味精安全问题

Umami/MSG: Safety Issues味精的安全问题John D. Fernstrom, Ph.D.Professor - University of Pittsburgh School of Medicine匹兹堡大学 医学院 教授Scientific Advisor - IGTCIGTC科学顾问Outline 内容纲要n Brief review of original issues leading to expression of concern in early 1970s简要回顾上世纪 70年代初引起关注的安全问题n Brief summary of safety views now简单总结当前关于味精安全的观点n Examination of two general issues两大类问题n Neurotoxicity神经毒性n General Adverse Effects (e.g., MSG Symptom Complex)n 所有不良反应（如味精综合症）n Conclusions 结论Kwok RHMChinese-Restaurant Syndrome中国餐馆综合症New Engl J Med 278: 796, 1968 (letter)1968年 新英格兰医学杂志 （通讯）n 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所添加的味精有关（也可能是其他添加成分）n An anecdotal case-report.n 单例报告（缺乏足够科学依据）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 科学 163期， 826-828页， 1969n Defined MSG “Symptom Triad“n 味精 “三种并发症状 ” 表现为nBurning 灼烧感nFacial Pressure 面部紧张nChest Pain 胸痛 Skeletal stunting骨萎缩 Marked obesity明显肥胖 Sterility 不育 Hypothalamic lesions下丘脑损伤 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现大脑损伤，肥胖以及其他系统紊乱1969年科学杂志n 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 teratologyn 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传性毒性和畸形学研究。The Safety Evaluation of Monosodium GlutamateWalker R, Lupien JRJournal of Nutrition 130: 1049S-1052S, 2000.味精的安全评估味精的安全评估 2000年营养学杂志年营养学杂志n GLU has very low acute toxicity (15,000+ mg/kg po) in rats and micen 谷氨酸对大、小白鼠具有极低的剧毒性（ 15000+mg/kg po）n 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%)n 两年内，在慢性、亚慢性研究试验中未有明显副作用（大、小白鼠食物中味精占 4%，小狗食物中添加 10%）n Reproductive and teratology studies negativen 生殖和畸形研究无异常Walker R, Lupien JR. J Nutr 130: 1049S-1052S, 2000.The Safety Evaluation of Monosodium Glutamate味精的安全评估味精的安全评估The Issues 问题nNeurotoxicity神经毒性研究2. CRS (MSG Symptom Complex)中国餐馆综合症（ 味精综合症）Neurotoxicity神经毒性研究Dietary MSG食用味精 Plasma (GLU)血浆（谷氨酸）上升 Brain (GLU)大脑（谷氨酸）上升Neuronal excitation & death神经兴奋和死亡Barriers to Neurotoxicityn Gastrointestinal Tract efficiently uses ingested GLU (MSG) as E-source (95+%).n 胃肠道能有效地吸收 95%以上的谷氨酸钠作为能源n Gut is thus a barrier to GLU entry into blood.n 肠道因此能阻止谷氨酸进入血液中n Blood-Brain Barrier prevents GLU penetration into brain.n 血脑屏障阻止谷氨酸渗透到大脑n Only very high oral doses of MSG by gavage can raise plasma GLU enough to get GLU into brainn 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n MSG in food does not have this effect.n 食物中添加的味精不会有这种效果Fernstrom JD et al. J Clin Endocrinol Metab 81: 184-191, 1996.1996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Tsai P-J, Huang P-C Metabolism 48: 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， 1800Daily MSG dose = 100 mg/kg:每日摄入味精量：每日摄入味精量： 100mg/kgBreakfast: 15 mg/kg早餐：早餐： 15mg/kgLunch: 40 mg/kg午餐午餐 : 40mg/kgDinner 45 mg/kg晚餐：晚餐： 45mg/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 GLU injection ip stimulates PRL secretion in rats Does GLU (MSG) ingestion stimulate PRL secretion in 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 subjects 雄性研究对象雄性研究对象 12.7克口服克口服Plasma PRL in rats injected with MSG (1000 mg/kg ip). From: Terry LC et al. Brain Research 217: 129-142, 1981.RatsHumansPlacental Barrier to Maternal 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Stegink LD et al Am J Obstet Gynecol 122: 70-78 (1975)Monkey study.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)Effect of oral MSG loading on breast milk free GLU concentrations 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：这一剂量使得血液谷氨酸浓度在 30-45分钟内从 45nmol/ml 提高到峰值约提高到峰值约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Brain Issues 大脑问题 n Relevance to human MSG ingestion:n 有关人体摄入味精n The placenta blocks GLU transfer from maternal into fetal blood: FETAL brain is safe.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n Breast milk (GLU) does not rise when mother ingests high-dose MSG: NEWBORN/INFANT brain is safe.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：新生儿的脑发育是安全的n Infant metabolizes GLU at same rate as adult (Stegink et al., Pediatric Res 20: 53-58, 1986).n 婴幼儿具有和成年人同样的谷氨酸代谢的能力Brain Issues大脑问题 n The human brain is unaffected by the very high plasma (GLU) following high dose MSG intaken 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n No dose of MSG has yet been given to humans high enough to induce CNS effects.n 至今亦未发现食用味精会影响人体中枢神经系统CRS/Allergy(MSG Symptom Complex)中国餐中国餐 馆综馆综 合症合症 /过过 敏症敏症味精味精 综综 合症合症Studying MSG Symptom Complex味精综合症研究n Can reproducible symptoms be defined?n 能定义这些重复性的症状么？n Are reproducible symptoms dose-related?n 这些重复性症状与摄入剂量有关吗 ?n Do MSG-sensitive individuals exist?n 对味精敏感的个体存在吗？SYMPTOMS ATTRIBUTED TO MSG:味精所致症状n 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n Dizziness, headache 眩晕，头疼n Chest pain, palpitation 胸口痛，心悸n Weakness 乏力n Nausea, vomiting 反胃呕吐n Bronchospasm (asthmatics)哮喘n Hives (urticaria)麻疹MECHANISMS UNKNOWN 机制未知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2000年年 过敏与临床免疫学过敏与临床免疫学 杂志杂志n Protocol A: 130 self-styled MSG-sensitive individuals. Fasted, challenge blind with placebo or MSG (5 g in liquid).n 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。n Protocol B: Subjects had positive response 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).n 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, 2000n Protocol C: Subjects had positive response 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.n 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。n 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.n 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, 2000SYMPTOMS RATED:症状表现n General Weakness虚弱n Muscle Tightness肌肉紧张n Muscle Twitching肌肉酸痛n Flushing脸颊发红n Sweating盗汗n Burning Sensation灼感n Headache-migraine偏头痛n Chest pain胸闷n Palpitations心悸n Numbness-Tingling发麻Geha RS et al., J Allergy Clin Immunol 106:973-80, 2000Protocol A Results:实验 A结果n n=5