http://groups.yahoo.com/group/aspartameNM/message/1190
study links aspartame to cancer, CBSNews.com, Daniel J Denoon,
Michael W Smith MD: Martin R Weihrauch, MD 2004 Oct, skeptical review, full
plain text; California OEHHA aspartame critique 2004.03.12: Murray 2005.07.30
[ Comments by Rich Murray are in square brackets.
Rich Murray, MA Room For All
rmforall@... 505-501-2298
1943 Otowi Road Santa Fe, New Mexico 87505 USA
http://groups.yahoo.com/group/aspartameNM/messages
group with 186 members, 1,191 posts in a public, searchable archive ]
http://annonc.oxfordjournals.org/cgi/content/full/15/10/1460 free full text
Ann Oncol. 2004 Oct; 15(10): 1460-5.
Artificial sweeteners-- do they bear a carcinogenic risk?
Weihrauch MR, Diehl V.
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany.
martin.weihrauch@...;
v.diehl@...;
Abstract
Artificial sweeteners are added to a wide variety of food, drinks, drugs and
hygiene products.
Since their introduction, the mass media have reported about potential
cancer risks,
which has contributed to undermine the public's sense of security.
It can be assumed that every citizen of Western countries uses artificial
sweeteners, knowingly or not.
A cancer-inducing activity of one of these substances would mean a health
risk to an entire population.
We performed several PubMed searches of the National Library of
Medicine for articles in English about artificial sweeteners.
These articles included 'first generation' sweeteners such as saccharin,
cyclamate and aspartame, as well as 'new generation' sweeteners such as
acesulfame-K, sucralose, alitame and neotame.
Epidemiological studies in humans did not find the bladder cancer-inducing
effects of saccharin and cyclamate that had been reported from animal
studies in rats.
Despite some rather unscientific assumptions,
there is no evidence that aspartame is carcinogenic.
Case-control studies showed an elevated relative risk of 1.3 for heavy
artificial sweetener use (no specific substances specified) of >1.7 g/day.
For new generation sweeteners, it is too early to establish any
epidemiological evidence about possible carcinogenic risks.
As many artificial sweeteners are combined in today's products,
the carcinogenic risk of a single substance is difficult to assess.
However, according to the current literature,
the possible risk of artificial sweeteners to induce cancer seems to be
negligible.
Publication Types: Review PMID: 15367404
Key words: aspartame, cancer, cyclamate, saccharin, sweeteners
Annals of Oncology 2004 15(10): 1460-1465; doi:10.1093/annonc/mdh256
© 2004 European Society for Medical Oncology
Artificial sweeteners-do they bear a carcinogenic risk?
M. R. Weihrauch* and V. Diehl
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany
* Correspondence to: Dr M. R. Weihrauch, Immunologisches Labor Haus 16,
Uniklinik Koeln, Joseph-Stelzmann-Strasse 9, 50924 Koeln, Germany.
Tel. +49-221-4784488; Fax: +49-221-4785912;
martin.weihrauch@...;
v.diehl@...;
"Aspartame entered the market in 1981 as the third artificial sweetener,
and was free of any suspicions regarding carcinogenicity."
[ In fact, at that time,the FDAs own expert Board of Inquiry voted against
approval of aspartame, due to unresolved concerns about its carcinogenicity,
and was arbitrarily overruled by the brand new Commissioner, Arthur Hull
Hayes, appointed by the new President Reagan:
http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 2000.07.10 rmforall
http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06 rmforall
http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall ]
Claim: "Animal studies showed that aspartame does not have any
cancer-inducing effects, even in very high doses [28, 29]."
[ Sources of funding are not given, nor are any possible linkages to vested
interests listed.
Both reviews are five pages long.
Is the 2004 review (in English) substantially different from the 2001 review (in
German)?
The most recent reference in the 2004 study is in 2001,
but refers to a January 1973 aspartame industry study,
which was not published in a peer-reviewed mainstream scientific journal:
32. Study E33-34 in Master file 134 on aspartame.
On file at the FDA Hearing Clerk's Office 2001.
At the end of this post I give the full text of the 3-page California OEHHA
aspartame critique 2004.03.12: Carcinogenicity Data Summary: Aspartame,
which is critical of the flawed aspartame industry study E33-34 (Searle
Laboratories, 1973), which stated:
"There is, however, some carcinogenicity concern over observations of brain
tumors in aspartame-treated rats.
Reliable animal studies have not been conducted despite the widespread human
exposure to this artificial sweetener.
Epidemiologic data provide inadequate information on which to judge
carcinogenicity....
Further epidemiologic and toxicologic studies are needed on the
carcinogenicity of this chemical.
No large epidemiological studies of carcinogenicity have been conducted."
Obviously, Weihrauch and Diehl are less than candid in their reference to this
biased study, and this in turn indicates their probable bias.
Remarkably, Weihrauch and Diehl do not mention stevia at all, although it
has been a dominant sweetener in Japan for decades,
while its safety is supported by 25 studies in the last twelve years:
http://groups.yahoo.com/group/aspartameNM/message/1179
Stevia (stevioside) is safe: Prof. Jan M.C. Geuns: Murray 2005.07.06
http://groups.yahoo.com/group/aspartameNM/message/1122
UN FAO & WHO approve Steviol glycosides as sweetener June 2004, imports to
UK no longer blocked: Martini: Murray 2004.10.17 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1084
26 stevia safety abstracts since 1993: aspartame vs stevia debate on
alt.support.diabetes, George Schmidt, OD: Murray 2004.05.25 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1164
artificial sweetener sales soar, stevia and tagatose available: Murray
2005.03.31 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1152
reply to Ferne Hudson, Tate & Lyle PLC, re Splenda (sucralose) policy:
Murray 2005.02.08 rmforall
Claim: "DNA repair assays for the evaluation of genotoxicity of substances
did not show any DNA-damaging properties for aspartame, cyclamate, saccharin,
acesulfame-K or sucralose [30]. "
Note the striking experimental evidence to the contrary for all of these
sweeteners, except acesulfame-K and stevia, reported by Yu F Sasaki's expert
team in Japan in 2002 August, summarized below, near the end of this post.
It is significant that they did not discuss or reference the seminal
experimental study by C Trocho and M Alameny in 1998 June that demonstrated
that aspartame at the low dose of 10 mg/kg for 10 days causes formaldehyde
adducts to DNA, RNA, and proteins in the cells of rats:
http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22 rmforall
So far, no aspartame toxicity studies, epidemological or experimental, have
controlled for other major simultaneous, ubiquitous sources of methanol and
formaldehyde in humans. However, the expert review of methanol
(formaldehyde, formic acid) toxicity by M Bouchard et al in 2001 makes it
clear that very little has been established about the nature and toxicity of
the substantial durable, cululative products of methanol in human tissues:
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 rmforall
Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text
Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]
http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@...
"K.H. Schulpis" <
inchildh@...> "G.J. Reclos"
reklos@... ]
****************************************************************
[ Daniel J. DeNoon in this and another article this year on aspartame
research gives candid, detailed, and balanced reportage that is unusual in
mainstream public media in the USA on this vital subject, in which adroit
vested interest PR campaigns have for decades orchestrated a prejudicial
climate, inimical to actual presentation and open discussion of the complex
strands of evidence. ]
http://www.cbsnews.com/stories/2005/07/28/health/webmd/main712605.shtml
Study Links Aspartame To Cancer July 28, 2005 (CBS)
By Daniel J. DeNoon
Reviewed by Michael W. Smith, MD
© 2005, WebMD Inc. All rights reserved.
"We cannot continue to use aspartame in 6,000 types of products, soft
drinks, yogurt, and whatever." Morando Soffritti, MD
*Are Artificial Sweeteners Safe?
*Dieticians Say Splenda is Not the Same as Sugar
(WebMD) A study of rats links low doses of aspartame -- the sweetener in
NutraSweet, Equal, and thousands of consumer products -- to leukemia and
lymphoma.
But food industry officials point out that many other studies have found no
link between aspartame and cancer.
The rats in the study were fed various doses of aspartame throughout their
lives.
In female but not male rats, lymphoma and leukemia were significantly
associated with daily aspartame doses as low as 20 milligrams (mg) per
kilogram (kg) of body weight.
And there was a trend toward these cancers at doses as low as 4 mg/kg of
body weight.
To reach a dose of 20 mg/kg, a 140-pound woman would need to drink three
cans of diet soda a day.
A 180-pound man would need to drink four cans of diet soda a day.
[ The correct figures, for 200 mg aspartame per 12 oz can, about are six and
eight cans daily, about 2 to 4 liters or quarts.
Many aspartame reactors actually have been using this much daily for years,
and often describe being addicted to it.
As little as 3.75 mg in Maxalt-MLT migraine medicine, which dissolves under
the tongue, is enough to trigger migraines;
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology
newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research
RLipton@... ]
And diet soda isn't the only source of aspartame.
The sweetener is in thousands of products, ranging from yogurt to
over-the-counter medicines.
The average person consumes about 2 or 3 mg/kg aspartame each day.
However, that figure goes way up for children and young women.
The study comes from an independent research team led by Morando Soffritti,
MD, scientific director of the European Ramazzini Foundation of Oncology and
Environmental Sciences in Bologna, Italy.
"What I am recommending is for healthy children and women -- if they do not
have diabetes -- to avoid consumer use of aspartame," Soffritti tells WebMD.
"We cannot continue to use aspartame in 6,000 types of products, soft
drinks, yogurt, and whatever."
Consumer Group Reacts
A consumer watchdog group, the Center for Science in the Public Interest,
has called for FDA action.
At a minimum, the FDA should start its own studies and warn consumers of the
potential danger, says CSPI Executive Director Michael F. Jacobson, PhD.
"The U.S. government really should analyze this study very carefully.
If it is accepted as top quality, it could lead to a ban on aspartame,"
Jacobson tells WebMD. "I think a lot of companies are going to see the
writing on the wall from this study and switch to newer artificial
sweeteners. Meanwhile, I think consumers should switch to Splenda, the
sweetener known as sucralose."
But Jacobson urges consumers not to panic.
"The risk to an individual is quite small," he says. "So people shouldn't
fear that if they have one diet soda a day they are going to develop cancer.
And I must say, the one qualm I have about the study is they found an
increased risk of cancer at such a low level of exposure. If aspartame were
that potent a carcinogen, I wonder if we wouldn't be seeing a real epidemic
of cancer."
Soffritti has presented his findings to the European Food Safety Authority.
In its 2002 review of aspartame safety, the EFSA found no cause for alarm.
It promises that the new data will get a "high priority" evaluation.
[
http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively, fairly critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references ]
"EFSA does not consider it appropriate to suggest any change in consumers'
diets relative to aspartame on the basis of the information it currently
has," the EFSA announced on July 14.
Low-Calorie Industry: No Cause for Alarm
The new findings fly in the face of all previous studies of aspartame
safety, says the Calorie Control Council, an international association
representing the low-calorie and reduced-fat food and beverage industry.
The Soffritti study findings "are not consistent with the extensive
scientific research and regulatory reviews done on aspartame," the CCC says
in a statement. "Aspartame has been used by hundreds of millions of
consumers around the world for over 20 years. With billions of man-years of
safe use, there is no indication of an association between aspartame and
cancer in humans."
The CCC points to four long-term studies on aspartame that failed to find
any relationship between aspartame and any form of cancer.
It's true that reports linking brain and breast cancer to aspartame had
little merit, says blood-cancer specialist Martin R. Weihrauch, MD, of the
University of Cologne, Germany.
Last year, Weihrauch reported on his analysis of all published studies on
artificial sweeteners in the Annals of Oncology.
"The entire stuff about brain tumors and breast cancer was really nonsense,
Weihrauch tells WebMD.
So what does he think of the new study linking aspartame to leukemia and
lymphoma?
"I think it is shocking news," he says. "However, the data have to be
carefully reviewed and the study redone. Not because of their methods,
probably they are fine. But for a study like this, which brings out data
that would make a big change in what consumers do every day, it certainly
has to be confirmed. It is worrisome."
What Happened to the Rats
Soffritti's study findings may be a first report, but the study was quite
thorough. It looked at 1,800 rats fed various doses of aspartame -- or no
aspartame at all -- from age 8 weeks until death. When the animals died, the
researchers did a thorough autopsy.
They found that:
A daily dose of 20 milligrams of aspartame per kilogram of body weight was
linked to lymphomas and leukemias in female -- but not male -- rats.
Rats that got daily doses of as little as 4 mg/kg aspartame got lymphomas
and leukemias 62% more often than those that got no aspartame, but this
finding could have been due to chance.
A few brain tumors were seen in rats fed aspartame, while those who did not
get the sweetener did not get brain tumors. But this finding, too, could
have been due to chance.
The findings are scheduled to appear in the European Journal of Oncology.
Sources:
Soffritti, M. European Journal of Oncology, 2005; vol 10.
Weihrauch, M.R. and Diehl, V. Annals of Oncology, 2004; vol 15: pp
1460-1465.
News release, Center for Science in the Public Interest.
News release, European Food Safety Authority.
News release, European Ramazzini Foundation for Oncology and Environmental
Sciences.
News release, Calorie Control Council.
FDA. The National Toxicology Program.
NutraSweet web site.
Morando Soffritti, MD, scientific director, European Ramazzini Foundation
for Oncology and Environmental Sciences, Bologna, Italy.
Michael F. Jacobson, PhD, executive director, Center for Science in the
Public Interest.
Martin R. Weihrauch, MD, research fellow, University of Cologne, Germany.
[ Molecular Tumor Biology and Tumor Immunology, University of Cologne,
Cologne, Germany.
martin.weihrauch@... ]
By Daniel J. DeNoon
Reviewed by Michael W. Smith, MD
© 2005, WebMD Inc. All rights reserved.
****************************************************************
CBSNews.com, 524 W. 57th St., New York, NY, 10019
http://groups.yahoo.com/group/aspartameNM/message/1177
diet soda (aspartame) goes with more obesity, Sharon P Fowler, University of
Texas Health Science Center, San Antonio, Daniel J. DeNoon, Charlotte E.
Grayson, MD, WebMD.com, foxnews.com 2005.06.15: related articles: Murray
2005.06.27
http://www.foxnews.com/story/0,2933,135751,00.html
Daniel J. DeNoon Senior Writer:
Daniel J. DeNoon is senior medical writer for WebMD, researching and
reporting daily news stories and health features. Before joining WebMD in
1999, he was senior editor for CW Henderson publications and a freelance
medical writer, editor, and communications consultant.
Mr. DeNoon began his career as a daily newspaper reporter. He became a
full-time medical journalist in 1985. A charter member of the International
AIDS Society, he was founding editor of the newsletters AIDSWeekly and
VaccineWeekly and is the author of AIDS Therapies, a 1,500-page encyclopedia
of AIDS treatments and vaccines.
He is the recipient of several professional awards, including a commendation
from the Centers for Disease Control for his work during the 2001-2
bioterror attacks. Mr. DeNoon earned a bachelor of arts degree in psychology
and religion from Emory University.
http://my.webmd.com/content/biography/6/1756_50215 [ photo ]
Michael W. Smith, MD Senior Medical Editor
As a senior medical editor at WebMD Health, Michael W. Smith, MD,
is the physician in charge of medical news and features.
He reviews multiple peer-reviewed journals and medical conferences in all
specialties and recommends stories to be published on WebMD Health.
In addition, Smith oversees a staff of full-time editors and writers as well
as editing and confirming medical accuracy of daily articles.
Smith graduated from Mercer University School of Medicine in Macon, Ga., in
1994 and then did his internship in internal medicine at the Medical Center
of Central Georgia in Macon.
He finished his internal medicine residency at Georgia Baptist Medical
Center in Atlanta, doing his last year as chief resident.
He became board-certified by the American Board of Internal Medicine and
then entered private practice as a primary care physician.
After almost two years of practicing in a primary care network in Atlanta,
Smith joined the staff of WebMD full-time.
****************************************************************
http://my.webmd.com/webmd_today/home/contactus.htm
Med Klin (Munich). 2001 Nov 15; 96(11): 670-5.
Erratum in:
Med Klin 2002 Mar 15;97(3):173.
[Artificial sweeteners--are they potentially carcinogenic?]
[Article in German]
Weihrauch MR, Diehl V, Bohlen H. [ Heribert Bohlen ]
Klinik I fur Innere Medizin, Universitat zu Koln.
martin.weihrauch@...;
v.diehl@...;
http://groups.yahoo.com/group/aspartameNM/message/1190
study links aspartame to cancer, CBSNews.com, Daniel J Denoon,
Michael W Smith MD: Martin R Weihrauch, MD 2004 Oct, skeptical review, full
plain text; California OEHHA aspartame critique 2004.03.12: Murray 2005.07.30
[ Comments by Rich Murray are in square brackets.
Rich Murray, MA Room For All
rmforall@... 505-501-2298
1943 Otowi Road Santa Fe, New Mexico 87505 USA
http://groups.yahoo.com/group/aspartameNM/messages
group with 186 members, 1,191 posts in a public, searchable archive ]
http://annonc.oxfordjournals.org/cgi/content/full/15/10/1460 free full text
Ann Oncol. 2004 Oct; 15(10): 1460-5.
Artificial sweeteners-- do they bear a carcinogenic risk?
Weihrauch MR, Diehl V.
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany.
martin.weihrauch@...;
v.diehl@...;
Abstract
Artificial sweeteners are added to a wide variety of food, drinks, drugs and
hygiene products.
Since their introduction, the mass media have reported about potential
cancer risks,
which has contributed to undermine the public's sense of security.
It can be assumed that every citizen of Western countries uses artificial
sweeteners, knowingly or not.
A cancer-inducing activity of one of these substances would mean a health
risk to an entire population.
We performed several PubMed searches of the National Library of
Medicine for articles in English about artificial sweeteners.
These articles included 'first generation' sweeteners such as saccharin,
cyclamate and aspartame, as well as 'new generation' sweeteners such as
acesulfame-K, sucralose, alitame and neotame.
Epidemiological studies in humans did not find the bladder cancer-inducing
effects of saccharin and cyclamate that had been reported from animal
studies in rats.
Despite some rather unscientific assumptions,
there is no evidence that aspartame is carcinogenic.
Case-control studies showed an elevated relative risk of 1.3 for heavy
artificial sweetener use (no specific substances specified) of >1.7 g/day.
For new generation sweeteners, it is too early to establish any
epidemiological evidence about possible carcinogenic risks.
As many artificial sweeteners are combined in today's products,
the carcinogenic risk of a single substance is difficult to assess.
However, according to the current literature,
the possible risk of artificial sweeteners to induce cancer seems to be
negligible.
Publication Types: Review PMID: 15367404
Key words: aspartame, cancer, cyclamate, saccharin, sweeteners
Annals of Oncology 2004 15(10): 1460-1465; doi:10.1093/annonc/mdh256
© 2004 European Society for Medical Oncology
Artificial sweeteners-do they bear a carcinogenic risk?
M. R. Weihrauch* and V. Diehl
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany
* Correspondence to: Dr M. R. Weihrauch, Immunologisches Labor Haus 16,
Uniklinik Koeln, Joseph-Stelzmann-Strasse 9, 50924 Koeln, Germany.
Tel. +49-221-4784488; Fax: +49-221-4785912;
martin.weihrauch@...;
v.diehl@...;
"Aspartame entered the market in 1981 as the third artificial sweetener,
and was free of any suspicions regarding carcinogenicity."
[ In fact, at that time,the FDAs own expert Board of Inquiry voted against
approval of aspartame, due to unresolved concerns about its carcinogenicity,
and was arbitrarily overruled by the brand new Commissioner, Arthur Hull
Hayes, appointed by the new President Reagan:
http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 2000.07.10 rmforall
http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06 rmforall
http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall ]
Claim: "Animal studies showed that aspartame does not have any
cancer-inducing effects, even in very high doses [28, 29]."
[ Sources of funding are not given, nor are any possible linkages to vested
interests listed.
Both reviews are five pages long.
Is the 2004 review (in English) substantially different from the 2001 review (in
German)?
The most recent reference in the 2004 study is in 2001,
but refers to a January 1973 aspartame industry study,
which was not published in a peer-reviewed mainstream scientific journal:
32. Study E33-34 in Master file 134 on aspartame.
On file at the FDA Hearing Clerk's Office 2001.
At the end of this post I give the full text of the 3-page California OEHHA
aspartame critique 2004.03.12: Carcinogenicity Data Summary: Aspartame,
which is critical of the flawed aspartame industry study E33-34 (Searle
Laboratories, 1973), which stated:
"There is, however, some carcinogenicity concern over observations of brain
tumors in aspartame-treated rats.
Reliable animal studies have not been conducted despite the widespread human
exposure to this artificial sweetener.
Epidemiologic data provide inadequate information on which to judge
carcinogenicity....
Further epidemiologic and toxicologic studies are needed on the
carcinogenicity of this chemical.
No large epidemiological studies of carcinogenicity have been conducted."
Obviously, Weihrauch and Diehl are less than candid in their reference to this
biased study, and this in turn indicates their probable bias.
Remarkably, Weihrauch and Diehl do not mention stevia at all, although it
has been a dominant sweetener in Japan for decades,
while its safety is supported by 25 studies in the last twelve years:
http://groups.yahoo.com/group/aspartameNM/message/1179
Stevia (stevioside) is safe: Prof. Jan M.C. Geuns: Murray 2005.07.06
http://groups.yahoo.com/group/aspartameNM/message/1122
UN FAO & WHO approve Steviol glycosides as sweetener June 2004, imports to
UK no longer blocked: Martini: Murray 2004.10.17 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1084
26 stevia safety abstracts since 1993: aspartame vs stevia debate on
alt.support.diabetes, George Schmidt, OD: Murray 2004.05.25 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1164
artificial sweetener sales soar, stevia and tagatose available: Murray
2005.03.31 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1152
reply to Ferne Hudson, Tate & Lyle PLC, re Splenda (sucralose) policy:
Murray 2005.02.08 rmforall
Claim: "DNA repair assays for the evaluation of genotoxicity of substances
did not show any DNA-damaging properties for aspartame, cyclamate, saccharin,
acesulfame-K or sucralose [30]. "
Note the striking experimental evidence to the contrary for all of these
sweeteners, except acesulfame-K and stevia, reported by Yu F Sasaki's expert
team in Japan in 2002 August, summarized below, near the end of this post.
It is significant that they did not discuss or reference the seminal
experimental study by C Trocho and M Alameny in 1998 June that demonstrated
that aspartame at the low dose of 10 mg/kg for 10 days causes formaldehyde
adducts to DNA, RNA, and proteins in the cells of rats:
http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22 rmforall
So far, no aspartame toxicity studies, epidemological or experimental, have
controlled for other major simultaneous, ubiquitous sources of methanol and
formaldehyde in humans. However, the expert review of methanol
(formaldehyde, formic acid) toxicity by M Bouchard et al in 2001 makes it
clear that very little has been established about the nature and toxicity of
the substantial durable, cululative products of methanol in human tissues:
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 rmforall
Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text
Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]
http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@...
"K.H. Schulpis" <
inchildh@...> "G.J. Reclos"
reklos@... ]
****************************************************************
[ Daniel J. DeNoon in this and another article this year on aspartame
research gives candid, detailed, and balanced reportage that is unusual in
mainstream public media in the USA on this vital subject, in which adroit
vested interest PR campaigns have for decades orchestrated a prejudicial
climate, inimical to actual presentation and open discussion of the complex
strands of evidence. ]
http://www.cbsnews.com/stories/2005/07/28/health/webmd/main712605.shtml
Study Links Aspartame To Cancer July 28, 2005 (CBS)
By Daniel J. DeNoon
Reviewed by Michael W. Smith, MD
© 2005, WebMD Inc. All rights reserved.
"We cannot continue to use aspartame in 6,000 types of products, soft
drinks, yogurt, and whatever." Morando Soffritti, MD
*Are Artificial Sweeteners Safe?
*Dieticians Say Splenda is Not the Same as Sugar
(WebMD) A study of rats links low doses of aspartame -- the sweetener in
NutraSweet, Equal, and thousands of consumer products -- to leukemia and
lymphoma.
But food industry officials point out that many other studies have found no
link between aspartame and cancer.
The rats in the study were fed various doses of aspartame throughout their
lives.
In female but not male rats, lymphoma and leukemia were significantly
associated with daily aspartame doses as low as 20 milligrams (mg) per
kilogram (kg) of body weight.
And there was a trend toward these cancers at doses as low as 4 mg/kg of
body weight.
To reach a dose of 20 mg/kg, a 140-pound woman would need to drink three
cans of diet soda a day.
A 180-pound man would need to drink four cans of diet soda a day.
[ The correct figures, for 200 mg aspartame per 12 oz can, about are six and
eight cans daily, about 2 to 4 liters or quarts.
Many aspartame reactors actually have been using this much daily for years,
and often describe being addicted to it.
As little as 3.75 mg in Maxalt-MLT migraine medicine, which dissolves under
the tongue, is enough to trigger migraines;
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology
newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research
RLipton@... ]
And diet soda isn't the only source of aspartame.
The sweetener is in thousands of products, ranging from yogurt to
over-the-counter medicines.
The average person consumes about 2 or 3 mg/kg aspartame each day.
However, that figure goes way up for children and young women.
The study comes from an independent research team led by Morando Soffritti,
MD, scientific director of the European Ramazzini Foundation of Oncology and
Environmental Sciences in Bologna, Italy.
"What I am recommending is for healthy children and women -- if they do not
have diabetes -- to avoid consumer use of aspartame," Soffritti tells WebMD.
"We cannot continue to use aspartame in 6,000 types of products, soft
drinks, yogurt, and whatever."
Consumer Group Reacts
A consumer watchdog group, the Center for Science in the Public Interest,
has called for FDA action.
At a minimum, the FDA should start its own studies and warn consumers of the
potential danger, says CSPI Executive Director Michael F. Jacobson, PhD.
"The U.S. government really should analyze this study very carefully.
If it is accepted as top quality, it could lead to a ban on aspartame,"
Jacobson tells WebMD. "I think a lot of companies are going to see the
writing on the wall from this study and switch to newer artificial
sweeteners. Meanwhile, I think consumers should switch to Splenda, the
sweetener known as sucralose."
But Jacobson urges consumers not to panic.
"The risk to an individual is quite small," he says. "So people shouldn't
fear that if they have one diet soda a day they are going to develop cancer.
And I must say, the one qualm I have about the study is they found an
increased risk of cancer at such a low level of exposure. If aspartame were
that potent a carcinogen, I wonder if we wouldn't be seeing a real epidemic
of cancer."
Soffritti has presented his findings to the European Food Safety Authority.
In its 2002 review of aspartame safety, the EFSA found no cause for alarm.
It promises that the new data will get a "high priority" evaluation.
[
http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively, fairly critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references ]
"EFSA does not consider it appropriate to suggest any change in consumers'
diets relative to aspartame on the basis of the information it currently
has," the EFSA announced on July 14.
Low-Calorie Industry: No Cause for Alarm
The new findings fly in the face of all previous studies of aspartame
safety, says the Calorie Control Council, an international association
representing the low-calorie and reduced-fat food and beverage industry.
The Soffritti study findings "are not consistent with the extensive
scientific research and regulatory reviews done on aspartame," the CCC says
in a statement. "Aspartame has been used by hundreds of millions of
consumers around the world for over 20 years. With billions of man-years of
safe use, there is no indication of an association between aspartame and
cancer in humans."
The CCC points to four long-term studies on aspartame that failed to find
any relationship between aspartame and any form of cancer.
It's true that reports linking brain and breast cancer to aspartame had
little merit, says blood-cancer specialist Martin R. Weihrauch, MD, of the
University of Cologne, Germany.
Last year, Weihrauch reported on his analysis of all published studies on
artificial sweeteners in the Annals of Oncology.
"The entire stuff about brain tumors and breast cancer was really nonsense,
Weihrauch tells WebMD.
So what does he think of the new study linking aspartame to leukemia and
lymphoma?
"I think it is shocking news," he says. "However, the data have to be
carefully reviewed and the study redone. Not because of their methods,
probably they are fine. But for a study like this, which brings out data
that would make a big change in what consumers do every day, it certainly
has to be confirmed. It is worrisome."
What Happened to the Rats
Soffritti's study findings may be a first report, but the study was quite
thorough. It looked at 1,800 rats fed various doses of aspartame -- or no
aspartame at all -- from age 8 weeks until death. When the animals died, the
researchers did a thorough autopsy.
They found that:
A daily dose of 20 milligrams of aspartame per kilogram of body weight was
linked to lymphomas and leukemias in female -- but not male -- rats.
Rats that got daily doses of as little as 4 mg/kg aspartame got lymphomas
and leukemias 62% more often than those that got no aspartame, but this
finding could have been due to chance.
A few brain tumors were seen in rats fed aspartame, while those who did not
get the sweetener did not get brain tumors. But this finding, too, could
have been due to chance.
The findings are scheduled to appear in the European Journal of Oncology.
Sources:
Soffritti, M. European Journal of Oncology, 2005; vol 10.
Weihrauch, M.R. and Diehl, V. Annals of Oncology, 2004; vol 15: pp
1460-1465.
News release, Center for Science in the Public Interest.
News release, European Food Safety Authority.
News release, European Ramazzini Foundation for Oncology and Environmental
Sciences.
News release, Calorie Control Council.
FDA. The National Toxicology Program.
NutraSweet web site.
Morando Soffritti, MD, scientific director, European Ramazzini Foundation
for Oncology and Environmental Sciences, Bologna, Italy.
Michael F. Jacobson, PhD, executive director, Center for Science in the
Public Interest.
Martin R. Weihrauch, MD, research fellow, University of Cologne, Germany.
[ Molecular Tumor Biology and Tumor Immunology, University of Cologne,
Cologne, Germany.
martin.weihrauch@... ]
By Daniel J. DeNoon
Reviewed by Michael W. Smith, MD
© 2005, WebMD Inc. All rights reserved.
****************************************************************
CBSNews.com, 524 W. 57th St., New York, NY, 10019
http://groups.yahoo.com/group/aspartameNM/message/1177
diet soda (aspartame) goes with more obesity, Sharon P Fowler, University of
Texas Health Science Center, San Antonio, Daniel J. DeNoon, Charlotte E.
Grayson, MD, WebMD.com, foxnews.com 2005.06.15: related articles: Murray
2005.06.27
http://www.foxnews.com/story/0,2933,135751,00.html
Daniel J. DeNoon Senior Writer:
Daniel J. DeNoon is senior medical writer for WebMD, researching and
reporting daily news stories and health features. Before joining WebMD in
1999, he was senior editor for CW Henderson publications and a freelance
medical writer, editor, and communications consultant.
Mr. DeNoon began his career as a daily newspaper reporter. He became a
full-time medical journalist in 1985. A charter member of the International
AIDS Society, he was founding editor of the newsletters AIDSWeekly and
VaccineWeekly and is the author of AIDS Therapies, a 1,500-page encyclopedia
of AIDS treatments and vaccines.
He is the recipient of several professional awards, including a commendation
from the Centers for Disease Control for his work during the 2001-2
bioterror attacks. Mr. DeNoon earned a bachelor of arts degree in psychology
and religion from Emory University.
http://my.webmd.com/content/biography/6/1756_50215 [ photo ]
Michael W. Smith, MD Senior Medical Editor
As a senior medical editor at WebMD Health, Michael W. Smith, MD,
is the physician in charge of medical news and features.
He reviews multiple peer-reviewed journals and medical conferences in all
specialties and recommends stories to be published on WebMD Health.
In addition, Smith oversees a staff of full-time editors and writers as well
as editing and confirming medical accuracy of daily articles.
Smith graduated from Mercer University School of Medicine in Macon, Ga., in
1994 and then did his internship in internal medicine at the Medical Center
of Central Georgia in Macon.
He finished his internal medicine residency at Georgia Baptist Medical
Center in Atlanta, doing his last year as chief resident.
He became board-certified by the American Board of Internal Medicine and
then entered private practice as a primary care physician.
After almost two years of practicing in a primary care network in Atlanta,
Smith joined the staff of WebMD full-time.
****************************************************************
http://my.webmd.com/webmd_today/home/contactus.htm
Med Klin (Munich). 2001 Nov 15; 96(11): 670-5.
Erratum in:
Med Klin 2002 Mar 15;97(3):173.
[Artificial sweeteners--are they potentially carcinogenic?]
[Article in German]
Weihrauch MR, Diehl V, Bohlen H.
Klinik I fur Innere Medizin, Universitat zu Koln.
martin.weihrauch@...;
v.diehl@...;
BACKGROUND: Artificial sweeteners have rapidly evolved over the last 20
years and are added to a broad variety of food, drinks, drugs, and hygiene
products. Since their introduction, especially mass media have reported
about potential cancer risks, which has attributed to undermine the people's
sense of security.
It can be assumed that every citizen of the western countries is using
artificial sweeteners--knowingly or not. A cancer-inducing activity of one
of these substances would mean a health risk to an entire population.
STUDIES: This article gives an overview about the most important
publications dealing with the cancerogenic potential of artificial
sweeteners.
Publication Types: Review Review, Tutorial
MeSH Terms:
Animals
Aspartame/adverse effects
Carbonated Beverages/adverse effects*
Carcinogenicity Tests
Carcinogens*
Clinical Trials
Cyclamates/adverse effects
English Abstract
Epidemiologic Studies
Humans
Rats
Risk
Saccharin/adverse effects
Sweetening Agents/adverse effects*
Substances:
Carcinogens
Cyclamates
Sweetening Agents
Aspartame
Saccharin
PMID: 11760654
Ann Hematol. 2000 Mar; 79(3): 110-3.
Poor clinical outcome of patients with Hodgkin's disease and elevated
interleukin-10 serum levels. Clinical significance of interleukin-10 serum
levels for Hodgkin's disease.
Bohlen H, Kessler M, Sextro M, Diehl V, Tesch H.
Klinik I fur Innere Medizin der Universitat zu Koln, Germany.
[ Heribert Bohlen ]
Ann Oncol. 1994 Apr; 5(4): 300-2.
CD30: cytokine-receptor, differentiation marker or a target molecule for
specific immune response?
Diehl V, Bohlen H, Wolf J. [ Heribert Bohlen ]
Publication Types: Editorial PMID: 8075025
Cancer Res. 1993 Sep 15; 53(18): 4310-4.
Cytolysis of leukemic B-cells by T-cells activated via two bispecific
antibodies. Bohlen H, Manzke O, Patel B, Moldenhauer G, Dorken B, von Fliedner
V, Diehl
V, Tesch H. [ Heribert Bohlen ]
Universitat zu Koln, Klinik I fur Innere Medizin, Germany. PMID: 7689932
Competence Network for Malignant Lymphoma, Germany
Prof. Dr. V. Diehl
v.diehl@...
http://annonc.oxfordjournals.org/cgi/content/full/15/10/1460 free full text
Ann Oncol. 2004 Oct; 15(10): 1460-5.
Artificial sweeteners--do they bear a carcinogenic risk?
Weihrauch MR, Diehl V.
Department of Internal Medicine I of the University of Cologne, Cologne,
Germany.
martin.weihrauch@...;
v.diehl@...;
Introduction
Methods
Results
Conclusions
References
Introduction
The fondness of humans for sweet foods is inborn:
studies have proved a preference for sweet-tasting nutrition in newborns
[1]. Therefore, mankind has always added sweet substances to their food.
The first recorded sweetener was honey,
which was used in the ancient cultures of Greece and China [2].
Honey was later replaced by saccharose, common sugar, which was
originally obtained from sugar cane.
During the World Wars, sugar beets were the major source of saccharose.
The first artificial sweetener was saccharin, which was synthesized in 1879
by Remsen and Fahlberg.
It was well accepted during World Wars I and II because of its low
production costs and the shortcoming of regular sugar [2].
As economies recovered and living standards increased after the wars,
sugar became affordable.
With a growing candy and fast food industry,
obesity increased in the Western societies, as we know today from our daily
clinical practice.
Since the 1950s, the reasons for using saccharin have shifted from cost to
calorie reduction.
A profitable market for calorie-reduced 'diet products' evolved, in which
sugar was substituted or supplemented with artificial sweeteners.
However, saccharin was known not only for its extreme sweetness,
but also for its bitter aftertaste,
so that there was a growing need
for new improved taste, calorie-reduced substances.
A breakthrough in the artificial sweetener industry was achieved with
cyclamate in the 1950s, which provided a better taste than saccharin.
In addition, it blended very well with saccharin.
Both substances were mixed together with other additives and were sold as
'Sweet'n'Low', which became a huge success in the USA.
Because of its characteristics, cyclamate was not only used in tablet or
liquid form ('table top sweetener'),
but also proved suitable for sweetening soft drinks.
The first insecurity shook the artificial sweetener market in 1970, when the
Food and Drug Administration (FDA) banned cyclamate from all dietary foods
and fruits in the USA.
The FDA had become suspicious of induced cancer in experimental animals [3].
In all other countries, cyclamate is still used today, especially in
combination with other sweeteners.
The next step in the development of artificial sweeteners was the approval
of aspartame in 1981 and its marketing as 'NutraSweet'.
For the first time, dairy products such as yogurts were calorie-reduced and
could be sold with the prefixes 'diet' or 'light' [4].
The first three substances, saccharin, cyclamate and aspartame, are referred
to as 'first generation sweeteners'.
These were followed by new generation or second generation sweeteners such as
acesulfame-K, sucralose, alitame and neotame, which have quite different key
market areas, as shown in Table 1 (from Lindley [4]).
However, even the new sweeteners have similar limitations to the older ones.
The taste is often accompanied by a bitter and metallic aftertaste
and does not provide the 'realistic' and 'voluminous' mouthfeel of regular
sugar.
The combination of many, synergic artificial sweeteners has led to an
improvement of the quality of sweetened products.
In soft drinks, a combination of acesulfame-K, aspartame and others has
found broad application (as shown in Figure 1).
View this table:
[in this window]
[in a new window]
Table 1. Current artificial sweeteners and their key market areas (taken
from Lindley [4])
View larger version (36K):
[in this window]
[in a new window]
Figure 1. Two product labels of a diet soda, taken from the USA (A) and
Germany (B). In the USA, only aspartame is used in this soda, whereas the
same product is sold in Germany with an artificial sweetener combination of
cyclamate, acesulfame-K and aspartame.
Today, many people have mixed feelings when using artificial sweeteners,
because they associate news about possible cancer risks with these substances.
Particularly in the 1980s,
when many sweeteners were newly synthesized and introduced to the food
market, the public press reported on the ostensible carcinogenic effects of
sweeteners.
News articles frequently lacked a fundamental scientific background or were
inattentively investigated, and added to a public insecurity.
Even some of the scientific publications in reliable medical journals, which
caught media attention, were not well researched, and ignored common
statistical knowledge as described later.
During the last decade, the cancer-inducing effect of artificial sweeteners
has not been discussed as frequently as in earlier years, although some of
the long-term studies about saccharin and cyclamate have recently been
completed and published.
Methods
Several PubMed searches of the National Library of Medicine were performed.
Relevant preclinical, clinical and epidemiological studies on artificial
sweeteners and possible health risks were identified.
All searches focused on English language journals only, but were not limited
to a certain period of time.
Where appropriate, cited references of articles were also reviewed.
Key words for the PubMed search included 'artificial sweetener', 'cancer'
and 'carcinogenic', as well as all artificial sweetener names.
To present an overview, the studies were sorted by the investigated
artificial sweetener, and will be discussed separately.
Results
Saccharin
Saccharin is the oldest chemical sugar substitute and the best researched of
all sweeteners.
More than 50 studies have been published about saccharin in laboratory rats.
Approximately 20 study groups analyzed the effect of saccharin in one generation
of rats, which were exposed to high doses of saccharin for at least 1.5 years.
Usually, the doses administered included a high concentration
of 5% of the various forms of saccharin in the diet, and
in several cases, animals started the study at 6 weeks of age.
Except for one study, none of the 20 groups found significantly more
neoplasias in the saccharin-fed animals than in controls.
The positive study reported an increased incidence of bladder cancers [5].
However, ACI rats were used in this trial, which are frequently infected
with the bladder parasite Trichosomoides crassicanda and are therefore
susceptible to saccharin-induced bladder cell proliferation [6].
After many 'one generation' studies, 'two generation' studies were conducted
feeding the parent (F0) and the following generation (F1) with saccharin.
In these studies, an increased risk for bladder cancer could be consistently
proven for the F1 generation.
Taylor et al. [7] showed that especially male rats developed bladder tumors
in up to 30% of all animals at a dose of 7.5% saccharin of their diet.
Later trials, the largest with 2500 F1 generation rats [8], found that the
risk for bladder cancers increases with a saccharin concentration of 4%.
Because of these results, saccharin was prohibited in Canada.
In the USA, since 1981, saccharin-containing products have had to be
labeled with a warning that saccharin can cause cancer in laboratory
animals.
However, the National Institute for Environmental Health Sciences,
which issues a biannual report, removed saccharin as a potential
cancer-causing agent, because it could be shown that the cancer-inducing
mechanisms in rats do not apply in humans.
Ascorbic acid (vitamin C), when fed in similar doses as saccharin, could
also cause bladder cancer in rats;
this could be prevented by adding prophylactic ammonium chloride.
Rodents have a high urine osmolarity,
which enhances the precipitation of calciumphosphate-containing crystals,
which are cytotoxic to the superficial layer of the bladder epithelium,
leading to regenerative hyperplasia and tumors [9].
Takayama et al. [10] in 1998 published a long-term study on 20 monkeys,
of three species, that were treated with sodium saccharin (25 mg in the diet/kg
daily for 5 days a week) for up to 24 years.
Sixteen monkeys served as controls.
None of the animals developed bladder cancer or urothelial proliferations.
The study was criticized for the small number of monkeys and for the
relatively low dosage of saccharin, which corresponds to a daily diet-soda
consumption of 1.5 L in a 70-kg person [11].
The first studies about the cancerogenous risk of saccharin in humans were
only of descriptive design.
In the UK, a longitudinal study did not show an increase in bladder cancer
incidence during World War II, when saccharin consumption was high [12].
The same authors analyzed 19,709 death certificates from the UK between 1966
and 1972 and compared the bladder cancer mortality between diabetics,
who used artificial sweeteners more frequently, and non-diabetics.
They did not find any significant differences between the groups [13].
A Danish study could not detect an increase of bladder cancer mortality in
people aged up to 30 years old, who were born between 1941 and 1945,
when saccharin use was higher than in the years before and after [14].
The authors concluded that an exposition to saccharin in utero does not
increase bladder cancer incidence during the first three decades of life.
A case-control study from China published in 1997 analyzed different risk
factors in 254 bladder cancer patients and 254 controls [15].
They reported an odd ratio of 3.9 for bladder cancer in patients with
frequent saccharin use of at least 19 consumptions per year for at least 15
years.
However, this study has to be critically assessed as to its worth,
because it was unable to identify the elevated risk of bladder cancer in
smokers,
which was proven by other large trials [16-18].
There are many case-control studies
from the USA and Europe about bladder cancer risk factors,
which not only investigate saccharin as a possible cause,
but also the use of artificial sweeteners in general.
Therefore, they will be discussed later in this review.
Cyclamate
Sodium cyclamate entered the US market after its FDA approval in 1951 [19].
Owing to a study by Wagner in 1970 [20],
which found an increased incidence of bladder carcinomas in rats,
the use of cyclamate was prohibited in several countries,
including the USA and UK.
Further evaluations by the Cancer Assessment Committee of the Center for
Food Safety and Applied Nutrition of the FDA, by the Scientific Committee
for Foods of the European Union and by the WHO concluded that cyclamate is
not a carcinogen, and readmitted it to the food market [21].
Cyclamate is converted to a metabolite, cyclohexylamine, which has been
reported to be rather toxic [22].
In experiments with rats and dogs, cyclohexylamine caused testicular atrophy
and impairment of spermatogenesis [23-26].
Takayama et al. [21] conducted a long-term toxicity study with cyclamate in
non-human primates, as described before for saccharin.
Twenty-one monkeys were fed either 100 or 500 mg/kg cyclamate per day over
24 years, and compared with 16 controls.
A dose of 500 mg/kg corresponds to 30 calorie-reduced drinks.
In 1994, after 24 years, the remaining 14 cyclamate and 16 control monkeys
were killed and autopsied.
In the cyclamate group, three animals showed malignancies,
whereas none were found in the controls.
The tumor stages and histologies of the cancers were a metastatic
adenocarcinoma of the colon (500 mg/kg),
a metastatic hepatocellular carcinoma (500 mg/kg) and
a local well-differentiated papillary adenocarcinoma of the prostate (100
mg/kg).
In addition, three benign tumors were found in the treatment group,
an adenoma of the thyroid gland and
two leiomyoma of the uterus,
whereas the control group remained free of tumors.
The authors concluded that there is no evidence for carcinogenicity of
sodium cyclamate,
because the tumors in the treatment groups were of different histologies and
the tumors occurred at a rate frequently observed in monkeys.
In particular, no bladder carcinomas were reported as in the rat study,
which had led to the ban of cyclamates.
The trial of Takayama et al. [21] was critcized for the small number of
animals, which was too low to reach any significance or to confirm a
negative result [27].
In addition, the critics claimed that the tumor incidence in the treatment
group (33%) was higher than the spontaneous neoplasia rate in respective
monkey strains,
and unlikely to be a chance occurrence.
There are no descriptive or case-control studies of cyclamate in humans,
because it was approved after saccharin, and products contained mixtures of
both artificial sweeteners.
It has to be assumed that most consumers have used both saccharin and
cyclamate since the introduction of cyclamate.
Aspartame [ see beginning of this post ]
Aspartame entered the market in 1981 as the third artificial sweetener,
and was free of any suspicions regarding carcinogenicity.
Animal studies showed that aspartame does not have any cancer-inducing
effects, even in very high doses [28, 29].
DNA repair assays for the evaluation of genotoxicity of substances did not
show any DNA-damaging properties for aspartame, cyclamate, saccharin,
acesulfame-K or sucralose [30].
[ Note the experimental evidence to the contrary for all of these except
acesulfame-K and stevia, reported by Yu F Sasaki's expert team in 2002
August, summarized below near the end of this post. ]
Fifteen years after the approval of aspartame, the Journal of Neuropathology
and Experimental Neurology published an article by Olney et al. [31] with
the title:
'Increasing brain tumor rates: Is there a link to aspartame?', which
received tremendous attention from the mass media, as well as the scientific
community.
The authors hypothesized that the increasing rate of brain tumors in humans
since 1980 could possibly be explained by the introduction of aspartame.
They supported their hypothesis with an FDA trial in 320 Sprague-Dawley
rats. Twelve rats developed malignant brain tumors after receiving an
aspartame-containing feed for 2 years [32].
They argued that another trial had shown that the aspartame molecule
acquires mutagenic activity when nitrosated [33].
The publication of Olney et al. [31] led to heavy criticism of the
scientific community, whereas the laymen press suggested abstaining from
aspartame-sweetened products [34].
In an editorial, Ross [35] demonstrated the weaknesses of the Olney study.
He explained that Olney et al. [31] linked two events that incidentally
occurred during roughly the same time period: the increase of brain tumors
and the introduction of aspartame.
This correlation is not admissible in epidemiology, and is called
'ecological fallacy'. There was no information available regarding whether
the individuals who developed brain tumors consumed aspartame.
As Ross states, one might also invoke home computers, VCR usage or the
depletion of the ozone layer to argue trends in brain tumors.
In addition, the introduction of aspartame and the rising brain tumor rate
occurred almost simultaneously.
For the development of brain tumors, a certain latency would have been
required.
The study that showed an increased brain tumor incidence in aspartame-fed
rats, which gave rise to the argument of Olney et al.,
could not be confirmed by later trials [36].
Ross [35] suggested evaluating the link between aspartame exposure and brain
tumors in a case-control or cohort study.
Indeed, a case-control study on aspartame consumption was conducted in
children with brain tumors [37].
The study group compared 56 patients with 94 controls in terms of aspartame
use and other known and suspected risk factors, such as maternal vitamin
consumption, cured meat intake, passive smoke exposure, X-ray exposure and
family history of brain cancer.
They observed no elevated brain tumor risk to the child
from maternal consumption of aspartame during pregnany,
nor did they find elevated risks during any trimester of pregnancy
or during breast-feeding.
[ As usual, this study did not control for such such relevant methanol
(formaldehyde) sources as dark wines and liquors, high levels of fruits and
vegetables, or common residential indoor sources. ]
After the questionable study of Olney et al. [31], Schwartz [38] wrote a
letter to the Western Journal of Medicine, which was published in 1999.
Schwartz hypothesized a link between aspartame and the increase of breast
cancer. He argued that aspartame is partly metabolized to methanol, which
itself is converted to formaldehyde,
which accumulates within cells and induces cancer [39].
In the same issue of the journal, Tichopoulos [40] responded to the letter.
He explained that the increase of the breast cancer rate occurred before the
introduction of aspartame, and has been declining during the last few years
[39, 41]. He concluded that Schwartz also succumbed to an ecological fallacy.
New generation sweeteners
Except for the toxicological animal data required for FDA approval, there
are no larger studies that investigate the potentially hazardous effects of
second generation sweeteners.
None of the substances such as acesulfame-K, neohisperidine, alitame or
sucralose has been suspected to cause cancer or to be genotoxic.
Epidemiological studies in humans
After cyclamate and aspartame had entered the food market, diseases such as
bladder cancer could not be linked to the consumption of saccharin alone,
because most consumers used different artificial sweeteners.
Also, substances were mixed in food products to improve the taste.
Therefore, most epidemiological studies in humans relate to sweetener
consumption in general, and not to single substances.
The most important publications in this field are case-control studies.
Many of these trials were conducted with small patient groups of up to 350
bladder cancer patients in the years 1965-1986 [42-46].
None of them showed a significantly increased risk of bladder carcinoma for
artificial sweetener use.
A study from the UK [47] included 622 existing and 219 new cases of bladder
cancer, and matched them to hospital-based controls for age and sex.
The study group found an increased relative risk (RR) for non-smoking males
[RR 2.2; 95% confidence interval (CI) 1.3-3.8] and
non-smoking females (RR 1.6; 95% CI 0.8-3.2),
but not for smokers.
Sweetener use was defined as regular use for over 1 year at
least 5 years prior to diagnosis.
The most recent case-control study was published by Sturgeon et al. [48]
with 1860 bladder cancer patients and 3934 controls.
They examined different factors,
among which were smoking, urinary tract infection, coffee consumption,
history of cystolithiasis and genetic predisposition for the risk of
inducing bladder cancer.
Artificial sweetener consumption was classified as
'low' (<1680 mg per day) or 'heavy' (>1680 mg per day).
The risk of bladder cancer was not associated with low sweetener use
in 966 patients and 3410 controls.
Heavy sweetener consumption (31 patients, 78 controls) led to a
significantly increased RR of 1.3 (95% CI 0.9-2.1).
Also, high coffee consumption of >50 cups per week was associated with an RR
of 1.4, and therefore was comparable to heavy artificial sweetener use or
the history of one to two urinary tract infections (RR 1.3).
The authors scrutinized the bladder cancer histologies.
Heavy artificial sweetener use was associated with higher grade, poorly
differentiated tumors.
Conclusions
Owing to the existing studies, the following statements can be made about
the carcinogenic potential of artificial sweeteners.
Saccharin induces bladder cancer in rats, when fed in high doses.
However, rodents react to most sodium salts, such as sodium ascorbate, with
urothel proliferation and neoplasia of the bladder.
Heavy artificial sweetener use (>1680 mg per day) leads to an increased
relative risk of 1.3 for bladder cancer in humans.
A more precise determination of the exact agents is not possible, because
many artificial sweeteners are combined in current food products.
Despite unscientific articles in the mass media and scientific press, there
is no evidence that the artificial sweetener aspartame bears a carcinogenic
risk.
The approvals of new generation sweeteners (acesulfame-K, sucralose, alitame
and neotame) are too recent to establish any epidemiological evidence about
possible carcinogenic risks.
Received for publication June 12, 2003. Accepted for publication January 6,
2004.
References
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IRDC two-generation bioassay of sodium saccharin.
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sodium ascorbate in male rats. Cancer Res 1998; 58: 2557-2561.[Abstract]
10. Takayama S, Sieber SM, Adamson RH et al. Long-term feeding of sodium
saccharin to nonhuman primates: implications for urinary tract cancer.
J Natl Cancer Inst 1998; 90: 19-25.[Abstract/Free Full Text]
11. Jacobson MF, Farber E, Clapp R. Re: Long-term feeding of sodium
saccharin to nonhuman primates: implications for urinary tract cancer.
J Natl Cancer Inst 1998; 90: 934-936.[Free Full Text]
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relation to cigarette smoking and saccharin consumption.
Br J Prev Soc Med 1974; 28: 233-240.[ISI][Medline]
13. Armstrong B, Doll R. Bladder cancer mortality in diabetics in relation
to saccharin consumption and smoking habits.
Br J Prev Soc Med 1975; 29: 73-81.[ISI][Medline]
14. Jensen OM, Kamby C. Intra-uterine exposure to saccharin and risk of
bladder cancer in man. Int J Cancer 1982; 29: 507-509.[ISI][Medline]
15. Yu Y, Hu J, Wang PP et al. Risk factors for bladder cancer: a
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Eur J Cancer Prev 1997; 6: 363-369.[ISI][Medline]
16. Brennan P, Bogillot O, Cordier S et al. Cigarette smoking and bladder
cancer in men: a pooled analysis of 11 case-control studies.
Int J Cancer 2000; 86: 289-294.[CrossRef][ISI][Medline]
17. Mikhailidis DP, Ganotakis ES, Papadakis JA, Jeremy JY. Smoking and
urological disease. J R Soc Health 1998; 118: 210-212.[ISI][Medline]
18. Teschke K, van Zwieten L. Perceptions of the causes of bladder cancer,
nasal cancer, and mesothelioma among cases and population controls.
Appl Occup Environ Hyg 1999; 14: 819-826.[CrossRef][Medline]
19. Bopp BA, Sonders RC, Kesterson JW. Toxicological aspects of cyclamate
and cyclohexylamine. Crit Rev Toxicol 1986; 16: 213-306.[Medline]
20. Wagner MW. Cyclamate acceptance. Science 1970; 168: 1605.[Medline]
21. Takayama S, Renwick AG, Johansson SL et al. Long-term toxicity and
carcinogenicity study of cyclamate in nonhuman primates.
Toxicol Sci 2000; 53: 33-39.[Abstract/Free Full Text]
22. Renwick AG. The metabolism of intense sweeteners.
Xenobiotica 1986; 16: 1057-1071.[ISI][Medline]
23. Gaunt IF, Sharratt M, Grasso P et al. Short-term toxicity of
cyclohexylamine hydrochloride in the rat.
Food Cosmet Toxicol 1974; 12: 609-624.[CrossRef][ISI][Medline]
24. James RW, Heywood R, Crook D. Testicular responses of rats and dogs to
cyclohexylamine overdosage.
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25. Roberts A, Renwick AG. The pharmacokinetics and tissue concentrations of
cyclohexylamine in rats and mice.
Toxicol Appl Pharmacol 1989; 98: 230-242.[ISI][Medline]
26. Roberts A, Renwick AG, Ford G et al. The metabolism and testicular
toxicity of cyclohexylamine in rats and mice during chronic dietary
administration. Toxicol Appl Pharmacol 1989; 98: 216-229.[ISI][Medline]
27. Huff J, Tomatis L. Re: Long-term toxicity and carcinogenicity study of
cyclamate in nonhuman primates (Takayama.Toxicol Sci. 53, 33-39).
Toxicol Sci 2000; 57: 186.[Free Full Text]
28. Hagiwara A, Fukushima S, Kitaori M et al. Effects of three sweeteners on
rat urinary bladder carcinogenesis initiated by
N-butyl-N-(4-hydroxybutyl)-nitrosamine.
Gann 1984; 75: 763-768.[ISI][Medline]
29. Ishii H. Incidence of brain tumors in rats fed aspartame.
Toxicol Lett 1981; 7: 433-437.[CrossRef][ISI][Medline]
30. Jeffrey AM, Williams GM. Lack of DNA-damaging activity of five
non-nutritive sweeteners in the rat hepatocyte/DNA repair assay.
Food Chem Toxicol 2000; 38: 335-338.[CrossRef][ISI][Medline]
31. Olney JW, Farber NB, Spitznagel E, Robins LN. Increasing brain tumor
rates: is there a link to aspartame?
J Neuropathol Exp Neurol 1996; 55: 1115-1123.[ISI][Medline]
32. Study E33-34 in Master file 134 on aspartame.
On file at the FDA Hearing Clerk's Office 2001.
33. Shephard SE, Wakabayashi K, Nagao M. Mutagenic activity of peptides and
the artificial sweetener aspartame after nitrosation.
Food Chem Toxicol 1993; 31: 323-329.[CrossRef][ISI][Medline]
34. Schwabe U. Health risk caused by sugar substitutes.
Internist (Berl) 1998; 39: 869.[Medline]
35. Ross JA. Brain tumors and artificial sweeteners? A lesson on not getting
soured on epidemiology.
Med Pediatr Oncol 1998; 30: 7-8.[CrossRef][ISI][Medline]
36. Anonymous. Aspartame. Review of safety issues. Council on Scientific
Affairs. JAMA 1985; 254: 400-402.[Abstract]
37. Gurney JG, Pogoda JM, Holly EA. Aspartame consumption in relation to
childhood brain tumor risk: results from a case-control study [published
erratum appears in J Natl Cancer Inst 1997; 89: 1460].
Natl Cancer Inst 1997; 89: 1072-1074.[Free Full Text]
38. Schwartz GR. Aspartame and breast and other cancers
[published erratum appears in West J Med 2000; 172: 233].
West J Med 1999; 171: 300-301.[ISI][Medline]
39. Adami HO, Signorello LB, Trichopoulos D. Towards an understanding of
breast cancer etiology. Semin Cancer Biol 1998; 8: 255-262.[ISI][Medline]
40. Trichopoulos D. Response. West J Med 1999; 171: 301.[ISI][Medline]
41. Chu KC, Tarone RE, Kessler LG et al. Recent trends in U.S. breast cancer
incidence, survival, and mortality rates.
J Natl Cancer Inst 1996; 88: 1571-1579.[Abstract/Free Full Text]
42. Simon D, Yen S, Cole P. Coffee drinking and cancer of the lower urinary
tract. J Natl Cancer Inst 1975; 54: 587-591.[ISI][Medline]
43. Wynder EL, Goldsmith R. The epidemiology of bladder cancer: a second
look. Cancer 1977; 40: 1246-1268.[ISI][Medline]
44. Wynder EL, Stellman SD. Artificial sweetener use and bladder cancer: a
case-control study. Science 1980; 207: 1214-1216.[ISI][Medline]
45. Morrison AS, Buring JE. Artificial sweeteners and cancer of the lower
urinary tract. N Engl J Med 1980; 302: 537-541.[Abstract]
46. Piper JM, Matanoski GM, Tonascia J. Bladder cancer in young women.
Am J Epidemiol 1986; 123: 1033-1042.[Abstract]
47. Cartwright RA, Adib R, Glashan R, Gray BK. The epidemiology of bladder
cancer in West Yorkshire. A preliminary report on non-occupational
aetiologies. Carcinogenesis 1981; 2: 343-347.[ISI][Medline]
48. Sturgeon SR, Hartge P, Silverman DT et al. Associations between bladder
cancer risk factors and tumor stage and grade at diagnosis. Epidemiology
1994; 5: 218-225.[ISI][Medline]
****************************************************************
"The PBOI also considered historical background incidence of brain tumors in
interpreting the study findings, and concluded that the available data did
not rule out the possibility that aspartame might induce brain tumors (FDA
Commissioner, 1981)."
http://www.oehha.ca.gov/prop65/docs_state/crnrbatch4final45.html#get
[ California ] OEHHA
Office of Environmental Health Hazard Assessment
Proposition 65 - Prioritization Notices
Availability of Final Data Summaries and Priorities for Chemicals With
Respect to Their Evaluation by the OEHHA Science Advisory Board's Carcinogen
Identification Committee [03/12/04]
Cynthia Oshita
coshita@... Subject: batch 4 priorities
Office of Environmental Health Hazard Assessment
P.O. Box 4010 Sacramento, California 95812-4010
FAX: (916) 323-8803 Telephone: (916) 445-6900
http://www.oehha.ca.gov/prop65/docs_state/pdf/bat4final45sums.pdf
Final prioritized candidate chemicals under consideration for carcinogenicity
evaluation: forty-five batch #4 chemicals
Office of Environmental Health Hazard Assessment
California Environmental Protection Agency March 2004
On October 17, 2003, OEHHA announced the release of draft priority
assignments and draft data summaries for 47 of 50 chemicals ("Batch 4")
selected for prioritization with respect to their potential to cause cancer.
Final priority assignments and data summaries for 45 of the 47
chemicals for which draft priorities had been assigned are presented here.
BATCH #4 PRIORITIZED CHEMICALS FINAL MARCH 2004 page 35
CARCINOGENICITY DATA SUMMARY: ASPARTAME
Preliminary evaluation of carcinogenicity and exposure data
Aspartame [Equal®; NutraSweet®; L-aspartyl-L-phenylalanine methyl ester; CAS
No. 22839-47-0] did not reach a level of carcinogenicity concern sufficient
to be placed on the candidate list.
There is, however, some carcinogenicity concern over observations of brain
tumors in aspartame-treated rats.
Reliable animal studies have not been conducted despite the widespread human
exposure to this artificial sweetener.
Epidemiologic data provide inadequate information on which to judge
carcinogenicity.
One small epidemiologic study found no evidence of an effect of aspartame
consumption on brain tumor risk in children.
Aspartame has been suggested as an explanation for increased rates of human
brain cancer.
Further epidemiologic and toxicologic studies are needed on the
carcinogenicity of this chemical.
No large epidemiological studies of carcinogenicity have been conducted.
Olney et al. (1996), performing a descriptive analysis of national cancer
data, suggested the possibility that aspartame might be associated with
increased incidence of brain tumors in the U.S.
A small study (Gurney et al., 1997) of aspartame consumption in children and
brain tumor risk found no evidence that cases (n=56) were more likely to
consume foods containing aspartame than controls (n=90).
There have been multiple carcinogenicity studies of aspartame in animals,
each of which is inadequate for judging carcinogenicity.
[ The 2005 Remazzini study used doses of 0, 0.004, 0.020, 0.100, 0.500,
2.500, and 5.000 grams per kilogram body weight = g/kg ]
Searle Laboratories has conducted two sets of studies in rats.
In the first set, referred to as Study E-33/34, female and male Charles
River CD Sprague-Dawley albino rats were fed 0, 1, 2, 4, or 8 g/kg aspartame
daily for 104 weeks.
In female rats, one 4 g/kg dose animal was observed with brain tumor
(ependymoma) and three high dose females were (2 meningioma, 1 glioma)
(Searle Laboratories, 1973).
The brain tumor incidences in the Searle Laboratories (1973) report (number
of tumors/number of animals examined) in the 0, 1, 2, 4, and 8 g/kg females
were 0/59, 0/4, 0/4,1/4, 3/39, respectively, a statistically significant
increase with increasing dose (p = 0.0206,
Fisher Exact trend test; p = 0.0167, Cochran-Armitage trend test).
In male rats, one brain tumor, a meningioma, was observed in the high dose
group.
The incidences were: 0/58, 0/4, 0/3, 0/1, 1/40 (Searle Laboratories, 1973).
Searle Laboratories (1973) reported that these findings were not
statistically significant (although Fisher Exact trend test for females
indicates otherwise).
The FDA Commissioner (1981) noted "variations in tumor count among the
several persons or groups who viewed the slides."
The FDA's Public Board of Inquiry (PBOI) reported the following brain tumors
incidences (number of tumors/"total number of animals at risk"):
females, 0/59, 2/40, 0/40, 1/40, 2/38;
males, 1/59, 2/40, 0/40, 1/40, 2/38.
These data, as reported by the PBOI, do not reflect the limited numbers of
animals examined for brain histopathology in the low-, mid-, and
midhigh-dose groups of both sexes,
nor do these data reflect a significant increase in brain tumors with
increasing dose in females.
The PBOI expressed concern over the early occurrence of brain tumors in some
animals (FDA Commissioner, 1981).
There was disagreement among examining pathologists as to the positive
finding in the male control group, with one of three finding no tumor (FDA
Commissioner, 1981).
The PBOI also considered historical background incidence of brain tumors in
interpreting the study findings, and concluded that the available data did
not rule out the possibility that aspartame might induce brain tumors (FDA
Commissioner, 1981).
In the second set of Searle Laboratory studies, referred to as study E-70,
aspartame was fed to female Charles River Sprague-Dawley rat dams during
pregnancy and lactation and to their offspring after weaning for 104 weeks.
Daily dose levels were 0, 2, and 4 g/kg.
Five of 160 aspartame-fed rats and four of 120 controls were reported with
brain tumors.
Hyperplastic liver nodules were increased in treated females.
An FDA review panel concluded that Searle Laboratories did not employ a feed
analysis program to monitor their incorporation of test compound into feed.
FDA's PBOI (Nauta et al., 1980) considered this a deficient study (FDA
Commissioner, 1981).
Ishii (1981) fed groups of SCL Wistar rats 0, 1, 2 or 4 g/kg aspartame,
or 4 gm/kg aspartame + diketopiperazine (DKP) (3:1)
for 104 weeks and evaluated brain tumorigenicity.
Interim sacrifice included 10 animals/sex/group at
26 weeks and 16 animals/sex/group at 52 weeks.
No brain tumors were observed in the interim sacrifice animals.
Total number of animals in the main groups was 60 sex/group; the number
surviving to 104 weeks was reduced in some groups to as few as 16 (1 g/kg
males),
and in all groups was less than 30 in males and lower in males than females.
Among females, one control had an "atypical astrocytoma"; two brain tumors
were found at 2 g/kg (1 astrocytoma, 1 ependymoma) and one at 4 g/kg
(oligodendroglioma).
In males, one treated at 1 mg/kg was found with oligodendroglioma and one at
4 g/kg with astrocytoma.
Studies in mice fed aspartame in diet found no indication of increased tumor
incidence (FDA Commissioner, 1981).
Details of study results have not been published.
BATCH #4 PRIORITIZED CHEMICALS FINAL MARCH 2004 page 36
The National Toxicology Program (NTP, 2003a) has conducted non-standard
bioassays in both sexes of genetically altered (p53 haploinsufficent) mice.
Animals in groups of 15 were fed aspartame for nine months at feed
concentrations ranging from 3,125 to 50,000 ppm.
There was no evidence of treated-related carcinogenicity.
This provides limited information on the potential for aspartame to induce
cancer in humans; group sizes were small and the use of the genetically
altered mouse is a new model.
Thus, there is uncertainty as to whether the study possessed sufficient
sensitivity to detect a carcinogenic effect (NTP, 2003b).
Aspartame breaks down spontaneously to diketopiperazine (DKP), which
normally comprises less than 2% of the final aspartame product (FDA
Commissioner, 1981).
DKP was tested for brain tumorigenic activity in Sprague-Dawley rats fed DKP
for 115 weeks (FDA Commissioner, 1981), in a study referred to as E-77/78,
at doses of 0, 0.75, 1.5, and 3.0 g/kg.
No increased incidence of brain tumors compared to untreated rats was observed.
An FDA inspection team investigated the laboratory carrying out this study
and found irregularities that included evidence of improper feed mixing (the
chow was ground to a fine powder, but the DKP was present in large chunks),
which may have allowed the rats to avoid eating the DKP (Bressler, 1977).
The team also noted methodological quality control issues that could impact
on the study findings.
The promoting potential of aspartame on urinary bladder carcinogenesis,
initiated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), was studied in
male F344 rats who received 0.01% BBN in drinking water for four weeks
followed by 5% aspartame in the diet for 32 weeks (total aspartame intake,
400 gm/kg).
The incidences of bladder lesions were not increased in the 28 rats
surviving to the end of the experiment, 36 weeks (Hagiwara et al., 1984).
Aspartame was not mutagenic in TA 100 and TA 98 Salmonella tester strains
(Shephard et al., 1993).
Aspartame, nitrosated in vitro (to simulate the nitrosation that occurs in
the stomach), was mutagenic towards TA100, TA104, and TA98 without metabolic
activation, but not toward TA102 (Shephard et al., 1993).
Aspartame was not clastogenic, in vivo, in mice (Durnev et al., 1995).
Jeffrey and Williams (2000) reported that aspartame in vitro did not induce
DNA synthesis in rat hepatocytes.
Mukhopadhyay et al. (2000) report in vivo co-exposure of aspartame and
acesulfame potassium was negative for the induction of chromosome
aberrations in male Swiss mice bone marrow cells.
Aspartame adducts were found in nucleic acids and proteins from
aspartame-fed rats, and the authors concluded aspartame-derived formaldehyde
was responsible for adduct formation (Trocho et al., 1998).
There is a HIGH level of concern over the extent of exposure to aspartame.
Aspartame is a low-calorie sweetener, first approved in 1981, currently
consumed by more than 100 million people around the world (Calorie Control
Council, 2002).
In the U.S., aspartame is available for use in more than 1500 products,
including table-top sweeteners, carbonated beverages, baked goods, chewable
multi-vitamins, hot and cold breakfast cereals, chewing gum, puddings and
fillings, candies, cough drops, pharmaceuticals, and many other products
(Calorie Control Council, 2002).
The "acceptable daily intake" of aspartame, established by FDA, is 50 mg/kg;
a food intake survey conducted by U.S. Department of Agriculture found some
people in the U.S. consumed more than 16 mg/kg/day (Butchko et al., 1994).
References
Bressler J (1977). FDA field inspection report pertaining to E-77-78,
Diketopiperazine 2-year rat feeding study.
Submitted to FDA Bureau of Foods, August 1977.
Butchko HH, Tschanz C, Kotsonis FN (1994). Postmarketing surveillance of
food additives. Reg Tox Pharm 20: 105-118.
[
http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 2002.12.09 rmforall ]
Calorie Control Council (2002). Low-Calorie Sweeteners: Aspartame. Available
at: www.caloriecontrol.org/aspartame.html.
Durnev AD, Oreshchenko AV, Kulakova AV, Berensten NF, Seredenin SB (1995).
Clastogenic activity of dietary sugar substitutes.
Voprosy Meditscinskoi Icimii 41(4): 31-33.
FDA Commissioner (1981). Aspartame: Commissioner's Final Decision.
Department of Health and Human Services, Public Health Service, Food and
Drug Administration. Docket No. 75F-0355. 46 Fed Reg 38285: 471-523.
Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S (1997). Aspartame
consumption in relation to childhood brain tumor risk: results from a
case-control study. Brief communication.
J Natl Cancer Inst 89(14): 1072-1074.
Hagiwara A, Fukushima S, Kitaori M, Shibata M, Ito N (1984). Effects of
three sweeteners on rat urinary bladder carcinogenesis initiated by
N-butyl-N-(4-hydroxybutyl)-nitrosamine. Gann 74(9): 763-768.
Ishii H (1981). Incidence of brain tumors in rats fed aspartame.
Toxicology Lett 7: 433-437.
Jeffrey AM, Williams GM (2000). Lack of DNA-damaging activity of five
non-nutritive sweeteners in the rat hepatocyte/DNA repair assay.
Food Chem Toxicol 38(4): 335-8.
Mukhopadhyay M, Mukherjee A, Chakrabarti J (2000). In vivo cytogenetic
studies on blends of aspartame and acesulfame-K.
Food Chem Toxicol 38(1): 75-7.
Nauta W, Lampert P, Young V (1980). Aspartame: decision of the public board
of inquiry. FDA Docket No. 75F-0355. Federal Register 45:69558.
National Toxicology Program (NTP, 2003a). DRAFT NTP Technical Report on the
Toxicity Studies of Aspartame (CAS No. 22839-47-0) in FVB/N-TgN(v-Ha-ras)Led
(Tg.AC) Hemizygous Mice and Carcinogenicity Studies of Aspartame in
B6.129-Trp53tn1Brd (N5) Haplosufficient Mice (Feed Studies).
NTP, NTP GMM 1, NIH Publication
No. 03-4459. U.S. Department of Health and Human Services, Public Health
Service, National Institute of Health.
National Toxicology Program (NTP, 2003b). Actions on Draft Technical Reports
by the NTP Board of Scientific Counselors, Technical Reports Review
Subcommittee, May 22, 2003. Available at:
http://ntpserver.
niehs.nih.gov/Meetings/2003/May2003Actions.html.
Olney JW, Farber NB, Spitznagel E, Robins, LN (1996). Increasing brain tumor
rates: is there a link to aspartame?
J Neuropath Experimental Neurol 56(1): 1115-23.
Searle Laboratories (1973). SC-188862: Two Year Toxicity Study in the Rat.
P-T 838H71, Final report. Entry E-34. Submitted to Searle Laboratories by
Hazleton Laboratories, Inc. dated January 12, 1973. Obtained from FDA's
Hearing Clerk's office, as "Study E33/34 in Master File 134 on Aspartame".
Shepard SE, Wakabayashi K, Nagao M (1993). Mutagenic activity of peptides
and the artificial sweetener aspartame after nitrosation.
Food Chem Toxicol 31(5): 323-329.
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandex-Lopez JA,
Alemany M (1998). Formaldehyde derived from dietary aspartame binds to
tissue components in vivo. Life Sci 63(5): 337-349.
[
http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22 rmforall ]
BATCH #4 PRIORITIZED CHEMICALS FINAL MARCH 2004 page 37
****************************************************************
Rich Murray, MA Room For All
rmforall@... 505-501-2298
1943 Otowi Road Santa Fe, New Mexico 87505 USA
http://groups.yahoo.com/group/aspartameNM/messages
group with 186 members, 1,191 posts in a public, searchable archive
http://groups.yahoo.com/group/aspartameNM/message/1186
aspartame induces lymphomas and leukaemias in rats, free full plain text, M
Soffritti, F Belpoggi, DD Esposti, L Lambertini, 2005 April, 2005.07.14:
main results agree with their previous methanol and formaldehyde studies,
Murray 2005.07.19
http://groups.yahoo.com/group/aspartameNM/message/1185
Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at
human use levels causes cancer (methanol, formaldehyde, formic acid), M
Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray
2005.07.15
http://groups.yahoo.com/group/aspartameNM/message/1189
Michael F Jacobson of CSPI now and in 1985 re aspartame toxicity, letter to
FDA Commissioner Lester Crawford; California OEHHA aspartame critique
2004.03.12; Center for Consumer Freedom denounces CSPI: Murray 2004.07.27
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). If 30% of
the methanol is turned into formaldehyde, the amount of formaldehyde is 18
times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2
L water.
http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall
Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
both ordinary amino acids, bound loosely together by methanol (wood alcohol,
11%). The readily released methanol from aspartame is within hours turned
by the liver into formaldehyde and then formic acid, both potent, cumulative
toxins.
http://groups.yahoo.com/group/aspartameNM/message/1182
Joining together: short review: research on aspartame (methanol,
formaldehyde, formic acid) toxicity: Murray 2005.07.08 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1071
research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray
2004.04.29 rmforall
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 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1131
genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text,
Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray
2004.11.06 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1088
Murray, full plain text & critique: chronic aspartame in rats affects
memory, brain cholinergic receptors, and brain chemistry, Christian B,
McConnaughey M et al, 2004 May: 2004.06.05 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2004.03.30 rmforall
Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
toxicology@...
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text
Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]
http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@...
"K.H. Schulpis" <
inchildh@...> "G.J. Reclos"
reklos@...
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 rmforall
Finally, an intripid and much published team in Japan has found DNA damage
in 8 tissues from single non-lethal doses of aspartame (near-significant
high levels of DNA damage in 5 tissues) and many other additives in groups
of just 4 mice:
Mutat Res 2002 Aug 26; 519(1-2): 103-19
The comet assay with 8 mouse organs: results with 39 currently used food
additives.
Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K,
Taniguchi K, Tsuda S.
Laboratory of Genotoxicity, Faculty of Chemical and Biological
Engineering, Hachinohe National College of Technology,
Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
yfsasaki-c@... s.tsuda@...
We determined the genotoxicity of 39 chemicals currently in use as food
additives.
They fell into six categories-dyes, color fixatives and
preservatives, preservatives, antioxidants, fungicides, and sweeteners.
We tested groups of four male ddY mice once orally with each additive at
up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet
assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung,
brain, and bone marrow 3 and 24 h after treatment.
Of all the additives, dyes were the most genotoxic.
Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and
Rose Bengal induced dose-related DNA damage in the glandular stomach, colon,
and/or urinary bladder.
All seven dyes induced DNA damage in the gastrointestinal organs at a
low dose (10 or 100mg/kg).
Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced
DNA damage in the colon at close to the acceptable daily intakes (ADIs).
Two antioxidants (butylated hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
o-phenylphenol, and thiabendazole), and four sweeteners (sodium
cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA
damage in gastrointestinal organs.
Based on these results, we believe that more extensive assessment of
food additives in current use is warranted. PMID: 12160896
http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 2002.12.31 rmforall
http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S Aug 2002: Murray 2003.01.01 rmforall
[ Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]
http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 2003.01.27 rmforall [A detailed look at the data] ]
C. Trocho (1998):
"In all, the rats retained, 6 hours after administration, about 5% of the
label, half of it in the liver."
They used a very low level of aspartame ingestion, 10 mg/kg, for rats, which
have a much greater tolerance for aspartame than humans.
So, the corresponding level for humans would be about 1 or 2 mg/kg.
Many headache studies in humans used doses of about 30 mg/kg daily.
http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 1998.06.26: Murray 2002.12.22 rmforall
http://ww.presidiotex.com/barcelona/index.html full text
Formaldehyde derived from dietary aspartame binds to tissue components in vivo.
Life Sci June 26 1998; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html Lķnies de Recerca: Toxicitat de
l'aspartame
http://www.bq.ub.es/grupno/grup-no.html
Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, Dr. Xavier Remesar, Dr. Jose Antonio
Fernandez-Lopez, Dr. Marią Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544,
FAX: (93)4021559
alemany@... bioq@... josefer@...
rafecas@... remesar@...
Abstract:
Adult male rats were given an oral dose of 10 mg/kg aspartame,
14C-labeled in the methanol carbon.
At timed intervals of up to 6 hours, the radioactivity in plasma and several
organs was investigated.
Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to
protein.
Label present in liver, plasma and kidney was in the range of 1-2% of total
radioactivity administered per g or mL, changing little with time.
Other organs (brown and white adipose tissues, muscle, brain, cornea and
retina) contained levels of label in the range of 1/12th to 1/10th of that of
liver.
In all. the rats retained, 6 hours after administration, about 5% of the label,
half of it in the liver.
The specific radioactivity of tissue protein, RNA and DNA was quite uniform.
The protein label was concentrated in amino acids, different from methionine,
and largely coincident with the result of protein exposure to labeled
formaldehyde.
DNA radioactivity was essentially in a single different adduct base,
different from the normal bases present in DNA.
The nature of the tissue label accumulated was, thus, a direct consequence
of formaldehyde binding to tissue structures.
The administration of labeled aspartame to a group of cirrhotic rats
resulted in comparable label retention by tissue components, which suggests
that liver function (or its defect) has little effect on formaldehyde
formation from aspartame and binding to biological components.
The chronic treatment of a series of rats with 200 mg/kg of non-labeled
aspartame during 10 days results in the accumulation of even more label when
given the radioactive bolus, suggesting that the amount of formaldehyde
adducts coming from aspartame in tissue proteins and nucleic acids may be
cumulative.
It is concluded that aspartame consumption may constitute a hazard because
of its contribution to the formation of formaldehyde adducts. PMID: 9714421
[ Extracts ]
"The high label presence in plasma and liver is in agreement with the
carriage of the label from the intestine to the liver via the portal vein.
The high label levels in kidney and, to a minor extent, in brown adipose
tissue and brain are probably a consequence of their high blood flows (45).
Even in white adipose tissue, the levels of radioactivity found 6 hours
after oral administration were 1/25th those of liver.
Cornea and retina, both tissues known to metabolize actively methanol
(21,28) showed low levels of retained label.
In any case, the binding of methanol-derived carbon to tissue proteins was
widespread, affecting all systems, fully reaching even sensitive targets
such as the brain and retina....
The amount of label recovered in tissue components was quite high in all the
groups, but especially in the NA rats.
In them, the liver alone retained, for a long time, more than 2 % of the
methanol carbon given in a single oral dose of aspartame, and the rest of
the body stored an additional 2 % or more.
These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects (33), that has also
been considered carcinogenic (34,47).
The repeated occurrence of claims that aspartame produces headache and other
neurological and psychological secondary effects-- more often than not
challenged by careful analysis-- (5, 9, 10, 15, 48) may eventually find at
least a partial explanation in the permanence of the formaldehyde label,
since formaldehyde intoxication can induce similar effects (49).
The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame may
result in the progressive accumulation of formaldehyde adducts.
It may be further speculated that the formation of adducts can help to
explain the chronic effects aspartame consumption may induce on sensitive
tissues such as brain (6, 9, 19, 50).
In any case, the possible negative effects that the accumulation of
formaldehyde adducts can induce is, obviously, long-term.
The alteration of protein integrity and function may needs some time to
induce substantial effects.
The damage to nucleic acids, mainly to DNA, may eventually induce cell death
and/or mutations.
The results presented suggest that the conversion of aspartame methanol into
formaldehyde adducts in significant amounts in vivo should to be taken into
account because of the widespread utilization of this sweetener.
Further epidemiological and long-term studies are needed to determine the
extent of the hazard that aspartame consumption poses for humans."
http://groups.yahoo.com/group/aspartameNM/message/864
Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats: Murray 2002.09.08 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by W.C. Monte. ]
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@... 919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 2002.12.09 rmforall
http://groups.yahoo.com/group/aspartameNM/message/846
aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks: Murray 2002.07.16 rmforall
Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology
newmanache@...
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research
RLipton@...
http://groups.yahoo.com/group/aspartameNM/message/855
Blumenthall & Vance: aspartame chewing gum headaches Nov 1997:
Murray 2002.07.28 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches. Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA.
neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [ 6-8 mg aspartame per stick chewing gum ]
Subject: Re: Murray: Butchko:
Tephly: critique of Trocho report Apr 2002 8.29.2
Date: Fri, 30 Aug 2002 09:49:56 +0200
From: Marią Alemany <
alemany@...>
To: "Rich Murray" <
rmforall@...>
References: 1
Dear Rich,
Thank you for the opportunity to say something about the "paper" by Tephly
that followed our study on the incorporation of aspartame-derived methanol
label into DNA and protein of rats.
I don't know if responding to that publication is worth the effort.
Surprisingly, a serious journal, such as Life Sciences published a rebuttal
of our previous paper as a normal "research paper", but including no new
information neither experimental work.
This is only a sample of the "scientific" power of the advocates of
aspartame.
Anybody can extract conclusions from this anomaly, but it seems to me that
there was nothing new in that pamphlet that may add information to what we
already explained in our paper.
The responses to the questions raised by Tephly are already in our paper,
which means that either that it was not read or, worst, it was misread.
The presence of aspartame-derived label in DNA and protein adducts is
unquestionable and unquestioned, and agrees with previous studies.
Then, what importance has the mechanism of incorporation?
There were adducts, and they represent loss of function and mutation.
That was our thesis.
The reference to previous studies showing very low levels of formaldehyde in
blood do not refute our data.
First of all, measuring formaldehyde is tricky,
and in any case, the circulating levels would be below the current limit of
detection for most of the methods used.
That is the current explanation for the low levels of methanol in plasma
after aspartame loading: they are zero, using most of the methods available
for methanol, since the expected levels are currently below the limit of
detection...
In addition, it is not logical to expect to find measurable levels of
formaldehyde in a medium (blood) containing a huge amount of protein.
Formaldehyde reacts immediately with proteins because it is highly reactive:
that is the reason why we have found it in cell protein and DNA.
It is absurd to expect it to forfeit binding with cell proteins and go all
the way into the bloodstream!
Remember that formaldehyde is used to preserve corpses precisely because it
binds protein (including those of putrefactive bacteria) and prevents its
degradation.
The "alternative" point expressed by Tephly, suggesting that aspartame
methanol-label goes all the way into formic acid and the C1 pathway was
thoroughly refuted by us, using experimental data.
There was no labelled methionine nor thymine in protein and DNA respectively
in the rat protein we recovered from rats treated with aspartame.
This means--unequivocally-- that the label present in DNA and protein
adducts was NOT incorporated into amino acids or nucleic acid bases.
The only explanation for our data was that the label was in the form of
formaldehyde adducts.
If this explanation does not satisfy other scientists, they are free to
repeat the experiment and show where we went wrong, or to probe and prove
experimentally their hypotheses.
Otherwise, our results stand unchecked and, consequently, should be deemed true.
I hope that this information will help any attentive reader understand why
we have left for good this field of study.
Best regards.
------------------------------
Prof.Dr. Marią Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutrició i Bromatologia
Facultat de Biologia, Universitat de Barcelona
Av. Diagonal, 645; 08028 Barcelona Espanya/Espańa/Spain
tel. +34 93 403 4606; fax: +34 93 403 7064; E-mail:
alemany@...
Life Sci 1999; 65(13): PL157-60. [ letter, usually not peer reviewed ]
Comments on the purported generation of formaldehyde and adduct
formation from the sweetener aspartame.
Tephly TR Thomas R. Tephly 319-335-7979
thomas-tephly@...
ttephly@... Department of Pharmacology
The University of Iowa, Iowa City 52242, USA.
A recent paper by Trocho et al. (1) describes experiments meant to show that
formaldehyde adducts are formed when rats are administered the sweetener
aspartame.
These authors assume that the methanol carbon of aspartame generates
formaldehyde which then forms adducts with protein, DNA, and RNA.
Doses employed range widely.
In this letter, studies which have been published previously and which were
not cited by these authors are reviewed in order to put into perspective the
disposition of methanol and formaldehyde in monkeys and humans, species
relevant to the toxicity of methanol and its toxic metabolite, formic acid.
PMID: 10503962, UI: 99431287
[ A number of pro-aspartame studies by Tephly and associates, invariably
funded by the aspartame industry (Monsanto, NutraSweet) are criticized in
detail at:
http://www.HolisticMed.com/aspartame mgold@...
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"
Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels. ]
http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references
http://www.eatright.org/Nutritive(1).pdf
J Am Diet Assoc. 2004 Feb; 104(2): 255-75.
Position of the American Dietetic Association: use of nutritive and
nonnutritive sweeteners. American Dietetic Association.
http://groups.yahoo.com/group/aspartameNM/message/1068
critique of aspartame review by American Dietetic Association Feb 2004,
Valerie B. Duffy & Madeleine J. Sigman-Grant: Murray 2004.04.03 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA 2002.05.07
aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13
http://groups.yahoo.com/group/aspartameNM/message/1184
corporate corruption of health sciences, International Journal of
Occupational and Environmental Health, entire issue, 2005 Oct-Dec: Gary N
Greenburg, OEM-L: aspartame (methanol, formaldehyde, formic acid) toxicity,
Murray 2005.07.14
"Survey of aspartame studies: correlation of outcome and funding sources,"
1998, unpublished:
http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed medical
literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501 330-740-3621
rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm
http://groups.yahoo.com/group/aspartameNM/message/857
www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31 rmforall
http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re
aspartame and MSG toxicity: Murray 2002.08.01 rmforall
http://www.truthinlabeling.org/ Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999; 6: 259-310. 52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333
adandjack@...
http://www.dorway.com/upipart1.txt
http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon, UPI reporter:
Murray 2000.07.10 rmforall
http://www.dorway.com/enclosur.html
http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06 rmforall
http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall
http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1184
corporate corruption of health sciences, International Journal of
Occupational and Environmental Health, entire issue, 2005 Oct-Dec: Gary N
Greenburg, OEM-L: aspartame (methanol, formaldehyde, formic acid) toxicity,
Murray 2005.07.14
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). If 30% of
the methanol is turned into formaldehyde, the amount of formaldehyde is 18
times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2
L water.
http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1108
faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
lipid peroxidation, green tea, aging: Murray 2004.08.08 2005.07.11
http://groups.yahoo.com/group/aspartameNM/message/1140
EPA Preliminary Remedial Goals, PRGs, 2003 Oct, air and tap water --
methanol, formaldehyde, formic acid -- not mentioned is methanol from
aspartame, dark wines and liquors: Murray 2004.11.20 rmforall
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 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1183
UK Co-op chain bans MSG and 21 food dyes; health food desire in UK, Asia,
France: Feed Me Better school lunch campaign, Jamie Oliver: Caroline Walker
Trust: Lindsay Partos, Novis NutraIngredients.com: Murray 2005.07.13
Alcohol Clin Exp Res. 1997 Aug; 21(5): 939-43.
Endogenous production of methanol after the consumption of fruit.
Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W.
Institut fur Ionenphysik, Leopold Franzens Universitat Innsbruck, Austria.
After the consumption of fruit, the concentration of methanol in the human
body increases by as much as an order of magnitude.
This is due to the degradation of natural pectin (which is esterified with
methyl alcohol) in the human colon.
In vivo tests performed by means of proton-transfer-reaction mass
spectrometry show that consumed pectin in either a pure form (10 to 15 g)
or a natural form (in 1 kg of apples) induces a significant increase of
methanol in the breath (and by inference in the blood) of humans.
The amount generated from pectin (0.4 to 1.4 g) [ 400 to 1400 mg ]
is approximately equivalent to the total daily endogenous production
(measured to be 0.3 to 0.6 g/day) [ 300 to 600 mg ]
or that obtained from 0.3 liters of 80-proof brandy
(calculated to be 0.5 g). [ 500 mg ]
This dietary pectin may contribute to the development
of nonalcoholic cirrhosis of the liver. PMID: 9267548
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.
PMID: 8561283 [ Corrected 2005.07.11:
24 ml means 19 g ethanol, and 0.19 ml means 0.15 g = 150 mg methanol.
One L diet soda has 61.5 mg methanol in the aspartame molecule, so 100 ml
diet soda has 6.15 mg methanol, so the brandy has 24.4 times more methanol
than diet soda.
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