Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/864

Marià Alemany <alemany@...>,
Thomas R. Tephly <thomas-tephly@...>,
Kenneth E. McMartin <kmcmar@...>,
Harriett H. Butchko <harriett.h.butchko@...>,
Susan S. Schiffman <sss@...>,
Arthur S. Leon <leonx002@...>,
Christian Benninger <Christian_Benninger@...>,
George L. Blackburn <gblackbu@...>,
Leo M.J. de Sonneville <lmj.sonneville@...>,
Raif S. Geha <raif.geha@...>,
Edward J. Novotny, Jr. <edward.novotny@...>,
Andrew G. Renwick <agr@...>,
Donald L. Schomer <dschomer@...>,
Bennett A. Shaywitz <bennett.shaywitz@...>

Subject: Re: Murray: Butchko:
Tephly: critique of Trocho report Apr 2002 8.29.2
Date: Fri, 30 Aug 2002 09:49:56 +0200
From: Marià 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. Marià Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutrició i Bromatologia
Facultat de Biologia, Universitat de Barcelona
Av. Diagonal, 645; 08028 Barcelona Espanya/España/Spain
tel. +34 93 403 4606; fax: +34 93 403 7064; E-mail: alemany@...
***********************************************************

Full report http://www.presidiotex.com/barcelona/index.html
Here is research in 1998 by C. Trocho et al, using 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.) This proves that aspartame causes
binding of methanol's product, formaldehyde, a potent, cumulative
toxin, into tissues. Life Sci June 26 1998; 63(5): 337-49. ["Trok-ho"]

Formaldehyde derived from dietary aspartame binds to tissue components
in vivo. Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html
Línies 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. Marià Alemany Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
alemany@... [male] bioq@...
josefer@...
rafecas@... remesar@...
Sra. Carme Trocho Fac. Biologia Tel.: (93)4021544, FAX: (93)4021559

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, UI: 98378223

[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.
***********************************************************

Life Sci 1999; 65(13): PL157-60. [letter, 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:

"Scientific Abuse in Aspartame Research"
http://www.holisticmed.com/aspartame/abuse/methanol.html
Aspartame Toxicity Information Center Mark D. Gold
www.HolisticMed.com/aspartame 603-225-2100
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
***********************************************************

pages S36 to S41 of S1 to S93

Safety of Methanol from Aspartame and the Diet

[Thomas R. Tephly (Methanol) thomas-tephly@...
Department of Pharmacology, The University of Iowa, Iowa City, Iowa

Kenneth E. McMartin (Methanol) kmcmar@...
Department of Pharmacology and Therapeutics, Louisiana State University]

page S39 [Extract]

Evaluation of Recent Issues Regarding Methanol Safety from Aspartame

Trocho et al. (1998) concluded from a study in rats
that aspartame may be hazardous because formaldehyde
adducts from aspartame may accumulate in
tissue proteins and nucleic acids. However, according
to Tephly (1999), the dose of aspartame used in the
study (20 mg/kg body wt =2 mg of methanol/kg body wt)
would not yield blood methanol concentrations outside
control values. Further, the administration of aspartame
at 200 mg/kg body wt (equal to that in a single bolus
of about 25 liters of beverage sweetened 100% with
aspartame) to adult humans results in no detectable
increase in blood formate concentrations (Stegink
et al., 1981). Administration of [14 C] methanol itself at
3000 mg/kg body wt to monkeys produces no detectable
[14 C] formaldehyde in body fluids and tissues (McMartin
et al., 1979), while there is ample accumulation of formate.
An alternative explanation for tissue incorporation
of label from [14 C] aspartame as described by Trocho
et al. (1998) would be incorporation into amino acids
and nucleotides via one-carbon moieties from the folate-dependent
metabolism of formate. The lack of formaldehyde
accumulation at very high doses of methanol
question considerably the conclusion that formaldehyde
adducts are forming from low doses of methanol (derived
from high doses aspartame). Thus, Tephly (1999)
concluded, “the normal flux of one-carbon moieties
whether derived from pectin, aspartame, or fruit juices
is a physiologic phenomenon and not a toxic event.”

page S1 0273-2300/02 $35.00
C 2002 Elsevier Science (USA) All rights reserved.

Regulatory Toxicology and Pharmacology 35, S1–S93 (2002)
doi:10.1006/rtph.2002.1542, available online at
http://www.idealibrary.com $ 35.00
Aspartame: Review of Safety
Harriett H. Butchko 1
Medical and Scientific Affairs, The NutraSweet Company,
Mt. Prospect, Illinois
W. Wayne Stargel
Research and Development, The NutraSweet Company,
Mt. Prospect, Illinois

C. Phil Comer
Graystone Associates, Inc., Macon, Georgia
Dale A. Mayhew
Regulatory Affairs, The NutraSweet Company, Mt. Prospect, Illinois
Christian Benninger (EEGs and Cognitive Function in PKU Heterozygotes)
Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
George L. Blackburn (Appetite, Food Intake, and Weight Control)
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, Massachusetts
Leo M. J. de Sonneville (Neuropsychological Function and Phenylalanine)
Departments of Pediatrics and Neurology, Vrije Universiteit, Medical
Center, Amsterdam, The Netherlands
Raif S. Geha (Allergy)
Division of Immunology, The Children’s Hospital, Harvard Medical School,

Boston, Massachusetts
Zsolt Hertelendy (Liver Disease)
Division of Pharmaceutical Sciences, College of Pharmacy, University of
Cincinnati, Cincinnati, Ohio
Adalbert Koestner (Brain Tumors)
Department of Veterinary Biosciences, Ohio State University School of
Veterinary Medicine, Columbus, Ohio
Arthur S. Leon (Long-Term Safety in Humans)
Division of Kinesiology, College of Education and Human Development and
Department of Medicine, The Medical School,
University of Minnesota, Minneapolis, Minnesota
George U. Liepa (Renal Disease)
Department of Human, Environmental, and Consumer Resources, Eastern
Michigan University, Ypsilanti, Michigan
Kenneth E. McMartin (Methanol)
Department of Pharmacology and Therapeutics, Louisiana State University
Medical Center, Shreveport, Louisiana
Charles L. Mendenhall (Liver Disease)
Digestive Diseases Section, Department of Veterans Affairs Medical
Center, Cincinnati, Ohio
1 To whom correspondence should be addressed at Medical and Scientific
Affairs, The NutraSweet Company, 699 Wheeling Road, Mt.
Prospect, IL 60056. Fax: (847) 463-1755. E-mail:
harriett.h.butchko@....

page S2 BUTCHKO ET AL.

Ian C. Munro (Preface)
Cantox Health Sciences, Inc., Mississauga, Ontario, Canada
Edward J. Novotny (Seizures and EEGs)
Department of Pediatrics and Neurology, Yale University School of
Medicine, New Haven, Connecticut
Andrew G. Renwick (Preface)
Department of Pharmacology, University of Southampton, Southampton,
United Kingdom
Susan S. Schiffman (Headaches)
Department of Psychiatry, Duke University Medical Center, Durham, North
Carolina
Donald L. Schomer (Neurochemistry, Seizures and EEGs, Behavior,
Cognitive Function, and Mood)
Department of Neurology, Division of Neurophysiology and Epilepsy, Beth
Israel Deaconess Medical Center,
Harvard Medical School, Boston, Massachusetts
Bennett A. Shaywitz (Behavior, Cognitive Function, Mood in Children,
Seizures, and EEGs)
Departments of Pediatrics, Neurology, and Child Study, Yale University
School of Medicine, New Haven, Connecticut
Paul A. Spiers (Behavior, Cognition, and Mood)
Department of Psychiatry, Boston University School of Medicine, and
Clinical Research Center,
Massachusetts Institute of Technology, Boston, Massachusetts
Thomas R. Tephly (Methanol)
Department of Pharmacology, The University of Iowa, Iowa City, Iowa
John A. Thomas (Metabolism and Endocrine)
Department of Pharmacology, The University of Texas Health Science
Center at San Antonio, San Antonio, Texas
Friedrich K. Trefz (Phenylketonuria)
Department of Pediatrics, Children’s Hospital of Reutlingen, University
of Tubingen, Reutlingen, Germany
Received January 8, 2002

DEDICATION
The authors dedicate this supplement to the memories of Lewis D.
Stegink, Ph.D., and L. J. Filer, Jr., M.D.,
Ph.D., from the University of Iowa. Their early research on aspartame
metabolism in humans formed the basis for
much of the future research on aspartame that is discussed in this
supplement. Their objectivity and long-standing
dedication to science as well as their medical and scientific expertise
are greatly missed.
***********************************************************

Rich Murray, MA Room For All rmforall@...
1943 Otowi Road, Santa Fe NM 87505 USA 505-986-9103

http://groups.yahoo.com/group/aspartameNM/messages
for 864 posts in a public searchable archive

http://groups.yahoo.com/group/aspartameNM/message/861 brief review

http://groups.yahoo.com/group/aspartameNM/message/862 long review

http://groups.yahoo.com/group/aspartameNM/message/860
RTM: FDA: objections to neotame approval 8.3.2 rmforall 38 pages

http://groups.yahoo.com/group/aspartameNM/message/830
RTM: Tholen: Diet Coke has 5 ppm formaldehyde from aspartame
5.29.2 rmforall [~200 mg aspartame in 12-oz diet soda]
For 6 cans of diet soda, this is 5 times the daily limit of 1 PPM for
formaldehyde in drinking water, set by the EPA.
http://www.geocities.com/aspartame_survivors/tholen.html
For a science project, Randy Tholen, age 11, paid $ 180 to have
six cans of Diet Coke analyzed on Mar 7 2002 by Bill Katz 952-942-1774
at Braun Intertec Corporation Lab
Braun Intertec Corporation http://www.brauncorp.com/
(800) 279-6100 (952) 941-5600 fax (952) 833-4701
Mail: 6875 Washington Ave. S. Minneapolis, MN 55439
E-Mail: Webmaster@...

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 1.17.2 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702–706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment
modalities with limited success. All had complete, or nearly complete,
resolution of their symptoms within months after eliminating monosodium
glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@...
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital
West Oak Clinic Gainesville, FL 32608-3629 352-376-5071

Debbie J. Hypes painfreeliving@... 304-872-4141 (Case # 1 of 4)
P.O Box 25 Lookout, WV 25868-0025 She has about 1,000 on her local
mailing list, and has been a volunteer activist since 1997. Her guide
first came out in 1997: http://www.Pain-Free-Living.net
"The Food Plan: How To Do It" $ 5 by mail, free by email.
Her sister Darlene, now 47, cured her own severe fibromyalgia in 1995
by using an elimination diet, and then Debbie also cured herself by
1997. Their doctor, Siegfried Schmidt, paying attention, tried it on
two selected women, who got well, and are his third and fourth cases.

http://groups.yahoo.com/group/aspartameNM/message/846
RTM: 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 7.16.2 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@...

Mark D. Gold has a fine, detailed analysis, "Scientific Abuse in
Methanol / Formaldehyde Research Related to Aspartame" at:
http://www.holisticmed.com/aspartame/abuse/methanol.html#discussion
http://www.HolisticMed.com/aspartame 603-225-2100
Aspartame Toxicity Information Center Mark D. Gold
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/628
Rich Murray: Professional House Doctors: Singer: EPA: CPSC:
formaldehyde toxicity 6.10.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/863
Murray: Wilson: CIIN: EPA: Gold: Thrasher & Kilburn: Shaham:
formaldehyde toxicity 8.22.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/645
Rich Murray: 18 recent formaldehyde toxicity [Comet assay] abstracts
6.25.1 rmforall

http://google.com gives 105,000 websites for "aspartame" , while
http://groups.google.com/ finds on 700 MB of posts from 20-years of
Usenet groups, 72,300 posts, and
http://www.AllTheWeb.com gives 177,012, the top four being leading and
very well informed volunteer anti-aspartame sites.
http://www.ncbi.nlm.nih.gov/PubMed/ lists 714 aspartame items.
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