味精安全问题精.ppt

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1、味精安全味精安全问题第1页，本讲稿共36页Outline 内容纲要内容纲要n nBrief review of original issues leading to expression of concern Brief review of original issues leading to expression of concern in early 1970sin early 1970s 简要回顾上世纪简要回顾上世纪7070年代初引起关注的安全问题年代初引起关注的安全问题n nBrief summary of safety views nowBrief summary of safety

2、 views now 简单总结当前关于味精安全的观点简单总结当前关于味精安全的观点n nExamination of two general issuesExamination of two general issues两大类问题两大类问题n nNeurotoxicity神经毒性神经毒性n nGeneral Adverse Effects(e.g.,MSG Symptom Complex)n n所有不良反应（如味精综合症）所有不良反应（如味精综合症）n nConclusionsConclusions 结论结论第2页，本讲稿共36页Kwok RHMChinese-Restaurant Syndr

3、ome中国餐馆综合症中国餐馆综合症中国餐馆综合症中国餐馆综合症New Engl J Med 278:796,1968 (letter)19681968年年年年 新英格兰医学杂志新英格兰医学杂志新英格兰医学杂志新英格兰医学杂志 （通讯）（通讯）（通讯）（通讯）n nFirst report of adverse symptoms in humans associated with First report of adverse symptoms in humans associated with the ingestion of Chinese food that suggested a pos

4、sible link the ingestion of Chinese food that suggested a possible link to MSG(to MSG(as well as many other ingredientsas well as many other ingredients).).首例报道人体摄入中国食品后出现不适症状可能与所添加的味精有关首例报道人体摄入中国食品后出现不适症状可能与所添加的味精有关（也可能是其他添加成分）（也可能是其他添加成分）n nAn anecdotal case-report.An anecdotal case-report.n n单例报告

5、（缺乏足够科学依据）单例报告（缺乏足够科学依据）第3页，本讲稿共36页Schaumberg HH et al.Monosodium L-Glutamate:Its Pharmacology&Role in the Chinese Restaurant SyndromeScience 163:826-828,1969谷氨酸单钠的药理学及其在中国餐馆并发症中的角色谷氨酸单钠的药理学及其在中国餐馆并发症中的角色谷氨酸单钠的药理学及其在中国餐馆并发症中的角色谷氨酸单钠的药理学及其在中国餐馆并发症中的角色科学科学科学科学163163期，期，期，期，826-828826-828页，页，页，页，196919

6、69n nDefined MSG Symptom Triad“n n味精味精“三种并发症状三种并发症状”表现为表现为n nBurning 灼烧感灼烧感n nFacial Pressure 面部紧张面部紧张n nChest Pain 胸痛胸痛第4页，本讲稿共36页Skeletal stunting骨萎缩骨萎缩Marked obesity明显肥胖明显肥胖Sterility 不育不育Hypothalamic lesions下丘脑损伤下丘脑损伤MSG INJECTED注射味精后注射味精后Olney JW.Olney JW.Brain Lesions,Obesity and Brain Lesions,

7、Obesity and Other Disturbances in Mice Other Disturbances in Mice Treated with Monosodium Treated with Monosodium Glutamate.Glutamate.SCIENCE 164:719-721,1969.SCIENCE 164:719-721,1969.小白鼠注射味精后出现大脑损伤，小白鼠注射味精后出现大脑损伤，小白鼠注射味精后出现大脑损伤，小白鼠注射味精后出现大脑损伤，肥胖以及其他系统紊乱肥胖以及其他系统紊乱肥胖以及其他系统紊乱肥胖以及其他系统紊乱19691969年科学杂志年科学

8、杂志年科学杂志年科学杂志第5页，本讲稿共36页n nConventional Toxicologic database for review by JECFA was Conventional Toxicologic database for review by JECFA was very extensive,including acute,subchronic&chronic toxicity very extensive,including acute,subchronic&chronic toxicity studies in rats,mice&dogs,together with

9、studies on studies in rats,mice&dogs,together with studies on reproductive toxicity and teratologyreproductive toxicity and teratologyn n供食品添加剂联合专家委员会审查的常规毒性数据资料非常完整，供食品添加剂联合专家委员会审查的常规毒性数据资料非常完整，包括大白鼠、小白鼠和狗的急性，亚慢性，慢性毒性研究以及遗包括大白鼠、小白鼠和狗的急性，亚慢性，慢性毒性研究以及遗传性毒性和畸形学研究。传性毒性和畸形学研究。The Safety Evaluation of Mo

10、nosodium GlutamateWalker R,Lupien JRWalker R,Lupien JRJournal of NutritionJournal of Nutrition 130:1049S-1052S,2000.130:1049S-1052S,2000.味精的安全评估味精的安全评估 20002000年营养学杂志年营养学杂志第6页，本讲稿共36页n nGLU has very low acute toxicity(15,000+mg/kg po)in rats and GLU has very low acute toxicity(15,000+mg/kg po)in rat

11、s and micemicen n谷氨酸对大、小白鼠具有极低的剧毒性（谷氨酸对大、小白鼠具有极低的剧毒性（15000+mg/kg po15000+mg/kg po）n nNo specific adverse effects in chronic and sub-chronic studies up No specific adverse effects in chronic and sub-chronic studies up to 2 yr(to 2 yr(MSG added to rat and mouse diets up to 4%,to dog diets up to MSG ad

12、ded to rat and mouse diets up to 4%,to dog diets up to 10%10%)n n两年内，在慢性、亚慢性研究试验中未有明显副作用（大、小白两年内，在慢性、亚慢性研究试验中未有明显副作用（大、小白鼠食物中味精占鼠食物中味精占4%4%，小狗食物中添加，小狗食物中添加10%10%）n nReproductive and teratology studies negativeReproductive and teratology studies negativen n生殖和畸形研究无异常生殖和畸形研究无异常Walker R,Lupien JR.Walke

13、r R,Lupien JR.J NutrJ Nutr 130130:1049S-1052S,2000.:1049S-1052S,2000.The Safety Evaluation of Monosodium GlutamateThe Safety Evaluation of Monosodium Glutamate味精的安全评估味精的安全评估第7页，本讲稿共36页The Issues 问题问题1.1.Neurotoxicity 神经毒性研究神经毒性研究神经毒性研究神经毒性研究2.CRS(MSG Symptom Complex)中国餐馆综合症（中国餐馆综合症（中国餐馆综合症（中国餐馆综合症（味

14、精综合症）味精综合症）味精综合症）味精综合症）第8页，本讲稿共36页Neurotoxicity神经毒性研究神经毒性研究Dietary MSG食用味精食用味精 Plasma(GLU)血浆（谷氨酸）上升血浆（谷氨酸）上升 Brain(GLU)大脑（谷氨酸）上升大脑（谷氨酸）上升Neuronal excitation&death神经兴奋和死亡神经兴奋和死亡第9页，本讲稿共36页Barriers to Neurotoxicityn nGastrointestinal TractGastrointestinal Tract efficiently uses ingested GLU(MSG)as E-e

15、fficiently uses ingested GLU(MSG)as E-source(95+%).source(95+%).n n胃肠道能有效地吸收胃肠道能有效地吸收95%95%以上的谷氨酸钠作为能源以上的谷氨酸钠作为能源n nGut is thus a barrier to GLU entry into blood.Gut is thus a barrier to GLU entry into blood.n n肠道因此能阻止谷氨酸进入血液中肠道因此能阻止谷氨酸进入血液中n nBlood-Brain BarrierBlood-Brain Barrier prevents GLU pene

16、tration into brain.prevents GLU penetration into brain.n n血脑屏障阻止谷氨酸渗透到大脑血脑屏障阻止谷氨酸渗透到大脑n nOnly Only very highvery high oral doses of MSG by gavage can raise plasma GLU oral doses of MSG by gavage can raise plasma GLU enough to get GLU into brainenough to get GLU into brainn n只有灌喂大剂量的味精，才会致血浆中的谷氨酸含量升高

17、，而进入到只有灌喂大剂量的味精，才会致血浆中的谷氨酸含量升高，而进入到大脑大脑n nMSG in foodMSG in food does does notnot have this effect.have this effect.n n食物中添加的味精不会有这种效果食物中添加的味精不会有这种效果第10页，本讲稿共36页Fernstrom JD et al.Fernstrom JD et al.J Clin Endocrinol MetabJ Clin Endocrinol Metab 8181:184-:184-191,1996.191,1996.19961996年，临床内分泌代谢杂志年，临

18、床内分泌代谢杂志Adult males(80 kg)quickly ingested MSG,12.7 g(150 mg/kg)in solution.成年男子（体重约80公斤）能很快吸收溶液中12.7g（约150毫克每公斤）的味精第11页，本讲稿共36页Tsai P-J,Huang P-C Tsai P-J,Huang P-C Metabolism Metabolism 4848:1455-1460,1999.:1455-1460,1999.Arrows=meal or snack 箭头代表摄取的食物或点心Meals:0745,1215,1800 h 饮食时间：0745，1215，1800D

19、aily MSG dose=100 mg/kg:Daily MSG dose=100 mg/kg:每日摄入味精量：每日摄入味精量：每日摄入味精量：每日摄入味精量：100mg/kg100mg/kgBreakfastBreakfast:15 mg/kg15 mg/kg早餐：早餐：早餐：早餐：15mg/kg15mg/kgLunch:40 mg/kgLunch:40 mg/kg午餐午餐午餐午餐:40mg/kg:40mg/kgDinner 45 mg/kgDinner 45 mg/kg晚餐：晚餐：晚餐：晚餐：45mg/kg45mg/kgData are means sem(n=10)数据：均值标准差Bl

20、ack circle:no MSG黑圈表示不含味精White circle:MSG.白圈表示含有味精第12页，本讲稿共36页 GLU GLU injectioninjection ip stimulates PRL ip stimulates PRL secretion in ratssecretion in rats Does GLU(MSG)ingestion Does GLU(MSG)ingestion stimulate PRL secretion in stimulate PRL secretion in humans?humans?腹腔注射谷氨酸钠会刺激小白鼠催乳腹腔注射谷氨酸钠会

21、刺激小白鼠催乳素的分泌，它会对人体产生同样的作用素的分泌，它会对人体产生同样的作用吗？吗？12.7 g oral load of MSG in male 12.7 g oral load of MSG in male subjects subjects 雄性研究对象雄性研究对象12.712.7克口服克口服Plasma PRL in ratsPlasma PRL in rats injected injected with MSG(1000 mg/kg ip).with MSG(1000 mg/kg ip).From:From:Terry LC et al.Terry LC et al.Brai

22、n Research Brain Research 217217:129-142,1981.:129-142,1981.RatsRatsHumansHumans第13页，本讲稿共36页Placental Barrier to Maternal Placental Barrier to Maternal Glutamate Glutamate 胎盘屏障母体中的谷氨酸钠胎盘屏障母体中的谷氨酸钠胎盘屏障母体中的谷氨酸钠胎盘屏障母体中的谷氨酸钠Stegink LD et al Am J Obstet Gynecol 122:70-78(1975)Monkey study.猴子实验猴子实验Highest

23、 dose(400 mg/kg iv,open circles)produced plasma GLU 70-times normal.Battaglia FC.J Nutrition 130:974S-977S(2000)第14页，本讲稿共36页Effect of oral MSG loading on breast milk free GLU Effect of oral MSG loading on breast milk free GLU concentrations in lactating womenconcentrations in lactating women哺乳妇女食用味精

24、后母乳不会有谷氨酸钠哺乳妇女食用味精后母乳不会有谷氨酸钠哺乳妇女食用味精后母乳不会有谷氨酸钠哺乳妇女食用味精后母乳不会有谷氨酸钠第15页，本讲稿共36页Lactating women ingested 100 mg/kg MSG in capsules with water,and milk samples were taken at the indicated times thereafter.This This dose dose raised raised plasma plasma GLU GLU from from 45 45 nmol/ml nmol/ml to to peak p

25、eak values values of of about about 300 300 nmol/ml nmol/ml in in 30-45 30-45 min.min.From:Baker GL et al.,Factors influencing dicarboxylic amino acid content of human milk.In:Glutamic Glutamic Acid:Acid:Advances Advances in in Biochemistry Biochemistry&PhysiologyPhysiology,Filer LJ et al.,ed.New Yo

26、rk,Raven Press,1979,pp.111-123.哺乳期女性加水摄入 100 mg/kg 的胶囊，对其后特定时间的母乳样品进行检验表明：这这一一剂剂量量使使得得血血液液谷谷氨氨酸酸浓浓度度在在30-45分分钟钟内内从从45nmol/ml 45nmol/ml 提提提提高高高高到到到到峰峰峰峰值值值值约约约约300 300 nmol/ml nmol/ml。From:Baker GL et al.,Factors influencing dicarboxylic amino acid content of human milk.In:Glutamic Glutamic Acid:Acid

27、:Advances Advances in in Biochemistry Biochemistry&PhysiologyPhysiology,Filer LJ et al.,ed.New York,Raven Press,1979,pp.111-123.影响人体母乳二氨基酸浓度的因素谷氨酸：生物化学和生理学进展第16页，本讲稿共36页Brain Issues 大脑问题大脑问题 n nRelevance to human MSG ingestion:Relevance to human MSG ingestion:n n有关人体摄入味精有关人体摄入味精有关人体摄入味精有关人体摄入味精n nTh

28、e placenta blocks GLU transfer from maternal into fetal blood:The placenta blocks GLU transfer from maternal into fetal blood:FETAL brain is safe.FETAL brain is safe.n n胎盘会阻止谷氨酸从母体传递给胎儿：胎儿大脑不会受到影响胎盘会阻止谷氨酸从母体传递给胎儿：胎儿大脑不会受到影响胎盘会阻止谷氨酸从母体传递给胎儿：胎儿大脑不会受到影响胎盘会阻止谷氨酸从母体传递给胎儿：胎儿大脑不会受到影响n nBreast milk(GLU)does

29、 not rise when mother ingests high-dose MSG:Breast milk(GLU)does not rise when mother ingests high-dose MSG:NEWBORN/INFANT NEWBORN/INFANT brain is safe.brain is safe.n n当母体摄入大剂量的味精母乳中的谷氨酸含量不会上升：新生儿的脑发育当母体摄入大剂量的味精母乳中的谷氨酸含量不会上升：新生儿的脑发育当母体摄入大剂量的味精母乳中的谷氨酸含量不会上升：新生儿的脑发育当母体摄入大剂量的味精母乳中的谷氨酸含量不会上升：新生儿的脑发育是安全

30、的是安全的是安全的是安全的n nInfant metabolizes GLU at same rate as adult (Stegink et al.,Infant metabolizes GLU at same rate as adult (Stegink et al.,Pediatric Res Pediatric Res 20:53-58,1986).20:53-58,1986).n n婴幼儿具有和成年人同样的谷氨酸代谢的能力婴幼儿具有和成年人同样的谷氨酸代谢的能力第17页，本讲稿共36页Brain Issues大脑问题大脑问题 n nThe human brain is unaffe

31、cted by the very high plasma(GLU)The human brain is unaffected by the very high plasma(GLU)following high dose MSG intakefollowing high dose MSG intaken n摄入大量的味精导致的血浆中高谷氨酸含量不会对摄入大量的味精导致的血浆中高谷氨酸含量不会对人体大脑产生影响人体大脑产生影响n nNo dose of MSG has yet been given to humans high enough No dose of MSG has yet been

32、 given to humans high enough to induce CNS effects.to induce CNS effects.n n至今亦未发现食用味精会影响人体中枢神经系统至今亦未发现食用味精会影响人体中枢神经系统第18页，本讲稿共36页第19页，本讲稿共36页CRS/Allergy(MSG Symptom Complex)中国餐馆综合症中国餐馆综合症/过敏症过敏症味精综合症味精综合症第20页，本讲稿共36页第21页，本讲稿共36页Studying MSG Symptom Complex味精综合症研究味精综合症研究n nCan reproducible symptoms

33、be defined?n n能定义这些重复性的症状么？能定义这些重复性的症状么？n nAre reproducible symptoms dose-related?n n这些重复性症状与摄入剂量有关吗这些重复性症状与摄入剂量有关吗?n nDo MSG-sensitive individuals exist?n n对味精敏感的个体存在吗？对味精敏感的个体存在吗？第22页，本讲稿共36页SYMPTOMS ATTRIBUTED TO MSG:味精味精所致症状所致症状n nBurning,tightness,numbness in upper chest,neck and face.Burning,t

34、ightness,numbness in upper chest,neck and face.发烧，身体发紧，胸腔上部发闷，脖子、面部发麻发烧，身体发紧，胸腔上部发闷，脖子、面部发麻n nDizziness,headache Dizziness,headache 眩晕，头疼眩晕，头疼n nChest pain,palpitation Chest pain,palpitation 胸口痛，心悸胸口痛，心悸n nWeakness Weakness 乏力乏力n nNausea,vomiting Nausea,vomiting 反胃呕吐反胃呕吐n nBronchospasm(asthmatics)Br

35、onchospasm(asthmatics)哮喘哮喘n nHives(urticaria)Hives(urticaria)麻疹麻疹MECHANISMS UNKNOWN MECHANISMS UNKNOWN 机制未知机制未知机制未知机制未知第23页，本讲稿共36页Multicenter,double-blind,placebo-controlled,multiple-challenge evaluation of reported reactions to monosodium glutamate.Geha RS et al.Geha RS et al.J Allergy Clin Immuno

36、lJ Allergy Clin Immunol 106106:973-80,2000:973-80,2000味精反应的多中心、双盲、安慰剂控制、多重治疗评估报告味精反应的多中心、双盲、安慰剂控制、多重治疗评估报告20002000年年 过敏与临床免疫学过敏与临床免疫学 杂志杂志第24页，本讲稿共36页n nProtocol A:Protocol A:130130 self-styled MSG-sensitive individuals.Fasted,self-styled MSG-sensitive individuals.Fasted,challenge challenge blindbli

37、nd with placebo or MSG(5 g with placebo or MSG(5 g in liquidin liquid).).n n实验实验A A：130130例自认为例自认为MSGMSG过敏者，禁食，以安慰剂或过敏者，禁食，以安慰剂或MSG(5MSG(5克液体克液体)进行盲试。进行盲试。n nProtocol B:Protocol B:Subjects had positive response of 2 symptoms toSubjects had positive response of 2 symptoms toeither or both either or b

38、oth treatments in treatments in A A(i.e.,placebo responders(i.e.,placebo responderstoo).Fast,too).Fast,blindblind challenge with 0,1.25,2.5 or 5 g challenge with 0,1.25,2.5 or 5 gMSG(MSG(in liquidin liquid).).n n实验实验B:B:对对A A中，出现阳性反应的实验对象，超过中，出现阳性反应的实验对象，超过2 2种症状（例如：对安种症状（例如：对安慰剂反应也一样）。禁食，以慰剂反应也一样）。

39、禁食，以0 0，1.251.25，2.52.5或或5 5克克MSG(MSG(液体液体)进行盲试。进行盲试。Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第25页，本讲稿共36页n nProtocol C:Protocol C:Subjects had positive response of 2 symptoms to 5Subjects had positive response of 2 symptoms to 5g MSG g MSG but not placebobut not placebo in in A A or or

40、B B.Fast,placebo(suc-.Fast,placebo(suc-rose)or MSG(5 g),rose)or MSG(5 g),in capsules in capsules(blindblind).Do twice.).Do twice.n n实验实验实验实验C:C:对对A A和和B B中阳性反应的实验对象中阳性反应的实验对象-对对5 5克克MSGMSG出现超过出现超过2 2种症状（对安慰剂种症状（对安慰剂没有），禁食，以胶囊性的安慰剂（蔗糖）或没有），禁食，以胶囊性的安慰剂（蔗糖）或MSG(5MSG(5克克)，进行盲试。重复实验。，进行盲试。重复实验。n nProtoco

41、l D:Protocol D:Subjects had positive response to Subjects had positive response to bothboth MSG chal-MSG chal-lenges in lenges in C C.Fast,breakfast&placebo(sucrose).Fast,breakfast&placebo(sucrose)or MSG(5 g),or MSG(5 g),in capsules in capsules(blindblind).Do three times.).Do three times.n n实验实验实验实验

42、D:D:对对C C中中MSGMSG治疗出现阳性反应的实验对象，禁食，早餐加胶囊性安慰剂（蔗糖）治疗出现阳性反应的实验对象，禁食，早餐加胶囊性安慰剂（蔗糖）或或MSG(5MSG(5克克)，进行盲试。重复，进行盲试。重复3 3次实验次实验Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第26页，本讲稿共36页SYMPTOMS RATED:症状表现症状表现n nGeneral Weakness虚弱虚弱n nMuscle Tightness肌肉紧张肌肉紧张n nMuscle Twitching肌肉酸痛肌肉酸痛n nFlushing脸颊发红脸颊发

43、红n nSweating盗汗盗汗n nBurning Sensation灼感灼感n nHeadache-migraine偏头痛偏头痛n nChest pain胸闷胸闷n nPalpitations心悸心悸n nNumbness-Tingling发麻发麻Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第27页，本讲稿共36页Protocol A Results:实验实验A结果结果n nn=50:n=50:2 symptoms with MSG&0/1 with placebo.2 symptoms with MSG&0/1 with pl

44、acebo.n n MSGMSG组超过组超过2 2种症状出现种症状出现+安慰剂组安慰剂组1 1个个n nn=19n=19:2 symptoms with MSG&:2 symptoms with MSG&placebo.placebo.n n 超过超过2 2种症状出现，味精和安慰剂种症状出现，味精和安慰剂n nn=17n=17:2 symptoms with placebo&0/1 with MSG.:2 symptoms with placebo&0/1 with MSG.n n 安慰剂组超过安慰剂组超过2 2种症状出现种症状出现+MSG+MSG组组1 1个个n nn=44n=44:0 or

45、 1 symptoms with MSG&placebo.0 or 1 symptoms with MSG&placebo.n n 没有或没有或1 1种症状出现：种症状出现：MSG+MSG+安慰剂安慰剂Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第28页，本讲稿共36页Protocol B Results:实验实验B结果结果n nn=86 from A had 2 symptoms with a treatment(blinded:placebo or MSG),and included in B.69 completed.n n对

46、对2 2种症状进行治疗（双盲：安慰剂或种症状进行治疗（双盲：安慰剂或MSGMSG）n nOvernight fast,challenge with 0,1.25,2.5 or 5 g MSG.n n禁食过夜，按禁食过夜，按0 0，1.251.25，2.52.5或或5 5克克MSGMSG看结果看结果第29页，本讲稿共36页Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000n nn=19/69 reported 2 symptoms to 5 g MSG but not placebo.n n19/6919/69例报道，例报道，5 5克克MS

47、GMSG下有超过下有超过2 2种症状出现，没有安慰剂种症状出现，没有安慰剂n nn=14/19 the same symptoms occurred in B as in A.n n14/1914/19例中同样症状出现，类似于例中同样症状出现，类似于A A实验实验n nHence,14/130 showed reproducible response to 5 g MSG.n n因此，因此，14/13014/130表现出对表现出对5 5克克MSGMSG的可重复性反应的可重复性反应第30页，本讲稿共36页Protocol C Results:实验实验C结果结果Geha RS et al.,J A

48、llergy Clin Immunol 106:973-80,2000n n1995 FASEB MSG Panel:1995 FASEB MSG Panel:3 placebo-MSG challenges must 3 placebo-MSG challenges must give give samesame positive response to MSG,no response to placebo.positive response to MSG,no response to placebo.Give MSG Give MSG in capsulesin capsules.n n1

49、9951995年美国实验生物学联合会味精组：年美国实验生物学联合会味精组：3 3种安慰剂种安慰剂-味精治味精治疗必须引起同样的对味精的阳性反应，对安慰剂没有疗必须引起同样的对味精的阳性反应，对安慰剂没有反应，味精应该以胶囊的形式给予。反应，味精应该以胶囊的形式给予。n nn=19 had 2 symptoms inn=19 had 2 symptoms in A A&B B with MSG&no symptoms with MSG&no symptoms with placebo.with placebo.n=12n=12 agreed to be studied.agreed to be

50、studied.n nN=19N=19时，实验时，实验A A和和B B的味精组都有超过的味精组都有超过2 2种症状出现，种症状出现，安慰剂组没有症状出现，安慰剂组没有症状出现，n=12n=12时，实验一致。时，实验一致。第31页，本讲稿共36页Protocol C Results:实验实验C结果结果Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000n nTwo separate tests of MSG(5 g)vs placebo.Two separate tests of MSG(5 g)vs placebo.n n分开测试味精（分开