Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality

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   Figure 1. Flow diagram of the trial selection process.
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   Figure 2. Area of each square is proportional to inverse of study variance in the analysis. Horizontal lines represent 95% CIs. ADCS = Alzheimer's Disease Cooperative Study; AREDS = Age-Related Eye Diseases Study; ATBC = Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group; CHAOS = Cambridge Heart Antioxidant Study; DATATOP = Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism; GISSI-Prevenzione = Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarcto Miocardio Prevenzione; HOPE = Heart Outcomes Prevention Evaluation; MIN.VIT.AOX = The Geriatrie/MINéraux, VITamines, et AntiOXydants Network; MRC/BHF HPS = Medical Research Council/British Heart Foundation Heart Protection Study; PPP = Primary Prevention Project; PPS = Polyp Prevention Study; REACT = Roche European American Cataract Trial; SPACE = Secondary Prevention with Antioxidants of Cardiovascular disease in Endstage renal disease; SU.VI.MAX = SUpplementation en VItamines et Minéraux AntioXydants; VECAT = Vitamin E, Cataracts, and Age-Related Maculopathy; WAVE = Women's Angiographic Vitamin and Estrogen. Risk difference in all-cause mortality for randomized, controlled trials of vitamin E supplementation and pooled results for low-dosage (<400 IU/d) and high-dosage (≥400 IU/d) vitamin E trials.
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   Figure 3. We obtained the risk trend ( ) and its 95% confidence band ( ) by using a quadratic-linear spline model. Circled areas are proportional to inverse of study variance in the analysis. ADCS = Alzheimer's Disease Cooperative Study; AREDS = Age-Related Eye Diseases Study; ATBC = Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group; CHAOS = Cambridge Heart Antioxidant Study; DATATOP = Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism; GISSI-Prevenzione = Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarcto Miocardio Prevenzione; HOPE = Heart Outcomes Prevention Evaluation; MIN.VIT.AOX = The Geriatrie/MINéraux, VITamines, et AntiOXydants Network; MRC/BHF HPS = Medical Research Council/British Heart Foundation Heart Protection Study; PPP = Primary Prevention Project; PPS = Polyp Prevention Study; REACT = Roche European American Cataract Trial; SPACE = Secondary Prevention with Antioxidants of Cardiovascular disease in Endstage renal disease; SU.VI.MAX = SUpplementation en VItamines et Minéraux AntioXydants; VECAT = Vitamin E, Cataracts, and Age-Related Maculopathy; WAVE = Women's Angiographic Vitamin and Estrogen. Dose–response relationship between vitamin E supplementation and all-cause mortality in randomized, controlled trials.solid curveshaded region
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   Figure 4. Area of each square is proportional to inverse of study variance in the analysis. Horizontal lines represent 95% CIs. We restricted data from factorial trials to participants who were not exposed to the second factorial intervention, except for the Heart Outcomes Prevention Evaluation ( ) study and the Medical Research Council/British Heart Foundation Heart Protection Study ( ) (in which no disaggregated data were available) and for the Linxian A trial (which used a fractional factorial design). For these trials and the trials that did not use a factorial design, we kept the results from 2-way analyses. ADCS = Alzheimer's Disease Cooperative Study; AREDS = Age-Related Eye Diseases Study; ATBC = Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group; CHAOS = Cambridge Heart Antioxidant Study; DATATOP = Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism; GISSI-Prevenzione = Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarcto Miocardio Prevenzione; MIN.VIT.AOX = The Geriatrie/MINéraux, VITamines, et AntiOXydants Network; PPP = Primary Prevention Project; PPS = Polyp Prevention Study; REACT = Roche European American Cataract Trial; SPACE = Secondary Prevention with Antioxidants of Cardiovascular disease in Endstage renal disease; SU.VI.MAX = SUpplementation en VItamines et Minéraux AntioXydants; VECAT = Vitamin E, Cataracts, and Age-Related Maculopathy; WAVE = Women's Angiographic Vitamin and Estrogen. Risk difference in all-cause mortality for randomized, controlled trials of vitamin E supplementation and pooled results for low-dosage (<400 IU/d) and high-dosage (≥400 IU/d) vitamin E trials based on 4-way analyses of trials that used a factorial design.HOPE(44)MRC/BHF HPS(49)(36)