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Betty Martini (fwd)

Mark Gold mgold at max.tiac.net
Tue Jul 11 23:17:12 EST 1995

: Newsgroups: bionet.neuroscience
: From: asa3h at avery.med.Virginia.EDU (Adam S. Arthur)
: Subject: Re: Betty Martini (fwd)
: Date: Tue, 11 Jul 1995 03:43:41 GMT
: Just an attempt to bring some real science into this,


Actually, a discussion of the pre-approval "experiments" is a 
discussion of real science.  The FDA requires testing of new 
chemicals (i.e., food additives) that are put into the food supply 
and that do not have a history of safe use.  This makes some sense, 
otherwise we could simply begin randomly dumping chemicals into our 
food supply without testing.

Pre-approval tests are used to give clues as to a product's safety 
once it enters the food supply.  Even when pre-approval tests are
performed correctly, it does not guarantee a safe product (Oraflex,
for example).  Most of the tests are concerned with cancer and birth 
defects and quite often do not look at countless other possible health 

It is clear to anyone who has looked at the FDA Investigation reports 
and the Congressional testimony that the pre-approval "experiments" 
were a disaster.  Therefore, that key aspect of the scientific safety 
process goes out the window and we are then in a situation that we 
are using a "product" without safety testing.  In addition, at least 
one test showed a significant increase in brain tumors in animals and 
the manufacturer admited to a significant increase in uterine polyps 
and cholesterol levels (over time).  This was despite the fact that 
evidence showed that the animals probably got a much lower dose than 
intended.  Don't forget that one of the first studies on primates 
caused a number of grand mal seizures.  See Enclosure #1 for some
testimony from scientists and FDA Investigators who *are not receiving
money from NutraSweet*.

If you do not consider the pre-approval tests "real science," are you 
suggesting that we do away with them or ignore them?  I certainly do 
not think so.  I believe that these tests (or lack thereof in this 
case) are a key part of the scientific process.

: Or is this just anecdotal "my (fill-in-your-condition
: here) got better when I stopped eating nutrasweet" sort of
: evidence?

You appear to be discounting another key aspect of the scientific 
process.  How do we determine whether a chemical in the food supply 
has serious, adverse effects from long-term use?  I would propose 
that science currently uses the following tools:

1.  Pre-approval tests
2.  Case histories
3.  Epidemiological studies

Double-blind experiments are generally too short and have too few 
subjects to determine serious adverse effects from long-term use in a 
sub-set of the population.  No one would be dumb enough to suggest 
testing cigarettes by giving 10 people 2-packs a day for a few weeks 
to see if they cause lung cancer.  The same is true for a high fat 
diet -- a four week, double-blind experiment to see if it causes 
heart disease would not be of much use.

That's not to say that double-blind experiments are worthless.  They 
are useful for looking at reactions such as headaches, for 
example.  But they cannot judge what one year, five years, or a 
lifetime of use will do to a person.

The pre-approval tests (#1 above) were worthless at best and gave 
some clues of danger.

The case histories (#2 above) are piling up -- especially serious reactions
from long-term use.  I could post a few that I have approval to share, but 
there are many, many more that could be found in the literature and 
from people accepting case reports from the public.  For example, 
just the other day, I saw a case report on the Net of a lady who suffered
dizzy spells which gradually worsened to seizures.  Eventually, she ended 
up in a coma.  When she came out of the coma, a friend suggested that 
she go off NutraSweet.  All of her seizures stopped, she was able to 
get off medication and has no problems *as long as she avoids 
NutraSweet*.  I've seen quite a few case histories like this on the 
Net and many more from other sources.  In most cases, the suggestion to 
stop aspartame comes not from the physician, who has invariably been 
duped into believing aspartame must be safe by reading the lousy 
NutraSweet reviews, but from friends and family.

It's sad that some some scientists seem so quick to discount case 
histories even when a) in many cases there are no other known 
possible causes, and b) the patient repeatedly has the same probelm 
when ingesting aspartame, even *unknowingly*.  It's easy to smile and 
say, "Well, it just one of thousands of 'anecdotal' reports.  There's 
no *proof* so let's chalk it up to some lunatic conspiracy theory."
It's fun, in a way -- that is until you realize that more and more 
people are losing faith in researchers and physicians and are
quickly giving up on Western Medicine rather than having their 
"anecdotal" experiences ignored, discounted, or belittled.

So, we have worthless yet worrisome pre-approval tests.  We have 
serious "anecdotal" reports piling up.  What about the 
epidemiological studies???  Well, despite experienced, independent 
researchers virtually begging the U.S. Congress and FDA to provide 
funds for more testing, almost no funds are available.  Here is just 
one example of a researcher unable to get funds.

     Dr. Richard Wurtman, Director of the Clinical
     Research Center and Professor at Massachusetts
     Institute of Technology, in April 1988 urged the
     FDA to issue warnings to physicians that aspartame
     may be associated with a syndrome including severe
     headaches, and in some cases, grand mal seizures.
     Wurtman had received over 1,000 complaints at
     M.I.T. directly into his department
     . . . . .
     Wurtman tried for over a year to get support for
     his research [to study aspartame and seizures], to
     no avail. He said, "The present system, in which
     the companies that sell our synthetic foods--like
     NutraSweet--fund virtually all of the studies, FDA-
     mandated or not...is too vulnerable to
     misuse...when outside investigators propose
     studies that might yield the 'wrong' answer, a
     large bag of 'dirty tricks' is available for
     derailing those studies." [P.J. Lisa]

The only epidemiological study I am aware of was by Stellman and 
Garfinkel (I believe) showing that women ingesting artificial 
sweeteners over the course of a year showed a weight gain slightly 
greater than those not ingesting artificial sweeteners (even when the 
diets were similar otherwise).

The scientific status looks something like this:

1.  Pre-approval tests          Worthless and worrisome

2.  Case Histories              Piling up serious reactions

3.  Epidemiological Studies     Essentially none

4.  Other Studies & Reviews     Virtually all by *independent* 
                                scientists have found problems with
                                aspartame (that includes double-
                                blind studies).  Lack of properly
                                designed experiments by NutraSweet

: Is it the fact that nutrasweet may offer a source of free
: glutamate?  If so, what about BBB penetration issues?

That is a very good question.  The answer is that much of the concern 
about the adverse effects from exogenous excitoxic amino acids has revolved 
around areas of the brain that are not protected by the blood brain 
barrier (BBB) such as the circumventricular organs (CVOs).  

NutraSweet researchers have known this fact since the early 1970s, 
yet still sometimes continue to use the BBB as "proof" that glutamate and 
aspartate have no adverse effects.  Even *if* they didn't have 
adverse effects, it is still dishonest, I believe, to use knowingly 
avoid the real issue to try and prove "safety."  (And believe me, if
you want to discuss avoiding the issue or spurious information from
industry, the glutamate and aspartate issues are a good place to start.)

: but WHAT
: is the proposed mechanism of nutrasweet's putatively terrible
: effects?  I mean is the research you allude to the safety
: studies, because I've read those and to anyone with even a
: rudimentary knowledge of medicine theres clearly no smoking gun
: there.

As for the proposed mechanism, that is a very broad question because 
there are a number of breakdown products from aspartame and a number 
of possible problems with each breakdown product.  Therefore, the 
discussion could get very long.  I will try to summarize a few of the 
main mechanisms.  But since I am not a "real researcher," I will have 
to do the best I can with the terminology and details.

For *specific* areas, I would be more than happy to go over references
and conflicting studies that you may find in the literature.

Two short notes first:

1.  I gave a fairly detailed description of the history of aspartame 
    including references for you so that you can follow up.  
    Also in Enclosure #2 you will see a more detailed 
    description (with references) of NutraSweet's lobbying effort to test 
    less aspartame than the FDA's Allowable Daily Intake.  Please 
    keep these issues in mind if you read some "review" that states 
    "aspartame proved safe in countless, rigourous pre-approval tests" 
    (try not to gag), or "the average intake of aspartame is
    1 to 2 mg/kg/day" (or whatever figure NutraSweet wants to come 
    up with at that moment).

2.  I don't expect anyone to agree with me on all the issues.  But 
    please keep in mind that by defending horrendous experiments
    (and we've only touched on portion of the bad ones with the
    pre-approval studies), a person may be contributing to the
    death of the scientific process.  It is important that the 
    scientific community have some standards.  If those standards
    aren't set or they aren't protected, we're left with companies
    making a mockery of the scientific process.


A.  Phenylalanine (50% of aspartame)

Plasma Phenylalanine Level
The plasma level of the amino acid phenylalanine can rise as much
as seven (7) times its average baseline (fasting) value after
aspartame ingestion (in liquids such as carbonated beverages).
The spike in the plasma phenylalanine level lasts about 2 hours
(average).  Plasma phenylalanine levels gradually rise after a high
protein meal, for example, but the levels do not rise nearly as high.

Plasma Phenylalanine/Large Neutral Amino Acids (LNAA) Ratio
When a high protein meal is eaten, a number of amino acids gradually
enter the bloodstream.  Other Large Neutral Amino Acids (LNAAs) in 
addition to phenylalanine enter the bloodstream after the proteins 
from the foods are broken down.  The other LNAAs are:


These amino acids tend to be more abundant in foods than 
phenylalanine.  When a protein food is eaten the plasma level of all 
the LNAAs (including phenylalanine) rises gradually.  However, since 
the other LNAAs are more abundant than phenylalanine, the 
Phenylalanine/(Other LNAA) ratio goes down.  In other words the 
plasma phenylalanine level rises, but to a much less extent than the 
plasma level of the other LNAAs.

Aspartame is the only "food" that contains phenylalanine and *no* other 
large neutral amino acids (LNAAs).  Therefore, not only does the 
plasma phenylalanine level spike to high levels after aspartame 
ingestion, but the plasma phenylalanine/LNAA ratio also spikes to very 
high levels after aspartame ingestion.  In other words the 
phenylalanine level rises, and the other LNAA levels do not rise at 

Brain Uptake of Large Neutral Amino Acids (LNAAs)
In humans, it is believed that large neutral amino acids (LNAAs) 
compete for entry into the brain across the Blood Brain Barrier 
(BBB).  For example, when plasma phenylalanine levels are low, uptake 
of the LNAA methionine into the brain has been shown to *increase*.  
When plasma phenylalanine levels increase, uptake of the LNAA 
methionine into the brain has been shown to *decrease*.

A rise in the plasma phenylalanine/LNAA ratio leads to an increased 
uptake of phenylalanine into the brain and a decreased uptake of 
other LNAAs into the brain.  The reduced uptake of other LNAA such as 
tyrosine and tryptophan reduces the production of certain 
neurotransmitters made from those amino acids such as serotonin, 
norepinephrine and dopamine.  Also, high levels of phenylalanine can
inhibit enzymes such as tyrosine hydroxylase which is needed to
synthesize neurotransmitters.

Other Effects and Brain Chemistry Change Rate
Other potential effects from increased brain phenylalanine levels 
include (in part): increased susceptibility to seizures, behavioral
changes, insomnia, neuroendocrine disorders, blood pressure changes,
reduction in I.Q., and blockade to CNS drug therapy.  All of these 
changes in brain chemistry occur very gradually in most people and 
therefore linking the cause to 1, 5, or 10 years of regular aspartame 
ingestion is very difficult.  This makes 1 day or even 1 month 
studies on aspartame ingestion of limited or no use for studying 
brain chemistry changes.

Other Notes
1.  Some experiments which measured average phenylalanine levels in 
    the brains of animals found no significant increase.  This is partly 
    because the phenylalanine increases in selected areas of the brain.  
    Therefore, measuring the average phenyalanine levels throughout the
    *whole* brain will not show much of an increase after aspartame 
    ingestion.  It is important to measure the correct area of the brain.

2.  Studies with rats are difficult because the rat's liver 
    metabolizes phenylalanine very rapidly.  A very high dosage is
    needed in such studies to simulate what happens in humans.

3.  When ingesting aspartame with a sugary snack (which is lacks much 
    protein), the secretion of insulin lowers the plasma level of certain 
    LNAAs (not phenyalanine though) causing an even greater rise in the 
    plasma phenyalalanine/LNAA ratio.  This can as much as double the 
    aspartame's effect on brain phenyalalanine.

4.  If a PKU carrier -- one of 10 million people in the U.S. -- 
    ingests aspartame, this can significantly increase the plasma 
    phenyalalanine and plasma phenyalalanine/LNAA levels above what is 
    seen in non-carriers.  Most people do not know if they are PKU 

5.  The fetal brain will concentrate phenylalanine to a level 4 times 
    that of the mother or 28 times that of the mother's fasting level 
    in some cases after aspartame ingestion.  Quite a "healthy" 
    environment for the development of the child, don't you think?

6.  I know of at least one case where a non-PKU individual had serious 
    health problems, wide mood swings, and other neurological problems 
    after years of aspartame ingestion.  He had an extremely high level
    of phenyalanine.  After stopping aspartame, the level went way 
    down, and his health problems disappeared.

Suggested Reading
Pardridge, William M., 1986.  "Potential Effect of the Dipeptide 
  Sweetener Aspartame on the Brain," In "Nutrition and the Brain, 
  Volume 7," Edited by R.J. Wurtman and J.J. Wurtman, Raven Press, New 
  York, c1986, page 199-241.

Matalon, Reuben, et al., "Aspartame Consumption in Normal
  Individuals and Carriers for Phenylketonuria (PKU),"
  Dietary Phenylalanine and Brain Function. Proceedings of
  the First International Meeting on Dietary Phenylalanine
  and Brain Function, Washington, D.C., May 8-10, 1987.
  Center for Brain Sciences and Metabolism Charitable
  Trust, P.O. Box 64, Kendall Square, Cambridge, MA 02142.
  Reprinted in "Dietary Phenyalalnine and Brain Function", 
  c1988, Birkhauser, Boston, MA USA.


B.  Aspartate (40% of aspartame)

  Aspartate and glutamate are important neurotransmitters,
  a chemical which allows neurons (cells) in the brain to
  communicate between each other. Normally, excess
  aspartate and glutamate is pumped back in the the glial
  cells surrounding the neurons. However, when cells are
  exposed to excessive amount of aspartate and glutamate,
  the neuron cells are overstimulated and, at a certain
  level of aspartate and/or glutamate, the cells die.
  Aspartate and glutamate can open the calcium channel in
  the neurons so that calcium can move into the cell. A
  number of chemical reactions occur within the cell which
  eventually leads to the release of chemicals which
  stimulate connected neurons and so on. One of the
  products of this chemical reaction in the neuron is
  arachidonic acid. Arachidonic acid then reacts with two
  different enzymes causing the production of free radicals
  such as the hydroxyl radical. The hydroxyl radical, left
  unchecked can kill brain cells. Fortunately, the
  potentially destructive free radicals are absorbed by
  antioxidant vitamins such as C, E, and beta carotene.
  Magnesium, chromium, zinc and selinium are all very
  important protectors of neural cells.
  Magnesium normally blocks the calcium channel from
  opening. Aspartate and glutamate can remove this block
  and opens the calcium channel -- a normal reaction.
  However, when the glutamate levels become excessive, the
  calcium channels in some neural cells can get stuck open,
  leading to the overstimulation or destruction of those
  cells and adjacent cells. Not every nearby brain cell is
  affected -- only the cells with glutamate receptors.
  The pumping action to remove excess glutamate back into
  the glial cells takes an enormous amount of energy in the
  form of thechemical ATP (adenosine triphosphate). In
  addition, it is important that there is adequate
  magnesium, and vitamins C, E, and beta carotene in order
  to prevent cell damage. If brain energy or any of the
  proper vitamins or minerals are lacking, neural cell
  death can occur. In severe cases of lack of brain energy
  or vitamins or minerals, a normal glutamate level can
  lead to cell death.
  Normally, there is a blood brain barrier to prevent
  excessive glutamate levels from occuring in the brain.
  The blood-brain barrier is a system in the walls of the
  capillaries within the brain that is used to keep toxic
  substances from entering the brain. However, there are
  areas of the brain which are not protected by this
  barrier including the hypothalamus (a part of the brain
  which controls the release of hormones from the pituitary
  gland), the circumventricular organs, a part of the brain
  stem, and the pineal gland (a gland which controls the
  production of the hormone melatonin and stops the release
  of the luteinizing hormone (LH) which plays a part in sex
  hormone control -- estrogen (females) and testosterone
  It has been shown experimentally that prolonged high
  levels of glutamate in the blood plasma, as might be the
  case if a person with eating three meals a day with
  excessive free glutamate, causes glutamate to seep
  through the blood brain barrier. In addition,the blood
  brain barrier is not fully developed during infancy and
  childhood allowing excess glutamate to be delivered to
  the brain.
  Finally, there are a number of conditions which can
  damage the bloodbrain barrier to some extent and allow
  excess glutamate levels in the brain:
  - head injuries
  - certain diseases (e.g., diabetes, poor blood
     oxygenation, alzheimer's, ALS, etc.)
  - hypertension
  - physical overexertion (which can also block glucose's
     availability to the brain)
  - severe low blood sugar
  - exposure to chemical toxins
  - infections
  - brain tumors
  - strokes or mini-strokes which happen frequently in the
  - aging may cause a partial breakdown especially if there
     is poor health

  The excess glutamate and aspartate have been shown to cause
  irreversible brain lesions in a wide variety of animals including 
  primates.  This happened at a level that could conceivably be reached
  by an infant ingesting free glutamate and aspartate.  At many times 
  less than the level needed to cause brain lesions, excitotoxins 
  such as glutamate and aspartate have been shown to cause significant 
  changes in the release of pituitary hormones.  I would not suggest 
  that anyone constantly "excite" brain neurons day after day, 
  especially a developing child.

Suggested Reading
Olney, John W., 1994. "Excitotoxins in Foods," Neurotoxicology, 
15(3): 535-544.

Olney, John W., 1990. "Excitotoxic Amino Acids and Neuropsychiatric 
Disorders," Annual Review of Pharmacology and Toxicology, 30: 47-71.


C.  Methanol (10% of aspartame)

Methanol from aspartame is released in the small intestine
when the methyl group of aspartame encounters the enzyme

The absorbed methanol is then slowly converted to
formaldehyde by alcohol dehydrogenase in the liver.  If
methanol is co-ingested with a significant amount of ethanol,
the methanol conversion is temporarily blocked since ethanol
has nine times the affinity for alcohol dehydrogenase as does
methanol. This allows the body time to eliminate methanol via
the lungs and urine before it gets converted to
formaldehyde. The formaldehyde is then rapidly converted to
formic acid by aldehyde dehydrogenase in the liver, by
formaldehyde dehydrogenase in the blood, or through the
tetrahydrofolic acid-dependent one-carbon pool.

Methanol, also known as wood alcohol, is a deadly poison in
small amounts. The toxic effects of methanol vary widely
from person to person.  As little as 15 ml (2 tablespoons) of
methanol has killed a person.  In extremely small amounts
and taken without the protective factor, ethanol, methanol
can be a cumulative poison.

Formic acid can accumulate in the brain, kidneys, spinal
fluid, and other organs because of the slow excretion from
the body.  Formic acid inhibits cytochrome oxidase which leads
to a decrease in the synthesis of ATP.

The most well-known effect caused by acute or chronic
poisoning of methyl alcohol is damage to the optic nerve
fibers. However, there are many other symptoms and optic
nerve damage is not always one of the symptoms which appear.  For 
example, headaches, ear buzzing, dizziness, nausea, unsteady gait, 
gastrointestinal disturbances, vertigo, memory lapses, numbness, and 
shooting pains are other symtpoms of chronic methanol poisoning.

Formaldehyde has also been shown to cause a wide range of health 
problems, especially in persons with immune system disorders.  This 
includes non-respiratory disorders even when exposed to very low 
levels.  In addition, the excess formaldehyde from aspartame likely 
has a cumulative effect with the formaldehyde found in many common 
household products.

Suggested Reading
Monte, Woodrow C., 1984. "Aspartame: Methanol and the Public
  Health," Journal of Applied Nutrition, Volume 36, No. 1,
  page 42-54.

Kavet, Robert, Kathleen M. Nauss, 1990. "The Toxicity of Inhaled 
  Methanol Vapors," Critical Reviews in Toxicology, Voume 21, Issue 1,
  1990, page 21-50.

Brooks, Stuart M., Charles F. Reinhardt, 1981. "Health Effects of 
  Formaldehyde," IN "Formaldehyde and Other Aldehydes," National 
  Academy Press, Washington, D.C., c1981.


That only leaves DKP, beta-aspartame, racemized amino acids 
and a few other odds and ends that I didn't dicuss in this post.

Best regards,
                          - Mark
                       mgold at tiac.net

                   BEGIN ENCLOSURE #1

Brain Tumors
FDA Toxicology, Dr. Andriene Gross concluded, in part, the
following in his testimony before the US Senate (1987, page

     Even if, contrary to the FDA's view in 1976, the
     quality of the conduct of those studies could be
     relied upon by the same agency to even begin
     making such a determination, at least one of those
     studies had revealed a highly significantly dose-
     related increase in the incidence of brain tumors
     as a result of exposure to aspartame.
     The full incidence of those brain tumors was not
     disclosed by G.D. Searle & Co. to the FDA prior to
     the initial approval for the marketing of
     aspartame in 1974; moreover, the review of that
     study in the FDA was so flawed that the Agency
     apparently did not even realize at that time that
     only a portion of the observations on brain tumors
     had in fact been submitted by G.D. Searle & Co. in
     their petition for that approval.
     Quite aside from the remarkable significane of the
     increased incidence with dose of those brain
     tumors, the ADI [Acceptable Daily Intake] of 50
     mgm/kgm body-weight recently set by the FDA for
     the human consumption of aspartame is alarmingly
     dangerous in that it involves an extremely high
     and, therefore, a totally unacceptable upper limit
     on the risk for those consuming aspartame: between
     1/1,000 and 5/1,000 population to develop brain
     tumors as a result of such exposure.

In this testimony, Dr. Gross goes into detail to prove that
at least one G.D. Searle study proves that aspartame can
cause brain tumors (US Senate 1987, page 453).

In his testimony before Congres on August 1, 1985 Dr. Gross
details many of the problems with the G.D. Searle studies
(Congressional Record 1985b, page 10835-10840). He goes on
to show how these experiments point to aspartame as a cancer-
causing agent. Concluding these remarks, he states:

     In view of all these indications that the cancer-
     causing potential of aspartame is a matter that
     had been established way beyond any reasonable
     doubt, one can ask: What is the reason for the
     apparent refusal by the FDA to invoke for this
     food additive the so-called Delaney Amendment to
     the Food, Drug, and Cosmetic Act? Is it not clear
     beyond any shadow of a doubt that aspartame had
     caused brain tumors or brain cancer in animals,
     and is this not sufficient to satisfy the
     provisions of that particular section of the law?
     Given that this is so (and I cannot see any kind
     of tenable argument opposing the view that
     aspartame causes cancer) how would the FDA justify
     its position that it views a certain amount of
     aspartame (50 mg/mg body-weight) as constituting
     an ADI (Allowable Daily Intake) or "safe" level of
     it? Is that position in effect not equivalent to
     setting a "tolerance" for this food additive and
     thus a violation of that law? And if the FDA
     itself elects to violate the law, who is left to
     protect the health of the public?

Dr. John W. Olney, Neuroscientist and researcher testified
as follows regarding the brain tumor issue (US Senate 1987,
page 473-474):

     "There were other problematic aspects of the brain
     tumor data. In the pre-1975 records that I
     reviewed, it was clear that several competent
     pathologists had carefully examined the original
     microscopic slides from the first study and agreed
     that there were 12 brain tumors in the NutraSweet-
     fed rats and zero brain tumors in the controls.
     When the FDA conducted a task force investigation
     of these laboratories in 1975, they singled out
     these studies for further investigation and
     ordered that all laboratory records, including
     microscopic slides etc. be impounded under FDA
     seal. Several years later when a group of
     pathologists (UAREP) was sent to authenticate
     these studies, they could not find the microscopic
     slides. The UAREP pathologists were finally taken
     to a laboratory where the slides were not supposed
     to be and there they found some but not all of the
     original slides. Clearly they had not been kept
     under FDA seal and by mysterious coincidence the
     slides that were finally presented to the UAREP
     pathologists contained evidence for 11 brain
     tumors in Nutrasweet-fed rats and 1 tumor in
     contols. It is important to recognize that if
     there are zero tumors in the controls, it is very
     difficult to argue that the tumor incidence in the
     control and Nutrasweet-fed rats is the same. But
     if there is 1 tumor in the control group, it is
     possible with statistical acrobatics to reach the
     conclusion that the incidence is the same. And,
     indeed, this is exactly the argument that the
     manufacturer and the FDA Bureau of Foods pressed
     at the Public Board of Inquiry. .... Even more
     seriously I wonder why FDA allows microscopic
     slides to disappear (while supposedly impounded)
     and why they do not question the de novo emergence
     of a brain tumor among the controls when the
     slides reappear."

     "The PBOI panel member who was primarily
     responsible for reviewing the brain tumor issue
     was Peter Lampert, M.D., Neuropathologist and
     chairman of the pathology department at Univ. of
     Calif. San Diego. Dr. Lampert personally examined
     the microscopic slides pertaining to the brain
     tumor studies and told me a year or so after the
     PBIO report was completed that he had been
     surprised at the large size of the brain tumors in
     the Nutrasweet-fed rats. This reinforced his
     impression that they had been caused by some
     tumorigenic agent since spontaneous brain tumors
     are not only rare in laboratory rats but when they
     do occur they are usually not so large. Dr.
     Lampert is now deceased; he died in 1986 of
     cancer. At the time he participated in the PBIO,
     he was the President of the American Association
     of Neuropathologists."

In 1991, Dr. H.J. Roberts published an article in the
Journal of Advancement in Medicine (Roberts 1991), which
showed a possible correlation between the sudden, rising
incidence of Primary Brain Cancer and Primary Brain Lymphoma
and the years soon after aspartame went on the market. Dr.
Roberts concludes with a recommendation for a closer look at
the relationship between aspartame and brain cancer:

     The relationship between aspartame consumption and
     the development of primary brain cancers in humans
     requires careful analysis by corporate-neutral
     investigators. In the event that such a
     correlation is shown and brain cancer incidence
     rates continue to rise, the FDA should declare
     aspartame products an "imminent public health

Uterine Tumors
As discussed above, there was evidence that the rats in the
DKP study were able to avoid most of the DKP because the DKP
chunks were so large they would simply eat around them. The
FDA and G.D. Searle

Florence Graves of Common Cause Magazine described the
uterine tumor situation (Graves 1984):

     "FDA officials and Searle defend the study, saying
     that although there may have been problems, the
     study was still valid. Both the FDA and Dr. Daniel
     Azarnoff, president of Searle's research and
     development division, say one of several
     indications that the rats ate the required amount
     of DKP is the fact that a statistically
     significant number of rats developed tumors in
     their wombs (called 'uterine polyps')."

In testimony before the U.S. Congress, former FDA
Toxicologist, Dr. Jacqueline Verrett stated (US Senate 1987,
page 388-389):

     "This (DKP) is the famous study with the uterine
     polyps, and it is also the study in which there
     were changes in serum cholesterol, significant
     changes over the dose range.
     "Now, we still are not sure exactly how much of
     DKP each group of animals or any individual animal
     got; they may not have gotten whatt would be
     calculated on the basis of daily consumption had
     the diet been homogeneous.
     "The fact is, in spite of that, there were
     significant increases--and I think everybody
     agrees with that--of uterine polyps and also
     changes in blood cholesterol.
     "When that was then taken into consideration, they
     said, oh, well, obviously, they must have gotten
     the diet, because we have these changes. But then
     they disregarded the changes as being significant-
     -you know, uterine polyps were not pre-
     carcinogenic. Well, I can rustle up 15 million
     women by this afternoon who will disagree with

                   BEGIN ENCLOSURE #2

2.   Average Daily Intake of Aspartame


     "The replacement of all sweeteners with aspartame
     has been estimated to yield an intake of 867 mg of
     aspartame/day, which translates to only 87 mg of

Before we can discuss aspartame toxicity, it is crucial to
set the record straight regarding aspartame intake.

The statement in the article has three problems:

a. The increasing use of aspartame has not lead to a
   decreased use in caloric sweeteners such as sucrose.
   According to the U.S. Department of Agriculture, the per
   capita consumption of aspartame quadrupled between the
   years 1983 and 1988 (USDA 1988). Since that time, the
   use of aspartame has continued to increase. Dr. H.J.
   Roberts reported on Wall Street Journal articles which
   stated that "the diet beverage market was increasing at
   a rate of 20-25% annually" and that "consumers began
   drinking up to six times as many diet drinks as those
   using sugared sodas." (WSJ 1988, WSJ 1989) Gregory
   Gordon wrote in a UPI Investigation that "Roy Burry, an
   analyst with Kidder-Peabody, Inc., said the exploding
   diet market now accounts for 24 percent of soft drink
   sales, compared with 10 percent in the late 1970s, and
   is growing at 20 to 25 percent a year (Gordon 1987).

   From 1982 to 1988, the per capita consumption of caloric
   sweeteners jumped from 123.2 pounds to 133.5 pounds per
   year. Therefore the increased use of aspartame has not
   decreased the use of caloric sweetener products in the
   United States (USDA 1988).

b. Studies have shown that most people use aspartame in
   addition to sugar products and not instead of sugar
   products (Ryan-Harshman 1987, Knoop 1976). Therefore,
   the suggestion to increase the use of aspartame will not
   alter the sugar-craving feeding behavior of the large
   majority of persons. If they consume a non-sugar,
   aspartame-containing beverage at one point in the day,
   they will simply make up for the lack of sugar at some
   other point in the day. Some studies have shown an
   increased consumption of sugar due to aspartame
   (Blundell 1986).

c. Since diet products with aspartame have few calories and
   since many people have been conned into believing that
   it is safe, a significant percentage of people would
   likely "throw caution to the wind" and drink large
   quantities of diet soft drinks and eat large quantities
   of other products with aspartame. This is something that
   they would not be as likely to do with high-calorie,
   sugar-containing products.

The NutraSweet Company has been trying to convince people
that persons who ingesting aspartame regularly --
approximately 50% of the U.S. population (US Senate 1987, page
418) -- ingest only 1-3 mg/kg body weight/day of aspartame
(Butchko 1991, Abrams 1992). This is based on surveys and
diaries of consumers. What these surveys do not mention is
that aspartame-containing products are often ingested as
part of snacks and that people often forget what snacks
they've eaten. This was aptly described by Dr. Richard
Wurtman of MIT in a meeting with FDA officials on April 21,
1986 (Lisa 1994, page 201):

     "[NutraSweet's estimates of current use] show,
     among other things, that people consume less
     aspartame in the summer than in other months, a
     finding which violates good sense and reason.
     (This probably reflects the fact -- affirmed in
     our laboratories at MIT -- that people have much
     more difficulty accurately remembering snack than
     meal intakes . . . and most of the aspartame in
     the American diet comes via cold beverages and
     other snack foods.)"

Another set of similar surveys shows that Canada (7-day
survey) which has fairly cold average temperature has more
than 2.5 times the daily intake of aspartame than in U.S.
which has much hotter average temperatures (Butchko 1994).
This is ridiculous not only because aspartame ingestion in
warm climates would almost certainly be larger than in cold
climates, but also aspartame net sales outside the U.S.
amounts to only 10% of all net sales (Monsanto 1994) and
Canada's population is 10.8% of the U.S. population (CIA
1994). Therefore, Canada's intake of aspartame per person
cannot possibly be even equal to that in the U.S., even in
the extremely unlikely scenerio where all aspartame sold
outside the U.S. is sold only to Canada. (Note: The
percentage of regular aspartame users in the United States
and Canada are approximately the same if you believe
information provided by NutraSweet (Farber 1989, page 56,
Butchko 1991).

Another preposturous claim can be seen in a paper by Butchko
(1991). In this paper aspartame consumption for 6-12 year
old children was shown to decrease significantly from 1984
(the year after aspartame was approved for use in carbonated
beverages) to 1989 despite nearly tripling the sales of
aspartame from the middle of 1984 to 1989. (USDA 1988,
Monsanto 1990). By the time this survey began the percentage
of regular aspartame eaters in this age category was
approximately 25% (Abrams 1991). Therefore, an increase in
the percentage of regular aspartame users could not have
possibly accounted for the bulk of the increase in sales.
Who are they kidding!? It shows that these surveys cannot be
trusted to show anything close to accurate figures.

Perhaps another reason the average daily intake of aspartame
from these surveys is so low is due to the way that the
amount of aspartame ingested is calculated. For example,
Abrams (1991) points out that what is recorded on these
surveys is not the amount of aspartame ingested, but only
"the number of times an APM [aspartame] containing item of
food was eaten on that day by that person." This value is
then multiplied by the "average number of grams per eating
occasion of that food for a person of that age and sex
group" to give the total number of milligrams of aspartame
ingested. However, the "average number of grams per eating
occasion of that food for a person of that age and sex
group" is drawn from a 1977-1978 USDA National Food
Consumption Survey. Therefore, the calculations for the
total milligrams of aspartame ingested is based on an old
survey which may be equally inaccurate as far as snack food
ingestion goes and is most likely out of date. For example,
these calculations assume that the average person would
ingest the exact same amount of soft drink or diet food in
one sitting in 1977 as they would in 1994. With the
skyrocketing popularity of one- and two-liter bottles of
soft drinks and the marketing push for diet foods, this is a
ridiculous assumption.

What the NutraSweet tries to show with flawed studies and
surveys is often contradicted by other studies which they
fund or by statements made by their representatives. In
1976, Frey showed that children who are 7 to 12 years old
can have an aspartame intake anywhere from 35 mg/kg to 76
mg/kg per day when aspartame-containing snack food is
notrestricted (Frey 1976). Three studies on obese
individuals showed that their aspartame intake averaged 20
mg/kg per day (ranging from 8 to 36 mg/kg per day) (Porikos
1984). The Frey study and the three studies by Porikos
monitored aspartame intake much more closely than the
surveys often quoted by NutraSweet executives. Those surveys
relied on the ability of people to remember their snacks.

In an article from Science Times, Jane E. Brody states the
following (Congressional Record 1985a, page S5494):

     "The drug agency has set an allowable daily intake
     of 50 milligrams of aspartame per kilogram of body
     weight, and the agency predicted that actual
     average use would run around eight to ten
     milligrams. According to Dr. Gaull of Searle,
     levels of use found in a national survey last
     spring showed that the average was then already
     twice that--19 milligrams--and the maximum level
     consumed by 'aspartame abusers' was 28 milligrams.
     A United States attorney representing the F.D.A.
     said in court last month that average consumption
     is now 30 milligrams and that many consumers are
     above the 50 milligrams maxiumum suggested."

Farber gave an example of what a typical aspartame
consumption may be for a child (Farber 1989):

     "An 8-year-old of 20 kg, might eat the following:

       Cereal         250.0 mg
       Soda           200.0 mg
       Milkshake      350.0 mg
       Ice Pop        250.0 mg

       Total        1,050.0 mg of aspartame

     "This would equal 52.5 mg/kg of aspartame
     consumption....' [Note that even for a 60 kg
     adult, the above-listed example  would amount to
     over 17 mg/kg per day.]

On a hot Summer day, the child may ingest the aspartame
listed above and several more carbonated beverages. There
may be many children who are ingesting a full 2-liter bottle
of pop during an active Summer day (1100 mgs. of aspartame).
On top of that ingestion, there may be Jello, cereal, gum,
and many other aspartame-containing foods.

It is important to note that all aspartame-containing
products of the same type do not contain the same amount of
aspartame. For example, a one liter bottle of diet cola
averages aproximately 560 mg of aspartame. However, orange
soda contains as much as 930 mg of aspartame per liter
(Federal Register 1984).

Neuroscience researcher and Professor of Medicine at the
University of California, Dr. William Partridge testified
about the intake of aspartame before the U.S. Senate (US
Senate 1987, page 367):

     "The first question is the dosage problem. We are
     led to believe by the FDA this morning that the
     typical consumer will have 2 to 4 milligrams per
     kilogram of aspartame per day; that the 99th
     percentile intake is 34 milligrams per kilograms
     per day; and that the advisable daily intake or
     ADI is 50 milligrams per kilogram per day.
     "Now, the layperson sitting in the audience is
     really in no position to analyze these esoteric
     numbers. But if we put it in a different context
     and recognize that 50 milligrams per kilogram per
     day is equal to 5 servings of NutraSweet per 50-
     pound body weight, we can see that children, owing
     to their reduced body weight, are at a great risk
     for overconsumption of NutraSweet.
     "All one has to do in t his room is look up at
     that chart and ask yourself if a 50-pound or 60-
     pound 7 year-old is going to consume 5 or 6
     servings of that per day. If they are, then they
     have consumed 50 milligrams per kilogram per day,
     or the advisable daily intake.
     "Now, an 11-year[-old] study in the literature has
     already shown this, that the average 7-to-12-year-
     old, when made freely available to products like
     that, consumes 5 servings per 50-pound body weight
     per day, and up to 77 milligrams per kilogram per

In the National Soft Drink Association's draft objection to
use of aspartame in carbonated beverages it was stated (NSDA

     "FDA relied upon an intake value of 34 mg/kg/day
     in assessing the possible risks of aspartame,
     describing that level as the '. . . highest
     obtained from any estimate of potential
     consumption and exceed[ing] the 99th percentile
     consumption (25 mg/kg) for all age groups . . .'
     48 Fed. Reg. at 31377. For a 30 kg child, however,
     it would not be unualual for that level to be
     achieved or, in terms of the effect on plasma PHE
     (phenylalanine) levels, even exceeded. For
     example, if a 30 kg child consumed on a warm day
     after exercise approximately two-thirds of a two-
     liter bottle of soft drink sweetened soley with
     aspartame, that child would be consuming 700 mg of
     aspartame, or approximately 23 mg/kg. This alone
     roughly equals what FDA considered, the 99th
     percentile consumption level. If during the day
     this child consumed other aspartame-sweetened
     products, the exposure level could quickly [reach]
     FDA's so called 'loading dose' of 34 mg/kg. 48
     Fed. Reg. at 31377."

Had the child in the above example consumed two-thirds of a
two-liter bottle of aspartame-sweetened orange soda, the
values would be as high as 1240 mg of aspartame or 41.3
mg/kg/day for a 30 kg child.

What is generally agreed upon when discussing the intake
amounts of aspartame is the following:

   The majority of aspartame users ingest a relatively
   small (but  not necessarily safe) amount of aspartame.
   When plotting milligrams per day of aspartame ingested
   against the percentage of  U.S. population, a smaller
   percentage of the population will ingest the largest

Looking a studies I have seen in the literature as well as
USDA figures for artificial sweetener usage, I would
estimate that the average person who ingests aspartame
regularly ingests approximately 8 mg/kg per day. However, I
believe that at least 10 percent of regular aspartame users
ingest at least 20 mg/kg per day. This may amount to over 8
million people in the U.S. I would estimate that at least 1
percent of aspartame users ingest at least 50 mg/kg per day.
This may amount to nearly 1 million people. For most of
these people, the warm and hot weather intake will far
exceed their Winter intake, such that a person ingesting 20
mg/kg per day in the Winter may ingest 40 mg/kg per day in
the hot Summer months. According to Dr. Woodrow Monte,
Director of the Arizona State University Food Science and
Nutrition Laboratory, a significant number of people in
Arizona drink as much as two or three liters of diet soda
every day during the Summer (Monte 1995).

Even if we accept the FDA's projection that only 1% of the
regular aspartame users will consume more than 34 mg/kg/day
of aspartame, that still may amount to nearly 1 million
people. While the national average may be lower than 34
mg/kg/day of aspartame, there are undoubtedly several
hundreds of thousands of people who are consuming well over
34 mg/kg/day of aspartame, especially on hot Summer days.

Some researchers try to argue that they can use much less
than the current FDA Acceptable Daily Intake (ADI) in their
experiments as long as they use a test dosage well above the
average intake of aspartame as deterimined by these (flawed)
surveys. Stegink states the following (Stegink 1989):

     Initial consideration of these projected intakes
     might lead one to question their validity since 12
     oz of aspartame-sweetened beverage ingested by a
     27-kg 8-year-old child would account for 7.4 mg
     aspartame/kg body weight. However, when beverage
     intake data are examined, the projected aspartame
     intake values are consistent with these data. For
     example, Morgan et al reported that 7- to 8-year-
     old children ingest, on average 6.0 ± 4.2 oz soft
     drink daily (mean ± SD; value includes both
     regular and diet beverage) (Morgan 1985). Thus, an
     average 27-kg 8-year-old child would ingest 3.7 mg
     aspartame/kg body weight daily if all 6 oz of
     beverage were sweetened with aspartame. A 27-kg
     child ingesting beverage at 2 SD above the mean
     (approximately 97% of expected values) would
     ingest 14.4 oz of beverage. This would provide 8.9
     mg aspartame/kg body weight if all beverage
     consumed was sweetened with aspartame. Therefore,
     young children would have to drink unusually large
     quantities of beverage to ingest much larger
     quantities of aspartame."

What Stegink neglects to mention is the following:

1. The study cited
   by Stegink (Morgan 1985), does not take into account
   that, as Dr. Wurtman stated, snacks are commonly
   forgotten in daily food surveys so that the average
   ingestion of soft drinks would likely be much greater.

2. The study cited
   by Stegink uses data from a three-day survey instead of
   the more traditional seven-day survey making it less

3. The study cited
   by Stegink was published in 1985. This study was an
   evaluation of data from the 1977-78 Nationalwide Food
   Consumption Survey. Thus, the data was over ten years
   old when Stegink cited it and is now over 16 years old!
   Any adult in the U.S. who was not in a coma for the
   last 16 years knows that soft drink consumption has
   increased tremendously since the late 1970s.

4. Stegink neglects
   to mention that there are thousands of products with
   aspartame and that 7- to 8-year-old children can be
   ingesting significant amounts from foods and beverages
   othan than soft drinks.

5. While the average
   intake may be relatively low, although much higher than
   reported by Stegink and not necessary safe, there are
   undoubtedly a significant number of 7- to 8-year old
   children who are ingesting large quantities of aspartame
   by their own choice or by the choice of their parents to
   avoid sugar. It is ridiculous to use the "average" (even
   if it was accurately determined) to judge test amounts
   of aspartame.

The NutraSweet Company researchers have begun a concerted
effort to convince scientists and laypersons that they are
testing high doses of aspartame. This is based on consumer
surveys. The reality is that a) their surveys are flawed; b)
their own studies show subjects ingesting much higher
intakes of aspartame than they use in test; and c) they are
often testing using doses significantly below the FDA's
Allowable Daily Intake (ADI).

What should be used in experiments is double the ADI of real
world aspartame. Any argument for using less should be taken
as an admission that the ADI is not a safe amount of


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  Estimate Dietary Intake: Postmarket Surveillance of
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Blundell, J.E., A.J. Hill, 1986. "Paradoxical effects of an
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Butchko, Harriett H., Frank N. Kotsonis 1991. "Acceptable
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Butchko, Harriett H., Frank N. Kotsonis 1994. "Postmarketing
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Gordon, Gregory, 1987. "NutraSweet: Questions Swirl," UPI
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