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Medical Forum / General / Nutrition / November 2004

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Lenore S. Greenstein on sweeteners: "Managing Sweetness" Mexico City conference: Oldways Preservation Trust; review of recent toxicity research on aspartame, methanol, formaldehyde, formic acid: Murray 2004.11.09

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Rich Murray - 10 Nov 2004 05:44 GMT
http://groups.yahoo.com/group/aspartameNM/message/1135
Lenore S. Greenstein on sweeteners: "Managing Sweetness" Mexico City
conference: Oldways Preservation Trust; review of recent toxicity research
on aspartame, methanol, formaldehyde, formic acid: Murray 2004.11.09

2004.11.09   Sirs:  Lenore S. Greenstein has 273 items on Google that show
that she is an expert, informed, conscientious dietician who regularly
provides lifesaving information about healthy foods and very undesirable
toxins.  However, since I have been writing for six years very long, civil,
detailed, balanced reviews of recent scientific research on aspartame
toxicity, citing mainstream scientific journals, I wish to improve her level
of service by providing copious information about a very simple fact:

The 11% methanol component of aspartame is invariably immediately released
in full in the human GI tract, and largely turned into formaldehyde, and
then largely into formic acid -- both potent, cumulative toxins that affect
every cell and tissue.

Those who use more than 6 cans daily diet soda ( perhaps 1% of the
population, looking around at the people I know here in Santa Fe, New
Mexico, where I've worked 16 years as a home hospice care giver ) will, if
only 10% of the methanol stays in the body as toxic reaction products, will
be taking in over sixty times the EPA limit for formaldehyde in daily
drinking water.  The result for the many vulnerable people will be a gradual
progression of increasingly severe, complex symptoms.  One of my recent
scientific reviews is provided herein after Greenstein's article.

Since even extremely prestigious institutions like MIT ( from which I
graduated in 1964 with a BS in physics and history ) and Harvard have been
coopted into publishing biased research to impute the safety of aspartame, I
am not surprised that the very valuable work of Oldways Preservation Trust
has also been subverted. ( Psst, I've been a vegan 6 years, now. ).

" Sponsorship

Oldways is pleased to acknowledge the support of the Beverage Institute for
Health and Wellness, Coca-Cola, Ajinomoto, Cargill, Nutrinova and Tate &
Lyle on this project.

`"We are really pleased that they accepted our proposal for a scientific
conference to develop the new concept of "managing sweetness," said Oldways
President K. Dun Gifford. "The lessons of history teach that working
cooperatively with    industry    technical experts     and     independent
scientific experts    has the highest possible chance for reaching
realistic, successful and effective outcomes." "

Uh, huh...sure...

In mutual service,  Rich Murray, MA

Rich Murray, MA    Room For All    rmforall@comcast.net
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-501-2298
http://groups.yahoo.com/group/aspartameNM/messages
132 members,  1,133 posts in a public searchable archive   also Co-Moderator

http://groups.yahoo.com/group/aspartame/messages  bryanth@brooksdata.net
Aspartame Victims Support Group    Edward Bryant Holman, Chief Moderator
837 members, 17,585 posts in a public, searchable archive
http://www.presidiotex.com/aspartame/    bryanth@presidiotex.net

http://www.HolisticMed.com/aspartame    mgold@holisticmed.com
Aspartame Toxicity Information Center    Mark D. Gold     also Co-Moderator
12 East Side Drive #2-18 Concord, NH 03301     603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall  EU Scientific Committee on Food, a whitewash

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.naplesnews.com/npdn/ne_columnists/article/0,2071,NPDN_14929_3313979,0
0.html


Lenore S. Greenstein: Sweeteners are safe, yet rumors persist
By LENORE S. GREENSTEIN, special to the Daily News    Naples, Florida
November 9, 2004

In a recent survey, 84 percent of consumers said they regularly include
low-calorie or sugar-free products as part of meals or snacks, yet for some
they are still are the center of controversy.
Is there sound science behind their doubts?

At a recent conference on "Scientific Straight Talk on Sweetness and
Health," sponsored by the Oldways Preservation Trust, a think-tank on issues
of nutrition and culinary excellence, scientists analyzed the chemistry and
safety of non-nutritive sweeteners.

Most non-caloric sweeteners are made from common foodstuffs or amino acids
by rearranging their chemical bonds using heat or other techniques.
These low- or no-calorie sweeteners lead to satiety, or the feeling of
satisfaction, in the same way as regular sugar or honey.

By the time any sweetener is marketed, it has been reviewed by hundreds of
scientists around the world, and the final petition for its approval
involves 20,000 to 30,000 pages in support of its safety.
All low-calorie sweeteners approved since 1980 have been subjected to
intense international scientific scrutiny.
They have been thoroughly tested and the question of their safety has been
resolved.

There are many non-nutritive or non-calorie sweeteners on the market today,
so the consumer has a choice depending on individual preferences.

Sucralose, marketed as Splenda or Sunnet.
The most recent sweetener to be approved (in 2003), it is 600 times sweeter
than sugar.
Sucralose doesn't break down when used in cooking and baking, and has many
culinary advantages.
There has been little controversy about its use.

Aspartame, marketed as Equal or Nutrasweet.
More than 200 studies confirmed its safety, and yet there are still
allegations questioning its safety and misinformation circulating on the
Internet.
Studies published by the New England Journal of Medicine have shown that
there is no evidence that aspartame causes headaches or brain tumors, as
alleged by some people.
The Acceptable Daily Intake, which is the amount safely consumed each day
for a lifetime, allows 50 milligrams of aspartame per killigram of body
weight.
That factor would compute to 20 12-ounce cans of carbonated soft drinks a
day for adults, and six cans a day for children.
It has been estimated that nine out of 10 consumers are only drinking 5-10
percent of this amount. [ What about the top 1 out of 10, and the top 1 out
of 100, which would be about 2 million users in the USA alone...? ]

Some kids may come close to drinking that amount, which means they are
probably substituting diet drinks for healthy beverages such as milk and
fruit juice.
In this case, the guidelines may be helpful for parents.

Saccharin, known as Sweet and Low.
The question of its safety has been resolved.
Earlier animal studies citing tumors that developed in rats after consuming
large amounts of saccharin have been shown not to be relevant to humans.
You would have to be fed the equivalent of 500-750 cans of soft drinks
daily, for life, to approximate the amount of saccharin consumed by those
rodents.

One area that still remains a concern is the use of sweeteners by children,
relative to body weight of the growing child.

Pregnant women are often cautioned as well, when the goal of the prenatal
diet is to support the health of the mother and the fetus.

Taken as a whole, both caloric and non-caloric sweeteners approved by the
Food and Drug Administrations are safe for children and pregnant women,
since there is
little       direct clinical evidence     showing negative long-term effects
on overall health.
Lenore S. Greenstein is a registered dietitian in private practice in the
Naples area.
lenoresue@swfla.rr.com    naplesnutrition@swfla.rr.com
******************************************************************

2004.11.09  Introductory overview by Rich Murray:

http://groups.yahoo.com/group/aspartameNM/message/927   Donald Rumsfeld,
1977 head of Searle Corp., got aspartame FDA approval: Turner: Murray
2002.12.23

http://groups.yahoo.com/group/aspartameNM/message/1065  politicians and
celebrities hooked on diet sodas (aspartame): Murray 2004.03.24
Senator John Edwards still has a dozen Diet Cokes daily -- a gallon,
which gives as much methanol as a half-gallon of red wine.
President Bush is also very probably a victim -- aching knee joints are a
well-known symptom of chronic low-level formaldehyde toxicity, often
reported by aspartame reactors.

The moderated newsgroup, bionet.toxicology , has accepted 23 of my long
reviews since March 24:

Dr. Charles "Chuck" A. Miller III   rellim@tulane.edu
Associate Professor of Environmental Health Sciences
374 Johnston Building, SL29
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Avenue  New Orleans, LA 70112   (504)585-6942
Bionet.toxicology news group  http://www.bio.net/hypermail/toxicol/current

http://groups.yahoo.com/group/aspartameNM/message/1128
hangover symptoms from methanol from dark wines and liquors or 11% methanol
part of aspartame, review of research: Jones AW 1988:  Murray 2004.10.23
rmforall

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).   However,
about 30% of the methanol remains in the body as cumulative durable toxic
metabolites of formaldehyde and formic acid, 37 mg daily, a gram every
month, accumulating in and affecting every tissue -- over 60 times the USA
EPA limit for formaldehyde in drinking water.

Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
both ordinary amino acids, bound loosely together by methanol (wood alcohol,
11%).   Similar amounts of methanol in many fruits and vegetables, locked up
in complex pectin molecules, and always paired with ethanol, its natural
antidote, are not usually released by human digestion and so are harmless.
But the readily released methanol from aspartame is within hours largely
turned by the liver into formaldehyde and then formic acid, both potent,
cumulative toxins.

Red wine contains twice as much methanol as does diet soda as an impurity,
about one part in ten thousand.  It is the natural conversion by the body of
this methanol into formaldehyde and formic acid that is the main cause of
the well known "morning after" hangover symptoms: headache, nausea,
weakness, impaired memory, irritability, anxiety, "brain fog", body pains --
the same symptoms as aspartame victims.

Jones AW.
Elimination half-life of methanol during hangover.
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.   PMID: 3588516

" But higher blood-methanol concentrations are definitely associated with
higher blood-ethanol in this sample of Swedish drinking drivers.

Frequent exposure to methanol and its toxic products of metabolism,
formaldehyde and formic acid, might constitute an additional health risk
associated with heavy drinking in predisposed individuals. "   Jones AW 1988

Forensic Sci Int. 1988 Jun; 37(4): 277-85.
Relationship between the concentration of ethanol and methanol in blood
samples from Swedish drinking drivers.
Jones AW, Lowinger H.
Department of Alcohol Toxicology, University Hospital, Linkoping, Sweden.
Jones AW has 341 items in PubMed.

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW: also some
methanol from fruit pectin in colon: Murray 2004.09.11 rmforall

http://bmj.bmjjournals.com/search.dtl      search to get free full text
British Medical Journal 1997 (4 January); 314(7073): 2.
Ian Calder, F.R.C.A. [ Tel/Fax: 0171 720 9279   Consultant Anaesthetist at
the National Hospital for Neurology and Neurosurgery,
London  WCIN 3BG, UK ]

Editorials         Hangovers: Not the ethanol - perhaps the methanol

" Pawan compared the hangover produced by different types of drink (but only
one brand of each) in his study of 20 volunteers. The severity of hangover
symptoms declined in the order of brandy, red wine, rum, whisky, white wine,
gin, vodka, and pure ethanol.(6)  Vodka and pure ethanol caused only mild
headaches in two volunteers. "

6. Pawan GL.
Alcoholic drinks and hangover effects.
Proc Nutr Soc 1973 May; 32: 15A.  PMID: 4760771

J.A. Oppermann's Searle Co. lab  proved that 30% of the methanol in
aspartame fed once to monkeys remained --  surely as formaldehyde and formic
acid in all tissues (1973, 1976, 1979).
********************************************************************

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

[ Comments and corrections by Rich Murray are in square brackets.  Spacing
has been added, without changing text, to increase readability and clarity,
and add emphasis. ]

Obviously, it hardly is conclusive to simply place aspartame in contact with
isolated living cells, without doing detailed explorations to determine the
degree of
disassociation into phenylalanine, aspartic acid, and methanol,
with resulting formation of formaldehyde and formic acid,
as well as studying long-term accumulations in animals and humans --
except as a very valuable initial pilot study.

Nevertheless, their evidence and conclusions are devastating.

Rich Murray, MA    Room For All    rmforall@comcast.net
1943 Otowi Road, Santa Fe, New Mexico 87505 USA  505-501-2298
http://groups.yahoo.com/group/aspartameNM/messages
134 members,  1,133 posts in a public searchable archive   also Co-Moderator

http://groups.yahoo.com/group/aspartame/messages  bryanth@brooksdata.net
Aspartame Victims Support Group    Edward Bryant Holman, Chief Moderator
831 members, 17,573 posts in a public, searchable archive
http://www.presidiotex.com/aspartame/    bryanth@presidiotex.net

http://www.HolisticMed.com/aspartame    mgold@holisticmed.com
Aspartame Toxicity Information Center    Mark D. Gold     also Co-Moderator
12 East Side Drive #2-18 Concord, NH 03301     603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall  EU Scientific Committee on Food, a whitewash

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
***************************************************************

"Schwartz ( 1999 ) also reported that methanol is converted to formaldehyde
which then accumulates in the cells.
Formaldehyde has been considered an inducer of cancer and acts to alter DNA
( Ewertz, 1993;
Ewertz and Gill, 1990 ).

Olney et al. ( 1996 ) reviewed and explained that ASP had mutagenic
potential.....

In this study, we found that, ASP did appear to have genotoxic potential
consistent with potential carcinogenicity.

According to these results, phenyalanine and methanol, which are metabolic
products of ASP, have a genotoxic risk for humans.

In contrast, ASP was not found as a mutagen in in vivo studies.

However, in the present study, ASP induced CA and micronuclei in human
lyphocytes dose-dependently.

ASP did not change the osmolality of the medium at the maximum
concentrations ( 346 milliosmol) when compared with untreated medium (342
milliosmol ).

It was reported that a deviation from physiological osmolality
( approximately 300 milliosmol ) can lead to genotoxic effects
( Nowak, 1984, 1997;
Seeberg et al., 1989 ).

According to these results, we can conclude that ASP induced CA and
percentage of micronuclei by itself because it did not alter the pH and
osmolality of the medium.

As shown, there are several contradictory studies about genotoxicity and
carcinogenicity of ASP.

However, it must be taken into account that ASP induced the CA and
micronuclei formation in a dose-dependent manner.

It is not possible to conclude that ASP is safe according to these results.

Therefore, it is necessary to be careful when using it in food and beverages
as a sweetener."

Genotoxicity of aspartame 2004.07.29 plain text, Rencuzogullari E et al,
Cukurova University, Adana, Turkey 2004 Aug

Drug Chem Toxicol. 2004 Aug; 27(3): 257-68.
Genotoxicity of aspartame.
Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler
SB.
Biology Department, Faculty of Arts and Sciences, Natural and Applied
Sciences Institute, Cukurova University, Adana, Turkey.
reyyup@mail.cu.edu.tr

http://www.cu.edu.tr/Content/Asp/English/index.asp

http://rektorluk.cukurova.edu.tr/en/rehber.asp

In the present study, the genotoxic effects of the low-calorie sweetener
aspartame (ASP), which is a dipeptide derivative, was investigated using
chromosome aberration (CA) test,
sister chromatid exchange (SCE) test,
micronucleus test in human lymphocytes       and also
Ames/Salmonella/ microsome test.

ASP induced CAs at all concentrations ( 500, 1000 and 2000 microg/ml)  and
treatment periods ( 24 and 48 h ) dose-dependently,
while it did not induce SCEs.

On the other hand, ASP decreased the replication index ( RI ) only at
the highest concentration for 48 h treatment period.
However, ASP decreased the mitotic index ( MI ) at all concentrations and
treatment periods dose-dependently.
In addition, ASP induced micronuclei at the highest concentrations only.
This induction was also dose-dependent for 48 hours treatment period.
ASP was not mutagenic for Salmonella typhimurium TA98 and TA100 strains in
the absence and presence of S9 mix.   PMID: 15478947

http://www.dekker.com/servlet/product/DOI/101081DCT120037506

Dekker is a digital publisher that offers authoritative scientific,
technical, & medical content accessible at the article level with linked
references.

To contact Dekker customer service by phone, please call 1-800-228-1160
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or +44 1264 343039 ( Europe, Far East, Middle East & Africa ).

Genotoxicity of Aspartame
Published in Drug and Chemical Toxicology , Volume 27 , Issue 3
Print ISSN: 0148-0545     Online ISSN: 1525-6014

Online Article World Price: $24.00

Eyy?p Renc?zoullar *Corresponding   reyyup@mail.cu.edu.tr

[  http://lokman.cu.edu.tr/ent/
?ukurova University Medical School
Adana, Turkey
This page was last updated on 07/06/00.

Webmaster: Assoc.Prof.Mete Kiroglu M.D.  metekbb@mail.cu.edu.tr

?ukurova University  Department of Biophysics
Address:  Balcali,   01330 Turkey
Email:  biyofiz@pamuk.cc.cu.edu.tr
Website:  http://lokman.cu.edu.tr/biophysics/     Chair: Dr. Ismail Guenay ]

Berrin Ayaz T?yl? 3

Mehmet Topakta 1   Mehmet Topaktas  mtopaktas@mail.cu.edu.tr

Hasan Basri la 1

Ahmet Kayraldz 2

Mehmet Arslan 2

Song?l Budak Diler 2

1 Biology Department, Faculty of Arts and Sciences, ?ukurova University
01330, Adana, Turkey

2 Biology Department, Natural and Applied Sciences Institute, ?ukurova
University 01330, Adana, Turkey

3 Biology Department, Faculty of Sciences, Anadolu University
26470, Eskiehir, Turkey

Journal Article | Print Published: 08/01/2004 | Online Published: 07/29/2004
Pages: 257 - 268 | PDF File Size: 104 KB
DOI: 10.1081/DCT-120037506

Keywords

Sweeteners, Aspartame, Chromosome aberrations, Sister chromatid exchange,
Micronuclei, Ames test
***************************************************************

Genotoxicity of Aspartame  07/29/2004

Drug Chem Toxicol. 2004 Aug; 27(3): 257-68.
Genotoxicity of aspartame.
Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler
SB.
Biology Department, Faculty of Arts and Sciences, Natural and Applied
Sciences Institute, Cukurova University, Adana, Turkey.
reyyup@mail.cu.edu.tr

http://www.cu.edu.tr/Content/Asp/English/index.asp

http://rektorluk.cukurova.edu.tr/en/rehber.asp

In the present study, the genotoxic effects of the low-calorie sweetener
aspartame ( ASP) , which is a dipeptide derivative, was investigated using
chromosome aberration ( CA ) test,
sister chromatid exchange ( SCE ) test,
micronucleus test in human lymphocytes       and also
Ames/Salmonella/ microsome test.

ASP induced CAs at all concentrations ( 500, 1000 and 2000 microg/ml)  and
treatment periods ( 24 and 48 h ) dose-dependently, while it did not induce
SCEs.

On the other hand, ASP decreased the replication index ( RI ) only at
the highest concentration for 48 h treatment period.

However, ASP decreased the mitotic index ( MI ) at all concentrations and
treatment periods dose-dependently.
In addition, ASP induced micronuclei at the highest concentrations only.
This induction was also dose-dependent for 48 hours treatment period.
ASP was not mutagenic for Salmonella typhimurium TA98 and TA100 strains in
the absence and presence of S9 mix.   PMID: 15478947

Introduction

Many non-nutritive sweeteners have been used in foods and beverages to allow
people to enjoy the sweet taste without consuming sugar-associated calories,
and therefore inducing weight gain. One of these sweeteners is aspartame.
Aspartame ( alpha-l-aspartyl-l-phenylalanine 1-methylester ) is a dipeptide
artificial sweetener that is widely used as a non-nutritive sweetener in
foods and drinks. ASP was discovered in 1965. In 1981, ASP became the first
low calorie sweetener approved by the Food and Drug Administration ( FDA )
in more than 26 years.

ASP is used as a sweetener in food products including dry beverage mixes,
chewable multi-vitamins, breakfast cereals, chewing gum, puddings and
fillings, carbonated beverages, refrigerated and non-refrigerated ready to
drink beverages, yogurt-type products and pharmaceuticals.

The ministry of Agricultural ( of Turkey ) suggested that ASP may be used at

a maximum
dose of 5500 mg/kg ( The ministry of Agricultural of Turkey, 1997 ).

Butchko et al. ( 2002 ) reviewed a study on safety of ASP and reported that
ASP is safe.

It was reported that ASP did not induce DNA damage in rat hepatocytes
( Jeffrey and Williams, 2000 ) and
was not clastogenic in mice when given orally ( Durnev et al., 1995 ).
In addition, Molinary ( 1984 ) reported that ASP was not mutagenic in Ames
Test and had no genotoxic effect in dominant-lethal and host mediated assay.

However, Shephard et al. ( 1991 ) reported that ASP has a weak mutagenic
effect in Salmonella typhimurium TA100 and TA98 strains after nitrosation.
As shown, some of the sweeteners have mutagenic effects and some of them
such as saccharin caused cancer.
Olney et al. ( 1996 ) reported that ASP may be carcinogenic in
Sprague-Dawley rats.
However, Ishii ( 1981 ) reported that ASP does not cause brain cancer in
rats.

As shown, there are several studies suggesting that ASP has genotoxic
effects but there are also several studies suggesting that ASP has no
genotoxicity.

At present, there is no published data on the induction of CA, SCE and
micronuclei by ASP in human lymphocytes or mutagenic effects in S.
typhimurium without nitrosation.

These studies have been completed and are presented here.

Materials and Methods

The test substance Aspartame phenylalanine methyl ester was obtained from
Sigma ( Cat. no: A5139, CAS no: 22839-47-0, FW: 294, 3 ).
Purity of ASP is 99.9%.
The osmolality of ASP was measured using Roebling automatic osmometer.
The pH of the medium was measured using WTW 315i ( Germany ) pH meter.
The chemical structure and formula of ASP is shown in Fig. 1 .

Figure 1. N-l-alpha-aspartyl-l-phenylalanine 1-methylester.

CA and SCE Assay

Whole blood ( 0.2 ml ) from four healthy donors
( two male, two female, non-smokers, age: 18-19 )
was added to 2.5 ml chromosome medium B ( Seromed, Biochrom cat. no.:
F5023 )
supplemented with 10 ?g/ml bromodeoxyuridine ( Sigma cat. no.: B5002 ).

The cultures were incubated at 37?C for 72 h.

The cells were treated with 500, 1000 and 2000 ?g/ml concentrations of ASP

for 24 h ( ASP was added 48 h after initiating the culture ) and

48 h ( ASP was added 24 h after initiating the culture ).

These concentrations were selected according to cytotoxicity of ASP.

A negative control ( untreated cultures ) and a positive control
( mitomycin-C,  0.3 ?g/ml, Kyowa, Hakko, Japan ) were used.

The test substance, ASP, and positive control mitomycin-C ( MMC ) were
dissolved in bidistilled water.
Colchicine ( 0.06 ?g/ml, Sigma cat. no.: C9754 ) was present for the last 2
h of culture.
To collect the cells, the cultures were centrifuged ( 1200 rpm, 15 min ),
treated with hypotonic solution ( 0.4% KCl ) for 20 min at 37?C, and then
fixed in cold methanol:glacial acetic acid ( 3:1 ) for 20 min at room
temperature.
The treatment with fixative was repeated three times.
Then the cells were spread on glass slides and air dried.

The slides were stained with Giemsa according to fluorescence plus Giemsa
technique ( Speit and Haupter, 1985 ). 100 well spread metaphases per donor
(a total of 400 metaphases per concentration) were examined at
1000 ? magnification for occurrence of different types of CA.

The number of abnormal cells per concentration and treatment period were
determined and the mean frequency of abnormal cells was calculated.

The number of CA per cell ( CA/cell ) was calculated as well.

For the occurrence of SCEs, a total 100 cells ( 25 cells from each donor )
under second metaphases were examined.
The metaphases were examined at 1000 ? magnification.
The results were used to determine the mean number of SCE ( SCE/cell ).

In addition, a total 400 cells ( 100 cells from each donor ) were scored for
the determination of the replication index ( RI ).

The MI was also determined by scoring 3000 cells from each donor.
The MI explained the effects of the chemicals on G2 stage of cell cycle, and
the RI reflects the effects of chemicals on S and G2 stages of the cycles.

The RI was calculated according to the formula as follows: RI = ( M1 ? 1 ) +
( M2 ? 2 ) + ( M3 ? 3 )/total scored cells.

M1, M2 and M3 are the fraction of cells undergoing the first, second and
third mitosis during 72 hours cells culture times.

Micronucleus Assay

The micronucleus test was performed as described by Rothfus et al. (2000).

The peripheral blood from 4 healthy donors was added to 2.5 ml chromosome
medium B and incubated at 37?C for 68 h.

The cells were treated with 500, 1000 and 2000 ?g/ml concentrations of ASP
for 24 and 48 hours as mentioned above.

A negative and a positive control ( 0.3 ?g/ml Mitomycin-C ) was also used.
Cytochalasin B was added to cultures at a final concentrations of 6 ?g/ml 44
hours after initiating of the cultures.
Cultures were harvested 24 hours later.
Then, the cells were treated with hypotonic solution (0.4% KCl), fixed once
with fixative ( methanol:glacial acetic acid, 5:1 ) mixed with an equal
amount of 0.9% NaCl for 20 min, and then
fixed twice with methanol/glacial acetic acid ( 5:1 ) for 20 min.
The slides were air-dried and stained with 5% Giemsa.

The micronucleus frequency was determined by analysing 2000 binucleated
cells for each donor from blinded slides.

In addition, the ratio of binucleated to mononucleated cells was also scored
by analysing 2000 cells for each donor.

Salmonella/Microsome Test

Bacterial Strains

Histidine deficient ( his-) tester strains TA98 and
TA100 of Salmonella typhimurium were kindly provided by
L. K. Nakamura ( Microbiologist Emeritus, Microbial Properties Research,
United States Department of Agriculture, 1815 North University Street,
Peoria, Illinois, 61604, USA ).

The TA98 strain is used for the detection of frameshift mutagens and TA100
strain for the detection of base pair substitution mutagens.
Prior to use in the assay, each strain was checked for the presence of
strain-specific marker as described by Maron and Ames ( 1983 ).

Mutagenicity Assay

The standard plate-incorporation assay was examined with Salmonella
typhimurium TA98 and TA100 strains in the presence and absence of S9 mix
according to Maron and Ames ( 1983 ). 0.5 ml of S9 mix containing 50 ?l of
S9 factor per plate was used for the assay.

For the test, ASP was dissolved in distilled water and
50, 100, 250, 500, 1000 and 2000 ?g per plate were used.

On the other hand, 4-NPD ( 4-nitrophenylene diamine ) was used as a positive
mutagen (200 ?g/plate) for TA98 and TA100.

In the presence of S9 mix, 2-AF ( 2-aminoflourene ) was used as positive
mutagen ( 20 ?g/plate ) for both TA98 and TA100 strains.

Each sample was evaluated with three replicate plates and all experiments
were performed twice.

Preparation of S9

The male albino rats ( Rattus norvegicus var. albinos)  weighing 200 gr were
pre-treated with 80 mg/kg concentration of 3-methylcholanthrene ( Oekanal,
Cat. no: 45794 ) ( dissolved in sunflower seed oil ) for 5 days and the
S9 fraction and S9 mix were prepared following the procedure of Maron and
Ames ( 1983 ).
The S9 tablets were purchased from Roche (Cat. no: 1.745.425).
The freshly prepared S9 fraction is distributed in 1-ml portions in small
plastic tubes frozen immediately and stored at - 35?C.
The S9 mix was prepared fresh for each mutagenicity assay.
Each tablet was dissolved in 18 ml bidistilled water supplemented with 2 ml
of S9 fraction.

Statistical Significance

Chromosome and chromatid gaps were not evaluated as CA ( Mace et al.,
1978 ).

The significance between the percentage of abnormal cell,
CA/cell, mean SCE,
percentage of the micronucleated cells,
RI and MI in treated cultures and
their controls were determined using the t-test.

Dose response relationships were determined from the correlation and
regression coefficients and the corresponding regression lines for the
percentage of
abnormal cell,
CA/cell,
mean SCE,
percentage of micronuclei,
RI and MI.
The significance between control revertants and revertants of treated groups
were also determined using t-test.
Dose-response relationships were also determined using regression and
correlation ( r ) test systems.

Result

ASP induced a significant increase of CAs at all concentrations and
treatment periods compared to control ( Table 1  ).

However this increase was not dose-dependent.

The potency of ASP on induction of CAs was lower than that caused by the
positive control MMC. However, ASP did not induce the SCE ( Table 2  ).

Table 1. Chromosome Aberrations in Cultured Human Lymphocytes Treated with
Aspartame # .
SE = Standard Error

Test substance     Treatment            Abnormalites a

Period ( hours )  Conc. ( ?g/ml )   B',  B", SU, DS, SCU, CE , P

Abnormal  Cell ? SE (%)   CA/Cell ? SE

Control               --, 8, 3, 1, 1, --, --

3.25 ? 1.11           0.035 ? 0.013

MMC    24 h       0.3     62, 19, 4, 5, 1, 10, --

20.25 ? 2.66          0.255 ? 0.038

Asp.       24 h   500     15, 5, 7, 2, 7, --, 2

8.50 ? 0.96 *       0.090 ? 0.007 **

                    1000      11, 4, 8, 3, 5, --, 3

8.75 ? 1.11 *       0.080 ? 0.008 *

                 2000        32, 8, 11, 3,  5, --, --

13.50 ? 0.29 ***   0.147 ? 0.006 ***

MMC    48 h     0.3     146, 43, 2, 4, 5, 6, --

40.25 ? 3.97          0.540 ? 0.039

Asp.      48 h   500    14, 3, 13, --, 5, --, 2

10.75 ? 0.75 **    0.110 ? 0.009 **

                 1000       23, 2, 4, 1, 4, --, --

8.00 ? 1.41 *      0.085 ? 0.018 *

              2000       29, 8, 4, --, 10, --, --

11.50 ? 1.55 *      0.127 ? 0.018 *

 # A total of 400 cells were scored the number of polyploid cells was not
included in the ratio of the CA/cell.

a

B', chromatid break;
B", chromosome break;
SU, sister union;
DS, dicentric chromosome;
SCU, single chromatid union;
CE, chromatid exchanges,
P, polyploidy.

     *p < 0.05.
   **p < 0.01.
 ***p < 0.001.

Table 2. Frequency of SCE, RI and MI in Cultured Human Lymphocytes Treated
with Aspartame. #
SE = Standard Error

Test substance    Treatment

   Period ( hours )    Conc. ( ?g/ml )

                   Min-Max SCE   SCE/cell ? SE
                                                            M1   M2   M3
RI ? SE   MI ? SE

Control  -- --   2-26   7.47 ? 0.74   48  160  192  2.36 ? 0.09  3.35?0.48

MMC 24  0.3   8-44  23.345 ? 2.48  149  221   30  1.70 ? 0.10    2.05 ?0.31

Asp. 24  500   2-17   8.175 ? 1.16   77  147  176   2.24 ? 0.15 2.77?0.24

    1000   1-20   7.110 ? 0.61  61   148  191  2.32 ? 0.12  2.46 ?0.10 ***

 2000    3-20    7.980 ? 0.44   58   214 128   2.17 ? 0.09  2.23?0.20 *

MMC 48 0.3 24-104  56.625 ? 4.66  236   160    4    1.42 ? 0.03  1.95 ?0.20

Asp. 48  500   3-20   7.900 ? 0.60   73   133 194   2.30 ? 0.13   2.98?0.08*

  1000    3-15    8.280 ? 0.66    83   170  147   2.16 ? 0.11 2.21 ?0.22*

2000  3-16    8.550 ? 0.38  130   215   55  1.81 ? 0.07 **  1.49? 0.14***

 # A total 100 cells were scored for the SCE assay; 400 cells were scored
for RI.

     *p < 0.05.
   **p < 0.01.
 ***p < 0.001.

Chromatid breaks,
chromosome breaks,
sister union (union of sister chromatids of a chromosome) and
single chromatid union (union of one chromatid of different chromosomes)
were the most common chromosomal abnormalities.

ASP did not decrease the RI except the highest concentration for 48 h
treatment period.

However, ASP significantly decreased the MI at all concentrations for 24 and
48 h treatment periods when compared with control ( Table 2  ).

This decrease was dose-dependent ( r = - 0.96 and r = - 0.97,
respectively ).

ASP induced micronucleus formation at 2000 ?g/ml concentrations
for 24 and 48 h treatment periods ( Table 3 ).

This effect was also dose-dependent for 48 hours treatment period ( r =
0.97 ).

ASP also dose-dependently decreased the ratio of binucleated to
mononucleated cells for 24- and 48-hour treatment periods
( r = - 0.81 and r = - 0.98, respectively ) ( Table 3 ).

This decrease was clearly related with the decreasing the MI in Table 2 .

Table 3. The Frequency of Micronuclei in Cultured Human Lymphocytes Treated
with Aspartame  # .

Test subst. Treatment

    Periods ( hours )  Concentr. ( ?g/ml )

    Percent micronucleated  binucleated cells    Binucleated
cells/mononucleated cells

Control      --      --                     0.270 ? 0.04   0.130 ? 0.01

MMC a   24       0.3 ?g/ml          1.130 ? 0.14    0.061 ?0.00

ASP        24   500                      0.373 ? 0.14    0.096? 0.01

                    1000                     0.335 ? 0.07    0.072 ? 0.00*

                    2000                     0.597 ? 0.12 * 0.069 ? 0.00 *

MMC a  48        0.3 ?g/ml          5.697 ? 0.35       0.069 ?0.00

ASP       48    500                      0.298 ? 0.06      0.062? 0.00 *

                   1000                      0.322 ? 0.04     0.058 ?0.00 *

                   2000                     0.522 ? 0.08 *   0.040 ? 0.00*

 #  A total of 8000 binucleated cells were scored.
 a  Only 7000 cells were scored due to excessive toxicity.
 *  p < 0.05.

ASP did not change the pH and the osmolality of the medium.
The osmolality was measured as 342 milliosmol in control and
346 milliosmomol in the maximum dose of ASP (2000 ?g/ml).

ASP did not increase the number of revertants of TA98 in the absence or
presence of S9 mix.

ASP slightly increased the number of revertants of TA100 in the absence of
S9 mix but this is not considered to represent a positive response.

There is no dose-dependent effect ( Table 4 ).

The effect of ASP on TA100 strain was greater than TA98 strain.

Table 4. The Mutagenicity of Aspartame on S.typhimurium TA98 and TA100
Strains in the Presence or Absence of S9 Mix.

Test substance  Conc. ( ?g/plate )

Strains                     TA98                   TA100

                  - S9                + S9              - S9          +S9

Control   --     16.00 ? 1.52     27.33 ? 3.96  73.33 ? 7.22    75.33? 3.67

4-NPD 200         488.00 ? 24.79    --             653.33 ? 16.23        --

2-AF    20           --     293.83 ? 10.04        --      409.00?30.26

ASP    50   9.00 ? 1.46 *    25.50 ? 2.89    81.33 ? 4.13    79.00?3.42

       100  18.33 ? 1.62 *    29.16 ? 2.18    90.50 ? 2.89 **  94.16?5.61*

      250   19.66 ? 2.15    37.00 ? 4.89   87.00 ? 5.64 *  86.00 ? 4.00*

     500   21.83 ? 1.70 *   33.00 ? 2.85   100.00 ? 4.41 **  90.00?2.88**

   1000  20.66 ? 1.85 *   27.33 ? 3.15   103.33 ? 5.14 **    84.66?6.73

  2000  17.50 ? 1.38     24.33 ? 1.94    96.33 ? 6.72 *   81.00 ?3.34

   *  p < 0.05.
 **  p < 0.01.

Discussion

In this study, ASP significantly induced CA and micronucleus formation and
showed a cytotoxic effect by decreasing the MI.

However, ASP did not induce the SCE and
it had no mutagenic effect on the tester strains TA98 and TA100 of S.
typhimurium in the presence and absence of S9 mix.

ASP is hydrolysed in the gut to yield aspartic acid, phenylalanine, methanol
and cyclised diketopiperazine ( Maher, 1987; Ranney and Oppermann, 1979 ).

There are a lot of studies on genotoxicity of metabolities of ASP
( Austin et al., 1992;
Brook and Chandley, 1985;
Generoso et al., 1995;
Sargentini and Smith, 1986 ).

Shephard et al. ( 1991 ) reported that ASP
has a weak mutagenic effect in Ames test after nitrosation.

Shephard et al. ( 1993 ) reported that, in the human stomach, the chain
nitrosation of the amino acids (Phe) and aspartame might be more important
than the reactions at the primary amino group.

However, Butchko et al. ( 2002 ) reported that ASP is safe and it was also
reported that ASP was not mutagenic and clastogenic in animals
( Durnev et al., 1995;
Jeffrey and Williams, 2000;
Molinary, 1984 ).

In the present study, it was found that ASP had a genotoxic effect using CA
and micronuclei test in human lymphocytes but
had no mutagenic effect using Ames/Salmonella/microsome test and
did not induce SCE, in human lymphocytes.

It has been reported that ASP does not cause brain and bladder tumours
( Hagiwara et al., 1984;
Ishii, 1981;
Ito et al., 1984 )
however, there are some reports that ASP ( Olney et al., 1996 ) and
especially its metabolites, phenylalanine and methanol ( Schwartz, 1999 )
increased the breast, brain and prostate cancer incidence.

The data obtained from a study carried out by FDA supported the report of
Olney et al., 1996 in the assay on 320 Sprague-Dawley rats fed with ASP
which caused brain cancer [ According to Study E33-34 in master file 134 on
ASP from Weihrauch et al. (2001) ].

Schwartz ( 1999 ) also reported that methanol is converted to formaldehyde
which then accumulates in the cells.
Formaldehyde has been considered an inducer of cancer and acts to alter DNA
( Ewertz, 1993;
Ewertz and Gill, 1990 ).

Olney et al. ( 1996 ) reviewed and explained that ASP had mutagenic
potential.

Ahmed and Thomas ( 1992 ) reported that cyclamate (sweetener) was not
carcinogenic by itself;
however, it might have cancer-promoting or carcinogenic activities.

In this study, we found that, ASP did appear to have genotoxic potential
consistent with potential carcinogenicity.

According to these results, phenyalanine and methanol, which are metabolic
products of ASP, have a genotoxic risk for humans.

In contrast, ASP was not found as a mutagen in in vivo studies.

However, in the present study, ASP induced CA and micronuclei in human
lyphocytes dose-dependently.

ASP did not change the osmolality of the medium at the maximum
concentrations ( 346 milliosmol ) when compared with untreated medium ( 342
milliosmol ).

It was reported that a deviation from physiological osmolality
( approximately 300 milliosmol ) can lead to genotoxic effects
( Nowak, 1984, 1997;
Seeberg et al., 1989 ).

According to these results, we can conclude that ASP induced CA and
percentage of micronuclei by itself because it did not alter the pH and
osmolality of the medium.

As shown, there are several contradictory studies about genotoxicity and
carcinogenicity of ASP.

However, it must be taken into account that ASP induced the CA and
micronuclei formation in a dose-dependent manner.

It is not possible to conclude that ASP is safe according to these results.

Therefore, it is necessary to be careful when using it in food and beverages
as a sweetener.

Acknowledgments

This study was funded by ?ukurova University Research Fund FEF 2002 BAP 21.
We also thank Mr. L.K. Nakamura for his kind collaboration.

Ahmed F. E. , Thomas D. B., Assessment of the carcinogenicity of the
nonnutritive sweetener cyclamate,
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Austin M. J. , Han Y. H. , Povirk L. F., DNA sequence analysis of mutations
induced by melphalan in the CHO aprt locus,
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 Brook J. D. , Chandley A. C., Testing of 3 chemical compounds for
aneuploidy induction in the female mouse,
Mutat. Res., 157 (2-3) , (1985) 215-220.

 Butchko H. H. , Stargel W. W. , Comer C. P. , Mayhew D. A. , Benninger C.,
Blackburn G. L. , de Sonneville L. M. , Geha R. S. , Hertelendy Z. ,
Koestner A. , Leon A. S. , Liepa G. U. , McMartin K. E. , Mendenhall C. L. ,
Munro I. C. , Novotny E. J. , Renwick A. G. , Schiffman S. S. , Schomer D.
L. , Shaywitz B. A. , Spiers P. A. , Tephly T. R. , Thomas J. A. , Trefz F.
K.,
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 Durnev A. D. , Oreshchenko A. V. , Kulakova A. V. , Beresten N. F. ,
Seredenin S. B., Clastogenic activity of dietary sugar substitutes,
Vopr. Med. Khim., 41 (4) , (1995) 31-33.

 Ewertz M., Breast cancer in Denmark. Incidence, risk factors, and
characteristics of survival,
Acta Oncol., 32 (1993) 595-615.

 Ewertz M. , Gill C., Dietary factors and breast-cancer risk in Denmark,
Int. J. Cancer, 46 (1990) 779-784.

 Generoso W. M. , Witt K. L. , Cain K. T. , Hughes L. , Cacheiro N. L. ,
Lockhart A. M. , Shelby M. D., Dominant lethal and heritable translocation
test with chlorambucil and melphalan in male mice,
Mutat. Res., 345 (3-4) , (1995) 167-180.

 Hagiwara A. , Fukushima S. , Kitaori M. , Shibata M. , Ito M., Effects of
three sweeteners on the rat urinary bladder carcinogenesis initiated by
N-butyl-N-(4-hydroxybuthyl)-nitrosamine,
Gann, 75 (9) , (1984) 763-768.

 Ishii H., Incidence of brain tumors in rats fed aspartame,
Toxicol. Lett., 7 (6) , (1981) 433-438.

 Ito N. , Fukushima S. , Shirai T. , Hagiwara A. , Imaida K., Drugs, food
additives and natural products as promoters in rat urinary bladder
carcinogenesis,
IARC Sci. Publ., 56 (1984) 399-407.

 Jeffrey A. M. , Williams G. M., Lack of DNA-damaging activity of five
non-nutritive sweeteners in the rat hepatocyte/DNA repair assay,
Food Chem. Toxicol., 38 (4) , (2000) 335-338.

 Mace M. L. , Daskal Y. , Wray W., Scanning-electron microscopy of
chromosome aberrations,
Mutat. Res., 52 (1978) 199-206.

 Maher T. J., Natural food constituents and food additives: the
pharmacologic connection,
J. Allergy Clin. Immunol., 79 (1987) 413-422.

 Maron D. M. , Ames B. N., Revised method for the Salmonella mutagenicity
test,
Mutat. Res., 113 (1983) 173-215.

 Molinary S. V. Preiclinical Studies of Aspartame in Non-primate Animals,
Aspartame, Physiology and Biochemistry, Stegink L. D. , Tiler L. S.
Marcel Dekker, New York, 1984, pp. 289-306.

 Nowak C., Induction of chromosomal aberrations by hypotonic culture
conditions is dependent of the S-phase in V79 hamster cells,
Environ. Mol. Mutagen., 13 (1) , (1984) 44-49.

 Nowak C., Studies on the ability of hypotonic solutions to induce
chromosomal aberrations in V79 cells,
Teratog. Carcinog. Mutagen., 7 (6) , (1997) 515-525.

 Olney J. W. , Farber N. B. , Spitznagel E. , Robins L. N., Increasing
brain tumors rates: is there a link to aspartame?,
J. Neuropathol. Exp. Neurol., 55 (11) , (1996) 1115-1123.

 Ranney R. E. , Oppermann J. A., A review of the metabolism of the aspartyl
moiety of aspartame in experimental animals and man,
J. Environ. Pathol. Toxicol., 2 (4) , (1979) 979-985.

 Rothfus A. , Sch?tz P. , Bochum S. , Volm T. , Eberhardt E. , Kreirenberg
R. , Vogel W. , Speit G., Induced micronucleus frequencies in peripheral
lymphocytes as a screening test for carriers of a BRCA1 mutation in breast
cancer families,
Cancer Res., 60 (2000) 390-394.

 Sargentini N. J. , Smith K. C., Mutagenesis by normal metabolites in
Escherichia coli: phenylalanine mutagenesis is dependent on error-prone DNA
repair,
Mutat. Res., 161 (2) , (1986) 113-118.

 Schwartz G. R., Aspartame and breast and other cancers,
West J. Med., 171 (1999) 300-301.

 Seeberg A. H. , Mosesso P. , Forster R., High-dose-level effects in
mutagenicity assays utilizing mammalian cells in culture,
Mutagenesis, 3 (3), (1989) 213-218.

 Shephard E. E. , Meier I. , Lutz W. K., Alkylating potency of nitrosated
amino acids and peptides,
IARC Sci. Publ., 105 (1991) 383-387.

 Shephard S. E. , Wakabayashi K. , Nagao M., Mutagenic activity of peptides
and the artificial sweetener aspartame after nitrosation,
Food Chem. Toxicol., 31 (5) , (1993) 323-329.

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of bromodeoxyuridine-substituted chromosomes. II Differences between the
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Hum. Genet., 70 (1985) 126-129.

 The ministry of Agricultural of Turkey Food Codex,
Globus World Publications, Turkey, 1997, pp. 46-47.

 Weihrauch M. R. , Diehl V. , Bohlen H., K?nstliche S?stoffe -- Haben sie
ein kanzerogenes potential?,
Med. Klin., 96 (2001) 670-675.
*********************************************************************

http://www.ldb.org/vl/geo/mid_east/5tur.htm
UN links for public health in Turkey

http://www.tubitak.gov.tr/english/
The Scientific and Technical Research Council of Turkey

(+90 312) 4677798
(+90 312) 4673002
(+90 312) 4685300 / 4400-4401
fax:(+90 312) 4272672
E-mali:  aysegul@tubitak.gov.tr
Adress: Adres: T?BITAK Atat?rk Bulvari No:221, Kavaklidere,
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Turkish Journal of Medical Science    medsci@tubitak.gov.tr  free full texts

Turkish Journal of Biology       biol@tubitak.gov.tr  free full texts
*********************************************************************

PubMed  Items 1 - 5 of 5   One page.

1: Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M,
Diler SB.
Genotoxicity of aspartame.
Drug Chem Toxicol. 2004 Aug; 27(3): 257-68.
PMID: 15478947 [PubMed - in process]

2: Topaktas M, Rencuzogullari E, Ila HB, Kayraldiz A.
Chromosome aberration and sister chromatid exchange in workers of the iron
and steel factory of Iskenderun, Turkey.
Teratog Carcinog Mutagen. 2002; 22(6): 411-23.
PMID: 12395403 [PubMed - indexed for MEDLINE]

3: Rencuzogullari E, Ila HB, Topaktas M, Kayraldiz A, Budak S, Arslan M.
No significant increase in chromosome aberrations and sister chromatid
exchanges in cultured human lymphocytes treated with spiramycin.
Teratog Carcinog Mutagen. 2002; 22(1): 51-8.
PMID: 11754387 [PubMed - indexed for MEDLINE]

4: Rencuzogullari E, Ila HB, Kayraldiz A, Topaktas M.
Chromosome aberrations and sister chromatid exchanges in cultured human
lymphocytes treated with sodium metabisulfite, a food preservative.
Mutat Res. 2001 Feb 20; 490(2): 107-12.
PMID: 11342236 [PubMed - indexed for MEDLINE]

5: Topaktas M, Rencuzogullari E, Ila HB.
In vivo chromosomal aberrations in bone marrow cells of rats treated with
Marshal.
Mutat Res. 1996 Dec 20; 371(3-4): 259-64.
PMID: 9008727 [PubMed - indexed for MEDLINE]
*********************************************************************

Rich Murray, MA    Room For All    rmforall@comcast.net
1943 Otowi Road Santa Fe, New Mexico 87505   USA         505-501-2298
http://groups.yahoo.com/group/aspartameNM/messages    group with 134
members, 1,133 posts in a public, searchable archive.

The moderated newsgroup, bionet.toxicology , has accepted 23 of my long
reviews since March 24:

Dr. Charles "Chuck" A. Miller III   rellim@tulane.edu
Associate Professor of Environmental Health Sciences
374 Johnston Building, SL29
Tulane Univ. School of Public Health and Tropical Medicine
1430 Tulane Avenue  New Orleans, LA 70112   (504)585-6942
Bionet.toxicology news group  http://www.bio.net/hypermail/toxicol/current

http://groups.yahoo.com/group/aspartameNM/message/1128
hangover symptoms from methanol from dark wines and liquors or 11% methanol
part of aspartame, review of research: Jones AW 1988:  Murray 2004.10.23
rmforall

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).   However,
about 30% of the methanol remains in the body as cumulative durable toxic
metabolites of formaldehyde and formic acid, 37 mg daily, a gram every
month, accumulating in and affecting every tissue -- over 60 times the USA
EPA limit for formaldehyde in drinking water.

Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
both ordinary amino acids, bound loosely together by methanol (wood alcohol,
11%).   Similar amounts of methanol in many fruits and vegetables, locked up
in complex pectin molecules, and always paired with ethanol, its natural
antidote, are not usually released by human digestion and so are harmless.
But the readily released methanol from aspartame is within hours largely
turned by the liver into formaldehyde and then formic acid, both potent,
cumulative toxins.

Red wine contains twice as much methanol as does diet soda as an impurity,
about one part in ten thousand.  It is the natural conversion by the body of
this methanol into formaldehyde and formic acid that is the main cause of
the well known "morning after" hangover symptoms: headache, nausea,
weakness, impaired memory, irritability, anxiety, "brain fog", body pains --
the same symptoms as aspartame victims.

Jones AW.
Elimination half-life of methanol during hangover.
Pharmacol Toxicol. 1987 Mar; 60(3): 217-20.   PMID: 3588516

" But higher blood-methanol concentrations are definitely associated with
higher blood-ethanol in this sample of Swedish drinking drivers.

Frequent exposure to methanol and its toxic products of metabolism,
formaldehyde and formic acid, might constitute an additional health risk
associated with heavy drinking in predisposed individuals. "   Jones AW 1988

Forensic Sci Int. 1988 Jun; 37(4): 277-85.
Relationship between the concentration of ethanol and methanol in blood
samples from Swedish drinking drivers.
Jones AW, Lowinger H.
Department of Alcohol Toxicology, University Hospital, Linkoping, Sweden.
Jones AW has 341 items in PubMed.

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW: also some
methanol from fruit pectin in colon: Murray 2004.09.11 rmforall

http://bmj.bmjjournals.com/search.dtl      search to get free full text
British Medical Journal 1997 (4 January); 314(7073): 2.
Ian Calder, F.R.C.A. [ Tel/Fax: 0171 720 9279   Consultant Anaesthetist at
the National Hospital for Neurology and Neurosurgery,
London  WCIN 3BG, UK ]

Editorials         Hangovers: Not the ethanol - perhaps the methanol

" Pawan compared the hangover produced by different types of drink (but only
one brand of each) in his study of 20 volunteers. The severity of hangover
symptoms declined in the order of brandy, red wine, rum, whisky, white wine,
gin, vodka, and pure ethanol.(6)  Vodka and pure ethanol caused only mild
headaches in two volunteers. "

6. Pawan GL.
Alcoholic drinks and hangover effects.
Proc Nutr Soc 1973 May; 32: 15A.  PMID: 4760771

J.A. Oppermann's Searle Co. lab  proved that 30% of the methanol in
aspartame fed once to monkeys remained --  surely as formaldehyde and formic
acid in all tissues (1973, 1976, 1979).

This was confirmed by an expert team at the University of Barcelona (Trocho

C, Alemany M, et al, 1998):  " ...the binding of methanol-derived carbon [
from low levels of aspartame fed to rats for 10 days ] to tissue proteins
was widespread, affecting all systems, fully reaching even sensitive targets
such as the brain and retina...These are indeed extremely high levels for
adducts of formaldehyde, a substance responsible for chronic deleterious
effects (33), that has also been considered carcinogenic. "   Prof. Mari?
Alemany  alemany@bio.ub.es     Life Sci.  1998 June 26; 63(5): 337-49. PMID:
9714421

http://groups.yahoo.com/group/aspartameNM/message/1016  President Bush &
formaldehyde (aspartame) toxicity: Ramazzini Foundation carcinogenicity
results Dec 2002: Soffritti: Murray 2003.08.03  Ann N Y Acad Sci. 2002 Dec;
982: 87-105.  Results of long-term experimental studies on the
carcinogenicity of formaldehyde and acetaldehyde in rats.  M. Soffritti et
al.  Cancer Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr@tin.it     p. 88  " The
sweetening agent aspartame hydrolyzes in the gastrointestinal tract to
become free methyl alcohol, which is metabolized in the liver to
formaldehyde, formic acid, and CO2. (11) "   Ref. (11) is:  Medinsky MA &
Dorman DC. 1994; Assessing risks of low-level methanol exposure. CIIT Act.
14: 1-7.

http://groups.yahoo.com/group/aspartameNM/message/1128
hangover symptoms from methanol from dark wines and liquors or 11% methanol
part of aspartame, review of research: Jones AW 1988: genotoxicity in human
cells proven, Rencuzogullari E et al 2004 Aug: Murray 2004.10.23 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
Drug Chem Toxicol. 2004 Aug; 27(3): 257-68. Genotoxicity of aspartame.
Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler
SB.  Biology Dept, Faculty of Arts and Sciences, Natural and Applied
Sciences Institute, Cukurova University, Adana, Turkey.
reyyup@mail.cu.edu.tr   PMID: 15478947
This expert team found DNA damage in human  lymphocytes.
Rencuzogullari E has 4 other similar studies in PubMed.

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  Pharmacol Biochem Behav. 2004 May; 78(1): 121-7.  PMID: 15159141
Mona M. McConnaughey, Ph.D.  Research Assistant Professor  252-744-2756
mcconnaugheym@mail.ecu.edu   Twelve rats fed aspartame at otherwise nontoxic
levels for 4 months forgot how to turn right to get a treat, and had
specific brain changes.

http://groups.yahoo.com/group/aspartameNM/message/1067  eyelid contact
dermatitis by formaldehyde from aspartame, Hill AM & Belsito DV, Nov 2003:
Murray 2004.03.30
Contact Dermatitis. 2003 Nov; 49(5): 258-9.   PMID: 14996049
A mysterious dermatitis was caused by a dose the same as two packets Equal
daily.

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@aol.com
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton@aecom.yu.edu

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@aol.com
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 ]

http://groups.yahoo.com/group/aspartameNM/message/1077  eight depressed
people react strongly to aspartame, Prof. Ralph G. Walton, MD, 1993
double-blind study, full text: Murray 2004.04.26 rmforall   They reported
with aspartame, compared to placebo, much higher levels of anxiety, poor
memory, nausea, depression, anger, and malaise.  A 60 kg subject would
have had 1800 mg aspartame, the same as nine 12-oz diet sodas, daily for 7
days.      330-740-3621  rwalton193@aol.com  PMID: 8373935

http://groups.yahoo.com/group/aspartameNM/message/1133
Mark Gold, most recent of 14 Rapid Responses to Aspartame and its effects on
health, BMJ: Murray 2004.11.06 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1124
8 more Rapid Responses to Aspartame and its effects on health, BMJ:
Murray 2004.10.18 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1120
5 critical Rapid Responses to Aspartame and its effects on health, Michael E
J Lean and Catherine R Hankey, BMJ 2004; 329: 755-756: Murray 2004.10.05
rmforall

http://groups.yahoo.com/group/aspartameNM/message/1117
Aspartame and its effects on health, Michael E.J. Lean, Catherine R. Hankey,
Glasgow UK, British Medical Journal: 11% methanol component of aspartame,
and same level of methanol in dark wines and liquors, turns to formaldehyde
and formic acid, the main cause of chronic hangover symptoms: Murray
2004.10.04 rmforall
http://bmj.bmjjournals.com/cgi/eletters/329/7469/755#76712

http://groups.yahoo.com/group/aspartameNM/message/927   Donald Rumsfeld,
1977 head of Searle Corp., got aspartame FDA approval: Turner: Murray
2002.12.23

http://groups.yahoo.com/group/aspartameNM/message/1065  politicians and
celebrities hooked on diet sodas (aspartame): Murray 2004.03.24
Senator John Edwards still has a dozen Diet Cokes daily -- a gallon,
which gives as much methanol as a half-gallon of red wine.

http://groups.yahoo.com/group/aspartameNM/message/1071   Aspartame
(NutraSweet, Equal, Canderel, E951), after eight years of controversy, was
suddenly and capriciously approved in July 1981 by a new FDA commissioner,
Arthur Hull Hayes, Jr ( just appointed by President Reagan ),  disregarding
the negative vote of his own Scientific Board of Inquiry.

http://google.com  gives 249,000 websites for "aspartame", with the top 8
of 10 listings being anti-aspartame, while http://groups.google.com  finds
on 700 MB of posts from 20 years of Usenet groups, 101,000 posts.
http://news.google.com  many recent aspartame items from 4500 sources.
http://www.ncbi.nlm.nih.gov/PubMed   lists 771 aspartame items.

http://groups.yahoo.com/group/aspartame/messages  837 members, 17,585 posts
in their public archive    http://www.presidiotex.com/aspartame/
Aspartame Victims Support Group  bryanth@presidiotex.com

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

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 rmforall  EU Scientific Committee on Food, a whitewash

http://www.holisticmed.com/aspartame/scf2002-response.htm  a detailed
critique of European Commission Scientific Committee on Food re aspartame
( 2002.12.04 )
http://www.HolisticMed.com/aspartame    mgold@holisticmed.com
Aspartame Toxicity Information Center    Mark D. Gold     also Co-Moderator
12 East Side Drive #2-18 Concord, NH 03301     603-225-2110
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

Many scientific studies and case histories report:  * headaches  * many body
and joint pains (or burning, tingling, tremors, twitching, spasms, cramps,
stiffness, numbness, difficulty swallowing)  *  fever, fatigue, swollen
glands  * "mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech, sexual
problems,  poor vision, hearing (deafness, tinnitus), or taste  * red face,
itching, rashes, allergic dermatitis, hair loss, burning eyes or throat, dry
eyes or mouth, mouth sores, burning tongue * obesity, bloating, edema,
anorexia, poor appetite or excessive hunger or thirst  * breathing problems,
shortness of breath * nausea, diarrhea or constipation  * coldness
* sweating  * racing heart, low or high blood pressure, erratic blood sugar
levels  * hypothryroidism or hyperthyroidism * seizures  * birth defects
* brain cancers * addiction  * aggrivates diabetes, autism, allergies,
lupus, ADHD, fibromyalgia, chronic fatigue syndrome, multiple chemical
sensitivity, multiple sclerosis, pseudotumor cerebri,  Grave's disease,
Parkinson's disease, and interstitial cystitis (bladder pain).
**********************************************************************

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@hachinohe-ct.ac.jp ; s.tsuda@iwate-u.ac.jp

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 (2000 mg/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 100 mg/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.  Methanol is the only component of aspartame that can lead
to DNA damage. ]

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]     ]

J Toxicol Sci. 2002 Dec; 27 Suppl 1: 1-8.
[Genotoxicity studies of stevia extract and steviol by the comet assay]
[Article in Japanese]
Sekihashi K, Saitoh H, Sasaki Y.   yfsasaki-c@hachinohe-ct.ac.jp
Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shin-ei,
Kiyota-ku, Sapporo 004-0839, Japan.

The genotoxicity of steviol, a metabolite of stevia extract, was evaluated
for its genotoxic potential using the comet assay.
In an in vitro study, steviol at 62.5, 125, 250, and 500 micrograms/ml did
not damage the nuclear DNA of TK6 and WTK1 cells in the presence and absence
of S9 mix.
In vivo studies of steviol were conducted by two independent organizations.
Mice were sacrificed 3 and 24 hr after one oral administration of steviol at
250, 500, 1000, and 2000 mg/kg.
DNA damage in multiple mouse organs was measured by the comet assay as
modified by us.
After oral treatment, stomach, colon, liver, kidney and testis DNA were not
damaged.
The in vivo genotoxicity of stevia extract was also evaluated for its
genotoxic potential using the comet assay.
Mice were sacrificed 3 and 24 hr after oral administration of stevia extract
at 250, 500, 1000, and 2000 mg/kg.
Stomach, colon and liver DNA were not damaged.
As all studies showed negative responses, stevia extract and steviol are
concluded to not have DNA-damaging activity in cultured cells and mouse
organs.  PMID: 12533916
**********************************************************************

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@atlas.uoa.gr
"K.H. Schulpis" <inchildh@otenet.gr>  "G.J. Reclos" <reklos@otenet.gr>

http://groups.yahoo.com/group/aspartameNM/message/938
aspartame harms mice brain cells: Hetle & Eltervaag: 2001 thesis
abstract: Sonnewald 1995 study, full text: Murray 2003.01.05 rmforall

http://groups.yahoo.com/group/aspartameNM/message/760
Kovatsi L, Tsouggas M
The effect of oral aspartame administration on the
balance of magnesium in the rat.
Magnes Res 2001 Sep;14(3): 189-94.
Laboratory of Forensic Medicine & Toxicology, Faculty of Medicine
Aristotle University of Thessaloniki, Greece  kovatsi@med.auth.gr

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold:
Wilson: CIIN: Murray 2002.12.12 rmforall

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 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.  toxicology@drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 2002.12.09 rmforall

Environ Health Perspect. 2003 Sep; 111(12): 1461-4.
Elevated nitric oxide/peroxynitrite theory of multiple chemical sensitivity:
central role of N-methyl-D-aspartate receptors in the sensitivity mechanism.
Pall ML.
School of Molecular Biosciences, 301 Abelson Hall, Washington State
University, Pullman, WA 99164, USA. martin_pall@wsu.edu

The elevated nitric oxide/peroxynitrite and the neural sensitization
theories of multiple chemical sensitivity (MCS) are extended here to propose
a central mechanism for the exquisite sensitivity to organic solvents
apparently induced by previous chemical exposure in MCS.
This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA)
receptors by organic solvents producing elevated nitric oxide and
peroxynitrite, leading in turn to increased stimulating of and
hypersensitivity of NMDA receptors.
In this way, organic solvent exposure may produce progressive sensitivity to
organic solvents.
Pesticides such as organophosphates and carbamates may act via muscarinic
stimulation to produce a similar biochemical and sensitivity response.
Accessory mechanisms of sensitivity may involve both increased blood-brain
barrier permeability, induced by peroxynitrite, and cytochrome P450
inhibition by nitric oxide.
The NMDA hyperactivity/hypersensitivity and excessive nitric
oxide/peroxynitrite view of MCS provides answers to many of the most
puzzling aspects of MCS while building on previous studies and views of this
condition.   PMID: 12948884

Prof. Pall describes processes by which an initial trigger exposure, such as
carbon monoxide or formaldehyde, can generate hypersensitivity to many
substances.  He himself had recovered from a sudden, debilitating attack of
multiple chemical sensitivity in June/July 1997.

http://groups.yahoo.com/group/aspartameNM/message/1055
hormesis: possible benefits of low-level  aspartame (methanol, formaldehyde)
use: Calabrese: Soffritti:  Murray 3.11.4

http://groups.yahoo.com/group/aspartameNM/message/1056
disorders of NMDA glutamate receptors in brain range from high activity
(MCS, CF, PTSD, FM, from carbon monoxide or formaldehyde (methanol,
aspartame)-- Pall)
to low activity (schizophrenia-- Coyle, Goff, Javitts):
Murray 3.13.4 rmforall
*****************************************************************

http://www.e-guana.net/organizations.php3?action=printContentItem&orgid=61&typeI
D=203&itemID=9815&User_Session=b4ab653946086546f3318b44b6d91ec6


Media Contacts:
Wendy Thompson, 617-896-4888, wendy@oldwayspt.org
Sara Baer-Sinnott, 617-896-4848, sara@oldwayspt.org

November 8, 2004

SCIENTISTS REACH NEW CONSENSUS ABOUT SWEETNESS; RELEASE CONSENSUS STATEMENT
FROM MEXICO CITY CONFERENCE

Responding To Escalating Consumer Confusion About Diet/Health Links, Oldways
Gathers Leading Scientists and Communications Experts To Develop Tools
Consumers Can Use To Manage Sweetness and Focus on the Total Diet Instead of
"Bits and Pieces"

MEXICO CITY, November 8, 2004 - A scientific consensus statement released
this weekend concludes that "Sweetness is an innate and strong force in
shaping human evolution" that "continues as a strong force in food and drink
selection," adding that "Good health depends on wise management of calories
from all food and drink sources, coupled with wise lifestyle choices that
include regular exercise." The consensus was reached at a three-day
international scientific and communications conference in Mexico City titled
"Managing Sweetness."

The meeting introduced this innovative "Managing Sweetness" concept as a new
tool to help dietary educators and advisors reach clients and consumers
effectively, because the evidence of steadily-rising obesity and overweight
statistics makes clear that conventional tools are not motivating consumers
to follow sound dietary advice. This new "Managing Sweetness" tool departs
from the conventional by focussing on the inherent duality of foods and
drinks: they bring us the welcome pleasures of eating and drinking, but they
also require us to manage them wisely for a life of good health.

The Mexico City conference was organized by Oldways Preservation Trust, a
nonprofit food issues think tank and developer of the Mediterranean Diet
Pyramid. It brought together an international group of leading scientists
and communications experts to examine:

1. the latest research on sweetness sugars, sweeteners and carbohydrates;
2. the extent of consumer confusion on sweetness and its sources;
3. the history of dietary guides and other programs to change consumption
patterns, and
4. the potential for new dietary messages that will encourage consumers to
manage sweetness and other elements of their total diets.

The format for the conference was specifically designed as a search for
solutions, built on a process of scientific straight talk and not on a
series of debates.

"Conventional dietary guidance is failing to persuade American about the
'twin peaks' of wise eating and drinking, which are first, to stick with
solid advice and avoid fad eating patterns, and second, to stick with the
calorie equation by balancing calories taken in against calories burned
off," said K. Dun Gifford, President of Oldways. "We convened a panel of top
experts in carbohydrates and nutrition science to inject some common-sense
thinking and straight talk into the current fractious diet debate and to
help find common ground. We introduced the concept of "Managing Sweetness"
as a breakthrough that will help consumers who are confused and disheartened
in their search for successful, practical dietary guidance solutions."

"Fad diets or dietary advice based on demonizing any one food, including
sweetness and sugars, are diet plans that are doomed to fail," said John
Foreyt, PhD, Professor of Medicine and Director of the Behavioral Medicine
Research Center at Baylor College of Medicine, a co-chair of the Scientific
Consensus Committee as well as a leading US obesity expert. "The issue is
portion control, and the concept of managing sweetness is an innovative step
forward which has real potential to affect consumer behavior positively,"
Foreyt stated.

Click here to view Scientific Consensus Statement and the Conference context
for key findings.   [ gives meaningless garbled text ]

About Oldways Preservation Trust

Oldways Preservation Trust is the widely-respected nonprofit "food issues
think tank" praised for translating the complex details of nutrition science
into the familiar language of food. This synthesis converts high-level
science into consumer-friendly health-promotion tools for a wide array of
cultural preferences.

Best known for its Mediterranean Diet Pyramid, Oldways develops and
organizes a wide variety of programs and materials about healthy,
traditional and sustainable food choices for consumers, scientists, the food
industry, health professionals, chefs, journalists and policy makers, and
its effectiveness is well known.

Sponsorship

Oldways is pleased to acknowledge the support of the Beverage Institute for
Health and Wellness, Coca-Cola, Ajinomoto, Cargill, Nutrinova and Tate &
Lyle on this project. "We are really pleased that they accepted our proposal
for a scientific conference to develop the new concept of "managing
sweetness," said Oldways President K. Dun Gifford. "The lessons of history
teach that working cooperatively with industry technical experts and
independent scientific experts has the highest possible chance for reaching
realistic, successful and effective outcomes."

http://www.oldwayspt.org/

Oldways Preservation Trust   oldways@oldwayspt.org

266 Beacon Street  Boston, MA 02116  Tel: 617.421.5500  Fax: 617.421.5511

http://www.oldwayspt.org/about/about.html

What is Oldways?

Meet the Oldways staff

Oldways is the widely-respected nonprofit "food issues think tank" praised
for translating the complex details of nutrition science into "the familiar
language of food." This synthesis converts high-level science into a
consumer-friendly health-promotion tool for consumers, health professionals,
chefs, farmers, journalists, and the food industry.

The Encyclopedia Britannica explains it this way: "What makes Oldways
different from other organizations that promote sound nutrition or fine
cuisines is its combination of scholarly grounding in science, strong social
conscience, and commitment to culinary excellence."

Oldways education programs are effective: they impact government policies;
they reach decision-makers such as chefs and food service executives; their
focus on good foods has helped consumers to modify their eating behaviors;
and their trend forecasts are accurate.

The largest circulation US food magazine (Cooking Light) has acknowledged
Oldways' track record: "Since its founding in 1990, this much-acclaimed
organization has profoundly changed how Americans think about healthy food
and the practical wisdom of tradition."
For a decade Oldways warned that powerful waves of unhealthy "junk foods"
and no-fat or low-fat "techno-foods" were eroding healthy "real foods" and
fostering an epidemic of crippling chronic diseases. It argued that the
"anti-fat craze" was driving steep increases in calorie consumption and
surges of obesity and diabetes.

Acknowledging this in his December 2001 Annual Report, the US Surgeon
General concluded that overweight and obesity were overtaking smoking as the
largest single threat to lifelong good health.

Oldways responded to these waves of fake foods with conferences, symposiums,
and tours which accumulated persuasive scientific evidence that traditional
foods and eating patterns were far healthier than "westernized" ways.

With its scientific partners, Oldways consolidated these healthy patterns
into four pyramid-shaped eating guides - Mediterranean, Asian, Latin
American and Vegetarian. Over 500 scientists contributed to the development
and updating of these pyramids, now recognized as representing the "gold
standard" of current nutrition science.

Consumers enthusiastically embraced these Oldways "eating pyramids." For
example, consumption of Mediterranean food products soared since Oldways
introduced the Mediterranean Diet Pyramid in 1993; extra virgin olive oil
appeared on restaurant tables and retail sales quadrupled as consumers
sought out its healthfulness and flavors.
Reacting to the continuing fattening of America, Old-ways developed an
important new approach, called EATWISET, to help individuals and families
turn away from junk foods and return to the healthy real foods of the "old
ways."

EATWISET is modeled on the eating behaviors of healthy individuals and
families who are "wise eaters." It focuses on the simple techniques these
wise eaters use to balance their calories among carbohydrates, proteins and
fats, and introduces a set of new tools such as its "calorie thermometer."

Oldways creates and operates a wide range of domestic and international
programs based on science, traditional foods, and sustainability, all
accompanied by wise eating, regular exercise, and culinary pleasures.
Program attendees are retailers, importers, chefs, journalists, health
professionals, government officials, and Friends of Oldways.
These educational activities include high-level scientific and media
conferences on public and private policies; trends; ingredients; behavior
change; continuing education for health professionals (MDs, RDs, and
others); a cooking and nutrition curriculum for school children;
sustainability programs for chefs; and specific topics such as water
farming, whole grains, and "gold standard" eating patterns.

EATWISET is Oldways' focus for helping consumers to make wise food choices
for life.

Click here for a complete and chronological listing of all Oldways programs
and educational initiatives.

? 1999-2004 Oldways Preservation and Exchange Trust
******************************************************************

http://www.wholegrainscouncil.org/PR020904IntroWGC.html

For more information about the Whole Grains Council, or to arrange for
interviews of the Founding Charter Members or Scientific Advisory Committee,
please contact Sara Baer-Sinnott, Executive Vice President
(sara@oldwayspt.org) or Cynthia Harriman, Manager of Partner Services
(cynthia@oldwayspt.org).
Oldways Preservation Trust
266 Beacon Street, Boston, MA 02116   Tel (617) 421-5500

http://www.wholegrainscouncil.org/PR042504FMIhealth.html  fine health
studies

Members of the Whole Grains Council

While we work on the projects above, we will continue to seek out new
members, to enable the Council to fund new initiatives and create momentum
in its mission to increase consumption of whole grains.

Already, the Council includes an impressive mix of large and small companies
and commodity groups. Our founding members include: the American Institute
of Baking, Arrowhead Mills, Barbara's Bakery, Bob's Red Mill, Campbell Soup,
Farmer Direct Foods, Fleischmann's Yeast, Frito-Lay, General Mills, Hodgson
Mill, Kamut Association / Montana Flour & Grain, LeSaffre Yeast, Lotus
Foods, National Sorghum Grain Producers, Natural Ovens, Panera Bread, Roman
Meal Company, Rudi's Organic Bakery, Snyder's of Hanover, Sorghum Partners,
Sunnyland Mills and the USA Rcie Federation.  A list of all current industry
members, along with scientific, culinary and media collaborators and
advisors, is available at

www.wholegrainscouncil.org/members.html.

http://www.wholegrainscouncil.org/members.html

http://www.wholegrainscouncil.org/SciCuli.html     Advisors & Collaborators
Scientific, Culinary & Media

A list of advisors & collaborators to date

Len Marquart, PhD, RD
University of Minnesota
Co-Chair, Scientific Advisory Committee
Marquart, Len (Len)  lmarquar@umn.edu 612-624-3255 952-292-4719
Food Science and Nutrition

Julie Miller Jones, PhD, CNS, LN   Professor of nutrition and food science
College of St. Catherine     jmjones@stkate.edu   (651) 636-2275
holistic@stkate.edu   Minneapolis, MN 55454
Co-Chair, Scientific Advisory Committee  651-690-7836

James W. Anderson, MD     janders@uky.edu
University of Kentucky
http://www.ag.uiuc.edu/~stratsoy/anderson.html
Metabolic Research Group
VA Medical Center and
University of Kentucky
Lexington, KY 40511
Phone: (606) 281-4954
Fax: (606) 233-3832
Professor    Departmental Affiliation Endocrinology
Mailing Address 1030 South Broadway, Suite 5  Lexington,  KY  40504-2681
Office Telephone (859) 257-4058 Fax (859) 257-8410

Gary Fulcher, PhD
University of Minnesota
R G Fulcher
Title:Professor
Department:Food Science/Nutrition AFES (office: Food Sci and Nutrition)
Dept Campus:UMN Twin Cities
E-mail Address:   gfulcher@umn.edu
Internet ID:  gfulcher
Office Address:  Food Sci and Nutrition  167 F Sc N  1334 Eckles Ave
St Paul, MN 55108
Campus Mail: Food Sci and Nutrition  Room 225 FScN  6099
1334 Eckles Ave St Paul, MN 55108
Office Phone:+1 612-626-1220  Fax:+1 612-625-5272

Victor Fulgoni III, PhD  vic3rd@aol.com
Nutrition Impact, LLC    http://www.nutritionimpact.com/links.html
Nutrition Impact is a small consulting firm that specializes in helping
food & beverage companies develop and communicate aggressive, science-based
claims about their products and services.
The major staff person at Nutrition Impact is Dr. Victor Fulgoni, III. Dr.
Fulgoni worked for the Kellogg Company for over 15 years and was their Vice
President of Food and Nutrition Research.
Dr. Fulgoni completed his Bachelors degree at Rutgers University and his
Ph.D. at the University of Tennessee with a major in animal nutrition and a
minor in statistics.     http://www.nutritionimpact.com/resume.pdf
Nutrition Impact, LLC 9725 D Drive North
9725 D Drive North Battle Creek, MI 49014
Battle Creek, MI 49014
Phone: 616-962-0448 616-962-8254

Judith Hallfrisch, PhD
Nutrition Consultant
Judith Hallfrisch or Kay Behall, ARS Beltsville Human Nutrition Research
Center, Beltsville, Md., phone (301) 504-9014, fax (301) 504-9098,
hallfrisch@bhnrc.arsusda.gov and behall@bhnrc.arsusda.gov

David Jacobs, PhD
University of Minnesota
Jacobs Jr, David R. jacob004@umn.edu  612-624-4196   952-545-0471
Epidemiology

Pamela Keagy, PhD  pkeagy@pw.usda.gov
Nutrition Consultant
Pamela Keagy, U.S. Department of Agriculture-WRRC, 800 Buchanan St,
Berkeley, CA 94710, USA, Tel: +1-510-559-5664, Fax: +1-510-559-5626

Rui Hai Liu, PhD
Cornell University
EMAIL:  rl23@cornell.edu  Phone Numbers  CAMPUS:(607)255-6235
HOME: 607/257-4843  FAX: (607)254-4868

Addresses   CAMPUS:108 Stocking Hall
LOCAL:  HOME: 7 Coventry Walk, Ithaca, NY, 14850

Employment Information DEPARTMENT 1: Food Science
UNIV. TITLE 1: Prof Assoc  WORKING TITLE 1:  REGULAR/TEMP:R

Simin Liu, MD, ScD
Harvard School of Public Health
Brigham & Women's Hospital
Dr Simin Liu Appointment Title: Assistant Professor of Medicine; Assistant
Professor in the Department of Epidemiology in the Faculty of Public Health
Department: SPH^Epidem; HMS^Medcn-BWH Office Phone: +1 617 732 8108
BWH University Mailing Address: Brigham and Women's Hospital
900 Commonwealth Avenue East
Preventive Medicine
Boston MA 02215
Unit: Grad School of Public Health; Harvard Medical School
Simin Liu
Assistant Professor in the Department of Epidemiology
Department of Epidemiology
ontact Information
Department of Epidemiology
Division of Preventive Medicine
Brigham and Women's Hospital 900 Commonwealth Avenue  Boston, MA 02215
Phone: 617-732-8108  Fax: 617-731-3843    Email: siminliu@hsph.harvard.edu

Lloyd Rooney, PhD
Texas A&M University
Lloyd W. Rooney
Texas A&M University  Soil & Crop Science Dept  Cereal Q Lab
College Station, TX 77843-2474  E-mail: lrooney@tamu.edu

Joanne Slavin, PhD, RD
University of Minnesota
Joanne L Slavin
Title: Professor
Department: Food Science/Nutrition HE (office: Food Sci and Nutrition)
Dept Campus: UMN Twin Cities
E-mail Address: jslavin@umn.edu
Internet ID: jslavin
Office Address:Food Sci and Nutrition  166 F Sc N  1334 Eckles Ave
St Paul, MN 55108
Campus Mail: Food Sci and Nutrition  Room 225 FScN  6099
1334 Eckles Ave  St Paul, MN 55108  Office Phone:+1 612-624-7234

Culinary Advisory Committee

Jesse Cool, Chef/Owner
Flea Street Caf?, JZ Cool, the Cool Caf? at Cantor Art Gallery
Menlo Park, CA

Piper Mattson
Montebello Unified School District
Montebello, CA

Ana Sortun, Chef/Owner
Oleana
Cambridge, MA

Paula Wolfert, Author
The Slow Mediterranean Cookbook
Sonoma, CA

Media Collaboration

Ron Bottrell
Dome Communications
Chicago, IL
******************************************************************

http://www.bcm.edu/medicine/athero/foreyt.htm
John P. Foreyt, Ph.D.   Professor of Medicine
Director, Behavioral Medicine Research Center
Telephone: (713) 798-5757  Fax: (713) 798-4888  e-mail: jforeyt@bcm.tmc.edu
******************************************************************
Paul Rogers - 12 Nov 2004 21:27 GMT
"Those who use more than 6 cans daily diet soda ( perhaps 1% of the
population, looking around at the people I know here in Santa Fe) . . ."

For someone so apparently enthusiasitic about the scientific method and
evidence-based medicine, that seems a most revealing statement.

PR
 
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