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Mark Gold, most recent of 14 Rapid Responses to Aspartame and its effects on health, BMJ: Murray 2004.11.06 rmforall
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| | From: | Rich Murray | | Subject: | Mark Gold, most recent of 14 Rapid Responses to Aspartame and its effects on health, BMJ: Murray 2004.11.06 rmforall | | Date: | 9 Nov 2004 14:44:04 -0000 |
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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://bmj.bmjjournals.com/cgi/eletters/329/7469/755
[ Soon, BMJ plans to charge the public for online access. ]
Independent Scientific Information
20 October 2004 Mark D. Gold, Health / Medical Writer
mgold@holisticmed.com
12 East Side Dr., Suite 2-18, Concord, NH 03301 USA
Send response to journal:
Re: Independent Scientific Information
In their editorial, "Aspartame and its effects on health" ( 1 ), Professor
Lean and Catherine Hankey described my web page as "sensationalist
journalism." That web page contains nearly 400 pages of referenced
discussion related to the toxicity of aspartame and its metabolites. In
addition, there are several hundred pages of reports from individuals
detailing their experience of aspartame toxicity. I would invite healthcare
professionals to peruse a portion the scientific sections that address both
independent and aspartame industry-funded research in detail:
http://www.holisticmed.com/aspartame/abuse/
http://www.holisticmed.com/aspartame/scf2002.html
http://www.holisticmed.com/aspartame/aspfaq.html
In addition, there are numerous reasoned articles written by independent
researchers and phsycians that have been reproduced on the web:
http://www.dorway.com/doctors.html
Citations in the editorial that related to aspartame and health effects
included a web page published by an aspartame industry-funded public
relations organization ( 2 ) and a published review written by NutraSweet
company employees and others who have received funding from the manufacturer
( 3 ). It is not surprising, therefore, that the authors erroneously stated
that "aspartame comprises just two amino acids" and implied that the
evidence does not support the link between aspartame and health effects. On
the other hand, evidence from independent research and published case
reports (as detailed on the above-mentioned web pages) demonstrates that
aspartame can cause a wide range of adverse health effects.
Addressing the response by Dr. Finer, Medical Advisor to Ajinomoto
(aspartame manufacturer), he states that:
1) Individuals must consume 200 to 500 mg/kg of methanol in order to cause
toxicity. Kavet ( 4 ) estimated that as little as a single dose of 300
mg/kg of methanol can be lethal. Dr. Finer's comments related only to
single, lethal doses of methanol and not to chronic methanol and
formaldehyde toxicity.
2) Various manufacturer-sponsored studies of aspartame ingestion showed no
rise in plasma methanol levels. The methanol technique used in the studies
was a technique developed in 1969 ( 5 ) and incapable of reading rises in
plasma methanol less than 350 to 600%. Tephly ( 6 ) and other aspartame
manufacturer sponsored researchers involved in plasma methanol measurements
have refused to use sensitive testing methods despite their availability for
many years ( 7-9 ).
3) Dr. Briffa cited a study by Trocho et al. ( 10 ), that showed an
accumulation of significant levels formaldehyde adducts in various organs
and tissues (brain, liver, etc.) after ingestion of relatively small amounts
of aspartame. However, Dr. Briffa did not cite the letter by, Tephly ( 11 ),
a researcher involved in many of the aspartame manufacturer- funded studies
related to methanol and formate. However, the issues raised by Tephly ( such
as items #1 and #2 above ) have been refuted in numerous forums and by using
the data in the Trocho et al. study itself:
"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." ( 12 )
Dr. Finer did not discuss in detail other issues related to aspartame and
formaldehyde typically mentioned by the manufacturer: methanol in fruits,
formaldehyde in foods, long-term studies on non-human primates and
production of formaldehyde and methanol in the body. The above-mentioned web
pages addresses all of these issues as well as various industry-sponsored
double-blind studies often cited by the manufacturer.
Dr. Finer is correct about me being an "excited" responder to the editorial.
I am excited that busy healthcare professionals are finding the time to look
at the independent research and, based on case reports received, are
beginning to warn their patients off of aspartame. I am also excited that
the World Health Organization's recent approval of the sweetener stevia
( 13 ) allows diabetics and others in Europe a healthier, time-tested
alternative.
1. Michael Lean, Catherine Hankey. Aspartame and its effects on health BMJ
2004; 329: 755-756 ( 2nd October 2004 ).
http://bmj.bmjjournals.com/cgi/eletters/329/7469/755#76712
2. Aspartame Information Center. http://www.aspartame.org/ Web site owned by
the Calorie Control Council. "It represents 60 manufacturers and suppliers
of low-calorie, low-fat and light foods and beverages, including the
manufacturers and suppliers of more than a dozen different dietary
sweeteners, fat replacers and other low-calorie ingredients."
http://www.caloriecontrol.org/aboutCCC.html ( accessed 19 Oct 2004 ).
3. Butchko HH, Stargel WW. Aspartame: scientific evaluation in the
postmarketing period. Reg Toxic Pharma 2001; 34: 221-233.
4. Kavet R, et al. The Toxicity of Inhaled Methanol Vapors.
Critical Reviews in Toxicology 1990 21; 1: 21-50.
5. Baker, R.N., A.L. Alenty, J.F. Zack. Simultaneous determination of lower
alcohols, acetone and acetaldehyde in blood by gas chromatography. Journal
of Chromatographic Science, 1969; 7: 312-314.
6. Stegink, Lewis D., Tephly, Thomas R., et al. Repeated ingestion of
aspartame-sweetended beverages: further observations in individuals
heterozygous for phenylketonuria. Metabolism, 1990; 39(10): 1076-1081.
7. d'Alessandro, Alessandra, et al. Formate in serum and urine after
controlled methanol exposure at the threshold limit value.
Environmental Health Perspectives, 1994; 102(2): 178-181.
8. Davoli, E., et al. Trace analysis of methanol in rat serum by headspace
high resolution gas chromatography/selected ion monitoring,"
Journal of Chromatographic Science, 1986; 24: 113-116.
9. Cook, M.R., F.J. Bergman, et al. Effects of methanol vapor on human
neurobehavioral measures.
Research Report No. 42 (Peer Reviewed), Health Effects Institute, 141
Portland Street, Suite 7300, Cambridge, MA 02139, +1-617-621-0266, August
1991.
10. Trocho C, et al. Formaldehyde derived from dietary aspartame binds to
tissue components in vivo. Life Sciences 1998 63; 5: 337.
11. Tephly TR. Comments on the purported generation of formaldehyde and
adduct formation from the sweetener aspartame. Life Sci., 1999, 65(13),
157-160.
12. Alemany 2002. Letter from Dr. Maria Alemany to Rich Murray, September 8,
2002.
[ email sent 2002.08.30, quoted in full, below ]
http://groups.yahoo.com/group/aspartameNM/message/864 .
13. Joint FAO/WHO Expert Committee on Food Additives, 63rd Meeting, Geneva,
8-17 June 2004:
http://www.who.int/ipcs/publications/jecfa/en/Summary63final.pdf
Competing interests: None declared
******************************************************************
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, 1,134 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
830 members, 17,583 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://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
******************************************************************
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.
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.
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.
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/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17 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@shands.ufl.edu
Community Health and Family Medicine, U. Florida, Gainesville, FL
Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
352-376-5071
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/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
http://groups.yahoo.com/group/aspartameNM/message/1108
faults in 1999 July EPA 468-page formaldehyde profile:
Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
lipid peroxidation, green tea, aging, Lyme disease:
Murray 2004.08.08 rmforall
http://groups.yahoo.com/group/aspartameNM/message/1109
Toxicological Profile for Formaldehyde 1/4 plain text, start to 111 of 468
pages USA DHHS PHS ATSDR 1999 July: Murray 2004.08.30 rmforall
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
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/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
http://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall
http://ww.presidiotex.com/barcelona/index.html full text
Formaldehyde derived from dietary aspartame binds to tissue components in
vivo. Life Sci June 26 1998; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html 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. Mariā Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho" Fac. Biologia Tel.: (93)4021544,
FAX: (93)4021559
alemany@porthos.bio.ub.es ; bioq@sun.bq.ub.es
Abstract:
Adult male rats were given an oral dose of 10 mg/kg aspartame,
14C-labeled in the methanol carbon.
At timed intervals of up to 6 hours, the radioactivity in plasma and several
organs was investigated.
Most of the radioactivity found ( >98% in plasma, >75% in liver ) was bound
to
protein.
Label present in liver, plasma and kidney was in the range of 1-2% of total
radioactivity administered per g or mL, changing little with time.
Other organs ( brown and white adipose tissues, muscle, brain, cornea and
retina ) contained levels of label in the range of 1/12th to 1/10th of that
of liver.
In all, the rats retained, 6 hours after administration, about 5% of the
label, half of it in the liver.
The specific radioactivity of tissue protein, RNA and DNA was quite uniform.
The protein label was concentrated in amino acids, different from
methionine, and largely coincident with the result of protein exposure to
labeled formaldehyde.
DNA radioactivity was essentially in a single different adduct base,
different from the normal bases present in DNA.
The nature of the tissue label accumulated was, thus, a direct consequence
of formaldehyde binding to tissue structures.
The administration of labeled aspartame to a group of cirrhotic rats
resulted in comparable label retention by tissue components, which suggests
that liver function ( or its defect ) has little effect on formaldehyde
formation from aspartame and binding to biological components.
The chronic treatment of a series of rats with 200 mg/kg of non-labeled
aspartame during 10 days results in the accumulation of even more label when
given the radioactive bolus, suggesting that the amount of formaldehyde
adducts coming from aspartame in tissue proteins and nucleic acids may be
cumulative.
It is concluded that aspartame consumption may constitute a hazard because
of its contribution to the formation of formaldehyde adducts. PMID: 9714421
[ Extracts ]
"The high label presence in plasma and liver is in agreement with the
carriage of the label from the intestine to the liver via the portal vein.
The high label levels in kidney and, to a minor extent, in brown adipose
tissue and brain are probably a consequence of their high blood flows (
45 ).
Even in white adipose tissue, the levels of radioactivity found 6 hours
after oral administration were 1/25th those of liver.
Cornea and retina, both tissues known to metabolize actively methanol
( 21,28 ) showed low levels of retained label.
In any case, the binding of methanol-derived carbon to tissue proteins was
widespread, affecting all systems, fully reaching even sensitive targets
such as the brain and retina....
The amount of label recovered in tissue components was quite high in all the
groups, but especially in the NA rats.
In them, the liver alone retained, for a long time, more than 2 % of the
methanol carbon given in a single oral dose of aspartame, and the rest of
the body stored an additional 2 % or more.
These are indeed extremely high levels for adducts of formaldehyde, a
substance responsible of chronic deleterious effects ( 33 ), that has also
been considered carcinogenic ( 34,47 ).
The repeated occurrence of claims that aspartame produces headache and other
neurological and psychological secondary effects -- more often than not
challenged by careful analysis -- ( 5, 9, 10, 15, 48 ) may eventually find
at
least a partial explanation in the permanence of the formaldehyde label,
since formaldehyde intoxication can induce similar effects ( 49 ).
The cumulative effects derived from the incorporation of label in the
chronic administration model suggests that regular intake of aspartame may
result in the progressive accumulation of formaldehyde adducts.
It may be further speculated that the formation of adducts can help to
explain the chronic effects aspartame consumption may induce on sensitive
tissues such as brain ( 6, 9, 19, 50 ).
In any case, the possible negative effects that the accumulation of
formaldehyde adducts can induce is, obviously, long-term.
The alteration of protein integrity and function may needs some time to
induce substantial effects.
The damage to nucleic acids, mainly to DNA,
may eventually induce cell death and/or mutations.
The results presented suggest that the conversion of aspartame methanol into
formaldehyde adducts in significant amounts in vivo should to be taken into
account because of the widespread utilization of this sweetener.
Further epidemiological and long-term studies are needed to determine the
extent of the hazard that aspartame consumption poses for humans."
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [ 24 authors ], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 ( 2 Pt 2 ): S1-93, review
available for $35, [ an industry paid organ ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[ They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.
In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss@acpub.duke.edu 919-684-3303, 660-5657
http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall ]
[ http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall ]
Subject: Re: Murray: Butchko:
Tephly: critique of Trocho report Apr 2002 8.29.2
Date: Fri, 30 Aug 2002 09:49:56 +0200
From: Mariā Alemany alemany@bio.ub.es
To: Rich Murray rmforall@att.net
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. Mariā Alemany
Grup de Recerca Nitrogen-Obesitat
Departament de Nutriciķ i Bromatologia
Facultat de Biologia, Universitat de Barcelona
Av. Diagonal, 645; 08028 Barcelona Espanya/Espaņa/Spain
tel. +34 93 403 4606; fax: +34 93 403 7064; E-mail: alemany@bio.ub.es
Life Sci 1999; 65(13): PL157-60. [ letter, usually not peer reviewed ]
Comments on the purported generation of formaldehyde and adduct
formation from the sweetener aspartame.
Tephly TR Thomas R. Tephly 319-335-7979 thomas-tephly@uiowa.edu
ttephly@blue.weeg.uiowa.edu 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
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 ).
J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put into
the stomachs of 3 to 7 kg monkeys was eliminated within 8 hours, with little
additional elimination, as carbon dioxide in exhaled air and as water in
the urine.
They did not mention that this meant that about 30% of the methanol must
transform into formaldehyde and then into formic acid, both of which must
remain as toxic products in all parts of the body.
They did not report any studies on the distribution of radioactivity in body
tissues, except that blood plasma proteins after 4 days held 4% of the
initial methanol.
This study did not monitor long-term use of aspartame.
The low oral dose of aspartame and for methanol was 0.068 mmol/kg, about 1
part per million [ ppm ] of the acute toxicity level of 2,000 mg/kg, 67,000
mmol/kg, used by McMartin (1979).
Two L daily use of diet soda provides 123 mg methanol, 2 mg/kg for a 60 kg
person, a dose of 67 mmole/kg, a thousand times more than the dose in this
study.
By eight hours excretion of the dose in air and urine had leveled off at
67.1 +-2.1% as CO2 in the exhaled air and 1.57+-0.32% in the urine, so 68.7
% was excreted, and 31.3% was retained.
This data is the average of 4 monkeys.
"...the 14C in the feces was negligible."
"That fraction not so excreted (about 31%) was converted to body
constituents through the one-carbon metabolic pool."
"All radioactivity measurements were counted to +-1% accuracy..."
This indicates that the results could not be claimed to have a precision of
a tenth of a percent. OK, so this is a nit-pick -- but I believe espousing
spurious accuracy is a sign of scientific insecurity.
The abstract ends, "It was concluded that aspartame was digested to its
three constituents that were then absorbed as natural constituents of the
diet."
Thus, the concept is very subtly insinuated that methanol, as a
constituent of aspartame, is absorbed as a natural constituent of the diet.
"Dietary methanol is derived in large part from fresh fruits and
vegetables."
This is a serious error, since the large amounts of methanol in fresh fruits
and vegetables are not readily released by human digestion. ( W. C. Monte,
1984 )
Nowhere in this report are mentioned the dread words, "formaldehyde" and
"formic acid".
Of course, methanol and formaldehyde toxicity studies are highly relevant to
the issue of aspartame toxicity. [ Aspartame has to be turned into its
toxic products, formaldehyde and formic acid, in the body, before it is
toxic, so some pro-aspartame reseach studies test aspartame outside the
body, and then proclaim that they have proved that it is not toxic. ]
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 sensitity 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 2004.03.11 rmforall
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 2004.03.13 rmforall
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" "G.J. Reclos"
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
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
The moderated newsgroup, bionet.toxicology , has accepted 23 long reviews
by Rich Murray 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
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