OBJECTIONS TO NEOTAME APPROVAL
AND REQUESTS FOR HEARINGS

Posted: 28 May 2005

SECTION A: introduction, overview, and two objections.

TO: ADDRESSES: Submit written objections and requests for a hearing to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic objections to
http://www.fda.gov/dockets/ecomments

RE: DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 172 [Docket Nos. 98F-0052 and 99F-0187]
Food Additives Permitted for Direct Addition to Food for Human Consumption; Neotame

FDA published notices in the Federal Register on February 10, 1998, and February 8, 1999 (63 FR 6762 and 64 FR 6100, respectively), announcing that food additive petitions, FAP 8A4580 and FAP 9A4643, had been filed by Monsanto Co., Skokie, IL 60077. The petitions propose amending the food additive regulations to provide for the safe use of neotame as a nonnutritive sweetener for tabletop use (FAP 8A4580) and for general-purpose use in food (FAP 9A4643) where standards of identity do not preclude such use. Subsequently, the rights to the petitions were sold to the NutraSweet Co., 699 North Wheeling Rd., suite 103, Mount Prospect, IL 60056. This document grants the petitions via a regulation approving the general-purpose food use of neotame.

VIII. Objections

Any person who will be adversely affected by this regulation may at any time file with the Dockets Management Branch (see ADDRESSES) written objections by August 8, 2002. Each objection shall be separately numbered, and each numbered objection shall specify with particularity the provisions of the regulation to which objection is made and the grounds for the objection. Each numbered objection on which a hearing is requested shall specifically so state. Failure to request a hearing for any particular objection shall constitute a waiver of the right to a hearing on that objection. Each numbered objection for which a hearing is requested shall include a detailed description and analysis of the specific factual information intended to be presented in support of the objection in the event that a hearing is held. Failure to include such a description and analysis for any particular objection shall constitute a waiver of the right to a hearing on the objection. Three copies of all documents are to be submitted and are to be identified with the docket number found in brackets in the heading of this document. Any objections received in response to the regulation may be seen in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

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Sirs: I file these objections and requests for hearings, in triple copies in print, by certified mail, by the deadline of August 8, 2002, as well as by email.

As is my right, this document and all its supporting documents, are posted to my public archives, open to the entire Net and all major search engines, at http://groups.yahoo.com/group/aspartameNM/messages

Anyone is invited to respond to this objection and related matters, and to submit posts to the archive, which as the owner and moderator, I approve with the purpose of allowing all civil, evidence-based discussion in the highest tradition of scientific discourse. All points of view are welcome. I may choose to edit out uncivil language, replacing it with ******* in order to accept submissions of quality, whether for or against what may seem to be my own positions.

My paper version will be in simple consecutive order. This post will be first, and refer to successive documents. The Net versions will be hyperlinked, facilitating more flexible perusal and comprehension.

I am a scientific and medical layman, now sixty, who has worked for 14 years full-time and overtime as a home hospice care giver. My education includes a B.S. from Massachusetts Institute of Technology, 1964, Science (physics) and Humanities (history) and an M.A. in psychology, Boston University Graduate School, 1967. I have studied the toxicity of mercury amalgam in medical libraries since 1984. Active on the Net since Dec 1986, since Jan 1999, I have been a volunteer activist on the issue of aspartame toxicity, as a world citizen offering a public service.

My archive shows that I offer civil, balanced, evidence-based research summaries, drawing from mainstream medical literature, as well as some of the alternative medical literature, and with evidence-based reports by other activists, and articles from the public media. My Net discussion group now has 81 members, including 16 medical professionals and academics, mostly USA, 1 India. The archive has 860 posts, since Oct 1999.

It may be of interest that my ATT 56K Net access is $ 17 monthly, while my 1.4 GB system, 115 GB hard disk, 512 MB RAM, laser printer, costs me about $5/day over 2 years. I have about 1 GB of posts saved on my hard drive since 1996, and can search them efficiently within seconds. So, I am donating mainly my time, perhaps an average of 2 hours daily. I explained to my lady that I have a mistress, Lanette...

As a layman, I beg your indulgence in using an informal approach, which for many readers will facilitate appreciation of my quite serious concerns. The Net ensures that readers will be worldwide, years into the future. I bear that in mind with every word. What is expressed here shows new possibilities for the exercise of grassroots democracy on a global scale, as citizen networks constructively compliment the awesome powers and responsibilities of global governments and corporations.

http://www.nutrasweet.com/infocenter/index.asp
Company profile
On May 25, 2000, J.W. Childs Equity Partners II L.P. purchased The NutraSweet Company from Monsanto, a wholly owned subsidiary of Pharmacia Corporation.

Thus, the patent rights to neotame have been sold to http://www.jwchilds.com
J. W. Childs Associates, L.P.M
111 Huntington Avenue - Suite 2900
Boston, MA 02199-7610
617-753-1100 617-753-1101 info@jwchilds.com

Other prominent players: http://groups.yahoo.com/group/aspartameNM/message/841 RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co., JW Childs Assc.: aspartame-neotame toxicity 7.10.2

I raise now an important, valuable proposal: always place research on safety issues on the Net in public domain, with free, fully and conveniently searchable access, along with Net access to authors and their institutions, along with public discussion groups with permanent searchable public archives. As the very existence of this post demonstrates, this is inevitably and quickly evolving anyway, but I submit it would be excellent public policy to fully and actively support this extension of democracy. At present, if I understand correctly, there seems to exist access to industry funded studies of neotame safety only by a cumbersome and costly procedure of invoking the Freedom of Information Act. I expect soon corporations will realize the immense support to their pursuit of profits by serving the public that will be available by making all aspects of their safety research public, for this will allow feedback from the people that will prevent mistakes in marketing that can easily incur the scale of penalties accrued by tobacco, an addictive neurotoxin-- hundreds of billions of dollars, and growing.

As an example: http://groups.yahoo.com/group/GFCFKids/messages has an archive since Dec 15 1998 of 100,740 posts and 2600 members, discussing fervently the problems of families with kids who react severely to the gluten in wheat and the casein in milk, now about 100 daily posts.

http://www.google.com gives 105,000 websites for "aspartame", while http://groups.google.com finds on 700 MB of posts from 20-years of Usenet groups, 72,300 posts, and http://www.AllTheWeb.com gives 177,012, the top four being leading and very well informed volunteer anti-aspartame sites.

It is important to appreciate that science grows exponentially, doubling in personnel, the number of published studies and books, steadily about every 20 years since 1660. Thus, since the aspartame controversy started three decades ago, there has been probably nearly a four-fold growth in the world community of toxicologists and their accumulated research literature and texts, along with the usual astonishing improvements in instrumentation, while the advent of the Net has hugely stimulated the pace of research and innovation, and allowed many more players, such as myself, to participate.

This means that all new substances will run a much more severe, fast and fierce, gauntlet of evaluation. This is altogether to the world public good. All corporations and agencies must realistically accept, and actually enthusiastically support this emerging reality, which increases the safety, sanity, happiness, creativity, and wealth of the entire global community.

For no one is safe, unless everyone is safe.
And no one is safe, unless everyone supports safety.

Frankly, I want to have proof that my concerns about aspartame and its derivative neotame are unwarranted-- the accent is on the word "proof"-- when I submit that there is considerable evidence that aspartame is toxic, and therefore neotame, its derivative, has to be very carefully vetted in fully public venues, before it debuts as an unqualified boon to our species.

Since neotame is some forty times sweeter than aspartame, then only 2.5% of it has to be used for the same effect, which, on the face of it, would seem to reduce any toxic levels ascribable to aspartame, to perhaps insignificant levels, especially if indeed neotame replaces sugar and other sweeteners with known or suspected addictive and toxic properties. Note that qualified experts, as well as "anecdotal evidence" have suggested that aspartame can increase craving and consumption of sugar, and even obesity.

To cut to the chase, for me, the key fact revealed in the FDA approval report is: "In contrast, the methanol content of neotame-sweetened carbonated beverages is estimated to be 1.37 mg/L." This is the same as 1.37 ppm, about 18% of the EPA limit of 7.8 ppm for drinking water that sounds pretty safe, at first sight.

A liter of diet soda contains about 560 mg aspartame, of which 10% is methanol, 56 mg, which is 41 times the amount of 1.37 mg methanol from the neotame that gives the same sweetness.

However, we give in this complaint many reports of aspartame reactors reacting severely and quickly to aspartame doses of 1.5 mg for a breath mint, 4 mg for a medicine pill, and 6-8 mg for a stick of chewing gum. Since methanol is 10% of the aspartame, we find methanol doses of .15 mg for a breath mint, .4 mg for a medicine pill, and .6-.8 mg for a stick of chewing gum...

So, if the methanol from neotame is fairly fully released into the inner surfaces of the mouth, or into the GI tract, and an aspartame reactor consumes 1, 2, or 4 liters of neotame diet drink, he would have a dose of 1.37, 2.74, or 5.48 mg of methanol. A single can of neotame diet soda gives 0.25 mg methanol. So, these levels very probably would trigger unpleasant symptoms in aspartame reactors.

This means that the biochemical data and the voluminous case reports about aspartame toxicty are indeed relevant to making sound judgements about the safety of neotame. Neotame must be put to the test, and by independent researchers, given the necessary support to complete fully competent, definitive studies.

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OBJECTION and Request for a Hearing #1:
To: C: Toxicology/Safety Assesment of Neotame
1. Metabolism and Pharmacokinetics of Neotame.
a. Absorption of neotame.
d. Metabolites of neotame.

The FEA in {d. Metabolites of neotame.} states: "The agency concludes that at the 90th percentile EDI for neotame, exposure to resultant methanol will be insignificant, i.e., not more than 0.008 mg [sol] kg bw [sol] d." It is not clear if this estimate includes absorption through the inner surfaces of the mouth. This, I believe, is 0.48 mg for a 60 kg adult, well in the range at which aspartame reactors suffer quickly from absorption through the inner surfaces of the mouth from breath mints, medicines, and chewing gum.

Biochemical monitoring and reports of symptoms must determine the amount of absorption of neotame and its metabolites, especially methanol and any formaldehyde, directly through the inner surfaces of the mouth, specifically addressing the use of breath mints, medicines, and chewing gum, in a variety of vulnerable groups, for a year of heavy use, 6 mg daily for a 60 kg adult, the 90th% level of estimated daily use (EDI). Is there any cumulative absorption, especially for vulnerable groups? Are there co-factors that influence absorption and accumulation? Should there be a separate specific EDI 90th% level set for absorption through the mouth?

Do, in fact, the many aspartame reactors also react to neotame, as, for instance, many do to MSG? This question can not safely or sanely be evaded. It must be settled before neotame can be declared safe for all users. Therefore, aspartame itself must be reevaluated with detailed, throrough biochemical monitoring and study of all reported symptoms in a variety of vulnerable groups at the 90th % EDI level of use for a year.

Furthermore, independent studies must verify that a year of heavy neotame use, enough to provide 6 mg methanol daily, which is the estimated daily intake (EDI) at the 90th percentile for a 60 kg adult, in large populations, including a variety of groups of vulnerable people, do not create neotame reactors, who are highly sensitized to neotame.

Since, after any approval of neotame, there will be a period of years during which most users will be using both aspartame and neotame, then they are likely to become sensitized to aspartame, especially to its methanol and any formaldehyde metabolites. These aspartame sensitives may then be triggered by neotame. Obviously, this cross-sensitization has to be examined in detail by careful biochemical monitoring and by study of all reported symptoms, for a 90% EDI level of use for a year for both aspartame and neotame, and, in addition, any cross-sensitization to methanol, formaldehyde, and MSG, and, no doubt, other related chemicals, must also be studied in detail.

Finally, these studies must be replicated by fully independent, adequately funded researchers, with full, free, immediate publication of their studies on the Net.

I hereby request a Hearing on this objection and the questions raised. Supporting evidence and documentation is given in the rest of this document, along with Net links to the full body of supporting evidence and documentation, also included herein.

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OBJECTION and Request for a Hearing #2:
To: Critical Toxicology Studies and Issues
e. Clinical studies assessments-- human tolerance to neotame.

Since it is very easy to manipulate double-blind studies to support predetermined conclusions, all these industry funded clinical studies on humans must be available in complete detail for free on the Net for anyone to examine and discuss in an archived, searchable public discussion groups.

Were the number of subjects enough to reach conclusions about symptom incidence levels below 5%, since the entire population would be exposed within a few years of approval? Was the neotame tested in the actual form of ingested food and drinks, including heated and cooked, along with a variety of acid and basic conditions? Were a variety of vulnerable groups thoroughly and specifically tested, such as depressed, or those already sensitive to aspartame, methanol, formaldehyde, MSG, and related chemicals? Did the groups tested already have preexisting high levels of relevant symptoms, such as headache? Were the placebos used likely to be active agents for typical symptoms, such as headache? Were precautions taken to monitor the subjects use of symptom alleviating medications, such as analgesics and seizure preventing medications? Were the effects of different diets studied, such as non-dairy, non-meat, organic, etc? Was there consideration of confounding variables: pesticides, mercury amalgams, heavy metals in drinking water, fluoride, carbon monoxide, meat, fat, dairy, sugar, tobacco, alcohol, etc?

Finally, these studies must be replicated by fully independent, adequately funded researchers, with full, free, immediate publication of their studies on the Net.

I hereby request a Hearing on this objection and the questions raised. Supporting evidence and documentation is given in the rest of this document, along with Net links to the full body of supporting evidence and documentation, also included herein.

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Finally, after all this, if neotame is found to be safe for all vulnerable groups at heavy levels of use for a year, and it is approved for public use, then constant, ongoing thorough monitoring of all user and doctor complaints must be maintained, with complete public access to all information at all stages of the process. A hundred people die yearly from peanut allergy in the USA. Lightning does strike.

But the public good requires that the public be informed, so that the public may decide.

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The fact that neotame safety research has been so hidden for so long from public view gives me a baleful feeling for its prospects.

The FDA has, after over four years of consideration, been convinced of the safety of neotame by over 113 studies, apparently funded entirely by the industry, of its safety or toxicity on animals and humans.

You may search among 11 million medical citations on PubMed for any topic or author, and for many studies get an abstract summary: http://www.ncbi.nlm.nih.gov/PubMed

I checked PubMed for neotame, which gave 5 listings, none of which were about animal or human toxicity or dispositions in the body, whereas for aspartame there are now 712 listings.

It is remarkable to me that searches on Google or AllTheWeb reveal no published studies about neotame safety, although Sweetener 2000, the first inhouse name for neotame, is mentioned since 1987. Common sense would appraise that if neotame was soundly safe, the industry would rush to publicize the research. After all, the world sweetener market is fiercely competitive, with billion dollar stakes. It is also notable that few, if any, neotame products are in Australia and New Zealand since the ANZFA approval there last summer. Nor can I find suppliers anywhere in the world for neotame, although about five firms offer aspartame as low as $ 13.42/gram.

So, as a layman, I have been unable to locate neotame safety studies in the public domain, or the names of scientists and their institutions who have done the over 113 studies, whereas for aspartame, PubMed lists 61 items from Oct 1973 to Mar 1981, before the first FDA approval in July 1981, including many about metabolism, decomposition products, and safety-- the vast majority funded by industry.

This is naturally very disturbing, since both the official government record, competent reviews in the media, and expert testimony both from within and without the FDA reveal major, devastating flaws in that early era of aspartame research, as well as glaring improprieties in the approval process.

Like a circle of cats watching a mousehole, the network of citizen activists will react to the commercial availability of neotame by testing it on aspartame reactors and immediately publishing full details on the Net, along with any user complaints, and soon, biochemical studies on sensitive individuals.

Very truly yours,

Rich Murray, MA
Room For All
1943 Otowi Road
Santa Fe, New Mexico 87505, USA
505-986-9193
rmforall@comcast.net

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SECTION B: problems with aspartame and neotame research.

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: http://www.dorway.com: original documents and long reviews of flaws in aspartame toxicity research 7.31.2 [Extracts given here]

Three decades of aspartame history are difficult to review, grasp, and assimilate. Herein, I try to facilitate access to some basic documents and fairly objective reviews that challenge the industry PR slogan: "Aspartame is the most thoroughly tested food additive in history."

http://www.greatfallspro.com Many original government reports on aspartame are available here as a 48.864 MB zip file, which takes 3.5 hours to download at 56K. A CD is also available in either jpeg or bitmap too. If one does not have cable, that would most likely be the best way to obtain these reports that I have scanned. $7.00 (total) covers the cost of burning & mailing in the US. Over seas would cost more accordingly of course.

Bob Flint
Mission Possible Maine
Great Falls Professional Services
362 Webster St.
Lewiston, Maine 04240-4301
Office/fax 207-783-6200
greatfalls@gwi.net

http://www.dorway.com/verrett.txt
11.3.87 Testimony before Congress by FDA toxicologist, M. Jacqueline Verrett, Ph.D. on Aspartame: [Senior Scientist of FDA Bureau of Foods Task Force, until 1987] "It would appear that the safety of aspartame (and its breakdown products) has still not been satisfactorily determined, since many of the flaws cited in the studies referred to here were also present in other studies submitted by Searle." Statement of Dr. Jacqueline Verrett, Former Toxicologist, U.S. Food and Drug Administration before U.S. Senate Committee on Labor and Human Resources, November 3, 1987 regarding "NutraSweet Health and Safety Concerns." Document # Y 4.L11/4:S.HR6.100, page 383-390.

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http://groups.yahoo.com/group/aspartameNM/message/858
RTM: Samuels: Strong: Roberts: Gold: flaws in double-blind studies re aspartame and MSG toxicity 8.1.2 [Extracts given here]

Double-blind studies, labeled with sonorous adjectives, "experimental", "laboratory", "clinical", "controlled", "randomized", have great scientific and commercial prestige as the gold standard for "statistically significant" truth. A single such study can be used to cast doubt, disbelief, and dismissal on the "anecdotal evidence" of numerous citizen and doctor complaints, on careful, detailed clinical reports in thoroughly professional, peer-reviewed journals, and on conclusions that might otherwise arise logically from basic biochemical facts.

Actually, double-blind studies are extremely tricky, complex, subtle, dicey, susceptible to a multitude of mistakes, and amazingly easy to manipulate toward desired goals and preordained conclusions. And they are expensive-- easily a hundred thousand dollars for a scientists and a few assistants to run a few dozen human subjects for a month or two. But, what's a hundred grand, or a million, to a global corporation that is motivated to legitimize the effectiveness and safety of a product that can garner a billion dollars of sales in its first year?

Corporate funding can keep a pet scientific teams in lolly for decades, create a journals to publicize results in, set up yearly international conferences, and place expensive ads to influence the editors, publishers, and readers of independent journals. Favorable results are trumpeted over and over for years to doctors, government agencies, and the people: "Aspartame is the most tested food additive in history. No careful, scientific findings support any anecdotal claims of aspartame toxicity."

http://www.truthinlabeling.org Truth in Labeling Campaign [MSG] Adrienne Samuels, PhD P.O. Box 2532 Darien, Illinois 60561 858-481-9333 adandjack@aol.com "The Toxicity/Safety of Processed Free Glutamic Acid (MSG): A Study in Suppression of Information" Accountability in Research (1999) Vol 6, pp. 259-310 http://www.truthinlabeling.org/l-manuscript.html l-manuscript.html [Extracts] http://www.truthinlabeling.org/L-ref.htm References

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http://groups.yahoo.com/group/aspartameNM/message/844
RTM: layman lament: NutraSweet: aspartame & neotame toxicity 7.12.2 [Extract] Suppose aspartame causes 1 out of a 100 ordinary folk to have headaches. Suppose you spend a hundred grand to compare 100 users vs. 100 matched nonusers for a month. Well, the group of 100 users is fairly likely to have 0, 1, or 2 vulnerable persons, who would react by having maybe twice as many headaches. So, there is a good chance that the expensive experiment wouldn't pick up any excess headaches at all. Yet, for 200 million users in the USA, 1 out of a 100 would, in this example, be 2 million people with twice as many headaches. That's the problem with big expensive, double-blind laboratory tests.

If both the users and nonusers already have a fairly high and erratic incidence of headaches, then it will be far more problematic to prove the effects of a single factor like aspartame.

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Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio Universities, College of Medicine, Dept. of Psychiatry, Youngstown, OH 44501, Chairman, The Center for Behavioral Medicine, Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown, OH 44501 330-740-3621 rwalton193@aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

"Survey of aspartame studies: correlation of outcome and funding sources," 1998, unpublished: This study is available at http://www.dorway.com/peerrev.html Al Raetz has justly criticized bias in both sides of the debate: http://www.aspartametruth.freeservers.com/personal.html

Walton found 166 separate published studies in the peer reviewed medical literature, which had relevance for questions of human safety. The 74 studies funded by industry all (100%) attested to aspartame's safety, whereas of the 92 non-industry funded studies, 84 (91%) identified a problem. Six of the seven non-industry funded studies that were favorable to aspartame safety were from the FDA, which has a public record that shows a strong pro-industry bias.

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http://www.nutrasweet.com/search/index.asp
Consumer Center Answers on Aspartame Q5. Does aspartame cause headaches?

A5. No, aspartame does not cause headaches. Headaches are one of the most common human ailments. Many factors can cause headaches, ranging from stress and sleep disturbances to physical illnesses. It is potentially dangerous to assume that a headache is related to aspartame, when the cause may be a serious psychological or physical condition. If you are concerned about headaches, speak to your physician.

A carefully controlled clinical study published in the New England Journal of Medicine (1) supports the fact that aspartame does not cause headaches or migraines. The results showed that 35 percent of the subjects had headaches after taking aspartame, compared with 45 percent who had headaches after taking the placebo, confirming that aspartame does not trigger headaches.

(1) Schiffman S et al, "Aspartame and susceptibility to headache," New England Journal of Medicine, Vol. 317, 1987, pp. 1181-1185.

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The last extract shows a typical industry PR ploy: only the pro-aspartame study is cited to back up a lie. The Schiffman study, of course, was funded by the industry. It used a single large dose, 1800 mg for a 60 kg person, about the same a 9 12-oz cans or less than 2 L, a level often exceeded by aspartame reactors, on subjects who claimed that aspartame gave them symptoms. However, expert testimony exists that doses in drinks are far more quickly and fully absorbed than doses in capsules. In addition, evidence exists that the metabolites of aspartame are cumulative toxins, in which case a single-dose study is beside the point. Thirdly, a group of 40 subjects can suffice to reach conclusions only about effects that are more common than about 1 out of 20, or 5 %, whereas 1% of the aspartame users in the USA alone is over 2 million persons.

This misuse of science is pervasive in the history of aspartame. Presumably, the same management and the same research teams have been studying "Sweetener 2000", now known as neotame, since 1987. Shouldn't this industry-funded research be examined in full detail at least for a year by the world public and independent experts?

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SECTION C: The scientific legitimacy and value of the clinical reports and case studies by H.J. Roberts, MD; evidence for serious, immediate reactions to 1.5 to 8 mg aspartame doses, absorbed directly from the inner surfaces of the mouth: the role of methanol and formaldehyde metabolites.

In this review, I present evidence from H.J. Roberts' publications to show that his insights are competently based on a huge collection of cases, and related to over 600 references from the standard medical research literature. I quote cases that show strong symptoms from as little as a single stick of chewing gum [6-8 mg aspartame] or a peppermint mint [1.5 mg aspartame]. He and other notice that increasing headaches are often a precursor to the first occurrence of seizures. He also focus attention on the biochemical evidence that indicates that chronic, cumulative methanol and formaldehyde toxicity are a major feature of aspartame victims.

http://groups.yahoo.com/group/aspartameNM/message/859
RTM: Roberts: the life work of a brilliant clinician: aspartame toxicity 8.2.2 [Comments by Rich Murray are in square brackets.] [Extracts given here]

http://www.dorway.com/tldaddic.html 5-page review Roberts HJ Aspartame (NutraSweet) addiction. Townsend Letter 2000 Jan; HJRobertsMD@aol.com http://www.sunsentpress.com sunsentpress@aol.com Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416 800-814-9800 561-588-7628 561-547-8008 fax

Dr. Roberts is Director of the Palm Beach Institute for Medical Research (since 1964), and a member of the American College of Physicians, The Endocrine Society and the American Academy of Neurology. His writings include nine acclaimed texts and more than 220 original articles and letters. Many deal with original researches on challenging metabolic and neurological disorders.

http://groups.yahoo.com/group/aspartameNM/message/790
RTM: Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2

http://groups.yahoo.com/group/aspartameNM/message/669
Rich Murray: Roberts: "Aspartame Disease" 1038 page expert magnum opus 7.5.1 rmforall published May 30 2001 $ 85.00 postpaid data from 1200 cases available at http://www.amazon.com over 600 references from standard medical research http://www.aspartameispoison.com/contents.html 34 chapters

July 5 2001 I turned 59 July 3, and got a wonderful, long-anticipated gift from H.J. Roberts, MD, FACP, FCCP.: "Aspartame Disease: An Ignored Epidemic". I will be studying this very helpful comprehensive review carefully, and composing summary posts on almost all of the 34 chapters, to explore this immense tapestry of data, observations, conclusions, and questions, making it easier for potential readers to decide whether to pay the price, $ 85.00 postpaid. The size of a Santa Fe phone book, the 1038 pages are 8.5X11, and appear to be composed in HTML. I will quote various passages, and give comments. Roberts' style is throughout lucid, dignified, high-minded, plain-spoken, direct, calm, succinct, and often shows a dry wit.

p7 ADDITIONAL COMMENTS:
Several added points deserve clarification for critical readers. ITEM 1: I wrote this book myself. (The term "authentic" comes from a Greek word meaning "one who does things with his own hands.") There were no collaborators, "ghost writers," or editors.

p 8 Corporate Neutrality:
I take pride in my corporate neutrality. No grants or salary were received for this effort, which originated in clinical practice.

p 27 EVOLVING DOUBTS: "GOING PUBLIC'
Like most physicians, the author had no reason to doubt the scientific basis for its safety when aspartame was approved by the FDA [in July, 1981]. My attitude changed, however, after repeatedly encountering serious reactions in my patients (Section 2) that seemed justifiably linked to use of such products

These doubts increased after learning by mid-1986 that over 10,000 consumers had sent complaints to the FDA, the Centers for Disease Control (CDC), the manufacturer, interested investigators, and consumer organizations.

p 28 More On the Author's Background:
The reader is entitled to specifics about the author's interest and credentials.

At the time my observations on aspartame disease first evolved, I was a primary-care internist, medical consultant, and director of a corporate-neutral medical research organization. Patients with a broad spectrum of diagnostic and therapeutic difficulties were seen, generally after having consulted with a number of physicians and clinics. The unique role stemmed from having authored many scientific articles and books. The first, "Difficult Diagnosis: A Guide to the Interpretation of Obscure Illness (W.B. Saunders Company, 1958), has been used by more than 60,000 physicians in the United States.

In the mid-1980s, I became aware of subtle changes and challenges pertaining to both the diagnosis and management of patients whose difficulties later could be related directly to the use of aspartame products.

A 16-year-old girl (Case III-2) had recurrent seizures that baffled several neurologists. Her convulsions stopped after avoiding aspartame products. An attack was then reproduced within three hours following re-challenge with one small serving of an aspartame pudding."

[This paragraph epitomizes the 1200 case reports that are the foundation of this text.]

These insights led to routinely inquiring of "problem patients" about aspartame consumption. Their prompt improvement following abstinence indicated an evolving public health problem... at least within the context of my practice. Numerous persons having "mysterious ailments" came to realize that they were afflicted with aspartame disease when striking improvement occurred after stopping such products. Virtually every day became a learning experience as I delved into the numerous facets of aspartame disease.

[This indicates that a single doctor who inquires about aspartame use by all his own clients is likely to find many cases a week of aspartame disease, and this in turn is evidence for a huge degree of prevalence. Skeptical professionals have an opportunity to confirm or refute this in their own clinical practice. I will gladly post any observations, and critical reviews, pro or con, sent to me, on http://groups.yahoo.com/group/aspartameNM/messages ]

p 31 On July 30, 1986, I presented my data on 100 aspartame reactors at a press conference in West Palm Beach... I delivered my first scientific report on 360 aspartame reactors to the Section on Medicine of the Southern Medical Association on November 10, 1986. The first article on 496 aspartame reactors appeared in the January 1987 edition of "On Call", official publication of the Palm Beach County Medical Society.

The flood of calls and letters from grateful aspartame "victims" and their families dispelled my earlier misgivings about "going public." A husband wrote, "Without someone publishing this information that was so helpful to me, my wife could have died from illness due to this cause."

p 6 I have engaged in independent patient-based clinical research involving various realms for more than four decades. They include pesticides (notably pentachlorophenol), products contaminated with toxic metals, arbitrary severe caloric restriction, megadoses of vitamin E, anti-static clothes softeners, fluoridation of water, and even vasectomy. I repeatedly stressed two pertinent issues. First, a long time may be required to identify the hazards of new products and medical interventions, particularly drugs and industrial chemicals. Second, it may take even longer for these risks to be acknowledged by physicians and public health officials.

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[I spent about nine hours scanning Aspartame Disease for cases of small doses of aspartame in breath mints [1.5 mg aspartame per mint], pills [about 4 mg per pill], and chewing gum [6-8 mg aspartame per stick], since if there are a variety of symptoms to such small doses, then it is a foregone conclusion that much more serious reactions must exist to diet drinks [180-330 mg aspartame per 12 oz]. Many cases describe people who had become reactors to large doses of aspartame, who then find severe and immediate reactions to a stick or less of chewing gum.] [Excerpts, pp 79-85]

D: REACTIONS TO SMALL QUANTITIES

Some reactors evidenced severe symptoms and signs after ingesting or chewing small amounts of aspartame products.

• Mention was made of convulsions occurring in a nursing infant as its mother drank an aspartame soft drink.

• Children developed severe headache, convulsions, or both, within minutes after chewing either acetaminophen (given for fever) or gum containing aspartame...

• Case III-1, a 31-year-old nurse with an aspartame-induced seizure, subsequently drank "only three sips" of a drink believed to be "regular" soda, but which contained aspartame. She promptly became "very incoherent." [Case described on pages 113-115]

• A chemist who developed migraine from certain foods and additives performed six double-blind experiments on himself. He found that as little as 4.0 mg aspartame in a capsule predictably induced headache (Strong 2000).... [ http://groups.yahoo.com/group/aspartameNM/message/285 Strong FC Why do some dietary migraine patients claim they get headaches from placebos? Clin Exp Allergy 2000 May; 30(5): 739-43.]

E: ASPARTAME GUM

I have been impressed by the role of aspartame gum in patients suffering severe neurologic aspartame reactions, especially headache and seizures (see below):

• A 24-year-old woman stated that she was "on the very verge of dying" from aspartame disease. Dramatic improvement occurred when she learned about this disorder, and then stopped such products. She emphasized her marked sensitivity to even a single stick of aspartame gum. Symptoms would recur within minutes after chewing it, and lasted one week. [6-8 mg aspartame per stick of chewing gum]

• Aspartame gum was specifically incriminated by Case IX-C-16, a 35-year-old woman with shortness of breath, dizziness, irritability, fatigue, heavy menstrual bleeding, hair loss and weight gain. (She did not drink diet sodas.) These reactions-- "within the hour I could not catch my breath"-- reoccurred on multiple re-tests.

Owing to its prolonged sweetness, persons tend to chew aspartame as much as five times longer than regular gum....

The habitual sucking of popular mints containing aspartame may induce seizures and other neuropsychiatric disorders. An aspartame reactor with prior complaints (vision impairment; slurred speech; loss of muscle strength) remained symptom-free after avoiding aspartame. She then experienced "painfully dry eyes" immediately after taking a breath mint containing aspartame...[1.5 mg aspartame per mint]

ABSORPTION

Chewing gum exposes the body to aspartame thorough its absorption in the upper gastrointestinal tract, and from the lining of the mouth. Additional ingredients could pose added problems. For example, I have repeatedly encountered difficulty with peppermint gum and wafers (Roberts 1983). [See case on page 456]

The rapidity with which reactions can occur after chewing aspartame gum is not necessarily an "allergy". The prompt absorption of aspartame or its breakdown products (Chapter XXV) from the mouth is akin to placing nitroglycerine under the tongue for the rapid relief of angina pectoris.

Pharmacologists recognize that absorption through the oral mucosa (without swallowing) can be an efficient route of delivery for amino acids and small proteins because the basal lamina under the epithelial layer contains blood vessels. Moreover, the enzymatic activity of the oral cavity is relatively low (principally, an amylase that hydrolyzes only sugars).

• The blood flow in the buccal mucosa is comparable to that of the sublingual mucosa. Absorbed molecules are collected by the internal jugular veins, thereby directly reaching the circulating blood.

• The buccal route for drug administration is illustrated by its effectiveness in treating childhood seizures with midazolam (Scott 1999). The rich blood supply to the mouth enables absorption directly into the systemic circulation, thereby avoiding the considerable "first-pass" metabolism by the liver. A rapid effect on the central nervous system has been demonstrated electroencephalographically.

*********

http://www.dorway.com/tldaddic.html
Courtesy of Dr. Roberts and "The Townsend Letter for Doctors and Patients" Aspartame (NutraSweet) addiction. January, 2000; 52-57. HJRobertsMD@aol.com

http://www.sunsentpress.com sunsentpress@aol.com Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416 800-814-9800 561-588-7628 561-547-8008 fax [also discussed on pages 318-319 in Aspartame Disease]

SUMMARY

The habitual consumption of "diet" products containing the chemical aspartame not only risks aspartame disease but also clinical addiction. Thirty-three (5.6 percent) of 540 aspartame reactors in the author's recent series found it difficult or impossible to discontinue them because of severe withdrawal effects. They or their reporting relatives (especially parents of afflicted children) specifically used the terms "addict" and "addiction." Others who used comparable terms were excluded even though they experienced similar withdrawal symptoms. The FDA and members of Congress have been repeatedly urged by me and thousands of outraged aspartame reactors to declare aspartame products an "imminent public health hazard," and remove them from the market. The mounting evidence for their causation or aggravation of headache, seizures, depression, many neurologic disorders (most notably multiple sclerosis), visual difficulty, allergies, diabetic complications, and a host of other conditions - coupled with the potential for addiction - can be ignored no longer.

[Extract]
The habitual chewing of aspartame gum poses a unique threat, as evidenced by the dramatic development of generalized symptoms in some aspartame reactors. Its flavor and sweetness can last 30 minutes, compared to about five minutes for sugar-sweetened gum. The chemical may be absorbed through the mucosa of the mouth (as used therapeutically with nitroglycerin), and via simple diffusion from the oropharynx directly into the brain. The latter phenomenon has been demonstrated with small molecules such as glucose, sodium chloride and ethyl alcohol (20).

THE METHANOL ISSUE

The chronic intake of free methanol in significant amounts is highly germane to aspartame disease and addiction, particularly for alcoholics.

Six years before FDA approval of aspartame, Dr. Herbert S. Posner (21) of the National Institute of Environmental Health Sciences wrote a review titled, "Biohazards of Methanol in Proposed New Uses." He stressed the failure to recognize the "delayed and irreversible effects on the nervous system" of methanol...at widely varying levels of exposure and at rather low levels." Furthermore, he suggested "...when a safer compound is available, methanol should not be utilized."

The daily intake of methyl alcohol from natural sources averages less than 10 mg (22). Aspartame beverages contain 55 mg methanol per liter, and nearly double as much in some carbonated orange sodas. Persons ingesting five liters a day can therefore consume over 400 mg methanol.

These facts are pertinent:

• Methyl alcohol is probably the first component of aspartame released within the small intestine, and rapidly absorbed. Blood and methanol concentrations correlate with aspartame intake. "Abuse doses" (100 mg/kg or more) ingested by normal subjects significantly elevate blood methanol concentrations, remaining detectable for eight or more hours (23).

• Humans are more vulnerable to the toxic effects of methanol than animals because several enzymes required for its metabolism have been lost during evolution.

• The toxicity of methanol is enhanced by its slow rate of oxidation - only one-seventh that of ethyl alcohol - occurring chiefly in the liver and kidneys. Even though the half life in human volunteers ingesting small amounts (1-5 ml) is about three hours, complete oxidation to carbon dioxide usually requires several days.

• The body attempts to detoxify methyl alcohol by oxidizing it to formaldehyde (a deadly neurotoxin and Class A carcinogen), and then to formate or formic acid within minutes. Formate and formaldehyde each may contribute to toxicity and nervous system/immune dysfunction through various mechanisms. One is the conjugation of formaldehyde with human serum albumin (F-HSA) to form a new antigenic determinant. Patients with multiple health complaints who had been exposed chronically to formaldehyde develop anti F-HSA antibodies and elevated Tal cells (antigen memory cells), consistent with sustained antigenic stimulation of the immune system (24).

• Concerning the methyl alcohol component of aspartame, Hugh C. Cannon, Associate Commissioner for Legislative Affairs of the FDA, wrote in a letter dated September 8, 1986: "The Agency has recently become aware, however, of clinical data that indicate that the toxic effects of methanol are due to formate accumulation and not to formaldehyde or methanol itself. Formate is the oxidation product of formaldehyde which is itself formed from the metabolism of methanol."

***********************************************************

SECTION C: confirming research by Newman and Lipton on serious effects from 4 mg aspartame absorbed through the inner surfaces of the mouth; aspartame levels in products.

[This study and its references confirm Roberts' accounts of the strong effects of small doses of aspartame in aspartame reactors. Newman, Lipton, and Blumenthal are eminent officials of the American Headache Society.]

http://groups.yahoo.com/group/aspartameNM/message/854
RTM: Newman & Lipton: 3.75 mg aspartame in Merck Maxalt-MLT worsens migraine Oct 2001 7.28.2
[Comments by Rich Murray are in square brackets.]
[Extracts given here]
Headache 2001 Oct; 41(9): 899-901.
Migraine MLT-Down: An Unusual Presentation of Migraine in Patients With Aspartame-Triggered Headaches.
Newman LC, Lipton RB.
Headache Institute, St. Lukes-Roosevelt Hospital Center
New York NY
Department of Neurology Albert Einstein College of Medicine, Bronx, NY Innovative Medical Research

Aspartame, an artificial sweetener added to many foods and beverages, may trigger headaches in susceptible individuals. We report two patients with aspartame-triggered attacks in whom the use of an aspartame-containing acute medication (Maxalt-MLT) worsened an ongoing attack of migraine. PMID: 11703479

[Extracts]
Two patients successfully treated with triptans developed headache exacerbation following treament with an aspartame-containing formulation of rezatriptan (Maxalt-MLT). (1) [Contains 3.75 mg aspartame.]...
Anecdotal evidence and observational studies suggest that aspartame is a potential migraine trigger. (3, 4) Although two double-blinded studies support these results, a third study did not. (5-7) [The third study was the only one paid for by NutraSweet Co: Schiffman, 1987. For a detailed critique of these studies:

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity 6.4.1

*********

In 1981, the United States Centers for Disease Control reviewed consumer complaints related to the use of aspartame. (2) Neurologic or behavioral symptoms were reported in 67%: the most frequently mentioned single complaint, headache, was reported in 22%...

Survey data of a headache-prone population suggests that aspartame is a common headache trigger. In a sample of 171 consecutive patients with headache, regarding the role of dietary factors and headache, aspartame was reported as a headache precipitant by 8.2%, significantly more often than carbohydrates, the food used as a negative control. (3).

Johns described a patient who developed a vascular headaches and gastrointestinal symptoms following the ingestion of aspartame-containing soft drinks. (4) Similar symptoms occurred when the patient was rechallenged with solutions of aspartame but not with saccharin.

Blumenthal and Vance described 3 patients in whom aspartame-containing chewing gum induced typical migraine attacks. (8) [6-8 mg aspartame per stick] ... [ http://groups.yahoo.com/group/aspartameNM/message/854
RTM: Blumenthall & Vance:
Aspartame chewing gum headaches Nov 1997 7.28.2]

We have previously discussed some of the limitations of the Schiffman study. (9)...

*********

REFERENCES

1. Physicians' Desk Reference. 54th ed. Medical Economics Co; Montvale, N.J.: 2000: 1956-1960.

2. Anonymous. Evaluation of cusumer complaints related to aspartame use. MMWR Morb Mortal Wkly Rep. 1984; 33: 605-607.

3. Lipton, RB, Newman LC, Cohen JS, Solomon S. Aspartame as a dietary trigger of headache. Headache. 1989; 29: 90-92.

4. Johns DR.
   Migraine provoked by aspartame (letter).
   N Engl J Med. 1986; 315: 456

5. Schiffman SS, Buckley CE III, Sampson JA, et al.
   Aspartame and susceptibility to headache.
   N Engl J Med. 1987; 317: 1181-1185.

6. Koehler SM, Glaros A.
   The effect of asparame on migraine headache.
   Headache. 1988; 28: 10-14.

7. Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B.
   Aspartame ingestion and headaches: a randomized crossover trial.
   Neurology. 1994; 44: 1787-1793.

8. Blumenthal HJ, Vance DA.
   Chewing gum headaches.
   Headache. 1997; 37: 665-666.

9. Lipton RB, Newman LC, Solomon S.
   Asparame and headache (letter).
   N Engl J Med. 1988; 318: 1200-1202.

http://www.docnet.org/physicians/phys_bios.asp?phys_id=574
Lawrence C. Newman, MD 212-523-5869 newmanache@aol.com
St. Luke's-Roosevelt Hospital Center Headache Institute
1000 10th Avenue, Room 1C-10
New York, NY 10019
Prof. Neurology, Epidemiology & Social Medicine Albert Einstein College of Medicine at Yeshiva University

http://msl.montefiore.org/newmsl/default.htm
Dr. Richard B. Lipton, Department of Neurology
Montefiore Medical Center
111 East 210th Street
Bronx, NY 10467, USA
FAX 203-321-1044

Albert Einstein College of Medicine
1300 Morris Park Avenue
Bronx, NY 10461
718-430-3886 fax 3870
MMC - Headache Unit
111 E. 210th Street
Bronx , NY 10467 718-920-4638

http://www.imrinc.com webmaster@imrinc.com
nnovative Medical Research, Inc.
Alberto R. Yataco, M.D.
Richard B. Lipton, M.D., Chief Science Officer RLipton@IMRInc.com
1001 Cromwell Bridge Rd., Suite 302
Towson, MD 21286 USA
410-825-0500 Fax: 410-339-7086
http://www.centerwatch.com/professional/pro111.html

President American Headache Society
Richard B. Lipton, MD
Professor of Neurology, Epidemiology and Social Medicine
Albert Einstein College of Medicine Innovative Medical Research, Inc.
1200 High Ridge Road
Stamford, CT 06905
203-321-1050 fax 1044
rlipton@imrinc.com

Fall & Winter Symposium Co-Chairs
Lawrence C. Newman, MD
The Headache Institute
1000 Tenth Avenue
New York, NY 10019
212-523-5869 fax5902 (fax)
newmanache@aol.com

American Headache Society http://www.ahsnet.org
19 Mantua Road
Mt. Royal, NJ 08061
856.423.0043 fax 0082
ahshq@talley.com
Headache: The Journal of Head and Face Pain
http://ahsnet.org/journal

*********

http://www.nutrasweet.com/search/index.asp
Consumer Center All About NutraSweet NutraSweet Content

For specific information regarding individual products, the manufacturer should be contacted as exact formulations differ with each manufacturer. Here is approximate aspartame content in several product categories.

**********************************************************

SECTION D: confirmation by Blumenthal and Vance of serious, rapid symptoms from 6-8 mg aspartame absorbed through the inner surfaces of the mouth.

[Again, this study confirms the patterns of symptoms reported by H.J. Roberts, and the potency of small doses of aspartame to harm aspartame reactors. They cite H.J. Roberts as a reference.]

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthal & Vance: aspartame chewing gum headaches Nov 1997 7.28.2 Chewing Gum Headaches.
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Headache 1997 Nov-Dec; 37(10): 665-666.
Department of Neurology, University of Oklahoma College of Medicine, Tulsa, USA.

Aspartame, a popular dietetic sweetener, may provoke headache in some susceptible individuals. Herein, we describe three cases of young women with migraine who reported their headaches could be provoked by chewing sugarless gum containing aspartame. PMID: 9439090

[Excerpts] [Comments by Rich Murray are in square brackets.]
[Excerpts given here] Patient 1.--A 40-year-old housewife described migraine without aura beginning about age 25. When she first consulted the senior author in July 1994, she also had episodic tension-type headaches and mild depression...In February 1996, she reported worsening of her headache condition and described near-daily headaches with worsening of depressive symptoms...

Over the next 6 months, she did remarkably well. She was assiduous in keeping a headache calendar and felt she had better control over her life and her headache condition by taking an active part...She observed that certain nuts and skipping meals might provoke headaches. Most of all, she observed that the aspartame-containing sugarless gum was a great trigger of her typical migraine...

Patient 2.--A 32-year-old housewife and secretary presented in September 1995, with a 6-year history of migraine without aura... On subsequent inquiry about dietary triggers, she reported her observation of an inter-menstrual migraine provoked by chewing gum containing aspartame, but not by chewing gum which did not contain aspartame. A throbbing bi-temporal headache developed within 45 minutes of chewing the gum. Norgesic, ibuprofen, and aspirin did not help. The headache began at 1730 hours, persisted through the evening and she did not sleep that night because of headache. This gum-induced headache lasted approximately 10 hours, whereas her menstrual migraine usually lasts 4 to 5 days. The intensity was less than the menstrual migraine and the location was different, with the gum-induced headache being a throbbing bi-temporal headache and the menstrual migraine being very intense at the vertex but more generalized and accompanied by nausea.

Patient 3.--A 26-year-old laboratory technician consulted the senior author in January 1997. Her headaches began at age 14; these were mild and easily relieved by Tylenol. She was never disabled. Six months before consultation, the headaches became more severe and more frequent: she attributed this to work stress. She described throbbing bifrontal and temporal headaches accompanied by sonophobia, and she preferred to lie down in a dark room because the headaches worsened if she continued her usual activity. There was no nausea and no aura. The headaches usually lasted 24 hours and naproxen sodium affored better relief than acetaminophen. She never left work and reported, "I suffer through it." The patient also reported she never found any food or beverage to provoke headache, but when urged to quit smoking and chew gum instead, she commented that her typical headache could be provoked by chewing gum which contained aspartame...

The chewing gum referred to in this report contains aspartame, sorbitol, and phenylalanine. A representative of the manufacturer of the particular gum would not reveal the aspartame content in the gum.

We can add chewing gum which contains aspartame to our expanding list of substances which may trigger headache.

[Aspartame content:

1.5 mg per breath mint

4 mg per vitamin pill

6-8 mg per stick chewing gum

37 mg per packet Equal

200 mg per 12 ounces diet soda]

1. Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B
   Aspartame ingestion and headaches: a randomized crossover trial.
   Neurology. 1994; 44: 1787-1793.

2. Koehler SM, Glaros A
   The effect of aspartame on migraine headaches.
   Headache. 1988; 28: 10-14.

3. Levy PS, Hedeker D, Sanders PG
   Aspartame and headache.
   Neurology. 1995; 45: 1631-1632.

4. Roberts HJ
   Aspartame and headache.
   Neurology. 1995; 45: 1631.

http://www.ahsnet.org/committees/board.php
Board Members-at-Large American Headache Society
Harvey J. Blumenthal, MD
Neurological Associates of Tulsa
6565 South Yale Avenue, Suite 312
Tulsa, OK 74136
918-481-7711 fax 7725
neurotulsa@aol.com

Dwight A. Vance
The University of Oklahoma College of Pharmacy
P.O. Box 26901
Oklahoma City, OK 7319

********************************************************

SECTION E: role of methanol and formaldehyde toxicity.

[In this section, I present some of the evidence supporting the role of methanol-formaldehyde toxicity in aspartame reactors, including the seminal, prescient review by Woodrow C. Monte in 1984. An important conclusion is that aspartame reactors probably will react in much the same way to low doses of methanol and of formaldehyde.]

http://groups.yahoo.com/group/aspartameNM/message/830
RTM: Tholen: Diet Coke has 5 ppm formaldehyde from aspartame 5.29.2
For 6 cans of diet soda, this is 5 times the daily limit of 1 PPM for formaldehyde in drinking water, set by the EPA.

http://www.geocities.com/aspartame_survivors/tholen.html
For a science project, Randy Tholen, age 11, paid $ 180 to have six cans of Diet Coke analyzed on Mar 7 2002 by Bill Katz 952-942-1774
Braun Intertec Corporation Lab Braun Intertec Corporation http://www.brauncorp.com (800) 279-6100 (952) 941-5600 fax (952) 833-4701
Mail: 6875 Washington Ave. S. Minneapolis, MN 55439
E-Mail: Webmaster@brauncorp.com

*********

Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html
Línies de Recerca: Toxicitat de l'aspartame
http://www.bq.ub.es/grupno/grup-no.html Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas, Sr. Jordi Virgili, Dr. Xavier Remesar, Dr. Jose Antonio Fernandez-Lopez, Dr. Marià Alemany Fac. Biologia
Tel.: (93)4021521, FAX: (93)4021559
alemany@porthos.bio.ub.es [mail]
bioq@sun.bq.ub.es
josefer@porthos.bio.ub.es
rafecas@porthos.bio.ub.es
remesar@porthos.bio.ub.es
Sra. Carme Trocho Fac. Biologia Tel.: (93)4021544, FAX: (93)4021559

ABSTRACT:

Adult male rats were given an oral dose of 10 mg/kg aspartame, 14C-labeled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to protein. Label present in liver, plasma and kidney was in the range of 1-2% of total radioactivity administered per g or mL, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of label in the range of 1/12th to 1/10th of that of liver. In all, the rats retained, 6 hours after administration, about 5% of the label, half of it in the liver.

The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labeled formaldehyde. DNA radioactivity was essentially in a single different adduct base, different from the normal bases present in DNA. The nature of the tissue label accumulated was, thus, a direct consequence of formaldehyde binding to tissue structures.

The administration of labeled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labeled aspartame during 10 days results in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative.

It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts. PMID: 9714421, UI: 98378223

[Extracts]
The high label presence in plasma and liver is in agreement with the carriage of the label from the intestine to the liver via the portal vein. The high label levels in kidney and, to a minor extent, in brown adipose tissue and brain are probably a consequence of their high blood flows (45). Even in white adipose tissue, the levels of radioactivity found 6 hours after oral administration were 1/25th those of liver. Cornea and retina, both tissues known to metabolize actively methanol (21,28) showed low levels of retained label. In any case, the binding of methanol-derived carbon to tissue proteins was widespread, affecting all systems, fully reaching even sensitive targets such as the brain and retina...

The amount of label recovered in tissue components was quite high in all the groups, but especially in the NA rats. In them, the liver alone retained, for a long time, more than 2 % of the methanol carbon given in a single oral dose of aspartame, and the rest of the body stored an additional 2 % or more. These are indeed extremely high levels for adducts of formaldehyde, a substance responsible of chronic deleterious effects (33), that has also been considered carcinogenic (34,47). The repeated occurrence of claims that aspartame produces headache and other neurological and psychological secondary effects-- more often than not challenged by careful analysis-- (5,9,10,15,48) may eventually find at least a partial explanation in the permanence of the formaldehyde label, since formaldehyde intoxication can induce similar effects (49).

The cumulative effects derived from the incorporation of label in the chronic administration model suggests that regular intake of aspartame may result in the progressive accumulation of formaldehyde adducts. It may be further speculated that the formation of adducts can help to explain the chronic effects aspartame consumption may induce on sensitive tissues such as brain (6,9,19,50). In any case, the possible negative effects that the accumulation of formaldehyde adducts can induce is, obviously, long-term. The alteration of protein integrity and function may needs some time to induce substantial effects. The damage to nucleic acids, mainly to DNA, may eventually induce cell death and/or mutations. The results presented suggest that the conversion of aspartame methanol into formaldehyde adducts in significant amounts in vivo should to be taken into account because of the widespread utilization of this sweetener. Further epidemiological and long-term studies are needed to determine the extent of the hazard that aspartame consumption poses for humans.

*********

Mark D. Gold has a fine, detailed analysis, "Scientific Abuse in Methanol / Formaldehyde Research Related to Aspartame" at: http://www.holisticmed.com/aspartame/abuse/methanol.html#discussion

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer: EPA: CPSC: formaldehyde toxicity 6.10.1

http://groups.yahoo.com/group/aspartameNM/message/645
Rich Murray: 18 recent formaldehyde toxicity [Comet assay] abstracts 6.25.1

*********

Dr. Woodrow C. Monte, "Aspartame: Methanol, and the Public Health," Journal of Applied Nutrition 1984; 36(1): 42-54. This study is available at http://www.dorway.com/wmonte.txt

Abstract: Aspartame (L-aspartyl-L-phenylalanine methyl ester), a new sweetener marketed under the trade name NutraSweet, releases into the human bloodstream one molecule of methanol for each molecule of aspartame consumed.

This new methanol source is being added to foods that have considerably reduced caloric content and, thus, may be consumed in large amounts. Generally, none of these foods could be considered dietary methanol sources prior to addition of aspartame. When diet sodas and soft drinks, sweetened with aspartame, are used to replace fluid loss during exercise and physical exertion in hot climates, the intake of methanol can exceed 250 mg/day or 32 times the Environmental Protection Agency's recommended limit of consumption for this cumulative toxin (8). [EPA limit: 7.8 mg/day in water. A 12-oz can of diet soda gives 20 mg methanol.]

There is extreme variation in the human response to acute methanol poisoning, the lowest recorded lethal oral dose being 100 mg/kg [6,000 mg for a 60 kg person] with one individual surviving a dose over ninety times this level (55). Humans, due perhaps to the loss of two enzymes during evolution, are more sensitive to methanol than any laboratory animal; even the monkey is not generally accepted as a suitable animal model (42). There are no human or mammalian studies to evaluate the possible mutagenic, teratogenic, or carcinogenic effects of chronic administration of methyl alcohol (55).

The average intake of methanol from natural sources varies but limited data suggests an average intake of considerably less than 10 mg/day (8).

[A 12-oz can of diet soda has 20 mg methanol.] Alcoholics may average much more, with a potential range of between 0 and 600 mg/day, depending on the source and in some cases the quality of their beverages (15).

Ethanol, the classic antidote for methanol toxicity, is found in natural food sources of methanol at concentrations 5 to 500,000 times that of the toxin (Table 1). Ethanol inhibits metabolism of methanol and allows the body time for clearance of the toxin through the lungs and kidneys (40, 46).

The question asked is whether uncontrolled consumption of this new sweetener might increase the methanol intake of certain individuals to a point beyond which our limited knowledge of acute and chronic human methanol toxicity can be extrapolated to predict safety. [end of Abstract]

Monte's study explains:

"Methanol (methyl alcohol, wood alcohol), a poisonous substance (60), is added as a component during the manufacture of aspartame (47). This methanol is subsequently released within hours of consumption (51) after hydrolysis of the methyl group of the dipeptide by chymotrypsin in the small intestine (40) as it occurs in soft drinks after decomposition of aspartame during storage or in other foods after being heated (48). Regardless of whether the aspartame-derived methanol exists in food in its free form or still esterified to phenylalanine, 10% of the weight of aspartame intake of an individual will be absorbed by the bloodstream as methanol within hours after consumption (51).

[So, a daily dose of 2100 mg aspartame, used in some experimental tests, gives 210 mg of methanol.]

"Methanol has no therapeutic properties and is considered only as a toxicant (20). The ingestion of two teaspoons is considered lethal in humans (19).

"An average aspartame-sweetened beverage would have a conservative aspartame content of about 555 mg/liter (48, 51) and therefore, a methanol equivalent of 56 mg/liter (56 ppm). For example, if a 25 kg child consumed on a warm day, after exercising, two-thirds of a two-liter bottle of soft drink sweetened with aspartame, that child would be consuming over 732 mg of aspartame (29 mg/kg). This alone exceeds what the Food and Drug Administration considers the 99 + percentile daily consumption level of aspartame (48). The child would also absorb over 70 mg of methanol from that soft drink. This is almost ten times the Environmental Protection Agency's recommended daily limit of consumption for methanol.

"To look at the issue from another perspective, the literature reveals death from consumption of the equivalent of 6 gm of methanol (55, 59). It would take 200 12 oz. cans of soda to yield the lethal equivalent of 6 gm of methanol. [Monte's point is that the methanol dose from 2 L of diet soda, 5.6 12-oz cans, 20 mg/12-oz can methanol, 112 mg methanol, is too close to the lethal dose, 6000 mg, according to the usual standards for other toxins. The EPA limit is 7.8 mg/day in water for this cumulative poison.]

"A striking feature of methyl alcohol syndrome is the asymptomatic interval (latent period), which usually lasts 12 to 18 hours after consumption.

"Patients may complain of lethargy, confusion, and impairment of articulation, all frequently encountered signs in moderate central nervous system (CNS) intoxications resulting from other toxic compounds (20). Patients may also suffer leg cramps, back pain, severe headache, abdominal pain, labored breathing, vertigo and visual loss, the latter being a very important clue to making a diagnosis of methanol poisoning (20).

"Many of the signs and symptoms of intoxication due to methanol ingestion are not specific to methyl alcohol. For example, headaches, ear buzzing, dizziness, nausea and unsteady gait (inebriation), gastrointestinal disturbances, weakness, vertigo, chills, memory lapses, numbness and shooting pains in the lower extremities hands and forearms, behavioral disturbances, and neuritis (55). The most characteristic signs and symptoms of methyl alcohol poisoning in humans are the various visual disturbances which can occur without acidosis (55), although they unfortunately do not always appear (20). Some of these symptoms are the following: misty vision, progressive contraction of visual fields (vision tunneling), mist before the eyes, blurring of vision, and obscuration of vision (20, 55)."

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SECTION F: a brief review of aspartame toxicity research.

[This is my standard brief review, constantly upgraded. It offers a quick survey of the most prominent research, the most important activist web sites, a list of the typical suite of serious symptoms, and some related links, showing powerful volunteer groups that deal with other toxicity issues.]

RTM: Aspartame toxicity: recent research 8.3.2

http://groups.yahoo.com/group/aspartameNM/messages for 860 posts
http://groups.yahoo.com/group/aspartameNM/message/861 brief review
http://groups.yahoo.com/group/aspartameNM/message/862 long review
http://groups.yahoo.com/group/aspartameNM/message/860
RTM: FDA: objections to neotame approval 8.3.2

http://groups.yahoo.com/group/aspartameNM/message/846
RTM: Aspartame in Merck Maxalt-MLT worsens migraine, AstraZeneca Zomig, Eli Lilly Zyprexa, J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab, Pfizer Cool Mint Listerine Pocketpaks 7.16.2

http://groups.yahoo.com/group/aspartameNM/message/841
RTM: Merisant Co., MSD Capital, Dell Computer Corp., NutraSweet Co., JW Childs Assc.: aspartame-neotame toxicity 7.10.2

http://groups.yahoo.com/group/aspartameNM/message/830
RTM: Tholen: Diet Coke has 5 ppm formaldehyde from aspartame 5.29.2 For 6 cans of diet soda, this is 5 times the daily limit of 1 PPM for formaldehyde in drinking water, set by the EPA.

http://www.dorway.com/tldaddic.html 5-page review Roberts HJ Aspartame (NutraSweet) addiction. Townsend Letter 2000 Jan; HJRobertsMD@aol.com http://www.sunsentpress.com sunsentpress@aol.com Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416 800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text "Aspartame Disease: An Ignored Epidemic" published May 30 2001 $ 85.00 postpaid data from 1200 cases available at http://www.amazon.com over 600 references from standard medical research
http://www.aspartameispoison.com/contents.html 34 chapters
http://groups.yahoo.com/group/aspartameNM/message/790
http://groups.yahoo.com/group/aspartameNM/message/859
RTM: Roberts: the life work of a brilliant clinician: aspartame toxicity 8.2.2

RTM: Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2

http://groups.yahoo.com/group/aspartameNM/message/652
Smith JD, Terpening CM, Schmidt SO, Gums JG
Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins.
terpening@fpmg.health.ufl.edu cterpeni@ufl.edu
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
gums@fpmg.health.ufl.edu siggy@shands.ufl.edu
http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums: full text: aspartame, MSG, fibromyalgia 1.17.2

http://groups.yahoo.com/group/aspartameNM/message/804
RTM: Hetle & Eltervaag: 2001 thesis abstract: aspartame brain damage in mice: Sonnewald
1995 study full text 2.17.2

http://groups.yahoo.com/group/aspartameNM/message/752
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
Migraine MLT-Down: an unusual presentation of migraine in patients with aspartame-triggered headaches. [Merck 10-mg Maxalt-MLT, for migraine, has 4 mg aspartame, while 12 oz diet soda has 200 mg.]
Headache Institute, St. Lukes-Roosevelt Hospital Center
New York NY
Department of Neurology newmanache@aol.com
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research RLipton@IMRInc.com

http://groups.yahoo.com/group/aspartameNM/message/346
WebMD: Barclay: Barth: survey shows aspartame hurts memory in students 11.9.00
http://www.psy.tcu.edu/psy/barth.htm
Timothy M. Barth Department of Psychology t.barth@tcu.edu Texas Christian University TCU Box 298920 Fort Worth, TX 76129 Chairman, Physiological Psychology 817-921-7410

http://groups.yahoo.com/group/aspartameNM/message/760
Kovatsi L, Tsouggas M The effect of oral aspartame administration on the balance of magnesium in the rat.
Magnes Res 2001 Sep;14(3): 189-94.
Laboratory of Forensic Medicine & Toxicology, Faculty of Medicine Aristotle University of Thessaloniki, Greece kovatsi@med.auth.gr

http://groups.yahoo.com/group/aspartameNM/message/689
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@atlas.uoa.gr

Two teams find hot aspartame releases DKP, a potent carcinogen: Lin SY, Cheng YD Simultaneous formation and detection of the reaction product of solid-state aspartame sweetener by FT-IR/DSC microscopic system. Food Addit Contam 2000 Oct; 17(10): 821-7.
Biopharmaceutics Laboratory
Department of Medical Research & Education Veterans General Hospital-Taipei, Shih-Pai, Taiwan, Republic of China.
sylin@vghtpe.gov.tw
and
Leung SS, Padden BE, Munson EJ, Grant DJ
Hydration and dehydration behavior of aspartame hemihydrate.
J Pharm Sci 1998 Apr; 87(4): 508-13.
Department of Pharmaceutics, College of Pharmacy
University of Minnesota, Minneapolis 55455-0343, USA.
Sophie S. Leung, PhD
Dolores J. Grant, PhD grant1@niehs.nih.gov

http://www.medscape.com/MedGenMed/braintumors
Lennart Hardell, M.D., PhD, in 1999 reported in Sweden that both cell phone use and heavy aspartame use correlate with increased brain cancers lennart.hardell@orebroll.se +46 19 602 15 46

http://www.dorway.com/blayenn.html
Russell L. Blaylock, MD dodd@netdoor.com Excitotoxins, neurodegeneration and neurodevelopment. The Medical Sentinel Journal 1999 Fall; (95 references)
russell@misnet.com 601-982-1175

http://www.dorway.com/barua.html
Dr. J. Barua (ophthalmic surgeon), Dr. Arun Bal (surgeon) Emerging facts about aspartame.

Journal Of The Diabetic Association Of India 1995; 35 (4): (79 references)
barua@giasbm01.vsnl.net.in

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer: EPA: CPSC: formaldehyde toxicity 6.10.1

http://groups.yahoo.com/group/aspartameNM/message/645
Rich Murray: 18 recent formaldehyde toxicity [Comet assay] abstracts 6.25.1

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon: aspartame toxicity 6.4.1
http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers: aspartame toxicity 6.4.1

http://www.dorway.com/wmonte.txt
Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science
Director of the Food Science and Nutrition Laboratory
Arizona State University, Tempe, Arizona 85287
6411 South River Drive #61 Tempe, Arizona 85283-3337
602-965-6938 woody.monte@asu.edu

The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is 112 mg, 10% of the aspartame. The EPA limit for water is 7.8 mg daily for methanol (wood alcohol), a deadly cumulative poison. Many users drink 1-2 L daily. The reported symptoms are entirely consistent with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but, like all juices, has 16 times more ethanol, which strongly protects against methanol.)

http://www.truthinlabeling.org
Truth in Labeling Campaign [MSG] Adrienne Samuels, PhD The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Accountability in Research (1999); 6: 259-310.
P.O. Box 2532
Darien, Illinois 60561
858-481-9333 adandjack@aol.com

http://www.dorway.com 12,000 print pages
Mission-Possible-USA Betty Martini 770-242-2599 Bettym19@mindspring.com

http://www.dorway.com/asprlink.html many links
http://www.dorway.com/nslawsuit.txt Jeff Martin, Attorney
http://www.dorway.com/upipart1.txt UPI reporter Gregory Gordon: 96K 3-part expose Oct 1987
http://www.dorway.com/doctors.txt What many informed doctors are saying/have said about aspartame

http://www.HolisticMed.com/aspartame
603-225-2100
Aspartame Toxicity Information Center
Mark D. Gold mgold@tiac.net
12 East Side Drive #2-18
Concord, NH 03301

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://www.readthelabel.org.uk Additives Survivors' Network (UK)
geoffbrewer@eurobell.co.uk

http://www.aspartame.ca John T. Linnell admin@aspartame.ca
http://www.aspartame.ca/page_a10.html Canadian Class Action Law Suit

http://groups.yahoo.com/group/aspartameNM/message/802
RTM: 700.club.com: CBN: Totheroh & Robertson: aspartame expose 2.13.2

http://groups.yahoo.com/group/aspartameNM/message/805
RTM: Ive: UK Daily Mirror Magazine: aspartame toxicity 2.18.2

http://groups.yahoo.com/group/aspartameNM/message/813
[also on http://www.rense.com/general20/bushaspertameAL.htm Contact Jeff Rense jr@rense.com ] RTM: (corrected) danger to President Bush from aspartame toxicity 2.24.2

The great health advantages of a no-fat vegetarian diet are well described by Dr. John A. McDougall at http:www.drmcdougall.com , which has copious scientific references and Net links, and at http://www.vegsource.com

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SERIOUS SYMPTOM SYNDROME SUMMARY:

Serious symptom syndrome summary: Aspartame (NutraSweet, Equal, Canderel, Benevia) is reported by scientific studies and case histories to be toxic:

• Headaches

• Many body and joint pains (or burning, tingling, tremors, twitching, spasms, cramps, or numbness)

• Fever, fatigue

• "Mind fog", "feel unreal", poor memory, confusion, anxiety, irritability, depression, mania, insomnia, dizziness, slurred speech, ringing in ears, sexual problems, poor vision, hearing, or taste

• Red face, itching, rashes, burning eyes or throat, dry mouth or eyes, mouth sores

• Hair loss

• Obesity, bloating, edema, anorexia, poor or excessive hunger or thirst

• Breathing problems

• Nausea, diarrhea or constipation

• Coldness * sweating * racing heart, high blood pressure, erratic blood sugar levels

• Seizures * birth defects * brain cancers

• Addiction

• Aggravates diabetes, autism, ADHD, and interstitial cystitis (bladder pain)

http://www.aspartame.ca Canada
http://www.geocities.com/HotSprings/4578 Canada
http://www.cybernaute.com/earthconcert2000/AspartaMalcache.htm
http://www.reseauproteus.net/therapies/nutritio/aspartame.htm
http://ww2.grn.es/avalls/aspa1.htm Spain
http://www.geocities.com/HotSprings/Falls/8669 Brazil
http://www.phd.com.br/aspartame.htm
http://hem.passagen.se/mission.possible.sweden
http://home.online.no/~dusan/foods/aspartame.html Norway
http://www.ostara.org/aspartam/#anfang Germany
http://www.aspartaam.nl/info/product.htm Holland, in Dutch
http://www.laleva.org Italy
http://www.laleva.org/alimenti/dorwayaspartame.html
http://users.westnet.gr/~cgian/aspartame.htm Greece

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http://www.vegsource.com excellent diet info
http://www.mad-cow.org/BSE/nvCJD mad cow disease
http://www.litopia.com/jplant Jane Plant on breast cancer
http://groups.yahoo.com/group/aspartameNM/message/538 Plant
http://www.dorway.com aspartame toxicity
http://www.truthinlabeling.org MSG toxicity
http://www.asomat.com/links/links-content.htm amalgam mercury
http://groups.yahoo.com/group/aspartameNM/message/629 Boyd E. Haley
http://www.soyonlineservice.co.nz soy toxicity
http://www.thyroid-info.com Mary J. Shomon
http://www.npwa.freeserve.co.uk fluoride toxicity
http://www.electric-words.com/junk/junkindex.html junk science
http://www.pbs.org/tradesecrets/transcript.html Moyers on chemicals http://www.comeclean.org reform chemical industry

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G: Extracts from FDA approval of neotame.

http://groups.yahoo.com/group/aspartameNM/message/843
RTM: full text: Federal Register 7.9.2 Vol 67 Num 131 Pages 45300-45310:

http://frwebgate3.access.gpo.gov/cgi-bin/waisgate.cgi?WAISdocID=37400217485+0+0+0&WAISaction=retrieve

This document prints out to 22 pages, about 85K. To access this document and others, go to http://www.access.gpo.gov/su_docs/aces/aces140.html and search in Vol. 67 (2002) for neotame. This document is the first of four listed.

[Federal Register: July 9, 2002 (Volume 67, Number 131)]
[Rules and Regulations] [Page 45300-45310]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09jy02-5]

===============================================================

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 172 [Docket Nos. 98F-0052 and 99F-0187]

Food Additives Permitted for Direct Addition to Food for Human Consumption; Neotame

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is amending the food additive regulations to provide for the safe use of neotame as a nonnutritive sweetener in food. This action is in response to two petitions filed by Monsanto Co., which subsequently sold the rights to the petitions to the NutraSweet Co.

DATES: This rule is effective July 9, 2002. Submit objections and requests for a hearing by August 8, 2002. The Director of the Office of the Federal Register approves the incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain publication in 21 CFR 172.829, as of July 9, 2002.

ADDRESSES: Submit written objections and requests for a hearing to the Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, rm. 1061
Rockville, MD 20852.

Submit electronic objections to http://www.fda.gov/dockets/ecomments

FOR FURTHER INFORMATION CONTACT:

Blondell Anderson
Center for Food Safety and Applied Nutrition (HFS-265)
Food and Drug Administration
5100 Paint Branch Pkwy.
College Park, MD
20740-3835, 202-418-3106. [BAnderso@cfsan.fda.gov]

SUPPLEMENTARY INFORMATION:

Table of Contents:

1. Introduction
   
2. Safety Evaluation of Neotame
   
   1. Chemistry and Intake Considerations of Neotame
      
   2. Nature and Extent of Neotame Safety Studies Database
      
   3. Toxicology/Safety Assessment of Neotame
      

   1. Metabolism and Pharmacokinetics of Neotame

   a. Absorption of neotame

   b. Elimination, distribution, and potential tissue accumulation of neotame.

   c. Effect of neotame on drug metabolizing enzymes

   d. Metabolites of neotame

   2. Critical Toxicology Studies and Issues

   a. A 2-generation reproduction study in the rat--neurotoxicity and behavioral effects

   b. Chronic (52-week) dog study--toxicological significance of elevated serum (hepatic) alkaline phosphatase levels

   c. A 104-week mouse carcinogenicity study--body weight gain decrement effect

   d. A 104-week rat carcinogenicity study--body weight gain decrement effect at all dose levels tested

   e. Chronic (52-week) rat feeding study--body weight gain decrement effect f. Clinical studies assessments--human tolerance to neotame D. Estimating an Acceptable Daily Intake for Neotame

3. Comments
   
4. Conclusion
   
5. Environmental Effects
   
6. Paperwork Reduction Act of 1995
   
7. References
   
8. Objections