence of cardiovascular disease in this population. We sought to test the hypothesis that clearance of the Hp 2-Hb complex is slower in DM allowing more complex to bind to HDL thereby resulting in increased oxidative modification of HDL and inhibition of reverse cholesterol transport and determine if antioxidant therapy could restore normal HDL function in Hp 2–2 DM mice. Methods and Results. Injection of 125 I-labeled Hp 1 or Hp 2-Hb complexes into non-DM mice demonstrated that the half-life of the Hp 2-Hb complex was 2–3 fold longer than the Hp 1-Hb complex (57.8 ± 2.8 vs. 20.4 ± 1.7 min). Moreover, in DM the half-life of the Hp 2-Hb complex was doubled while the half-life of the Hp 1-Hb complex was unchanged (103 ± 3.9 vs. 18.6 ± 1.8 min). Coimmunoprecipitation studies demonstrated that over 25% of the injected Hp 2-Hb complex was associated with HDL in DM mice representing a greater than 10 fold increase compared to Hp 1-Hb complex in non-DM mice. Coimmunoprecipitation studies in Hp 0 (knockout) mice demonstrated that the Hp protein was absolutely necessary for the interaction of Hb with HDL. Reverse cholesterol transport was impaired by DM in Hp 2 mice but this impairment was prevented by high dose antioxidant supplementation to these mice. Conclusions. These data may explain why the Hp 2 genotype promotes less efficient reverse cholesterol transport in DM and suggests that strategies targeted to decrease oxidation of HDL by the Hp 2-Hb complex may improve HDL function.

Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes

Memory impairment is observed in adults with type 2 diabetes mellitus (T2DM), with further acute deficits after meal ingestion. This study explored whether postprandial oxidative stress was a contributor to these meal-induced memory deficits. Sixteen adults with T2DM (mean age, 63.5 +/- 2.1 years) who were not regularly taking high-dose antioxidant supplements were fed a high-fat meal, the same test meal with vitamins C (1000 mg) and E (800 IU) tablets, or water on 3 separate occasions. After meal ingestion, a battery of cognitive tests were administered, which included measures of delayed verbal memory, assessed at 60 and 105 minutes after meal ingestion. Relative to water consumption, the high-fat meal resulted in poorer performance at 105 minutes postingestion on measures of delayed verbal recall (word list and paragraph recall) and working memory (Digit-Span Forward). Coconsumption of antioxidant vitamins and high-fat meal prevented this meal-induced deficit such that performance on these tasks was indistinguishable from that after water intake. At the same time point, a small but significant improvement on the word-naming and color-naming components of Stroop was observed after meal ingestion, relative to water, irrespective of whether antioxidants were consumed, demonstrating the specificity of meal-induced impairments to memory function. Executive function, assessed by Trails Parts A and B, was not influenced by meal or antioxidant ingestion. In adults with T2DM, coconsumption of antioxidant vitamins minimizes meal-induced memory impairment, implicating oxidative stress as a potential contributor to these decrements.

Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and meta-analysis

The aim of this review was to examine the evidence as to whether antioxidant vitamin or mineral supplements prevent the development of AMD or slow down its progression. Randomised trials comparing antioxidant vitamin and/or mineral supplement to control were identified by systematic electronic searches (updated August 2007) and contact with investigators. Data were pooled after investigating clinical and statistical heterogeneity. There was no evidence that antioxidant (vitamin E or beta-carotene) supplementation prevented AMD. A total of 23 099 people were randomised in three trials with treatment duration of 4-12 years; pooled risk ratio=1.03 (95% CI, 0.74-1.43). There was evidence that antioxidant (beta-carotene, vitamin C, and vitamin E) and zinc supplementation slowed down the progression to advanced AMD and visual acuity loss in people with signs of the disease (adjusted odds ratio=0.68, 95% CI, 0.53-0.87 and 0.77, 95% CI, 0.62-0.96, respectively). The majority of people were randomised in one trial (AREDS, 3640 people randomised). There were seven other small trials (total randomised 525). Current evidence does not support the use of antioxidant vitamin supplements to prevent AMD. People with AMD, or early signs of the disease, may experience some benefit from taking supplements as used in the AREDS trial. Potential harms of high-dose antioxidant supplementation must be considered. These may include an increased risk of lung cancer in smokers (beta-carotene), heart failure in people with vascular disease or diabetes (vitamin E) and hospitalisation for genitourinary conditions (zinc).

Supplemental and Dietary Vitamin E, β-Carotene, and Vitamin C Intakes and Prostate Cancer Risk

Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental beta-carotene was associated with a decreased risk of prostate cancer among men with low baseline plasma beta-carotene levels. We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. We identified 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin E use. Supplemental beta-carotene intake at a dose level of at least 2000 microg/day was associated with decreased prostate cancer risk in men with low (below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced prostate cancer was 492 per 100,000 person-years in those who did not take supplemental vitamin E, 153 per 100,000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in those who took supplemental vitamin E for 10 or more years. Among men with low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was 1122 per 100,000 person-years in those who did not take supplemental beta-carotene, and 623 per 100,000 person-years in those who took at least 2000 microg/day of supplemental beta-carotene. Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and beta-carotene supplementation in men with low dietary beta-carotene intakes were associated with reduced risk of this disease.

Does Antioxidant Supplementation Alter the Effects of Acute Exercise on Erythrocyte Aggregation, Deformability and Endothelium Adhesion in Untrained Rats?

This study aimed to determine whether high-dose antioxidant supplementation had an impact on the acute exercise effects related to erythrocyte membrane mechanics. Experimental animals (n=32) were divided into four groups as control, exercised, supplemented, and supplemented + exercise. Four-week antioxidant supplementation (vitamin C, vitamin E, and zinc) was applied to experimental animals. Following acute exercise on a motor-driven rodent treadmill, erythrocyte aggregation and deformability, erythrocyte adhesion to endothelial cells, superoxide dismutase (SOD), and glutathione peroxidase activities of the erythrocytes were analyzed. In both supplemented and non-supplemented exercised groups, there was a significant decrease in SOD activities and erythrocyte aggregation, and an increase in adhesion to endothelial cell although there was no change on erythrocyte deformability. There were no differences in the responses to the exercise of supplemented and nonsupplemented rats. The data suggested that high-dose antioxidant supplementation did not alter the effects of acute exercise on erythrocyte membrane mechanics.

High-dose Antioxidant Supplementation and Cataract Risk

High-dose Antioxidant Supplementation and Cataract Risk

High-dose antioxidant supplementation and cataract risk.

In a recent clinical trial, supplementation with high-dose antioxidants lowered the progression of lens opacities. These results differ from those of several other larger trials, in which no benefit to high-dose antioxidant supplementation was observed. Although a large body of observational evidence suggests that supplement use is associated with lower risk for cataract, there is insufficient evidence that high-dose antioxidants slow the progression of cataracts beyond that provided by multivitamins or healthful diets.

High-dose Antioxidant Supplementation and Cataract Risk

High-dose Antioxidant Supplementation and Cataract Risk

High-dose Antioxidant Supplementation and Cataract Risk

High-dose Antioxidant Supplementation and Cataract Risk

High-dose antioxidant supplements and cognitive function in community-dwelling elderly women

Experimental data suggest that oxygen free radicals are probably involved in the deterioration of cognitive processes. Our objective was to investigate the relation of high-dose antioxidant supplements to cognition. Information on the use of specific supplements containing vitamins E and C was collected biennially via mailed questionnaires beginning in 1980 from 14 968 community-dwelling women who participated in the Nurses' Health Study. From 1995 to 2000, telephone tests of cognitive function [Telephone Interview of Cognitive Status (TICS), delayed recall of the TICS 10-word list, immediate and delayed recall of a short paragraph, a test of verbal fluency, and a digit span backwards test] were administered to the women, who were 70-79 y of age at that time. We used linear and logistic regression models to calculate multivariate-adjusted mean differences in test scores and relative risks of a low score for specific supplement users compared with nonusers. Long-term, current users of vitamin E with vitamin C had significantly better mean performance, as judged by a global score that combined individual test scores, than did women who had never used vitamin E or C (P = 0.03); there was a trend for increasingly higher mean scores with increasing durations of use (P = 0.04). These associations were strongest among women with low dietary intakes of alpha-tocopherol. Benefits were less consistent for women taking vitamin E alone, with no evidence of higher scores with longer durations of use. Use of specific vitamin C supplements alone had little relation to performance on our cognitive tests. The use of specific vitamin E supplements, but not specific vitamin C supplements, may be related to modest cognitive benefits in older women.

Combined Treatment with Vitamin E and Vitamin C Decreases Oxidative Stress and Improves Fetal Outcome in Experimental Diabetic Pregnancy

The aim was to investigate whether dietary supplementation of a combination of the two antioxidants, vitamin E and vitamin C, would protect the fetus in diabetic rat pregnancy at a lower dose than previously used. Normal and streptozotocin-induced diabetic rats were mated and given standard food or food supplemented with either 0.5% vitamin E + 1% vitamin C or 2% vitamin E + 4% vitamin C. At gestational d 20, gross morphology and weights of fetuses were evaluated. Vitamins E and C and thiobarbituric acid reactive substances were measured in maternal and fetal compartments. In addition, protein carbonylation was estimated in fetal liver. Maternal diabetes increased the rate of malformation and resorption in the offspring. High-dose antioxidant supplementation decreased fetal dysmorphogenesis to near normal levels. The low-dose group showed malformations and resorptions at an intermediate rate between the untreated and the high-dose groups. Thiobarbituric acid reactive substances were increased in fetal livers of diabetic rats and reduced to normal levels already by low-dose antioxidative treatment. Protein carbonylation rate was also increased in fetal liver of diabetic rats; it was normalized by high-dose treatment but only partially reduced by low-dose antioxidants. We conclude that combined antioxidative treatment with vitamins E and C decreases fetal malformation rate and diminishes oxygen radical-related tissue damage. However, no synergistic effect between the two antioxidants was noted, a result that may influence future attempts to design antiteratogenic treatments in diabetic pregnancy. Oxidatively modified proteins may be teratogenically important mediators in diabetic embryopathy.

Oxidative stress in HIV-1-infected injection drug users.

Low serum antioxidant levels observed in many HIV-infected populations could be largely due to an increase in oxidative stress (defined as a disturbance in the equilibrium status of prooxidant/antioxidant systems of intact cells). In HIV infection, oxidative stress may be caused by both overproduction of reactive oxygen intermediates (ROIs) and a simultaneous deficiency of antioxidant defenses. Furthermore, injection drug use has been associated with increased levels of oxidative stress in animal models. Currently, there is widespread use of self-prescribed antioxidant supplementation among the HIV-infected population and a prevailing belief that high-dose supplementation is beneficial, or at the very least, not harmful. Data from our studies show that HIV-positive injection drug users (IDUs) who are on antiretroviral combination therapies including a protease inhibitor have significantly higher mean serum levels of several antioxidants, independent of dietary and supplemental intake, compared with both HIV-negative IDUs and HIV-positive IDUs not taking protease inhibitors. This suggests that oxidative stress may be reduced in patients taking protease inhibitors. Preliminary data suggest that the future of antioxidant supplementation therapy, if any, will be one in which different doses of supplements are recommended for HIV-infected patients on the various antiretroviral treatment regimens. More research is needed to determine the interactions among injection drug use, oxidative stress, antiretroviral therapy, and the use of antioxidant supplements in HIV infection. Until more is known, caution should be exercised when using or recommending high-dose antioxidant supplementation in HIV-infected individuals, particularly in those on protease inhibitors, since moderate levels of oxidative stress are involved in a number of useful physiologic processes.

Oxidative Stress in HIV-1-Infected Injection Drug Users

Low serum antioxidant levels observed in many HIV-infected populations could be largely due to an increase in oxidative stress (defined as a disturbance in the equilibrium status of prooxidant/antioxidant systems of intact cells). In HIV infection, oxidative stress may be caused by both overproduction of reactive oxygen intermediates (ROIs) and a simultaneous deficiency of antioxidant defenses. Furthermore, injection drug use has been associated with increased levels of oxidative stress in animal models. Currently, there is widespread use of self-prescribed antioxidant supplementation among the HIV-infected population and a prevailing belief that high-dose supplementation is beneficial, or at the very least, not harmful. Data from our studies show that HIV-positive injection drug users (IDUs) who are on antiretroviral combination therapies including a protease inhibitor have significantly higher mean serum levels of several antioxidants, independent of dietary and supplemental intake, compared with both HIV-negative IDUs and HIV-positive IDUs not taking protease inhibitors. This suggests that oxidative stress may be reduced in patients taking protease inhibitors. Preliminary data suggest that the future of antioxidant supplementation therapy, if any, will be one in which different doses of supplements are recommended for HIV-infected patients on the various antiretroviral treatment regimens. More research is needed to determine the interactions among injection drug use, oxidative stress, antiretroviral therapy, and the use of antioxidant supplements in HIV infection. Until more is known, caution should be exercised when using or recommending high-dose antioxidant supplementation in HIV-infected individuals, particularly in those on protease inhibitors, since moderate levels of oxidative stress are involved in a number of useful physiologic processes.

High dose antioxidant supplementation to MS patients

High-dose antioxidant supplementation has recently been recommended for multiple sclerosis (MS) patients. This study tests the clinical safety, the glutathione peroxidase (GSH-px) activity, and the absorption of selenium during such supplementation. Eighteen MS patients were given 6 tablets especially made for this study, equivalent to 6 mg sodium selenite, 2 g vitamin C, and 480 mg vitamin E a day for five wk. GSH-px, which was lower than in non-MS controls before the start of treatment, increased fivefold during 5 wk of treatment. Side effects were scarce. Ten MS patients were subjected to a 24-h selenium absorption study after ingestion of 2 active tablets, equivalent to 2 mg sodium selenite. Selenium, which was low initially, increased 24% during the first 3 h and then stabilized. It is concluded that the tested antioxidant treatment seems to be safe and that MS patients have low GSH-px, which may be increased by the tested antioxidant treatment.