labs now quickly at low cost measure 100 exhaled gases at 1 part per
trillion levels in a single breath to instantly reveal opportunities to
study diseases and toxicities, possibly methanol and formaldehyde from
vehicle exhaust, wood and tobacco smoke, fruits and vegetables, dark
wines and liquors, aspartame: Murray 2007.11.08
http://groups.yahoo.com/group/aspartameNM/message/1486
"Of course, everyone chooses, as a natural priority, to enjoy peace,
joy, and love by helping to find, quickly share, and positively act upon
evidence about healthy and safe food, drink, and environment."
Rich Murray, MA Room For All
rmforall@...
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505
http://RMForAll.blogspot.com new primary archive
http://groups.yahoo.com/group/aspartameNM/messages
group with 111 members, 1,486 posts in a public,
searchable archive
http://rmforall.blogspot.com/2007_09_01_archive.htm
Saturday, September 15, 2007
http://groups.yahoo.com/group/aspartameNM/message/1472
bias, omissions, incuriosity = opportunity, aspartame safety evaluation,
Magnuson BA, Burdock GA, Williams GM, 7 more, 2007 Sept, Ajinomoto
funded 98 pages html [$ 32 781888262_content.pdf]: Murray 2007.09.15
////////////////////////////////////////////////////////////
"The extreme versatility of exhaled gas analysis (combining simultaneous
measurements of 100 or more exhaled gases in each breath with easy,
noninvasive, and painless collection methods) therefore appears
especially suitable for the definition and monitoring of the time course
of evolving, complex metabolic conditions, including, among others,
inflammation, dyslipidemia, and diabetes."
"The Rowland-Blake group analyzed the children's breath samples for more
than 100 gases at parts-per-trillion levels and found methyl nitrate
exhaled concentrations to be increased as much as 10 times more in
diabetic children during hyperglycemia than when they had normal glucose
levels.
The methyl nitrate concentrations corresponded with the children's
glucose levels -- the higher the glucose, the higher the exhaled methyl
nitrates."
[ Murray: Some relavalent toxins now measured include ethanol, methanol,
acetaldehyde, acetone, benzene, carbon monoxide, carbon dioxide, carbon
tetrachloride, carbon disulfide, and toluene, but not as yet
formaldehyde or formic acid, the two inevitable products in the human
body of methanol.
Some experts may be able to suggest any various exhaled gases that might
reveal formaldehyde and formic acid toxicity in humans at low level
chronic exposures. In that case, people who have symptoms from chronic
low-level exposures could readily give exhaled breath samples for
analysis, putting the results on the Net to allow free discussion among
experts worldwide. This could lead to collaboration and funding for
focused studies by mainstream research teams. ]
"Methyl nitrate is the least reactive of all alkyl nitrates that are
commonly observed in the atmosphere.
Their main sources are marine emissions, biomass burning, and
photochemical production in the atmosphere (13–15).
In healthy subjects, exhaled methyl nitrate concentrations are slightly
greater than room air concentration (normally by <10 pptv),
indicating a small net output of this gas by the human body.
The biochemical production of this gas has not been postulated; however,
from our results it is clear that oxidative processes play a major role
in its production.
As a byproduct of physiological, energy-generating oxidative reactions,
a small fraction of oxygen flowing through the mitochondria is converted
to superoxide ion (OFormula), a free radical potentially capable of
damaging cells and tissues (Fig. 4).
These deleterious effects are prevented by multiple antioxidant
mechanisms, such as the action of the enzyme superoxide dismutase, which
converts superoxide to the less reactive oxygen (O2) and hydrogen
peroxide (H2O2), via addition of protons (16).
However, superoxide can also react very rapidly with nitric oxide (NO)
(17, 18), forming a nitrate molecule that can be protonated (19),
the speed of this reaction is likely accelerated at lower pH.
This protonated nitrate species can react with methanol, yielding a
water molecule and a molecule similar to methyl nitrate, which can
isomerize to methyl nitrate.
Within the human body, some colonizing bacteria could produce methanol
directly or oxidize methane (CH4) to methanol (CH3OH) (20, 21),
providing the methyl radical (22, 23), or other metabolic sources may be
responsible for it.
When hyperglycemia occurs in diabetics, an accelerated metabolic flux
through the mitochondria may lead to increased superoxide formation,
possibly directly linking blood glucose levels with systemic oxidation;
in the extreme case of severe hyperketonemia, the pH shift toward
acidosis may further accelerate this chain of reactions."
"In conclusion, analysis of exhaled breath in children with T1DM during
euglycemia or spontaneous hyperglycemia revealed a strong correlation
between the kinetic profiles of plasma glucose and exhaled methyl nitrate.
The characteristics of methyl nitrate formation suggest that this gas
may reflect, rather than hyperglycemia per se, the specific and complex
pattern of metabolic alteration accompanying hyperglycemia in T1DM.
This pattern includes not only hypoinsulinemia and increased lipids and
ketones but also alterations in inflammatory and oxidative markers,
now considered main determinants of diabetic vascular complications.
Optimization of exhaled gas analysis in diabetes may prove invaluable
not only in monitoring glycemic control but also in determining the
actual pathogenic potential of a given glycemic state in terms of
onset/progression of diabetic complications."
[ Notably, an EU team is sharing openly on the Net its competent program
to develop carbon nanotube sensors for gases that promise outstanding
portability, low cost, speed, sensitivity, accuracy, flexibility, and
convenience:
www.nano2hybrids.net/5-project_background/abstract.php
[ this summary quoted at the end of this post ] ]
www.sciencedaily.com/releases/2007/09/070925081425.htm
Science News
Breath Analysis Offers Potential For Noninvasive Blood Sugar Monitoring
In Diabetes
ScienceDaily (Sep. 26, 2007)-- Breath-analysis testing may prove to be
an effective, non-invasive method for monitoring blood sugar levels in
diabetes, according to a University of California, Irvine study.
By using a chemical analysis method developed for air-pollution testing,
UC Irvine chemists and pediatricians have found that children with
type-1 diabetes exhale significantly higher concentrations of methyl
nitrates when they are hyperglycemic.
The study heralds the potential of a breath device that can warn
diabetics of high blood sugar levels and of the need for insulin.
Currently, diabetics monitor blood sugar levels using devices that break
the skin to attain a small blood sample.
Hyperglycemia is common in type-1 diabetes mellitus.
"Breath analysis has been showing promise as a diagnostic tool in a
number of clinical areas, such as with ulcers and cystic fibrosis," said
Dr. Pietro Galassetti, a diabetes researcher with the General Clinical
Research Center (GCRC) at UC Irvine. "While no clinical breath test yet
exists for diabetes, this study shows the possibility of non-invasive
methods that can help the millions who have this chronic disease."
In the study, Galassetti, Dr. Dan Cooper and Andria Pontello of the GCRC
conducted breath-analysis testing on 10 children with type-1 diabetes
mellitus.
The researchers took air samples during a hyperglycemic state and
progressively as they increased the children's blood insulin levels.
The breath samples were sent to the laboratory of UC Irvine chemists F.
Sherwood Rowland and Donald Blake, who examined the exhaled breath using
methods developed for their atmospheric chemistry work.
In that work, they measure the levels of trace gases in excess of the
parts-per-billion range that contribute to local and regional air pollution.
Their research group is one of the few in the world recognized for its
ability to measure accurately at such small amounts.
The Rowland-Blake group analyzed the children's breath samples for more
than 100 gases at parts-per-trillion levels and found methyl nitrate
exhaled concentrations to be increased as much as 10 times more in
diabetic children during hyperglycemia than when they had normal glucose
levels.
The methyl nitrate concentrations corresponded with the children's
glucose levels -- the higher the glucose, the higher the exhaled methyl
nitrates.
Galassetti said that during hyperglycemia, in type 1 diabetes there are
more fatty acids in the blood that cause oxidative stress.
Methyl nitrate is likely a by-product of this increased oxidative stress.
It is commonly present in ambient air at very low concentrations,
Galassetti noted, and normally appears in the exhaled breath samples of
healthy subjects at parts-per-trillion levels.
"Currently, we are involved with new studies looking at the correlation
of other gases with hyperglycemia and other variables, including
insulin," Galassetti said. "Eventually, we hope to put together a full
exhaled gas profile of diabetes, and our efforts look promising."
Study results appeared recently in the early online version of the
Proceedings of the National Academy of Sciences.
UC Irvine chemists Brian Novak and Simone Meinardi also participated in
the study, which was supported by grants from the National Institutes of
Health and the Juvenile Diabetes Research Foundation.
Adapted from materials provided by University of California, Irvine.
Need to cite this story in your essay, paper, or report? Use one of the
following formats:
APA
www.gcrc.uci.edu/index.cfm General Clinical Research Center
UCI Medical Center
General Info: (714) 456-2307
101 The City Drive South Bldg. 25, 2nd Floor, Orange, CA 92868-3298
Galassetti, Pietro
Bionutrition & Metabolic Core Director Bionutrition
(714) 456-5357
pgalasse@...,
Cooper, Dan Program Director Administration
(714) 456-2317
dcooper@...,
Pontello, Andria Bionutrition Manager Bionutrition
(714) 456-2309
apesca@...,
www.pnas.org/cgi/reprint/104/40/15613?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&f\
ulltext=Galassetti&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
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Published online before print September 25, 2007, 10.1073/pnas.0706533104
PNAS | October 2, 2007 | vol. 104 | no. 40 | 15613-15618
OPEN ACCESS ARTICLE
PHYSICAL SCIENCES / BIOLOGICAL SCIENCES / CHEMISTRY / MEDICAL SCIENCES
Exhaled methyl nitrate as a noninvasive marker of hyperglycemia
in type 1 diabetes
B. J. Novak *,
D. R. Blake *, Donald R. Blake
drblake@...,
www.chem.uci.edu/faculty/drblake/
"Gas chromatography utilizing flame ionization detection, electron
capture detection, and mass spectrometry is our main analytical tool. A
three gas chromatograph analytical system is used to quantify about 150
halocarbons, nonmethane hydrocarbons, and alkyl nitrates ranging in mole
fraction from about 2 parts per billion to 10 parts per quadrillion."
S. Meinardi *,
F. S. Rowland *,{dagger},
A. Pontello *,{d dagger},
D. M. Cooper *,{d dagger},
and P. R. Galassetti *,{d dagger}, §
* Department of Chemistry, University of California, Irvine, CA 92697;
and {d dagger}General Clinical Research Center, University of California
at Irvine, Orange, CA 92868
Contributed by F. S. Rowland, August 7, 2007
Department of Chemistry, Rowland Hall, University of California, Irvine,
CA 92697-2025. E-mail:
rowland@...,
(received for review June 11, 2007)
Abstract
Top
Abstract
Results and Discussion
Materials and Methods
Acknowledgements
References
Recent technical advances allow detection of several hundred volatile
organic compounds (VOCs) in human exhaled air, many of which reflect
unidentified endogenous pathways.
Our group has previously estimated plasma glucose levels in healthy
adults during a standard oral glucose tolerance test via exhaled VOC
analysis.
As a result of the metabolic characteristics of hyperglycemia in the
diabetic (low insulin and increased free fatty acids and ketones), we
hypothesized that different exhaled VOC profiles may be present in
children with type 1 diabetes mellitus (T1DM) during spontaneous
hyperglycemia.
Exhaled methyl nitrate strongly correlated specifically with the acute,
spontaneous hyperglycemia of T1DM children.
Eighteen experiments were conducted among 10 T1DM children. Plasma
glucose and exhaled gases were monitored during either constant
euglycemia (n = 5) or initial hyperglycemia with gradual correction
(n = 13); all subjects received i.v. insulin and glucose as needed.
Gas analysis was performed on 1.9-liter breath samples via gas
chromatography using electron capture, flame ionization, and mass
selective detection.
Among the {approx}100 measured exhaled gases, the kinetic profile of
exhaled methyl nitrate, commonly present in room air in the range of
5–10 parts per trillion, was most strongly statistically correlated with
that of plasma glucose (P = 0.003–0.001).
Indeed, the kinetic profiles of the two variables paralleled each other
in 16 of 18 experiments, including repeat subjects who at different
times displayed either euglycemia or hyperglycemia.
exhaled gases | volatile organic compounds | gas chromatography | plasma
glucose
The analysis of volatile organic compounds (VOCs) has been recognized
for decades as a diagnostic tool with great potential for application to
human breath, and several attempts have been made to use this technique
for metabolic monitoring.
However, intrinsic difficulties in measurement and analysis have
resulted in inconsistent results, severely limiting its practical
applicability.
Recent advances in VOC analytical technology may have reduced the impact
of these technical issues, lowering detection limit of measurable gas
concentrations, and increasing the repeatability and stability of
measurements.
Indeed, in recent years a rising number of studies centered on exhaled
VOC clinical applications have been generated (1–5).
Most studies, however, are focused on the detection of single disease
markers, i.e., exhaled gas profiles constantly present in definite
groups of patients, independent of their moment-by-moment metabolic changes.
We believe that this approach, while having the potential of detecting
important diagnostic markers, greatly under utilizes exhaled gas analysis.
Exhaled gas profiles are likely involved in endogenous metabolic
processes and are, therefore, constantly changing in response to the
extremely complex human endogenous biochemical milieu.
The extreme versatility of exhaled gas analysis (combining simultaneous
measurements of 100 or more exhaled gases in each breath with easy,
noninvasive, and painless collection methods) therefore appears
especially suitable for the definition and monitoring of the time course
of evolving, complex metabolic conditions, including, among others,
inflammation, dyslipidemia, and diabetes.
In recent years, our laboratory has concentrated on this approach for
the use of exhaled VOC analysis in pathological conditions (4, 5).
In this study, we describe the potential applications of VOC analysis to
the monitoring of hyperglycemia in type 1 diabetes mellitus (T1DM).
Blood glucose testing is the very base of diabetes management and can
currently be accurately performed only through a blood sample.
Attempts to develop alternative, noninvasive monitoring methods have
been pursued for decades and, if successfully developed, are likely to
have an immense global impact on diabetes screening, diagnosis,
monitoring, and prevention.
We have recently demonstrated that it is possible to monitor plasma
blood glucose during the transient hyperglycemia of a standard oral
glucose tolerance test (OGTT) in healthy subjects through multilinear
regression analysis of the combined exhaled profiles of ethanol and
acetone (5).
It is unlikely, however, that a similar exhaled gas profile would be
present in all hyperglycemic situations.
In T1DM, for instance, spontaneous (not postprandial) hyperglycemia is
metabolically very different from the postprandial hyperglycemia in the
healthy subject.
Whereas circulating insulin increases rapidly in response to
hyperglycemia in the healthy subject, hypoinsulinemia is present in the
diabetic (indeed, it is actually causing hyperglycemia).
Differing insulin concentrations affect lipolysis and, therefore,
circulating lipid and ketone concentrations, which in turn acutely
influence oxidative and inflammatory status, resulting in altered
concentrations of oxidative markers and pro- and antiinflammatory cytokines.
Because each of these correlated metabolic processes can conceptually
generate one or a series of discrete exhaled VOCs, it is possible that
each metabolic condition, in which hyperglycemia is one of the
measurable components, may result in a distinct, characteristic pattern
of exhaled VOCs.
In the present study, therefore, we analyzed the exhaled gas profiles of
children with T1DM during either a sustained euglycemic state or
spontaneous morning hyperglycemia and its gradual correction via i.v.
insulin infusion.
Results and Discussion
Glucose and Insulin.
Five of the participants were euglycemic (80–130 mg/dl) at the start of
the study; euglycemia was maintained for 2 h (average plasma glucose
during last 60 min, 98 ± 3 mg/dl), and the experiment was then concluded.
In the remaining 13 experiments, subjects had initial hyperglycemia
(range, 160–410 mg/dl) that was gradually corrected via tapered insulin
infusion, so that when euglycemia was achieved a basal rate of insulin
infusion was present; this condition was maintained for at least 60 min,
during which plasma glucose was not different from the euglycemic group
(102 ± 4 mg/dl) (Fig. 1).
Figure 1
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Fig. 1. Plasma glucose and exhaled methyl nitrate profiles in 18
experiments performed in 10 children with T1DM.
Children started experiments in either hyperglycemic or euglycemic
conditions;
if hyperglycemic, euglycemia was gradually restored by i.v. insulin
infusion;
if euglycemic, euglycemia was maintained for the duration of the study.
In 16 of 18 experiments, exhaled methyl nitrate profiles closely
paralleled plasma glucose.
The left y axis shows blood glucose levels in milligrams per deciliter,
the right y axis is exhaled ({Delta}) methyl nitrate in pptv, and the x
axis is time in hours.
Each subject is denoted by a letter, and multiple visits by a single
subject are denoted by a subscripted number following the letter.
At the end of the study, all participating subjects displayed similar
circulating insulin concentrations (14 ± 3 microunits/ml).
Insulin infusion rates were similar in all subjects during the last 60
min of the experiments (euglycemic group, 1.1 ± 0.2 units/h;
hyperglycemic group, 1.1 ± 0.3 units/h);
in the hyperglycemic group, initial infusion rates were higher
proportional to the levels of hyperglycemia
(mean 3.1 ± 0.2 units/h, range 2.5–5.0 units/h).
Exhaled Gases (Methyl Nitrate).
The exhaled gas profiles of {approx}100 gas species (List 1) were
defined and compared with plasma glucose concentrations.
The VOC displaying the greatest correlation with glucose was methyl
nitrate (CH3ONO2), a gas ubiquitously present in both urban and rural
air in the range of 3–15 parts per trillion by volume (pptv), with
natural oceanic sources, minor industrial use as an explosive, and
present in situ in urban atmospheric environments and in the University
of California at Irvine (UCI) General Clinical Research Center (GCRC).
For this reason, the exposure of lungs to inhaled trace amounts of
methyl nitrate is a commonplace in everyday life.
Its level in the UCI GCRC air varied from 5 to 10 pptv;
however, within each experiment, its room air concentration never varied
by >2 pptv.
None of the other six alkyl nitrates quantified (see List 1) followed
the trend with glucose of methyl nitrate.
View this table:
[in this window]
[in a new window]
List 1. Gases quantified for the T1DM study
Exhaled methyl nitrate profiles closely paralleled plasma glucose
profiles in 16 of 18 experiments (Fig. 1).
The methyl nitrate data in Fig. 1 are shown using a linear scale for
each subject with adjusted minima (not necessarily zero) and maxima to
show high correlation with the glucose data.
Individual differences in methyl nitrate absolute concentrations were
observed both from subject to subject but also for repeat measurements
with the same subject (e.g., Fig. 1, H1 and H2).
In the euglycemic group, methyl nitrate concentrations averaged 11 ± 3
pptv at the beginning of the study;
after euglycemia was maintained for 2 h, methyl nitrate concentrations
were not significantly different (8 ± 1 pptv; P = 0.32).
These data are consistent with our previous findings of the measurable
amount of 5 pptv of methyl nitrate in the breath of healthy subjects
({Delta}: room, 5 ± 2 pptv; breath, 10 ± 2 pptv) (4, 5).
Conversely, in the hyperglycemic group, initial methyl nitrate
concentrations were significantly greater (27 ± 6 pptv)
and decreased significantly after hyperglycemia was corrected
(15 ± 2 pptv; P = 0.01).
Once stable euglycemia was achieved in the hyperglycemic group,
the change in exhaled methyl nitrate for the remaining duration of the
study was –3.7 ± 1.2 pptv, similar to the change observed in the
euglycemic group (–3.1 ± 2.4 pptv; P = 0.080).
In Fig. 1, subject C displayed lower and constant methyl nitrate levels
in her breath when she was euglycemic upon study initiation, whereas,
when she arrived hyperglycemic, her methyl nitrate was significantly
elevated and then decreased as she approached euglycemia.
These data indicate that the same person may react differently depending
on their blood glucose levels.
Subject B arrived twice euglycemic and once hyperglycemic, and again
exhaled methyl nitrate followed the plasma glucose profile.
Data analysis with a mixed model for repeated measurement was performed,
and all of the terms of the interaction between methyl nitrate and
glucose over time displayed high statistical significance
(P = 0.003–0.001).
The levels of significance were further enhanced (P < 0.001) by
introduction of a 30-min lag time for methyl nitrate (this procedure was
suggested by the visual detection of a "rightward shift" of the two
curves in at least some subjects) (Fig. 2).
Finally, because the different degrees of hyperglycemia determined a
longer duration of the study for some subjects, resulting in different
clock times at which the actual euglycemic period started, the analysis
was repeated incorporating the different study starting point, again
confirming the highly significant correlation between glucose and
exhaled methyl nitrate.
Figure 2
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Fig. 2. Plasma glucose and exhaled methyl nitrate profiles in one
child (Fig. 1, H2) with T1DM who started the experiment in hyperglycemic
conditions, with gradual correction of hyperglycemia via i.v. insulin
infusion.
The two upper graphs show data as they were initially recorded, already
displaying a strong correlation between the two variables;
when corrected for a 30-min time lag (the lower two graphs),
the two curves appear to overlap almost exactly,
with further strengthening of their correlation,
suggesting that at least in some subjects a certain delay may exist
between changes in plasma glucose
and corresponding changes in exhaled VOCs.
In this separate study of healthy subjects,
after ingestion of noncaloric placebo,
exhaled methyl nitrate concentration moderately decreased by the end of
the study (Fig. 3).
Conversely, after ingestion of a fat-rich meal, exhaled methyl nitrate
markedly increased over time by {approx}10 pptv.
Figure 3
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Fig. 3. Exhaled methyl nitrate profiles in healthy children after
ingestion of either a noncaloric placebo (n = 8) or a high-fat
semiliquid meal (n = 11).
Exhaled methyl nitrate levels were significantly elevated after fat
ingestion, probably correlating with increased circulating lipid
concentrations.
The main finding of our study is that,
among the {approx}100 gases detected in the exhaled breath of children
with T1DM,
methyl nitrate displayed a kinetic profile closely paralleling that of
plasma glucose in 16 of 18 experiments,
during which plasma glucose was either constantly euglycemic or
initially hyperglycemic (160–410 mg/dl) with gradual correction and
reestablishment of euglycemia.
Our data confirm the potential use of exhaled gas analysis as a
noninvasive tool to monitor metabolic alterations, including
hyperglycemia, in diabetic patients and expands prior findings from ours
and other laboratories.
In a prior study (5) we were able to estimate with good accuracy plasma
glucose profiles during a standard OGTT in 10 healthy young adults via
multilinear regression analysis of exhaled ethanol and acetone, which in
that experiment were the two exhaled gases with the highest individual
correlations with circulating glucose.
In the present study, ethanol and acetone did not correlate closely with
plasma glucose, whereas methyl nitrate, a gas that did not correlate in
our previous OGTT study, did.
Although this lack of consistency may appear disconcerting after a
superficial analysis of our results, we believe this is actually a
strong supportive factor for the remarkable flexibility of exhaled gas
analysis as a metabolic monitoring tool.
Although it is, in fact, possible that no single exhaled gas or fixed
"set" of exhaled gases may consistently correlate with circulating
glucose concentrations per se, multiple gases or sets of gases may each
correlate with hyperglycemia in a different metabolic context.
By identifying these multiple sets of gases, our technique is therefore
likely to allow not only an accurate estimate of plasma glucose but also
of a series of additional related variables.
Hyperglycemia may occur in the context of very different metabolic
conditions generated by multiple simultaneous biochemical processes,
each potentially capable of independently altering the exhaled gas profile.
The physiological, transient postprandial hyperglycemia occurring in
healthy subjects, for instance, is paralleled by a rapid insulin response.
In turn, in addition to its glucoregulatory effect, insulin will
suppress lipolysis, transiently reducing circulating free fatty acids
and their oxidation, thereby also reducing ketone bodies (6).
Furthermore, gut bacteria may add to the circulation gaseous by-products
of their own metabolism of ingested food, such as ethanol from
carbohydrate fermentation (7–9), which may explain why a reduction in
exhaled acetone and a transient increase in exhaled ethanol paralleled
hyperglycemia in our previous OGTT study.
A very different situation, on the other hand, is present during
spontaneous hyperglycemia in T1DM.
Because no gut absorption of nutrients is occurring, the concentrations
of bacterial byproducts are unlikely to change.
Furthermore, insulin is not increased; in fact, hypoinsulinemia is most
likely the very cause of the hyperglycemic episode, with a reverse
effect on lipid metabolism, i.e., increased lipolysis, increased free
fatty acids and ketone concentrations, all factors favoring a
proinflammatory, prooxidative status (10, 11).
In this context, it is not surprising that the exhaled gas pattern in
the present study was markedly different from that observed during the
OGTT study.
Although we had not specifically predicted the observed strong
correlation of exhaled methyl nitrate with plasma glucose, this
correlation did not come as a surprise.
The known chemical characteristics of this gas, in fact, place it as one
of the possible candidates to track hyperglycemia indirectly via the
simultaneous presence of oxidative stress.
Indeed, when healthy children were studied after ingestion of either a
noncaloric placebo meal or a fat-rich meal, exhaled methyl nitrate
concentrations were significantly greater after lipid ingestion (Fig. 3)
(¶), a finding consistent with the effect of acutely elevated free fatty
acid concentrations and the consequent oxidative stress.
Although free fatty acids could not be measured in our T1DM children,
it is likely that they were similarly elevated as a consequence of the
relative hypoinsulinemia that must have caused hyperglycemia.
Methyl nitrate is the least reactive of all alkyl nitrates that are
commonly observed in the atmosphere.
Their main sources are marine emissions, biomass burning, and
photochemical production in the atmosphere (13–15).
In healthy subjects, exhaled methyl nitrate concentrations are slightly
greater than room air concentration (normally by <10 pptv),
indicating a small net output of this gas by the human body.
The biochemical production of this gas has not been postulated; however,
from our results it is clear that oxidative processes play a major role
in its production.
As a byproduct of physiological, energy-generating oxidative reactions,
a small fraction of oxygen flowing through the mitochondria is converted
to superoxide ion (OFormula), a free radical potentially capable of
damaging cells and tissues (Fig. 4).
These deleterious effects are prevented by multiple antioxidant
mechanisms, such as the action of the enzyme superoxide dismutase, which
converts superoxide to the less reactive oxygen (O2) and hydrogen
peroxide (H2O2), via addition of protons (16).
However, superoxide can also react very rapidly with nitric oxide (NO)
(17, 18), forming a nitrate molecule that can be protonated (19),
the speed of this reaction is likely accelerated at lower pH.
This protonated nitrate species can react with methanol, yielding a
water molecule and a molecule similar to methyl nitrate, which can
isomerize to methyl nitrate.
Within the human body, some colonizing bacteria could produce methanol
directly or oxidize methane (CH4) to methanol (CH3OH) (20, 21),
providing the methyl radical (22, 23), or other metabolic sources may be
responsible for it.
When hyperglycemia occurs in diabetics, an accelerated metabolic flux
through the mitochondria may lead to increased superoxide formation,
possibly directly linking blood glucose levels with systemic oxidation;
in the extreme case of severe hyperketonemia, the pH shift toward
acidosis may further accelerate this chain of reactions.
Figure 4
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Fig. 4. Schematic representation of methyl nitrate formation in vivo.
In vivo, a small but relatively constant fraction of superoxide ion
(OFormula) is diverted from its interaction with superoxide dismutase
(SOD) and reacts with nitric oxide (NO) to eventually form methyl
nitrate (CH3ONO2).
Although the large majority of the experiments included in this study
displayed the reported close correlation between plasma glucose and
exhaled methyl nitrate, two of 18 did not.
Interestingly, one of the two was the subject who started the study with
the highest plasma glucose, 410 mg/dl (>70 mg/dl above any other
participant).
His exhaled methyl nitrate levels were also among the highest but
remained elevated after correction of hyperglycemia (Fig. 1, subject J).
We can speculate that if blood glucose had remained elevated for a
prolonged period before the study (possibly even at concentrations
higher than those recorded at admission), this may have overstimulated
prooxidative mechanisms, preventing a prompt correction of the acute
inflammatory/oxidative milieu shortly after euglycemia was resumed.
Separate studies in a similar group of patients have indicated that
concentrations of proinflammatory cytokines, which closely parallel
oxidative stress markers, increase acutely during hyperglycemia and may
remain elevated for several hours after hyperglycemia is corrected.||
Even in subjects with good concordance between plasma glucose and methyl
nitrate, the latter appears to lag the former, as shown by the
statistical improvement of correlation introducing a 30-min lag.
Finally, this subject was undergoing growth hormone supplementation therapy.
Despite its beneficial effects, growth hormone is known to exert a
prooxidative effect (24) and may have contributed to the sustained
exhaled methyl nitrate levels.
The second subject with discordant glucose and methyl nitrate profiles
(Fig. 1, subject I) also was atypical in that although her prestudy
glucose concentration was not exceptionally elevated, although her
methyl nitrate concentrations were, and she displayed markedly greater
levels of discomfort during study procedures than the rest of the study
group.
Analysis of the data from these two atypical subjects suggests that
exhaled methyl nitrate may indeed reflect acute increases in systemic
oxidative stress, but data interpretation may be confounded when
oxidative processes are simultaneously stimulated by mechanisms
independent of hyperglycemia and its related metabolic alterations.
The above considerations are relevant to the overall practical
applicability of exhaled methyl nitrate as a hyperglycemic marker in
diabetes.
The ultimate goal of our line of experiments is to produce predictive
algorithms that will allow conversion of exhaled gas concentrations into
blood glucose readings.
Our present results allow estimation of glucose curves from exhaled gas
only on an individual basis, because a general algorithm applicable to
the whole study population will require identification and
quantification of the relative contribution of all pertinent covariates,
which can only be obtained through additional, more complete studies.
As stated above, a time-lag effect is probably one of the interfering
factors, but even this effect could only be incompletely defined because
of the relatively long intervals (30 min) between time points
(incidentally, a lag-time effect may probably explain why localized
discordance was present at the first or last time points in some
experiments, such as E1 and E3, despite an overall good concordance
between exhaled methyl nitrate and plasma glucose values).
Importantly, because prevention and reversal of hypoglycemia, in
addition to hyperglycemia, has recently become a major area of concern
in the management of T1DM, future studies must also include hypoglycemic
conditions (for obvious ethical reasons experimental hypoglycemia could
not be established in our pediatric-age population).
In conclusion, analysis of exhaled breath in children with T1DM during
euglycemia or spontaneous hyperglycemia revealed a strong correlation
between the kinetic profiles of plasma glucose and exhaled methyl nitrate.
The characteristics of methyl nitrate formation suggest that this gas
may reflect, rather than hyperglycemia per se, the specific and complex
pattern of metabolic alteration accompanying hyperglycemia in T1DM.
This pattern includes not only hypoinsulinemia and increased lipids and
ketones but also alterations in inflammatory and oxidative markers,
now considered main determinants of diabetic vascular complications.
Optimization of exhaled gas analysis in diabetes may prove invaluable
not only in monitoring glycemic control but also in determining the
actual pathogenic potential of a given glycemic state in terms of
onset/progression of diabetic complications.
Materials and Methods
All protocols were approved by the UCI Institutional Review Board;
subjects and parents/guardians signed informed assent and consent forms.
Studies were performed at the UCI GCRC,
and gas analysis was performed in the Laboratory of F.S.R. and D.R.B.
in the UCI Department of Chemistry.
Eighteen individual studies were performed among 10 children (seven
males and three females) with T1DM (diagnosed >2 years before enrollment).
The mean age of the participants was 13.8 ± 0.5 yr (range 11–15 yr).
The mean HbA1c level was 8.0 ± 0.8% (range 6.7–9.2%).
The participants took no medications other than insulin replacement
(with the single exception of patient J, who was on growth hormone
replacement).
In addition there were no tissue complications, autonomic neuropathy, or
other chronic pathology.
Participants were admitted at the UCI GCRC at 7 a.m. To reproduce a
real-life scenario, participants had been asked to eat a light breakfast
at approximately 6 a.m.
Patients on insulin pumps followed their usual regimen; those on
multiple insulin injections had their last slow-acting insulin
(glargine) injection no later than the night before and injected
fast-acting insulin only in the morning.
Upon admission, breath and room air samples were collected and i.v.
lines were placed in both arms for blood drawing and study infusions
(insulin and 20% dextrose).
A continuous insulin infusion was started (target: at least 90 min of
glycemia between 90 and 110 mg/dl).
If the participant was hyperglycemic at admission (and it should be
noted that, because hyperglycemia was spontaneous, its magnitude varied
across subjects), insulin was infused i.v. at a rate of 1.0 unit/h for
every 50 mg/dl above euglycemia and then gradually tapered down as blood
glucose approached euglycemia.
Once euglycemia was achieved, or if the patient's blood glucose was
already on target at admission, i.v. insulin infusion was continued at
the minimum level that allowed maintenance of euglycemia.
For patients on insulin pumps, this level corresponded to the their
normal basal rate (between 0.9 and 1.4 units/h), whereas in patients on
multiple injections, in which the last glargine injection had a residual
effect estimated as equivalent to the infusion of 0.7–1.0 units/h, the
additional i.v. infusion average was 0.35 ± 0.1 units/h.
Small amounts of i.v. glucose were infused if necessary to prevent
hypoglycemia, based on glucose readings taken at 10- to 15-min intervals.
Every 30 min, blood samples were matched by the collection of exhaled
gas samples.
To collect the gas samples, participants exhaled for 10–15 s into
specially designed, electropolished, 1.9-liter, stainless-steel
canisters that were sterilized before use by baking at 150°C for 12 h
and evacuated to <10–5 atm (1 atm = 101.3 kPa).
Subjects took a deep inspiration to total lung capacity and then slowly
exhaled until near residual volume through a mouthpiece connected to the
canister via a three-way valve.
Gas from the first 2–3 s of the exhalation maneuver was vented to the
room to clear the system of anatomic dead space.
A single practice was normally sufficient to train subjects for this
technique.
Measurement of the CO2 concentrations in the exhaled breath ({approx}5%)
demonstrated that the captured sample was almost entirely alveolar air.
A room air sample was simultaneously collected in an identical canister
for each exhaled gas sample.
Canisters containing breath and room air samples were then stored at
room temperature for later analysis.
All exhaled methyl nitrate data reported are in {Delta} values (breath
minus room).
In a separate set of experiments, 12 healthy children (six males and six
females, ages 11–15 yr), were studied after an overnight fast.
Children ingested either a noncaloric placebo or a fat-rich shake (1.5
grams of fat per kilogram of body weight), and repeated matched blood
and exhaled breath samples were collected over 150 min.
Circulating variables from this study have been previously published.¶
Laboratory Techniques. Immediately after blood draws, 0.4 ml of blood
was spun on a microcentrifuge for rapid glucose content determination on
a Beckman Glucose Analyzer II (Beckman Coulter, Fullerton, CA), using
the glucose oxidase method.
VOCs were cryogenically trapped and injected into a multicolumn/detector
gas chromatography system.
The detectors included two flame ionization detectors (FID), two
electron capture detectors (ECD), and a quadruple mass spectrometer (MSD).
Five different columns were used for separations and combined with the
detectors as follows:
PLOT/FID, DB-1/FID, DB-5/ECD, RTX-1701/ECD, and DB-5ms/MSD.
This analysis allows accurate quantification of a large variety of
different gas species.
For a more detailed discussion of gas analysis, see Colman et al. (12).
Acknowledgements
We thank the UCI GCRC nurses and staff for excellent research support
and Brent Love for the chromatographic analysis.
This research was supported by National Institutes of Health Grants
M01-RR00827-28 and K-23 RR018661-01 and Juvenile Diabetes Research
Foundation Grant 11-2003-332.
Footnotes
Abbreviations: GCRC, General Clinical Research Center;
OGTT, oral glucose tolerance test;
pptv, parts per trillion by volume;
T1DM, type 1 diabetes mellitus;
VOC, volatile organic compound;
UCI, University of California at Irvine.
{dagger}To whom correspondence may be addressed. E-mail:
rowland@...
§To whom correspondence may be addressed at: General Clinical Research
Center, University of California at Irvine, Building 25, Second Floor,
101 The City Drive, Orange, CA 92868. E-mail:
pgalasse@...
Freely available online through the PNAS open access option.
Author contributions: B.J.N., D.R.B., D.M.C., and P.R.G.
designed research; B.J.N., D.R.B., S.M., A.P., D.M.C., and P.R.G.
performed research; B.J.N., D.R.B., F.S.R., and P.R.G.
contributed new reagents/analytic tools; B.J.N., D.R.B., S.M., F.S.R.,
A.P., and P.R.G.
analyzed data; and B.J.N., D.R.B., F.S.R., D.M.C.,
and P.R.G. wrote the paper.
The authors declare no conflict of interest.
¶ Blake, D. R., Iwanaga, K., Novak, B. J., Meinardi, S. Pescatello, A.,
Cooper, D. M., Galessetti, P. R., American Diabetes Association 64th
Annual Scientific Sessions, June 4–8, 2004, Orlando, FL, abstr. 1549-P. Back
|| Galassetti, P., Flores, R., Larson, J., Zaldivar, F., Barnett, M.,
Rosa, J., American Diabetes Association 66th Annual Scientific Sessions,
June 9–13, 2006, Washington, DC, abstr. 235-OR. Back
© 2007 by The National Academy of Sciences of the USA
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List 1. Gases quantified for the T1DM study
Methane (CH4) Cyclohexane (C6H12)
1,2,4-Trimethylbenzene (C9H12) CFC-12 (CCl2F2)
Carbon monoxide (CO) 2,2-Dimethylbutane (C6H14) 1,3,5-Trimethylbenzene
(C9H12) CFC-11 (CCl3F)
Carbon dioxide (CO2) 2,3-Dimethylbutane (C6H14)
m-Ethyltoluene (C9H12) CFC-113 (C2Cl3F3)
Ethane (C2H6) 2-Methylpentane (C6H14)
p-Ethyltoluene (C9H12) Chloromethane (CH3Cl)
Ethene (C2H4) 3-Methylpentane (C6H14)
n-Decane (C10H22) Bromomethane (CH3Br)
Ethyne (C2H2) Methylcyclopentane (C6H12)
{alpha}-Pinene (C10H16) Iodomethane (CH3I)
Propene (C3H6) n-Heptane (C7H16)
beta-Pinene (C10H16) Trichloromethane (CHCl3)
Propane (C3H8) Methylcylohexane (C7H14)
d-Limonene (C10H16) Tribromomethane (CHBr3)
i-Butane (C4H10) 2-Methylhexane (C7H16)
1,3-Diethylbenzene (C10H14) Carbon tetrachloride (CCl4)
n-Butane (C4H10) 3-Methylhexane (C7H16)
1,4- Diethylbenzene (C10H14) Tetrachloroethylene (C2Cl4)
1-Butene (C4H8) 2,3-Dimethylpentane (C7H16) 1,2-Diethylbenzene
(C10H14) 1,2-Dichloroethene (C2H2Cl2)
i-Butene (C4H8) 2,4-Dimethylpentane (C7H16)
n-Undecane (C11H24) Methyl chloroform (CH3CCl3)
trans-2-Butene (C4H8) Toluene (C7H8)
Acetaldehyde (CH3CHO) Ethyl chloride (C2H5Cl)
cis-2-Butene (C4H8) n-Octane (C8H18)
Methanol (CH3OH) Trichloroethylene (C2HCl3)
1,3-Butadiene (C4H6) Ethylbenzene (C8H10)
Ethanol (CH3CH2OH) Bromodichloromethane (CHBrCl2)
i-Pentane (C5H12) m-Xylene (C8H10)
Acetone (CH3COCH3) Dichloromethane (CH2Cl2)
n-Pentane (C5H12) p-Xylene (C8H10)
Propan-1-ol (C3H8O) Dibromomethane (CH2Br2)
1-Pentene (C5H10) o-Xylene (C8H10)
Propan-2-ol (C3H8O) Methyl nitrate (CH3ONO2)
Isoprene (C5H8) 2-Methylheptane (C8H18)
Butanone (C4H8O) Ethylnitrate (C2H5ONO2)
cis-2-Pentene (C5H10) 3-Methylheptane (C8H18)
2-Pentanone (C5H10O) i-Propylnitrate (C3H7ONO2)
trans-2-Pentene (C5H10) 2,2,4-Trimethylpentane (C8H18)
3-Pentanone (C5H10O) n-Propylnitrate (C3H7ONO2)
2-Methyl-2-butene (C5H10) 2,3,4-Trimethylpentane (C8H18)
Methyl isobutyl ketone (C6H12O) 2-Butylnitrate (C4H9ONO2)
Cyclopentane (C5H10) n-Nonane (C9H20)
Carbonyl sulfide (OCS) 2-Pentylnitrate (C5H11ONO2)
n-Hexane (C6H14) i-Propylbenzene (C9H12)
Carbon disulfide (CS2) 3-Pentylnitrate (C5H11ONO2)
cis-3-Hexene (C6H12) n-Propylbenzene (C9H12)
Dimethyl disulfide (C2H6S2) Benzene (C6H6)
1,2,3-Trimethylbenzene (C9H12) Dimethyl selenide (C2H6Se)
In most cases, these compounds were quantitatively present in the room.
Levels in the exhaled breath depended largely on production or
absorption by the particular patient(s). CFC, chlorofluorocarbon.
Diabetes Technol Ther. 2005 Feb; 7(1): 115-23.
Breath ethanol and acetone as indicators of serum glucose levels: an
initial report.
Galassetti PR, Novak B, Nemet D, Rose-Gottron C, Cooper DM, Meinardi S,
Newcomb R, Zaldivar F, Blake DR.
Center for the Study of Health Effects of Exercise in Children,
University of California, Irvine, College of Medicine, Orange,
California 92868, USA.
pgalasse@...
BACKGROUND:
Many volatile organic compounds are present in exhaled breath and may
represent by-products of endogenous biological processes.
Ethanol is produced via alcoholic fermentation of glucose by gut
bacteria and yeast, while acetone derives from oxidations of free fatty
acids, influenced by glucose metabolism.
We hypothesized that the integrated analysis of breath ethanol and
acetone would provide a good approximation of the blood glucose profile
during a glucose load.
METHODS:
We collected simultaneous exhaled breath gas, ambient air, and serum
glucose and insulin samples from 10 healthy volunteers at baseline and
during an oral glucose tolerance test (OGTT) (ingestion of 75 g of
glucose followed by 120 min of sampling).
Gas samples were analyzed by gas chromatography/mass spectrometry.
RESULTS:
Mean glucose values displayed a typical OGTT pattern
(rapid increase, peak values at 30-60 min,
and gradual return to near baseline by 120 min).
Breath ethanol displayed a similar pattern early in the test,
with peak values at 30 min;
this was followed by a fast return to basal levels by 60 min.
Breath acetone decreased progressively below basal levels,
with lowest readings obtained at 120 min.
A multiple regression analysis of glucose, ethanol, and acetone was used
to estimate glucose profiles that correlated with measured glucose
values with an average individual correlation coefficient of 0.70, and
not lower than 0.41 in any subject.
CONCLUSION:
The integrated analysis of multiple exhaled gases may serve as a marker
of blood glucose levels.
Further studies are needed to assess the usefulness of this method in
different populations. PMID: 15738709
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1624700\
7
html full text
Proc Natl Acad Sci U S A. 2005 November 1; 102(44): 15762–15767.
Published online 2005 October 24. doi: 10.1073/pnas.0507263102.
Copyright © 2005, The National Academy of Sciences
Chemistry
Breath sulfides and pulmonary function in cystic fibrosis
M. A. Kamboures, *
D. R. Blake, *
D. M. Cooper, † ‡
R. L. Newcomb, §
M. Barker, ¶
J. K. Larson, ‡
S. Meinardi, *
E. Nussbaum, ?
and F. S. Rowland * **
Departments of * Chemistry and † Pediatrics,
‡ General Clinical Research Center,
and § Center for Statistical Consulting, University of California,
Irvine, CA 92697;
¶ Department of Pediatrics, University Hospital Rheinisch-Westfälische
Technische Hochschule, 52074 Aachen, Germany;
and ? Division of Pediatric Pulmonology, Miller Children's Hospital at
Long Beach Memorial Medical Center, Long Beach, CA 90806
** To whom correspondence should be addressed at: Department of
Chemistry, Rowland Hall, University of California, Irvine, CA
92697-2025. E-mail:
rowland@....
Contributed by F. S. Rowland, August 22, 2005
Abstract
We have determined the concentrations of carbonyl sulfide (OCS),
dimethylsulfide, and carbon disulfide (CS2) in the breath of a group of
cystic fibrosis (CF) patients and one of healthy controls.
At the detection sensitivity in these experiments, room air always
contained measurable quantities of these three gases.
For each subject the inhaled room concentrations were subtracted from
the time-coincident concentrations in exhaled breath air.
The most significant differences between the CF and control cohorts in
these breath-minus-room values were found for OCS.
The control group demonstrated a net uptake of 250 ± 20
parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net
uptake of 110 ± 60 pptv (P = 0.00003).
Three CF patients exhaled more OCS than they inhaled from the room.
The OCS concentrations in the CF cohort were strongly correlated with
pulmonary function.
The dimethylsulfide concentrations in breath were greatly enhanced over
ambient, but no significant difference was observed between the CF and
healthy control groups.
The net (breath minus room) CS2 concentrations for individuals ranged
between +180 and -100 pptv.
They were slightly greater in the CF cohort (+26 ± 38 pptv) vs. the
control group (-17 ± 15 pptv; P = 0.04).
Lung disease in CF is accompanied by the subsistence of chronic
bacterial infections.
Sulfides are known to be produced by bacteria in various systems and
were therefore the special target for this investigation.
Our results suggest that breath sulfide content deserves attention as a
noninvasive marker of respiratory colonization.
Keywords: bacterial emission, early detection, Pseudomonas aeruginosa,
carbonic anhydrase, mucin sulfation
Wien Klin Wochenschr. 2001 Mar 15; 113(5-6): 181-5.
Analysis of volatile organic compounds: possible applications in
metabolic disorders and cancer screening.
Rieder J,
Lirk P,
Ebenbichler C,
Gruber G,
Prazeller P,
Lindinger W,
Amann A.
Department of Anesthesiology and Critical Care Medicine,
Leopold-Franzens University, Innsbruck, Austria.
The human breath contains a variety of endogenous volatile organic
compounds (VOCs).
The origin and pathophysiological importance of these VOCs is poorly
investigated.
Little is known about the interaction of VOCs from ambient air, such as
those produced by plants and exhaust fumes, with the human organism.
Gas chromatographic determination of VOC concentrations is tedious.
Proton-transfer-mass spectroscopy (PTR-MS), a new technology for the
online detection of VOC patterns, is a valuable alternative.
We present two interesting molecular species, isoprene and ortho
(o)-toluidine, as examples of endogenously produced VOCs.
In a case study, breath isoprene reductions during lipid-lowering
therapy (36%) were shown to correlate with cholesterol (32%) and LDL
concentrations (35%) in blood (p < 0.001) over a period of 15 days.
Therefore, isoprene concentrations in human breath (measured by PTR-MS)
might serve as an additional parameter to complement invasive tests for
controlling lipid-lowering therapy.
Furthermore, it may be a useful parameter for lipid disorder screening.
Mass-108, which presumably represents o-toluidine in our breath samples,
was found in significantly higher concentrations in the breath of
patients with different tumors (1.5 +/- 0.8 ppbv) than in age-matched
controls (0.24 +/- 0.1 ppbv, p < 0.001).
Inflammatory reactions do not seem to alter the pattern of mass-108.
Therefore, it appears to be a currently underestimated carcinoma marker
that deserves further investigation. PMID: 11293947
http://groups.yahoo.com/group/aspartameNM/message/1469
highly toxic formaldehyde, the cause of alcohol hangovers, is made by
the body from 100 mg doses of methanol from dark wines and liquors,
dimethyl dicarbonate, and aspartame: Murray 2007.08.31
http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
( becomes formaldehyde in body ): EU Scientific Committee on Foods
2001.07.12: Murray 2004.01.22
http://europa.eu.int/comm/food/fs/sc/scf/out96_en.pdf
"...DMDC was evaluated by the SCF in 1990 and considered acceptable for
the cold sterilization of soft drinks and fruit juices at levels of
addition up to 250 mg/L (1)
...DMDC decomposes primarily to CO2 and methanol ...
[ Note: Sterilization of bacteria and fungi is a toxic process,
probably due to the inevitable conversion in the body of methanol
into highly toxic formaldehyde and then formic acid. ]
The use of 200 mg DMDC/L would add 98 mg/L of methanol to wine which
already contains an average of about 140 mg/L from natural sources.
A healthy person metabolises 1500 mg methanol/hr without any
physiological problems and this should be compared to the amount of up
to 240 mg/L methanol in wine, treated with DMDC up to 200 mg/L.
Metabolism of the amounts of methanol resulting from consumption of wine
containing such levels is therefore well within the capacity of the
human body.
Thus consumption of even large quantities of wine would not pose any
hazards from methanol.
Conclusion
The formation of methanol and other reaction products following the use
of DMDC for the treatment of alcoholic beverages and wine is similar to
that formed in non-alcoholic beverages.
Therefore the previous opinion on the use of DMDC for non-alcoholic
beverages (1) is equally applicable to wines treated with DMDC."
However, research shows that the methanol in dark wines and liquors is
made into formaldehyde by the body, causing the toxic symptoms of hangovers.
http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid) are main cause of
alcohol hangover symptoms [same as from similar amounts of methanol, the
11% part of aspartame]: YS Woo et al, 2005 Dec: Murray 2006.01.20
Addict Biol. 2005 Dec;10(4): 351-5.
Concentration changes of methanol in blood samples during
an experimentally induced alcohol hangover state.
Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT, Kim DJ.
Chuncheon National Hospital, Department of Psychiatry,
The Catholic University of Korea, Seoul, Korea.
http://www.cuk.ac.kr/eng/ sysop@...
Songsin Campus: 02-740-9714 Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm eight hospitals
[ Han-Kyu Lee ]
A hangover is characterized by the unpleasant physical and mental
symptoms that occur between 8 and 16 hours after drinking alcohol.
After inducing experimental hangover in normal individuals,
we measured the methanol concentration prior to
and after alcohol consumption
and we assessed the association between the hangover condition
and the blood methanol level.
A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric
or medical disorders.
The blood ethanol concentration prior to the alcohol intake
(2.26+/-2.08) was not significantly different from that
13 hours after the alcohol consumption (3.12+/-2.38).
However, the difference of methanol concentration
between the day of experiment (prior to the alcohol intake)
and the next day (13 hours after the alcohol intake)
was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).
A significant positive correlation was observed
between the changes of blood methanol concentration
and hangover subjective scale score increment when covarying
for the changes of blood ethanol level (r=0.498, p<0.05).
This result suggests the possible correlation of methanol
as well as its toxic metabolite to hangover. PMID: 16318957
[ The toxic metabolite of methanol is formaldehyde, which in turn
partially becomes formic acid -- both potent cumulative toxins
that are the actual cause of the toxicity of methanol.]
This study by Jones AW (1987) found next-morning hangover
from red wine with 100 to 150 mg methanol
(9.5 % w/v ethanol, 100 mg/l methanol, 0.01 %).
Fully 11% of aspartame is methanol --
1,120 mg aspartame in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol).
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.
Elimination half-life of methanol during hangover.
Jones AW.
wayne.jones@...
Department of Forensic Toxicology,
University Hospital, SE-581 85 Linkoping, Sweden.
This paper reports the elimination half-life of methanol in human
volunteers.
Experiments were made during the morning after the subjects had
consumed 1000-1500 ml red wine
(9.5 % w/v ethanol, 100 mg/l methanol)
the previous evening. [ 100 to 150 mg methanol ]
The washout of methanol from the body
coincided with the onset of hangover.
The concentrations of ethanol and methanol in blood were
determined indirectly by analysis of end-expired alveolar air.
In the morning when blood-ethanol dropped
below the Km of liver alcohol dehydrogenase (ADH)
of about 100 mg/l (2.2 mM),
the disappearance half-life of ethanol was 21, 22, 18 and 15 min.
in 4 test subjects respectively.
The corresponding elimination half-lives of methanol
were 213, 110, 133 and 142 min. in these same individuals.
The experimental design outlined in this paper can be used
to obtain useful data on elimination kinetics of methanol
in human volunteers without undue ethical limitations.
Circumstantial evidence is presented to link methanol
or its toxic metabolic products, formaldehyde and formic acid,
with the pathogenesis of hangover. PMID: 3588516
Alcohol Clin Exp Res. 1995 Oct; 19(5): 1147-50.
Methanol in human breath.
Taucher J, Lagg A, Hansel A, Vogel W, Lindinger W.
Institut fur Ionenphysik, Universitat Innsbruck, Austria.
Using proton transfer reaction-mass spectrometry for trace gas analysis
of the human breath, the concentrations of methanol and ethanol have
been measured for various test persons consuming alcoholic beverages and
various amounts of fruits, respectively.
The methanol concentrations increased from a natural (physiological)
level of approximately 0.4 ppm up to approximately 2 ppm a few hours
after eating about 1/2 kg of fruits,
and about the same concentration was reached after drinking of 100 ml
brandy containing 24% volume of ethanol and 0.19% volume of methanol.
[ 24 ml = 61 g ethanol, and 0.19 ml = 0.34 g = 340 mg methanol ]
PMID: 8561283 ]
http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full
plain text, 2001: substantial sources are degradation of fruit pectins,
liquors, aspartame, smoke: Murray 2005.04.02
www.nano2hybrids.net/5-project_background/abstract.php
nano2hybrids
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Project Abstract
Commercially available carbon nanotubes (CNTs) currently receive much
attention from scientists in many disciplines, for very different
applications.
However, some of these suffer from the lack of reactivity of the CNTs.
In order to overcome this issue, different methods to 'activate' or
'functionalize' their surface,
such as conventional wet chemistry (use of acids) [Satishkumar, J. Phys.
D: Appl. Phys. 29, 3173 (1996)],
treatment in reactive gas atmosphere [An, Appl. Phys. Lett., 80, 4235
(2002)],
electrochemistry [Wang, Chem. Phys. Lett., 407, 68 (2005)], etc. have
been studied.
Among the proposed methods for surface modification, the cold-low
pressure RF plasma has been tested by the " Laboratoire
Interdisciplinaire de Spectroscopie Electronique " of Namur University
(LISE, FUNDP, BELGIUM), co-ordinator of this project, to successfully
bind in a controlled way oxygen, amine and fluorine groups on the CNTs;
theoretical modelling has already helped to understand the different
reactivity of some chemical functions for CNTs with fixed curvature
[Felten, J. Appl. Phys., 98, 074308 (2005)].
At the present time, very promising application of the plasma modified
CNTs as gas sensors operating at room temperature have been also
demonstrated [Bittencourt, Sensors & Actuators. B, 115:33 (2006);
Ionescu, Sensors & Actuators. B, 113:36 (2006)].
The possibility to tune the plasma discharge operating parameters (gas
composition, pressure, plasma power and duration...) combined with its
diagnostic methods (Optical Emission Spectrometry, Mass spectrometry)
allow us to fine tune and understand the physical properties of these
treatments.
As a result, a further experiment confirmed that it is possible to
control the interfacial (structural and chemical) defects that control
the deposition and growth of metal nanoclusters deposited on CNTs by
using a plasma treatment.
It is important to highlight that real control of the metal nanocluster
growth on the carbon nanotubes appears possible, hence the acronym
nano2hybrids.
In parallel to our experimental work, interaction of metal nanoclusters
with CNTs has been modelled with different techniques, showing whether
or not and in which conditions there are charge transfer and chemical
bonds between the cluster and the CNT surface [Maiti, Chem. Phys. Lett.,
395, 7 (2004)].
The cited proof of principle, combined with the knowledge that highly
dispersed metal nanoparticles should bear a very high reactivity
suggests that the association of these two nanotechnologies can be an
important building block for new catalyst systems.
The reactivity of metal particles can be controlled by modulating
metal-support interaction and finite size (undercoordination) effects
[Biener Surf. Sc., 590, L259 (2005)].
Bearing in mind that cold plasma treatment inducing structural and
chemical defects, allows the control of the interfacial
physico-chemistry, diffusion processes and stabilization of metal
atoms/clusters (with metal atoms in different under-coordination), on
the highly curved CNTs surfaces, it can be proposed that the use of
plasma functionalization will permit to tailor important characteristics
of the hybrid system aiming application in catalysis or/and in devices
based on catalytic reactions such as chemical gas sensors.
In fact, the cluster morphology is dictated by the relative interactions
between the deposited atoms and the CNT surface; large binding energy
between atoms and the CNT surface will lead to a higher nucleation
density and a quasi continuous coverage or wetting of the CNTs; on the
contrary, for a weaker interaction -or a larger metal to metal
interaction- isolated metal nanoclusters will develop on the CNTs
[Zhang, Chem. Phys. Lett. 331, 35 (2000)].
However, the interaction between clusters and CNT surface can change if
defects are present. Thus, fine control of the local defects (type:
structural or chemical; density) can be used to tune the interfacial
properties of the metal clusters, that will determine their size and
shape (which will dictate their electronic properties), diffusion (or
not) avoiding aggregation, coalescence and complete wetting.
The underlying physics of the application of low temperature, low-
vacuum and atmospheric- reactive pressure plasmas as a versatile
nanofabrication tool [K. Ostrokov, Rev. Mod. Phys. 77, 489 (2005)]
should be studied in more details, as it appears competitive compared to
electrochemical deposition and to the other methods cited in [Guo, J.
Coll. Interf. Sc. 286, 274 (2005)].
Plasma treatment doesn't use (large quantity of) polluting chemicals and
is scalable to industrial production, especially within the atmospheric
plasma design.
Moreover, this treatment requires only few seconds or minutes to be
efficient, compared to hours or days required by classical methods used
to functionalize CNTs.
It is important to mention that industrial production of nanotubes is
now achieved (e.g. Nanocyl Co,
http://www.nanocyl.com), with reasonable
(reproducible) control of CNT characteristics.
Moreover, large scale (industrial) applications are foreseeable in
catalysis [Yin, J. of Catalysis, 224, 384 (2004)],
fuel cells [Baughman, Science, 297, 787 (2002)],
gas sensors [Zhao, Nanoletters 5, 847 (2005)],
biomaterials [Meng, Nanomed.: Nanotech., Biol. & Med., 2, 136, 2005]...
By combining synthesis, characterization, theoretical modelling,
practical testing and industrial applications with feedback to synthesis
for optimization of the nano2hybrids materials -- we will develop three
different schemes, using plasma treatments at different (laboratory and
industrial) scales, that will allow control of the chemistry, structure,
diffusion and energetics at interfaces comprising metal nanoclusters and
(modified) carbon nanotubes.
We focus on the following scientific, technological, and societal
objectives:
* Fully integrate in ONE treatment the cleaning, activation,
functionalization and metal deposition steps on the carbon nanotubes
* Control interfacial properties to tailor metal nanoparticles
shape, size, (under) coordination, diffusion
* Understand, control, select and fine tune the reactivity
(sensitivity, selectivity, response time...) of the hybrid materials for
gas sensors,
* Design, test and optimize a gas sensor,
* Involve public with documentaries and web video on "science as it
happens".
////////////////////////////////////////////////////////////
"Of course, everyone chooses, as a natural priority, to enjoy peace,
joy, and love by helping to find, quickly share, and positively act upon
evidence about healthy and safe food, drink, and environment."
Rich Murray, MA Room For All
rmforall@...
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505
http://RMForAll.blogspot.com new primary archive
http://groups.yahoo.com/group/aspartameNM/messages
group with 111 members, 1,486 posts in a public,
searchable archive
http://groups.yahoo.com/group/aspartameNM/message/1472
bias, omissions, incuriosity = opportunity, aspartame safety evaluation,
Magnuson BA, Burdock GA, Williams GM, 7 more, 2007 Sept, Ajinomoto
funded 98 pages html [$ 32 781888262_content.pdf]: Murray 2007.09.15
////////////////////////////////////////////////////////////
13 mainstream research studies in 24 months showing aspartame toxicity,
also 3 relevant studies on methanol and formaldehyde: Murray 2007.11.08
http://groups.yahoo.com/group/aspartameNM/message/1464
Aspartame toxicity was shown in thirteen detailed mainstream research
studies in 24 months in work by expert teams in USA, South Africa,
England, Italy, Greece, Hungary, and Mexico.
Very little has been publicized in mass print and broadcast media.
Also highly relevant are a study in South Korea that finds levels of
methanol similar to those from aspartame drinks cause the hangovers
from alcohol drinks, a study in China on Alzheimer's type damage in
nerve cells from low dose formaldehyde, and an IARC review by 25
experts that determines formaldehyde to be a human carcinogen.
////////////////////////////////////////////////////////////
http://RMForAll.blogspot.com October 12, 2007
http://groups.yahoo.com/group/aspartameNM/message/1479
13,620 seniors using more than 1 can/week artificially sweetened
[aspartame] soft drinks had 8 % higher death risk, 1981-2004, Paganini-
Hill A, Kawas CH, Corrada MM, U. Southern Cal., Prev. Med. 2007 April
44(4) 305-10: Murray 2007.10.12
http://groups.yahoo.com/group/aspartameNM/message/1475
19,000 people, the 4 % of users of aspartame who drink average 5 cans
daily, have more problems in NIH AARP study of 474,000 people: Murray
2007.09.21
http://RMForAll.blogspot.com September 21, 2007
Table 1. NIH-AARP Diet and Health Study aspartame intake levels from
beverages, 1995-2000 (N = 473,984)
[ adapted from article -- a 12-oz can diet soda has 200 mg aspartame ]
0 - under 100 - 100-200 - 200-400 - 400-600 - 600-1200 - over 1200 mg/d
cohort %
46 ------- 25 ------ 13 ------ 7 -------- 5 -- about 3 --- under 1
This is the first good data about the percentage of aspartame users
who use over 3 cans daily, averaging 5 cans daily at 200 mg per 12 oz
can diet soda.
About 4 % of 473,984 is 19,000 people, with a peak intake of 17 cans
daily, and average 5 cans daily.
It would be worthwhile to investigate a wide variety of symptoms for
the 0.1 % of highest level users, about 500 people.
For about 200 million USA aspartame users, this would be 200,000
people.
Table 1 reveals consistent increase in problems from
--------------------- zero to (400-600) to (over 600) mg/d
aspartame intake:
% of cohort ---------- 46 -------- 5 -------- 4 %
mean aspartame mg/d --- 0 -------441 ------ 986
16+ education -------- 37 ------- 40 ------- 34 %
diabetes history ------ 3 ------- 22 ------- 26 %
alcohol g/d ---------- 14 ------- 11 ------- 13
never smoke ---------- 36 ------- 31 ------- 29 %
Body Mass Index ------ 26 ------- 29 ------- 29
18.5 - 25 ------------ 42 ------- 21 ------- 19 %
30 - 35 -------------- 13 ------- 23 ------- 26 %
over 35 -------------- 4 ------- 10 ------- 13 %
Physical activity %:
under 3-4/mo --------- 32 ------- 32 ------- 37 %
under 1-2/wk --------- 22 ------- 21 ------- 19 %
over 3-4/wk ---------- 45 ------- 45 ------- 43 %
Calories kcal ----- 1,919 ---- 1,855 ---- 2,044 %
Caffeine mg/d ------ 393 ------ 364 ------ 424
There do seem to be many increases of problems
from the second to third row, as mean aspartame use doubles.
Granted, this is cherry picking the data, selecting interesting
patterns.
Correlations alone do not prove any direction of causation.
Nevertheless, it may be of value to study the correlations for
increasing aspartame intake among the 4 % using over 600 mg, the
equivalent of 3 cans 12-oz cans diet soda daily. The average use for
this group is 5 cans daily.
For instance, are a minority of these heavy users displaying the great
majority of the problems that are reflected in the mean for each level
of use, with most users only having little or no increase in problems?
This is a group of about 20,000 people.
http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21
The Nurses Health Study is a bonanza of information about the health
of probably hundreds of nurses who use 6 or more cans daily of diet soft
drinks -- they have also stored blood and tissue samples from their
immense pool of subjects, over 100,000 for decades.
Cancer Epidemiol Biomarkers Prev. 2006 Sep; 15(9): 1654-9.
Comment in:
Cancer Epidemiol Biomarkers Prev. 2007 Jul; 16(7): 1527-8;
author reply 1528-9.
Consumption of aspartame-containing beverages and incidence of
hematopoietic and brain malignancies.
Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R,
Campbell D, Hollenbeck AR, Schatzkin A.
Division of Cancer Control and Population Sciences,
National Cancer Institute, 6130 Executive Boulevard, EPN 4005,
Rockville, MD 20852-7344, USA. PMID: 16985027
Unhee Lim 1,
Amy F. Subar 2,
subara@...,
Traci Mouw 1,
Patricia Hartge 1,
Lindsay M. Morton 1,
Rachael Stolzenberg-Solomon 1,
David Campbell 3,
Albert R. Hollenbeck 4
and Arthur Schatzkin 1
1 Division of Cancer Epidemiology and Genetics,
2 Division of Cancer Control and Population Sciences, National Cancer
Institute, NIH, Department of Health and Human Services;
3 Information Management Services, Inc., Rockville, Maryland; and
4 AARP, Washington, District of Columbia
Requests for reprints: Amy Subar,
Division of Cancer Control and Population Sciences,
National Cancer Institute,
6130 Executive Boulevard, EPN 4005, Rockville, MD 20852-7344.
Phone: 301-594-0831; Fax: 301-435-3710. E-mail:
subara@...
http://cebp.aacrjournals.org/cgi/content/full/15/9/1654 free full
text
BACKGROUND:
In a few animal experiments, aspartame has been linked to
hematopoietic and brain cancers.
Most animal studies have found no increase in the risk of these or
other cancers.
Data on humans are sparse for either cancer.
Concern lingers regarding this widely used artificial sweetener.
OBJECTIVE:
We investigated prospectively whether aspartame consumption is
associated with the risk of hematopoietic cancers or gliomas
(malignant brain cancer).
METHODS:
We examined 285,079 men and 188,905 women ages 50 to 71 years in the
NIH-AARP Diet and Health Study cohort
Daily aspartame intake was derived from responses to a baseline self-
administered food frequency questionnaire that queried consumption of
four aspartame-containing beverages (soda, fruit drinks, sweetened
iced tea, and aspartame added to hot coffee and tea) during the past
year.
Histologically confirmed incident cancers were identified from eight
state cancer registries.
Multivariable-adjusted relative risks (RR) and 95% confidence
intervals (CI) were estimated using Cox proportional hazards
regression that adjusted for age, sex, ethnicity, body mass index, and
history of diabetes.
RESULTS:
During over 5 years of follow-up (1995-2000), 1,888 hematopoietic
cancers and 315 malignant gliomas were ascertained.
Higher levels of aspartame intake were not associated with the risk of
overall hematopoietic cancer
(RR for over 600 mg/d, 0.98; 95 % CI, 0.76-1.27),
glioma (RR for over 400 mg/d, 0.73; 95 % CI, 0.46-1.15;
P for inverse linear trend = 0.05),
or their subtypes in men and women.
CONCLUSIONS:
Our findings do not support the hypothesis that aspartame increases
hematopoietic or brain cancer risk. PMID: 16985027
"We cannot exclude the possibility that higher aspartame consumption
than that observed in this study may be associated with an elevated
risk of hematopoietic or brain cancers.
In the laboratory study with positive findings, animals were fed doses
starting from 4 mg up to 5,000 mg per kg body weight.
Significantly elevated lymphomas and leukemias were observed in female
rats fed 20 mg of aspartame and higher (e.g., 1,200 mg for humans
weighing 60 kg or 132 lb; refs. 13, 14).
The reported aspartame intake in our data ranged from 0 to 3,400 mg/d
with sparse numbers in the upper intake categories (under 1 %
consuming over 1,200 mg/d).
However, we did not detect any increase in risk estimates in the
highest categories (over 1,200 or 2,000 mg/d, which is equivalent to
about 7 to 11 cans of soft drinks daily) compared with the lowest
categories,
and the associations were similarly null in both men and women."
////////////////////////////////////////////////////////////
http://groups.yahoo.com/group/aspartameNM/message/1472
bias, omissions, incuriosity, opportunity, aspartame safety
evaluation, Magnuson BA, Burdock GA, Williams GM, 7 more, 2007 Sept,
Ajinomoto funded 98 pages html [$ 32 781888262_content.pdf]: Murray
2007.09.14
Eur J Clin Nutr. 2007 Aug 8; [Epub ahead of print]
Direct and indirect cellular effects of aspartame on the brain.
Humphries P,
Pretorius E,
resia.pretorius@...,
Naudé H.
[1] Department of Anatomy, University of Pretoria, Pretoria, Gauteng,
South Africa
[2] Department of Anatomy, University of the Limpopo, South Africa.
http://groups.yahoo.com/group/aspartameNM/message/1463
Ultrastruct Pathol. 2007 Mar-Apr; 31(2): 77-83.
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.
[ Humphries P also at
Department of Anatomy, University of Limpopo.
Medunsa Campus, Garankuwa. South Africa ]
*Correspondence to E. Pretorius,
BMW Building, PO Box 2034,
Faculty of Health Sciences,
University of Pretoria, Pretoria 0001, South Africa
http://groups.yahoo.com/group/aspartameNM/message/1452
aspartame decreases evoked extracellular dopamine levels in the rat
brain, Brian P Bergstrom, Muskingum College, Neuropharmacology
2007.09.29: Murray 2007.11.06
"These findings suggest that APM has a relatively potent effect of
decreasing evoked extracellular DA levels when administered systemically
under the conditions specified. "
Neuropharmacology. 2007 Sep 29; [Epub ahead of print]
Aspartame decreases evoked extracellular dopamine levels in the rat
brain: An in vivo voltammetry study.
Bergstrom BP,
brianb@...,
[ (2001), Associate Professor of Biology, B.S., Ph.D., Illinois State
University
Brian Bergstrom studies neurochemical changes in synaptic function of
dopamine neurons in response to neurodegenerative disease, drugs of
abuse, and pharmacological regulation.
He is Assistant Professor of Biology and teaches Intro to Cell and
Molecular Biology, Cell Physiology, and Advanced Neuroscience.]
Cummings DR,
bynehill@...,
Skaggs TA.
Department of Biology, Neuroscience Program,
Muskingum College, New Concord, OH 43762, USA.
http://groups.yahoo.com/group/aspartameNM/message/1485
[ not about aspartame, but highly suggestive... ]
http://groups.yahoo.com/group/aspartameNM/message/1471
Food additives and hyperactive behaviour in kids, McCann D, Grimshaw
K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06
pdf 454 KB: Murray 2007.09.06
www.dailymail.co.uk/pages/live/articles/health/womenfamily.html?in_article_id=45\
\3431&in_page_id=1799
By UK Daily Mail Newspaper
The proof food additives ARE as bad as we feared
By SEAN POULTER Last updated at 09:53am on 18th May 2007
[ This team will publish their confirming study later in 2007. ]
http://adc.bmj.com/cgi/content/full/89/6/506
Archives of Disease in Childhood 2004; 89(6): 506-511
Erratum in: Arch Dis Child. 2005 Aug; 90(8): 875.
© 2004 BMJ Publishing Group & Royal College of Paediatrics and Child
Health
The effects of a double blind, placebo controlled, artificial food
colourings and benzoate preservative challenge on hyperactivity in a
general population sample of preschool children
B Bateman 1,
J O Warner 1,
j.o.warner@...,
E Hutchinson 3,
T Dean 5,
tara.dean@...,
P Rowlandson 4, Dr. Piers Rolandson, Paediatric Tutor
C Gant 5,
J Grundy 5,
C Fitzgerald 3
and J Stevenson 2
jsteven@...,
1 Infection, Inflammation and Repair Division, University of
Southampton, Southampton, UK
2 Department of Psychology, University of Southampton, Southampton, UK
3 Department of Clinical Psychology, St Mary's Hospital, Isle of
Wight, UK
4 Department of Paediatrics, St Mary's Hospital, Isle of Wight, UK
5 David Hide Asthma and Allergy Research Centre, St Mary's Hospital,
Isle of Wight, UK
http://groups.yahoo.com/group/aspartameNM/message/1461
www.ehponline.org/members/2007/10271/10271.pdf free full text 24 pages
National Institutes of Health
U.S. Department of Health and Human Services
ENVIRONMENTAL HEALTH PERSPECTIVES
Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal
Life Increases Cancer Effects in Rats
doi:10.1289/ehp.10271 (available at
http://dx.doi.org/)
Online 13 June 2007
Morando Soffritti 1,
Fiorella Belpoggi 1,
Eva Tibaldi 1,
Davide Degli Esposti 1,
Michela Lauriola 1
1 Cesare Maltoni Cancer Research Center, European Ramazzini Foundation
of Oncology and Environmental Sciences, Bologna Italy
Address of the institution: Cesare Maltoni Cancer Research Center,
European Ramazzini Foundation of Oncology and Environmental Sciences
Castello di Bentivoglio, Via Saliceto, 3, 40010 Bentivoglio, Bologna,
Italy +39 051 6640460 fax +39 051 6640223
crcfr@..., www.ramazzini.it
Address correspondence to: M. Soffritti
Acknowledgements:
This research was supported entirely by the European Ramazzini
Foundation Environmental Sciences.
The authors declare that they have no competing financial interests.
http://groups.yahoo.com/group/aspartameNM/message/1441
http://www.ramazzini.it/fondazione/docs/NYAS_Aspartame_Ramazzini.pdf
Results of Long-Term Carcinogenicity Bioassay on Sprague-Dawley Rats
Exposed to Aspartame Administered in Feed
Ann. N.Y. Acad. Sci. 2006 Sep; 1076: 559-577.
Fiorella Belpoggi,
Morando Soffritti,
Michela Padovani,
Davide Degli Esposti,
Michelina Lauriola, and
Franco Minardi.
The end judges everything -- HERODOTUS (480-425 B.C.) The History
Cesare Maltoni Cancer Research Center,
European Foundation of Oncology and Environmental Sciences
'B. Ramazzini',ť 40010 Bentivoglio, Bologna, Italy
http://groups.yahoo.com/group/aspartameNM/message/1382
[ and, previously ]
First experimental demonstration of the multipotential
carcinogenic effects of aspartame administered in the feed to Sprague-
Dawley rats.
Environ. Health Perspect. 2006 Mar; 114: 379-385. PMID: 16507461
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E,
Rigano A.
Environmental Health Perspectives Volume 113, Number 11
November 2005 Current print issue
The full version of this article is available for free in PDF format.
http://ehp.niehs.nih.gov/members/2005/8711/8711.pdf 35 pages
First Experimental Demonstration of the
Multipotential Carcinogenic Effects of Aspartame
Administered in the Feed to Sprague-Dawley Rats.
Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti,
Luca Lambertini, Eva Tibaldi, and Anna Rigano.
doi:10.1289/ehp.8711 (available at
http://dx.doi.org/)
Online 17 November 2005
The National Institute of Environmental Health Sciences
National Institutes of Health
U.S. Department of Health and Human Services
http://www.ehponline.org/
Cesare Maltoni Cancer Research Center,
European Ramazzini Foundation of Oncology and
Environmental Sciences
Sofritti, M. et al. 2005.
Aspartame induces lymphomas and leukaemias in rats.
Eur. J. Oncol. 2005; 10: 107-116.
http://groups.yahoo.com/group/aspartameNM/message/1250
Food Chem Toxicol. 2007 Jun 16;[Epub ahead of print]
The effect of aspartame metabolites on the suckling rat
frontal cortex acetylcholinesterase. An in vitro study.
Simintzi I,
Schulpis KH,
inchildh@...,
Angelogianni P,
Liapi C,
Tsakiris S.
stsakir@...,
Department of Experimental Physiology, Medical School,
University of Athens,
P.O. Box 65257, GR 15401 Athens, Greece.
http://groups.yahoo.com/group/aspartameNM/message/1459
Toxicology. 2007 May 18; [Epub ahead of print]
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.
http://groups.yahoo.com/group/aspartameNM/message/1447
Pharmacol Res. 2007 May 13; [Epub ahead of print]
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.
http://groups.yahoo.com/group/aspartameNM/message/1444
Eur J Clin Nutr. 2005 Dec 14; [Epub ahead of print]
The effect of L-cysteine and glutathione on inhibition of
Na(+), K(+)-ATPase activity by aspartame metabolites
in human erythrocyte [red blood cell] membrane.
Schulpis KH, Kleopatra H. Schulpis, MD, PhD.
Institute of Child Health, Aghia Sophia Children's Hospital,
GR-11527 Athens (Greece) +30 1 7708291, Fax +30 1 7700111
inchildh@...
Papassotiriou I,
biochem@...,
Tsakiris T,
Tsakiris S. Stylianos Tsakiris.
stsakir@...,
1 Institute of Child Health, Research Center,
'Aghia Sophia' Children's Hospital, Athens, Greece.
ggbriass@... ersi_voskaridou@...
mmoschov@... siahanidou@...
http://groups.yahoo.com/group/aspartameNM/message/1279
Pharmacol Res. 2005 Aug 26; [Epub ahead of print]
The effect of aspartame metabolites on human [red blood cell]
erythrocyte membrane acetylcholinesterase activity.
Tsakiris S,
Giannoulia-Karantana A,
Simintzi I,
Schulpis KH.
Department of Experimental Physiology, Medical School,
University of Athens, P.O. Box 65257, GR-154 01 Athens, Greece.
Stylianos Tsakiris.
stsakir@...,
Giannoulia-Karantana A. First Department of Pediatrics,
Aghia Sophia Children's Hospital, University of Athens, Greece.
Kleopatra H. Schulpis, MD, PhD. Institute of Child Health,
Aghia Sophia Children's Hospital, GR-11527 Athens (Greece)
Tel. +30 1 7708291, Fax +30 1 7700111
inchildh@...
[ Papoutsakis T.
tina.papoutsakis@...,
Papadopoulos G. Department of Biochemistry and Biotechnology,
University of Thessaly, Ploutonos 26, 41221 Larisa, Greece
papg@..., ]
http://groups.yahoo.com/group/aspartameNM/message/1213
In Vivo. 2007 Jan-Feb; 21(1): 89-92.
The effect of aspartame administration on oncogene and suppressor gene
expressions.
Gombos K,
katalin_gombos@...,
Varjas T,
Orsos Z,
Polyak E,
Peredi J,
Varga Z,
Nowrasteh G,
Tettinger A,
Mucsi G,
Ember I.
Faculty of Medicine, Institute of Public Health University of Pecs,
Pecs, Hungary.
http://groups.yahoo.com/group/aspartameNM/message/1414
Hum Exp Toxicol. 2006 Aug; 25(8): 453-9.
The effect of aspartame on rat brain xenobiotic-metabolizing enzymes.
Vences-Mejia A 1,
Labra-Ruiz N 1,
Hernandez-Martinez N 1,
Dorado-Gonzalez V 1,
Gomez-Garduno J 1,
Perez-Lopez I 1,
Nosti-Palacios R 1,
Camacho Carranza R 2,
Espinosa-Aguirre JJ 2.
Laboratorio de Toxicologia Genetica,
1: Instituto Nacional de Pediatria, Insurgentes Sur, 3700-C,
04530 Mexico, DF Mexico.
2: Instituto de Investigaciones Biomédicas, UNAM, Apartado postal
70228,
Ciudad Universitaria 04510 México, D.F., México
http://www.biomedicas.unam.mx/index.asp
*Correspondence: JJ Espinosa-Aguirre, Instituto de Investigaciones
Biome´dicas, UNAM, Apartado postal 70228, Ciudad
Universitaria 04510 Me´xico, D.F., Me´xico
Human & Experimental Toxicology (2006) 25(8): 453 - 459.
www.sagepublications.com
c 2006 SAGE Publications 10.1191/0960327106het646oa
[ Dra. Araceli Vences M
Jefa de Laboratorio de Toxicologia Genetica
6° P de Hospital Laboratorios
10 84 09 00 Ext.1410 -1448
aritaven@..., ]
http://groups.yahoo.com/group/aspartameNM/message/1373
Toxicol Sci. 2006 Mar;90(1):178-87.
Synergistic interactions between commonly used food additives in a
developmental neurotoxicity test.
Lau K, McLean WG, Williams DP, Howard CV.
Developmental Toxicopathology Unit,
Department of Human Anatomy & Cell Biology,
University of Liverpool, Sherrington Buildings, Liverpool L69 3GE, UK;
Department of Pharmacology & Therapeutics,
University of Liverpool, Sherrington Buildings, Liverpool L69 3GE, UK.
W. Graham McLean
w.g.mclean@...,
C. V. Howard
c.v.howard@...,
D. P. Williams
dom@..., 0151 794 5791
http://www.liv.ac.uk/
Miss. Karen Lau
karenlau@..., 0151 795 4223
http://groups.yahoo.com/group/aspartameNM/message/1271
http://www.biomedcentral.com/content/pdf/1471-2202-8-9.pdf
free full text 28 pages
This Provisional PDF corresponds to the article as it appeared upon
acceptance.
Copyedited and fully formatted PDF and full text (HTML) versions will
be made available soon.
Amyloid-like aggregates of neuronal tau induced by formaldehyde
promote
apoptosis of neuronal cells
BMC Neuroscience 2007 Jan 23, 8(1): 9 doi: 10.1186/1471-2202-8-9
Chunlai Nie
niecl1022@...,
Xing sheng Wang
step@...,
Ying Liu
liuy@...,
Sarah Perrett
sperrett@...,
Rongqiao He
herq@...,
ISSN 1471-2202
Article type Research article
Submission date 15 August 2006
Acceptance date 23 January 2007
Publication date 23 January 2007
Article URL
http://www.biomedcentral.com/1471-2202/8/9
Chun Lai Nie 1,3,
Xing Sheng Wang 1,3,
Ying Liu 1,
Sarah Perrett 2 and
Rong Qiao He 1,3*
1 State Key Laboratory of Brain and Cognitive Science,
Institute of Biophysics, 15 Datun Rd, Chaoyang District, Beijing
100101, China
2 National Laboratory of Biomacromolecules,
Institute of Biophysics, 15 Datun Rd, Chaoyang District, Beijing
100101, China
3 Graduate School, Chinese Academy of Sciences, 19 Yuquan Rd,
Shijingshan
District, Beijing 100049, China
*Corresponding author
http://groups.yahoo.com/group/aspartameNM/message/1406
Addict Biol. 2005 Dec;10(4): 351-5.
Concentration changes of methanol in blood samples during
an experimentally induced alcohol hangover state.
Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT, Kim DJ.
Chuncheon National Hospital, Department of Psychiatry,
The Catholic University of Korea, Seoul, Korea.
http://www.cuk.ac.kr/eng/ sysop@...
Songsin Campus: 02-740-9714 Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm eight hospitals
http://groups.yahoo.com/group/aspartameNM/message/1394
" Absorbed formaldehyde can be oxidized to formate and carbon dioxide
or can be incorporated into biologic macromolecules. "
[ References include: Soffritti M, Belpoggi F, Lambertini L, Lauriola
M,
Padovani M, Maltoni C. 2002. Results of long-term experimental studies
on the carcinogenicity of formaldehyde and acetaldehyde in rats. Ann
NY Acad Sci 982: 87-105.
Soffritti M, Maltoni C, Maffei F, Biagi R. 1989. Formaldehyde: an
experimental multipotential carcinogen. Toxicol Ind Health 5:699-730.
"
Morando Soffritti is a member of the Working Group. ]
http://www.ehponline.org/members/2005/7542/7542.html free full text
After a thorough discussion of the epidemiologic, experimental, and
other relevant data, the working group concluded that formaldehyde is
carcinogenic to humans, based on sufficient evidence in humans and in
experimental animals.
In the epidemiologic studies, there was sufficient evidence that
formaldehyde causes nasopharyngeal cancer, "strong but not sufficient"
evidence of leukemia, and limited evidence of sinonasal cancer.
The working group also concluded that 2-butoxyethanol and
1-tert-butoxy-2-propanol are not classifiable as to their
carcinogenicity to humans, each having limited evidence in
experimental animals and inadequate evidence in humans.
These three evaluations and the supporting data will be published as
Volume 88 of the IARC Monographs. PMID: 16140628
Environ Health Perspect. 2005 Sep; 113(9): 1205-8.
Meeting report: summary of IARC monographs on formaldehyde, 2-
butoxyethanol, and 1-tert-butoxy-2-propanol.
Cogliano VJ, Vincent James Cogliano
cogliano@...,
Grosse Y, Yann Grosse
grosse@...,
Baan RA, Robert A. Baan
baan@...,
Straif K, Kurt
straif@...,
Secretan MB, Marie Béatrice Secretan
secretan@...,
El Ghissassi F, Fatiha El Ghissassi
elghissassi@...,
Working Group for Volume 88.
IARC, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France
Tel: +33 (0)4 72 73 84 85 - Fax: +33 (0)4 72 73 85 75
© IARC 2004 - All Rights Reserved
http://monographs.iarc.fr cie@...,
Monographs Recently Published
IARC Monographs Vol 88
Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol
December 2006
478 pages
ISBN 92 832 1288 6
US$ 40
This volume re-evaluates the available evidence on the carcinogenic
potential of formaldehyde, a substance that is found in the workplace
and in the environment.
Formaldehyde is widely used in resins that bind wood products, pulp
and paper; in glasswool and rockwool insulation; in plastics and
coatings, textile finishing, chemical manufacture; and as a
disinfectant and preservative.
Also evaluated are two glycol ethers, 2-butoxyethanol and 1-tert-
butoxypropan-2-ol,
which are widely used as solvents in paints and paint thinners,
coatings, glass and surface cleaners, inks, adhesives, personal-care
products, and as chemical intermediates.
As for formaldehyde, there is sufficient evidence in epidemiological
studies for nasopharyngeal cancer, strong but not sufficient evidence
for leukaemia, and limited evidence for sinonasal cancer.
The extensive scientific database on the mechanisms by which
formaldehyde can induce nasal-tract cancer in humans is considered.
These data provide strong support for the empirical observation of
nasopharyngeal cancer in humans.
In contrast, the lack of information on possible mechanisms by which
formaldehyde might increase the risk for leukaemia in humans tempered
the interpretation of the epidemiological data on that cancer.
Although this volume focuses on a qualitative assessment of the
carcinogenic potential of formaldehyde, subsequent predictions of the
risks for nasopharyngeal cancer should consider pertinent information
on mechanisms of carcinogenesis, including genotoxicity and dose-
dependent cytoxicity.
A theme common to the three evaluations is the consideration of
mechanistic information to develop and evaluate hypotheses on the
sequence of steps that lead to the induction of tumours in
experimental animals.
The hypothesized mechanisms described provide an interesting set of
cases that range from a vast literature on respiratory tract tumours
in rats induced by the inhalation of formaldehyde to some more
tentative hypotheses on the various tumours observed in animals
following exposure to both glycol ethers.
Recurring issues were the criteria that characterize a rare tumour or
how to introduce additional information to resolve difficult
questions; for example, how to consider the results of historical
controls.
International Agency for Research on Cancer, Lyon, France.
An international, interdisciplinary working group of expert scientists
met in June 2004 to develop IARC Monographs on the Evaluation of the
Carcinogenic Risk of Chemicals to Humans (IARC Monographs) on
formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol.
Each IARC Monograph includes a critical review of the pertinent
scientific literature and an evaluation of an agent's potential to
cause cancer in humans.
Key words: 1-tert-butoxy-2-propanol, 2-butoxyethanol, carcinogen,
formaldehyde, glycol ethers, hazard identification, IARC Monographs,
leukemia, nasopharyngeal cancer, sinonasal cancer. Environ Health
Perspect 113: 1205-1208 (2005) .
doi:10.1289/ehp.7542 available via
http://dx.doi.org/ [Online 12 May
2005]
Address correspondence to V.J. Cogliano, Carcinogen Identification and
Evaluation, International Agency for Research on Cancer, 150 cours
Albert Thomas, 69372 Lyon cedex 08, France.
33-4-72-73-84-76. fax 33-4-72-73-83-19
cogliano@...,
The Working Group for Volume 88 of the IARC Monographs includes:
Ulrich Andrae (Germany) ,
andrae@..., Dr. Ulrich Andrae, GSF-
Institut für Toxikologie,. Postfach 1129, D-85758 Neuherberg, Germany
Fax: 149-089-3187-3449 Sherwood Burge (UK),
Rajendra S Chhabra (USA) ,
http://dir.niehs.nih.gov/dirtob/chhabra.htm
chhabrar@..., General Toxicology Group, TOB, ETP, DIR
John Cocker (UK) , Health and Safety Laboratory, Buxton, UK
john.cocker@...,
David N Coggon (UK) , MRC Environmental Epidemiology Unit at the
University of Southampton, UK
dnc@...,
Rory Conolly (USA) ,
Rconolly@..., Senior Research Biologist,
National Center for Computational Toxicology, Office of Research and
Development, U.S. Environmental Protection Agency
Paul Demers (Canada) ,
pdemers@..., Occupational Hygiene
Institute, University of British Columbia
David A Eastmond (USA) ,
david.eastmond@..., Enviromental
Toxicology
Graduate Program, University of California Riverside, CA 92521 (951)
827-4497 (Voice) (951) 827-3087 (Fax)
Elaine Faustman (USA) ,
faustman@..., Professor, Env. and
Occ. Health Sciences, Adjunct Professor, Evans School 206-685-2269
Victor J Feron (the Netherlands) , TNO Nutrition and Food Research
(retired), The Netherlands TNO-CIVO TOXICOLOGY AND NUTRITION INSTITUTE
Utrechtseweg 48 3704 HE Zeist The Netherlands (31)-3404 44 144
Michel Gérin (Canada, Chair) ,
gerinm@..., Departement de
medecine du travail et d'hygiene du milieu, Universite de Montreal,
Quebec, Canada.
Marcel Goldberg (France) ,
marcel.goldberg@...,
France -- National Institute of Health and Medical Research INSERM
Unite 88, HNSM 14 Rue de Val d'Osne F-94410 St. Maurice France [33]
1-451-83859 [33] 1-451-83889 Departement Sante Travail, Institut de
Veille Sanitaire, 12, rue du Val d'Osne, 94410 Saint Maurice, France
Bernard D Goldstein (USA) ,
bdgold@..., Director of the
Environmental and Occupational Health Sciences Institute and Professor
and Chair of the Department of Environmental and Community Medicine at
UMDNJ - Robert Wood Johnson Medical School. Dean's Office, University
of Pittsburgh Graduate School of Public Health, A624 Crabtree Hall,
130 DeSoto St., Pittsburgh, PA 15261, USA.
Roland C Grafström (Sweden) ,
roland.grafstrom@..., Roland C
Grafström, Institute of Environmental Medicine, Karolinska Institutet,
Box 210, S−17177 Stockholm, Sweden Telefax: +46-8−329402
Johnni Hansen (Denmark) ,
johnni@..., PhD, Senior researcher,
Danish Cancer Registry , Institute of Cancer Epidemiology, Danish
Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
Michael Hauptmann (USA) , The National Cancer Institute
Kathy Hughes (Canada) , Head, Existing Substances Section 1, Health
Canada,
Ted Junghans (USA) ,
tjunghans@..., Technical Resources
International, Inc., 6500 Rock Spring Drive, Suite 650, Bethesda, MD
20817, USA.
Dan Krewski (Canada) , MHA, MSc, PhD
dkrewski@..., Professor
Director, R. Samuel McLaughlin Centre for Population Health Risk
Assessment, Institute of Population Healt, 1 Stewart Street, Room 320,
Phone: (613) 562-5381 Fax: (613)562-5380
Steve Olin (USA) ,
solin@..., ILSI International Life Sciences
Institute
Martine Reynier (France) ,
martine.reynier@..., Mme Martine
REYNIER,
Institut National de Recherche et de Sécurité (INRS), 30, rue Olivier
Noyer, 75680 Paris Cedex 14 (France) Tel : +33 (0)1 40 44 30 81 Fax :
+33 (0)1 40 44 30 54
Judith Shaham (Israel) ,
yshaham@..., Occupational Cancer
Department, National Institute of Occupational and Environmental
Health,
Raanana, Israel. MD, Occupational Cancer Unit, Occupational Health &
Rehabilitation Institute, P.O. Box 3, Raanana 43100, ISRAEL
Morando Soffritti (Italy) ,
crcfr@..., European Foundation of
Oncology and Environmental Sciences "B. Ramazzini", Cesare Maltoni
Cancer Research Center, Bologna, Italy
Leslie Stayner (USA) ,
lstayner@..., Division of Epidemiology and
Biostatistics, University of Illinois at Chicago School of Public
Health (M/C 923), 1603 West Taylor Street, Room 971, Chicago, IL
60612. E-mail:
Patricia Stewart (USA) , National Food Safety and Toxicology Center,
165 Food Safety and Toxicology Building, Michigan State University,
East Lansing, MI 48824; fax (517) 432-2310
Douglas Wolf (USA) ,
wolf.doug@..., DVM, PhD, USEPA, (Toxicology)
We gratefully acknowledge the important contributions of the
administrative staff of the IARC Monographs: S. Egraz, M. Lézčre, J.
Mitchell, and E. Perez.
The IARC Monographs are supported, in part, by grants from the U.S.
National Cancer Institute, the European Commission, the U.S. National
Institute of Environmental Health Sciences, and the U.S. Environmental
Protection Agency.
The authors declare they have no competing financial interests.
Received 31 August 2004 ; accepted 12 May 2005.
http://groups.yahoo.com/group/aspartameNM/message/1417
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http://groups.yahoo.com/group/aspartameNM/message/1467
4 cases of aspartame-induced thrombocytopenia [ very low platelets in
blood ], HJ Roberts MD, Letter in Southern Medical Journal 2007 May:
100(5); 543: Murray 2007.08.25
http://groups.yahoo.com/group/aspartameNM/message/1468
Formaldehyde induced urticarial vasculitis in male medical student,
age 40, Michael Pellizzari, Gillian Marshman, Flinders U.,
Australasian J. Dermatol. 2007 Aug: Murray 2007.08.29
http://groups.yahoo.com/group/aspartameNM/message/1469
highly toxic formaldehyde, the cause of alcohol hangovers, is made by
the body from 100 mg doses of methanol from dark wines and liquors,
dimethyl dicarbonate, and aspartame: Murray 2007.08.31
http://groups.yahoo.com/group/aspartameNM/message/1470
new details on how formaldehyde and formic acid from methanol are
neurotoxic: Chun Lai Nie, Rong Giao He, et al, PLoS ONE 2(7): e629
2007.07.18 Chinese Academy of Sciences, Beijing: Murray 20097.09.01
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http://groups.yahoo.com/group/aspartameNM/message/1457
aspartame bans, tis more an avalanche than a trend...: Rich Murray
2007.08.17
[ see also:
http://groups.yahoo.com/group/aspartameNM/message/1458
ASDA, Wal-Mart's UK supermarket chain, bans artificial colors, trans
fats, MSG and aspartame, Marguerite Kelly, The Washington Post: Murray
2007.08.03 ]
So far, USA print and broadcast media are deaf, blind, and dumb,
regarding recent major bans of aspartame and MSG in the UK and EU.
The EU Parliament voted July 12 to ban artificial sweeteners
in newly born and infant foods.
On May 15 four huge UK supermarket chains announced bans
of aspartame and MSG, food dyes, and many additives
to protect kids from ADHD --
Sainsbury, Tesco, Marks & Spencer, and ASDA, a unit of WalMart.
May 31: Coca-Cola and the much larger Cargill Inc.,
after years of secret development, with 24 patents,
will soon sell rebiana (stevia) in drinks and food
in the many nations where it is approved as a sweetener --
for decades a major sweetener in Japan, China, Korea, Taiwan,
Thailand, Malasia, Saint Kitts, Nevis,
Brazil, Peru, Paraguay, Uruguay, and Israel,
and an approved supplement in USA, Australia, and Canada,
according to Wikipedia.
http://groups.yahoo.com/group/aspartameNM/message/1454
recent research and news re aspartame and stevia: Murray 2007.08.16
http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray, brief fair summary of much more research:
Murray 2007.01.01
http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation
cancer studies 2007.06.25: Murray 2007.07.18
http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring
agents will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12
http://groups.yahoo.com/group/aspartameNMmessage/1437
stevia to be approved and cyclamates limited by
Food Standards Australia New Zealand:
JMC Geuns critiques of two recent stevia studies by Nunes:
Murray 2007.05.29
http://groups.yahoo.com/group/aspartameNM/message/1427
more from The Independent, UK, Martin Hickman, re ASDA
(unit of Wal-Mart Stores) and Marks & Spencer ban of
aspartame, MSG, artificial chemical additives and dyes
to prevent ADHD in kids: urray 2007.05.16
http://news.independent.co.uk/uk/health_medical/article2548747.ece
http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15
http://groups.yahoo.com/group/aspartameNM/message/1438
Coca-Cola and Cargill Inc., after years of development,
with 24 patents, will soon sell rebiana (stevia)
in drinks and foods: Murray 2007.05.31
http://RMForAll.blogspot.com October 17, 2007
http://groups.yahoo.com/group/aspartameNM/message/1480
the tobacco industry violated the Racketeer Influenced Corrupt
Organizations Act RICO law to "defraud the public." with huge amounts
of false research to mislead people about its addictive toxin, Elisa K
Tong, Stanton A Glantz, Circulation 2007 Oct. 16: Murray 2007.10.17
www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed search PubMed
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