補充抗氧化劑預防痴呆有用嗎？

研究者對來自PREADViSE試驗（補充維生素E和硒預防阿爾茨海默病）的眾多老年男性進行11年的隨訪發現，服用5年的抗氧化劑維生素E和硒補充劑並沒有顯示出任何預防痴呆的獲益。這項試驗在線發表於3月20日的JAMA Neurology雜誌上，由美國肯塔基大學的Richard J. Kryscio牽頭進行。

Kryscio指出，這是首個在無癥狀男性中探討補充抗氧化劑與痴呆發生率之間長期關聯的研究。他表示，「這將讓人們停止並仔細考慮抗氧化劑作為阿爾茨海默病預防策略的可能性。雖然已知氧化應激是痴呆的一個通路，但我個人認為這可能是利用抗氧化劑預防痴呆這一想法的盡頭。」

研究概述

這項試驗作為SELECT（利用硒和維生素E預防癌症）試驗的一部分始於2002年，SELECT旨在評估硒和維生素E預防前列腺癌的療效。試驗招募了7540例基線時無任何認知障礙癥狀的男性，平均年齡67歲。這些受試者被隨機分配服用維生素E（400 IU/d）、硒（200 μg/d）、兩種補充劑或安慰劑。

SELECT由於無意義和硒的毒性於2009年提前終止。來自PREADViSE研究的患者停止服用補充劑但繼續接受額外6年的隨訪。然而，在SELECT終止後，約半數研究地點停止了所有活動，因此這些患者失訪。所以研究者只獲得了一半的可用樣本——3786例患者——完成所有的隨訪。

在服用研究補充劑的同時，研究者利用兩階段篩查對參與者的痴呆進行評估。在隊列研究中，通過電話進行隨訪，並利用加強的兩階段認知篩查評估。在兩階段中，如果篩查結果提示潛在認知障礙則鼓勵病人去看醫生。

結果顯示，隨訪結束時，325例男性（4.4%）發生痴呆，但四個研究小組之間無顯著差異。在一個調整了參與者人口統計資料和基線自我報告並存症發生率的Cox模型中，與安慰劑相比維生素E的風險比為0.88（95% 置信區間 [CI]， 0.64 - 1.20），硒為0.83（95% CI， 0.60 - 1.13），兩者聯合使用為1.00（95% CI， 0.75 - 1.35）。

作者指出，SELECT中的數據監測顯示，硒似乎能夠提升2型糖尿病的程度，儘管這一升高比率隨後在額外隨訪中下降。而且維生素E似乎會增加前列腺癌的發生率。

這些補充劑對死亡率、其他癌症、心血管病、噁心、疲勞或指甲變化沒有影響。硒與脫髮和1、2級皮炎顯著增加相關。

最後，研究者總結道：「服用維生素E和硒補充劑並不能預防痴呆，因此不應推薦預防性使用。」但他們補充道，這一結論受到研究效力不足的影響，包括僅涉及男性、服用補充劑時間較短、劑量考慮，以及依賴真實世界報告發生率的方法學局限性。

Association of Antioxidant Supplement Useand Dementia in the Prevention of Alzheimer"s Disease by Vitamin E and SeleniumTrial (PREADViSE).

Kryscio RJ1,Abner EL2,Caban-HoltA3,Lovell M4,Goodman P5,Darke AK5,Yee M6,CrowleyJ6,Schmitt FA7.

Author information

Abstract

IMPORTANCE:

Oxidative stress is an established dementiapathway, but it is unknown if the use of antioxidant supplements can preventdementia.

OBJECTIVE:

To determine if antioxidant supplements(vitamin E or selenium) used alone or in combination can prevent dementia inasymptomatic older men.

DESIGN, SETTING, AND PARTICIPANTS:

The Prevention of Alzheimer"s Disease byVitamin E and Selenium (PREADViSE) trial began as a double-blind randomizedclinical trial in May 2002, which transformed into a cohort study from September2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and VitaminE Cancer Prevention Trial (SELECT), a randomized clinical trial of the sameantioxidant supplements for preventing prostate cancer, which closed in 2009owing to findings from a futility analysis. The PREADViSE trial recruited 7540men, of whom 3786 continued into the cohort study. Participants were at least60 years old at study entry and were enrolled at 130 SELECT sites, and Coxproportional hazards models were used in a modified intent-to-treat analysis tocompare hazard rates among the study arms.

INTERVENTIONS:

Participants were randomized to vitamin E,selenium, vitamin E and selenium, or placebo. While taking study supplements,enrolled men visited their SELECT site and were evaluated for dementia using a2-stage screen. During the cohort study, men were contacted by telephone andassessed using an enhanced 2-stage cognitive screen. In both phases, men wereencouraged to visit their physician if the screen results indicated possiblecognitive impairment.

MAIN OUTCOMES AND MEASURES:

Dementia case ascertainment relied on aconsensus review of the cognitive screens and medical records for men withsuspected dementia who visited their physician for an evaluation or by reviewof all available information, including a functional assessment screen.

RESULTS:

The mean (SD) baseline age of the 7540participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a collegeeducation or better, 754 (10.0%) reporting black race, and 505 (6.7%) reportingHispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was notdifferent among the 4 study arms. A Cox model, which adjusted incidence forparticipant demographic information and baseline self-reported comorbidities,yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83(0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination comparedwith placebo.

CONCLUSIONS AND RELEVANCE:

Neither supplement prevented dementia. Toour knowledge, this is the first study to investigate the long-term associationof antioxidant supplement use and dementia incidence among asymptomatic men.

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