ASPARTAME TRIGGERS: LIVER CANCER and LUNG CANCER IN LATEST STUDIES

______________________________________________

Am J Ind Med. 2010 Sep 30. 
Aspartame administered in feed through life span, induces cancers of the liver and lung in mice.
Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L.
Cesare Maltoni Cancer Research Center, Ramazzini Institute,
Bentivoglio, Bologna, Italy.

Abstract

BACKGROUND:
Aspartame (APM) is a well-known intense artificial sweetener used in more
than 6,000 products. Among the major users of aspartame are children and women of childbearing
age. In previous lifespan experiments conducted on Sprague-Dawley rats we have
shown that APM is a carcinogenic agent in multiple sites and that its
effects are increased when exposure starts from prenatal life.

OBJECTIVE:
The aim of this study is to evaluate the potential of APM to induce
carcinogenic effects in mice.

APM is metabolized in the gastrointestinal tract by esterases and
peptidases into three components: the amino acids phenylanine and
aspartic acid, and methanol [Ranney et al., 1976].

APM can be also absorbed into the mucosal cells prior to hydrolysis
and then metabolized within the cell to its three components which
then enter circulation [Mattews, 1984].

Methanol is not subject to metabolism within the enterocyte and
rapidly enters the portal circulation and is oxidized in the liver to
formaldehyde, an highly reactive chemical which strongly binds to
proteins [Haschemeyer and Haschemeyer, 1973] and nucleic acids
[Metzler, 1977] forming formaldehyde adducts.

In a study, in which APM, 14 C-labeled in the methanol carbon, was
given orally to adult male Wistar rats for 10 days, it was shown that
the carbon adducts of protein and DNA could have been generated only
from formaldehyde derived from APM methanol.
Moreover, it was suggested that the amount of formaldehyde adducts may
be cumulative [Trocho et al., 1998].

Several reviews conclude that APM is digested in all species in the
same way [Ranney et al., 1976].
Since APM is metabolized before entering the blood stream, there is no
distribution of APM outside the gastrointestinal tract.

Epidemiological studies conducted among users of artificial sweeteners
(including APM) did not show an increased carcinogenic risk, except in
one study which postulated an association of increased risk of brain
cancer and use of APM [Olney et al., 1996].

Studies performed by the US National ToxicologyProgram (NTP) in which
groups of 15 males and 15 females of transgenic mice, p53
haploinsufficient strain (p53) and Tg.AC homozygous strain (Tg.AC)
dermal exposure model were treated with diets containing 0, 3, 125,
6,250, 12,500, 25,000, or 50,000 ppm of APM for 40 weeks and then
sacrificed did not show any carcinogenic responses [NTP, 2005].
Overall there was no evidence of a positive response for tumors in
animals treated with APM in feed up to 50,000 ppm.
Although the studies did not show carcinogenic response, it should be
noted that altered genetic mice were evaluated by NTP with the intent
to develop faster, less costly and more predictive in vivo models for
identifying potential chemical carcinogenic agents and that APM was
selected as a presumed non-carcinogen.
Pritchard et al. [2003] evaluated the NTP findings regarding the
potential of transgenic mouse models to identify carcinogenic agents.
The authors concluded that the Tg.AC dermal exposure model and p53
oral exposure model had an overall accuracy of 74% in correctly
predicting chemicals that are listed by the International Agency for
Research on Cancer (IARC) and/or NTP in their respective lists of
chemicals classified carcinogenic or probably carcinogenic in humans.
The study concluded that the transgenic mouse models missed a number
of known or probable human carcinogens, whereas long-term rodent
bioassays missed none of these chemicals.

Indeed, the authors of the studies performed by NTP concluded that the
negative findings were of uncertain value:
''because this is a new model, there is uncertainty whether the
(aspartame) study possessed sufficient sensitivity to detect a
carcinogenic effect'' [NTP, 2005].
In fact the P53 deficient transgenic model does not respond to
non-genotoxic carcinogenic chemicals, and hence choosing that model
confirmed this fact with APM.
The NTP has since virtually discontinued the use of genetically
modified models for identifying carcinogens.

Long-term carcinogenicity bioassays performed on rats and mice in the
early 1970s by industry did not show any carcinogenic effects.
In female p53 haploinsufficient mice, the results of the micronucleus
test were judged to be positive, based on a significant trend test and
a small but statistically significant increased frequency of
micronucleated erythrocytes in the 50,000 ppm group
(P = 0.028) [NTP, 2005].

A detailed review and comments on the genotoxicity, long-term
carcinogenicity studies in rodents and epidemiological studies
available today on APM has been reported previously [Soffritti et al.,
2005, 2006, 2007].
Overall, we believe that the potential long-term toxic effects of APM,
and in particular the carcinogenic effects, had not been adequately
demonstrated by the long-term bioassays on rats and mice, mainly
because of the small number of animals used per sex per group and the
duration of the experiments (in which rodents were sacrificed at 110
weeks of age, corresponding to the two-thirds of the lifespan).

For these reasons we started a project encompassing several
experiments on rats and mice in which APM was administered in feed at
various doses to a large number of rats or mice per group per sex.
Treatment started at different ages and lasted for different periods;
rodents were always kept under observation until natural death to
allow APM to express all its full carcinogenic potential.

In the first experiment we demonstrated that APM, administered from 8
weeks of age for the lifespan to Sprague–Dawley rats, induced a
significantly increased incidence of lymphomas/leukemias and of
neoplastic lesions of the renal pelvis and ureter in females, and a
significantly increased incidence of malignant Schwannomas of the
peripheral nerves in males [Soffritti et al., 2006].

In a second experiment we showed that APM, administered from fetal
life until natural death, caused lymphomas/leukemias in male and
female rats and, for the first time, cancers of the mammary glands in
females [Soffritti et al., 2007].
Furthermore, this study demonstrated that when lifespan exposure
starts during fetal life, the incidences of lymphomas/leukemias were
increased in comparison to the treatment starting postnatally.
Neither cranial Schwannomas nor neoplasms of the renal pelvis and
ureter were observed in the second experiment.
This result may be explained by the fact that the number of rats per
sex per group in this study was lower and therefore the sensitivity of
the study for this type of tumors may have been reduced....

.... APM was pulverized in a standard pelleted diet at concentrations of
0, 2,000, 8,000, 16,000, or 32,000
to simulate an assumed daily APM intake of
0, 250, 1,000, 2,000, and 4,000 mg/kg b.w.,
and was administered to groups of 62–122 male and female Swiss mice
from the 12th day of fetal life until death.
The dose levels of APM were chosen on the basis of available data
reported in the literature.
The standard ''Corticella diet'' was provided by Laboratorio Dottori
Piccioni, Milan, Italy;
the same diet used for more than 30 years at the laboratory of the
Cesare Maltoni Cancer Research Center (CMCRC).
Fresh tap water was provided daily.
The major constituents of the diet were: water 12%; raw protein 24%;
raw fat 3.50%; raw fibers 5.50%; ashes 10.50%; non-nitrogenous extracts
56.50%.
The diet was analyzed for nutritional components, microorganisms, and
possible contaminants (pesticides, metals, estrogen activity,
nitrosamines, and aflatoxins) every 6 months, and disposed of if older
than 3 months from the date of manufacture.
The diet was formulated every 40–50 days.
At room temperature APM is stable in food and liquid.
The stability of APM in the feed was analyzed periodically during the
experiment.
Feed and water were supplied ad libitum.....

...DISCUSSION
The present study, in which APM was administered in feed at the dose
levels of 0, 2,000, 8,000, 16,000, or 32,000 ppm to Swiss mice from
prenatal life until death, further confirms that APM induces
carcinogenic effects in rodents.
The study shows:
(a) significant dose-related increase of hepatocellular carcinomas in
males (P < 0.01).
Incidences were also significantly increased at the two top dietary
concentrations of 32,000 ppm (P < 0.01) and 16,000 ppm (P < 0.05);
(b) a significant dose-related increase of the incidence of lung
alveolar/bronchiolar carcinomas (P < 0.01), and at 32,000 ppm (P <
0.05).
Since the survival of the males was not affected by APM exposure, we
used logistic analysis to evaluate the combined adenoma/carcinoma
results of the liver and of the lung.
The incidence of HCA and HCC combined resulted significantly increased
(P < 0.05) in the group treated at 16,000 ppm.
No significant dose–response was observed.
The reason for the lack of significance is that the dose–response is
flat over the exposure groups while the controls are lower (i.e., 12.8,
21.4, 21.0, 25.0, and 20.5).
It is noticeable that until 98 weeks of age 8/55 deceased males
(14.6%) treated at 32,000 ppm had HCC and no HCA.
On the contrary, three HCA and no HCC were observed among the 60
controls deceased in the same period.
This may depend on a more rapid progression of preneoplastic lesions to HCC.
However, others suggest that the response to carcinogens differ, and
that both HCA and HCC may develop de novo, without going through the
stage of foci of cellular alterations [Frith et al., 1979].
A significant dose-related trend (P < 0.05) of A/BA and A/BC combined
was observed among males.
Moreover, the incidence of A/BA plus A/BC in males treated at 32,000
ppm was significantly increased (P < 0.05) compared to controls.

Both liver and lung carcinomas in all exposure groups of males were
within the historical control range of these neoplasms in the CMCRC
laboratory.

Concerning the HCC, the concurrent control (5.1%) falls within the
lower range of our historical controls (0–26.3%) and because the
incidences of HCC in the groups treated at 32,000 (18.1%) and 16,000
(15.6%) were over three and two times the concurrent control, we
considered this effect related to the treatment.

Concerning A/BC, the concurrent  control (6.0%) falls also within the
lower range of our
historical controls (0–14.3%) and because the incidence observed at
the highest dose was more than double the concurrent control we
considered these effects to be related
to APM exposure [Haseman et al., 1984; Haseman, 1992, 1995].

No differences were observed in the incidences of liver and lung
tumors among the females of treated and control groups.
It has been reported that both spontaneously occurring and treatment
induced hepatocellular tumors occur with significantly greater
frequency and multiplicity in males
than in females even though occasionally exceptions do occur [Maronpot, 2009].
Male mice are also more susceptible to develop A/BA and A/BC than
females [Hahn et al., 2007; Dixon et al., 2008].

The carcinogenic effects observed in our mouse bioassay do not support
the negative outcome obtained with the CD-1 mouse study performed at
the Searle Laboratory in 1974 [Molinary, 1984].
In that experiment one group of 72 male and female CD-1 mice (control)
and three groups of 32 males and 32 females were treated,
respectively, with APM in feed at the dose levels of 0, 1, 2, 4 g/kg
from prenatal life for 2 years.
These studies are not comparable for two reasons:
(a) the number of the treated animals per sex per group is smaller in
comparison to the number in our experiment and to the number requested
by the current standard for carcinogenic bioassays (at least 50
animals per sex per group) used by NTP
and most others and
(b) the length of observation is much shorter (110 weeks compared to
130 weeks).
Both of these factors result in a loss of sensitivity for detecting a
carcinogenic effect.

As already reported [Soffritti et al., 1999; Haseman et al., 2001;
Huff et al., 2008; Soffritti et al., 2008], in longterm
carcinogenicity bioassays the number of animals per sex/group and life
span observation are critical points for identification and assessment
of diffuse carcinogenic risks, defined as the exposure to a single or
multiple agents or to mixtures that are expected to have limited
carcinogenic potential because of the agent type (weak carcinogen)
and/or dose/concentration (low), but that involve large group of the
population (as is the case with APM).

Concerning the prolonged (over 110 weeks of age) or lifespan duration
of the experiment, we must consider that neoplastic response depends
not only on the chemical–physical characteristics of the agent and its
toxicological properties, the mode of exposure, and the type of
animals, but also, to a greater extent, on the latency of the tumor
which varies and may be very long.
Truncating an experiment after 2 years (more or less two-thirds of the
natural life of rodents) as requested by several regulatory agencies
(and as practiced by NTP), may mask a possible carcinogenic response.
This has been shown by us in experiments on benzene, Mancozeb (a
widely used fungicide), vinyl acetate, toluene, and xylenes [Soffritti
et al., 2002].
It should be noted that in the experiment on toluene and xylenes
performed by NTP, in which the rats were sacrificed after 104 weeks of
treatment, no carcinogenic effects were found [Huff, 2002, 2003; Huff
et al., 2010], whereas lifetime studies conducted in the CMCRC showed
unequivocal carcinogenicity after 104 weeks [Maltoni et al., 1997;
Soffritti et al., 2004].
These two factors in our opinion makes the Searle study less sensitive
than ours.

Overall, the results of our integrated project of lifespan
carcinogenic bioassays on APM conducted on Sprague–Dawley rats and
Swiss mice are consistent in showing that under our experimental
conditions APM must be considered a trans-species carcinogenic agent
in multiple sites (Table V), inducing a significantly increased
incidence of malignant tumors in:
(a) multiple tissues in male and female rats;
(b) multiple organs in male mice;
(c) an earlier occurrence in treated animals and an higher incidence
and an anticipated onset of cancers when the treatment starts from
fetal life [Soffritti et al., 2007].

Finally, the carcinogenic effects of APM in rats were shown also at
dose levels of 100 and 20 mg/kg b.w. to which humans could be exposed
[Soffritti et al., 2006, 2007].

CONCLUSIONS

The present study demonstrates for the first time that APM administered
in feed to Swiss mice at doses of 32,000, 16,000, 8,000, 2,000, or 0
ppm, starting the dietary exposure on day 12 of gestation and lasting
until death, induces significant dose-related increases of
hepatocellular carcinomas (P<0.01) and of alveolar/bronchiolar
carcinomas (P < 0.05) in males.
In particular, the significant increased incidences of hepatocellular
carcinomas were observed at the dietary levels of 32,000 ppm (P<0.01)
and 16,000 ppm (P<0.05) and of lung alveolar/bronchiolar carcinomas at
32,000 ppm (P<0.05).
HCA and HCC (combined) resulted significantly increased (P<0.05) in the
male group treated at 16,000 ppm.
A/BA and A/BC (combined) resulted significantly increased (P<0.05) in
the male group treated at 32,000 ppm.
A significant dose-related trend (P<0.05) was also observed.

Given that APM is completely metabolized in the gastrointestinal tract
to phenylalanine, aspartic acid, and methanol, it may be concluded
that the observed carcinogenic effects were caused not by APM itself
but rather by its metabolites.

In particular, it cannot be disregarded that the conversion of APM
methanol into formaldehyde in the liver may result in a generation of
formaldehyde adducts [Trocho et al., 1998], which could explain the
plausibility of hepatocarcinogenic effects of APM in male mice.

The fact that females did not develop a significantly increased
incidence of liver tumors may be explained by the gender resistance,
as already reported.

On the basis of these results, together with previous carcinogenicity
bioassays conducted on rats in our laboratories, APM should be
considered a multiple site, transspecies carcinogenic agent.

A re-evaluation of the current regulations on APM remains, in our
opinion, urgent.

ACKNOWLEDGMENTS

This research was supported entirely by the Ramazzini Institute.
The authors declare that they have no competing financial interests.
The authors thank Dr. David Hoel for his great support in the
statistical evaluation of the results.
A special thanks to the U.S. National Toxicology Program for having
organized a meeting of a group of pathologists at NIEHS in order to
provide a second opinion regarding the pathological lesions observed
in the APM Swiss mice study.
Ten pathologists participated in the NTP histopathology review.
The number of slides reviewed was 100 of which 26 were the subject of
discussion.
In the remaining cases, the original Ramazzini Institute diagnoses
were confirmed.
The lesions reviewed were liver adenomas/carcinomas and angiosarcomas;
lung adenomas/carcinomas; lymphomas; skin fibrosarcomas; and a few
miscellaneous lesions.

With regard to the data presented in this manuscript (liver and lung
tumors) there were no discrepancies between NTP and RI pathology
evaluation.

A special thanks to Luana De Angelis and to all the CRCCM staff who
were involved in the study.

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"CONCLUSIONS
The present study demonstrates for the first time that APM (Aspartame), administered
in feed to Swiss mice at doses of 32,000, 16,000, 8,000, 2,000, or 0
ppm, starting the dietary exposure on day 12 of gestation and lasting
until death, induces significant dose-related increases of:
hepatocellular carcinomas (P<0.01) and of alveolar/bronchiolar
carcinomas (P < 0.05) in males.
In particular, the significant increased incidences of hepatocellular
carcinomas were observed at the dietary levels of 32,000 ppm (P<0.01)
and 16,000 ppm (P<0.05) and of lung alveolar/bronchiolar carcinomas at
32,000 ppm (P<0.05).
HCA and HCC (combined) resulted significantly increased (P<0.05) in the
male group treated at 16,000 ppm.
A/BA and A/BC (combined) resulted significantly increased (P<0.05) in
the male group treated at 32,000 ppm.
A significant dose-related trend (P<0.05) was also observed.

Given that APM is completely metabolized in the gastrointestinal tract
to phenylalanine, aspartic acid, and methanol, it may be concluded
that the observed carcinogenic effects were caused not by APM itself
but rather by its metabolites.

In particular, it cannot be disregarded that the conversion of APM
methanol into formaldehyde in the liver may result in a generation of
formaldehyde adducts [Trocho et al., 1998], which could explain the
plausibility of hepatocarcinogenic effects of APM in male mice.

The fact that females did not develop a significantly increased
incidence of liver tumors may be explained by the gender resistance,
as already reported.

On the basis of these results, together with previous carcinogenicity
bioassays conducted on rats in our laboratories, APM should be
considered a multiple site, transspecies carcinogenic agent.

*A re-evaluation of the current regulations on APM remains, in our
opinion, urgent. *
http://www.ncbi.nlm.nih.gov/pubmed/20886530

ACKNOWLEDGMENTS

This research was supported entirely by the Ramazzini Institute.
The authors declare that they have no competing financial interests.
The authors thank Dr. David Hoel for his great support in the
statistical evaluation of the results.
A special thanks to the U.S. National Toxicology Program for having
organized a meeting of a group of pathologists at NIEHS in order to
provide a second opinion regarding the pathological lesions observed
in the APM Swiss mice study.
Ten pathologists participated in the NTP histopathology review.
The number of slides reviewed was 100 of which 26 were the subject of
discussion.
In the remaining cases, the original Ramazzini Institute diagnoses
were confirmed.
The lesions reviewed were liver adenomas/carcinomas and angiosarcomas;
lung adenomas/carcinomas; lymphomas; skin fibrosarcomas; and a few
miscellaneous lesions.

With regard to the data presented in this manuscript (liver and lung
tumors) there were no discrepancies between NTP and RI pathology
evaluation."

METHODS:
Six groups of 62-122 male and female Swiss mice were treated with APM in
feed at doses of 32,000, 16,000, 8,000, 2,000, or 0 ppm from prenatal life
(12 days of gestation) until death.
At death each animal underwent complete necropsy and all tissues and organs
of all animals in the experiment were microscopically examined.
RESULTS:
APM in our experimental conditions induces in males a significant
dose-related increased incidence of hepatocellular carcinomas (P<0.01),
and a significant increase at the dose levels of 32,000?ppm (P<0.01) and
16,000 ppm (P<0.05).
Moreover, the results show a significant dose-related increased incidence of
alveolar/bronchiolar carcinomas in males (P<0.05),
and a significant increase at 32,000?ppm (P<0.05).
CONCLUSIONS:
The results of the present study confirm that APM is a carcinogenic agent in
multiple sites in rodents,
and that this effect is induced in two species,
rats (males and females) and mice (males).
No carcinogenic effects were observed in female mice.
Am. J. Ind. Med. © 2010 Wiley-Liss, Inc.
PMID: 20886530

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Abbreviations:
APM, aspartame;
CMCRC/RI, Cesare Maltoni Cancer Research Center/Ramazzini Institute;
EFSA, European Food Safety Authority;
EU, European Union;
FDA, Food and Drug Administration.

Cesare Maltoni Cancer Research Center, Ramazzini Institute,
Bentivoglio, Bologna, Italy
Contract grant sponsor: Ramazzini Institute.
*Correspondence to: Morando Soffritti, Cesare Maltoni Cancer Research
Center, Ramazzini Institute, Castello di Bentivoglio,Via Saliceto, 3,
40010 Bentivoglio, Bologna, Italy. 
Accepted 30 July 2010
DOI 10.1002/ajim.20896.
Published online 30 September 2010 in Wiley Online Library
(wileyonlinelibrary.com)

(Aspartame Consumer Safety Network and Pilot Hotline since 1987: http://www.aspartamesafety.com/); (marystod.blogspot.com); (marystod.Twitter.com); (marystod@youtube.com)

METHANOL IN ASPARTAME and NEOTAME - Peer Reviewed Journal Study Results

ASPARTAME: METHANOL AND THE PUBLIC HEALTH

DR. WOODROW C. MONTE

 ABSTRACT

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

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

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

 The average intake of methanol from natural sources varies but limited data suggests an average intake of considerably less than 10 mg/day8. Alcoholics may average much more, with a potential range of between 0 and 600 mg/day, depending on the source and in some cases the quality of their beverages.

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

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

*NutraSweet is a trademark of G.D. Searle & Co.

Director of the Food Science and Nutrition Laboratory Arizona State University Tempe, Arizona 85287

ASPARTAME

 Aspartame (L-aspartyl-L-phenylalanine methyl ester) has recently been approved as a sweetener for liquid carbonated beverages. It has had wide acceptance as an additive in many dry food applications after Food and drug Administration approval on July 24, 1981.

 The Food and Drug Administration, Dr. Richard Wurtman and myself have received well over a thousand written complaints relative to aspartame consumption. By far, the most numerous of these include dizziness, visual impairment, disorientation, ear buzzing, high SGOT, tunnel vision, loss of equilibrium, severe muscle aches, numbing of extremities, pancreatitis, episodes of high blood pressure, retinal hemorrhaging, menstrual flow changes, and depression. The validity of these complaints has yet to be scientifically evaluated. However, a thorough knowledge of just what makes this new sweetener stand apart from other nutritional substances might aid physicians in making dietary recommendations for their patients.

 Aspartame (NutraSweet)* is a small molecule made up of three components: Phenylalanine, aspartic acid, and methanol (wood alcohol)47. When digested, these components are released into the bloodstream.

 Phenylalanine and aspartic acid are both amino acids which are found in natural proteins, and under normal circumstances are beneficial, if not essential, for health. Proteins are complex molecules which contain many chemically bonded amino acids. it takes several enzymes to break these bonds and liberate the amino acids. This is a slow process and the amino acids are released gradually into the bloodstream. The quaternary structure of protein also slows the digestion of these amino acids: the amino acids in the center of the protein molecule aren't released until the outer layers of amino acids on the surface have been swept away. This natural time release process saves the body form large numbers of any one of the 21 amino acids being released into the bloodstream at any one time.

 Aspartame requires the breaking of only two bonds for absorptioin. This happens very quickly with the potential to raise component blood levels rapidly. The methyl ester bond of phenylalanine is the first to cleave due to its susceptibility to pancreatic enzymes. This is highly unusual; the methyl esters associated with pectin for instance are completely impervious to all human digestive enzymes.

 

AMINO ACID COMPONENTS

Phenylalanine

 Phenylalanine is an essential amino acid, the daily consumption of which is required to maintain life. However, Dr. Richard J. Wurtman, Professor of Neuroendocrine Regulation at the Massachusetts Institute of Technology, presented data to the FDA demonstration that in humans the feeding of a carbohydrate with aspartame significantly enhances aspartame's positive effect on plasma and brain phenylalanine and tyrosine levels (48 Federal Register at 31379). There are sound scientific reasons to believe that increasing the brain levels of these large neutral amino acids could affect the synthesis of neurotransmitters and in turn affect bodily functions controlled by the autonomic nervous system (e.g., blood pressure). The proven ability of aspartame to inhibit the glucose-induced release of serotonin within the brain may also affect behaviors, such as satiety and sleep.

Aspartic acid

 Aspartic acid, is not an essential amino acid but is normally easily utilized for human metabolism. However, under conditions of excess absorption it has caused endocrine disorders in mammals with markedly elevated plasma levels of luteinizing hormone and testosterone in the rat and release of pituitary gonadotropins and prolactin in the rhesus monkey. The amount of luteinizing hormone in the blood is a major determinant of menstrual cycling in the human female.

METHANOL

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

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

 Methyl alcohol produces the Methyl alcohol syndrome, consistently, only in humans and no other test animal, including monkeys. There is a clear difference between "toxicity", which can be produced in every living thing, and the "toxic syndrome".

 

 The greater toxicity of methanol to man is deeply rooted in the limited biochemical pathways available to humans for detoxification. The loss of uricase (EC 1.7.3.3.), formyl-tetrahydrofolate synthetase (EC 6.3.4.3.) and other enzymes during evolution sets man apart from all laboratory animals including the monkey. There is no generally accepted animal model for methanol toxicity. Humans suffer "toxic syndrome" at a minimum lethal dose of < 1 gm/kg, much less than that of monkeys, 3-6 g/kg. The minimum lethal dose of methanol in the rat, rabbit, and dog is 9.5, 7, and 8 g/kg, respectively; ethyl alcohol is more toxic than methanol to these test animals. No human or experimental mammalian studies have been found to evaluate the possible mutagenic, teratogenic or carcinogenic effects of methyl alcohol, though a 3.5% chromosomal aberration rate in testicular tissues of grasshoppers was induced by an injection of methanol.

 The United States Environmental Protection Agency in their Multimedia environmental Goads for Environmental Assessment recommends a minimum acute toxicity concentration of methanol in drinking water at 3.9 party per million, with a recommended limit of consumption below 7.8 mg/day. 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."

Role of Formaldehyde

 Recently the toxic role of formaldehyde (in methanol toxicity) has been questioned. No skeptic can overlook the fact that, metabolically, formaldehyde must be formed as an intermediate to formic acid production. Formaldehyde has a high reactivity which may be why it has not been found in humans or other primates during methanol poisioning. The localized retinal production of formaldehyde from methanol is still thought to be principally responsible fro the optic papillitis and retinal edema always associated with the toxic syndrome in humans. This is an intriguing issue since formaldehyde poisoning alone does not produce retinal damage.

 If formaldehyde is produced form methanol and does have a reasonable half life within certain cells in the poisoned organism the chronic toxilogical ramifications could be grave. Formaldehyde is a know carcinogen producing squamous-cell carcinomas by inhalation exposure in experimental animals. The available epidemiological studies do not provide adequate data for assessing the carcinogenicity of formaldehyde in man. However, reaction of formaldehyde with deoxyribonucleic acid (DNA) has resulted in irreversible denaturation that could interfere with DNA replication and result in mutation. Glycerol formal, a condensation product of glycerol and formaldehyde (which may be formed in vivo), is a potent teratogen causing an extremely high incidence of birth defects in laboratory animals. even the staunchest critic of formaldehyde involvement in methanol toxicity admits:

 "It is not possible to completely eliminate formaldehyde as a toxic intermediate because formaldehyde could be formed slowly within cells and interfere with normal cellular function without ever obtaining levels that are detectable in body fluid or tissues."34

Acute Toxicity in man "Toxic Syndrome"

 A striking feature of methyl alcohol syndrome the asymptomatic interval (latent period) which usually lasts 12 to 18 hours after consumption. This is followed by a rapid and severe acidosis caused partially by the production of formic acid. Insufficient formic acid is generated to account for the severity of metabolic acidosis produced and, therefore, other organic acids may be involved.

 Patients may complain of lethargy, confusion, and impairment of articulation, all frequently encountered signs in moderate central nervous system (CNS) intoxications resulting from other toxic compounds.

 Patients may also suffer leg cramps, back pain, severe headache, abdominal pain, labored breathing, vertigo and visual loss, the latter being a very important clue to making a diagnosis of methanol poisoning. Other striking clinical features associated only with the oral administration of methanol are elevated serum amylase are the finding of pancreatitis or pancreatic necrosis on autopsy.

 In fatal cases liver, kidneys and heart may show parenchymatous degeneration. the lungs show desquamation of epithelium, emphysema, edema, congestion and bronchial pneumonia.

Chronic Human Exposure

 This is the most important aspect of methanol toxicity to those who are interested in observing the effect of increased methanol consumption on a population.

 The data presented here were compiled by the Public Health Service. The individuals studied were working in methanol contaminated environments. It is interesting to note that the visual signs always associated with acute toxicity often do not surface under chronic conditions.

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

ALCOHOLICS: CHRONIC METHANOL CONSUMPTION

 Alcoholics in general, but particularly those who consume large quantities of wine or fruit liqueur, would seem, from the available evidence, to be the only population thus far exposed to consistently high levels of methanol ingestion (Table 1). The high ethanol/methanol ratio of alcoholic beverages must have a very significant protective effect, though enzyme kinetics mandate some constant but low level of methanol metabolism. One could speculate that the delicate balance which maintains this defense might be jeopardized by the general nutritional neglect and specifically the folic acid deficiency associated with the meager food intake of some alcoholics. Alcoholics have a much higher incidence of cancer and other degenerative diseases, none of which can be attributed to ethanol alone. The fascinating similarities linking unusual clinical features of methanol toxicity and alcoholism are worth noting.

 Neuritis:

 Chronic occupational exposure to methanol often produces human complaints of neuritis with paresthesia, numbing, prickling and shooting pains in the extremities.

 Alcoholic polyneuropathy or multiple peripheral neuritis21 differs symptomatically from the methanol induced syndrome only in its first and often exclusive affinity for legs. The unpleasant sensations of intolerable pain associated with slight tactile stimulation is not an uncommon anecdotal consumer complaint following long term consumption of aspartame. In one such case reported to me, my interpretation of an electromyogram indicated the signs of denervation indicative of alcoholic polyneuropathy. The individual's ischemic lactate pyruvate curve, before and after fasting, was flat. Less that six weeks after aspartame consumption ceased the major symptoms subsided and repetition of these tests produced normal responses, although the individual still experienced intermittent pain.

Pancreatitis:

 Methanol is one of the few etiologic factors associated with acute pancreatic inflammation. Microscopic findings of pancreatic necrosis on autopsy have been reported after acute oral methanol poisoning. In fact, pancreatic injury probably accounts for almost universal violent epigastric pain and occasional elevated serum amylase levels which marks the end of the latent period.

 There is a generally accepted association between alcoholism and pancreatitis. Most patients, however, give a history of 5 to 10 years of heavy drinking before the onset of the first attack. The fact that 40% of all cases of acute pancreatitis complaints are attributable to alcoholics, however, must be taken into consideration to avoid artifactual association. Pancreatitis has been a complaint associated with aspartame consumption.

Methanol and the Heart:

 A 21-year-old non-drinking male who had been exposed daily to the fine dust of aspartame at the packaging plant he had worked for over a year, was complaining of blurred vision, headaches, dizziness, and severe depression before his sudden death. An autopsy revealed (aside from the organ involvement one might expect from methanol toxicity) myocardial hypertrophy and dilatation with the myocardiopathy and left ventricle involvement reminiscent of alcoholic cardiomyopathy. Alcoholic cardiomyopathy however typically occurs in 30-55 year old men who have a history of alcohol intake in quantities comprising 30 to 50 percent of their daily caloric requirement over a 10 to 15 year period.

 It has been suggested that alcohol is the etiologic factor in a least 50 percent of the cases of congestive cardiomyopathy. The significantly lower hospitalization incidence for coronary disease among moderate drinkers than among nondrinkers and protection to coronary risk afforded the moderate drinker (less than two drinks a day) over the nondrinker seems contradictory. However, if we implicate methanol as the etiologic factor, then clearly the nondrinker is at a disadvantage with a much lower ethanol to methanol ration (Table 1) when consuming naturally occurring methanol in a diet otherwise equivalent to the drinkers. The chronic alcoholic for reasons already proposed might sacrifice this protection.

 As mentioned below, high temperature canning as developed late in the 19th century should increase significantly the methanol content of fruits and vegetables. The increased availability and consumption of these food products in various countries over the years may parallel better than most other dietary factors the increase in incidence of coronary disease in their populations. Cigarette smoke, a known coronary risk factor, contains four times as much methanol as formaldehyde and only traces of ethanol.

ETHANOL AND FOLIC ACID

 The importance of ethanol as an antidote to methanol toxicity in humans is very well established in the literature. The timely administration of ethanol is still considered a vital part of methanol poisoning management. Ethanol slows the rate of methanol's...

 

 conversion to formaldehyde and formate, allowing the body time to excrete methanol in the breath and urine. Inhibition is seen in vitro even when the concentration of ethyl alcohol was only 1/16th that of methanol. The inhibitory effect is a linear function of the log of the ethyl alcohol concentration, with a 72% inhibition rate at only a 0.01 molar concentration of ethanol.

 Oxidation of methanol, like that of ethanol, proceeds independently of the blood concentration, but a rate only one seventh to one fifth that of ethanol.

 Folacin may play an important role in the metabolism of methanol by catalyzing toe elimination of formic acid. If this process proves to be a protective for humans as has been shown in other organisms it may account, in part for the tremendous variability of human responses to acute methanol toxicity. Folacin in a nutrient often found lacking in the normal human diet, particularly during pregnancy and lactation.

METHANOL CONTENT OF ASPARTAME SWEETENED BEVERAGES

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

 To look at the issue from another perspective, the literature reveals death from consumption of the equivalent of 6 gm of methanol. It would take 200 12 oz. cans of soda to yield the lethal equivalent of 6 gm of methanol According to FDA regulations, compounds added to foods that are found to cause some adverse health effect at a particular usage level are actually permitted in foods only at much lower levels. The FDA has established these requirements so that an adequate margin of safety exists to protect particularly sensitive people and heavy consumers of the chemical. Section 170.22 of Title 21 of the Code of Federal Regulations mandates that this margin of safety be 100-fold below the "highest no-effect" level has tragically not been determined for methanol, but assuming very conservatively that the level is one tenth of the lethal dose, the FDA regulations should have limited consumption to approximately 2.4 ounces of aspartame sweetened soft drink per day,

 The FDA allows a lower safety margin only when "evidence is submitted which justifies use of a different safety factor." (21.C.F.R. 170.22) No such evidence has been submitted to the FDA for methanol. Thus, not only have the FDA's requirements for acute toxicity not been met, but also, no demonstration of chronic safety has been made. The fact that methyl alcohol appears in other natural food products increases greatly the danger of chronic toxicity developing by adding another unnatural source of this dangerous cumulative toxin to the food system.

NATURAL SOURCES OF METHANOL

 Methanol does appear in nature.

 To determine what impact the addition of a toxin will have on an environment it is very helpful to accurately determine the background levels of consumption.

 Fruit and vegetables contain pectin with variable methyl ester content. However, the human has no digestive enzymes for pectin, particularly the pectin esterase required for its hydrolysis to methanol. Fermentation in the gut may cause disappearance of pectin but the production of free methanol is not guaranteed by fermentation In fact, bacteria in the colon probably reduce methanol directly to formic acid or carbon dioxide (aspartame is completely absorbed before reaching the colon). Heating of pectins has been shown to cause virtually no demethoxylation: even temperatures of 120 C produced only traces of methanol. Methanol evolved during cooking of high pectin foods7 has been accounted for in the volatile fraction during boiling and is quickly lost to the atmosphere. Entrapment of these volatiles probably accounts for the elevation in methanol levels of certain fruit and vegetable products during canning.

 In the recent denial by the food and drug Administration of my request for a public hearing on this issue, the claim is made by them that methanol occurs in fruit juice at an average of 140 parts per million (a range of between 15-640 parts per million). This often used average originates from a informative table in a conference paper presented by Francot and Geoffroy. The authors explain that the data presented in the table "may not" represent their work but "other authors". There is no methodology given nor is the original source cited and only the identity of the lowest methanol source, grape juice (12 ppm), and the highest, black currant (680 ppm), are revealed. The other 22 samples used to generate this disarmingly high average are left completely to the imagination. The authors conclude their paper by insisting that "the content of methanol in fermented or non-fermented beverages should not be of concern to the fields of human physiology and public health." They imply that wines "do not present any toxicity" due to the presence of certain natural protective substances. When they present their original data relating to the methanol content of French wines (range 14-265 ppm) or when the methanol content of any alcoholic beverage is given, the ratio of methanol to ethanol is also presented. Of the wines they tested, the ratio associated with the highest methanol content (265 ppm) indicates over 262 times as much ethanol present as methanol. the scientific literature indicates that a fair estimate of methanol content of commonly consumed fruit juices is on the order of 40 parts per million (Table 1). Stegink, et al. points out that some neutral spirits contain as much as 1.5 grams/liter of methanol, what is not mentioned is the fact if these spirits are at least 60 proof (30% ethanol) this still represents the presence of over 200 molecules of ethanol for every molecule of methanol that is digested. An exhaustive search of the present literature indicates that no testing of natural substances has ever shown methanol appearing alone; in every case ethanol is also present, usually, in much higher concentrations. Fresh orange juices can have very little methanol (0.8 mg/liter), and have a concomitant ethyl alcohol content of 380 mg/liter. Long term storage in cans has a tendency to cause an increase in these levels, but even after three years of storage, testing has revealed only 62 mg/liter of methanol, with an ethanol content of 484 mg/liter. This is a ratio of almost eight times ethanol/methanol. Testing done recently in Spain showed orange juice with 33 mg/liter methanol and 651 mg/liter ethanol (20/1 ratio). The range for grapefruit juices are similar, ranging form 0.2 mg methanol/liter to 43 mg methanol/liter. The lowest ratio or any food item was found in canned grapefruit sections with 50- 70 mg/liter methanol and 200-400 mg/liter ethanol, thus averaging six molecules ethanol for every molecule of methanol.

 This high ethanol to methanol ratio, even a these low ethanol concentrations, may have some protective effect. As stated previously, ethanol slows the rate of methanol's conversion to formaldehyde and formate allowing the body time to excrete methanol in the breath and urine. Inhibition is seen in vitro even when the concentration of ethyl alcohol was only 1/16th that of methanol. The inhibitory effect is a linear function of the log of the ethyl alcohol concentration, with a 72% inhibition rate at only a 0.01 molar concentration of ethanol. Therefore if a liter of a high methanol content orange juice is consumed, with 33 mg/liter of methanol and a 20/1 ratio of ethanol/methanol, only one molecule of methanol in 180 will be metabolized into dangerous metabolites until the majority of the ethanol has been cleared from the bloodstream. If a similar amount of methanol equivalent from aspartame were consumed, there would be no competition.

 Another factor reducing the potential danger associated with methanol from natural juices is that they have an average caloric density of 500 Kcal/liter and high osmolarity which places very definite limits to their consumption level and rate.TABLE 1

AVAILABLE METHANOL IN VARIOUS BEVERAGES

 METHANOL mg/liter METHANOL (MG.) CALORIC DENSITY Calories/Liter RATIO Consumed per 1,000 Calories *Methanol (mg.) Ethanol (wt.) Methanol (wt.) Consumption per day Juices *Orange, fresh28 1 470 2 475 1 *Orange, fresh45 33470 70206 mg *Orange, fresh31 34470 72166 mg *Orange, canned2831470 66156 mg *Grapefruit, fresh27 1 400 1 2000 1 mg *Grapefruit31 43400 108 5 7 mg Grapefruit, Canned31 27400 689 5 mg Grape15 12660 18---- Alcoholic Beverages Beer (4.5%) 0 400 ------ Grain Alcohol55 1 2950 1 500000 -- Bourbon, 100 proof55 552950 199090 -- Rum, 80 proof15 732300 325000 -- Wines

 

 (French)15 White 32800 442500 -- Rose 78800 981000 -- Red 128 800 160 667 -- Pear 188 1370 137 250 -- Cherry 276 1370 201 294 -- Wines (American)30 Low 50800 622500 -- High 325 800 406 385 -- Aspartame Sweetened Beverages48 2 liters 5 liters Uncarbonated Drinks48 558 6875 0 110 mg 275 mg Cola (Carbonated)48 568 7000 0 112 mg 280 mg Orange (Carbonated)48 918 11375 0 182 mg 455 mg Aspartame, pure25000 *17.6% of U.S. Population consume an average of 185.5 gm of Orange juice a day1 *1.1% of the U.S. Population consume an average of 173.9 gm of Grapefruit Juice a day1

 Data obtained in a Department of Agriculture survey of the food intake of a statistically sampled group of over 17,000 consumers nationwide, indicate that the 17.6% of the population that consume orange juice daily take in an average of 185.5 gm of that juice. these statistics indicated that 1.1% of the population consume an average of 173.9 gm of grapefruit juice while only 1.8% drink approximately 201 gm of tomato juice daily. Table 1 shows that under normal conditions these individuals would only be expected to consume between 1 and 7 mg of methanol a day from the sources. Even if an individual consumed two juices in the same day or a more exotic juice such as black currant, there would still be some protection afforded by the ethanol present in these natural juices. Consumption of aspartame sweetened drinks at levels commonly used to replace lost fluid during exercise yields methanol intake between 15 and 100 times these normal intakes (Table 1). This is comparable to that of "winos" but without the metabolic reprieve afforded by ethanol. An alcoholic consuming 1500 calories a day from alcoholic sources alone my consume between 0 and 600 mg of methanol each day depending on his choice of beverages (Table 1).

 The consumption of aspartame sweetened soft drinks or other beverages is not limited by either calories or osmolarity, and can equal the daily water loss of an individual (which for active people in a state like Arizona can exceed 5 liters). The resultant daily methanol intake might then rise to unprecedented levels. Methanol is a cumulative toxin8 and for some clinical manifestations it may be a human-specific toxin.

CONCLUSION

 Simply because methanol is found "naturally" in foods, we can not dismiss the need for carefully documented safety testing in appropriate animal models before allowing a dramatic increase in its consumption.

 We know nothing of the mutagenic, teratogenic or carcinogenic effect of methyl alcohol on man or mammal5. Yet, if predictions are correct5 it won't be long before an additional 2,000,000 pounds of it will be added to the food supply yearly.

 Must this, then, constitute our test of its safety?

 

 References

1. Agricultural Research Service, U.S. Department of Agriculture, portion sizes and days intakes of selected foods. ARS-NE-67 (1975) 

2. Bartlett, G.R., Inhibition of Methanol Oxidation by Ethanol in the Rat. Am. J. Physiol., 163:619-621 (1950). 

3. Braverman, J. B. S. and Lifshitz, A., Pectin Hydrolysis in Certain Fruits During Alcoholic Fermentation. Food Tech., 356-358. July, (1957). 

4. Browing, E., Toxicity and Metabolism of Industrial Solvents. New your: Elsevier Publishing Company, (1965). 

5. Bylinsky, G., The Battle for America's Sweet Tooth. Fortune. 28-32, July (1982). 

6. Campbell, L.A., Palmer G.H., Pectin in topics in Dietary Fiber Research, Edited Spiller, G.A. and Amen. R.J. Plenum Press, NY (1978).

JOURNAL OF APPLIED NUTRITION, VOLUME 36, NUMBER 1, 1984 REPORT 

[from files of: Aspartame Consumer Safety Network and Pilot Hotline since 1987]

www.aspartamesafety.com

mary.blogspot.com

Mary Nash Stoddard, Spokesperson and Founder ACSN, 1987

 

ASPARTAME NEOTAME FACT SHEET

__________________________________________________________________

THE BITTER TRUTH ABOUT ASPARTAME AND NEOTAME

"Aspartame/Neotame - the most dangerous substances in our food supply today." -  Mary Nash Stoddard 

[Founder ACSN & Pilot Hotline]

75% of all consumer complaints to the FDA are aspartame related 

[5 deaths registered prior to 1987]

Illegal Operations and 

FDA Approval 

FDA approved aspartame [NutraSweet/Equal/Canderal] a new, bio-genetically engineered molecule in 1974.That approval was rescinded before aspartame got to market, because it was revealed a component of aspartame [diketopiperazine] causes brain tumors. Tests were "falsified."  Tumors were removed and the lab animals illegally returned tumor-free to the lab. Second approval occurred in 1981 under President Reagan's new FDA Director, Dr. Arthur H. Hayes. In 1983, Hayes' office approved the new molecule for aqueous solution [soft drinks, etc.] and three months later, Dr. Hayes left government, went to work for the NutraSweet public relations firm, Burson Marsteller for $1,000 a day. Dr. Hayes craftily dodges all media requests for interviews on the topic. In fact, many government officials connected with this issue have gone to work for the industry whose products they were entrusted to approve or reject.

In the laboratory, aspartame produced: 

• Brain Tumors

• Breast Tumors

• Uterine Tumors

• Pancreatic Tumors

• Seizures

• Deaths

 These went unreported, as did the deaths and seizures of other animals in the original tests. Tumors were removed then animals put back in test as tumor free, animals who died were brought back to life on paper when results officially submitted by G.D. Searle pharmaceutical to FDA.

Aspartame changes DNA:

In tests, the third generation of pups born to animals fed aspartic acid [component of aspartame]  were born: 

1) Morbidly obese and 

2) Sexually Dysfunctional

Components of aspartame and its breakdown products can adversely affect the brains and central nervous systems of children and adults who consume it.

"When you harm the brain, you harm the very expression of one's self." - Peter Breggin, M.D. [Psychiatrist - Bethesda, MD]

Reported psychological symptoms:

• Suicidal Depressions

• Panic Attacks and Anxiety [PAD] - Manias

• Sleep Disorders 

• Severe Mood Disorders [rages, mood swings]

• Brain Chemical Imbalance 

• Brain Wave Malfunctions [shows up in EEGs]

• Personality Disorders

• Hallucinations

• Aberrant Behaviors

Medicine In Our Food?

Aspartame Components & Breakdown Products: 

Phenylalanine 50% - Lowers the seizure threshold. Causes mental retardation in some. Blocks production of serotonin [key neurotransmitter which controls: Moods / Sleep Patterns / Satiety ] Cultured in e-coli bacteria in the lab.

 

Aspartic Acid 40% - Caused lesions or holes in the brains of lab animals. Neuroexcitatory [excites brain cells to death] amino acid. Causes motor-neuronal disorders in studies.

Methanol 10% - Damages the liver and eye. Two teaspoons can be lethal to humans. [Not processed the same in humans and animals, so lab tests do not show full impact of toxicity] Breaks down into formaldehyde [embalming fluid] and formic acid [venom in insect stings]. Implicated in birth defects and fetal alcohol syndrome in newborn infants. As a constituent of other foods in nature, it is found in combination with ethyl alcohol, which counteracts or neutralizes the toxic affects of methanol as it is metabolized by the body. There is no ethyl alcohol in aspartame, therefore methanol in aspartame is in "free form" and is immediately absorbed into the bloodstream. For every molecule of aspartame, there is a molecule of methanol released. Classic signs of methanol poisoning include: lethargy, confusion, leg cramps, back pain, severe headache, abdominal pain, slurred speech, fainting, visual loss/blindness, labored breathing. 

Diketopiperazine [DKP] - Caused brain tumors in laboratory tests. Thirteen out of 320 lab animals developed brain tumors in testing. Aspartame breakdown products cross the blood brain barrier to damage the brain.

Aspartame is known to exacerbate or trigger onset of the following medical conditions:

• Epilepsy

• Parkinson's

• Alzheimer's 

• Multiple Sclerosis

• Chronic Fatigue Syn.

• Lymphoma

• Fibromyalgia / Eosinophilia Myalgia

• Mental Retardation / Birth Defects

• Diabetes / Hypoglycemia

• Graves Disease

• Heart Disease

• Lung Disease

• Liver Disease

• Kidney Disease

•  Brain Tumors [astrocytoma/glioblastoma]

• Pancreatic Disease

• Kidney / Adrenal Disease

• Arthritis

• Blindness

• Tinnitus 

• PMS

• Carpal Tunnel

• Lyme Disease

• Muniere's Disease

• Other: Rare / Hard to diagnose disorders

[Aspartame has been called a "systemic" toxin - which means it may virtually adversely affect the function of every organ of the body. The effects are "cumulative" and do not show up in short term testing.]

Aspartame  and Flying Safety:

Many military, general aviation and commercial airline pilots have lost medical certification to fly based on seizures which occurred while they were ingesting aspartame. Grand mal seizures have been reported in flight in the cockpits of commercial airliners. A pilots' hotline in Dallas,TX was established by ACSN, in 1988 for the anonymous reporting of adverse reactions and safety-of-flight incidents. USAF Flying Safety magazine published warnings re: aspartame use by pilots. Pilot's publications around the globe have warned  readers. The FAA will not send out an official memo - because the FDA refuses to recall aspartame as a safety hazard to consumers. Is aspartame the unacknowledged "terrorist" in every cockpit on every flight?

Legal:

ACSN co-founders Turner & Stoddard have both qualified in court as medical Expert Witnesses. Many consumer lawsuits have been dropped or settled out of court since the mid-eighties. The Washington D.C. Supreme Court refused to hear a case brought against the FDA by James Turner, Esq. Aspartame is illegal because it violated The Delaney Clause, which states no substance can be approved that is shown to cause cancer.

In 1995, a stealth law crept across the land, which made it illegal to say anything disparaging about a perishable food product  - example: yogurt sweetened with aspartame. Oprah was later sued under this law. [Agriculture Defamation Act]

In 1985, G.D. Searle and NutraSweet Co. became wholly-owned subsidiaries of Monsanto chemical company in St. Louis. Controversial Supreme Court Judge, Clarence Thomas is a former Monsanto attorney.

(Monsanto later  sold their sweetener divisions and in 2011, aspartame and neotame are produced by the NutraSweet Co. of Deerfield, IL.).

1998, Monsanto applied for FDA approval for a monster molecule, "based on the aspartame formula" with one addition: 3-dimethylbutyl [listed on EPA's most hazardous chemical list]. Thus, Neotame becomes 13,000 times sweeter than sugar.

July 5, 2002 - Neotame, Monsanto's super bio-manipulated molecule [new fake sweetener] was approved by FDA over formally  registered objections of the Aspartame Consumer Safety Network and others. Long term effects on humans are unknown.

Aspartame is  in over-the-counter drugs like: Tums, Pepsid AC, Metamucil, Alka Seltzer Plus, tooth whiteners, breath mints/strips and more. 

Diabetes and Aspartame / Neotame:

Diabetics are most insidiously harmed , because they are told aspartame is their "life line" to good health, when, in fact, just the opposite is true. Remember, aspartame caused pancreatic tumors in the lab. A diabetic may see the real life effects of aspartame on blood sugar by performing this simple test with a finger-stick test kit:

• Confirm blood sugar levels to be well within normal limits. If they are, then continue. Drink 2-3 cans [or the bottled equivalent]  of Diet Soda containing aspartame, without stopping. Then, begin to retest for blood sugar level readings approximately one hour later. In this way, the adverse effects on blood sugar levels may be proven. This test is NOT recommended for anyone except individuals who already drink more than 2 diet drinks per day. 

Parents the FDA does not protect 

your children. 

Greed and avarice have made government officials, industry and mainstream science, turn a deaf ear to the truth. Children are at least 4 times more susceptible to aspartame toxicity because of the developing central nervous system. Read labels. If it says:"phenylalanine" don't buy it. Insist your child's pediatric medical records contain this warning - "Never prescribe any medications containing phenylalanine [always present in aspartame and neotame]." Aspartame is a multi-billion dollar a year industry in more than 7,000 food products, chewing gums, children's antibiotics and meds, children's vitamins and pain medications for kids. In the lab, aspartame caused tragic birth defects.

 The "real villains" in today's society are those who poison our food supply and that of our children - for profit.

____________________________________

Aspartame Consumer Safety Network

Mary Nash Stoddard, Founder and President

P.O. Box 2001 - Frisco, TX 75034

214.387.4001

website:   http://www.aspartamesafety.com/

email: marystod@airmail.net