硒的人体最大安全摄入量研究——五、硒的日摄入量和血、尿以及组织中硒含量的相关性分析

用回归分析方法,在双对数纸上计算并绘制出日平均硒摄入量和全血硒浓度、24小时尿硒排出量及奶硒浓度间的回归方程式及线图。通过这些回归方程,可从人的全血或其它体液中硒的含量计算出日平均硒摄入量。同时又测定出全血与发、趾甲及指甲组织中硒含量间的相关性,从而可将其它组织中硒的浓度换算为全血硒浓度,最终计算出日平均硒摄入量。此外,通过血浆硒和24小时尿硒排出量间的相关性可将血浆硒浓度换算为日平均硒摄入量。在高硒地区,由于每日硒进食量的变动性,通过短期内的膳食调查,难以测出某一受试者有代表性的日硒摄入量。由于血硒浓度的相对稳定性,通过血硒值换算为摄入量,结果稳定而具有代表性。     

硒的人体最大安全摄入量研究 五、硒的日摄入量和血、尿以及组织中硒含量的相关性分析

用回归分析方法,在双对数纸上计算并绘制出日平均硒摄入量和全血硒浓度、24小时尿硒排出量及奶硒浓度间的回归方程式及线图。通过这些回归方程,可从人的全血或其它体液中硒的含量计算出日平均硒摄入量。同时又测定出全血与发、趾甲及指甲组织中硒含量间的相关性,从而可将其它组织中硒的浓度换算为全血硒浓度,最终计算出日平均硒摄入量。此外,通过血浆硒和24小时尿硒排出量间的相关性可将血浆硒浓度换算为日平均硒摄入量。在高硒地区,由于每日硒进食量的变动性,通过短期内的膳食调查,难以测出某一受试者有代表性的日硒摄入量。由于血硒浓度的相对稳定性,通过血硒值换算为摄入量,结果稳定而具有代表性。     

硒的化学形式对人血中含硒组分的影响

在低膳食硒地区的农村,对健康男性受试者进行了为期一年的补硒干预试验。所有受试者每天服硒200μg,以硒酸钠或硒蛋氨酸形式供给。血样分析结果表明,这两种形式的硒均能有效地提高低硒人体的谷胱甘肽过氧化物酶(GPx)活力,因而在预防克山病工作中可采用较为经济的硒酸钠;但补硒蛋氨酸后可见“富裕”硒进入了红细胞的Hb和血浆的白蛋白中,而补硒酸钠后未见“富裕”硒,因而为提高人体硒营养水平,以补充硒蛋氨酸形式的硒为宜。     

淮北市居民硒营养水平调查与评价

目的了解淮北市居民微量元素硒的营养水平状况,并为建立全国微量元素营养数据库提供有效的数据。方法于2003年9月—2004年6月,随机选取在淮北市出生或在淮北市居住10a以上健康居民513人,采用催化极谱法测定发硒含量,并划分硒丰度区;以发硒含量估算膳食硒摄入量,按照《中国居民膳食营养素参考摄入量》进行评价。结果淮北市居民发硒含量为(0.3903±0.1045)μg/g,仅有51.9%(266/513)的居民发硒含量属于适硒区水平。淮北市居民膳食硒摄入量为(31.92±9.93)μg/d;除0～6岁人群外,其他各年龄段人群膳食硒摄入量远低于中国营养学会推荐的摄入量。达到推荐摄入量(RNI)、平均需要量(EAR)标准的居民分别占19.9%(102/513)和32.9%(169/513),也远未达到满足群体中50%个体生理需要量的摄入水平。结论淮北市民从膳食中摄取的硒量严重不足,提醒市民应适当补充微量元素硒。     

富硒食品含硒量范围标准的研究

目的:制定富硒食品含硒量范围标准,规范富硒食品的生产、加工与销售行为。方法:采集不同硒区农副产品、预包装食品和居民膳食样品,按GB5009.93食品中硒的测定方法进行检测,参考国内相关资料提出的富硒食品含硒量量值设定范围,下限设置注重补硒有效性,上限设置注重食物安全性。结果:谷物硒含量0.1~0.4 mg/kg,蔬菜0.03~0.25 mg/kg,肉食品0.2~1.0 mg/kg范围内的富硒食品,可使居民每天硒的摄入量稳定在50~250μg/d的最适宜摄入量范围之内。     

不同剂量补硒对大鼠氧化应激损伤的保护作用

目的观察不同剂量补硒对大鼠生理功能和氧化应激的保护作用。方法雄性成年SD大鼠40只分为空白对照组、模型对照组和补硒低、中、高,共5组。补硒实验组大鼠每天灌胃富硒菌粉,灌胃量分别为45、90、180 mg/(kg·bw)(相当成年人硒日摄入量为250、500和1000μg),空白对照组和模型对照组灌胃蒸馏水。饲养38d后,给模型对照组和实验组大鼠按照12ml/(kg·bw)一次性灌胃给予50%乙醇,6h后收集血液和组织样品,测定血清生化指标、血常规、抗氧化指标及组织中硒含量。结果随硒摄入量增加,大鼠增重呈下降趋势,但补硒各剂量组间无显著性差异。低剂量硒摄入组血清抗氧化物酶(totalantioxidantcapacity,T-SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)和黄嘌呤氧化酶(xanthine oxidase, XOD)活性较模型对照组有显著提高(P<0.05)。补硒组肝组织中GSH-Px活性较模型对照组显著提高(P <0.05),血清和肝组织中脂质过氧化产物丙二醛(malondialdehyde,MDA)和8-表氢氧异前列腺素(8-Isoprostane)的含量三个剂量组较模型对照组都显著性降低(P<0.05)。血清和肝组织中蛋白质羰基含量在中、高剂量组较模型对照组有显著降低(P<0.05)。三个补硒剂量组大鼠血清中谷胱甘肽(glutathione,GSH)的含量随硒摄入量增加而升高,但与模型对照组无统计学差异(P>0.05)。低剂量组大鼠肝组织中GSH含量较模型对照组有显著升高(P>0.05),结论不同剂量硒摄入未对大鼠生理功能产生不良影响,且不同剂量硒摄入可保护大鼠机体由一次性大量乙醇摄入引起的氧化应激损伤。[营养学报,2019,41(1):63-67]     

补硒对克山病病区粮饲养大鼠心肌线粒体单胺氧化酶活性的影响

90只断乳两周的Spragul-Dawley纯种大鼠,随机分为低硒、补硒及常备饲料三组,分别饲以克山病病区低硒粮(含Se 0.009ppm)、克山病病区低硒粮补亚硒酸钠(含Se 0.232ppm)及常备饲料(含Se 0.169ppm),观察硒对心肌线粒体单胺氧化酶活性(MAO)的影响,结果表明:与补硒和常备饲料组相比,低硒组心肌线粒体MAO活性明显下降。饲喂30,60,90天血浆硒含量和红细胞GSH-Px活性显著下降,补硒组心肌线粒体MAO和红细胞GSH-Px活性接近常备饲料组水平。     

我国人民硒需要量的研究 五、硒生理需要量的再研究和有关硒需要量问题的讨论

对本所12名职工分别补充不同剂量的亚硒酸钠(8人)和硒蛋氨酸(4人),每组男女各半。实验膳供给硒量男女分别为48.3±20.2和42.8±20.4μg/日。实验结果表明:不论补充哪一种形式的硒和补充剂量的大小,受试者血浆GSHpx活力在实验期始终保持不变。因此,本次观察天然膳食所得男子摄入量≤48.3和以往用补充的方法在低硒地区的结果是一致的,但若单独考虑本次实验结果成年男子应为60μg。此外,为了确定实验对象血浆硒水平是否在补充前已达到最高恒定水平,给另一组6人(男女各半),每天补充相当于20μg硒的亚硒酸钠,结果显示:受试者血浆硒对补充的硒有反应,在男女分别摄入硒的量达到68.3±20.2和62.8±20.4μg/日时,血浆硒达到最高恒定水平。文内简单地讨论了血浆GSHpx和补充亚硒酸钠后血浆硒的最高恒定水平的营养意义。     

硒的人体最大安全摄入量研究 六、硒的最高界限摄入量和最大安全摄入量

体检349名成年居民结果,发现血硒水平在1.02μg/ml以下者无硒中毒病人,又5名指甲变形长期不能恢复正常者,他们中间最低血浓度为1.054μg/ml(硒日摄入量910μg)。生化检查结果发现当血硒浓度上升到1μg/ml(硒日摄入量850μg)时,凝血酶原时间延长的病例显著上升;此外,在血硒浓度接近0.9μg/ml(硒日摄入量743μg)时,血浆硒/红血球硒的比值下降至低血硒状态时的1/3至1/4。据上述结果,界限日硒摄入量应在750～850μg范围内。考虑到个体差异,建议用2.0作为安全因子,即最高安全摄入量为400μg。又考虑我国高硒区的某些具体情况如居民适应性及环境中某些拮抗元素的存在等,建议在高硒区用1.3作为安全因子,即最高安全摄入量约为每日550μg。     

硒的人体最大安全摄入量研究 六、硒的最高界限摄入量和最大安全摄入量

体检349名成年居民结果,发现血硒水平在1.02μg/ml以下者无硒中毒病人,又5名指甲变形长期不能恢复正常者,他们中间最低血浓度为1.054μg/ml(硒日摄入量910μg)。生化检查结果发现当血硒浓度上升到1μg/ml(硒日摄入量850μg)时,凝血酶原时间延长的病例显著上升;此外,在血硒浓度接近0.9μg/ml(硒日摄入量743μg)时,血浆硒/红血球硒的比值下降至低血硒状态时的1/3至1/4。据上述结果,界限日硒摄入量应在750～850μg范围内。考虑到个体差异,建议用2.0作为安全因子,即最高安全摄入量为400μg。又考虑我国高硒区的某些具体情况如居民适应性及环境中某些拮抗元素的存在等,建议在高硒区用1.3作为安全因子,即最高安全摄入量约为每日550μg。     

Differential responses to selenomethionine supplementation by sex and genotype in healthy adults

A year-long intervention trial was conducted to characterise the responses of multiple biomarkers of Se status in healthy American adults to supplemental selenomethionine (SeMet) and to identify factors affecting those responses. A total of 261 men and women were randomised to four doses of Se (0, 50, 100 or 200 μg/d as L-SeMet) for 12 months. Responses of several biomarkers of Se status (plasma Se, serum selenoprotein P (SEPP1), plasma glutathione peroxidase activity (GPX3), buccal cell Se, urinary Se) were determined relative to genotype of four selenoproteins (GPX1, GPX3, SEPP1, selenoprotein 15), dietary Se intake and parameters of single-carbon metabolism. Results showed that supplemental SeMet did not affect GPX3 activity or SEPP1 concentration, but produced significant, dose-dependent increases in the Se contents of plasma, urine and buccal cells, each of which plateaued by 9-12 months and was linearly related to effective Se dose (μg/d per kg0·75). The increase in urinary Se excretion was greater for women than men, and for individuals of the GPX1 679 T/T genotype than for those of the GPX1 679 C/C genotype. It is concluded that the most responsive Se-biomarkers in this non-deficient cohort were those related to body Se pools: plasma, buccal cell and urinary Se concentrations. Changes in plasma Se resulted from increases in its non-specific component and were affected by both sex and GPX1 genotype. In a cohort of relatively high Se status, the Se intake (as SeMet) required to support plasma Se concentration at a target level (Se(pl-target)) is: Se(in) = [(Se(pl - target) - Se(pl))/(18.2ng d kg?.??/ml per mu g)] .     

Genetic variation in GPX1 is associated with GPX1 activity in a comprehensive analysis of genetic variations in selenoenzyme genes and their activity and oxidative stress in humans

Previous studies suggest some effects of selenium on risk of several chronic diseases, which may be mediated through a small number of selenoenzymes with antioxidant properties. In this cross-sectional analysis of 195 participants from the Seattle Barrett's Esophagus Study who were free of esophageal cancer at the time of blood draw, we examined whether the number of the minor alleles in 26 tagging single nucleotide polymorphisms (SNP) of five selenoenzyme genes [i.e., glutathione peroxidase 1-4 (GPX1-4) and selenoprotein P (SEPP1)] was associated with activity of GPX1 in white blood cells and GPX3 in plasma, and concentrations of SEPP1 and markers of oxidative stress [malondialdehyde (MDA) and protein carbonyl content] in plasma. At the gene level, associations were observed between overall variation in GPX1 and GPX1 activity (P = 0.02) as well as between overall variation in GPX2 and SEPP1 concentrations (P = 0.03). By individual SNP, two variants in GPX1 (rs8179164 and rs1987628) showed a suggestive association with GPX1 activity (P = 0.10 and 0.08, respectively) and two GPX2 variants (rs4902346 and rs2071566) were associated with SEPP1 concentration (P = 0.004 and 0.002, respectively). Furthermore, two SNP in the SEPP1 gene (rs230813 and rs230819) were associated with MDA concentrations (P = 0.03 and 0.02, respectively). Overall, our study supports the hypothesis that common genetic variants in selenoenzymes affect their activity.     

我国人民硒需要量的研究 四、推荐供给量标准的补充

最近Levander根据我们以往人体硒需要量研究结果,换算为美国人的硒需要量,但换算过程中,需要个体变异数字。本文报告了用不同方法计算前报告中平均硒摄入量的标准差,以及以往推荐的硒供给量标准的根据。根据计算结果结合我国广大高硒及低硒地区居民实际摄入硒的情况,更详细地分别提出成人最低硒需要量的观察值为每日17μg,建议成人硒供给量标准为每日50μg。     

Biomonitoring of selenoprotein P in human serum by fast affinity chromatography coupled to ICP-MS

Most of the Se in human serum is bound to selenoprotein P (SEPP1) in which Se is present in form of selenocysteine. The SEPP1 is a new possible biomarker for the Se status and for this reason we developed a fast, simple and reliable method for the quantitative determination of SEPP1 in serum by affinity chromatography coupled to ICP-MS. It is possible to separate SEPP1 from other selenoproteins in serum in only 5?min, which allows high sample throughput in clinical laboratories. Measured and certified concentrations of total Se and Se(SEPP1) are in good agreement for the reference material SRM 1950. The SEPP1 concentration was stable in serum samples of 3 persons for a minimum of 2 weeks. Further results of method validation were described including internal and external quality assurance.The analytical method was applied for a biomonitoring study of the SEPP1 and total Se concentration in human serum of 50 occupationally non-exposed persons living in northern Germany. Concentration ranges and mean concentrations for Se(SEPP1) are 31.1–59.7 and 46.2?μg/L, respectively. The corresponding values for total Se are 62–120 and 83.5?μg/L. The mean percentage of total Se in serum present as SEPP1 is 58%.     

Selenate-supplemented nutritional formula increases plasma selenium in hemodialysis patients.

OBJECTIVE: The purpose of this study was to determine the short-term effect of feeding selenium-supplemented formulas on the selenium status of end-stage renal disease patients on hemodialysis. DESIGN AND SETTING: The prospective, randomized, single-blind study of parallel design was conducted at three hemodialysis clinics. PATIENTS: A total of 79 hemodialysis patients were randomly assigned into one of three groups. INTERVENTION: Liquid nutritional formula supplemented with either selenite (28 microg Se/8 oz, n = 26), selenate (28 microg Se/8 oz, n = 26), or nonfortified (7 microg Se/8 oz, n = 27) was fed to hemodialysis patients as their sole source of nutrition for 14 days. MAIN OUTCOME MEASURE: Plasma and red blood cell (RBC) selenium and glutathione peroxidase (GPX) activities were measured in predialysis blood both before (day 1) and after (day 8) a 7-day baseline period, and after subjects received the formula as the sole source of nutrition (approximately 35 kcal/kg/d) for 14 days (day 22). RESULTS: Selenium intake (Mean +/- SEM, microg/d) was 134 +/- 9, 140 +/- 9, and 35 +/- 2 for patients receiving selenite-, selenate-, or non-supplemented formula, respectively. On day 22, plasma selenium (micromol/L) was greater (P <.032) in the selenate-supplemented group (1.5 +/- 0.1) compared with the nonsupplemented group (1.2 +/- 0.1), but not compared with the selenite-supplemented group (1.4 +/- 0.1). Plasma GPX activity was 44% to 60% that of healthy controls and not different among groups. RBC selenium and GPX activities were within the normal range and were not different among groups. CONCLUSION: The results of this study indicate that a liquid formula supplemented with selenium as selenate is successful at maintaining selenium concentrations within normal range, as well as significantly increasing plasma selenium levels compared with nonsupplementation.     

北京市机关职工及托幼儿童每日硒摄入量的评价

北京市内居民平均每日膳食硒摄入量为66.4μg,托幼儿童为34.7μg,已达到目前的推荐膳食供给量标准。在成人膳食中,硒主要来源于谷类,占摄入量的63.6％,其次是动物性食品,占25.9％,其它植物性食品占10.5％;儿童膳食硒主要来源于谷类和动物性副食,各占48.9％和44.3％。 全血平均硒含量为0.146ppm,发硒含量0.578ppm。全血硒和发硒含量与每日膳食硒摄入量间均呈显著的正相关。 汞、砷及镉的每日摄入量分别为3.4,52.7和42.7μg,未超过正常地区的允许范围,不致于显著增加硒的需要量。 由于调查对象硒的营养状况正常,且每日摄入的拮抗元素为量不多,故所调查出的每日硒摄入量应为我国健康人的正常摄入量,可供制定供给量时参考。     

硒的生物标志物

人体必需微量元素硒具有多种生物学活性,这依赖于硒摄入的水平。相对较低的硒摄入决定含硒酶的表达,含硒酶是人体质量主要的组份。较高水平的硒摄入已被证明具有抗肿瘤的潜能,而非常高的硒摄入可对机体产生不良影响。这种生物活性的层次性要求不同水平的硒暴露有不同的生物标志物信息。一些硒的生物标志物,如硒蛋白,特别是GPX3和SEPP1,可直接提供功能相关的信息,并在识别营养性硒缺乏及追踪硒缺乏个体补硒治疗疗效方面有重要价值。它们在硒摄入情况下可有效的调节范围内硒蛋白的表达。其他硒生物标志物通过基于食品、组织、尿液或粪便中硒含量的推论间接的提供信息。它们可以提示硒缺乏或不良反应的可能性,却不能提供其直接证据。它们的价值在于提供广泛的硒摄入量的硒状态信息,特别是来自食物形式的。     

An estimation of selenium requirements for New Zealanders.

BACKGROUND: Current US dietary recommendations for selenium are based on maximization of plasma glutathione peroxidase (GSHPx) activity according to data from one study of Chinese men. OBJECTIVE: The effect of various amounts of supplemental selenium on GSHPx activities in blood of New Zealand adults was investigated to calculate a selenium requirement for New Zealanders. The effect on plasma selenoprotein P and thyroid hormones was also investigated. DESIGN: Fifty-two adults with low blood selenium concentrations ingested a placebo or 10, 20, 30, or 40 microgram Se as L-selenomethionine daily for 20 wk. RESULTS: Plasma and whole-blood GSHPx activities increased in all supplemented groups but reached a plateau only in the group receiving 40 microgram Se, as determined by statistical analysis. Increases in selenoprotein P were greater than those for selenium and GSHPx at all supplement intakes. Thyroxine concentrations decreased in supplemented groups but the decrease was significantly different from that in the control group only for the 10-microgram group and for all supplemented groups combined. CONCLUSIONS: An upper estimated requirement of 90 microgram Se/d was calculated as the intake necessary for maximization of plasma GSHPx activity, as used in the derivation of the US recommended daily allowance. Our lower estimated requirement of 39 microgram Se/d was the intake necessary to reach two-thirds of maximal GSHPx activity, as was used in calculating the World Health Organization normative requirement. The lower estimate is a realistic goal for New Zealand but the upper estimate could be achieved only with regular inclusion of high-selenium foods.     

大鼠谷胱苷肽过氧化物酶发挥最佳活性所需的最低饲料硒水平

目的　测定大鼠谷胱苷肽过氧化物酶活性达到最高时所需的饲料硒水平。方法　以低硒酵母配制低硒基础饲料 ,在此基础上加不同剂量的亚硒酸钠配成 8种不同硒水平的饲料来喂养雄性 Wistar断乳大鼠。饲料硒水平分别为 0 .0 1、0 .0 2、0 .0 3、0 .0 4、0 .0 5、0 .0 6、0 .1 0和 0 .2 0mg/kg。 2 0周时处死大鼠 ,分别对各种组织中的硒 ( Se)、细胞内谷胱苷肽过氧化物酶 ( c GPX)、细胞外谷胱甘肽过氧化物酶 ( e GPX)、磷脂氢谷胱甘肽过氧化物酶 ( PHGPX)活性进行测定。结果　在Wistar大鼠的各种组织中 c GPX发挥最佳活性时的最低饲料硒水平高于其它两种硒蛋白。雄性Wistar大鼠发挥最佳 c GPX活性所需最低饲料硒水平为 0 .2 0 mg/kg,e GPX和 PHGPX发挥最佳活性所需的最低饲料硒水平分别为 0 .0 4和 0 .0 5mg/kg。结论　确保满足雄性大鼠 c GPX、e GPX和 PHGPX三种硒蛋白合成的饲料硒水平为 0 .2 0 mg/kg。     

克山病病区粮食中补充蛋氨酸对大鼠膳食硒生物利用的影响

为研究在克山病病区粮食中补充蛋氨酸对大鼠组织硒和谷胱甘肽过氧化物酶 (GPX)活性的影响 ,用克山病病区生产的低硒粮食为主配成低硒基础饲料 ,其硒含量为 0 .0 0 7mg/kg。在此基础上添加不同量的硒蛋氨酸 ,使饲料硒水平分别达到 0 .0 0 7、0 .0 6和 0 .5 0 mg/kg。每一硒水平又分别补充或不补充 4g/kg DL -蛋氨酸 ,配制成含不同硒和蛋氨酸的 6种饲料 ,分别喂养雄性 Wistar断乳大鼠 8周。结果在饲料硒水平为0 .0 0 7mg/kg时 ,补充蛋氨酸组动物除肌肉硒含量低于未补充组外 ,其它组织硒含量和各组织 GPX活力与不补充蛋氨酸动物无显著差异 ;在饲料硒水平为 0 .0 6 mg/kg时 ,补充蛋氨酸组动物组织中的硒含量出现了重新分布 ,最明显的是补充蛋氨酸组动物肌肉的硒含量减少 ,而肝脏和血硒含量增加 ,且各组织中 GPX活力显著大于未补充蛋氨酸组的动物 ;在饲料硒水平为 0 .5 0 mg/kg时 ,补充蛋氨酸组动物组织中硒含量有不同程度下降 ,但 GPX活力仍保持不变。研究结果认为病区粮食中蛋氨酸不足时 ,机体首先利用膳食中的硒蛋氨酸(谷类食物中硒的主要形式 )以替代蛋氨酸参与组织蛋白质的合成。补充蛋氨酸后 ,硒蛋氨酸即可发挥其应有生理功能。进一步提示病区粮食中蛋氨酸不足可能是与克山病发病有关的另一因素。