1、生物微量元素研究生物利用性與生物強(qiáng)化Topics to CoverIntroduction to Biological Trace Elements12Models to Evaluate Trace Elements Bioavailability3Biofortification of Trace Elements2Trace Elementsp Definitionsn Macroelements VS. Microelementsn Macronutrients VS. Micronutrientsp Absorption of Trace Elementsp Functions &a

2、mp; Deficiencies of Trace Elementsn Iron (Fe), Zinc (Zn), Iodine (I), Selenium (Se)p Why Do Trace Elements Deficiencies Occur?3Definitionsp Marcoelementsn Include calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K) and chloride (Cl), etc.n Macroelements are required in amounts g

3、reater than 100 mg/day.占人體質(zhì)量萬分之一以上占人體質(zhì)量萬分之一以上4Definitionsp Microelementsn Include iron (Fe), zinc (Zn), copper (Cu), selenium (Se), fluorine (F), iodine (I), etc.低于人體質(zhì)量萬分之一低于人體質(zhì)量萬分之一n Required in small quantities and are also known as trace elements5p Macronutrients include：Macronutrients VS. Micron

4、utrientsn Proteinn Lipidsn Carbohydrates6Macronutrients VS. Micronutrientsp Micronutrients include:macromicron Mineralsn Vitaminsfat soluble (Vitamin A,D)water soluble (Vitamin B, C)維持人體的正常生理代謝，攝入不足會導(dǎo)致嚴(yán)重的疾病，甚至造成死亡！7Absorption of TEsp Digestion/absorptionn 吸收吸收：胃腸道，呼吸道，也可以是皮膚8Absorption of TEsp Excre

5、tionn 主要通過消化道消化道（糞便）、腎臟腎臟（尿），呼吸、汗液也可排出少量9Absorption of TEsp pH affects absorption of TEsn Some minerals (Ca, Fe, Zn, Cu) are present in foods as insoluble salts.n Minerals from foods are solubilized in the stomach due to the acidity (HCl).n This solubility does not last long, since the intestine is

6、more alkaline (pH 7).10Absorption of TEsp pH affects absorption of TEsn An antacid with our foods do not favor the solubility and absorption of TEs. Why ? pH of stomach is increased.n In alkaline environments, TEs tend to precipitate and not be absorbed (instead are excreted).n Whether precipitation

7、 of TEs happen or not depends on the presence of certain food components that bind to the TEs, and enhance their absorption (enhancers)n There are also mineral inhibitors.enhancer (Vit C)inhibitor (phytate)11Absorption of TEs p Foods components affect the absorption of some TEsn Iron (Fe) absorption

8、：n Enhanced by vitamin C and meatn Inhibited by fiber, phytate, tannins (tea), oxalate (spinach) and certain proteins (soy bean protein, egg protein, casein)meatteaspinacheggoxalatetannin12Absorption of TEsn Zinc (Zn) absorption：n Inhibited by fiber, phytate and tannins (tea) and oxalate (spinach)n

9、Oxalate (or oxalic acid) present in foods like chocolate and spinach binds to TEs and inhibits their absorption.n Likewise, phytate (or phytic acid) present in many plant crops, is a mineral inhibitor.oxalatephytatefiber13Functions & Deficiencies of TEsp Functionsn Catalytic functions of enzyme

10、systemn Essential/assistant component of hormone and vitaminn Functional proteinn Immune functionn Nucleic acid血紅蛋白血紅蛋白 (Fe)維生素維生素B12 (Co)鋅指鋅指 (Zn)谷胱甘肽過氧谷胱甘肽過氧化物酶化物酶(Se)14Functions & Deficiencies of TEsp Deficiency VS. Excessn 必需微量元素在機(jī)體中有一個最適濃度范圍最適濃度范圍。當(dāng)其不 足即小于該范圍時，就會導(dǎo)致生物體生長遲緩，繁殖 衰退，甚至死亡；當(dāng)其濃度超過某

11、一限度時，則會引 起中毒中毒。15Functions & Deficiencies of TEsTable 1: Recommended daily intakes (RDIs) of trace elements16Functions & Deficiencies of TEsp Iron (Fe)n Iron deficiency is the micronutrient deficiency most prevalent in the world.n It is followed by vitamin A, iodine and zinc.n Iron is a part

12、 of heme (亞鐵血紅素亞鐵血紅素) present in:n hemoglobin (which transports oxygen in blood)n myoglobin (which stores oxygen in muscle)n cytochromes involved in the electron transport chain (unit 6) and in cytochrome P450 (involved in metabolism of drugs, pesticides, carcinogens, alcohol metabolism)血紅蛋白血紅蛋白(hem

13、oglobin)肌紅蛋白肌紅蛋白(myoglobin)17Functions & Deficiencies of TEs細(xì)胞色素細(xì)胞色素C (cytochrome)p Iron (Fe)n Iron is also forms part of many metalloenzymes involved in many reactions occurring in the body.NADH-Q還原酶還原酶18Functions & Deficiencies of TEsp Iron deficiencyn Deficiency of iron can lead to fatigu

14、e, anemia (where hemoglobin levels drop below 120 g/dL), poor school performance and poor immunity, brain function, premature birth, death.疲勞疲勞 (fatigue)貧血貧血 (anemia)鐮狀紅細(xì)胞貧血癥鐮狀紅細(xì)胞貧血癥19Functions & Deficiencies of TEsp Toxicityn Toxicity could occur due to (a) over supplementation, (b) repeated bl

15、ood transfusions, or (c) a genetic disease that predisposes individual to absorb Fe (hemochromatosis)n Fe deficiency is as deleterious to human health as iron overload. n Why? Fe participates in the Fenton reaction, which results in the production of free radicals. These free radicals damage cell me

16、mbranes (phospholipids), proteins and DNA/RNA.芬頓反應(yīng)芬頓反應(yīng)20Functions & Deficiencies of TEsp Zinc (Zn)n Zinc plays key roles in growth and immunity.生殖發(fā)育生殖發(fā)育味覺和食欲味覺和食欲視覺視覺免疫功能免疫功能21Functions & Deficiencies of TEsp How to determine Zn status? n It is difficult to determine whether a person is zinc

17、 deficient.n Measuring Zn levels in blood is not reliable, since zinc changes with the time of the day. It has a circadian rhythm. Zn levels are also affected by illness and periods of rapid growth.n Others methods involve:n Measuring levels of alkaline phosphatase or alcohol dehydrogenase in blood

18、which are enzymes that require zincn Zinc concentrations in hairn It is difficult to diagnose Zn deficiency since symptoms are similar to those of Fe deficiency.堿性磷酸酶堿性磷酸酶 (ALP)乙醇脫氫酶乙醇脫氫酶22Functions & Deficiencies of TEsp Zinc deficiency營養(yǎng)性侏儒癥營養(yǎng)性侏儒癥 (伊朗鄉(xiāng)村病伊朗鄉(xiāng)村病)腸源性肢體皮炎腸源性肢體皮炎厭食厭食n 原發(fā)性男性不育癥 (prim

19、ary male infertility)n 口腔潰瘍 (dental ulcer)n 夜盲癥 (visus diurnus)23Functions & Deficiencies of TEsp Iodine (I)n Iodine forms part of two hormones synthesized by the thyroid gland. n Tetraiodothyronine (T4)n Triiodothyronine (T3)n About 90% of the hormone released by the thyroid gland is T4, while

20、10% is T3.四碘甲腺原氨酸四碘甲腺原氨酸 (T4)三碘甲腺原氨酸三碘甲腺原氨酸 (T3)24Functions & Deficiencies of TEsp Iodine deficiency disorder (IDD)n Iodine deficiency is the most important cause of brain damage and mental retardation.n IDD consists of a wide spectrum of disorders ranging from simple goiter, characterized by an

21、 enlargement of the thyroid gland, to cretinism, an irreversible form of mental retardation.甲狀腺腫甲狀腺腫呆小癥呆小癥 (克汀病克汀病)智力缺陷智力缺陷25Functions & Deficiencies of TEsp Selenium (Se) n Selenium is incorporated into proteins to make selenoproteins, which are important antioxidant enzymes.n The antioxidant p

22、roperties of selenoproteins help prevent cellular damage from free radicals.n Selenium also participates in thyroid hormone metabolism.GSH-Px26Functions & Deficiencies of TEsp Selenium deficiency克山病克山病 (Keshan disease)大骨節(jié)病大骨節(jié)病 (Kashin-Bek syndrome)白內(nèi)障白內(nèi)障 (caligo lentis)27Why do TEs deficiencies

23、occur?p Poor consumption of minerals.n low trace elements intakep High consumption of foods that inhibit their absorption.n Phytate (plant foods) inhibits Ca, Zn, Fe; chemicals present in cassava, cabbage, turnips affects I metabolism; oxalates (spinach) affects Ca & Fen low trace elements bioav

24、ailability28Bioavailability of TEsp Definitionp How to Evaluate Bioavailability of Trace elements?n In vivo modeln In vitro modeln Cell modelp Our research work29Bioavailability of TEsp Definitionn Bioavailability, i.e. the percentage of the ingested amount of the element that can be absorbed during

25、 digestion and subsequently transformed into metabolically active species.p How to evaluate the bioavailability of Trace Elementsn In vivo modeln In vitro modeln Cell model人體消化系統(tǒng)人體消化系統(tǒng)30In Vivo Modelp Bioavailability should be determined by in vivo measurementsn Ideally, this kind of research should

26、 have been performed in humans.n Advantage: ideal, reliable and actual methodn Animal assays (mice, wistar, rabbit, piggy)humanWistachickenminipigrabbitmodel animals31In Vivo Modelp Bioavailability should be determined by in vivo measurementsn where I = intake, F = faecal excretion, and U = urinary

27、excretion.p Disadvantage of in vivo modeln In vivo methods using radiotracers in humans give the best estimation of bioavailability, but the use of radiotracers present problems in many laboratories (expensive or unavailable for many key trace elements) -(+) 100 (%) =IFUBioavailabilityIFdifficult&am

28、p;laboriousradiotracer32In Vivo Modelp Disadvantage of in vivo modeln ethical scruple of the use of human subjectsn significant difference between individualsn animal absorption studies are somewhat limited by uncertainties with regard to differences in metabolism between animals and humans. 33In Vi

29、tro Modelp In vitro methods have been developed to evaluate trace elements bioavailabilityn Miller et al. firstly (1981) developed an in vitro method based on element dialysability to determine iron bioavailability.n The in vitro methods are usually based on the simulation of gastric and intestinal

30、digestion of food and measure the fraction of the element available for absorption.n The in vitro methods offer an appealing alternative to animal and human models.Dennis D. Miller gastric juice: HCl (pH 1.52.0), pepsin34In Vitro Modelp In vitro methods have been developed to evaluate trace elements

31、 bioavailabilityn Advantage: These methods are simple, rapid, inexpensive and easy to control.n Evaluation of bioavailability of TEs involves measurement of the TEs soluble fraction or the TEs fraction that dialyses through a semipermeable membrane of a certain pore size (molecular weight cutoff, MW

32、CO).pancreatic juice (pH 7.88.4):pancreatin, bile salt and HCO-3 Dialysis(passive transport)35In Vitro Modelp In vitro digestion method (dialysis method)100 (%)=DDialysisC36In Vitro Modelp In vitro digestion method (solubility method)SAMPLE (25 g)+ 75 mL gastric juice (pepsine, sodium chloride, pH=1

33、.8)Shaking water bath (pH=3, 37, 4h)Centrifugation 3500 rpmSupernatant at pH 2.5Adjust pH=6.8 (NaHCO3)+ 50 mL intestinal juice (pancreatin, sodium chloride and bile salts)Shaking water bath (37, 4h)Adjust pH=7, centrifugation 3500 rpm, filtration (0.45 m)Supernatant at neutral pHGASTRIC DIGESTIONINT

34、ESTINAL DIGESTION100(%) = SSolubilityC37In Vitro Modelp In vitro methods have been developed to evaluate trace elements bioavailabilityn Disadvantagen the in vitro methods only measure the amount of TEs available in the gastrointestinal tract for absorption, i.e., its so-called bioaccessibility. n p

35、assive transportationn in vivo conditions can never be completely simulated under in vitro conditions. (factors: enzyme activity, ionic composition, digestion times and pH)n static gastrointestinal models vs. dynamic gastrointestinal models38In Vitro Modelp Dynamic gastrointestinal modelsn a followi

36、ng stream of dialyzing solutionn dialysate pH was monitoredA dynamic continuous-flow dialysis methodDialyzed components ware continuously removed in the digestive tract39Cell Modelp Cell culture models have also been utilized as part of in vitro digestion models. n The Caco-2 cell (the human colon a

37、denocarcinoma cell lines) culture model has been widely used as a predictive tool for the absorption of bioactive components from foods and pharmaceutical preparations. n The in vitro digestion/Caco-2 cell culture model developed by Glahn et al. (1998)n Other cell models：MDR1-MDCK, MDCK, ECV304.Glah

38、n R.P. 40Caco-2 單層細(xì)胞模型單層細(xì)胞模型p Caco-2 單層細(xì)胞模型特點(diǎn)單層細(xì)胞模型特點(diǎn) n 在一定條件下培養(yǎng)時，能產(chǎn)生細(xì)胞極性，形成刷狀 緣，分化出絨毛面頂側(cè)（分化出絨毛面頂側(cè)（Apical, AP）和基底側(cè)基底側(cè) （basolateral, BL），形成類似小腸上皮細(xì)胞。n 優(yōu)點(diǎn)：與人體小腸上皮細(xì)胞在形態(tài)和功能上十分相優(yōu)點(diǎn)：與人體小腸上皮細(xì)胞在形態(tài)和功能上十分相 似似。在腸腔側(cè)分化出的絨毛面含有典型的小腸微絨含有典型的小腸微絨 毛水解酶毛水解酶（如蔗糖酶、氨基肽酶和蛋白酶等）和各 種營養(yǎng)物質(zhì)轉(zhuǎn)運(yùn)載體營養(yǎng)物質(zhì)轉(zhuǎn)運(yùn)載體 如 P-糖蛋白（P-gp），多藥 耐藥蛋白（MRP）、二

39、價金屬離子轉(zhuǎn)運(yùn)載體等。n 用于研究小腸的吸收特征。Caco-2 細(xì)胞單層示意細(xì)胞單層示意圖（圖（人體結(jié)腸及直腸癌人體結(jié)腸及直腸癌細(xì)胞細(xì)胞）41Caco-2 單層細(xì)胞模型單層細(xì)胞模型p Caco-2 單層細(xì)胞培養(yǎng)單層細(xì)胞培養(yǎng) Caco-2 細(xì)胞單層培養(yǎng)模型細(xì)胞單層培養(yǎng)模型n Transwells 聚碳酸酯膜n 測定跨膜電阻跨膜電阻 （transepithelium electrical resistance， TEER） 確定細(xì)胞單層的 完整性和緊密性n 觀測細(xì)胞形態(tài)特征細(xì)胞形態(tài)特征，驗(yàn)證 其完整性42Caco-2 單層細(xì)胞模型單層細(xì)胞模型p Caco-2 單層細(xì)胞模型標(biāo)準(zhǔn)操作規(guī)程單層細(xì)胞模型標(biāo)

40、準(zhǔn)操作規(guī)程 轉(zhuǎn)運(yùn)實(shí)驗(yàn)示意圖轉(zhuǎn)運(yùn)實(shí)驗(yàn)示意圖王夔王夔 院士（北大）院士（北大）n APBL或BLAP雙向轉(zhuǎn)運(yùn)后，測定AP或BL側(cè)培養(yǎng)液 中待測物含量（轉(zhuǎn)運(yùn)量轉(zhuǎn)運(yùn)量）和細(xì)胞中待測物含量（攝取攝取 量量），兩者總和為物質(zhì)的吸收量總和為物質(zhì)的吸收量，用于評估生物利用性評估生物利用性。43Caco-2 單層細(xì)胞模型單層細(xì)胞模型p Caco-2 單層細(xì)胞模型標(biāo)準(zhǔn)操作規(guī)程單層細(xì)胞模型標(biāo)準(zhǔn)操作規(guī)程n 測定加入轉(zhuǎn)運(yùn)蛋白抑制劑后TEs在Caco-2 細(xì)胞單層 模型中的表觀滲透系數(shù)表觀滲透系數(shù)（apparent permeability coefficient, Papp），確定TEs的轉(zhuǎn)運(yùn)機(jī)制轉(zhuǎn)運(yùn)機(jī)制（主動運(yùn)輸 或

41、被動運(yùn)輸）。p Caco-2 單層細(xì)胞模型缺點(diǎn)單層細(xì)胞模型缺點(diǎn)n Caco-2 細(xì)胞在模擬小腸上皮細(xì)胞時存在缺乏分泌粘 液的杯狀細(xì)胞，缺少小腸上皮中黏液層的模擬缺少小腸上皮中黏液層的模擬。44汞元素生物利用性研究汞元素生物利用性研究n 朱砂中汞元素生物利用性研究的實(shí)驗(yàn)條件朱砂中汞元素生物利用性研究的實(shí)驗(yàn)條件 （體外消化透析法）（體外消化透析法）圖圖1 液液/ /固比對朱砂中汞元素溶出固比對朱砂中汞元素溶出率的影響率的影響 圖圖2 pH對朱砂中汞元素溶出率的對朱砂中汞元素溶出率的影響影響 45汞元素生物利用性研究汞元素生物利用性研究n 朱砂中汞元素生物利用性研究的實(shí)驗(yàn)條件朱砂中汞元素生物利用性研

42、究的實(shí)驗(yàn)條件 （體外消化透析法）（體外消化透析法）圖圖3 胃蛋白酶量對朱砂汞的溶出率胃蛋白酶量對朱砂汞的溶出率的影響的影響 圖圖4 接觸時間對朱砂中汞元素溶接觸時間對朱砂中汞元素溶出率的影響出率的影響 46汞元素生物利用性研究汞元素生物利用性研究n 朱砂中汞元素生物利用性研究的實(shí)驗(yàn)條件朱砂中汞元素生物利用性研究的實(shí)驗(yàn)條件 （體外消化透析法）（體外消化透析法）圖圖5 胰液膽鹽量對朱砂中汞相對透胰液膽鹽量對朱砂中汞相對透析率影響析率影響 圖圖6 透析時間對朱砂中汞透析率的透析時間對朱砂中汞透析率的影響影響 47汞元素生物利用性研究汞元素生物利用性研究n 含朱砂中成藥中汞的健康風(fēng)險評估指標(biāo)的提出含朱

43、砂中成藥中汞的健康風(fēng)險評估指標(biāo)的提出n 總汞量不能客觀地反映出朱砂對人體的毒副作用。基于對基于對 朱砂和含朱砂中成藥中汞元素生物可接受率的測定，提出朱砂和含朱砂中成藥中汞元素生物可接受率的測定，提出 評價含朱砂中成藥汞的汞生物可接受量限度，以含朱砂中評價含朱砂中成藥汞的汞生物可接受量限度，以含朱砂中 成藥中汞的生物利用性評價其安全性成藥中汞的生物利用性評價其安全性。n 人體內(nèi)蓄積汞量達(dá)到2 mgkg1表現(xiàn)為中毒，以成人體重 60 kg計，易知人體內(nèi)蓄積120 mg汞可表現(xiàn)汞中毒。汞在人體 內(nèi)半衰期為6570 d，以70 d計，設(shè)日攝入含朱砂中成藥中 汞生物可接受量為m（單位mg），服用f天后，

44、人體內(nèi)蓄積 汞量N可表示為： 48汞元素生物利用性研究汞元素生物利用性研究n 朱砂中汞元素生物利用性研究（體外消化透析法）朱砂中汞元素生物利用性研究（體外消化透析法）n 含朱砂中成藥中汞的健康風(fēng)險評估指標(biāo)閾值閾值 ：1.19 mg/（人（人天）天）49汞元素生物利用性研究汞元素生物利用性研究n 植物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響植物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響圖圖7 幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響 50汞元素生物利用性研究汞元素生物利用性研究n 植物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響植

45、物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響 圖圖7 幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響51汞元素生物利用性研究汞元素生物利用性研究n 植物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響植物源成分對復(fù)方蘆薈膠囊中汞生物利用性的影響 圖圖7 幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響幾種植物化學(xué)物質(zhì)源食品對復(fù)方蘆薈膠囊中汞生物利用性的影響52汞元素生物利用性研究汞元素生物利用性研究n 汞中毒劑量反推評估模型汞中毒劑量反推評估模型n 參考日本熊本和新瀉水俁病患者所攝入有毒魚貝的汞濃度 和估計攝入量而推算出體內(nèi)100

46、 mg的蓄積量為中毒劑量以 及邊振考等人曾報道人體汞蓄積中毒量為人體汞蓄積中毒量為100 mg。汞在人汞在人 體內(nèi)半衰期體內(nèi)半衰期為6570 d，為計算簡單此處以70 d計，設(shè)日攝 入含朱砂中成藥中汞生物可接受量為m（單位mg），服用f 天后，人體內(nèi)蓄積汞量N可表示為： 53汞元素生物利用性研究汞元素生物利用性研究n 汞中毒劑量反推評估模型汞中毒劑量反推評估模型汞生物可接受量超過汞生物可接受量超過0.099 mg /（人（人天）將對人體存天）將對人體存在較大中毒風(fēng)險在較大中毒風(fēng)險 54生物強(qiáng)化研究概況生物強(qiáng)化研究概況p 研究背景: 人體微量營養(yǎng)素營養(yǎng)不良 （Micronutrient Maln

47、utrition，MNM ）n 微量營養(yǎng)素（Micronutrients，即微量元素和維 生素）是維持人體正常生命活動的必需營養(yǎng)物質(zhì)，量微而作用大。如Fe、Zn、I、Se等微量元素在人體中承擔(dān)著多種重要的功能。n Humans require various mineral elements. Some are required in large amounts, but others, such as Fe, Zn, Cu, I and Se, are required in trace amounts because higher concentrations can be harmful

48、.55生物強(qiáng)化研究概況生物強(qiáng)化研究概況56n 基本上，這些礦質(zhì)元素（mineral elements）都是通過植物（谷物等主食）進(jìn)入人類食物鏈中。食用作物中礦質(zhì)元素的缺乏以及人體對其較低的生物利用性（bioavailability），導(dǎo)致人體微量營養(yǎng)素缺乏，也稱之為“隱形饑餓隱形饑餓”（hidden hunger）。生物強(qiáng)化研究概況生物強(qiáng)化研究概況57 原因： 主食（staple food）中微量營養(yǎng)素本身本身 （inherent）含量較低）含量較低，盡管蔬菜、水果和動物源食品富含微量營養(yǎng)素； 植物生長的環(huán)境土壤中礦質(zhì)元素缺乏環(huán)境土壤中礦質(zhì)元素缺乏； 植物對土壤中礦質(zhì)元素利用能力（利用能力（p

49、hytoavailablilty）較低）較低。 食物中礦質(zhì)元素的化學(xué)形態(tài)化學(xué)形態(tài)（chemical form）決定了人體對其吸收和同化（absorb and assimilate）的能力。 Some essential mineral elements, such as K and Na, occur solely as soluble inorganic ions in plants. However, most mineral elements also occur in organic compounds or inorganic salts, in both soluble and i

50、nsoluble forms.生物強(qiáng)化研究概況生物強(qiáng)化研究概況58 植物體內(nèi)含有促營養(yǎng)物質(zhì)（promoter）和抗?fàn)I養(yǎng)物質(zhì)（antinutrients），影響人體對其必需礦質(zhì)元素的吸收。促營養(yǎng)物質(zhì)：抗壞血酸（ascorbate），-胡蘿卜素（- carotene）和胱氨酸多肽（cysteine-rich polypeptides）等?？?fàn)I養(yǎng)物質(zhì)：草酸（oxalate），鞣酸（polyphenolics） 和植酸（phytate）等。n 世界范圍內(nèi)人群受到微量營養(yǎng)素缺乏的不良影響。 It is estimated that, of the worlds 6 billion people, 60-

51、80% are Fe deficient, 30% are Zn deficient, 30% are I deficient and about 15% are Se deficient.生物強(qiáng)化研究概況生物強(qiáng)化研究概況59 It is estimated that at least 1/3 of the world population is affected by the Zn deficiency problem, particularly children. Nearly 450 000 children under 5 years die annually because of Zn deficiency.生物強(qiáng)化研究概況生物強(qiáng)化研究概況60n 控制人體微量