safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF: Murray 1.12.3 rmforall: FDA Docket 02P-0317 Recall Aspartame as a Neurotoxic Drug
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 1.12.3 rmforall:
FDA Docket 02P-0317 Recall Aspartame as a Neurotoxic Drug
Please post this to the FDA Dockets website.
Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-986-9103
Jan 12 2003 How sad and how harmful is this "review", which
parrots the industry's standard PR lines,
dismisses without adaquate assessment key contrary studies,
accepts uncritically very weak supportive studies,
justifies ignoring thousands of customer and physician reports,
omits very relevent recent studies,
are uninformed about new general theories about toxic processes in
various diseases in the catagory of fibromyalgia and multiple chemical
sensitivity, and fails to see the urgent need to do
competent, unbiased, thorough, detailed, and definitive research on the
actual biochemical disposition of the toxic metabolites of aspartame in
long-term heavy users, who in unknown numbers develop the typical
complex serious symptom syndrome, often becoming extremely sensitive to
doses as small as a single migraine pill, 4 mg aspartame, 2% of the
aspartame in a single 12-oz diet soda.
Links to scores of reviews and full texts of studies in the mainstream
scientific literature are given at the end of this post.
B-1049 Bruxelles/ B-1049 Brussels- Belgium
Telephone: exchange (+32-2) 299 11 11 Fax: (+32-2) 299 48 91
EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
Directorate C-- Scientific Opinions C2-- Management of scientific
committees II; scientific co-operation and networks
Scientific Committee on Food SCF/CS/ADD/EDUL/222 Final
10 December 2002 Opinion of the Scientific Committee on Food:
Update on the Safety of Aspartame (expressed on 4 December 2002) [p2]
Terms of Reference
The Committee is asked to review all new scientific information on
aspartame not having been examined by the SCF previously, taking into
account, notably, the literature search carried out in the UK.
The intense sweetener, aspartame, is used in a wide range of food
products in many countries around the world and is authorised for use in
the EU (E951). It has the following structure:
The Scientific Committee for Food (SCF) initially evaluated aspartame
(L-aspartyl-L-phenylalanine methyl ester) during 1984 (SCF, 1985) and
subsequently during 1988 (SCF, 1989).
At its 107th meeting in June 1997, the SCF also examined the issue of an
alleged connection between aspartame and increase in incidence of brain
tumours in the USA (SCF, 1997).
Aspartame has also been considered by other bodies including the Joint
FAO/WHO Expert Committee on Food Additives (JECFA, 1980) the US Food and
Drug Administration (FDA, 1984), and the UK Committee on Toxicity (COT,
The toxicity data on aspartame were used by the JECFA, SCF and COT to
establish an Acceptable Daily Intake (ADI) of 40 mg/kg body weight/day
and an ADI of 50 mg/kg bw/d was established by the FDA.
An ADI of 7.5 mg/kg bw/d was also established for a minor cyclic
dipeptide derivative of aspartame, a diketopiperazine (DKP), which
is formed in some aqueous solutions (JECFA, 1980; SCF, 1985).
The safety issues that have been raised in the past about aspartame have
(1) the possibility of toxicity from methanol, one of the breakdown
products of aspartame;
(2) elevations in plasma concentrations of phenylalanine (Phe) and
aspartic acid, which could result in increased transport of these amino
acids into the (p3) brain, altering the brain's neurochemical
(3) the possibility of neuroendocrine changes, particularly increased
concentrations in the brain, synaptic ganglia and adrenal medulla of
catecholamines derived from Phe and its hydroxylation product, tyrosine;
and (4) a postulated link with epilepsy and brain tumours.
All these areas have been addressed in the pre-1988 literature and in
more recent reviews (Meldrum, 1993; Lajtha et al., 1994; Tschanz et al.,
The safety of aspartame and its metabolic breakdown products
(phenylalanine, aspartic acid and methanol) has been assessed in humans
generally and in several subgroups, including healthy infants, children,
adolescents, adults, obese individuals, diabetics, lactating women, and
individuals heterozygous for the genetic disease, phenylketonuria (PKU),
who have a compromised ability to metabolise the essential amino acid,
Since its approval, aspartame has undergone further investigation
through clinical and laboratory research, intake studies and
postmarketing surveillance of anecdotal reports of adverse health
The present review updates the previous SCF opinions in the light of new
reports on the consumption of aspartame in relation to the onset of
brain tumours and seizures, headaches, allergies, and changes in
behaviour and cognitive function.
Information on the safety of aspartame was available from a variety of
sources including scientific papers, conference proceedings, abstracts
and magazine articles.
This review focuses on papers published in the open scientific
literature from 1988 to 2001 and draws on the recent extensive review by
the Agence Française de Sécurité Sanitaire des Aliments (AFSSA, 2002),
which covered mutagenic, carcinogenic and neurological effects.
European Commission report on Food Additive Intake
In the European Commission report on Dietary Food Additive Intake in the
European Union (EC, 2001), estimates of intake were calculated using a
Tier 1 is based on theoretical food consumption data and maximum usage
levels for additives as permitted by relevant Community legislation.
The second and third tiers refer to assessment at the level of
individual Member States, combining national data on food consumption
with the maximum permitted usage levels for the additive (Tier
with its actual usage patterns (Tier 3).
Aspartame has been examined at Tier 1 for adults and
at Tier 2 for children.
Aspartame intakes for adults were estimated at Tier 1 to be 21.3 mg/kg
bw/day in the European Union. The Tier 1 approach is likely to be an
overestimate of actual intake even by high level consumers of
More refined intake [p4] estimates (Tier 2) were performed for children.
Information from individual member states showed that the refined
estimated intake for children was 1-40% of the ADI.
Therefore aspartame was excluded from further consideration as both
adults and children were shown to be unlikely to exceed the ADI of 40
Other published intake estimates for European countries
In addition to the Commission report, a number of reports have been
published from 1990 onwards with estimates of aspartame intake in
European countries (Bär and Biermann, 1992; Butchko and Stargel, 2001;
Garnier-Sagne et al., 2001; Hinson and Nicol, 1992; Leclercq et al.,
1999; MAFF, 1990 and 1995; Renwick, 1990; Salminen and Penttilä, 1999).
The table below shows the highest reported intake estimates for
different age groups of the general population and people with diabetes.
The data are based on actual food consumption combined with the actual
sweetener levels present in the foods (equivalent to Tier 3 in the
Commission report) or the maximum permitted aspartame levels (Tier 2).
The estimates of intake by mean and high level consumers are fairly
consistent between European countries even though slightly different
approaches were used.
High level consumers, both adults and children, are unlikely to exceed
the ADI of 40 mg/kg bw for aspartame.
Special groups such as diabetics that are likely to be high consumers of
foods containing aspartame are also well below the ADI.
Therefore, from the available data it appears that no group is likely to
exceed the ADI for aspartame on a regular basis.
Table: Highest reported intake estimates for aspartame
Mean consumer intake in mg/kg bw/d
High level consumer intake in mg/kg bw/d
Children 1-5 years old UK - 2.8 (90) Hinson & Nicol, 1992
Children 1-6 years old Finland - <4 (-) Salminen & Penttilä, 1999
All ages Netherlands - 2.4 7.5 (95) Butchko & Stargel, 2001
All ages Norway 3.4 - Butchko & Stargel, 2001
Diabetics* 2-20 years old France 2.4 7.8 (97.5) Garnier-Sagne et
Diabetics 2-65 years old UK - 10.1 (97.5) MAFF, 1995
* using maximum permitted level of sweeteners in different food
categories (Tier 2 approach). All the other figures are derived using
actual sweetener levels present in foods. [p5]
Absorption, distribution, metabolism and excretion
The metabolism of aspartame and its metabolic breakdown products in
animals, healthy individuals and in PKU subjects has been
comprehensively reviewed by Lajtha et al. (1994).
Aspartame is metabolised by gut esterases and peptidases to three common
dietary components-- two amino acids (aspartic acid and Phe) and
Animal studies have demonstrated that the metabolic breakdown products
of aspartame are absorbed and metabolised similarly whether they are
given alone or derived from aspartame.
The extensive presystemic metabolism of aspartame results in little or
no parent compound reaching the general circulation.
Initial studies focused on the effects of ingesting single bolus doses
of aspartame on plasma aspartate and Phe levels and blood methanol
concentrations in normal adults.
These studies were done with doses of aspartame approximating current
levels of dietary exposure (4 and 10 mg/kg bw), doses representative of
premarketing projections of the high level intake and the ADI (34 and 40
mg/kg bw respectively), and abuse doses of 100, 150 and 200 mg/kg bw
(Stegink and Filer 1996).
The plasma Phe concentrations in healthy adults administered various
doses of aspartame have been compared to values obtained:
(1) in the fasting and postprandial state;
(2) in individuals who are heterozygous for PKU; and
(3) in subjects with various forms of hyperphenylalaninaemia other than
PKU (Stegink et al 1990; Stegink and Filer, 1996).
The data indicated that the plasma Phe concentrations after single bolus
doses (ranging between 4 and 50 mg/kg bw) and repeated doses (30 and
69 mg/kg bw given as 3 and 8 divided doses respectively) of aspartame
were generally within the normal postprandial range for this amino acid
and well below those measured in subjects homozygous for PKU after
ingestion of aspartame.
The aspartate component is rapidly metabolised and thus the plasma
aspartate concentrations are not significantly elevated following
aspartame doses of 34 to 50 mg/kg bw, whereas plasma Phe concentrations
may increase depending on dose (Stegink, 1984).
Methanol is also rapidly metabolised and blood levels are usually
not detectable unless large bolus doses of aspartame (>50 mg/kg bw) are
Genotoxicity and carcinogenicity
The available mutagenicity and long-term carcinogenicity studies on
aspartame were recently reviewed by AFSSA (2002). AFSSA noted that:
Aspartame is not genotoxic in a reverse mutation test on S.
typhimurium, in two chromosome aberration tests in vivo on somatic cells
and in Rodent [p6] dominant lethal test on germ cells (JECFA, 1980).
Recently, two studies have confirmed the absence of clastogenic
potential (Durnev et al., 1995; Mukhopadhyay et al., 2000) of the
The AFSSA report also noted:
Trocho et al., (1998) demonstrated that aspartame, radio-labelled on
the methanol, induced in the liver stable DNA and protein adducts.
According to these authors, the accumulation of these adducts after
repeated administration of aspartame could pose problems of toxicity and
carcinogenicity in the long term. Besides the fact that aspartame at
high doses has never induced liver cancer in rats, Trocho's studies did
not identify the radioactivity found in the proteins and DNA.
Consequently, the formation of adducts of formaldehyde
on the proteins and nucleic acids from aspartame, in vivo, remains to be
proved (Tephly, 1999).
As regards the long-term studies, the AFSSA report noted that:
In a carcinogenicity study on CD-1 mice (FDA, FR 1981), aspartame
administered in feed at doses of 1, 2 and 4 g/kg bw/day for 110 weeks,
showed no carcinogenic potential.
Three carcinogenicity studies were conducted in Sprague Dawley and
Wistar rats. In the first study (1973), post-weaning Sprague Dawley rats
were fed doses of aspartame corresponding to 1, 2, 4, 6/8 g/kg bw/day
for 104 weeks (6/8 i.e. dose of 6 was increased during the study to 8
g/kg bw/day). In the second study (1974), male and female Sprague Dawley
rats, from a twogeneration study, were exposed during gestation,
lactation and after weaning for 104 weeks, to doses of 0, 2 and 4 g/kg
bw/day in their food. The results of these two studies have been widely
discussed by the scientific community and the regulatory authorities
(FDA). In the first study, the incidence of brain tumours in the treated
animals was higher than in the control animals but without any
dose-response relationship. In contrast, in the second study the
incidence of tumours in the treated rats was lower than in the control
For these reasons, a third study was conducted under conditions of Good
Laboratory Practice in order to ensure the reliability of the
In this third study (Ishii, 1981), groups of male and female Wistar rats
were given doses of aspartame of 0, 1, 2, 4 g/kg bw/day for 104 weeks.
Under these conditions, aspartame did not cause any increase in the
incidence of brain tumours.
AFSSA concluded as follows on carcinogenicity:
Taking into account all the studies that have been conducted, the
frequency of spontaneous tumours in laboratory rats, the types of
tumours observed and the absence of a dose-response relationship, it was
concluded that aspartame had no carcinogenic potential on the brain in
experimental animals (FDA FR, 1981-1984; Koestner, 1984; Cornell et al.,
1984; Flamm, 1997). [p7]
Concerning the epidemiological data on brain tumours, the AFSSA (2002)
report noted that:
In 1996, Olney et al. published an article on a possible link between
the increase in the frequency of brain tumours in humans and the
consumption of aspartame in the United States. Based on the data from
the National Cancer Institute (10% of the population) from 1975-1992,
the authors concluded that there was a significant increase in the
frequency of brain tumours in the mid-1980s, that is to say the period
following aspartame came onto the market. The conclusions of this
epidemiological study have been criticised by a number of scientists who
questioned the methodology, the use of the data and their
interpretation (Levy et al., 1996; Linet et al., 1999; Ross, 1998;
Seife, 1999; Smith et al., 1998). One of the major criticism is that the
authors only took into account the frequency of brain tumours during a
selected period (1975-1992). When all the epidemiological data are used
(1973-1992) a different conclusion is reached, as the frequency of brain
cancers began to increase in 1973 and stabilised from the mid-1980s
(Levy et al., 1996). Furthermore, Olney et al. did not provide any
quantitative or qualitative relationship between the exposure of the
population to aspartame and the observed frequency of brain tumours.
Finally, an increase in the incidence of the tumours can have many
causes including, among others, improvements in diagnostic methods
(Modan et al., 1992).
More recently, Gurney et al., (1997) published the results of a
case-control study on the relationship between the consumption of
aspartame and the frequency of brain tumours. The study covered 56
patients affected by tumours in childhood and 94 controls. According to
these authors, no relationship could be established between the
consumption of aspartame and the frequency of brain tumours.
In France, data on the incidence of and mortality from brain cancers
were supplied by the FRANCIM network (F. Ménégoz et al., 2001). These
cancers include meninges tumours and tumours of the brain itself.
Between 1980 and 1997, the incidence (number of new cases appearing each
year) of cerebral tumours was relatively stable in men and showed a
slight increase in women. The trend towards an increase in mortality
from cancer of the brain and other parts of the nervous system is a
longstanding one, as it first appeared in 1950 and continues to the
present day, for both sexes. However, during the last decade, mortality
in men stabilised and the increase in mortality from brain cancer in
women was less pronounced than during the preceding period.
In France, the epidemiological data from the cancer registers do not
enable a definitive indication to be given on a possible aspartame-brain
tumour relationship, but they do show that, at the present time, the
sale of this food additive in France is not being accompanied by an
increase in the frequency of brain tumours or increased mortality from
this disease in the general population. [p8]
Reproduction and Developmental toxicity
The derivation of an ADI for aspartame by JECFA (1980) and the SCF
(1985) included assessment of single- and multi-generation studies in
animals that were specifically designed to examine the possible effects
of aspartame and its metabolic conversion products on reproduction, and
development, including neuro-development.
The data used by JECFA (1980) were discussed in more recent reviews
(Kotsonis and Hjelle, 1996; London and Rorick, 1996; Shaywitz, 1997;
AFSSA, 2002), but no additional studies were identified which would
impact on the no-observed-adverse-effect-level (NOAEL).
Neurological effects Much of the recent interest in the safety of
aspartame has explored whether its consumption is linked with
neurological effects. Therefore this end point has been given special
consideration in this review.
Shortly after the widespread marketing of aspartame, there were a number
of anecdotal reports of health effects, which some consumers related to
their consumption of aspartame-containing products (Hull, 1999). Most of
the earlier complaints and reports of aspartame-related adverse
reactions were analysed by experts at the Centres for Disease Control
(CDC) in Atlanta on behalf of the FDA, who concluded that there was no
symptom complex that could be assigned to the ingestion of aspartame
(Janssen and Van der Heijden, 1988; Tollefson, 1988).
A number of complaints were of a neurological or behavioural type
(Tollefson, 1988) and these received special consideration, in part
because experiments in animals have shown that high doses (1000mg/kg bw
and above in rats) can alter the concentrations of neurotransmitters and
their precursors within the central nervous system (Lajtha et al.,
As regards the potential effect of aspartame on neurotransmitter levels,
the underlying hypothesis was that aspartame, as a source of Phe without
the other large neutral amino acids (LNAA) (i.e. tryptophan, valine,
leucine, methionine, histidine) which compete for transport across the
blood-brain barrier, would increase the serum ratio of Phe to the other
LNAA, thereby selectively increasing Phe concentrations in brain. It
was further suggested that such increased entry of Phe into the brain
may result in disturbances in monoaminergic neurotransmission (Wurtman,
A number of animal studies were conducted to determine whether increases
in plasma Phe concentrations secondary to large doses of aspartame may
result in changes in brain concentrations of norepinephrine, dopamine,
or serotonin and their metabolites (reviewed by Schomer et al., 1996;
Lajtha et al., 1994). Although effects on neurotransmitter levels were
noted in some acute and repeat-dose studies at high doses in rodents, it
was apparent that these effects were not consistent or reproducible.
For instance, acute doses of up to 2000 mg/kg bw/d and repeated doses of
up to 863 mg/kg bw/d (for 28 days) failed to induce significant changes
in brain serotonin or dopamine levels and had no effect on seizure
severity in rats genetically prone to epilepsy (Dailey et al., 1991).
Some changes in neurotransmitter levels in rodents were also identified
in some of the older studies on aspartame (Lajtha et al., 1994). In mice
given aspartame orally at 13,130 and 650 mg/kg bw, increases of 12, 49
and 47% respectively in norepinephrine were found after 3 hours in the
hypothalamus; significant increases in norepinephrine in the medulla
oblongata (in the low- and high-dose group animals) and corpus striatum
(in the low-dose group animals) were also observed (Coulombe and Sharma,
1986). However, these increases were not dose-related and were
accompanied by non-significant changes in serotonin levels.
Lack of any significant effects on biogenic amine levels, following
higher bolus doses (1000 mg/kg bw) of aspartame, have also been reported
in both Sprague-Dawley and Fischer 344 rats (Freeman et al., 1990).
Glutamic and aspartic acids act as excitatory neurotransmitters at
glutamate receptor sites to which aspartic acid also shows affinity.
A more recent study evaluated brain glutamatergic receptor kinetics
following perinatal exposure to large doses of aspartame (500 mg/kg
bw/day) (Reilly and Lajtha, 1995). In this study aspartame in drinking
water was administered to Sprague-Dawley rats throughout gestation and
lactation. The kinetics of the N-methyl-D-aspartate receptor and total
glutamatergic binding in cerebral cortex and hippocampus of the
offspring (20-22 days old) were found to be unaffected by perinatal
exposure to aspartame. However, statistically significant but reversible
reductions in glutamic acid levels in both brain regions and of
aspartate in the hippocampus were noted.
The same group of workers reported an absence of effects on
dopaminergic, adrenergic and serotonergic receptor binding kinetics in
adult rat brain with chronic exposure to aspartame (Reilly et al.,
Behaviour, Cognition and Mood
Some years ago, it was hypothesised that aspartame, primarily due to its
content of Phe, could have an effect on human behaviour, cognition, and
possibly on measures of physiological function (Wurtman, 1985). However,
no consistent and reproducible effects were observed in a number of
older animal studies investigating the effects of aspartame on
neurotransmitter levels. [p10]
Only a limited number of studies on behavioural aspects in animals have
been published in the last ten years. A proportion of these focused on
seizure activity but a causal link with aspartame could not be
established; no adverse effects on other aspects of behaviour and
cognition were reported in experimental animals when aspartame was given
at oral dose levels of up to 2000 mg/kg bw/day (Yirmiya et al., 1989;
Tilson et al., 1991; Mullenix et al., 1991; Vitulli et al., 1996; LaBuda
and Hale, 2000; Goerss et al., 2000).
A number of anecdotal reports in humans were received by the
manufacturers of aspartame in early to mid 1980's relating to a variety
of symptoms following the marketing of aspartame in the USA. About
two-thirds of these symptoms fell into the neurobehavioural category
(Butchko and Stargel, 2001). These consisted mostly of headaches (see
below), mood alterations, insomnia, and dizziness. More than 500
reports were received by CDC, and almost half underwent follow-up and
A post-marketing surveillance system was developed by the NutraSweet
company (Butchko and Kotsonis, 1994; Butchko et al., 1996), which was
followed by scientific research on these neurological symptoms (see
A number of scientific studies were carried out in healthy and
potentially sensitive individuals, including children, to test whether
the consumption of aspartame was associated with behavioural and
cognitive changes. The potentially sensitive individuals studied were,
heterozygotes for PKU, individuals suffering from depression, Attention
Deficit Disorder (ADD), Parkinsons Disease, epilepsy or other
suspected seizures. They included double-blind studies in children
(Saravis et al., 1990; Shaywitz et al., 1994) in which no effects were
observed on behaviour, mood or learning when aspartame was given as a
drink at single and multiple doses of 34 mg/kg bw/day for up to two
The longer term study of Shaywitz et al.(1994) examined the effect of
aspartame in children with ADD and included an assessment of
liver function as well as measurement of plasma levels of amino acids,
serotonin and monoamine metabolites.
Treatment-related effects were also absent in a study of preschool
children who were given aspartame at 32 mg/kg bw/day and described as
sugar sensitive by their parents (Wolraich et al., 1994).
A number of double-blind behavioural studies of variable quality in
healthy adults, involving single and repeated administrations of
aspartame have also been conducted. No treatment-related effects were
noted in tests on a range of cognitive parameters in studies employing
single administrations of aspartame at doses of up to 60 mg/kg
bw/day (Lieberman et al., 1988; Lapierre et al., 1990; Pivonka and
Grunewald, 1990; Stokes et al., 1991, 1994).
However, it can be argued that single dosing studies employing high
amounts of aspartame do not reflect typical consumption patterns.
A number of longer term studies with a double-blind design involving
multiple dosing in healthy individuals also failed to highlight any
treatment-related adverse effects on [p11] behaviour (Spiers et al.,
1998; Leon et al., 1989).
As noted with shorter-term studies, no treatment-related effects on
behaviour were noted even when aspartame was tested at 74 mg/kg bw/day
for periods extending up to 24 weeks. Although Phe concentrations
increased significantly as a result of treatment with aspartame, there
were no significant effects noted on behaviour, mood or
electroencephalogram (EEG) patterns, nor on a comprehensive battery of
clinical laboratory tests. Headache was the most frequently reported
adverse effect in placebo- and aspartame-treated groups but there were
no significant differences noted between groups.
Several subpopulations of individuals who may potentially be sensitive
to aspartame have also been studied. From a double-blind study with a
cross-over design in 13 depressed patients, Walton et al. (1993)
concluded that aspartame (30 mg/kg bw/day for 7 days) increased the
frequency and severity of adverse experiences in these individuals.
These authors concluded that the use of aspartame in individuals with
mood disorder should be discouraged. However, it is difficult to
interpret this study since the authors numerically combined unrelated
adverse effects to show a statistically significant result in depressed
patients and only a limited number of subjects were available for
evaluation due to premature termination of the study.
The effect of aspartame on behaviour, cognition and EEG patterns has
also been investigated in PKU heterozygotes. Older studies in PKU
homozygotes and those heterozygous for the condition have been reviewed
elsewhere (de Sonneville and Benninger, 1996, and references therein).
Overall, the authors concluded that aspartame did not affect cognitive
function and EEG profiles in either the general population or those
heterozygous for PKU.
In a more recent double-blind study, which included assessment of plasma
amino acid levels and EEG patterns (Trefz et al., 1994), the subjects
ingested aspartame (15 or 45 mg/kg bw/day) and placebo for 12 weeks. The
battery of behavioural tests included tests for short-term memory,
reaction time and various attention tasks. Although headaches were among
the mild adverse symptoms reported, there was no statistically
significant difference between treatments. There was a significant rise
in Phe in the high-dose group in contrast to the low-dose group and this
was also the case for the ratio of Phe to LNAA. However, aspartame had
no significant effect on cognitive function or EEG profiles.
[ Continued on Part 2/2 ]
aspartame: methanol, formaldehyde, formic acid toxicity:
brief review: Murray 1.10.3 rmforall
for 958 posts in a public searchable archive
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall
It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans) is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time become carbon dioxide and water-- however, about 30% of the
methanol remains in the body as cumulative durable toxic metabolites of
formaldehyde and formic acid-- 37 mg daily, a gram every month.
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in
Bear in mind that the EPA limit for formaldehyde in
drinking water is 1 ppm,
or 2 mg daily for a typical daily consumption of 2 L of water.
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and leading to
vision and eye problems and even seizures. In many cases there is
addiction. Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.
Confirming evidence and a general theory are given by Pall (2002):
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall
Functional Therapeutics in Neurodegenerative Disease Part 1/2:
Perlmutter 7.15.99: Murray 1.10.3 rmforall
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall
comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3 rmforall
aspartame harms mice brain cells: Hetle & Eltervaag: 2001 thesis
abstract: Sonnewald 1995 study, full text: Murray 1.5.3 rmforall
http://www.dorway.com/tldaddic.html 5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan; HJRobertsMD@...
Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg.]
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.]
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 1.5.3 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall
Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science
Director of the Food Science and Nutrition Laboratory
Arizona State University, Tempe, Arizona 85287
6411 South River Drive #61 Tempe, Arizona 85283-3337
602-965-6938 woody.monte@... [now retired in New Zealand]
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame. The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
"Fruit and vegetables contain pectin with variable methyl ester
content. However, the human has no digestive enzymes for pectin (6, 25)
particularly the pectin esterase required
for its hydrolysis to methanol (26).
Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3). In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3). Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).
Entrapment of these volatiles probably accounts for the elevation in
methanol levels of certain fruit and vegetable products
during canning (31, 33)."
Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:
"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:
"is considered a cumulative poison
due to the low rate of excretion once it is absorbed.
In the body, methanol is oxidized to formaldehyde and
formic acid; both of these metabolites are toxic." (8)....
Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34). No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
Formaldehyde has a high reactivity which may be why it
has not been found in humans or other primates during methanol
If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.
Formaldehyde is a known
carcinogen (57) producing squamous-cell carcinomas by inhalation
exposure in experimental animals (22). The available epidemiological
studies do not provide adequate data for assessing the carcinogenicity
of formaldehyde in man (22, 24, 57).
However, reaction of formaldehyde
with deoxyribonucleic acid (DNA) has resulted in irreversible
denaturation that could interfere with DNA replication and result in
Dr. J. Barua (ophthalmic surgeon), Dr. Arun Bal (surgeon)
Emerging facts about aspartame.
Journal Of The Diabetic Association Of India 1995; 35 (4):
(79 references) barua@...
"...the total amount of methanol absorbed will be approximately
10% of aspartame ingested. An EPA assessment of methanol states
that methanol, 'is considered a cumulative poison due to the low rate
of excretion once it is absorbed. The absorbed methanol is then
slowly converted to formaldehyde...'"
"Reaction of formaldehyde with DNA has been observed,
by spectrophotometry and electron microscopy, to result in
"DKP has been implicated in the occurence of brain tumors."
aspartame, cell phones, brain cancer July 1999 Hardell:
Murray 1.9.3 rmforall
Lennart Hardell, M.D., PhD, in 1999 reported in Sweden that both
cell phone use and heavy aspartame use correlate with increased
brain cancers lennart.hardell@... +46 19 602 15 46
http://www.truthinlabeling.org/ Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999; 6: 259-310. 52-page review
P.O. Box 2532 Darien, Illinois 60561
http://www.msgmyth.com/ Debby Anglesey <avenger@...>
Battling the "MSG Myth", A Survival Guide and Cookbook - $19.00
P.O. Box 895 Richland, WA 99352 509-735-3397
Lancet website aspartame letter 7.29.99:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 1.14.0 rmforall
The Medical Sentinel Journal 1999 Fall; (95 references)
Russell L. Blaylock, MD 601-982-1175 Madison, Mississippi
http://www.bioterrorismbook.com/ "Bioterrorism: How You Can Survive"
Advanced Nutritional Concepts,LLC PO Box 2670 Ridgeland, MS 39158-2670
"Excitotoxins: The Taste that Kills", 1977, 298 p., 493 references.
"Health and Nutrition Secrets that can save your life", 2002, 459 p.,
558 + 30 references, $ 30 http://www.healthpress.com/
goodbooks@... PO Box 37470 Albuquerque, NM 87176
505-888-1394 fax 505-888-1521 Kathleen Frazier, Publisher
George R. Schwartz, MD "In Bad Taste: The MSG Syndrome", 1988, 123 p.
Aspartame Toxicity Information Center Mark D. Gold
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
"Scientific Abuse in Aspartame Research"
"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished: http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501 330-740-3621 rwalton193@...
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall
UPI reporter Gregory Gordon: 96K 3-part expose Oct 1987
aspartame history Part 1/4 1964-1976: Gold: Murray 11.6.9: rmforall
http://google.com gives 133,000 websites for "aspartame" , while
http://groups.google.com/ finds on 700 MB of posts from 20-years of
Usenet groups, 75,700 posts, and
http://www.AllTheWeb.com gives 261,750, the top three being leading and
very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp gives 34,100 websites.
http://www.ncbi.nlm.nih.gov/PubMed/ lists 719 aspartame items.
http://www.dorway.com/tldaddic.html 5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan; HJRobertsMD@...
Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax
1038-page medical text "Aspartame Disease: An Ignored Epidemic"
published May 30 2001 $ 85.00 postpaid data from 1200 cases
available at http://www.amazon.com
over 600 references from standard medical research
http://www.aspartameispoison.com/contents.html 34 chapters
Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
Palm Beach Institute for Medical Research, Inc.
P.O. Box 17799, West Palm Beach, FL 33416
fax 561-547-8008 dr.roberts@...
aspartame disease pages 627-685, 778-780 .
RTM: Roberts: the life work of a brilliant clinician:
aspartame toxicity 8.2.2 rmforall
review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2 rmforall
hyperthyroidism (Graves disease) in George and Barbara Bush, 1991--
aspartame toxicity? Roberts 1997: Murray 10.9.2 rmforall
aspartame & diabetes: Roberts 8.9.94:
Murray 1.11.3 rmforall
aspartame & eye problems: Roberts Jan 1994: Murray 1.11.3 rmforall
aspartame and brain cancers: Roberts 1991: Murray 9.15.0
three texts by H.J. Roberts, 1958, 1971, 1979: Murray 1.2.3 rmforall
Roberts, 45 clinical research reports in mainstream journals:
Murray 10.20.2 rmforall