Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality
- PMID: 15537682
- DOI: 10.7326/0003-4819-142-1-200501040-00110
Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality
Abstract
Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality.
Purpose: To perform a meta-analysis of the dose-response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials.
Patients: 135,967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d).
Data sources: PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied.
Data extraction: 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available.
Data synthesis: 9 of 11 trials testing high-dosage vitamin E (> or =400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10,000 persons (95% CI, 3 to 74 per 10,000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was -16 per 10,000 persons (CI, -41 to 10 per 10,000 persons; P > 0.2). A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d.
Limitations: High-dosage (> or =400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult.
Conclusion: High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
Comment in
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Vitamin E supplements: good in theory, but is the theory good?Ann Intern Med. 2005 Jan 4;142(1):75-6. doi: 10.7326/0003-4819-142-1-200501040-00112. Epub 2004 Dec 3. Ann Intern Med. 2005. PMID: 15579660 No abstract available.
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Vitamin E not helpful, perhaps harmful.J Fam Pract. 2005 Mar;54(3):199-200. J Fam Pract. 2005. PMID: 15755368 No abstract available.
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Review: high-dose vitamin E supplementation is associated with increased all-cause mortality.ACP J Club. 2005 Jul-Aug;143(1):1. ACP J Club. 2005. PMID: 15989289 No abstract available.
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Review: high dose vitamin E supplementation is associated with increased all cause mortality.Evid Based Nurs. 2005 Jul;8(3):82. doi: 10.1136/ebn.8.3.82. Evid Based Nurs. 2005. PMID: 16021711 No abstract available.
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An editorial update: Annus horribilis for vitamin E.Ann Intern Med. 2005 Jul 19;143(2):143-5. doi: 10.7326/0003-4819-143-2-200507190-00014. Ann Intern Med. 2005. PMID: 16027457 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):150-1; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00018. Ann Intern Med. 2005. PMID: 16027460 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):151-2; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00020. Ann Intern Med. 2005. PMID: 16027461 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):151; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00019. Ann Intern Med. 2005. PMID: 16027462 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):152-3; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00022. Ann Intern Med. 2005. PMID: 16027463 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):152; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00021. Ann Intern Med. 2005. PMID: 16027464 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):153-4; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00024. Ann Intern Med. 2005. PMID: 16027465 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):153; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00023. Ann Intern Med. 2005. PMID: 16027466 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):154; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00025. Ann Intern Med. 2005. PMID: 16027467 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):155-6; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00028. Ann Intern Med. 2005. PMID: 16027468 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):155; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00027. Ann Intern Med. 2005. PMID: 16027469 No abstract available.
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High-dosage vitamin E supplementation and all-cause mortality.Ann Intern Med. 2005 Jul 19;143(2):155; author reply 156-8. doi: 10.7326/0003-4819-143-2-200507190-00026. Ann Intern Med. 2005. PMID: 16027470 No abstract available.
Summary for patients in
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Summaries for patients. Vitamin E supplements may be harmful.Ann Intern Med. 2005 Jan 4;142(1):I40. doi: 10.7326/0003-4819-142-1-200501040-00111. Epub 2004 Nov 10. Ann Intern Med. 2005. PMID: 15537683 No abstract available.
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