味精安全问题.pptx

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1、Kwok RHMChinese-Restaurant Syndrome中国中国餐馆综合症餐馆综合症New Engl J Med 278:796,1968 (letter)1968年年 新英格兰医学杂志新英格兰医学杂志（通讯）（通讯）First report of adverse symptoms in humans associated with the ingestion of Chinese food that suggested a possible link to MSG(as 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

2、所添加的味精有关（也可能是其他添加成分）An anecdotal case-report.单例报告（缺乏足够科学依据）第1页/共35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科学科学163期，期，826-828页，页，1969Defined MSG Symptom Triad“味精味精“三种并发症状三

3、种并发症状”表现为表现为Burning 灼烧感灼烧感Facial Pressure 面部紧张面部紧张Chest Pain 胸痛胸痛第2页/共35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.Brain Lesions,Obesity and Other Disturbances in Mice Treated with Monosodium Glutamate.SCIENCE 164:719-721,

4、1969.小白鼠注射味精后出现大脑小白鼠注射味精后出现大脑损伤，肥胖以及其他系统紊损伤，肥胖以及其他系统紊乱乱1969年科学杂志年科学杂志第3页/共35页Conventional Toxicologic database for review by JECFA was very extensive,including acute,subchronic&chronic toxicity studies in rats,mice&dogs,together with studies on reproductive toxicity and teratology供食品添加剂联合专家委员会审查的常规毒

5、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传性毒性和畸形学研究。The Safety Evaluation of Monosodium 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4页/共35页GLU has very low acute toxicity(15,000+mg/kg

6、 po)in rats and mice谷氨酸对大、小白鼠具有极低的剧毒性（15000+mg/kg po）No specific adverse effects in chronic and sub-chronic studies up to 2 yr(MSG added to rat and mouse diets up to 4%,to dog diets up to 10%)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4%，小狗食物中添加10%）Reproductive and teratology studies negative生殖和畸形研究无异常Walke

7、r R,Lupien JR.Walker R,Lupien JR.J NutrJ Nutr 130130:1049S-1052S,2000.:1049S-1052S,2000.The Safety Evaluation of Monosodium Glutamate味精的安全评估味精的安全评估第5页/共35页The Issues 问题问题1.Neurotoxicity 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（味精综合症）味精综合症）第6页/共35页Neurotoxicity神经毒性研究神经毒性研究Dietary MSG食用味精

8、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7页/共35页Barriers to NeurotoxicityGastrointestinal Tract efficiently uses ingested GLU(MSG)as E-source(95+%).胃肠道能有效地吸收95%以上的谷氨酸钠作为能源Gut is thus a barrier to GLU entry into blood.肠道因此能阻止谷氨酸进入血液中Blood-

9、Brain Barrier prevents GLU penetration into brain.血脑屏障阻止谷氨酸渗透到大脑Only very high oral doses of MSG by gavage can raise plasma GLU enough to get GLU into brain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MSG in food does not have this effect.食物中添加的味精不会有这种效果第8页/共35页Fernstrom JD et al.Fernstrom JD et al.J Clin Endocr

10、inol MetabJ Clin Endocrinol Metab 8181:184-191,1996.184-191,1996.19961996年，临床内分泌代谢杂志年，临床内分泌代谢杂志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9页/共35页Tsai P-J,Huang P-C Tsai P-J,Huang P-C Metabolism Metabolism 4848:1455-1460,1999.:1455-146

11、0,1999.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：0745，1215，1800Daily 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

12、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Black circle:no MSG黑圈表示不含味精White circle:MSG.白圈表示含有味精第10页/共35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

13、 secretion in stimulate PRL secretion in humans?humans?腹腔注射谷氨酸钠会刺激小白鼠催腹腔注射谷氨酸钠会刺激小白鼠催乳素的分泌，它会对人体产生同样乳素的分泌，它会对人体产生同样的作用吗？的作用吗？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(100

14、0 mg/kg ip).with MSG(1000 mg/kg ip).From:Terry LC et al.From:Terry LC et al.Brain Research Brain Research 217217:129-142,1981.:129-142,1981.RatsRatsHumansHumans第11页/共35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Ste

15、gink LD et al Am J Obstet Gynecol 122:70-78(1975)Monkey study.猴子实验猴子实验Highest dose(400 mg/kg iv,open circles)produced plasma GLU 70-times normal.Battaglia FC.J Nutrition 130:974S-977S(2000)第12页/共35页Effect of oral MSG loading on breast milk free GLU Effect of oral MSG loading on breast milk free GLU

16、concentrations in lactating womenconcentrations in lactating women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哺乳妇女食用味精后母乳不会有谷氨酸钠第13页/共35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 ra

17、ised plasma plasma GLU GLU from from 45 45 nmol/ml nmol/ml to to peak peak 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 B

18、iochemistry Biochemistry&PhysiologyPhysiology,Filer LJ et al.,ed.New York,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 nmol/ml 300 nmol/ml。From:Baker GL et al.,Factors influencing dicar

19、boxylic amino acid content of human milk.In:Glutamic Glutamic Acid:Acid: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14页/共35页Brain Issues 大脑问题大脑问题 Relevance to human MSG ingestion:有关人体摄入味精

20、有关人体摄入味精The placenta blocks GLU transfer from maternal into fetal blood:FETAL brain is safe.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Breast milk(GLU)does not rise when mother ingests high-dose MSG:NEWBORN/INFANT brain is safe.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

21、安全的的脑发育是安全的Infant metabolizes GLU at same rate as adult (Stegink et al.,Pediatric Res 20:53-58,1986).婴幼儿具有和成年人同样的谷氨酸代谢的能力第15页/共35页Brain Issues大脑问题大脑问题 The human brain is unaffected by the very high plasma(GLU)following high dose MSG intake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No dose of MSG has yet been giv

22、en to humans high enough to induce CNS effects.至今亦未发现食用味精会影响人体中枢神经系统第16页/共35页第17页/共35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18页/共35页第19页/共35页Studying MSG Symptom Complex味精综合症研究味精综合症研究Can reproducible symptoms be defined?能定义这些重复性的症状么？能定义这些重复性的症状么？Are reproducible symptoms do

23、se-related?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?Do MSG-sensitive individuals exist?对味精敏感的个体存在吗？对味精敏感的个体存在吗？第20页/共35页SYMPTOMS ATTRIBUTED TO MSG:味精所致症状味精所致症状Burning,tightness,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Dizziness,headache 眩晕，头疼Chest pain,palpitation 胸口痛，心悸Weakness 乏力Nausea,vo

24、miting 反胃呕吐Bronchospasm(asthmatics)哮喘Hives(urticaria)麻疹MECHANISMS UNKNOWN 机制未知机制未知第21页/共35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 ImmunolJ Allergy Clin Immunol 106106:973-80,20

25、00:973-80,2000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22页/共35页Protocol A:130 self-styled MSG-sensitive individuals.Fasted,challenge blind with placebo or MSG(5 g in liquid).实验A：130例自认为MSG过敏者，禁食，以安慰剂或MSG(5克液体)进行盲试。Protocol B:Subjects had positive response

26、of 2 symptoms toeither or both treatments in A(i.e.,placebo responderstoo).Fast,blind challenge with 0,1.25,2.5 or 5 gMSG(in liquid).实验B:对A中，出现阳性反应的实验对象，超过2种症状（例如：对安慰剂反应也一样）。禁食，以0，1.25，2.5或5克MSG(液体)进行盲试。Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第23页/共35页Protocol C:Subjects had positive re

27、sponse of 2 symptoms to 5g MSG but not placebo in A or B.Fast,placebo(suc-rose)or MSG(5 g),in capsules(blind).Do twice.实验实验C:对A和B中阳性反应的实验对象-对5克MSG出现超过2种症状（对安慰剂没有），禁食，以胶囊性的安慰剂（蔗糖）或MSG(5克)，进行盲试。重复实验。Protocol D:Subjects had positive response to both MSG chal-lenges in C.Fast,breakfast&placebo(sucrose)o

28、r MSG(5 g),in capsules(blind).Do three times.实验实验D:对C中MSG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MSG(5克)，进行盲试。重复3次实验Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第24页/共35页SYMPTOMS RATED:症状表现症状表现General Weakness虚弱虚弱Muscle Tightness肌肉紧张肌肉紧张Muscle Twitching肌肉酸痛肌肉酸痛Flushing脸颊发红脸颊发红Sweating盗汗盗汗Burning Sens

29、ation灼感灼感Headache-migraine偏头痛偏头痛Chest pain胸闷胸闷Palpitations心悸心悸Numbness-Tingling发麻发麻Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第25页/共35页Protocol A Results:实验实验A结果结果n=50:2 symptoms with MSG&0/1 with placebo.MSG组超过2种症状出现+安慰剂组1个n=19:2 symptoms with MSG&placebo.超过2种症状出现，味精和安慰剂n=17:2 symptoms wi

30、th placebo&0/1 with MSG.安慰剂组超过2种症状出现+MSG组1个n=44:0 or 1 symptoms with MSG&placebo.没有或1种症状出现：MSG+安慰剂Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000第26页/共35页Protocol B Results:实验实验B结果结果n=86 from A had 2 symptoms with a treatment(blinded:placebo or MSG),and included in B.69 completed.对2种症状进行治疗（双盲：

31、安慰剂或MSG）Overnight fast,challenge with 0,1.25,2.5 or 5 g MSG.禁食过夜，按0，1.25，2.5或5克MSG看结果第27页/共35页Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000n=19/69 reported 2 symptoms to 5 g MSG but not placebo.19/69例报道，5克MSG下有超过2种症状出现，没有安慰剂n=14/19 the same symptoms occurred in B as in A.14/19例中同样症状出现，类似于A实验

32、Hence,14/130 showed reproducible response to 5 g MSG.因此，14/130表现出对5克MSG的可重复性反应第28页/共35页Protocol C Results:实验实验C结果结果Geha RS et al.,J Allergy Clin Immunol 106:973-80,20001995 FASEB MSG Panel:3 placebo-MSG challenges must give same positive response to MSG,no response to placebo.Give MSG in capsules.19

33、95年美国实验生物学联合会味精组：3种安慰剂-味精治疗必须引起同样的对味精的阳性反应，对安慰剂没有反应，味精应该以胶囊的形式给予。n=19 had 2 symptoms in A&B with MSG&no symptoms with placebo.n=12 agreed to be studied.N=19时，实验A和B的味精组都有超过2种症状出现，安慰剂组没有症状出现，n=12时，实验一致。第29页/共35页Protocol C Results:实验实验C结果结果Geha RS et al.,J Allergy Clin Immunol 106:973-80,2000Two separa

34、te tests of MSG(5 g)vs placebo.分开测试味精（5克）和安慰剂n=2/12 had 2 symptoms with MSG&none with placebo;but symptoms were not the same.n=2/12，味精组超过2种症状出现，安慰剂组没有症状出现，但症状不同。n=0/130 met FASEB criteria for MSG sensitivityn=0/130 时符合时符合FASEB的的MSG过敏性实验标过敏性实验标准准第30页/共35页Geha RS et al.,J Allergy Clin Immunol 106:973-

35、80,2000CONCLUSION:Using criteria established by the 1995 FASEB panel,none of the individuals who claimed a sensitivity to MSG actually showed this sensitivity when tested under blinded conditions.结论：根据1995年美国实验生物学联合会（FASEB）制定的标准，对那些声称味精过敏的个体进行双盲试验表明他们未表现出敏感性。第31页/共35页CRS Symptoms in Humans人体的人体的MSG症

36、状症状Asthma:Early studies claiming that MSG induces asthma in asthma patients have not been confirmed in recent studies involving greater numbers of patients.哮喘：早期研究声称味精会导致哮喘病人病情发作，但近期众多数量病人的研究中未得到证实Stevenson DD.Monosodium glutamate and asthma.J Nutr 130:1067S-1073S,2000味精和哮喘 2000年 营养学杂志.第32页/共35页MSG

37、Symptoms in Humans人体的人体的MSG症状症状Urticaria:65 subjects with idiopathic urticaria;single-and double-blind studies using 2.5 g MSG challenges vs placebo(capsules).荨麻疹：使用2.5g味精和安慰剂（胶囊）治疗65例特发性荨麻疹，单盲和双盲研究“.MSG is a distinctly uncommon cause or exacerbant of chronic urticaria,if it induces urticaria at all

38、.We were certainly unable to demonstrate MSG-induced urticaria in any of our chronic urticaria patients,even those who believed MSG provoked their urticaria in the past.”即使味精会引发荨麻疹，那也很少会引起或加剧慢性荨麻疹。我们无法确证慢性麻疹病人中多少是由味精所致的，尽管有些人认为是因为过去食用味精所致病。Simon RA.Additive-induced urticaria:Experience with monosodi

39、um glutamate(MSG).J Nutr 130:1063S-1066S,2000.第33页/共35页 Bazzano G,DElia JA,Olson RE Science 169:1208-1209,1970.Adult human subjects ingested a chemically-de-fined diet supplying all of the essential amino acids in optimum amounts,plus glutamic acid as the sole source of non-essential nitrogen,for 14-42 days.No subjects developed the Chinese restaurant syndrome.No changes in weight,irrita-bility,appetite or mentation were noted.给予成人研究对象适量的化学性饮食包含所有必须氨基酸，并以谷氨酸作为非必须氮源，14-42天后，没有发现中国餐馆综合症，体重、情绪、胃口以及智力都没有变化。第34页/共35页感谢您的观看。第35页/共35页