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ASPARTAME IS NEUROTOXIC GENOTOXIC
MOLECULAR FOOD & VACCINE
PHARMACO-GENOCIDE
Dr Bill Deagle MD FCFP DABFP AAEM A4M ACOEM CIME
Aspartame was approved by the FDA for food and medicine in the 1980s after the
intervention of Donald Rumsfeld, recently Minister of Defense to Geo Bush Jr.
Terms 1 and 2. The poison of Aspartame dipeptide is a deadly neurotoxin and
genotoxin. This paper will analyze results of extensive animal studies, human
case reviews, cellular pathology and a logical analysis of biochemical and cellular
toxicology. It is not a matter of incompetence but of malicious pharmacogenocide that this toxin is present in from 6,000 and over 90 countries. It is even
registered with MSG, Ethyl Salicylate Mercury Thiomerosal, and other adjuvant
immunologic and neurotoxic substances that are now approved by FDA for
vaccine antigenic amplification as an adjuvants.
Aspartame is manufactured in North America in Aiken, South Carolina with a
genetic engineered GMO bacterial factory. The sludge of bacterial proteins is
centrifuged to separate out differing molecular weights, and the dipeptide is spun
out for transfer to tankers to transport for packing and marketing at other
facilities. During my work at the Humana - Augusta Regional Trauma Center in
Family Practice and as a near full time at the Emergency Department, we had the
emergency occupational contract with this facility. Our director of the
Emergency and the ARTC director told us not to talk to media at any time about
reactions to the airborne particulates in the facility, neurological emergencies
such as seizures, neuropathy, disabilities or any other illness including other acute
or chronic serious and unusual medical conditions. During this time, I observed a
disproportionate high rate of polyneuropathy, organic brain dysfunction, ALS
amyotrophic lateral sclerosis, MS multiple sclerosis, seizures, aggressive brain
tumors of multicentric gliomas and astrocytomas, to name of few, and high
incidence of diabetes, obesity, and optic neuropathy and autoimmune disorders.
It was evident from the warnings, that any physician whistleblower would be
dismissed and defrocked via the hospital administration.
Dr Olney personally advised me in 1978 of his preliminary Aspartame research
that identified chromatin clumping of the DNA similar to the DNA changes of
gliomas of the most aggressive type of multicentric astrocytomas. Dr Roberts
found diabetic control induction and endocrine disorders of Hashimoto’s throiditis,
cancer and neurological disorders such as transverse myelitis, ALS amyotrophic
lateral sclerosis etc. Dr Blaylock has written extensively on the Glutamate
toxicity of Aspartame and Hydroperoxyl Radical damage to glial cells, brain cell
damage and neuron death, and biochemical toxicology of methanol and the
genotoxic effects of the Aspartame metabolites. Reduced Glutathione depletion is
serious with oral or injected Aspartame and co-toxicity with Mercury, MSG, GMO
organic acids, and other polytoxins in air, food and water and ubiquitous
Xenoestrogenic Antifolate toxins such as Halides of Chlorine, Chloramines,
Bromides and Bromamines and Fluorides and Fluoramines. Cancers of brain, and
many organs and significant lymphomas and leukemic induction is proven with
animal studies induced by Aspartame. Cellular replication is reduced and
micronuclei result similar to radiation exposure.
Aspartame is a ELF electromagnetic wave sensitizer, and induces phasic brain and
peripheral nerve entrainment to fire neurons to external pulsed magnetic field
effects. WiFi networks, AC power fields, and other electromagnetic fields from
cell phones, computers, appliances effects on cells are amplified by Aspartame
Glutamate neural network amplification and lowering of threshold to activation
potential.
Searle Pharmaceuticals identified for the C.I.A. Dr Delgado MD at Yale and his
mind influencing technologies as a ‘mind tenderizer’ for entraining brains of
animals for externally pulse training electromagnetic field IS Induced Stimulus for
paradigms of control of brain function. ELF pollution 1,000,000 fold more than
in 1998 in Western Nations is a major cotoxin with Aspartame and other lesser
NMDA receptor toxins in food and medicines.
Aspartame directly affects the NMDA N-Methyl D-Aspartate subtype Glutamate
receptors, injuring neurons and directly and indirectly interfer with AChE
Acetylcholinesterase receptors, functionally interfering with the ability to learn
new tasks and causing a functional frontal lobotomy of those suffering toxicity.
Cytochrome P450 Phase I enzyme induction depletes the brain of Glutathione
Peroxidase Phase II enzymatic ability to clear hydroperoxynitate free radical. This
is cotoxic with MSG, DU and organic acids in new GMO foods that induce
NMDA receptor Glutamate pathways.
Loss of executive inhibitory influences may explain more violent or spontaneous
out of control behavior, autism of all forms, and onset and progression of many
neurological disorders from cortical to midbrain motor interneuron Parkinson’s to
ALS amyotrophic lateral sclerosis and peripheral motor and sensory neuropathic
disorders. Increased mental illness, behavioral and learning disorders, autism,
dementia and violent behaviors can be now explained by population neurotoxicity.
Autism rates have gone up 2800% in three decades, organic dementia in the over
60 age group 1000% in 20 years, and Aspartame is a major player in this toxic
soup that has pushed the canary in the mineshaft, the neuron to sing its swan song.
Aspartame is directly toxic to Beta Islet cells and induces diabetes as does MSG to
a lesser extent in animal models. This would explain MODY Mature Onset
Diabetes of the Young and the exploding diabetes and obesity with Glutamate
toxins that destroy insulin production and amplify tissue insulin resistance. It is a
major factor destroying appestat control of appetite control with blood sugar, and
endorphin related hypothalamic pituitary axis. I conclude that along with DU
NotSo Depleted Uranium, MSG and other toxins that have similar or lesser
toxicities of these types, are contributors to the diabetes and obesity global
pandemic.
Testing of Aspartame enzymatic induction which can cause accumulative effects
can be evaluated with Genova Labs organic acids, amino acids, and Gene panels
for Phase I and II pathway polymorphisms. Those people with GSMT1 pathway
deletions or abnormal polymorphisms, will be more toxically damaged by
Aspartame and other NMDA toxins. Mitochondrial damage results from
enzymatic induction and peroxynitrate radicals, results in tissue targeted longstanding mitochondrial pathology. Mitochondriopathy is a final pathway for
much of the chronic effects of Aspartame. Also, iNOS, Induce Nitric Oxide
Synthase enzymatic induction and production of Hydroperoxyl Free Radical is the
step resulting in mitochondrial gene damage, and loss of cellular energetic
metabolism. This explains the vaccine suit evidence in the Poling Federal Vaccine
Damage Suit, where mitochondrial defects from adjuvants resulted in
neurological deficits and autism. Aspartame is the worst of NMDA toxins in our
food and vaccines, but MSG and many others are cotoxins.
Protocols for evaluation may include quantitive EEG or QEEG demonstrates
coherent frequency anomalies, voltage pattern from frontal to occipital and
temporal cortex, and P300 index abnormalities, that can monitor dynamic higher
cortical function and neural net plasticity and learning capacities for holographic
learning paradigms. SPECT scans indentify blood flow abnormalities consistent
with microvascular defects consistent with loss of glial cell energetic metabolic
support of neurotransmitters, myelinated neuron action potentials and proper
neural network cortical to cortical learning and motor, sensory and abstract
concept processing functions. fMRI Functional MRI can demonstrate abnormal
myelination and neural pathway functioning with changes in neural traffic and
dysmyelination patterns that can be verified on T2 Weighted MRI. PET Positron
Emission Tomography is most sensitive at identification of abnormal AChE
Acetylcholinesterase metabolism and Positron-Fluoro-Glucose metabolism
deficits in neural tissues. Frontal lobe hypofunction, loss of temporal and
transcortical metabolic patterns should correlate with full tracking
neuropsychological testing and QEEG voltage patterns and coherence pattern
analysis of intercortical frequencies. Enzymatic induction of Phase I CYP450 and
Reduced Glutathione levels with high levels of Peroxynitrate should show in urine
and blood analysis. Platelet bioamines in blood, urine or saliva for NE
norepinephrine, Dopamine and Serotonin, Melatonin, Acetylcholine, GABA should
reflect NMDA induction and depletion of presynaptic inhibitory
neurotransmitters.
Core Asparatame acute or chronic exposure testing should include QEEG available
from PhD psychologists certified on QEEG testing in America, Canada and
overseas; Genova Labs or similar functional medicine lab - organic acids and
amino acids and oxymarkers with Gene polymorphisms for Phase I and II Detox
pathways; PET Scan for brain hypometabolism AND / OR SPECT Scan for
abnormal microcirculation; fMRI scans for neural pathway traffic abnormalities
and neuropsychological evaluation of higher cortical functions to identify deficits
correlated with above imaging and neurological studies.
Essential testing should be QEEG and organic acids and Gene Phase I & II Detox
polymorphisms. The cotoxic effects of MSG, GMO Frankenfoods with organic
acids that induce NMDA receptors, and 7,700 ppm water drug, heavy metals,
chemical toxins in our water.
Aspartame cell toxic effects are the tip of the spear against human biology, made
worse by Agribusiness, Big Pharma, Big GMO, and world trade with reintroduced
previously banned pesticides forced on nations acception the WTO Codex
Alimentarius Food Rules. Aspartame has already received a nod across the board
approval by WTO UN FAO bureaucrats, to the danger of the world’s peoples.
When you review the extensive analysis by Dr HJ Roberts MD, Dr Russell Blaylock
MD and Dr Olney MD and the Ramazzini Foundation cancer research, there is no
excuse for continued toxic contamination of food of vaccines. Aspartame must be
banned from all foods, medicines, and vaccines. It is the first step for mankind, of
many to steps needed to restore healthy functional support for future generations of
the nations of Earth.
ABSTRACTS:
1: Crit Rev Toxicol. 2007;37(8):629-727.
Links
Aspartame: a safety evaluation based on current use
levels, regulations, and toxicological and
epidemiological studies.
Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer
PS, Waddell WJ, Walker R, Williams GM.
Burdock Group, Washington, DC, USA. [email protected]
Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in
over 90 countries worldwide in over 6000 products. The purpose of this investigation was
to review the scientific literature on the absorption and metabolism, the current
consumption levels worldwide, the toxicology, and recent epidemiological studies on
aspartame. Current use levels of aspartame, even by high users in special subgroups,
remains well below the U.S. Food and Drug Administration and European Food Safety
Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day,
respectively. Consumption of large doses of aspartame in a single bolus dose will have an
effect on some biochemical parameters, including plasma amino acid levels and brain
neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid
following administration of aspartame at doses less than or equal to 50 mg/kg bw do not
exceed those observed postprandially. Acute, subacute and chronic toxicity studies with
aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs
have consistently found no adverse effect of aspartame with doses up to at least 4000
mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame
found no credible evidence that aspartame is carcinogenic. The data from the extensive
investigations into the possibility of neurotoxic effects of aspartame, in general, do not
support the hypothesis that aspartame in the human diet will affect nervous system
function, learning or behavior. Epidemiological studies on aspartame include several
case-control studies and one well-conducted prospective epidemiological study with a
large cohort, in which the consumption of aspartame was measured. The studies provide
no evidence to support an association between aspartame and cancer in any tissue. The
weight of existing evidence is that aspartame is safe at current levels of consumption as a
nonnutritive sweetener. – LIES AND MISINFORMATION !!
PMID: 17828671 [PubMed - indexed for MEDLINE]
1: Environ Health Perspect. 2007 Sep;115(9):1293-7.
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Life-span exposure to low doses of aspartame beginning
during prenatal life increases cancer effects in rats.
Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
BACKGROUND: In a previous study conducted at the Cesare Maltoni Cancer Research
Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the
first time that aspartame (APM) is a multipotent carcinogenic agent when various doses
are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the
life span. OBJECTIVE: The aim of this second study is to better quantify the
carcinogenic risk of APM, beginning treatment during fetal life. METHODS: We studied
groups of 70-95 male and female Sprague-Dawley rats administered APM (2,000, 400, or
0 ppm) with feed from the 12th day of fetal life until natural death. RESULTS: Our
results show a) a significant dose-related increase of malignant tumor-bearing animals in
males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a
significant increase in incidence of lymphomas/leukemias in males treated with 2,000
ppm (p < 0.05) and a significant dose-related increase in incidence of
lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p <
0.01); and c) a significant dose-related increase in incidence of mammary cancer in
females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). CONCLUSIONS: The
results of this carcinogenicity bioassay confirm and reinforce the first experimental
demonstration of APM's multipotential carcinogenicity at a dose level close to the
acceptable daily intake for humans. Furthermore, the study demonstrates that when lifespan exposure to APM begins during fetal life, its carcinogenic effects are increased.
PMID: 17805418 [PubMed - indexed for MEDLINE]
PMCID: PMC1964906
1: Drug Chem Toxicol. 2004 Aug;27(3):257-68. Links
Genotoxicity of aspartame.
Rencüzoğullari E, Tüylü BA, Topaktaş M, Ila HB, Kayraldiz A, Arslan M, Diler SB.
Biology Department, Faculty of Arts and Sciences, Natural and Applied Sciences
Institute, Cukurova University, Adana, Turkey. [email protected]
In the present study, the genotoxic effects of the low-calorie sweetener aspartame (ASP),
which is a dipeptide derivative, was investigated using chromosome aberration (CA) test,
sister chromatid exchange (SCE) test, micronucleus test in human lymphocytes and also
Ames/Salmonella/ microsome test. ASP induced CAs at all concentrations (500, 1000
and 2000 microg/ml) and treatment periods (24 and 48 h) dose-dependently, while it did
not induce SCEs. On the other hand, ASP decreased the replication index (RI) only at the
highest concentration for 48 h treatment period. However, ASP decreased the mitotic
index (MI) at all concentrations and treatment periods dose-dependently. In addition,
ASP induced micronuclei at the highest concentrations only. This induction was also
dose-dependent for 48 hours treatment period. ASP was not mutagenic for Salmonella
typhimurium TA98 and TA100 strains in the absence and presence of S9 mix.
PMID: 15478947 [PubMed - indexed for MEDLINE]
1: Drug Chem Toxicol. 2006;29(3):269-78.
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The cytogenetic effects of food sweetener maltitol in
human peripheral lymphocytes.
Canimoğlu S, Rencüzoğullari E.
Cukurova University, Natural and Applied Sciences Institute, Department of Biology,
Adanna, Turkey.
The effects of the low-calorie artifical sweetener maltitol (E965), a sugar alcohol
(Polyol), on sister chromatid exchange (SCE), chromosome aberration (CA), and
micronucleus formation (MN) were investigated in human peripheral lymphocytes.
Maltitol did not induce SCE at all concentrations (1.25, 2.5, and 5 mg/mL) and treatment
periods (24 and 48 h). Maltitol induced CA, although not statistically significantly.
Maltitol induced the frequency of MN at 24 and 48 h in a non-dose-dependent manner. In
addition, maltitol did not decrease the replication index (RI) and the mitotic index (MI) at
all concentrations and treatment periods. Maltitol did not alter the pH and osmolality of
the medium. In conclusion, it can be concluded that maltitol has a weak genotoxic
potential and it appears non-cytotoxic to human peripheral lymphocytes in vitro.
PMID: 16777705 [PubMed - indexed for MEDLINE]
1: Food Chem Toxicol. 2007 Dec;45(12):2397-401. Epub 2007 Jun 16.
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The effect of aspartame metabolites on the suckling rat
frontal cortex acetylcholinesterase. An in vitro study.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology, Medical School, University of Athens, P.O.
Box 65257, GR 15401 Athens, Greece.
Aspartame (ASP) consumption is suggested to be implicated with muscarinic
dysfunction. The aim of this work was to evaluate the effect of ASP and its metabolites
on acetylcholinesterase (AChE) activity in rat frontal cortex and pure enzyme. Rat frontal
cortex homogenate or pure enzyme AChE (eel E. Electricus) were incubated with ASP
and each of ASP components, phenylalanine (Phe), aspartic acid (asp), and methanol
(MeOH) for 1 h at 37 degrees C. AChE was measured spectrophotometrically. The
results showed that incubation of rat tissue or pure enzyme with the sum of ASP
metabolites, as reported to be found in the CSF after 150 or 200 mg/kg ASP
consumption, inhibited frontal cortex and pure AChE about -11% to -29% (p<0.001).
Asp, Phe or MeOH concentrations related to their CSF levels after ingestion of abuse or
toxic ASP doses, when separately incubated with frontal cortex or pure AChE, resulted in
a significant decrease of the enzyme activities. IN CONCLUSION: ASP compounds may
directly and/or indirectly act on the frontal cortex AChE. High or toxic doses of the
sweetener remarkably decreased the enzyme activity. If this in vitro finding comes into
human reality, it may be suggested that cholinergic symptoms are related to the
consumption of the above ASP doses.
PMID: 17673349 [PubMed - indexed for MEDLINE]
1: Neurology. 1992 May;42(5):1000-3. Links
Comment in:
Neurology. 1993 Mar;43(3 Pt 1):630-1.
Neurology. 1993 Oct;43(10):2154-5.
Aspartame exacerbates EEG spike-wave discharge in
children with generalized absence epilepsy: a doubleblind controlled study.
Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF.
IWK Children's Hospital, Halifax, Nova Scotia, Canada.
There are anecdotal reports of increased seizures in humans after ingestion of aspartame.
We studied 10 children with newly diagnosed but untreated generalized absence seizures.
Ambulatory cassette recording of EEG allowed quantification of numbers and length of
spike-wave discharges in a double-blind study on two consecutive days. On one day the
children received 40 mg/kg aspartame and on the other day, a sucrose-sweetened drink.
Baseline EEG was the same before aspartame and sucrose. Following aspartame
compared with sucrose, the number of spike-wave discharges per hour and mean length
of spike-wave discharges increased but not to a statistically significant degree. However,
the total duration of spike-wave discharge per hour was significantly increased after
aspartame (p = 0.028), with a 40% +/- 17% (SEM) increase in the number of seconds per
hour of EEG recording that the children spent in spike-wave discharge. Aspartame
appears to exacerbate the amount of EEG spike wave in children with absence seizures.
Further studies are needed to establish if this effect occurs at lower doses and in other
seizure types.
PMID: 1579221 [PubMed - indexed for MEDLINE]
1: Neurotoxicology. 1994 Fall;15(3):535-44. Links
Excitotoxins in foods.
Olney JW.
Department of Psychiatry, Washington University School of Medicine, St. Louis,
Missouri 63110.
Evidence is reviewed pertaining to excitatory neurotoxins (excitotoxins) encountered in
human food supply. The most frequently encountered food excitotoxin is glutamate (Glu)
which is commercially added to many foods despite evidence that it can freely penetrate
certain brain regions and rapidly destroy neurons by hyperactivating the NMDA subtype
of Glu receptor. Hypersensitivity of NMDA receptors during development makes the
immature nervous system especially sensitive to Glu excitotoxicity. On the other hand,
elderly consumers are particularly sensitive to domoic acid, a powerful excitotoxic Glu
analog that activates both NMDA and non-NMDA receptors. A high content of domoic
acid in shell fish caused a recent food poisoning incident that killed some elderly victims
and caused brain damage and memory impairment in others. Neurolathyrism is a
crippling neurodegenerative condition associated with ingestion of a legume that
naturally contains BOAA, an excitotoxic Glu analog that hyperactivates non-NMDA
receptors. Thus, the human food supply is a source of excitotoxins that can damage the
brain by one type of mechanism to which immature consumers are hypervulnerable, or by
other mechanisms to which adult and elderly consumers are peculiarly sensitive.
PMID: 7854587 [PubMed - indexed for MEDLINE]
1: Basic Clin Pharmacol Toxicol. 2008 Feb;102(2):118-24.
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Consequences of exposure to carcinogens beginning
during developmental life.
Soffritti M, Belpoggi F, Esposti DD, Falcioni L, Bua L.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
The increased incidence of cancer over the last 50-60 years may be largely attributed to
two factors: the ageing of the population and the diffusion of agents and situations
presenting carcinogenic risks. Today, we have entered into a new era in which
populations are ever-increasingly exposed to diffuse carcinogenic risks, present not only
in the occupational, but also in the general environment. We must now also consider an
additional factor in the carcinogenic process, that is, the age in which exposure to
carcinogenic risks begins. Apart from the paradigmatic cases of diethylstilboestrol and
ionizing radiation, the available epidemiological data concerning the adult consequences
of developmental exposure to carcinogens is very limited. However, important data have
been provided by long-term experimental carcinogenicity bioassays conducted using
rodents. This paper reports a selection of studies conducted in the laboratories of the
Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation in which
exposure to the chemical agents vinyl acetate monomer, ethyl alcohol and aspartame was
started during developmental life and continued into adulthood. The results of these
studies provide supporting evidence that lifespan exposure to carcinogenic agents
beginning during developmental life produces an overall increase in the carcinogenic
effects observed. Moreover, when comparing prenatal and postnatal exposure, the data
demonstrate that the development of cancers may appear earlier in life.
PMID: 18226064 [PubMed - indexed for MEDLINE]
1: Environ Health Perspect. 2006 Mar;114(3):379-85.
Links
Comment in:
Environ Health Perspect. 2006 Mar;114(3):A176.
Environ Health Perspect. 2006 Sep;114(9):A516; author reply A516-7.
Environ Health Perspect. 2007 Jan;115(1):A16-7; author reply A17.
First experimental demonstration of the multipotential
carcinogenic effects of aspartame administered in the
feed to Sprague-Dawley rats.
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has
conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener.
APM was administered with feed to 8-week-old Sprague-Dawley rats (100150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm.
The treatment lasted until natural death, at which time all deceased animals underwent
complete necropsy. Histopathologic evaluation of all pathologic lesions and of all organs
and tissues collected was routinely performed on each animal of all experimental groups.
The results of the study show for the first time that APM, in our experimental conditions,
causes a) an increased incidence of malignant-tumor-bearing animals with a positive
significant trend in males (p < or = 0.05) and in females (p < or = 0.01), in particular
those females treated at 50,000 ppm (p < or = 0.01); b) an increase in lymphomas and
leukemias with a positive significant trend in both males (p < or = 0.05) and females (p <
or = 0.01), in particular in females treated at doses of 100,000 (p < or = 0.01), 50,000 (p <
or = 0.01), 10,000 (p < or = 0.05), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.01); c) a
statistically significant increased incidence, with a positive significant trend (p < or =
0.01), of transitional cell carcinomas of the renal pelvis and ureter and their precursors
(dysplasias) in females treated at 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000
(p < or = 0.01), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.05); and d) an increased
incidence of malignant schwannomas of peripheral nerves with a positive trend (p < or =
0.05) in males. The results of this mega-experiment indicate that APM is a multipotential
carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the
current acceptable daily intake. On the basis of these results, a reevaluation of the present
guidelines on the use and consumption of APM is urgent and cannot be delayed.
PMID: 16507461 [PubMed - indexed for MEDLINE]
1: Hum Exp Toxicol. 2006 Aug;25(8):453-9.
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The effect of aspartame on rat brain xenobioticmetabolizing enzymes.
Vences-Mejía A, Labra-Ruíz N, Hernández-Martínez N, Dorado-González V,
Gómez-Garduño J, Pérez-López I, Nosti-Palacios R, Camacho Carranza R,
Espinosa-Aguirre JJ.
Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur,
3700-C, 04530 México, DF Mdxico.
This study demonstrates that chronic aspartame (ASP) consumption leads to an increase
of phase I metabolizing enzymes (cytochrome P450 (CYP)) in rat brain. Wistar rats were
treated by gavage with ASP at daily doses of 75 and 125 mg/kg body weight for 30 days.
Cerebrum and cerebellum were used to obtain microsomal fractions to analyse activity
and protein levels of seven cytochrome P450 enzymes. Increases in activity were
consistently found with the 75 mg/kg dose both in cerebrum and cerebellum for all seven
enzymes, although not at the same levels: CYP 2E1-associated 4-nitrophenol hydroxylase
(4-NPH) activity was increased 1.5-fold in cerebrum and 25-fold in cerebellum; likewise,
CYP2B1-associated penthoxyresorufin O-dealkylase (PROD) activity increased 2.9- and
1.7-fold respectively, CYP2B2-associated benzyloxyresorufin O-dealkylase (BROD) 4.5and 1.1-fold, CYP3A-associated erythromycin N-demethylase (END) 1.4- and 3.3-fold,
CYP1A1-associated ethoxyresorufin O-deethylase (EROD) 5.5- and 2.8-fold, and
CYP1A2-associated methoxyresorufin O-demethylase (MROD) 3.7- and 1.3-fold.
Furthermore, the pattern of induction of CYP immunoreactive proteins by ASP paralleled
that of 4-NHP-, PROD-, BROD-, END-, EROD- and MROD-related activities only in the
cerebellum. Conversely, no differences in CYP concentration and activity were detected
in hepatic microsomes of treated animals with respect to the controls, suggesting a brainspecific response to ASP treatment.
PMID: 16937917 [PubMed - indexed for MEDLINE]
1: Pharmacol Res. 2007 Aug;56(2):155-9. Epub 2007 May 13.
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The effect of aspartame on acetylcholinesterase activity
in hippocampal homogenates of suckling rats.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology, Medical School, University of Athens, P.O.
Box 65257, GR-15401 Athens, Greece.
BACKGROUND: Neurological disturbances have been implicated with aspartame (ASP)
consumption and the cholinergic system with acetylcholinesterase (AChE) seems actively
involved. AIM: To evaluate the effect of ASP and its metabolites on rat hippocampal
AChE activity. METHODS: Hippocampal homogenate or pure enzyme AChE (eel E.
electricus) was incubated with the sum or each of ASP components, phenylalanine (Phe),
aspartic acid (asp) and methanol (MeOH) for 1h at 37 degrees C. AChE activity was
measured spectrophotometrically. RESULTS: Incubation of rat tissue or pure enzyme
with the sum of ASP metabolites in concentrations in CSF (the concentrations were
calculated according to the CSF/plasma concentration ratios) following 150 or
200mgkg(-1) of ASP consumption, resulted in significant enzyme activity reductions of
25 and 31% for hippocampal AChE and 11% (p<0.01) and 19% for pure enzyme,
respectively. Aspartic acid concentrations of 0.42 or 0.56mM significantly reduced the
enzyme activities by 13 and 20% for hippocampal AChE and 15 and 18% for pure
enzyme, respectively. Phe concentrations of 0.042 or 0.083mM decreased the enzyme
activity by 12% (p<0.01) and 20% (p<0.001) for hippocampal AChE and 15 and 18%
(p<0.001) for pure enzyme, respectively. Methanol concentrations of 0.60 or 0.80mM
remarkably inhibited hippocampal AChE by about 18 and 22% and pure enzyme by
about 14 and 20%, respectively. CONCLUSIONS: Low concentrations of ASP
components had no effect on hippocampal and pure AChE activity, whereas high or toxic
concentrations remarkably decreased both enzyme activities. Muscarinic symptoms may
be related to the latter concentrations of ASP metabolites.
PMID: 17580119 [PubMed - indexed for MEDLINE]
1: Eur J Clin Nutr. 2006 May;60(5):593-7.
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The effect of L-cysteine and glutathione on inhibition of
Na+, K+-ATPase activity by aspartame metabolites in
human erythrocyte membrane.
Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S.
Institute of Child Health, Research Center, Aghia Sophia Children's Hospital, Athens,
Greece.
BACKGROUND: Reports have implicated Aspartame (N-L-a-aspartyl-L-phenylalanine
methyl ester, ASP) in neurological problems. AIM: To evaluate Na(+), K(+)-ATPase
activities in human erythrocyte membranes after incubation with the ASP metabolites,
phenylalanine (Phe), methanol (MeOH) and aspartic acid (Asp). METHODS:
Erythrocyte membranes were obtained from 12 healthy individuals and were incubated at
37 degrees C for 1 h with the sum or each of the ASP metabolites separately, which are
commonly measured in blood after ASP ingestion. Na(+), K(+)-ATPase and Mg(2+)ATPase activities were measured spectrophotometrically. RESULTS: Membrane
Mg(2+)-ATPase activity was not altered. The sum of ASP metabolite concentrations
corresponding to 34, 150 or 200 mg/kg of the sweetener ingestion resulted in an
inhibition of the membrane Na(+), K(+)-ATPase by -30, -40, -48%, respectively. MeOH
concentrations of 0.14, 0.60 or 0.80 mM decreased the enzyme activity by -25, -38, 43%, respectively. Asp concentrations of 2.80, 7.60 or 10.0 mM inhibited membrane
Na(+), K(+)-ATPase by -26, -40, -46%, respectively. Phe concentrations of 0.14, 0.35 or
0.50 mM reduced the enzyme activity by -24, -44, -48%, respectively. Preincubation with
L-cysteine or reduced glutathione (GSH) completely or partially restored the inhibited
membrane Na(+), K(+)-ATPase activity by high or toxic ASP metabolite concentrations.
CONCLUSIONS: Low concentrations of ASP metabolites had no effect on Na(+), K(+)ATPase activity. High or abuse concentrations of ASP hydrolysis products significantly
decreased the membrane enzyme activity, which was completely or partially prevented
by L-cysteine or reduced GSH.
PMID: 16391576 [PubMed - indexed for MEDLINE]
1: Toxicology. 2007 Jul 31;237(1-3):177-83. Epub 2007 May 18.
Links
L-Cysteine and glutathione restore the reduction of rat
hippocampal Na+, K+-ATPase activity induced by
aspartame metabolites.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology, Medical School, Athens University, P.O. Box
65257, GR-15401 Athens, Greece.
Studies have implicated aspartame (ASP) ingestion in neurological problems. The aim of
this study was to evaluate hippocampal Na(+),K(+)-ATPase and Mg(2+)-ATPase
activities after incubation with ASP or each of ASP metabolites, phenylalanine (Phe),
methanol (MeOH) and aspartic acid (asp) separately. Suckling rat hippocampal
homogenates or pure Na(+),K(+)-ATPase were incubated with ASP metabolites.
Na(+),K(+)-ATPase and Mg(2+)-ATPase activities were measured
spectrophotometrically. Incubation of hippocampal or pure Na(+),K(+)-ATPase with
ASP concentrations (expected in the cerebrospinal fluid (CSF)) after ASP consumption
of 34, 150 or 200mg/kg resulted in hippocampal enzyme activity reduction of 26%, 50%
or 59%, respectively, whereas pure enzyme was remarkably stimulated. Moreover,
incubation with hippocampal homogenate of each one of the corresponding in the CSF
ASP metabolites related to the intake of common, high/abuse doses of the sweetener,
inhibited Na(+),K(+)-ATPase, while pure enzyme was activated. Hippocampal Mg(2+)ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) in
ASP mixtures, related with high/toxic doses of the sweetener, completely or partially
restored the inactivated membrane Na(+),K(+)-ATPase, whereas the activated pure
enzyme activity returned to normal. CSF concentrations of ASP metabolites related to
common, abuse/toxic doses of the additive significantly reduced rat hippocampal
Na(+),K(+)-ATPase activity, whereas pure enzyme was activated. Cys or GSH
completely or partially restored both enzyme activities.
PMID: 17602817 [PubMed - indexed for MEDLINE]
1: Pharmacol Res. 2006 Jan;53(1):1-5. Epub 2005 Aug 29.
Links
The effect of aspartame metabolites on human
erythrocyte membrane acetylcholinesterase activity.
Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH.
Department of Experimental Physiology, Medical School, University of Athens, Greece.
[email protected]
Studies have implicated aspartame (ASP) with neurological problems. The aim of this
study was to evaluate acetylcholinesterase (AChE) activity in human erythrocyte
membranes after incubation with the sum of ASP metabolites, phenylalanine (Phe),
methanol (met) and aspartic acid (aspt), or with each one separately. Erythrocyte
membranes were obtained from 12 healthy individuals and were incubated with ASP
hydrolysis products for 1 h at 37 degrees C. AChE was measured spectrophotometrically.
Incubation of membranes with ASP metabolites corresponding with 34 mg/kg, 150
mg/kg or 200 mg/kg of ASP consumption resulted in an enzyme activity reduction by 33%, -41%, and -57%, respectively. Met concentrations 0.14 mM, 0.60 mM, and 0.80
mM decreased the enzyme activity by -20%, -32% or -40%, respectively. Aspt
concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited membrane AChE activity by 20%, -35%, and -47%, respectively. Phe concentrations 0.14 mM, 0.35 mM or 0.50mM
reduced the enzyme activity by -11%, -33%, and -35%, respectively. Aspt or Phe
concentrations 0.82 mM or 0.07 mM, respectively, did not alter the membrane AChE
activity. It is concluded that low concentrations of ASP metabolites had no effect on the
membrane enzyme activity, whereas high or toxic concentrations partially or remarkably
decreased the membrane AChE activity, respectively. Additionally, neurological
symptoms, including learning and memory processes, may be related to the high or toxic
concentrations of the sweetener metabolites.
PMID: 16129618 [PubMed - indexed for MEDLINE]
1: Food Chem Toxicol. 2007 Dec;45(12):2397-401. Epub 2007 Jun 16.
Links
The effect of aspartame metabolites on the suckling rat
frontal cortex acetylcholinesterase. An in vitro study.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Experimental Physiology, Medical School, University of Athens, P.O.
Box 65257, GR 15401 Athens, Greece.
Aspartame (ASP) consumption is suggested to be implicated with muscarinic
dysfunction. The aim of this work was to evaluate the effect of ASP and its metabolites
on acetylcholinesterase (AChE) activity in rat frontal cortex and pure enzyme. Rat frontal
cortex homogenate or pure enzyme AChE (eel E. Electricus) were incubated with ASP
and each of ASP components, phenylalanine (Phe), aspartic acid (asp), and methanol
(MeOH) for 1 h at 37 degrees C. AChE was measured spectrophotometrically. The
results showed that incubation of rat tissue or pure enzyme with the sum of ASP
metabolites, as reported to be found in the CSF after 150 or 200 mg/kg ASP
consumption, inhibited frontal cortex and pure AChE about -11% to -29% (p<0.001).
Asp, Phe or MeOH concentrations related to their CSF levels after ingestion of abuse or
toxic ASP doses, when separately incubated with frontal cortex or pure AChE, resulted in
a significant decrease of the enzyme activities. IN CONCLUSION: ASP compounds may
directly and/or indirectly act on the frontal cortex AChE. High or toxic doses of the
sweetener remarkably decreased the enzyme activity. If this in vitro finding comes into
human reality, it may be suggested that cholinergic symptoms are related to the
consumption of the above ASP doses.
PMID: 17673349 [PubMed - indexed for MEDLINE]
1: Food Chem Toxicol. 2008 Feb 8 [Epub ahead of print]
Links
l-Cysteine and glutathione restore the modulation of rat
frontal cortex Na(+), K(+)-ATPase activity induced by
aspartame metabolites.
Simintzi I, Schulpis KH, Angelogianni P, Liapi C, Tsakiris S.
Department of Physiology, Medical School, Athens University, P.O. Box 65257, GR15401 Athens, Greece.
BACKGROUND: Studies have suggested that aspartame (ASP) ingestion is implicated in
neurological problems. AIM: The aim of this study was to evaluate rat frontal cortex
Na(+), K(+)-ATPase and Mg(2+)-ATPase activities after incubation with ASP or each of
its metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp)
separately. METHOD: Suckling rat frontal cortex homogenates or pure Na(+), K(+)ATPase were incubated with ASP metabolites. Na(+), K(+)-ATPase and Mg(2+)-ATPase
activities were measured spectrophotometrically. RESULTS: Incubation of frontal cortex
homogenate or pure Na(+), K(+)-ATPase with various ASP concentrations as expected in
the cerebrospinal fluid (CSF) after ASP consumption of 34, 150 or 200mg/kg, decreased
the frontal cortex enzyme activity by 33%, 53% or 57%, respectively, whereas pure
enzyme was remarkably stimulated. Moreover, incubation of frontal cortex homogenate
with each one of the expected ASP metabolites in the CSF, except MeOH, which are
related to the intake of the above mentioned doses of the sweetener, resulted in an
activation of the membrane Na(+), K(+)-ATPase, as well as pure enzyme. Frontal cortex
Mg(2+)-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione
(GSH) to ASP metabolites mixtures, corresponding to 150 or 200mg/kg doses of the
sweetener, completely or partially restored to normal the modulated membrane and pure
Na(+), K(+)-ATPase activities. CONCLUSION: CSF concentrations of the sum of ASP
metabolites corresponding to the intake of common, abuse or toxic doses (34 or 150 or
200mg/kg, respectively) of the additive significantly increased rat frontal cortex Na(+),
K(+)-ATPase and pure enzyme activities. Cys or GSH completely or partially restored to
normal both enzyme activities, possibly due to amelioration of the cellular GSH
reduction from the action of MeOH, a metabolite of the sweetener and/or by their
scavenging effect.
PMID: 18343556 [PubMed - as supplied by publisher]
1: Ultrastruct Pathol. 2007 Mar-Apr;31(2):77-83.
Links
Ultrastructural changes to rabbit fibrin and platelets
due to aspartame.
Pretorius E, Humphries P.
Department of Anatomy, Faculty of Medicine, University of Pretoria, South Africa.
[email protected]
The coagulation process, including thrombin, fibrin, as well as platelets, plays an
important role in hemostasis, contributing to the general well-being of humans. Fibrin
formation and platelet activation are delicate processes that are under the control of many
small physiological events. Any one of these many processes may be influenced or
changed by external factors, including pharmaceutical or nutritional products, e.g., the
sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is known that
phenylalanine is present at position P(9) and aspartate at position P(10) of the alpha-chain
of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin
by the catalyst alpha-thrombin. The authors investigate the effect of aspartame on platelet
and fibrin ultrastructure, by using the rabbit animal model and the scanning electron
microscope. Animals were exposed to 34 mg/kg of aspartame 26x during a 2-month
period. Aspartame-exposed fibrin networks appeared denser, with a thick matted fine
fiber network covering thick major fibers. Also, the platelet aggregates appeared more
granular than the globular control platelet aggregates. The authors conclude by
suggesting that aspartame usage may interfere with the coagulation process and might
cause delayed fibrin breakup after clot formation. They suggest this, as the fibrin
networks from aspartame-exposed rabbits are more complex and dense, due to the netlike
appearance of the minor, thin fibers. Aspartame usage should possibly be limited by
people on anti-clotting medicine or those with prone to clot formation.
PMID: 17613990 [PubMed - indexed for MEDLINE]
1: Anat Rec (Hoboken). 2007 Feb;290(2):188-98.
Links
Ultrastructural comparison of the morphology of three
different platelet and fibrin fiber preparations.
Pretorius E, Briedenhann S, Marx J, Smit E, Van Der Merwe C, Pieters M, Franz
C.
Department of Anatomy, School of Health Sciences, Medical Faculty, University of
Pretoria, Pretoria, South Africa. [email protected]
The aim of the current study was to investigate the ultrastructural morphology of three
different sources of fibrin networks and platelets, namely, lyophilized human platelet-rich
plasma (LPRP), freshly prepared human platelet-rich plasma (FPRP), and human platelet
concentrate (HPC). The ultrastructural morphology of the three different fibrin networks
was studied using the scanning electron microscope (SEM). Turbidity curves were drawn
at 405 nm at room temperature and fibrinogen concentrations were measured. Scanning
electron micrographs showed that all clots produced thick major fibrin fibers as well as a
well-defined fine fibrin network, which appeared to be a superimposed process that
occurred after the major fibrin network was established. These features were decidedly
more pronounced in the HPC specimens. Turbidity curves of the three types of plasma
showed differences in LPRP and FPRP. Fibrinogen concentrations of all three
preparations were in the normal ranges. Because of the great similarity between LPRP,
HPC, and FPRP, we suggest that LPRP could be used successfully to study
morphological changes in fibrin fibers and platelets, which may occur after exposure to
certain therapeutic agents. However, functionality studies such as turbidity curves should
concurrently be included. We therefore conclude that from a basic science point of view,
LPRP is a valuable research tool and that such results may add information that could be
valuable for clinical application.
PMID: 17441211 [PubMed - indexed for MEDLINE]
1: Microsc Res Tech. 2007 Sep;70(9):823-7.
Links
Comparative ultrastructural analyses of mouse, rabbit,
and human platelets and fibrin networks.
Pretorius E, Humphries P, Ekpo OE, Smit E, van der Merwe CF.
Department of Anatomy, School of Health Sciences, Faculty of Health Sciences,
University of Pretoria, South Africa. [email protected]
Platelets and fibrin play an important role in the coagulation process, where they are
involved in the maintenance of hemostasis. Fibrin dysfunction is associated with the
development of vascular complications, while proneness to the formation of tight and
rigid fibrin networks is independently associated with thrombotic disease. Here we
investigate the ultrastructure of human, rabbit, and mouse platelets and fibrin networks,
using the scanning electron microscope. Human and rabbit fibrin and platelets, with
regards to morphology as well as size of major and minor fibers compare well with each
other. However, mouse fibers are much thinner and form a flimsy branching network.
Platelet aggregate morphology of all three species compare well with each other. We
conclude that rabbit platelet and fibrin networks could be used successfully when
studying the effect of pharmaceutical products in preclinical trials, when looking at the
effects of these products on morphology and ultrastructure.
PMID: 17576129 [PubMed - indexed for MEDLINE]
1: Ann N Y Acad Sci. 2006 Sep;1076:559-77.
Links
Results of long-term carcinogenicity bioassay on
Sprague-Dawley rats exposed to aspartame
administered in feed.
Belpoggi F, Soffritti M, Padovani M, Degli Esposti D, Lauriola M, Minardi F.
Cesare Maltoni Cancer Research Center, European Foundation of Oncology and
Environmental Sciences B. Ramazzini, 40010 Bentivoglio, Bologna, Italy.
Aspartame (APM) is one of the most widely used artificial sweeteners in the world. Its
ever-growing use in more than 6000 products, such as soft drinks, chewing gum, candy,
desserts, etc., has been accompanied by rising consumer concerns regarding its safety, in
particular its potential long-term carcinogenic effects. In light of the inadequacy of the
carcinogenicity bioassays performed in the 1970s and 1980s, a long-term megaexperiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the
European Ramazzini Foundation on groups of male and female Sprague-Dawley rats
(100-150/sex/group), 8 weeks old at the start of the experiment. APM was administered
in feed at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. Treatment
lasted until spontaneous death of the animals. The results of the study demonstrate that
APM causes: (a) an increased incidence of malignant tumor-bearing animals, with a
positive significant trend in both sexes, and in particular in females treated at 50,000 ppm
(P < or = 0.01) when compared to controls; (b) an increase in lymphomas-leukemias,
with a positive significant trend in both sexes, and in particular in females treated at doses
of 100,000 (P < or = 0.01), 50,000 (P < or = 0.01), 10,000 (P < or = 0.05), 2000 (P < or =
0.05), and 400 ppm (P < or = 0.01); (c) a statistically significant increased incidence, with
a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in
females and particularly in those treated at 100,000 ppm (P < or = 0.05); and (d) an
increased incidence of malignant schwannomas of the peripheral nerves, with a positive
trend in males (P < or = 0.05). The results of this mega-experiment indicate that APM, in
the tested experimental conditions, is a multipotential carcinogenic agent.
PMID: 17119233 [PubMed - indexed for MEDLINE]
1: Environ Health Perspect. 2006 Mar;114(3):379-85.
Links
Comment in:
Environ Health Perspect. 2006 Mar;114(3):A176.
Environ Health Perspect. 2006 Sep;114(9):A516; author reply A516-7.
Environ Health Perspect. 2007 Jan;115(1):A16-7; author reply A17.
First experimental demonstration of the multipotential
carcinogenic effects of aspartame administered in the
feed to Sprague-Dawley rats.
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has
conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener.
APM was administered with feed to 8-week-old Sprague-Dawley rats (100150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm.
The treatment lasted until natural death, at which time all deceased animals underwent
complete necropsy. Histopathologic evaluation of all pathologic lesions and of all organs
and tissues collected was routinely performed on each animal of all experimental groups.
The results of the study show for the first time that APM, in our experimental conditions,
causes a) an increased incidence of malignant-tumor-bearing animals with a positive
significant trend in males (p < or = 0.05) and in females (p < or = 0.01), in particular
those females treated at 50,000 ppm (p < or = 0.01); b) an increase in lymphomas and
leukemias with a positive significant trend in both males (p < or = 0.05) and females (p <
or = 0.01), in particular in females treated at doses of 100,000 (p < or = 0.01), 50,000 (p <
or = 0.01), 10,000 (p < or = 0.05), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.01); c) a
statistically significant increased incidence, with a positive significant trend (p < or =
0.01), of transitional cell carcinomas of the renal pelvis and ureter and their precursors
(dysplasias) in females treated at 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000
(p < or = 0.01), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.05); and d) an increased
incidence of malignant schwannomas of peripheral nerves with a positive trend (p < or =
0.05) in males. The results of this mega-experiment indicate that APM is a multipotential
carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the
current acceptable daily intake. On the basis of these results, a reevaluation of the present
guidelines on the use and consumption of APM is urgent and cannot be delayed.
PMID: 16507461 [PubMed - indexed for MEDLINE]
1: Environ Health Perspect. 2007 Sep;115(9):1293-7.
Links
Life-span exposure to low doses of aspartame beginning
during prenatal life increases cancer effects in rats.
Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
BACKGROUND: In a previous study conducted at the Cesare Maltoni Cancer Research
Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the
first time that aspartame (APM) is a multipotent carcinogenic agent when various doses
are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the
life span. OBJECTIVE: The aim of this second study is to better quantify the
carcinogenic risk of APM, beginning treatment during fetal life. METHODS: We studied
groups of 70-95 male and female Sprague-Dawley rats administered APM (2,000, 400, or
0 ppm) with feed from the 12th day of fetal life until natural death. RESULTS: Our
results show a) a significant dose-related increase of malignant tumor-bearing animals in
males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a
significant increase in incidence of lymphomas/leukemias in males treated with 2,000
ppm (p < 0.05) and a significant dose-related increase in incidence of
lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p <
0.01); and c) a significant dose-related increase in incidence of mammary cancer in
females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). CONCLUSIONS: The
results of this carcinogenicity bioassay confirm and reinforce the first experimental
demonstration of APM's multipotential carcinogenicity at a dose level close to the
acceptable daily intake for humans. Furthermore, the study demonstrates that when lifespan exposure to APM begins during fetal life, its carcinogenic effects are increased.
PMID: 17805418 [PubMed - indexed for MEDLINE]
PMCID: PMC1964906
1: Basic Clin Pharmacol Toxicol. 2008 Feb;102(2):118-24.
Links
Consequences of exposure to carcinogens beginning
during developmental life.
Soffritti M, Belpoggi F, Esposti DD, Falcioni L, Bua L.
Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology
and Environmental Sciences, Bologna, Italy. [email protected]
The increased incidence of cancer over the last 50-60 years may be largely attributed to
two factors: the ageing of the population and the diffusion of agents and situations
presenting carcinogenic risks. Today, we have entered into a new era in which
populations are ever-increasingly exposed to diffuse carcinogenic risks, present not only
in the occupational, but also in the general environment. We must now also consider an
additional factor in the carcinogenic process, that is, the age in which exposure to
carcinogenic risks begins. Apart from the paradigmatic cases of diethylstilboestrol and
ionizing radiation, the available epidemiological data concerning the adult consequences
of developmental exposure to carcinogens is very limited. However, important data have
been provided by long-term experimental carcinogenicity bioassays conducted using
rodents. This paper reports a selection of studies conducted in the laboratories of the
Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation in which
exposure to the chemical agents vinyl acetate monomer, ethyl alcohol and aspartame was
started during developmental life and continued into adulthood. The results of these
studies provide supporting evidence that lifespan exposure to carcinogenic agents
beginning during developmental life produces an overall increase in the carcinogenic
effects observed. Moreover, when comparing prenatal and postnatal exposure, the data
demonstrate that the development of cancers may appear earlier in life.
PMID: 18226064 [PubMed - indexed for MEDLINE]
1: J Neuropathol Exp Neurol. 1996 Nov;55(11):1115-23. Links
Comment in:
J Neuropathol Exp Neurol. 1996 Dec;55(12):1280.
J Neuropathol Exp Neurol. 1997 Jan;56(1):105-6.
J Neuropathol Exp Neurol. 1997 Jan;56(1):107-9.
Increasing brain tumor rates: is there a link to
aspartame?
Olney JW, Farber NB, Spitznagel E, Robins LN.
Department of Psychiatry, Washington University Medical School, St. Louis, MO 63110,
USA.
In the past two decades brain tumor rates have risen in several industrialized countries,
including the United States. During this time, brain tumor data have been gathered by the
National Cancer Institute from catchment areas representing 10% of the United States
population. In the present study, we analyzed these data from 1975 to 1992 and found
that the brain tumor increases in the United States occurred in two distinct phases, an
early modest increase that may primarily reflect improved diagnostic technology, and a
more recent sustained increase in the incidence and shift toward greater malignancy that
must be explained by some other factor(s). Compared to other environmental factors
putatively linked to brain tumors, the artificial sweetener aspartame is a promising
candidate to explain the recent increase in incidence and degree of malignancy of brain
tumors. Evidence potentially implicating aspartame includes an early animal study
revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared
to no brain tumors in concurrent controls, the recent finding that the aspartame molecule
has mutagenic potential, and the close temporal association (aspartame was introduced
into US food and beverage markets several years prior to the sharp increase in brain
tumor incidence and malignancy). We conclude that there is need for reassessing the
carcinogenic potential of aspartame.
PMID: 8939194 [PubMed - indexed for MEDLINE]
1: J Neuropathol Exp Neurol. 1996 Nov;55(11):1115-23. Links
Comment in:
J Neuropathol Exp Neurol. 1996 Dec;55(12):1280.
J Neuropathol Exp Neurol. 1997 Jan;56(1):105-6.
J Neuropathol Exp Neurol. 1997 Jan;56(1):107-9.
Aspartame bioassay findings portend human cancer
hazards.
Huff J, LaDou J.
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27514,
USA. [email protected]
The U.S. Food and Drug Administration (FDA) should reevaluate its position on
aspartame as being safe under all conditions. Animal bioassay results predict human
cancer risks, and a recent animal study confirms that there is a potential aspartame risk to
humans. Aspartame is produced and packaged in China for domestic use and global
distribution. Japan, France, and the United States are also major producers. No study of
long-term adverse occupational health effects on aspartame workers have been
conducted. The FDA should consider sponsoring a prospective epidemiologic study of
aspartame workers.
PMID: 18085058 [PubMed - indexed for MEDLINE]
Glutamatergic Influences on the Basal Ganglia.
Review
Clinical Neuropharmacology. 24(2):65-70, March/April 2001.
Greenamyre, J. Timothy
Abstract:
Summary: Glutamate is the predominant excitatory neurotransmitter of the basal
ganglia, where it acts on ionotropic and metabotropic receptors. In the best studied of
the basal ganglia disorders, Parkinson's disease, there is compelling evidence that the
activities of glutamatergic pathways are altered. Of particular importance, the
glutamatergic subthalamic nucleus becomes overactive. Pharmacologic blockade of
subthalamic neurotransmission has antiparkinsonian symptomatic effects and may also
help to protect the remaining dopamine neurons of the substantia nigra from excitotoxic
neurodegeneration. Development of drugs to manipulate the glutamatergic system with
appropriate pharmacologic and anatomic selectivity is likely to dramatically improve our
ability to treat disorders of the basal ganglia.
(C) 2001 Lippincott Williams & Wilkins, Inc.
First Page Image
Annual Review of Neuroscience
Vol. 13: 171-182 (Volume publication date March 1990)
(doi:10.1146/annurev.ne.13.030190.001131)
The Role of Glutamate Neurotoxicity in Hypoxic-Ischemic Neuronal Death
D W Choi, and S M Rothman
In lieu of an abstract, this is the article's first page. See the link to the full PDF below.
PDF
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Tex Heart Inst J. 2004;
PMCID: PMC387446
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Copyright © 2004 by the Texas Heart® Institute,
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Aspartame Disease
A Possible Cause for
Concomitant Graves' Disease and
Pulmonary Hypertension
H. J. Roberts, MD, FACP, FCCP
Palm Beach Institute for Medical Research,
West Palm Beach, Florida
Top
References
To the Editor:
In a recent issue of the Texas Heart Institute Journal,
Virani and co-authors. 1 reported the cases of 2 women,
ages 38 and 40, with concomitant Graves' disease and
pulmonary hypertension. They also cited 5 reports in
the literature since 1999 concerning this combination of
conditions.
I have written about aspartame disease for more than 2
decades, because of the profound adverse neurologic,
cardiopulmonary, endocrine, and allergic effects of
aspartame products. 2,3 These “diet” sodas, along with
thousands of other products containing aspartame, are
currently being consumed by an estimated 70% of the
population. My own database exceeds 1,300 victims of
aspartame-related illnesses, with a 3:1 preponderance of
women—a difference that is germane to the disorders
under consideration.
My 1st report on aspartame-related Graves' disease. 4
described 4 weight-conscious women with
hyperthyroidism who experienced dramatic remissions
within several weeks to 3 months of avoiding
aspartame. Four other women who had been treated
previously for Graves' disease developed symptoms
suggestive of this condition within a few weeks to 6
months after beginning aspartame consumption;
symptoms subsided after cessation. These symptoms
promptly recurred (generally within 2 days) on multiple
rechallenges. The number of patients in this series has
doubled since the initial report.
The problem of aspartame-induced pulmonary
hypertension was raised by a 27-year-old woman with
severe dyspnea and other features attributable to
aspartame disease who was found to have primary
pulmonary hypertension at autopsy. 5 This association
assumed increased relevance because of my database,
which revealed that dyspnea was a major symptom in
110 of 1,200 persons (9%) who reacted to aspartame
products. In no case could the dyspnea be attributed to a
known heart or lung disorder. Most of the patients were
weight-conscious women in their 20s to 40s, who
experienced marked improvement after avoiding
aspartame. Their dyspnea promptly recurred after
rechallenge, both upon self-challenge and upon in
advertent exposure.
Aspartame consists of the amino acids phenylalanine
(50%), aspartic acid (40%), and a methyl ester (10%)
that promptly becomes free methanol after entering the
stomach. 3 The breakdown of phenylalanine to highly
vasoactive substances—such as dopamine,
norepinephrine, and epinephrine—is clearly relevant to
pulmonary hypertension, systemic hypertension, and
the frequent cardiac arrhythmias experienced by
persons with aspartame disease. In my opinion, potent
new drugs aimed at reducing pulmonary hypertension
should be administered in a patient consuming these
products only after a trial of aspartame abstinence.
Footnotes
Letters to the Editor should be no longer than 2 double-spaced
typewritten pages and should contain no more than 4 references.
They should be signed, with the expectation that the letters will be
published if appropriate. The right to edit all correspondence in
accordance with Journal style is reserved by the editors.
Top
References
1.
Virani SS, Mendoza CE, Ferreira AC, de Marchena E. Graves' disease
and pulmonary hypertension: report of 2 cases. Tex Heart Inst J
2003;30:314–5. [PubMed].
2.
Roberts HJ. Aspartame (NutraSweet®): is it safe? Philadelphia: The
Charles Press; 1989.
3.
Roberts HJ. Aspartame disease: an ignored epidemic. West Palm
Beach: Sunshine Sentinel Press; 2001.
4.
Roberts HJ. Aspartame and hyperthyroidism: a presidential affliction
reconsidered. Townsend Letter for Doctors & Patients 1997;May:86–
8.
5.
Roberts HJ. Aspartame-induced dyspnea and pulmonary hypertension.
Townsend Letter for Doctors & Patients 2003; January:64–5.
Articles from Texas Heart Institute Journal are provided
here courtesy of
Texas Heart Institute
Tex Heart Inst
PMCID: PMC387446
J. 2004; 31(1):
105.
Copyright © 2004 by the Texas Heart®
Institute, Houston
Aspartame Disease
A Possible Cause for
Concomitant Graves'
Disease and Pulmonary
Hypertension
H. J. Roberts, MD, FACP,
FCCP
Palm Beach Institute for Medical
Research, West Palm Beach,
Florida
Top
References
To the Editor:
In a recent issue of the Texas Heart Institute Journal, Virani
and co-authors. 1 reported the cases of 2 women, ages 38 and
40, with concomitant Graves' disease and pulmonary
hypertension. They also cited 5 reports in the literature since
1999 concerning this combination of conditions.
I have written about aspartame disease for more than 2
decades, because of the profound adverse neurologic,
cardiopulmonary, endocrine, and allergic effects of aspartame
products. 2,3 These “diet” sodas, along with thousands of other
products containing aspartame, are currently being consumed
by an estimated 70% of the population. My own database
exceeds 1,300 victims of aspartame-related illnesses, with a
3:1 preponderance of women—a difference that is germane to
the disorders under consideration.
My 1st report on aspartame-related Graves' disease. 4
described 4 weight-conscious women with hyperthyroidism
who experienced dramatic remissions within several weeks to
3 months of avoiding aspartame. Four other women who had
been treated previously for Graves' disease developed
symptoms suggestive of this condition within a few weeks to 6
months after beginning aspartame consumption; symptoms
subsided after cessation. These symptoms promptly recurred
(generally within 2 days) on multiple rechallenges. The
number of patients in this series has doubled since the initial
report.
The problem of aspartame-induced pulmonary hypertension
was raised by a 27-year-old woman with severe dyspnea and
other features attributable to aspartame disease who was found
to have primary pulmonary hypertension at autopsy. 5 This
association assumed increased relevance because of my
database, which revealed that dyspnea was a major symptom
in 110 of 1,200 persons (9%) who reacted to aspartame
products. In no case could the dyspnea be attributed to a
known heart or lung disorder. Most of the patients were
weight-conscious women in their 20s to 40s, who experienced
marked improvement after avoiding aspartame. Their dyspnea
promptly recurred after rechallenge, both upon self-challenge
and upon in advertent exposure.
Aspartame consists of the amino acids phenylalanine (50%),
aspartic acid (40%), and a methyl ester (10%) that promptly
becomes free methanol after entering the stomach. 3 The
breakdown of phenylalanine to highly vasoactive substances—
such as dopamine, norepinephrine, and epinephrine—is clearly
relevant to pulmonary hypertension, systemic hypertension,
and the frequent cardiac arrhythmias experienced by persons
with aspartame disease. In my opinion, potent new drugs
aimed at reducing pulmonary hypertension should be
administered in a patient consuming these products only after a
trial of aspartame abstinence.
Footnotes
Letters to the Editor should be no longer than 2 double-spaced typewritten
pages and should contain no more than 4 references. They should be
signed, with the expectation that the letters will be published if appropriate.
The right to edit all correspondence in accordance with Journal style is
reserved by the editors.
References
Top
1.
Virani SS, Mendoza CE, Ferreira AC, de Marchena E. Graves' disease and
pulmonary hypertension: report of 2 cases. Tex Heart Inst J 2003;30:314–5.
[PubMed].
2.
Roberts HJ. Aspartame (NutraSweet®): is it safe? Philadelphia: The Charles
Press; 1989.
3.
Roberts HJ. Aspartame disease: an ignored epidemic. West Palm Beach:
Sunshine Sentinel Press; 2001.
4.
Roberts HJ. Aspartame and hyperthyroidism: a presidential affliction
reconsidered. Townsend Letter for Doctors & Patients 1997;May:86–8.
5.
Roberts HJ. Aspartame-induced dyspnea and pulmonary hypertension.
Townsend Letter for Doctors & Patients 2003; January:64–5.
Articles from Texas Heart Institute Journal are provided here
courtesy of
Texas Heart Institute
REFERENCES:
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Items 21 - 40 of 101
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22:
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23:
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24:
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25:
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PMID: 10503962 [PubMed - indexed for MEDLINE]
26:
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PMID: 10454219 [PubMed - indexed for MEDLINE]
27:
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McMasters DR, Vedani A.
Ochratoxin binding to phenylalanyl-tRNA synthetase: computational approach to the mechanism
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J Med Chem. 1999 Aug 12;42(16):3075-86.
PMID: 10447951 [PubMed - indexed for MEDLINE]
28:
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Danilova V, Hellekant G, Tinti JM, Nofre C.
Gustatory responses of the hamster Mesocricetus auratus to various compounds considered sweet
by humans.
J Neurophysiol. 1998 Oct;80(4):2102-12.
PMID: 9772264 [PubMed - indexed for MEDLINE]
29:
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Creppy EE, Baudrimont I, Anne-Marie.
How aspartame prevents the toxicity of ochratoxin A.
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PMID: 9760456 [PubMed - indexed for MEDLINE]
30:
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Belmadani A, Tramu G, Betbeder AM, Creppy EE.
Subchronic effects of ochratoxin A on young adult rat brain and partial prevention by aspartame,
a sweetener.
Hum Exp Toxicol. 1998 Jul;17(7):380-6.
PMID: 9726534 [PubMed - indexed for MEDLINE]
31:
Related Articles, Links
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernández-López JA, Alemany M.
Formaldehyde derived from dietary aspartame binds to tissue components in vivo.
Life Sci. 1998;63(5):337-49.
PMID: 9714421 [PubMed - indexed for MEDLINE]
32:
Related Articles, Links
Baudrimont I, Ahouandjivo R, Creppy EE.
Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several
agents.
Chem Biol Interact. 1997 Apr 18;104(1):29-40.
PMID: 9158693 [PubMed - indexed for MEDLINE]
33:
Related Articles, Links
Vedani A, Zbinden P.
[Target proteins and mechanisms of ochratoxin toxicity. A contribution to the identification of
potential ochratoxin antagonists]
ALTEX. 1997;14(4):155-164.
PMID: 11178501 [PubMed - as supplied by publisher]
34:
Related Articles, Links
Baudrimont I, Betbeder AM, Creppy EE.
Reduction of the ochratoxin A-induced cytotoxicity in Vero cells by aspartame.
Arch Toxicol. 1997;71(5):290-8.
PMID: 9137807 [PubMed - indexed for MEDLINE]
35:
Related Articles, Links
Koestner A.
"Increasing brain tumor rates: is there a link to aspartame?".
J Neuropathol Exp Neurol. 1997 Jan;56(1):107-9. No abstract available.
PMID: 8990135 [PubMed - indexed for MEDLINE]
36:
Related Articles, Links
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"Increasing brain tumor rates: is there a link to aspartame?".
J Neuropathol Exp Neurol. 1997 Jan;56(1):105-6. No abstract available.
PMID: 8990134 [PubMed - indexed for MEDLINE]
37:
Related Articles, Links
Creppy EE, Baudrimont I, Belmadani A, Betbeder AM.
Aspartame as a preventive agent of chronic toxic effects of ochratoxin A in experimental
animals.
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PMID: 8972353 [PubMed - indexed for MEDLINE]
38:
Related Articles, Links
Creppy EE, Baudrimont I, Betbeder AM.
Prevention of nephrotoxicity of ochratoxin A, a food contaminant.
Toxicol Lett. 1995 Dec;82-83:869-77. Review.
PMID: 8597155 [PubMed - indexed for MEDLINE]
39:
Related Articles, Links
Durnev AD, Oreshchenko AV, Kulakova AV, Beresten' NF, Seredenin SB.
[Clastogenic activity of dietary sugar substitutes]
Vopr Med Khim. 1995 Jul-Aug;41(4):31-3. Russian.
PMID: 8571583 [PubMed - indexed for MEDLINE]
40:
Related Articles, Links
Rowan AJ, Shaywitz BA, Tuchman L, French JA, Luciano D, Sullivan CM.
Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive
individuals.
Epilepsia. 1995 Mar;36(3):270-5.
PMID: 7614911 [PubMed - indexed for MEDLINE]
Items 21 - 40 of 101
Previous Page
2
of 6Nex
Items 61 - 80 of 101
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4
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61:
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Guiso G, Caccia S, Vezzani A, Stasi MA, Salmona M, Romano M, Garattini S.
Effect of aspartame on seizures in various models of experimental epilepsy.
Toxicol Appl Pharmacol. 1988 Dec;96(3):485-93.
PMID: 2974654 [PubMed - indexed for MEDLINE]
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Fountain SB, Hennes SK, Teyler TJ.
Aspartame exposure and in vitro hippocampal slice excitability and plasticity.
Fundam Appl Toxicol. 1988 Aug;11(2):221-8.
PMID: 3220201 [PubMed - indexed for MEDLINE]
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Janssen PJ, van der Heijden CA.
Aspartame: review of recent experimental and observational data.
Toxicology. 1988 Jun;50(1):1-26. Review.
PMID: 3291200 [PubMed - indexed for MEDLINE]
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Drenth JP, Kleinjans JC.
[Aspartame, a sweet alternative]
Ned Tijdschr Geneeskd. 1988 Apr 16;132(16):712-5. Dutch. No abstract available.
PMID: 3374651 [PubMed - indexed for MEDLINE]
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Pinto JM, Maher TJ.
Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in
mice.
Neuropharmacology. 1988 Jan;27(1):51-5.
PMID: 3352866 [PubMed - indexed for MEDLINE]
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Okholm L.
[Aspartame--its status following 20 years of toxicology studies]
Tandlaegebladet. 1987 Aug;91(11):493-7. Danish. No abstract available.
PMID: 3478828 [PubMed - indexed for MEDLINE]
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Dews PB.
Summary report of an International Aspartame Workshop.
Food Chem Toxicol. 1987 Jul;25(7):549-52. No abstract available.
PMID: 3623346 [PubMed - indexed for MEDLINE]
68:
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Stegink LD.
The aspartame story: a model for the clinical testing of a food additive.
Am J Clin Nutr. 1987 Jul;46(1 Suppl):204-15. Review.
PMID: 3300262 [PubMed - indexed for MEDLINE]
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Zametkin AJ, Karoum F, Rapoport JL.
Treatment of hyperactive children with D-phenylalanine.
Am J Psychiatry. 1987 Jun;144(6):792-4.
PMID: 3296793 [PubMed - indexed for MEDLINE]
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Maher TJ.
Natural food constituents and food additives: the pharmacologic connection.
J Allergy Clin Immunol. 1987 Mar;79(3):413-22. Review. No abstract available.
PMID: 2880886 [PubMed - indexed for MEDLINE]
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Maher TJ.
Neurotoxicology of food additives.
Neurotoxicology. 1986 Summer;7(2):183-96. Review. No abstract available.
PMID: 3537851 [PubMed - indexed for MEDLINE]
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Sturtevant F.
Does aspartame cause methanol toxicity?
Food Chem Toxicol. 1985 Oct;23(10):961. No abstract available.
PMID: 4065772 [PubMed - indexed for MEDLINE]
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[No authors listed]
Aspartame. Review of safety issues. Council on Scientific Affairs.
JAMA. 1985 Jul 19;254(3):400-2.
PMID: 2861297 [PubMed - indexed for MEDLINE]
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Sturtevant FM.
Use of aspartame in pregnancy.
Int J Fertil. 1985;30(1):85-7. Review.
PMID: 2862125 [PubMed - indexed for MEDLINE]
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Olney JW.
Excitotoxic food additives--relevance of animal studies to human safety.
Neurobehav Toxicol Teratol. 1984 Nov-Dec;6(6):455-62. Review.
PMID: 6152304 [PubMed - indexed for MEDLINE]
76:
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Hagiwara A, Fukushima S, Kitaori M, Shibata M, Ito N.
Effects of three sweeteners on rat urinary bladder carcinogenesis initiated by N-butyl-N-(4hydroxybutyl)-nitrosamine.
Gann. 1984 Sep;75(9):763-8.
PMID: 6500232 [PubMed - indexed for MEDLINE]
77:
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Sadler MJ.
Recent aspartame studies.
Food Chem Toxicol. 1984 Sep;22(9):771-3. No abstract available.
PMID: 6149179 [PubMed - indexed for MEDLINE]
78:
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Grasso P, Cohen J, Roe F.
Aspartame: succession of false alarms.
Hum Toxicol. 1984 Aug;3(4):257-9. No abstract available.
PMID: 6480003 [PubMed - indexed for MEDLINE]
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Shahangian S, Ash KO, Rollins DE.
Aspartame not a source of formate toxicity.
Clin Chem. 1984 Jul;30(7):1264-5. No abstract available.
PMID: 6733917 [PubMed - indexed for MEDLINE]
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Ito N, Fukushima S, Shirai T, Hagiwara A, Imaida K.
Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis.
IARC Sci Publ. 1984;(56):399-407.
PMID: 6536604 [PubMed - indexed for MEDLINE]
Items 61 - 80 of 101
Items 81 - 100 of 101
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81:
Related Articles, Links
Stegink LD, Filer LJ Jr, Baker GL.
Plasma amino acid concentrations in normal adults fed meals with added monosodium Lglutamate and aspartame.
J Nutr. 1983 Sep;113(9):1851-60.
PMID: 6886827 [PubMed - indexed for MEDLINE]
82:
Related Articles, Links
Stegink LD, Brummel MC, Filer LJ Jr, Baker GL.
Blood methanol concentrations in one-year-old infants administered graded doses of aspartame.
J Nutr. 1983 Aug;113(8):1600-6.
PMID: 6875695 [PubMed - indexed for MEDLINE]
83:
Related Articles, Links
Horwitz DL, Bauer-Nehrling JK.
Can aspartame meet our expectations?
J Am Diet Assoc. 1983 Aug;83(2):142-6. Review.
PMID: 6348131 [PubMed - indexed for MEDLINE]
84:
Related Articles, Links
Filer LJ Jr, Baker GL, Stegink LD.
Effect of aspartame loading on plasma and erythrocyte free amino acid concentrations in oneyear-old infants.
J Nutr. 1983 Aug;113(8):1591-9.
PMID: 6135765 [PubMed - indexed for MEDLINE]
85:
Related Articles, Links
Stegink LD, Filer LJ Jr, Baker GL.
Effect of aspartame plus monosodium L-glutamate ingestion on plasma and erythrocyte amino
acid levels in normal adult subjects fed a high protein meal.
Am J Clin Nutr. 1982 Dec;36(6):1145-52.
PMID: 7148735 [PubMed - indexed for MEDLINE]
86:
Related Articles, Links
Uribe M.
Potential toxicity of a new sugar substitute in patients with liver disease.
N Engl J Med. 1982 Jan 21;306(3):173-4. No abstract available.
PMID: 7054663 [PubMed - indexed for MEDLINE]
87:
Related Articles, Links
Ishii H.
Incidence of brain tumors in rats fed aspartame.
Toxicol Lett. 1981 Mar;7(6):433-7.
PMID: 7245229 [PubMed - indexed for MEDLINE]
88:
Related Articles, Links
Olney JW.
Excitatory neurotoxins as food additives: an evaluation of risk.
Neurotoxicology. 1981 Jan;2(1):163-92. Review. No abstract available.
PMID: 15622732 [PubMed - indexed for MEDLINE]
89:
Related Articles, Links
Ishii H, Koshimizu T, Usami S, Fujimoto T.
Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104
weeks.
Toxicology. 1981;21(2):91-4.
PMID: 7281205 [PubMed - indexed for MEDLINE]
90:
Related Articles, Links
Stegink LD, Filer LJ Jr, Baker GL, McDonnell JE.
Effect of an abuse dose of aspartame upon plasma and erythrocyte levels of amino acids in
phenylketonuric heterozygous and normal adults.
J Nutr. 1980 Nov;110(11):2216-24.
PMID: 7431122 [PubMed - indexed for MEDLINE]
91:
Related Articles, Links
Lederer J.
[Sweetening agents: saccharin--cyclamate and its metabolites--aspartame]
Rev Med Suisse Romande. 1980 Jan;100(1):87-100. Review. French. No abstract available.
PMID: 6770435 [PubMed - indexed for MEDLINE]
92:
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Brunner RL, Vorhees CV, Kinney L, Butcher RE.
Aspartame: assessment of developmental psychotoxicity of a new artificial sweetener.
Neurobehav Toxicol. 1979 Spring;1(1):79-86. No abstract available.
PMID: 551307 [PubMed - indexed for MEDLINE]
93:
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[No authors listed]
Effect of aspartame and aspartate loading upon plasma and erythrocyte free amino acids in
normal adult volunteers.
Nutr Rev. 1978 Apr;36(4):110-2. Review. No abstract available.
PMID: 353592 [PubMed - indexed for MEDLINE]
94:
Related Articles, Links
Stegink LD, Filer LJ Jr, Baker GL.
Effect of aspartame and aspartate loading upon plasma and erythrocyte free amino acid levels in
normal adult volunteers.
J Nutr. 1977 Oct;107(10):1837-45.
PMID: 903828 [PubMed - indexed for MEDLINE]
95:
Related Articles, Links
Okuizumi K, Kuribara H, Ogawa H, Tadokoro S.
[Effects of sweetners on licking behavior in schedule-induced polydipsia]
Nippon Yakurigaku Zasshi. 1977 Jan;73(1):1-13. Japanese. No abstract available.
PMID: 558939 [PubMed - indexed for MEDLINE]
96:
Related Articles, Links
Reynolds WA, Butler V, Lemkey-Johnston N.
Hypothalamic morphology following ingestion of aspartame or MSG in the neonatal rodent and
primate: a preliminary report.
J Toxicol Environ Health. 1976 Nov;2(2):471-80.
PMID: 827619 [PubMed - indexed for MEDLINE]
97:
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Knopp RH, Brandt K, Arky RA.
Effects of aspartame in young persons during weight reduction.
J Toxicol Environ Health. 1976 Nov;2(2):417-28.
PMID: 796476 [PubMed - indexed for MEDLINE]
98:
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Reif-Lehrer L.
Possible significance of adverse reactions to glutamate in humans.
Fed Proc. 1976 Sep;35(11):2205-11. Review.
PMID: 782921 [PubMed - indexed for MEDLINE]
99:
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Olney JW.
Letter: 1-Glutamic and L-aspartic acids--a question of hazard?
Food Cosmet Toxicol. 1975 Oct;13(5):595-6. No abstract available.
PMID: 811518 [PubMed - indexed for MEDLINE]
100:
Related Articles, Links
[No authors listed]
Synthetic sweetners: cyclamates, saccharin, aspartame.
Med Lett Drugs Ther. 1975 Jul 18;17(15):61-2. No abstract available.
PMID: 1152816 [PubMed - indexed for MEDLINE]
Items 81 - 100 of 101
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