aspartameNM : Message: critique of aspartame review, French Food Safety Agency AFSSA 2002.05.07 aspartamgb.pdf (18 pages, in English), Martin Hirsch: Murray 2004.04.13

http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA 2002.05.07
aspartamgb.pdf (18 pages, in English), Martin Hirsch: Murray 2004.04.13

[ Without changing text, I have converted this to plain text, so it can be
put out widely on the world Net, corrected minor typos, and added spacing to
increase the readability of the dense scientific prose. My comments are in
square brackets.

Now Secretary of Defense, Rumsfeld has neither warned his country nor
President Bush, who uses diet soda and has typical symptoms, such as
troublesome knee pain:
http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

Col. Richard Jay Tubb, MD MC, USAF, SFS
Physician to the President
White House Medical Unit #105
Washington., D.C. 20502
202-757-2481 202-757-2483 fax
Family Practice, Alexandria, VA 22312

Creppy EE, Baudrimont I, Betbeder AM. How aspartame prevents the toxicity of
ochratoxin. A. J. Toxicol. Sci., 1998, 23(suppl 2), 165-172.
Department of Toxicology, Laboratory of Toxicology and Applied Hygiene,
University Victor Segalen Bordeaux 2, 146, rue Leo-Saignat, 33076 Bordeaux,
France. edmond.creppy@... ]

http://www.afssa.fr/ftp/basedoc/aspartamgb.pdf
http://www.afssa.fr/ftp/afssa/basedoc/aspartam%202002aaat2000sa0249.pdf

Agence française de sécurité sanitaire des aliments AFSSA
27/31, avenue du général Leclerc - BP 19 - 94701 Maisons-Alfort
Tél: +33(0) 1 49 77 13 50 - Fax: +33(0) 1 49 77 26 12
Mél: wb.internet@... ;

andre.lhoir@...:
johan.vancalster@... ;
lionel.laurier@... ;
danoneinstituteworldwide@...;
laplace@... ; Societe Francaise de Nutrition SFN
cerdacc@...; Le Journal des Accidents et des Catastrophes
tex@... ;
paul.bowden@... ; +44 20 7832 7273
anja.van-impe@... ;

Maisons-Alfort May 7, 2002 French Food Safety Agency

ASSESSMENT REPORT
by Martin Hirsch, AFSSA Director ( started 1999 ) m.hirsch@...

[
http://www.iutcolmar.uha.fr/internet/recherche/Jcerdacc.nsf/0/e575c5a0ca5197bac1\
256ba40026ac0f?OpenDocument
Author of the book "These fears which control us" (see Lu for you ), Martin
Hirsch is a general manager of the French Agency of Medical Safety of Food
(AFSSA), an organization to which the JAC often refers. It seemed to us
interesting to go to discovered from this man who with the obviousness knows
that each opinion of the AFSSA is watched for, weighed up, commented on,
vilified, encensé according to interests' of the ones and others.

Neurobiologist of formation, énarque (promotion Jean Monnet), Martin Hirsch
directed himself towards the Council of State of which it is Maitre of
requests. This senior civil servant of the State, noticed by Bernard
Kouchner became his principal private secretary of 1997 to 1999 before
endorsing the responsibilities for first general manager of the AFSSA as of
his creation in 1999. Incidentally - if one dares to write Martin Hirsch is
also a president of the central Union of the Emmaüs communities which caps
more than 30 Emmaüs communities in France.

Is this book that you have just written a valve with possible frustrations
which you could test?
- Oh not. I believe that it is the complement essential to my work. There
are keys which I know, I wished to deliver them to the public with the most
possible accuracy. It is to some extent like an external control!

Are contaminated blood, ESB, légionelle, listéria, OGM, foot-and-mouth
disease etc... Where us today in France?
- is to the scientists to be able to explain, to justify. In any case, we
have a real scientific independence. Each one of these subjects was
loccasion to learn the lessons on lefficacity from our medical protection
system. The work of the AFSSA is to be there the bridge between these
subjects and the whatever the difficulty, field realities which arise and
with a real scientific independence. And you think well that it is difficult
also to articulate the scientific work which we make with the requirements
of the policy.

Which is your major concern as regards food safety in next times?
- I see at least three of them who occupy us. The nutrition and worrying
lévolution of obesity, the unknown factors on let us request because we do
not have enough retreat yet on this subject and the contaminant agents, the
such possible dioxane and their bonds with carcinogenic risks.

For some time one attends a true explosion of the lawsuits. There how do you
see the role of justice in these cases?
- justice must have a well defined role of sanction of the faults. It nest
not in itself a medical instrument of safety. There should be dautres modes
of controls, devaluation of the led policies, which I estimate for my
essential part to avoid drifts.

In your work, you evoke new modes of consultation. What understand exactly
by there?
- All the means which make it possible not to impose a choice but to combine
collective management of the risks and several liability. They can take
several forms, as the success of the conferences citoyennes shows it on the
OGM.

You are with the head of some 800 collaborators of which many scientists
(and of a budget of 90 million euros note). Which are the relationship
between them and the political world?
- It is before a a whole question of confidence between the two. The rules
of the game were fixed by the policies with the legitimacy of the law. The
scientific organizations, like lAFSSA, thus have a framework clearly
governed by principles: transparency, independence, anticipation,
reactivity.

But you are often taken between the hammer and the anvil. On a side policies
charged to make sometimes hard decisions and other consumers and/or "persons
in charge" for such or such problem?
- Yes, it is true that the AFSSA often was in the heart of significant
subjects, of crises, having taken a scientific dimension, medical, economic,
political, international. It is essential to distinguish these various
stakes and that each actor does his work with full knowledge of the facts
constraints of the others. There are a time for the scientist and another
for the policy.

It is a question of creating a European Agency of food safety. Can you say
some to us a little more?
- It is on the rails since its statute was adopted and that its authorities
are in the course of nomination. It will have, on the level of lUnion, the
same missions about that those of the AFSSA and will be operational as of
the next year.

Always in do your book, you evoke "the work of Sisyphus and - at the
beginnings to have wanted sometimes to throw sponge"?
- It is completely exact. We live within the AFSSA in the permanent concern
to have the best possible analyses of a situation. And with a listened aim
dêtre. And then by definition, when a problem arises, the crisis is not
far. But we are not any more at the beginnings of the AFSSA and our duty is
to take care that our credibility is always justified. ]

Opinion on a possible link between the exposure to aspartame and the
incidence of brain tumours in humans

1 - Context of the request:

The French Food Safety Agency (Agence française de sécurité sanitaire des
aliments; AFSSA) was requested, on October 16, 2000, by the "Direction
générale de la concurrence, de la consommation et de la répression des
fraudes" to assess the possible link between the exposure to aspartame and
the incidence of brain tumours in humans.

Aspartame is authorised in France as a sweetener to be used in table-top
products and in a number of foods (French Official Journal, October 2,
1997).

In articles published in the media and on the Internet (ATIC, 1998),
[ http://www.HolisticMed.com/aspartame 603-225-2100
Aspartame Toxicity Information Center Mark D. Gold
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research" ] consumption of
aspartame has been implicated in the occurrence of a number of adverse
effects in humans.

According to these publications, this sweetener could have toxic effects on
the central nervous system, and, in particular, it might be implicated in an
increase in the incidence of brain cancers in the United States.

This report has been produced by the AFSSA Specialist Experts Committee on
Additives, Flavourings and Processing Aids, based on the available
scientific literature. The aim of this report would be to reassess:
(i) the toxicity of aspartame on the central nervous system in laboratory
animals and in humans,
(ii) the exposure of French consumers to this sweetener and,
(iii) the public health risk related to the consumption of aspartame.

At the European community level, the Scientific Committee on Food (SCF) is
currently conducting an assessment of the scientific data on the effects
attributed to aspartame. This assessment is being conducted by the British
Food Standards Agency (FSA).

Accordingly, the AFSSA and the FSA are working in partnership, with the
AFSSA's contribution on the evaluation of the neurological effects of
aspartame, which will be included in the FSA report.
[ http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall EU Scientific Committee on Food

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/989 On 4.10.2003
the European Union Parliament voted 440 to 20 to approve sucralose,
limit cyclamates & reevaluate aspartame & stevia: Murray 4.12.3 rmforall ]

page 2

2 - Introduction:

Aspartame was discovered in 1965 by a chemist working for the American
company Searle, and an initial marketing authorisation (MA) was granted in
the United States by the Food and Drug Administration (FDA) in 1974.

This MA was suspended a few months later following an appeal against the
authorisation on the grounds that the toxic and carcinogenic effects on the
brain of this compound and its metabolites had not been properly evaluated
during the experimental studies.

[ The flaws in Searle's research were many, manifold, clumsy and obviously
deliberate: http://groups.yahoo.com/group/aspartameNM/message/857
www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31 rmforall

Corporate corruption of government was persistent and remarkably effective:
http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 7.10.0 rmforall

http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall

Now Secretary of Defense, Rumsfeld has neither warned his country nor
President Bush, who uses diet soda and has typical symptoms, such as
troublesome knee pain:
http://groups.yahoo.com/group/aspartameNM/message/927
Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 12.23.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 12.23.2 rmforall ]

Following a reassessment of the studies on experimental animals and an
examination of new data (including a study of carcinogenicity in the rat),
the FDA granted this product a new MA in 1981 (FDA, FR 1981) for use in
solid food. [ This bland statement glosses over the public record that
testifies that Arthur Hull Hayes, Jr., newly appointed by Reagan as FDA
Commissioner, despite lack of qualifications, soon arbitrarily approved
aspartame in July 1981, overruling the vote of his own Scientific Board of
Inquiry. ]

This authorisation was extended to soft drinks in 1983 (FDA, FR 1983) and
for its use as a general sweetener in 1996. [ This was despite an
unprecendented level of citizen and physician complaints of toxic symptoms.
An eminent, distinguished clinician, author of several medical texts and
dozens of clinical research papers in the mainstream medical literature,
describes:

http://groups.yahoo.com/group/aspartameNM/message/669
"Aspartame Disease: An Ignored Epidemic", H.J. Roberts, MD,
1038 page expert magnum opus: Murray 2001.07.05 rmforall

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.

[ http://groups.yahoo.com/group/aspartameNM/message/883
three texts by H.J. Roberts, 1958, 1971, 1979: Murray 1.2.3 rmforall:
FDA Docket 02P-0317 Recall Aspartame as a Neurotoxic Drug

The Countway Libray of Harvard University School of Medicine had about six
copies of Difficult Diagnosis, 1958, when Roberts was 34, and the title page
has a pencil notation, "Reprinted December, 1958".
W.B. Saunders Company Philadelphia, London

[ Roberts says this 913-page tome sold over 60,000 copies.]

Title Page:
Diplomate of the American Board of Internal Medicine;
Fellow of the American College of Chest Physicians;
Associate of the American College of Physicians;
Staff, Good Samaritan Hospital and St. Mary's Hospital,
West Palm Beach, Florida;
Formerly, Research Fellow and Instructor in Medicine,
Tufts University Medical School;
Formerly, Research Fellow and Instructor in Medicine,
Georgetown Medical School.

v Preface
"Was man weiss man sicht"
(What one knows one sees.) Goethe

vii Acknowledgements
[Reviewers listed are Drs. Ralph Myerson, Jacob Neber, Lewis Hurxthal,
Victor McKusick, Mark Lepper, Walter Shelley.

1-8 Introduction
"Satus est initius maderi quam fini"
(It is better to doctor at the beginning than at the end.) Erasmus

"He will manage the cure best who has foreseen what is to happen from
the present state of matters." Hippocrates

In an era which abounds in the mass of medical texts and literature that
is characteristic of ours, I have been asked what the indications for
another volume on medical diagnosis might be (and particularly so in
view of its basic "organic" orientation). Accordingly, I am taking the
author's prerogative in this introduction to set forth those considerations
which not only prompted me to attempt such a treatise, but which also served
as guides in choosing and assembling its present content and form.

This book will pesent the system of a practising internist that has
served him well as a valuable and practical Ariadne's guiding thread
through the diagnostic labyrinth of obscure illness. It is not set
forth as a "primer" in diagnostics, even though the author has made
every effort to make the text as readable as possible. Rather, its
orientation is on an advanced postgraduate level for clinicians whose
experience and skepticism will critically dictate to them its place in
the analysis of difficult case material.
Conversely, for one who is not thoroughly grounded in the disciplines of
everyday diagnostics, it is cautioned that there are many potential pitfalls
in this type of medical reading.

I am keenly and humbly cognizant of the many omissions and commissions
the very nature of this book necessitates.
A similar feeling relates to the limitations of knowledge which arise when a
single physician attempts such a comprehensive volume in this age of
multiple authorships. In the final analysis, the present effort stemmed largely
from an admonition similar to that expressed by Hobbes of the importance
"for any man that aspires to true knowlege to examine the definitions of
former authorities; and either to correct them when they are negligently
set down, or make them for himself."

In the course of the practice of medicine, every physician and
consultant encounters problem patients who, after careful history and
examination, appear to be suffering from persistent symptoms of both a
general nature and from those referable to several specific systems of
the body. The routine laboratory and x-ray diagnostic procedures may be
either "negative," "borderline," or "inconclusive." He is then faced
with the problem of: (1) biding his time, hoping that subsequent events
in the clinical course may clarify the nature of the patient's
condition; (2) diagnosings the symptom complex as psychosomatic, if
significant elements of anxiety or depression are present; or (3)
intensively pursuing further diagnostic approaches in the hope that a
specific treatment or prognosis may be more readily ascertained.
It has repeatedly impressed the author that these difficult diagnostic
problems are definitely on the increase in this transitional age of medicine,
characterized as it is by both the continuing effective control of acute
illness and the undeniable emphasis upon disease affecting the middle
and older age groups.

...our ever improving ability to maintain patients with many chronic
disorders in states of relative good health not only introduces the
factor of the known degenerative or malignant complications
characteristic of these disorders-- as is so well exemplified in the
instances of diabetes mellitus and pernicious anemia-- but also, the
masking effect of a second and unrelated disease once the "tag" of the
initial condition is applied...

...It is apparent that both study and experience are prerequisites for
the complete disclosure of clinical details, and especially the
employment of this form of analysis, since lacking knowledge of any
given disease, one would obviously not know how to seek out its
manifestations...

One must naturally be aware of the following shortcomings in the
approach to diagnostics used here.
The wizened and humble diagnostician appreciates more than do most others
Oscar Wilde's quip to the effect that
"experience is the name everyone gives to his mistakes."

First, as a result of his reading and training, particularly at
clinicopathologic conferences, the physician tends to attribute all the
patient's symptoms to one disease entity. By following this pedagogic
rule too closely in practice, he may readily overlook other concomitant
and treatable organic or emotional afflictions.

Secondly, the temptation might occur to "fit the patient to the disease."
This is an unfortunate situation if in either the "riding of
a hobby" or the "grasping at straws," one overlooks the more common and
probable conditions, and subjects his patients to undue expense, anxiety and
potential physical danger (as with excessive diagnostic radiation or
from anaphylactoid reactions to test substances)...

Thirdly, these can be no short cuts to accurate diagnosis without the
collection and careful, systematic and logical analysis of as many facts as
can be obtained concerning a given case, depending on both circumstances and
the urgency of the problem.
It is apparent that those clinicians who enjoy the respect of their
colleagues as astute diagnosticians usually achieve this status primarily as
a result of the time and interest they give their patients.
This does not doubt the propriety for the clinician of experience to
occasionally trust and respect his intuitive "hunch" about the nature and
management of an obscure illness. In fact, such perception is often necessary,
so that a seriously ill patient will not suffer further from
over-rationalized diagnosis or treatment...

Bearing all these considerations in mind, one stands to gain much from
this type of orientation and aid in diagnostics. Most significant of
all is the possible opportunity afforded of being able to offer the
patient with an obscure symptom complex a specific therapy-- if not a
cure-- when others have not been able to do so because of an incorrect
diagnosis. The continual improvement of one's diagnostic skills derived
from "pearls" relating to history taking and physical diagnosis, along
with the capacity of being able to extract the greatest help from the
least amount of laboratory work, is inherent in this attitude.
Finally, as he reads the literature with greater interest and keenness in an
active attempt to add constantly to this foundation, one succeeds in
evolving a truly personal and integrated approach to the diagnostics of
medicine.

...I am in general accord with Hutchison's "Dont's for Diagnosticians,"
the first two of which read,
"Don't be too clever" and "Don't diagnose rarities."...

11-559 Part I: Groupings of related diseases frequently producing
puzzling illness [17 groupings]

after 514, An atlas of systemic dermadromes
[64 pages of graphic photos, color and black & white]

560-663 References for Part I [104 pages]

667-913 Part II. A classification and analysis of useful
diagnostic procedures [Introduction and 16 Sections]

831-850 References for Part II [20 pages]

851-874 Index of signs, symptoms, and laboratory manifestations

875-913 General index [39 pages]

[ I have selected items that show the immense scope of this highly
successful work, and the capacity of mind, memory, originality, will,
and ethical depth of the author. If aspartame toxicity is indeed a
real illness, then Roberts would seem to be fatefully well equipped to
see in his own practice the complex patterns of its signs and signals. ] ]

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 rechallenge 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 grate aspartame "victims" and their
families dispelled my earlier misgivingts 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, antistatic 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. ] ]

The safety of aspartame has been assessed and recognised by a number of
other national and international organisations including the FAO/WHO
Committee of Experts on Food Additives (JECFA) and, at EU level, by the
Scientific Committee on Food.
It was authorised by Directive 94/35/EC of the European Parliament and of
the Council on sweeteners for use in foodstuffs (adopted on 30 June 1994)
and its use is permitted in more than 90 countries.
In France, aspartame has been permitted since 1988.

The Acceptable Daily Intake (ADI) of aspartame for humans was fixed at 40
mg/kg body weight/day by the JECFA (1980). [ The USA FDA ADI is 50 mg/kg
body weight/day, 25% more.
This was arrived at from animal studies, not by direct assessments of the
actual disposition and accumulation over years in human tissues of the
highly toxic metabolites, formaldehyde and formic acid, from the 11%
methanol component of aspartame in heavy users.
Such data, if ever actually measured, has never been published.
Only misleading information about blood levels, using outdated and
insensitive assays, has been piously offered up to reassure and mislead
people and physicians alike.
The pro-aspartame reviews always assume the ADA is a given, and thus avoid
raising any questions as to its possible deficiencies.
This closing off of important, critical lines of legitimate inquiry
paralyzes any fundamental progress in the polarized arena of aspartame
toxicity research, resulting in the striking lack of progress and current
work in a field that
demands competent, priority attention for the world public health and
welfare. ]

In 1996, an article by J.W. Olney, suggesting a link between an increased
incidence of brain tumours in the United States and the marketing of
aspartame, relaunched the debate on the risks to human health posed by its
consumption.

The debate has been covered by the media, notably on the Internet where
several thousand websites are devoted to the effects of aspartame. These
contain allegations claiming that this additive is responsible for a large
number of adverse effects (more than fifty), some of which are very serious,
such as: multiple sclerosis, lupus erythematosus, Gulf War syndrome, brain
tumours, epileptic seizures, complications of diabetes, etc.

[ http://google.com gives 221,000 websites for "aspartame" , with the top
9 of 10 listings being anti-aspartame, while
http://groups.google.com finds on 700 MB of posts from 20 years of
Usenet groups, 83,800 posts, the top 10 being anti-aspartame.
http://news.google.com 28 recent aspartame items from 4500 sources.
http://www.AllTheWeb.com gives 291,700, the top 7 of 10 being
leading and very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp gives 85,700 websites, top 8 of 10 anti.
http://www.ncbi.nlm.nih.gov/PubMed lists 753 aspartame items.

http://groups.yahoo.com/group/aspartameNM/messages
for 1070 posts in a public searchable archive 123 members

http://groups.yahoo.com/group/aspartame/messages 778 with 16,757 posts ]

At the same time, the health authorities in a number of countries have
reacted by informing the public on the studies available or underway and on
the data based on scientific evidence.

[ http://groups.yahoo.com/group/aspartameNM/message/1018
aspartame toxicity coverup increases danger of corporate meltdown:
Michael C. Carakostas of Coca-Cola: Murray 8.11.3 rmforall
http://www.isrtp.org/new_members/members1.htm
The International Society of Regulatory Toxicology and Pharmacology
Carakostas, Michael C., DVM, PhD Director/Scientific & Regulatory
Affairs The Coca-Cola Company PO Drawer 1734 Atlanta, GA 30301
T. 404/676-4234 F. 404/676-7166 E-mail: mcarakostas@...
http://www2.coca-cola.com/ourcompany/columns_aspartame.html [photo]
Aspartame: The world agrees it's safe By Michael Carakostas, DVM, PhD
Director, Scientific and Regulatory Affairs, Coca-Cola

It is commendable that Carakostas mentions the core problem, albeit
disparagingly: "During digestion, aspartame yields a very small amount
of methanol-- as do many other food substances. The body converts this
methanol to formaldehyde, which is instantly converted to formate.
Formate is quickly eliminated as carbon dioxide and water."

Plenty of evidence in the mainstream scientific literature since 1973 shows
that as much as 30% of the formaldehyde is retained in the body as toxic,
cumulative adducts to the DNA, RNA, and proteins in all cells and tissues,
leading to pointed reports by informed doctors and experts.
Clearly, there are no safe levels for chronic, low-level formaldehyde
exposure. If just 10% of the methanol from six cans of diet soda is
retained in the body as toxic products of formaldehyde and formic acid, that
is sixty times the EPA limit for allowable formaldehyde from daily drinking
water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.

http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 4.3.4 rmforall ]

Following a recap of the physical and chemical properties of aspartame, this
report will review,
firstly, the available toxicological and epidemiological data on the
effects of this additive on the nervous system (cancer and seizures) and
secondly, the estimates of the consumption of this sweetener by the
general population and
by specific populations such as children and diabetic adolescents.
For these specific populations, there may be a potential risk arising from
heavy consumption, low body mass
or finally, a special metabolic susceptibility.

3 - Identity, physical and chemical properties and stability of aspartame:

The E number of aspartame in France and Europe is E 951. It was first
marketed by NutraSweet AG and more recently by Ajinomoto and Holland
Sweetener Company.

This sweetener is incorporated into a number of foodstuffs (drinks,
desserts, sweets, etc.) and in table sweeteners, under the name Canderel,
Pouss'suc and into some 600 medicines; this report does not consider the
possible intake (very limited compared with dietary intake) of aspartame
from this later source.
[ http://www.beautycenter.co.uk/fiche_produit.php?id_article=2115
Pouss'suc: Table sweetener in tablet form, containing aspartame.
Packaging: plastic dispenser box..
Counter-indications: children under 3. Precautions: contains
phenylalanine.
Ingredients : glycine, carboxyméthylcellulose, aspartame 18 mg, L-leucine.
Laboratoire : Hermes Edulcorants ]

Its sweetening power is 180 to 200 times greater than that of saccharose.
[ saccharine ]

page 3

Aspartame is a dipeptide methyl ester of L-aspartyl-L-phenylalanine. It is a
white, odourless, crystalline powder. Its molecular weight is 294.3 Daltons
and its rotatory power [á]D 22 = 2.3° in 1M HCl.
CH
C
NH2
O
NH
CH CH2
C
O
CH3
O
aspartic acid
methyl ester
phenylalanine
H2C C
OH
O

Its main impurity (approximately 2%) is diketopiperazine, a degradation
product of aspartame, which has no sweetening properties.

The solubility of aspartame in water is dependent on pH and temperature, the
maximum solubility is reached at pH 2.2 (20 mg/ml at 25°C) and the minimum
solubility at pH 5.2 (pHi) is 13.5 mg/ml at 25°C.

The stability of aspartame is dependent on time, temperature, pH and water
activity (Dziezak, 1986; Bell et al., 1991; Tsoubeli et al., 1991; Homler,
1984; Graves et al., 1987; Huang et al., 1987; Neiderauer, 1998).

Aspartame is very stable in the dry state: at 105°C a loss of approximately
5% (formation of diketopiperazine) is observed after 100 hours of treatment.
At 120°C, a 50% loss is obtained after 80 hours of treatment.

In solution, when stored at temperatures ranging from 30 to 80°C, aspartame
is progressively degraded into diketopiperazine (Pattanaargson et al.,
2000).
It is therefore not usable in foods heated at higher temperature (cooking,
sterilisation, etc.).

At room temperature its stability is good at pH values of between 3.4 and 5
and it is maximum at pH 4.3. At pH below 3.4 the dipeptide is hydrolysed
and at a pH greater than 5, cyclisation occurs with the formation of
diketopiperazine.
In both cases, this transformation results in the loss of sweetness.

page 4

HO
C
O
CH2 CH
C
NH2
O
NH
CH CH2
C
O O CH3
HO
C
O
CH2 CH
C
NH2
O
NH
CH CH2
C
O O H
+ CH3OH
aspartame
HO
C
O
CH2 CH
C
NH
O
NH
CH CH2
C
O
HO
C
O
CH2 CH
C
NH2
O
NH2
CH CH2
C O
O H
OH
phenylalanine
aspartic acid
H2O
H2O

L-aspartyl-L-phenylalanine

diketopiperazine derivative

In foods with a low or moderate water content (water activities between 0.34
and 0.66), the maximum stability is observed at pH 5.0.

Aspartame has good stability in deep frozen products.

4 - Metabolism and toxicology:

Both in laboratory animals and in humans, aspartame is metabolised in the
gastrointestinal tractus into methanol, aspartic acid and phenylalanine.

On a weight basis, metabolism of aspartame generates approximately 50%
phenylalanine, 40% aspartic acid and 10% methanol. [ 11% exactly ]

Metabolism occurs in the intestinal lumen and in the enterocytes (Karim et
al., 1996; Stegink et al., 1996).

It has been reported that a small proportion of the aspartame (10-12% of the
intake) might be absorbed without metabolisation but this result requires
confirmation (Creppy et al., 1998).
[ Creppy EE, Baudrimont I, Betbeder AM. How aspartame prevents the toxicity
of ochratoxin. A. J. Toxicol. Sci., 1998, 23(suppl 2), 165-172.
Department of Toxicology, Laboratory of Toxicology and Applied Hygiene,
University Victor Segalen Bordeaux 2, 146, rue Leo-Saignat, 33076 Bordeaux,
France. edmond.creppy@...

"The protective effects of aspartame on OTA-induced nephrotoxicity could be
based on several mechanisms related to competitive binding to plasma
proteins, to transport or tissue distribution in the kidney..."
This quixotic claim amounts to using one deadly toxin to interfere with
another, similar toxin, and, in addition, gives evidence that aspartame is a
complex drug, not a "food additive", with largely unknown effects in humans.

Arch Toxicol. 2001 May; 75(3): 176-83.
Aspartame prevents the karyomegaly induced by ochratoxin A in rat kidney.
Baudrimont I, Sostaric B, Yenot C, Betbeder AM, Dano-Djedje S, Sanni A,
Steyn PS, Creppy EE.
UFR des Sciences Pharmaceutiques, Universite Victor Segalen, Bordeaux,
France. isabelle.baudrimont@...

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well
as other moulds.
This mycotoxin contaminates animal feed and food. OTA is immunosuppressive,
genotoxic, teratogenic, carcinogenic and is nephrotoxic in all animal
species studied so far.
OTA inhibits protein synthesis and induces lipid peroxidation.
Since it seems impossible to avoid completely contamination of foodstuffs by
toxigenic fungi, it is necessary to investigate the possible ways of
limiting such toxicity.
An attempt to prevent OTA-induced nephrotoxic and genotoxic effects, mainly
the karyomegaly, has been made in vivo using aspartame
(L-aspartyl-L-phenylalanine methyl ester), a structural analogue of both OTA
and phenylalanine.
Aspartame (25 mg/kg body weight) prevented most of the nephrotoxic effects
induced by OTA (289 microg/kg body weight).
It also showed some utility in preventing morphological and histological
damage, mainly the karyomegaly.
The protective effects of aspartame on OTA-induced nephrotoxicity could be
based on several mechanisms related to competitive binding to plasma
proteins, to transport or tissue distribution in the kidney or to the
elimination of the toxin in the urine. PMID: 11409539

"Obviously the molecular mechanism mediating the preventive effect of
Aspartame is the delivery of phenylalanine by cleavage of the peptide but
also the direct effect of the peptide on the bending capacity and transport
of the toxin in vivo and in vitro.
As a matter of fact when Aspartame is given to animals or added in culture
medium the amount of peptide found unchanged (10-15%) may account for a
preventive effect as entire peptide. "

J Toxicol Sci. 1998 Jul; 23 Suppl 2: 165-72.
How aspartame prevents the toxicity of ochratoxin A.
Creppy EE, Baudrimont I, Anne-Marie.
Toxicology Department, University of Bordeaux, France.

The ubiquitous mycotoxin ochratoxin A (OTA) is found as a frequent
contaminant of a large variety of food and feed and beverage such as beer,
coffee and wine.
It is produced as a secondary metabolite of moulds from Aspergillus and
Penicillium genera.
Ochratoxin A has been shown experimentally to inhibit protein synthesis by
competition with phenylalanine its structural analogue and also to enhance
oxygen reactive radicals production.
The combination of these basic mechanisms with the unusual long plasma
half-life time (35 days in non-human primates and in humans), the
metabolisation of OTA into still active derivatives and glutathione
conjugate both potentially reactive with cellular macromolecules including
DNA could explain the multiple toxic effects, cytotoxicity, teratogenicity,
genotoxicity, mutagenicity and carcinogenicity.
A relation was first recognised between exposure to OTA in the Balkan
geographical area and Balkan Endemic Nephropathy (BEN) with a high incidence
(nearly 50 times higher than normal) of urinary tract tumours. Exposure
rates of OTA are measurable in blood of humans and animals and are
established in several countries including Scandinavia, Germany, France,
Italy, Canada, Japan and Northern Africa mainly Tunisia and Egypt.
The impact of OTA exposure in non- endemic areas in the world is not known,
the rates of exposure being not correlated with the disease records,
especially in developed countries, due to lake of well- designed
epidemiological studies, genetic polymorphism and maybe to dietary contents
of radical scavengers and antioxidants.
However the incidence and mortality rates of renal cancer are increasing in
European countries and Northern Africa which could be a global resultant of
human exposure to natural compounds in food such as mycotoxins and
especially ochratoxin A.
In addition to special care to prevent the growth of moulds and
detoxification measures there was a need for the prevention of the
OTA-induced toxic effects once the toxin is ingested.
For this purpose several compound have been studied including some
therapeutic agents such as piroxicam which cannot be proposed for a large
scale use in humans for preventive purpose.
Among other compounds, Aspartame, already used as sweetener has shown a real
effectiveness in vivo confirmed largely in vitro.
When rats exposed to OTA (289 micrograms/kg) by oral route every two days
are given 25 mg/kg similarly for several weeks, all the toxic effects
including genotoxicity are very efficiently prevented as shown for example
by the disappearance of DNA- adducts in tissues excised from treated
animals.
Aspartame is also effective in washing out the toxin when given afterwards
to animals intoxicated by the same OTA doses for several weeks.
In vitro, provided that it is added in cell culture medium before OTA it
prevents significantly the inhibition of protein synthesis and lipid
peroxidation induced by the toxin.
Obviously the molecular mechanism mediating the preventive effect of
Aspartame is the delivery of phenylalanine by cleavage of the peptide but
also the direct effect of the peptide on the bending capacity and transport
of the toxin in vivo and in vitro.
As a matter of fact when Aspartame is given to animals or added in culture
medium the amount of peptide found unchanged (10-15%) may account for a
preventive effect as entire peptide. PMID: 9760456

Hum Exp Toxicol. 1998 Jul; 17(7): 380-6.
Subchronic effects of ochratoxin A on young adult rat brain and partial
prevention by aspartame, a sweetener.
Belmadani A, Tramu G, Betbeder AM, Creppy EE.
Laboratory of Toxicology and Applied Hygiene, Bordeaux, France.

1. Ochratoxin A (OTA) is a mycotoxin produced by several fungi, especially
Aspergillus and Penicillium species.
Many food and foodstuffs can be contaminated by ochratoxin A, which is
consequently found in blood of animals and humans.
2. The distribution into the brain of young adult rats fed OTA for 1 to 6
weeks and some consequences have been investigated in the present study.
3. Our results on rats given OTA (289 microg/kg/48 h) indicated that OTA
accumulated in the whole brain as function of time according to a regression
curve, Y=-8.723 a+16.72 with a correlation coefficient of r=0.989, where
Y-axis is the OTA concentration in ng/g of brain and X-axis is the duration
of the treatment in weeks.
The brain OTA contents was 11.95 +/- 2.2, 23.89 +/- 4.4, 39.9 +/- 4.5, 50.3
+/- 7.3, 78.8 +/- 6.3, 94 +/- 16 ng/g of brain in the mycotoxin-treated
animals for respectively 1, 2, 3, 4, 5 and 6-weeks treatment.
OTA induced modifications of free amino-acid concentrations in the brain,
mainly, Tyrosine (Tyr) and phenylalanine (Phe).
Tyr decreased significantly as compared to control (p < 0.05).
Phe increased significantly as compared to control (p < 0.05).
4. Aspartame, (25 mg/kg/48 h) a structural analogue of OTA largely modified
the distribution and prevented the accumulation of OTA in the brain since
the respective brain OTA contents decreased respectively to 9.6 +/- 7.9,
19.2 +/- 3.0, 26.8 +/- 4.2, 19.7 +/- 1.9, 13.7 /- 5.6 and 11.0 +/- 6.0 ng/g of
tissue, for the same duration of treatment.
It also prevented the modifications of Tyr and Phe levels.
5. The histological investigations showed several necrotic cells with
pyknotic nucleus, detected in OTA treated animals with higher frequency as
compared to the controls and Aspartame treated ones.
Aspartame appeared to significantly prevent this nuclear effect as well, the
meaning of which is discussed. PMID: 9726534

Arch Toxicol. 1997; 71(5): 290-8.
Reduction of the ochratoxin A-induced cytotoxicity in Vero cells by
aspartame.
Baudrimont I, Betbeder AM, Creppy EE.
Laboratoire de Toxicologie et d'Hygiene Appliquee, Universite de Bordeaux 2,
France.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well
as other moulds.
This mycotoxin contaminates animal feed and human food and is nephrotoxic
for all animal species studied so far.
OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic.
Recently lipid peroxidation induced by OTA has been reported.
OTA, a structural analogue of phenylalanine, inhibits protein synthesis by
competition with phenylalanine in the phenylalanine-tRNA aminoacylation
reaction, constituting the main mechanism of OTA-induced cytotoxicity.
Since it seems impossible to avoid contamination of foodstuffs by toxigenic
fungi, investigation is required for preventing the toxicity of OTA.
An attempt to prevent its toxic effect, mainly the inhibition of protein
synthesis, has been made using aspartame (L-aspartyl-L-phenylalanine methyl
ester) a structural analogue of both OTA and phenylalanine.
Protein synthesis was assayed in monkey kidney cells (Vero cells) treated by
increasing concentrations of OTA (10-100 microM).
After 24 h incubation, protein synthesis was inhibited by OTA in a
concentration dependent manner (the 50% inhibitory concentration, IC50, was
c. 14.5 microM).
Aspartame (A19), at tenfold higher concentrations than OTA (100-1000
microM), was found to partially protect against the OTA-induced inhibition
of protein synthesis in Vero cells, and more efficiently when added 24 h
prior to the toxin (IC50 34 microM) than together (IC50 22 microM).
As expected A19(250 microM) prevented the OTA-induced leakage of certain
enzymes, including lactate dehydrogenase, gamma-glutamyl transferase,
alkaline phosphatase, into the culture medium, and the concomitant decrease
of their intracellular activity in OTA (25 microM)-treated cells.
In order to investigate the effect of aspartame (A19) on OTA-protein binding
as explanation of the above results, the mycotoxin time- and
concentration-dependent binding to human samples was studied in static
diffusion cells with two compartments separated by a dialysis membrane.
When A19 (34 microM) was added to the upper compartment containing plasma
before installing OTA (50, 250, 1240 microM) in the lower one, OTA binding
was largely prevented (95-98%).
When A19 (34 microM) was added to the lower compartment simultaneously with
the toxin (50, 250, 1240 microM), for the lowest concentration of OTA, the
same efficiency was shown in preventing OTA binding, but at the two high
concentrations A19 seemed less efficient. PMID: 9137807

Food Addit Contam. 1996; 13 Suppl: 51-2.
Aspartame as a preventive agent of chronic toxic effects of ochratoxin A in
experimental animals.
Creppy EE, Baudrimont I, Belmadani A, Betbeder AM.
University of Bordeaux 2, Toxicology Department, France.
Publication Types: Review Review, Tutorial PMID: 8972353 ]

4.1 - Long term toxicity and carcinogenicity of aspartame:

Experimental data:

Aspartame is not genotoxic in a reverse mutation test on S. typhimurium, in
two chromosome aberration tests in vivo on somatic cells and in Rodent
dominant lethal test on germ cells (JECFA, 1980).

Recently, two studies have confirmed the absence of clastogenic potential
(Durnev et al., 1995; Mukhopadhyay et al., 2000) of the compound.

In a carcinogenicity study on CD-1 mice (FDA, FR 1981), aspartame
administered in feed at doses of 1, 2 and 4 g/kg bw./day for 110 weeks,
showed no carcinogenic potential.

page 5

Three carcinogenicity studies were conducted in Sprague Dawley and Wistar
rats.

In the first study (1973), post-weaning Sprague Dawley rats were fed doses
of aspartame corresponding to 1, 2, 4, 6/8 g/kg bw./day for 104 weeks (6/8
i.e. dose of 6 was increased during the study to 8 g/kg bw./day).

In the second study (1974), male and female Sprague Dawley rats, from a
two generation study, were exposed during gestation, lactation and after
weaning for 104 weeks, to doses of 0, 2 and 4 g/kg bw./day in their food.

The results of these two studies have been widely discussed by the
scientific community and the regulatory authorities (FDA).

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

In the first study, the incidence of brain tumours in the treated animals
was higher than in the control animals but without any dose response
relationship.

In contrast, in the second study the incidence of tumours in the treated
rats was lower than in the control group.

For these reasons, a third study was conducted under conditions of Good
Laboratory Practice in order to ensure the reliability of the experimental
data.

In this third study (Ishii, 1981), groups of male and female Wistar rats
were given doses of aspartame of 0, 1, 2, 4 g/kg bw./day for 104 weeks.
[ study done in an Anjinomoto lab ]

Under these conditions, aspartame did not cause any increase in the
incidence of brain tumours.

Taking into account all the studies that have been conducted, the frequency
of spontaneous tumours in laboratory rats, the types of tumours observed and
the absence of a dose-response relationship, it was concluded that aspartame
had no carcinogenic potential on the brain in experimental animals (FDA FR,
1981-1984; Koestner, 1984; Cornell et al., 1984; Flamm, 1997).

[ A number of studies undermine this complacent picture.

It is certain that high levels of aspartame use, above 2 liters daily for
months and years, must lead to chronic formaldehyde-formic acid toxicity,
since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz cans) is 123 mg
methanol (wood alcohol), immediately released into the body after drinking
(unlike the large levels of methanol locked up in molecules inside many
fruits), then quickly transformed into formaldehyde, which in turn becomes
formic acid, both of which in time are partially eliminated as carbon
dioxide and water.

However, about 30% of the methanol remains in the body as cumulative
durable toxic metabolites of formaldehyde and formic acid-- 37 mg daily,
a gram every month. [ Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
J. Nutrition 1973 Oct; 103(10): 1454-1459. ]
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in water.

Bear in mind that the EPA limit for formaldehyde in drinking water is
1 ppm, or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical patterns of
increasingly severe complex symptoms, starting with headache, fatigue, joint
pain, irritability, memory loss, and leading to vision and eye problems, and
even seizures. In many cases there is addiction. Probably there are immune
system disorders, with a hypersensitivity to these toxins and other
chemicals.

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put into
the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little
additional elimination, as carbon dioxide in exhaled air and as water in
the urine.
They did not mention that this meant that about 30% of the methanol must
transform into formaldehyde and then into formic acid, both of which must
remain as toxic products in all parts of the body.
They did not report any studies on the distribution of radioactivity in body
tissues, except that blood plasma proteins after 4 days held 4% of the
initial methanol.
This study did not monitor long-term use of aspartame.

The low oral dose of aspartame and for methanol was 0.068 mmol/kg, about 1
part per million [ppm] of the acute toxicity level of 2,000 mg/kg, 67,000
mmol/kg, used by McMartin (1979).
Two L daily use of diet soda provides 123 mg methanol, 2 mg/kg for a 60 kg
person, a dose of 67 mmole/kg, a thousand times more than the dose in this
study.
By eight hours excretion of the dose in air and urine had leveled off at
67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine, so 68.7
% was excreted, and 31.3% was retained.
This data is the average of 4 monkeys.
"...the 14C in the feces was negligible."
"That fraction not so excreted (about 31%) was converted to body
constituents through the one-carbon metabolic pool."
"All radioactivity measurements were counted to +-1% accuracy..."
This indicates that the results could not be claimed to have a precision of
a tenth of a percent. OK, so this is a nit-pick-- but I believe espousing
spurious accuracy is a sign of scientific insecurity.

The abstract ends, "It was concluded that aspartame was digested to its
three constituents that were then absorbed as natural constituents of the
diet."
Thus, the concept is very subtly insinuated that methanol, as a constituent
of aspartame, is absorbed as a natural constituent of the diet.
"Dietary methanol is derived in large part from fresh fruits and
vetetables."
This is a serious error, since the large amounts of methanol in fresh fruits
and vegetables are not readily released by human digestion. (W. C. Monte,
1984)
Nowhere in this report are mentioned the dread words, "formaldehyde" and
"formic acid".

The same three reserchers, plus F.G. McMahon of Tulane University Medical
School, published a follow-up study, "Comparative metabolism of aspartame in
experimental animals and humans",
J. Toxicology and Environmental Health 2: 441-451, 1976.

The abstract says, "Hydrolysis of the methyl group by intestinal esterases
yielded methanol, which was oxidized in the one-carbon metabolic pool to
CO2."
The inevitable conversion by the liver of methanol into formaldehyde and
formic acid, both potent, cumulative toxins, is simply not even hinted at.
This is clear evidence of a deliberate scientific coverup to advance vested
interests regardless of the cost to public health.

"The hypothetical pathways of metabolism, which aspartame was expected to
follow, are diagrammed in Fig. 1....The principle used to test the validity
of this hypothetical description of the metabolism of aspartame..."

Figure 1. shows in an nice orderly sequence that:
(a) MeOH ---> one-carbon metabolic pool ---> CO2 + formyl metabolites .

Meanwhile, this sentence jumps from p. 441 to 442 under Figure 1., "The
absorbed methanol would be incorporated into the one-carbon pool and would
be converted [ page jump in sentence ] primarily to CO2 (Makar et.al., 1968;
Tephly et al, 1964), although a small fraction might be incorporated into
body constituents."
Again the crucial production of formaldehyde and formic acid are diguised by
the diffident term, on a diagram, "formyl metabolites".
This is shameful science.

The graphs present the same methanol in monkey data as in 1973, but the
nowhere is the specific percentage of exhaled CO2 mentioned.
Methanol and aspartame were also given to a few [ unspecified ] number of
rats: "The major fraction of the 14C was excreted in the expired air (Fig.
2)...Plasma
levels of 14C reached a peak [ absolute data not given ] at about 3 hr..."
[ Important specific data that would allow one to estimate the amount of
retained toxic products of formaldehyde and formic acid in tissues are
omitted. ]

In this follow-up report, for methanol and the methyl group in aspartame,
excretion in urine and feces were not mentioned in either the former monkey
or the new rat studies, the absolute plasma levels were not given, and, of
course, no measures were taken of 14C in body tissues.
The only hint of the possible role of formaldehyde and formic acid was the
rather diffident term "formyl metabolites" in Figure 1.
Overall, we see consistent patterns of avoiding any focus on the actual
disposition of extremely toxic formaldehyde and formic acid, both
persistent and cumulative, products in body tissues.
Subtle equivocation and qualification was expressed by such words as
"hypothetical", "was expected to follow", "would be", "primarily",
"although a small fraction might be incorporated into body constituents",
"major fraction".
Aspartame research sponsored by vested interests has continued ever since to
show evidence of biases that serve vested corporate interests, while
misleading the public and physicians about real, and largely unresearched
toxicity hazards.

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished: http://www.dorway.com/peerrev.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.
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@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

Life Sci 1991; 48(11): 1031-41. The toxicity of methanol. Tephly TR.
Department of Pharmacology, University of Iowa, Iowa City 52242.

"Abstract:
Methanol toxicity in humans and monkeys is characterized by a latent period
of many hours followed by a metabolic acidosis and ocular toxicity.
This is not observed in most lower animals.
The metabolic acidosis and blindness is apparently due to formic acid
accumulation in humans and monkeys, a feature not seen in lower animals.
The accumulation of formate is due to a deficiency in formate metabolism
which is, in turn, related, in part, to low hepatic tetrahydrofolate (H4
folate).
An excellent correlation between hepatic H4 folate and formate oxidation
rates has been shown within and across species.
Thus, humans and monkeys possess low hepatic H4 folate levels, low rates of
formate oxidation and accumulation of formate after methanol.
Formate, itself, produces blindness in monkeys in the absence of metabolic
acidosis.
In addition to low hepatic H4 folate concentrations, monkeys and humans
also have low hepatic 10-formyl H4 folate dehydrogenase levels, the enzyme
which is the ultimate catalyst for conversion of formate to carbon dioxide.
This review presents the basis for the role of folic acid-dependent
reactions in the regulation of methanol toxicity.
Publication Types: Review Review, Academic PMID: 1997785"

p. 1035 "In the past, formaldehyde has often been suggested as the methanol
metabolite which produces toxicity (34,35). Today, a great deal of
information is available concerning its lack of such a role. The presence
of elevated formaldehyde levels in body fluids or tissues following methanol
administration has not been observed. No formaldehyde has been detected in
blood, urine or tissues obtained from methanol-treated animals (36,37) and,
in methanol-poisoned humans, formaldehyde increases have not been
observed....
About 85% of a low dose of 14C-formaldehyde [radioactive label] is
excreted as pulmonary 14CO2 (49,50)....."

[ This suggests that 15% of the formaldehyde and its inevitable product,
formic acid, is indeed retained in the body of rats, a very significant
result, considering their extreme, complex, and tenacious toxicity.
Of course, this pro-aspartame stalwart does not direct any attention to this
substantial and unknown 15%.
Note that this is a general review article, widely cited, published in 1991
in Life Sciences, the same journal that bravely accepted the seminal study
by C. Trocho et al (June 26 1998) that proved that aspartame ingestion in
rats leads to formaldehyde adducts, bound to DNA, RNA, and proteins in many
tissues.
It would be naive to accept any research by Tephly and his ilk without
thorough and skeptical scrutiny.
The most dangerous Internet myth is this: "Aspartame is the most thoroughly
tested food additive in history."]

49. W.B. Neely, Biochem. Pharmacol. 13: 1137-1142 (1964).

50. Xenobiotica 1982 Feb; 12(2): 119-24.
Formaldehyde metabolism by the rat: a re-appraisal.
Mashford PM, Jones AR.

Biochemical Pharmcacology 1979: 28; 645-649.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
and Thomas R. Tephly
The Toxicology Center, Dept. of Pharmacology,
University of Iowa, Iowa City, Iowa 52242

K.E. McMartin and T.R. Tephly, authors of many pro-aspartame studies, in
Biochemical Pharmacology (1979) remarked, "It is now generally accepted
that the toxicity of methanol is due to the formation of toxic metabolites,
either formaldehyde or formic acid."
They put damage doses of methanol into the stomachs of three monkeys, and,
using insensitive tests, found no formaldehyde in many tissues-- except for
a single datum in the midbrain, 1.5 times the detection limit.
This certainly suggests that modern, much more sensitive assays would have
found formaldehyde from methanol in many tissues.
They did report widespread accumulation of formic acid in five tissues.
The use of inadequate tests is common in industry research that is funded to
claim the safety of profitable toxins.
Since then, industry scientists have been very wary of doing studies on
primates, which all too easily show the dangers to humans.

Modern studies in Japan have found very high levels of retention of
formaldehyde and its toxic metabolites in humans:

J. D. Thrasher (2001): "The major difference is that the Japanese
demonstrated the incorporation of FA and its metabolites into the placenta and
fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [Ref. 14-16]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH. toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

C. Trocho (1998):
"In all, the rats retained, 6 hours after administration, about 5% of the
label, half of it in the liver."

They used a very low level of aspartame ingestion, 10 mg/kg, for rats, which
have a much greater tolerance for aspartame than humans.
So, the corresponding level for humans would be about 1 or 2 mg/kg. (Many
headache studies in humans used doses of about 30 mg/kg daily.)

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html full text
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo.
Life Sci June 26 1998; 63(5): 337-49.
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 [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544,
FAX: (93)4021559
alemany@... bioq@... josefer@...
rafecas@... remesar@...

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

[ 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."

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte. ]
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@... 919-684-3303, 660-5657

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/846
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: Murray 7.16.2 rmforall

Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research RLipton@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall

Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA. neurotulsa@...
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
gum sweetened with aspartame. [ 6-8 mg aspartame per stick chewing gum ]

Subject: Re: Murray: Butchko:
Tephly: critique of Trocho report Apr 2002 8.29.2
Date: Fri, 30 Aug 2002 09:49:56 +0200
From: Marià Alemany <alemany@...>
To: "Rich Murray" <rmforall@...>
References: 1

Dear Rich,

Thank you for the opportunity to say something about the "paper" by Tephly
that followed our study on the incorporation of aspartame-derived methanol
label into DNA and protein of rats.
I don't know if responding to that publication is worth the effort.

Surprisingly, a serious journal, such as Life Sciences published a rebuttal
of our previous paper as a normal "research paper", but including no new
information neither experimental work.
This is only a sample of the "scientific" power of the advocates of
aspartame.

Anybody can extract conclusions from this anomaly, but it seems to me that
there was nothing new in that pamphlet that may add information to what we
already explained in our paper.
The responses to the questions raised by Tephly are already in our paper,
which means that either that it was not read or, worst, it was misread.

The presence of aspartame-derived label in DNA and protein adducts is
unquestionable and unquestioned, and agrees with previous studies.
Then, what importance has the mechanism of incorporation?
There were adducts, and they represent loss of function and mutation.
That was our thesis.

The reference to previous studies showing very low levels of formaldehyde in
blood do not refute our data.
First of all, measuring formaldehyde is tricky,
and in any case, the circulating levels would be below the current limit of
detection for most of the methods used.
That is the current explanation for the low levels of methanol in plasma
after aspartame loading: they are zero, using most of the methods available
for methanol, since the expected levels are currently below the limit of
detection...

In addition, it is not logical to expect to find measurable levels of
formaldehyde in a medium (blood) containing a huge amount of protein.
Formaldehyde reacts immediately with proteins because it is highly reactive:
that is the reason why we have found it in cell protein and DNA.
It is absurd to expect it to forfeit binding with cell proteins and go all
the way into the bloodstream!
Remember that formaldehyde is used to preserve corpses precisely because it
binds protein (including those of putrefactive bacteria) and prevents its
degradation.

The "alternative" point expressed by Tephly, suggesting that aspartame
methanol-label goes all the way into formic acid and the C1 pathway was
thoroughly refuted by us, using experimental data.
There was no labelled methionine nor thymine in protein and DNA respectively
in the rat protein we recovered from rats treated with aspartame.
This means--unequivocally-- that the label present in DNA and protein
adducts was NOT incorporated into amino acids or nucleic acid bases.
The only explanation for our data was that the label was in the form of
formaldehyde adducts.

If this explanation does not satisfy other scientists, they are free to
repeat the experiment and show where we went wrong, or to probe and prove
experimentally their hypotheses.
Otherwise, our results stand unchecked and, consequently, should be deemed
true.

I hope that this information will help any attentive reader understand why
we have left for good this field of study.

Best regards.
------------------------------
Prof.Dr. Marià Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutrició i Bromatologia
Facultat de Biologia, Universitat de Barcelona
Av. Diagonal, 645; 08028 Barcelona Espanya/España/Spain
tel. +34 93 403 4606; fax: +34 93 403 7064; E-mail: alemany@...

Life Sci 1999; 65(13): PL157-60. [ letter, usually not peer reviewed ]
Comments on the purported generation of formaldehyde and adduct
formation from the sweetener aspartame.
Tephly TR Thomas R. Tephly 319-335-7979 thomas-tephly@...
ttephly@... Department of Pharmacology
The University of Iowa, Iowa City 52242, USA.

A recent paper by Trocho et al. (1) describes experiments meant to show that
formaldehyde adducts are formed when rats are administered the sweetener
aspartame.
These authors assume that the methanol carbon of aspartame generates
formaldehyde which then forms adducts with protein, DNA, and RNA.
Doses employed range widely.
In this letter, studies which have been published previously and which were
not cited by these authors are reviewed in order to put into perspective the
disposition of methanol and formaldehyde in monkeys and humans, species
relevant to the toxicity of methanol and its toxic metabolite, formic acid.
PMID: 10503962, UI: 99431287

[ A number of pro-aspartame studies by Tephly and associates, invariably
funded by the aspartame industry (Monsanto, NutraSweet) are criticized in
detail at:

"Scientific Abuse in Aspartame Research"
http://www.holisticmed.com/aspartame/abuse/methanol.html
Aspartame Toxicity Information Center Mark D. Gold
www.HolisticMed.com/aspartame 603-225-2100
mgold@... 12 East Side Drive #2-18 Concord, NH 03301

Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels.

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.

Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Formaldehyde was administered for 104 weeks in drinking water supplied
ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
rats beginning at six weeks of age at concentrations of 2,500, 1,500,
500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase in total
malignant tumors in the treated groups and showed specific carcinogenic
effects on various organs and tissues. PMID: 12562630

Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
Results of long-term experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@...

Methyl alcohol was administered in drinking water supplied ad libitum at
doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female
Sprague-Dawley rats 8 weeks old at the start of the experiment.
Animals were kept under observation until spontaneous death.
Ethyl alcohol was administered by ingestion in drinking water at a
concentration of 10% or 0% supplied ad libitum to groups of male and
female Sprague-Dawley rats; breeders and offspring were included in the
experiment.
Treatment started at 39 weeks of age (breeders), 7 days before mating,
or from embryo life (offspring) and lasted until their spontaneous death.
Under tested experimental conditions, methyl alcohol and ethyl alcohol
were demonstrated to be carcinogenic for various organs and tissues.
They must also be considered multipotential carcinogenic agents.
In addition to causing other tumors, ethyl alcohol induced malignant
tumors of the oral cavity, tongue, and lips.
These sites have been shown to be target organs in man by epidemiologic
studies. Publication Types: Review Review, Tutorial PMID: 12562628

Surely the authors deliberately emphasized that aspartame is well-known
to be a source of formaldehyde, which is an extremely potent, cumulative
toxin, with complex, multiple effects on all tissues and organs.

This is even more significant, considering that they have already tested
aspartame, but not yet released the results:

p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
Project of [200] Long-Term Carcinogenicity Bioassays: Agents Studied

No. No. of Bioassays Species No. Route of Exposure
108. "Coca-Cola" 4 Rat 1,999 Ingestion, Transplantal Route
109. "Pepsi-Cola" 1 Rat 400 Ingestion
110. Sucrose 1 Rat 400 Ingestion
111. Caffeine 1 Rat 800 Ingestion
112. Aspartame 1 Rat 1,800 Ingestion

http://members.nyas.org/events/conference/conf_02_0429.html
Soffritti said that Coca-Cola showed no carcinogenicity.

It may be time to disclose these important aspartame results.

Finally, an intripid and much published team in Japan has found DNA damage
in 8 tissues from single non-lethal doses of aspartame (near-significant
high levels of DNA damage in 5 tissues) and many other additives in groups
of just 4 mice:

Mutat Res 2002 Aug 26; 519(1-2): 103-19
The comet assay with 8 mouse organs: results with 39 currently used food
additives.
Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K,
Taniguchi K, Tsuda S.
Laboratory of Genotoxicity, Faculty of Chemical and Biological
Engineering, Hachinohe National College of Technology,
Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
yfsasaki-c@... s.tsuda@...

We determined the genotoxicity of 39 chemicals currently in use as food
additives.
They fell into six categories-dyes, color fixatives and
preservatives, preservatives, antioxidants, fungicides, and sweeteners.

We tested groups of four male ddY mice once orally with each additive at
up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet
assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung,
brain, and bone marrow 3 and 24 h after treatment.

Of all the additives, dyes were the most genotoxic.
Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and
Rose Bengal induced dose-related DNA damage in the glandular stomach, colon,
and/or urinary bladder.

All seven dyes induced DNA damage in the gastrointestinal organs at a
low dose (10 or 100mg/kg).

Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced
DNA damage in the colon at close to the acceptable daily intakes (ADIs).

Two antioxidants (butylated hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
o-phenylphenol, and thiabendazole), and four sweeteners (sodium
cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA
damage in gastrointestinal organs.

Based on these results, we believe that more extensive assessment of
food additives in current use is warranted. PMID: 12160896

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall [A detailed look at the data] ]

The Acceptable Daily Intake (ADI) of aspartame for humans was established at
40 mg/kg bw. (JECFA, 1980) based on a no-observed effect level (NOEL) of 4
g/kg of bw./day, which was the highest dose retained during the
carcinogenicity studies in rats, divided by a safety factor of 100.

Epidemiological data:

In 1996, Olney et al. published an article on a possible link between the
increase in the frequency of brain tumours in humans and the consumption of
aspartame in the United States.

Based on the data from the National Cancer Institute (10% of the population)
from 1975- 1992, the authors concluded that there was a significant increase
in the frequency of brain tumours in the mid-1980s, that is to say the
period following aspartame came onto the market.

The conclusions of this epidemiological study have been criticised by a
number of scientists who questioned the methodology, the use of the data and
their interpretation (Levy et al., 1996; Linet et al., 1999; Ross, 1998;
Seife, 1999; Smith et al., 1998).

One of the major criticism is that the authors only took into account the
frequency of brain tumours during a selected period (1975-1992).

When all the epidemiological data are used (1973-1992) a different
conclusion is reached, as the frequency of brain cancers began to increase
in 1973 and stabilised from the mid-1980s (Levy et al., 1996).

Furthermore, Olney et al. did not provide any quantitative or qualitative
relationship between the exposure of the population to aspartame and the
observed frequency of brain tumours.

Finally, an increase in the incidence of the tumours can have many causes
including, among others, improvements in diagnostic methods (Modan et al.,
1992). [ These criticisms of the initial Olney claims are cogent, but
hardly definitive, in view of the fact that M. Soffritti et al in the
extensive Ramazinni Foundation rat studies proved both ingested methanol and
formaldehyde, inevitable products of aspartame, are carcinogenic.
The remarkable Yu F. Sasaki et al results suggests now it would be easy for
any motivated team to prove DNA damage in human white blood cells and other
tissues from formaldehyde and formic acid accumulation from long-term, heavy
use of diet soda, above 6 12-oz cans daily (~2 L).
It is tiresome to see again and again in pro-aspartame "research reviews"
the degree to which provokative and alarming results, old and new, are
dismissed, misinterpreted, or simply ignored.
It is surely easier, and safer for corporate vested interests, for a busy
team player to compose each "new" review by rehashing previous reviews.

http://epi.grants.cancer.gov/ResPort/Biomarkers.html
Technology for DNA Damage Analysis and Biomarkers
X.C. Le, Ph.D. xc.le@...
University of Alberta. Edmonton, Canada
Characterization of environmental determinants of cancer is an important
goal for development of effective public health strategies for cancer
prevention and control.
Informative epidemiological investigations of relationships between the
environment and cancer rely on accurate, quantifiable exposure measurements.
In traditional population surveys that attempt to link a substance with
cancer occurrence, exposure data often is obtained indirectly by
questionnaires or personal interviews.
The uncertainty associated with errors in exposure assessment has obscured
or limited identification of cancer etiologies.
Rather than the current reliance on external dose estimation and
extrapolation from high-dose exposure with rodent models, sufficiently
sensitive biomarkers based on DNA damage measurements could permit more
realistic assessment of environmental risk.
X.C. Le, Ph.D., and colleagues are working to develop innovative,
cost-effective, and reliable technology for quantifying exposures,
especially low-level exposures.
They aim to develop highly sensitive technology for measuring minute amounts
of DNA damage, and improve biomarkers for epidemiological investigations of
environment and cancer relationships.
The technology combines the specificity of antibodies and capillary
electrophoresis separation with the high sensitivity of laser-induced
fluorescence detection.
In addition, specific DNA-recognition proteins will be used to bind with
various DNA lesions to detect a range of DNA lesions.
Automated and high throughput assay formats will be explored that make use
of the high-sensitivity technology. The sensitive DNA damage measurements
will be used as potential biomarkers for exposure assessment.
The technology also will be useful to monitor DNA damage induced by
anticancer agents and to study DNA repair, which is an essential protection
mechanism against cancer initiation. ]

page 6

More recently, Gurney et al., (1997) published the results of a case-control
study on the relationship between the consumption of aspartame and the
frequency of brain tumours.
The study covered 56 patients affected by tumours in childhood and 94
controls. According to these authors, no relationship could be established
between the consumption of aspartame and the frequency of brain tumours.

[ Think about what it took to prove that tobacco causes lung cancer in a
small percentage of long-term, heavy users. People who smoked 2-3 packs
daily for decades had to be carefully surveyed, and all other factors had to
be taken into account.
What can you prove with a one-day, one-week, one-month, or even 1-year study
with 50 to 100 healthy people, often young college students, except that
the incidence of rapid radical harm is not over, say, one in ten such users?
Nothing at all would be established about a possible incidence of one in a
hundred, which would be millions of American victims, suffering from a huge
variety of difficult, puzzling symptoms in all tissues, gradually getting
worse over the months and years-- the legacy to be expected from gradual
accumulation of tissue damage from formaldehyde and formic acid from the 11%
methanol component of aspartame.
Yet a 1% rise in a variety of diseases over, say, ten years, would be
impossible to discern.
Only diligent attention to the complaints of heavy users and their
physicians would discover the reality-- exactly what the Net has made
possible. It is impudent and imprudent to use inadequate
double-blindlaboratory tests to justify wholesale ignoring of the thousands
of case reports. ]

In France, data on the incidence of and mortality from brain cancers were
supplied by the FRANCIM network (F. Ménégoz, 2001).

These cancers include meninges tumours and tumours of the brain itself (see
graphs in the annex).
Between 1980 and 1997, the incidence (number of new cases appearing each
year) of cerebral tumours was relatively stable in men
and showed a slight increase in women.

The trend towards an increase in mortality from cancer of the brain and
other parts of the nervous system is a longstanding one, as it first
appeared in 1950 and continues to the present day, for both sexes.
However, during the last decade, mortality in men stabilised and
the increase in mortality from brain cancer in women was less pronounced
than during the preceding period.

Within this context, it is worth noting that a case-control study is
currently underway in France (CEREPHY - Laboratoire Santé, Travail,
Environnement, Université de Bordeaux II) which concerns the relationship
between brain cancers and exposure to plant protection products and also
lifestyles (including the consumption of sweeteners). The results of this
study could provide additional information and act as a guide for future
epidemiological research.

[ Economic parameters of a checking routine of the additives and food
contaminants (in the sectors: breweries, soft drinks, confectioneries, meat
preparations).
person in charge Prof M. Walter Hecq whecq@...
equip Chang Xing DI Sarah REEVES Paul SAFONOV Ali TAHI
Center economic and social surveys of the environment
such +32-2-650.33.77, fax +32-2-650.46.91, whecq@...
http://www.ulb.ac.be/ceese
Campus of Solbosch , Building S, level 10, local S.10.232
CP124, which occurred F.D. Roosevelt 50, 1050 Brussels

http://www.interdisciplines.org/people/authors/walter_hecq

Dr. Sc J.C. AUBRY, director; L Jacob, associated, ALTEHA, Association of
Laboratories for Toxicological, Environmental and Health Analysis, Brussels,
Belgium ]

Similarly, the results to be published from the epidemiological study
conducted by the National Cancer Institute between 1994 and 1998 will
require careful analysis.

This study has assessed the possible relationship between various factors
(mobile phones, dietary factors such as sweeteners, etc.) and the incidence
of brain tumours in adults.

[ http://www.cspinet.org/reports/saccomnt.htm
CSPI REPORTS October 24, 1997
To: National Toxicology Program Board of Scientific Counselors' Report on
Carcinogens Subcommittee
"The dosages of saccharin that appear to have elicited an effect in small
rodent studies are not much greater than the amounts that some Americans
consume....
Thus, in numerous studies, artificial-sweetener consumption was
associated with significant increased risks of bladder cancer, though there
were inconsistencies in risks to men and women.
Some (mostly smaller) studies did not find an association.
The NTP acknowledges that "a small increased risk in some subgroups, such as
heavy users of artificial sweeteners, cannot be unequivocally excluded."
That is an understatement that could have been expressed equally accurately
as: Several studies found an increased risk in some subgroups, and it is
the subgroup of heavy consumers about whom we should be especially
concerned.

That some studies did not detect an increased risk could be real , or due to
the limited duration of subjects' exposure to artificial sweeteners
-- particularly in light of the long latency period for cancer and the
limited consumption of saccharin in the U.S. before the mid 1960s (many subjects
were exposed for under 15 years in the U.S. studies) --
lack of exposure in utero,
small numbers of cases and limited power to detect small risks,
and loss of sensitivity due to lumping occasional users of artificial
sweeteners in with heavy users.
Those and other limitations reduce the likelihood that saccharin's link to a
higher rate of bladder cancer could be detected.
Furthermore, no epidemiologic research has evaluated whether saccharin might
cause tumors at sites other than the urinary bladder, despite known
differences in organ specificity between species in the case of most
carcinogens.
In light of several rodent studies documenting higher rates of cancer in
other organs, that absence of information is troubling and suggests the need
for more research.
New research would also benefit from the increased duration of exposure to
saccharin."
[ Yu F. Sasaki's team in 2000 used the Comet assay on groups of just 4 mice
to prove substantial DNA damage from single high doses of sucralose,
cyclamate, and saccharin (with near significant high levels of DNA damage
from aspartame in 5 of 8 tested tissues).
This shows how, world-wide, increasingly subtle, complete human
epidemological studies; long-term, large-scale animal exposure experiments;
and extremely fast, sensitive, low-cost assays are simultanously evolving to
make it inevitably easy to definitively test the safety of any possibly
genotoxic drug.
It is high time for everyone involved in the aspartame controversy to alert
these new teams to the urgent need to test aspartame, methanol,
formaldehyde, and formic acid in humans. ]

In France, the epidemiological data from the cancer registers do not enable
a definitive indication to be given on a possible aspartame-brain tumour
relationship, but they do show that, at the present time, the sale of this
food additive in France is not being accompanied by an increase in the
frequency of brain tumours or increased mortality from this disease in the
general population.

4.2 - Relationship between aspartame and epileptic seizures in animals and
humans:

Among the possible adverse effects of aspartame, researchers have paid
particular attention to seizures.

Several studies have suggested a relationship between the consumption of
large amounts of aspartame and the triggering of epileptic seizures.

In an old study (1972), on new-born monkeys (2-3 animals per group) treated
with doses of aspartame of 1, 3 and 4 g/kg bw./day for 52 weeks, epileptic
seizures were recorded at the highest doses, after 218 days of treatment.
Thereafter, sporadic convulsions were observed during handling of the
animals.

These symptoms were identical with those observed in young monkeys
treated with phenylalanine.

In contrast, in a similar study also conducted on young monkeys, no effect
was observed at doses of aspartame of 2 and 2.7 g/kg bw./day.

[ http://groups.yahoo.com/group/aspartameNM/message/857
www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31 rmforall ]

The different results observed in the two studies could be explained by
differences in the exposure conditions, the food and the state of health of
the animals (JECFA, 1980).

Walton et al. (1993) reported, in a study conducted on 13 patients suffering
from depression, that the administration of 30 mg/kg bw./day of aspartame
for 7 days caused severe side effects in these patients which led the
authors to conclude that the use of this sweetener in depressive patients
should be avoided. The same author (Walton, 1986) reported a case of

page 7

epileptic seizure and serious behavioural problems in a woman being treated
with antidepressants who ingested large quantities of tea containing
aspartame.

Wurtman (1985) indicated that the administration of aspartame,
due to an increase in phenylalanine absorption in the brain, could affect
the synthesis of catecholamines or serotonin and cause seizures.

He based his findings on three examples of heavy consumers of "diet" drinks
and on experimental studies on animals demonstrating that the consumption of
aspartame reduced the threshold of sensitivity to chemically induced
seizures (Maher et al., 1987 ; Guiso et al., 1988; Pinto et al., 1988).

Finally Camfield et al. (1992) demonstrated that aspartame could increase
the duration of certain types of epileptic seizure in children.

The ATIC [ Mark Gold's Aspartame Toxicity Information Center ] on the
Internet reported a large amount of evidence from people who have
identified aspartame as the cause of their health problems and in particular
of seizures.

These statements should be taken into account but with the reservation that
they have not been examined according to any academic standard.

They may, however, in certain cases, reflect the hypersensitivity of certain
individuals to aspartame or its metabolites. [ Exactly! ]

Effects on seizures have been reported with phenylalanine, aspartic acid and
methanol but these were under specific conditions (high doses, individual
sensitivity, types of seizures, etc.) which are not representative of the
general population and of current use of this sweetener in food (Anderson et
al., 1996).

This causal relationship between aspartame and epileptic seizures has been
refuted by a large number of scientists who base their opinions on numerous
experimental studies conducted on laboratory animals or on clinical or
tolerance studies in humans (Anderson et al., 1996; Gaull, 1985; Rowan et
al., 1995; Shaywitz et al., 1994; Tollefson et al., 1992; 1993; Dailey et
al., 1991; Zhi et al., 1989; Sze, 1989; Tilson et al., 1989).

[ http://www.HolisticMed.com/aspartame 603-225-2100
Aspartame Toxicity Information Center Mark D. Gold
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research" ]

The Epilepsy Institute in the USA has also concluded that aspartame is not
the cause of epileptic seizures (Congressional Record, June 20, 1986).
[ Anyone who studies the behavior of the Epilepsy Institute, the American
Diabetes Association, the Multiple Sclerosis Association, etc., will find
they regularly deny hazards that are widely discussed on the Net by their
clients. ]

In the United States various consumer complaints about aspartame have been
collected by the Special Nutritionals Adverse Event Monitoring System
(SN/AEMS). The sources of these reports were the FDA, federal and local
health agencies, consumers and health professionals.

Of 2621 side effects reported, concerning 3451 products, some ten cases
concerned preparations concerning aspartame (mixtures also containing
vitamins, amino acids and various nutritional supplements).
The effects reported included seizures, death, nervous and cardiac symptoms,
oedema and fever.

Still in the United States, the Center for Disease Control assessed 517
complaints about aspartame (1983). The symptoms reported were
headaches, mood changes, insomnia, abdominal pain, nausea, convulsions, etc.

These symptoms are observed frequently in the general population.
Although it might be possible that certain individuals are particularly
sensitive to aspartame, these data, which relate to a large number of
people, have not enabled any relationship to be demonstrated between the
consumption of aspartame and the occurrence of convulsive seizures.
[ Every pro-aspartame research review always dismisses reports by users
and their physicians, rather than study them respectfully for the obvious
typical
patterns:
the gradual increase in variety and intensity of symptoms,
the inability to settle on a diagnosis or find an effective treatment,
the over-prescription of many useless drugs with debilitating side effects,
the onset of actual craving and addiction,
the withdrawal and recovery phases after discontinuing aspartame,
followed by immediate recurrence of symptoms upon inadvertant reexposure.

http://www.dorway.com/tldaddic.html 5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan; HJRobertsMD@...
http://www.sunsentpress.com/ sunsentpress@...
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 $ 60.00 postpaid data from 1200 cases
available at http://www.amazon.com
over 600 references from standard medical research

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

Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
aspartame disease, pages 627-685, 778-780

http://groups.yahoo.com/group/aspartameNM/message/859
RTM: Roberts: the life work of a brilliant clinician:
aspartame toxicity 8.2.2 rmforall ]

4.3 - Toxicity of aspartame metabolites on the nervous system:

In both laboratory animals and in humans, aspartame is metabolised in the
intestinal tract into methanol, aspartic acid and phenylalanine.

page 8

Methanol:

Methanol accounts for approximately 10% [ 11% exactly by weight-- one
molecule of methanol is released by every molecule of aspartame. ]
of aspartame in terms of weight.

It is metabolised into formaldehyde, formic acid and CO2.

One litre of "diet" drink containing aspartame produces approximately 48 mg
of methanol whereas a litre of fruit or vegetable juice contains
approximately 200 to 280 mg of methanol.
This indicates that the quantities of methanol provided by aspartame as a
food additive are lower than those provided by certain natural foods (Maher,
1986).
In humans, ingestion of methanol at a dose of 200-500 mg/kg body
weight is required to induce an accumulation of formate in the blood and
toxic effects on the vision and the central nervous system.
These doses are more than 100 times greater than the maximum dose of
methanol provided by aspartame (FDA, FR 1984).

These data put into perspective the potential toxic effects of the
metabolites of methanol (formaldehyde and formic acid) following exposure to
aspartame.

[ This is straight-out, invariable, word-for-word aspartame industry PR
spin, except that that spiel rarely mentions the words "formaldehye" and
"formic acid". The PR never mentions or attempts to refute the facts given
by W.C. Monte in 1984, that the methanol in fruits is not readily released
by digestion, and that fruits always have many times more ethyl alcohol
(ethanol), easily released, which happens to be a widely used antidote for
methanol toxicity.
In addition, the toxicity from daily exposure to low doses of formaldehyde
and formic acid is cumulative in tissues, not in blood, as the complex
biochemical reactions build up in cells in all tissues.
Along with the build-up of toxic products and damage, there is also
increasing
sensitivation and hyper-sensitivation, for which formaldehyde is a specific,
well-known cause.

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Metanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

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 [retired 1992]
Arizona State University, Tempe, Arizona 85287 woodymonte@...
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.)

"Fruit and vegetables contain pectin with variable methyl ester content.
However, the human has no digestive enzymes for pectin (6, 25) particularly
the pectin esterase required for its hydrolysis to methanol (26).

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3).
In fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon).
Heating of pectins has been shown to cause virtually no demethoxylation;
even temperatures of 120 deg C produced only traces of methanol (3).
Methanol evolved during cooking of high pectin foods (7) has been accounted
for in the volatile fraction during boiling and is quickly lost to the
atmosphere (49).
Entrapment of these volatiles probably accounts for the elevation in
methanol levels of certain fruits and vegetable products during canning (31,
33)."

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day (8).
This report clearly indicates that methanol:

"...is considered a cumulative poison due to the low rate of excretion
once it is absorbed. In the body, methanol is oxidized to formaldehyde
and formic acid; both of these metabolites are toxic." (8)...

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34).
No skeptic can overlook the fact that, metabolically, formaldehyde must be
formed as an intermediate to formic acid production (54).

Formaldehyde has a high reactivity which may be why it has not been found in
humans or other primates during methanol posisioning (59)....

If formaldehyde is produced from methanol and does have a reasonable half
life within certain cells in the poisoned organism the chronic toxicological
ramifications could be grave.

Formaldehyde is a known carcinogen (57) producing squanous-cell carcinomas
by inhalation exposure in experimental animals (22).
The available epidemiological studies do not provide adequate data for
assessing the carcinogenicity of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde with deoxyribonucleic acid (DNA) has
resulted in irreversible denaturation that could interfere with DNA
replication and result in mutation (37)..."

http://www.drthrasher.org/formaldehyde_1990.html full text Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223. "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation." PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

Environ Health Perspect. 2003 Sep; 111(12): 1461-4.
Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity:
central role of N-methyl-D-aspartate receptors in the sensitivity mechanism.
Pall ML.
School of Molecular Biosciences, 301 Abelson Hall, Washington State
University, Pullman, WA 99164, USA. martin_pall@...

The elevated nitric oxide/peroxynitrite and the neural sensitization
theories of multiple chemical sensitivity (MCS) are extended here to propose
a central mechanism for the exquisite sensitivity to organic solvents
apparently induced by previous chemical exposure in MCS.
This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA)
receptors by organic solvents producing elevated nitric oxide and
peroxynitrite, leading in turn to increased stimulating of and
hypersensitivity of NMDA receptors.
In this way, organic solvent exposure may produce progressive sensitivity to
organic solvents.
Pesticides such as organophosphates and carbamates may act via muscarinic
stimulation to produce a similar biochemical and sensitivity response.
Accessory mechanisms of sensitivity may involve both increased blood-brain
barrier permeability, induced by peroxynitrite, and cytochrome P450
inhibition by nitric oxide.
The NMDA hyperactivity/hypersensitivity and excessive nitric
oxide/peroxynitrite view of MCS provides answers to many of the most
puzzling aspects of MCS while building on previous studies and views of this
condition. PMID: 12948884

Prof. Pall describes processes by which an initial trigger exposure, such as
carbon monoxide or formaldehyde, can generate hypersensitivity to many
substances. He himself had recovered from a sudden, debilitating attack of
multiple chemical sensitity in June/July 1997.

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti: Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2004.04.04 rmforall [ 150 KB ]

"A 60-year-old Caucasian woman presented with a 6-month history of eyelid
dermatitis...

By strictly avoiding formaldehyde and all formaldehyde releasers for the
next 3 weeks, she improved only slightly.

Her problem, however, was subsequently solved when a local pharmacist
advised her to avoid aspartame.

She had begun using an aspartame-based artificial sweetener 5 months prior
to the onset of her dermatitis. [ 12 months of low-level aspartame use until
stopping. ]

Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
completely and has not recurred over 18 months without specific
treatment....

Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
daily, well below the levels previously studied."

[ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
soda gives 200 mg aspartame.
An aspartame reactor can have immediate strong symtoms from an
under-the-tongue wafer with 4 mg aspartame. ]

Contact Dermatitis. 2003 Nov; 49(5): 258-9.
Systemic contact dermatitis of the eyelids caused by formaldehyde derived
from aspartame?
Hill AM, Belsito DV. DBelsito@...
Division of Dermatology, University of Kansas Medical Center, 3901 Rainbow
Blvd., Kansas City, KS 66160, USA. PMID: 14996049

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment modalities with limited success.
All had complete, or nearly complete, resolution of their symptoms within
months after eliminating monosodium glutamate (MSG) or MSG plus aspartame
from their diet.
All patients were women with multiple comorbidities prior to elimination of
MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071

Debbie J. Hypes painfreeliving@... 304-872-4141 (Case # 1 of 4)
P.O Box 25 Lookout, WV 25868-0025 She has about 1,000 on her local
mailing list, and has been a volunteer activist since 1997. Her guide
first came out in 1997: http://www.Pain-Free-Living.net
"The Food Plan: How To Do It" $ 5 by mail, free by email.
Her sister Darlene, now 47, cured her own severe fibromyalgia in 1995
by using an elimination diet, and then Debbie also cured herself by
1997. Their doctor, Siegfried Schmidt, paying attention, tried it on
two more patients, who got well, and are his third and fourth cases.

http://www.perque.org/Fibromyalgia.pdf
A Novel Treatment for Fibromyalgia Imrpoves Clinical Outcomes in a
Community-Based Study.
Patricia A. Deuster, Russell M. Jaffe. RJaffe@...
Journal of Musculoskeletal Pain. 1998; Vol. 6(2): 133-149.
http://www.perque.com/ info@... 800-525-7372

Using blood tests, the researchers ran a panel of 350 antigens
including environmental chemicals, food additives and preservatives,
crustaceans, diary products, fish, fruits, grains, meats, mollusks,
and oils.

Normal, healthy people react to only two or less of this panel. The
greatest offenders were:

MSG 42.5 % (17 out of 40 patients)
Candida albicans 37.5 %
Caffeine 37 %
Chocolate/cocoa 37 %
Food colorings 37 %
Cola beverages 37 %
Cow Dairy Products 25 %
Sulfite/metabisulfite 22.5%
Xylene 22.5%
Yogurt 22.5%
Aspartame 20%
BHA 20%
Cadmium 20%
Lead 20%
Tylenol 20%
Yeast 20%
Sodium benzoate 20%
Orange 20% ]

Trocho et al., (1998) demonstrated that aspartame, radio-labelled on the
methanol, induced in the liver stable DNA and proteins adducts.

According to these authors, the accumulation of these adducts after repeated
administration of aspartame could pose problems of toxicity and
carcinogenicity in the long term.

Besides the fact that aspartame at high doses has never induced liver cancer
in rats, Trocho's studies did not identify the radioactivity found in the
proteins and DNA.

Consequently, the formation of adducts of formaldehyde on the proteins and
nucleic acids from aspartame, in vivo, remains to be proved (Tephly, 1999).

Aspartic acid:

The transformation of aspartame into aspartic acid do not pose any
neurotoxicity effects , notably due to the characteristics of the transport
system for this amino acid across the blood-brain barrier which prevents its
accumulation in the brain by promoting its transport toward the blood
(Maher, 1986).

Aspartic acid is mostly eliminated through the lungs in the form of CO2. In
humans, plasma levels of aspartic acid do not increase significantly
following oral administration of aspartame at a dose of 34 mg/kg bw.
(Stegink, 1984).

Phenylalanine:

Some of the phenylalanine formed in the intestine following ingestion of
aspartame is excreted in the form of CO2, most of it is incorporated into
the pool of amino acids and contributes to protein synthesis.

The following table shows the plasma concentrations of phenylalaninee
measured after oral administration of aspartame at different doses in adult
men (Trefz et al., 1996; Stegink et al., 1996):

page 9

Phenylalanine (µmol/l)
Aspartame (mg/kg)
Baseline Concentrations Plasma Peak
Concentrations
34 50- 60 110 - 120
50 - 160 - 170
100 - 200
150 - 350
200 - 500
Children with PKU 1200 - 6000
PKU = phenylketonuria

Even for doses far higher than normal exposure doses, baseline blood
concentrations of phenylalanine likely to cause side effects in children
suffering from phenylketonuria are not reached.

Furthermore, the administration of repeated doses of aspartame does not lead
to an accumulation of phenylalanine in the blood.

According to Maher et al. (1986, 1987), the ability of phenylalanine to
reach the brain differs depending on whether it originates from the
consumption of aspartame or from the ingestion of dietary proteins.

There may be a competition results at the blood-brain barrier between
phenylalanine and other amino acids.

This means that the consumption of aspartame other than at mealtimes would
be liable to increase selectively the level of phenylalanine in the brain.

This phenomenon could lead to a special risk for people with a
phenylalaninehydroxylase deficiency and individuals with neurological
disorders such as epilepsy.

This latter point is supported by Wurtman (1985) who indicated that the
administration of aspartame, by increasing the absorption of phenylalanine
in the brain, could affect the synthesis of catecholamines or serotonin and
cause convulsions.

According to the FDA (FDA, FR 1984) and several authors (reviewed by Stegink
et al., 1996; Stegink et al., 1996(a); Trefz et al., 1996), the doses of
phenylalanine liable to produce toxic effects on the brain are much greater
than those which could be produced by the consumption of aspartame tablets
or in "diet" drinks.

Furthermore, the effects of aspartame on the synthesis of neurotransmitters
are still working hypotheses.

4.4 - Toxicity of dicetopiperazine in terms of effects on the nervous
system:

The toxicity of diketopiperazine, a degradation product of aspartame, has
been studied in laboratory animals.

This substance is neither genotoxic nor carcinogenic in rats and mice.

The Acceptable Daily Intake of diketopiperazine for humans has been
established at 7.5 mg/kg body weight (JECFA, 1980) based on the no observed
effect level of 750 mg/kg bw./day obtained in a long term toxicity study on
rats, divided by a safety factor of 100.

page 10

4.5 - Conclusion:

The hypothesis of Olney that suggested that the exposition to aspartame
could be a possible cause of the increase in the incidence of brain tumours
in humans has not, to date, been confirmed by experimental data on animals
or by the epidemiological data on humans.

A review of published data demonstrates the lack of evidence for
establishing a causal link between aspartame and epileptic seizure or
abnormal electroencephalograms in humans.

In comparison with current foodstuffs, aspartame is a minor source of
phenylalanine, aspartic acid and methanol.

These compounds cannot therefore be the source of toxic effects in consumer
under normal conditions of use of this sweetener.

The safety of aspartame has been assessed and acknowledged by a number of
national and international authorities, including the FDA, the JECFA and the
SCF.

Aspartame was authorised by the Directive 94/35/CE of the European
Parliament and of the Council on sweeteners for use in foodstuffs (adopted
on 30 June 1994) and its use is approved in more than 90 countries.

The ADI for humans has been 40 mg per kg of body weight since 1980.

[ Like other pro-aspartame reviews, sponsored by vested interests, firm,
officious, one-sided summary statements are presented without regard to the
complexities and subtleties of whatever partial evidence happens to be
selected in the main body of the document.

Instead of highlighting unresolved questions and asking for urgent,
thorough, open-ended explorations of unresolved, complex issues vital for
public health and safety, the debate is closed with a barrage of deceptive
conclusions.

This strategy has proven its remarkable effectiveness in spreading the use
of a potent source of formaldehyde and formic acid to hundreds of millions
of world citizens as a very profitable multibillion dollar industry, with a
huge annual advertising and PR budget, that powerfully influences media,
medicine, science, and government. We might well term this: "Orwellian
Science".

Meanwhile, the cadres of industry funded researchers continue to earnestly,
piously cite and quote one another, and, no doubt, perform reciprocal peer
reviews. Their style is marked by a certain ineluctable dullness.

Hear the mantrum of NutraSweet, "Aspartame is the most thoroughly tested
food additive in history."

The term "food additive" is emphasized, for unlike "drugs", the makers of
"food additives" need not prove safety nor keep records of citizen and
physician complaints.

Year after year, decade after decade, the party line is studiously repeated
and reinforced, becoming an entrenched scientific orthodoxy, a manipulated
apparent concensus, fairly convincing to laypersons-- and, realistically,
everyone outside a limited network of specialists is a layperson.

Dissenters are criticized roundly and soon marginalized, and only with delay
and difficulty allowed a voice in mainstream journals.

Those who continue to publish in more open venues, like the Townsend Letter
for Doctors and Patients, are further stigmatized for this lapse.

Having followed this course for decades, for whole careers, the industry
funded experts involved are hardly likely to be the ones to inspect the
actual range of
evidence, come to fresh conclusions, and take prompt and innovative actions
for the public welfare.

The Devil does indeed lie in the details, in both senses of the word. How
many professionals can afford any time to delve into the myriad details of
obscure studies, caught up as they are in the compelling onrush of their
demanding responsibilities?

I have a BS in physics and history from MIT in 1964, and a MA in psychology
from Boston University Graduate School in 1967. I've worked a home hospice
care giver full time and more since 1988. Having never taken even a single
biology or medical course, I have absolutely no qualifications to evaluate
complex medical issues.

However, like the little boy who pipes up in the hypnotized crowd, "The
Emperor has no clothes," it is feasible for a person of moderate ability and
fickle tenacity, limited time and funds, no resume, no expertise, no
connections, to zero in on the essential simple core of an important issue
and speak it clearly for all to hear, especially with the miraculous growth
of the Net since 1995 to some 800 million.

There are world-wide volunteer activist networks, self-originated,
self-organizing, pure democracies, decentralized, fun while fundless, that
build up memberships in the hundreds and thousands, with thousands to
hundreds of thousands of posts in their public, searchable, perpetual
archives. The groups are free, a fine computer system costs $20 weekly,
while cable broadband is $ 50, and, voila! yours is a bully pulpit indeed.
With Google on broadband, my desktop is the world.

Those who serve, rule. Those who competently and politely give, receive att
ention and support, and their posts start to be copied and placed
uncontrolably in all kinds of venues on the Net, gradually eliciting a
cumulative, benevolent rating from Google.

All my email since 1996 is on my hard drive, and I can search it all in a
trice, and in an evening compose a choice ten-pager, or in a weekend a
substantial fifty-pager, while scanning, assimilating, and responding to
similar posts from others in diverse networks. Several times, a week, an
opportunity calls,
"Do me now," and I do it now, passing on and integrating huge blocks of
information, always giving sources and credit, always providing links and
email addresses, always giving my own full address.

I serve by serving up reviews of competent media and mainstream science,
long, detailed, balanced, lucid, civil, honest, and honorable, for those
who need them, who therefore choose to glance at or study them. My
archive is my resume. You determine my credibility. You use me. Your
listenning creates my voice. I speak to serve the highest common good. For that
is what I want spoken to me.

Safe and maximally heathy food and drink are inherently fundamendal issues
for the single human family. The universal need is for fast, democratic
global consensus building, flexible, subtle, supple, that organically
integrates all points of view. The Net is already the legislature of our
world. On it consensus naturally, inevitably, authoritatively emerges
about every issue on every level.

As a result of each spontaneous, actual, largely unheralded, leaderless,
unmanaged, unplanned, ownerless, consensus, the operations of business,
science, education, and government are forced to follow. I've noticed the
striking inability of any organization, business, or government on any level
to commit to coming to grip with the issue of aspartame (methanol,
formaldehyde, formic acid) toxicity. The USA FDA, to which I've submitted
hundreds of pages of carefully composed documents in the last two years, has
been very true to its own bureaucratic reality-- totally impervious,
inpenetrable, unresponsive.

The FDA and all its ilk are simply being bypassed. The increasing depth and
eloquence of the consensus on aspartame toxicity is resounding and
resonating, a chain reaction of beneficial information, daily on the Net, on
groups, blogs, personal posts, science abstracts and full texts, media at
all levels all over the world, talk shows, advertising-- along with
unprecendented and ever deepening debates about related issues of diet and
toxicity: food dyes, preservatives, and additives, mercury, fluoride,
pesticides, medicines, milk products, meat, excess saturated fats, soy,
supplements, hypersensitivity diseases, the precautionary principle, the
personal diets of politicians and other celebrities.

I have always been healthy. For 5 years, as soon as I did my first Google
search on dietary issues in January 1999, I have been swiftly, gradually
changing my own diet to organic vegan with some sensible supplements, and
enjoy a huge increase in my capacity to enjoy my service on the Net. I am
my own client, and I have benefitted mightily and magically. What's
actually unstopably, palpably going on now in our world is
transorganizational global democracy.

Since the simple, incontrovertible reality is that the 11% methanol
component of aspartame can not be other than a potent source of at least two
dangerous, cumulative toxins, formaldehyde and formic acid, then the natural
exponential expansion of science, enormously aided by the stunning growth of
the world Net, must inevitably expose this fact.
The necessary research on humans is well within the capabilities of a single
graduate student.
Stunning results could be quickly achieved from a full biochemical survey of
a single aspartame reactor.

A single politician or celebrity with aspartame disease ( which might well
be termed Rumsfeld's Disease), a talk show host who persistently highlights
aspartame reactors, a single school, business, or governmental agency
anywhere on Earth could initiatite a chain reaction of publicity that would
lead to the implosion of aspartame as a viable business commodity, while
igniting a legal conflagration that could match the level of tobaacco
litigation -- decades of suits with hundreds of billions of dollars of
penalties, and lengthly prison sentences.

This realistic probability is surely obvious to vulnerable insiders, who
stand to benefit enormously by being the first whistle-blowers, while alert,
capable executives still have an open window of opportunity to save or
radically advance the prospects of their firms.

The longer and more extensive the coverup, the more certain its implosion
and the greater the damage.

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. 52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333 adandjack@...

Regulatory Toxicology and Pharmacology 35, S1-S93 (2002)
doi:10.1006/rtph.2002.1542, available online at
http://www.idealibrary.com $ 35.00
Aspartame: Review of Safety [ 24 authors in an industry house organ ]
page S1 0273-2300/02 $35.00
C 2002 Elsevier Science (USA) All rights reserved.

Harriett H. Butchko 1
Medical and Scientific Affairs, The NutraSweet Company,
Mt. Prospect, Illinois
1 To whom correspondence should be addressed at Medical and Scientific
Affairs, The NutraSweet Company, 699 Wheeling Road, Mt.
Prospect, IL 60056. Fax: (847) 463-1755. harriett.h.butchko@....
W. Wayne Stargel
Research and Development, The NutraSweet Company,
Mt. Prospect, Illinois
C. Phil Comer
Graystone Associates, Inc., Macon, Georgia
Dale A. Mayhew
Regulatory Affairs, The NutraSweet Company, Mt. Prospect, Illinois
Christian Benninger (EEGs and Cognitive Function in PKU Heterozygotes)
Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
George L. Blackburn (Appetite, Food Intake, and Weight Control)
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, Massachusetts
Leo M. J. de Sonneville (Neuropsychological Function and Phenylalanine)
Departments of Pediatrics and Neurology, Vrije Universiteit, Medical
Center, Amsterdam, The Netherlands
Raif S. Geha (Allergy)
Division of Immunology, The

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