《味精安全問題》PPT課件.ppt

Umami/MSG: Safety Issues 味精的安全問題,John D. Fernstrom, Ph.D. Professor - University of Pittsburgh School of Medicine 匹茲堡大學 醫(yī)學院 教授 Scientific Advisor - IGTC IGTC科學顧問,Outline 內容綱要,Brief review of original issues leading to expression of concern in early 1970s 簡要回顧上世紀70年代初引起關注的安全問題 Brief summary of safety views now 簡單總結當前關于味精安全的觀點 Examination of two general issues兩大類問題 Neurotoxicity神經毒性 General Adverse Effects (e.g., MSG Symptom Complex) 所有不良反應（如味精綜合癥） Conclusions 結論,Kwok RHM Chinese-Restaurant Syndrome中國餐館綜合癥 New Engl J Med 278: 796, 1968 (letter) 1968年 新英格蘭醫(yī)學雜志 （通訊）,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). 首例報道人體攝入中國食品后出現不適癥狀可能與所添加的味精有關（也可能是其他添加成分） An anecdotal case-report. 單例報告（缺乏足夠科學依據）,Schaumberg HH et al. Monosodium L-Glutamate: Its Pharmacology & Role in the Chinese Restaurant Syndrome Science 163: 826-828, 1969 谷氨酸單鈉的藥理學及其在中國餐館并發(fā)癥中的角色 科學163期，826-828頁，1969,Defined MSG “Symptom Triad“ 味精“三種并發(fā)癥狀” 表現為 Burning 灼燒感 Facial Pressure 面部緊張 Chest Pain 胸痛,Skeletal stunting骨萎縮 Marked obesity明顯肥胖 Sterility 不育 Hypothalamic lesions下丘腦損傷 MSG INJECTED注射味精后,Olney JW. Brain Lesions, Obesity and Other Disturbances in Mice Treated with Monosodium Glutamate. SCIENCE 164: 719-721, 1969. 小白鼠注射味精后出現大腦損傷，肥胖以及其他系統(tǒng)紊亂 1969年科學雜志,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 供食品添加劑聯合專家委員會審查的常規(guī)毒性數據資料非常完整，包括大白鼠、小白鼠和狗的急性，亞慢性，慢性毒性研究以及遺傳性毒性和畸形學研究。,The Safety Evaluation of Monosodium Glutamate Walker R, Lupien JR Journal of Nutrition 130: 1049S-1052S, 2000. 味精的安全評估 2000年營養(yǎng)學雜志,GLU has very low acute toxicity (15,000+ mg/kg po) in rats and mice 谷氨酸對大、小白鼠具有極低的劇毒性（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%) 兩年內，在慢性、亞慢性研究試驗中未有明顯副作用（大、小白鼠食物中味精占4%，小狗食物中添加10%） Reproductive and teratology studies negative 生殖和畸形研究無異常,Walker R, Lupien JR. J Nutr 130: 1049S-1052S, 2000.,The Safety Evaluation of Monosodium Glutamate 味精的安全評估,The Issues 問題,Neurotoxicity 神經毒性研究 2. CRS (MSG Symptom Complex) 中國餐館綜合癥（ 味精綜合癥）,Neurotoxicity神經毒性研究,Dietary MSG食用味精 Plasma (GLU)血漿（谷氨酸）上升 Brain (GLU)大腦（谷氨酸）上升 Neuronal excitation & death神經興奮和死亡,Barriers to Neurotoxicity,Gastrointestinal Tract efficiently uses ingested GLU (MSG) as E-source (95+%). 胃腸道能有效地吸收95%以上的谷氨酸鈉作為能源 Gut is thus a barrier to GLU entry into blood. 腸道因此能阻止谷氨酸進入血液中 Blood-Brain Barrier prevents GLU penetration into brain. 血腦屏障阻止谷氨酸滲透到大腦 Only very high oral doses of MSG by gavage can raise plasma GLU enough to get GLU into brain 只有灌喂大劑量的味精，才會致血漿中的谷氨酸含量升高，而進入到大腦 MSG in food does not have this effect. 食物中添加的味精不會有這種效果,Fernstrom JD et al. J Clin Endocrinol Metab 81: 184-191, 1996. 1996年，臨床內分泌代謝雜志,Adult males (80 kg) quickly ingested MSG, 12.7 g (150 mg/kg) in solution. 成年男子 （體重約80公斤）能很快吸收溶液中12.7g（約150毫克每公斤）的味精,Tsai P-J, Huang P-C Metabolism 48: 1455-1460, 1999.,Arrows = meal or snack 箭頭代表攝取的食物或點心 Meals: 0745, 1215, 1800 h 飲食時間：0745，1215，1800 Daily MSG dose = 100 mg/kg: 每日攝入味精量：100mg/kg Breakfast: 15 mg/kg 早餐：15mg/kg Lunch: 40 mg/kg 午餐: 40mg/kg Dinner 45 mg/kg 晚餐：45mg/kg Data are means sem (n = 10)數據：均值標準差 Black circle: no MSG 黑圈表示不含味精 White circle: MSG. 白圈表示含有味精,GLU injection ip stimulates PRL secretion in rats Does GLU (MSG) ingestion stimulate PRL secretion in humans? 腹腔注射谷氨酸鈉會刺激小白鼠催乳素的分泌，它會對人體產生同樣的作用嗎？ 12.7 g oral load of MSG in male subjects 雄性研究對象12.7克口服,Plasma PRL in rats injected with MSG (1000 mg/kg ip). From: Terry LC et al. Brain Research 217: 129-142, 1981.,Rats,Humans,Placental Barrier to Maternal Glutamate 胎盤屏障母體中的谷氨酸鈉 Stegink LD et al Am J Obstet Gynecol 122: 70-78 (1975) Monkey study.猴子實驗 Highest dose (400 mg/kg iv, open circles) produced plasma GLU 70-times normal.,Battaglia FC. J Nutrition 130: 974S-977S (2000),Effect of oral MSG loading on breast milk free GLU concentrations in lactating women 哺乳婦女食用味精后母乳不會有谷氨酸鈉,Lactating women ingested 100 mg/kg MSG in capsules with water, and milk samples were taken at the indicated times thereafter. This dose raised plasma GLU from 45 nmol/ml to peak values of about 300 nmol/ml in 30-45 min. From: Baker GL et al., Factors influencing dicarboxylic amino acid content of human milk. In: Glutamic Acid: Advances in Biochemistry & Physiology, Filer LJ et al., ed. New York, Raven Press, 1979 , pp. 111-123.,哺乳期女性加水攝入 100 mg/kg 的膠囊，對其后特定時間的母乳樣品進行檢驗表明： 這一劑量使得血液谷氨酸濃度在30-45分鐘內從45nmol/ml 提高到峰值約300 nmol/ml 。 From: Baker GL et al., Factors influencing dicarboxylic amino acid content of human milk. In: Glutamic Acid: Advances in Biochemistry & Physiology, Filer LJ et al., ed. New York, Raven Press, 1979 , pp. 111-123. 影響人體母乳二氨基酸濃度的因素 谷氨酸：生物化學和生理學進展,Brain Issues 大腦問題,Relevance to human MSG ingestion: 有關人體攝入味精 The placenta blocks GLU transfer from maternal into fetal blood: FETAL brain is safe. 胎盤會阻止谷氨酸從母體傳遞給胎兒：胎兒大腦不會受到影響 Breast milk (GLU) does not rise when mother ingests high-dose MSG: NEWBORN/INFANT brain is safe. 當母體攝入大劑量的味精母乳中的谷氨酸含量不會上升：新生兒的腦發(fā)育是安全的 Infant metabolizes GLU at same rate as adult (Stegink et al., Pediatric Res 20: 53-58, 1986). 嬰幼兒具有和成年人同樣的谷氨酸代謝的能力,Brain Issues大腦問題,The human brain is unaffected by the very high plasma (GLU) following high dose MSG intake 攝入大量的味精導致的血漿中高谷氨酸含量不會對人體大腦產生影響 No dose of MSG has yet been given to humans high enough to induce CNS effects. 至今亦未發(fā)現食用味精會影響人體中樞神經系統(tǒng),CRS/Allergy (MSG Symptom Complex),中國餐館綜合癥/過敏癥 味精綜合癥,Studying MSG Symptom Complex 味精綜合癥研究,Can reproducible symptoms be defined? 能定義這些重復性的癥狀么？ Are reproducible symptoms dose-related? 這些重復性癥狀與攝入劑量有關嗎? Do MSG-sensitive individuals exist? 對味精敏感的個體存在嗎？,SYMPTOMS ATTRIBUTED TO MSG:味精所致癥狀,Burning, tightness, numbness in upper chest, neck and face. 發(fā)燒，身體發(fā)緊，胸腔上部發(fā)悶，脖子、面部發(fā)麻 Dizziness, headache 眩暈，頭疼 Chest pain, palpitation 胸口痛，心悸 Weakness 乏力 Nausea, vomiting 反胃嘔吐 Bronchospasm (asthmatics)哮喘 Hives (urticaria)麻疹 MECHANISMS UNKNOWN 機制未知,Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate. Geha RS et al. J Allergy Clin Immunol 106:973-80, 2000 味精反應的多中心、雙盲、安慰劑控制、多重治療評估報告 2000年 過敏與臨床免疫學 雜志,Protocol A: 130 self-styled MSG-sensitive individuals. Fasted, challenge blind with placebo or MSG (5 g in liquid). 實驗A：130例自認為MSG過敏者，禁食，以安慰劑或MSG(5克液體)進行盲試。 Protocol B: Subjects had positive response of 2 symptoms to either or both treatments in A (i.e., placebo responders too). Fast, blind challenge with 0, 1.25, 2.5 or 5 g MSG (in liquid). 實驗B: 對A中，出現陽性反應的實驗對象，超過2種癥狀（例如：對安慰劑反應也一樣）。禁食，以0，1.25，2.5或5克MSG(液體)進行盲試。,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,Protocol C: Subjects had positive response of 2 symptoms to 5 g MSG but not placebo in A or B. Fast, placebo (suc- rose) or MSG (5 g), in capsules (blind). Do twice. 實驗C: 對A和B中陽性反應的實驗對象-對5克MSG出現超過2種癥狀（對安慰劑沒有），禁食，以膠囊性的安慰劑（蔗糖）或MSG(5克)，進行盲試。重復實驗。 Protocol D: Subjects had positive response to both MSG chal- lenges in C. Fast, breakfast & placebo (sucrose) or MSG (5 g), in capsules (blind). Do three times. 實驗D: 對C中MSG治療出現陽性反應的實驗對象，禁食，早餐加膠囊性安慰劑（蔗糖）或MSG(5克)，進行盲試。重復3次實驗,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,SYMPTOMS RATED:癥狀表現 General Weakness虛弱 Muscle Tightness肌肉緊張 Muscle Twitching肌肉酸痛 Flushing臉頰發(fā)紅 Sweating盜汗 Burning Sensation灼感 Headache-migraine偏頭痛 Chest pain胸悶 Palpitations心悸 Numbness-Tingling發(fā)麻,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,Protocol A Results:實驗A結果,n=50: 2 symptoms with MSG & 0/1 with placebo. MSG組超過2種癥狀出現+安慰劑組1個 n=19: 2 symptoms with MSG & placebo. 超過2種癥狀出現，味精和安慰劑 n=17: 2 symptoms with placebo & 0/1 with MSG. 安慰劑組超過2種癥狀出現+MSG組1個 n=44: 0 or 1 symptoms with MSG & placebo. 沒有或1種癥狀出現：MSG+安慰劑,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,Protocol B Results:實驗B結果,n=86 from A had 2 symptoms with a treatment (blinded: placebo or MSG), and included in B. 69 completed. 對2種癥狀進行治療（雙盲：安慰劑或MSG） Overnight fast, challenge with 0, 1.25, 2.5 or 5 g MSG. 禁食過夜，按0，1.25，2.5或5克MSG看結果,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,n=19/69 reported 2 symptoms to 5 g MSG but not placebo. 19/69例報道，5克MSG下有超過2種癥狀出現，沒有安慰劑 n=14/19 the same symptoms occurred in B as in A. 14/19例中同樣癥狀出現，類似于A實驗 Hence, 14/130 showed reproducible response to 5 g MSG. 因此， 14/130表現出對5克MSG的可重復性反應,Protocol C Results:實驗C結果,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,1995 FASEB MSG Panel: 3 placebo-MSG challenges must give same positive response to MSG, no response to placebo. Give MSG in capsules. 1995年美國實驗生物學聯合會味精組：3種安慰劑-味精治療必須引起同樣的對味精的陽性反應，對安慰劑沒有反應，味精應該以膠囊的形式給予。 n=19 had 2 symptoms in A & B with MSG & no symptoms with placebo. n=12 agreed to be studied. N=19時，實驗A和B的味精組都有超過2種癥狀出現，安慰劑組沒有癥狀出現，n=12時，實驗一致。,Protocol C Results:實驗C結果,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,Two separate tests of MSG (5 g) vs placebo. 分開測試味精（5克）和安慰劑 n=2/12 had 2 symptoms with MSG but symptoms were not the same. n=2/12，味精組超過2種癥狀出現，安慰劑組沒有癥狀出現，但癥狀不同。 n=0/130 met FASEB criteria for MSG sensitivity n=0/130 時符合FASEB的MSG過敏性實驗標準,Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000,CONCLUSION: 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. 結論：根據1995年美國實驗生物學聯合會（FASEB）制定的標準，對那些聲稱味精過敏的個體進行雙盲試驗表明他們未表現出敏感性。,CRS Symptoms in Humans 人體的MSG癥狀,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：早期研究聲稱味精會導致哮喘病人病情發(fā)作，但近期眾多數量病人的研究中未得到證實,Stevenson DD. Monosodium glutamate and asthma. J Nutr 130: 1067S-1073S, 2000 味精和哮喘 2000年 營養(yǎng)學雜志.,MSG Symptoms in Humans 人體的MSG癥狀,Urticaria: