Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
Free Radic Biol Med. 2018 Nov 1;127:46-54. doi: 10.1016/j.freeradbiomed.2018.02.015. Epub 2018 Feb 14.
Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ~ 125 µg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained concentrations higher than this are beneficial, or indeed detrimental, is unknown.
In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels.
The Denmark PRECISE study was a single-centre, randomised, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. Participants were 491 male and female volunteers aged 60-74 years, recruited at Odense University Hospital, Denmark. The trial was initially designed as a 6-month pilot study, but supplemental funding allowed for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 µg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015).
During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis, the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 µg selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up period. The 100 and 200 µg/d doses showed non-significant decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects on cancer and cardiovascular mortality appeared similar.
A 300 µg/d dose of selenium taken for 5 years in a country with moderately-low selenium status increased all-cause mortality 10 years later. While our study was not initially designed to evaluate mortality and the sample size was limited, our findings indicate that total selenium intake over 300 µg/d and high-dose selenium supplements should be avoided.
硒是一种必需的微量元素，它被纳入具有广泛健康影响的硒蛋白中。当血浆硒浓度达到约 125μg/L 时，硒蛋白可能达到饱和，此时硒蛋白 P 的浓度达到平台期；目前尚不清楚持续高于此浓度是否有益，甚至是否有害。
在硒含量相对较低的人群中，我们旨在确定长期补充不同剂量硒对死亡率的影响。
丹麦 PRECISE 研究是一项单中心、随机、双盲、安慰剂对照、多臂、平行临床试验，共有四组。参与者为 491 名年龄在 60-74 岁的男性和女性志愿者，在丹麦欧登塞大学医院招募。该试验最初设计为 6 个月的试点研究，但补充资金允许延长研究和评估死亡率。参与者于 1998-1999 年随机分配接受 100、200 或 300μg/d 的硒作为富硒酵母或安慰剂酵母治疗 5 年，并在随访 10 年后（截至 2015 年 3 月 31 日）评估死亡率。
在 6871 人年的随访期间，发生了 158 例死亡。在意向治疗分析中，与安慰剂相比，300μg/d 硒的全因死亡率的危险比（95%置信区间）在治疗 5 年后为 1.62（0.66，3.96），在整个随访期间为 1.59（1.02，2.46）。100 和 200μg/d 剂量在干预期间显示出死亡率的非显著下降，但在治疗停止后消失。尽管我们缺乏除全因死亡率以外的终点的效力，但癌症和心血管死亡率的影响似乎相似。
在一个硒含量中等偏低的国家，5 年每天摄入 300μg 的硒会增加 10 年后的全因死亡率。虽然我们的研究最初不是为了评估死亡率，而且样本量有限，但我们的发现表明，硒总摄入量超过 300μg/d 和高剂量硒补充剂应避免。
