Decender 8, 1987 Senator Howard M. Metzendaum United States Senate 140 Russell Senate Office Building Washington, 0.C. 20510 Dear Senator Metzenbaum: {have been asked to update the Comittee on my position regarding the severa? Deurotoxicology issues that I end other neurosclentists presented before the Public Board of Inquiry (PBOI) on aspartane (Nutrasweet) in 1980. Three Separate neurotoxicity {ssues were focused upot: at the PROT, one pertaining to the neurotoxic properties of aspartate (a major component’ of the Nutrasweet molecule), another to the neurotoxic properties of phenylalanine (the other BaJor component of the Nutrasweet molecule) and the third to brain tumorss 7 will dfscuss the status of each Issue as I see it today. 1. Aspartate neurotoxicity. Asparcate (Asp) and the related conpound, glutamate (Glu), are present in high concentration in the brain where they Serve as excitatory neurotransnitters and participate in mich of the information processing that occurs in the samalian central nervous system. Paradoxically, these substences have striking neurotoxic potenttal--tf allowed to have. sustained contact with receptors on the extertor surface of the nerve cell, they literally excite the cell to death. The reason they do not nm» iifest neurotoxic activity under ordinary circumstances is that they are synthesized and contained inside the nerve cells end are enitted outside only in tiny anounts for. transmitter purposes: after transmitting a signal (exciting a neighbor cell), they are immediately (within milliseconds) taken beck up into the cell Etghteen years ago, before the above information was known, my research group aiscovered that when Glu or Asp are adainistered orally to animals of various Species including monkeys, they destroy nerve cells in certain parts ‘oF the brain. We found that Glu and Asp act in concert such that when. ingested together they add to one anothers toxicity. Although we found animals at any age susceptible to Glu/Asp neurotoxicity, immature animals were mich more sensitive than adults. Over the years nevrosctentists have developed & much better understanding of this neurotoxte phenomenon. When Glu or Asp are ingested, they are absorbed into the blood very rapidls which causes blood Prose: (314) 262 1007 ‘a0 Rotation Avro Sen Minor 0 (Medial Shot Be 84)Sevstyr umara m. netsana levels O° tnese aming acids to ne transiently elevated. This, voses no hazard fer most portions of che brain becauce Gly and Asp are prevented by Diood srain-barriers from entering most regions of the brein. However, there are several smal! regions of brain that Tack blood orain barriers, and bloodborne Glu and sz freely oenetrate these brain regions. This brings Glu and Asp In Girect contact with receators on ihe evtertor surfaces of nerve cells, ard Zlaces sucn nerve cells in seapardy of being excited to death. Nerve cells in immature brain are at greatest risk of neing destroyed because important protective nechanisas are not yet functionally competent. In the neurosc lence Equnity today, this 1s comonly referred to as excitotonic cell death aed Stu and’Asp are ‘known a5 excitotox ins. The Glu and Asp contained tn the orate are called endogenous excttotoxing and tne Glu and Asp encountered in the onviranent are calTed eogenous excitotonins. najor sgurce of hemas contact with exogenous exc!totoxins is through the 4 supply. Glu, tn tne form of !1 sedium salty monosodium }+ 15 8 very heavily used food additive. Im 1969 when T first Gescr bed the extreme sensitivity of the tnmature brain to the toxic effect af Gre, daby Food sarufacturers were adding very lerge amounts of Glu to beby feods. After I presented my research Findings in test mony before the Sonera Select Commsttee on Mutrition ang Human Needs (1970), the Nixon white horse yorked out en agreement between FOA ard the industries concerned whereby baby food manufacturers (who comprised a small fraction of the Glu market): mound woluntartly" sult adding Gtu te baby foods. I applauded this pert of the agreenent dut not the accompanying quid pro quo which was that FLA wou td Continue to cl sify Glu as GRAS (generally regarded as safe) and would Continue to allow other food manufacturers (comprising the bulk of “the Glo market) to add unlimited anounts of Glu to "aduit" foods destined to. be ingested by consumers of al} ages. Thus, Glu was taken out of taby foods bur yas rot taken ovt of foods fed to dabies. And, to this day, FOR strat Class.fles Glu as GRAS, thereby conveying the dangerous message’ to parents that ft is perfectly sate to feed Glu to Davies. Another major source of Glu and Asp In foods 1s hydrolysed vegetable protein (uve). 4B 4s 9 mixture of Glu, Asp and other amino actés. “Ie is because oF IS5 exceedingly igh Glu concentration that MVP 1s used as a fond Flavoring agent. | After the baby food industry quit adding Glu to baby foods tn 19/0) they mediately began adding HVP tn huge amounts tn order to bring the Gla level (1.e., the Flavor evel) back to where it had been before. Throughout the 1970's I wrote letters, testified at hearings, etc. tryirg to get the bady food companies to quit adding HVP to baby foods and trying to get FDA to tare 4 Rore responsible position. In the late 1370's, the baby food industry {nally decided that their subterfuge was working more against them than fox fhen so they opted for a clean image and quit adding excitotoxins to. baby Foods. Mo headway was made with FDA: che agency {5 still misleading and Biseducating mothers into thinking that It is perfectly safe to feed Glu, WE for any other excitutoxins to babies.Senator Howard M, Metzenbaum Pane 3. hen Yutrasweet was first propased as a swectener, I was concerned because SUL OF the Sutrasweet molecule is Asp and they wore Sroposing to add it primar’ ly te childrens Foois and beverages (00! aid, coated Dreaxfast cereal, etc.) In 19%, FO8 approved Nutraswoet for such’ uses without even requiring the manufacturer io determine whether it Has the kind of neurotoxicity that Asy. mat known to have. Therefore, 1 obtained sone Nutrasueet in. 1974, adminis. lered it crai'y to infant rice and cenonstrated that it destroys nerve cel !s just ke Glu ‘and Asp uo. | sent thls evidence to FA and tiled a forma! Brotest against their approval of the adgitive Because of Information that was surfacing at that tine implicating the manufacturer in apparent Traudu- Tent practices, FA stayed thefr approval of Nutrasweet and granted me the Fight to ¢ hearing which was to take place after FOR completed their. Invest i= gation of the narufacturer. The nearing finally took place in 1980 es a POOL. In Framing the issues for the POO!, 3 insisted that the Issue of Asp neurotoxicity not be considered Im the narrow canter: of Asp alone but rather in the content of adding Asp to a food supply that already contains a similar excttotovin (Glu) im amounts potentially dangerous Far immature consumers. In 1979 the Commissioner of FDA (Acting Commissioner, Sherwin Gardner) Selected 1 newer panel of scientists to serve as judges for the POO. | strongly oppesed the apcointment of one of these judges on grounds of conflict Of Interest au lack of qualifications. The Commissioner arbitrarily over- ruled my abject 'ens aitowing re no alternative but to participate in the PBOL under protest. Asst turned out, the pane? member whom {considered inappropriate mas given a \sproportionately large snare of responsiblity For deciding the Aso issue. The other 2 Judges focused primarily on the brain tuner Issue which they Consivered of overriding importance because It provided. ample basis in, itself for recommending disapproval of the additive, The result of this "division of Tabor" arrangenent was that although al] 3 judges Signed the report, a single inappropriate judge decided that the Asp component. OF Nutrasweet did not pose any safety hazerd. He based his decision on a Consideration of Asp alone without regard to the real issue, I.e., 15 it safe to add Ase to the large amounts of Glu thet are already aduiterating the food supply? My opinion regeriting the status of the Asp neurotovicity Issum is that it was handled in an inappropriate manner by the PBOL pare!: the real safety issue Still remains unrescived and human young are being exposed to potentially dangerous ard ever Increasing amounts of Glu and Asp, both of which are exogenous excitotoxins that can rapidly destroy nerve ceils in the developing brain. the anount of Glu being added to foods today is dangerous In Itself: adding a second excitotoxin (&sp) to the sane food supply Increases. the Ganger. To put the issue in proper perspective, let me bring you up to date on other developments in the field of excitotoxicology. It is now becoming abundant ly Clear that endogenous excitotoxins (1-e., the Glu and Asp naturally present in the brain) are responsib's for several very comon types of brain damage that