A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia. Vitamin E in the treatment of tardive dyskinesia. Long-term treatment effects of vitamin E for tardive dyskinesia. Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized, double-blind, placebo-controlled study. Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial. Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental. Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group. Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: results of the HOPE study. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease.
This study was designed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia (TD).
                Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were randomly assigned to receive 800 IU b.i.d. of vitamin E and 18 were assigned to placebo for 2 months. Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder. Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale (mAIMS), Simpson-Angus Scale for extrapyramidal side effects, and Brief Psychiatric Rating Scale. Additionally, a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia.
                There was a significant reduction of dyskinesia in the vitamin E group, but not the placebo group, on both the mAIMS and the instrumental assessments. The overall reduction in mAIMS in the active group was 24%, with 5 (29%) of 17 patients demonstrating greater than 33% reduction in score. There was a greater reduction in mean mAIMS score (35%) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction (11%) in patients with TD for greater than 5 years. No change was observed in parkinsonism. In the patients with schizophrenia, there was a reduction in positive symptoms after vitamin E.
                Vitamin E appears to be effective in reducing the severity of TD, especially in patients who have had TD for 5 years or less. In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD) was studied in 32 patients. After a two week wash-out phase a baseline (0 week) TD rating was assessed on the tardive dyskinesia rating scale (TDRS). Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg) and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week. All patients were rated on the TDRS at the end of each week. The baseline TDRS score in the vitamin E group was significantly higher than the placebo group. This was hence adjusted and the results were then subjected to analysis of co- variance. The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03). Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment.
                To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.
                Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score.
                The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo. Vitamin E has been shown to protect against liver damage induced by oxidative stress in animal experiments. Based on our previous findings of diminished vitamin E levels in patients suffering from viral hepatitis, we treated 23 hepatitis C patients refractory to alpha-interferon therapy with high doses of vitamin E (2 x 400 IU RRR-alpha-tocopherol/day) for 12 weeks. Study design: pro-spective randomized double-blind crossover design. Clinical parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined for monitoring the disease state, in parallel vitamin E plasma levels and plasma lipids were determined. The plasma levels of the alpha-tocopherol were increased about 2-fold in all 23 patients. In 11 of 23 patients the clinical parameters indicative of liver damage were improved during the phase of vitamin E treatment (48% responders). ALT levels in responders were lowered by 46% and AST levels were lowered by 35% after 12 weeks of vitamin E treatment. Cessation of vitamin E treatment was followed by a rapid relapse of ALT and AST elevation, whereas retreatment led to a reproducible ALT decrease by 45% and AST decrease of 37% after a 6 months followup. Since vitamin E is non-toxic even at elevated doses ingested over extended periods, we suggest the treatment of patients refractory to alpha-interferon therapy suffering from hepatitis C with vitamin E as a supportive therapy. Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases.
                We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months.
                The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019).
                Vitamin E supplementation might be effective in the treatment of chronic hepatitis B. There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitamin E, we found two groups. In the first group, "respondents" to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group, "non-respondents", consisted of patients in which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient. Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E.
                The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo.
                Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales.
                This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia. A controlled trial reported cardiovascular benefits of vitamin E in terminal renal insufficiency. There are no data for renal insufficiency before the stage of terminal renal failure. We evaluated effects of vitamin E supplementation on cardiovascular and renal outcomes in 993 people with a serum creatinine > or =1.4 to 2.3 mg/dL.
                Post-hoc analysis of a randomized trial that compared treatment with natural source vitamin E (400 IU/day) to placebo in 9541 people, 993 of which had renal insufficiency. Participants had either known cardiovascular disease or diabetes and at least one additional coronary risk factor. Exclusion criteria included a serum creatinine > 2.3 mg/dL and dipstick-positive proteinuria. The primary study outcome after an average of 4.5 years was the composite of myocardial infarction, stroke, or cardiovascular death. Secondary outcomes included revascularizations, total mortality, and clinical proteinuria.
                In renal insufficiency, vitamin E supplementation had a neutral effect on the primary study outcome, on each component of the composite primary outcome, and on all secondary outcomes. Two hundred twenty-four primary outcomes, 23% of the vitamin E group and 22.1% of the placebo group, relative risk 1.03 (95% CI, 0.79-1.34; P= 0.82), were observed, and 585 secondary outcomes, including death in 17% and 18.8% of the vitamin E and placebo groups, respectively (RR 0.88, 95% CI, 0.66-1.18; P= 0.40). There was no effect of vitamin E on progression of proteinuria.
                In people with mild-to-moderate renal insufficiency at high cardiovascular risk, vitamin E at a dose of 400 IU/day had no apparent effect on cardiovascular outcomes. A number of nutrients are known to be effective in preventing cardiovascular disease (CVD). We investigated the possible effects of a daily intake of low amounts of these nutrients on risk factors and clinical parameters in patients with peripheral vascular disease and intermittent claudication (PVD-IC). Male PVD-IC patients (n = 60) were randomly allocated into 2 groups. The supplement (S) group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), oleic acid, folic acid, and vitamins A, B-6, D, and E. The control (C) group consumed 500 mL/d of semiskimmed milk with added vitamins A and D. The patients received lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical explorations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of EPA, DHA, oleic acid, folic acid, and vitamins B-6 and E increased after treatment with supplements (P < 0.05). Plasma total cholesterol and ApoB concentrations decreased in the S group, and total homocysteine decreased in those patients with high initial concentrations. Walking distance before the onset of claudication increased in the S group (P < 0.001), and ankle-brachial pressure index values increased (P < 0.05). The inclusion in the everyday diet of certain nutrients known to promote cardiovascular health improved clinical outcomes while reducing a variety of risk factors in men with PVD-IC, providing new evidence of the potential role of nutrition in the reduction of PVD-IC symptoms.
Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.