http://groups.yahoo.com/group/aspartameNM/message/986
aspartame protects eye lens proteins from ascorbic acid toxicity:
Argirova & Argirov, March 2003: Murray 4.8.3 rmforall

March 8 2003 Do these studies indicate that ascorbic acid (Vitamin C)
can harm the lenses of the elderly and of diabetics?

Probably, the researchers are unaware of the steadily accumulating
research that all three components of aspartame-- phenylalanine 50%,
aspartic acid 39%, and methanol 11% (immediately metabolized into
formaldehyde and then into formic acid) are especially toxic for the
elderly and for diabetics, when ingested in heavy doses for years--
exemplifying 'in vivo' effects.

Laboratory 'in vitro' studies on aspartame in non-human species will not
usually reveal the toxicity of its three components, which are quickly
broken apart in the human GI tract.

Also, the potent effects of aspartame clearly vitiates the industry's
claim that it is a "food additive", Generally Regarded As Safe (GRAS),
not a "drug", which should be vetted for safety by stringent and
thorough studies.

Does this mean that aspartame interferes with the many beneficial
effects of ascorbic acid (Vitamin C)?

Contrariwise, would large doses of Vitamin C offer protection against
some of the toxicity of aspartame?
************************************************************************

J Pept Sci 2003 Mar;9(3):170-6
Inhibition of ascorbic acid-induced modifications in lens proteins by
peptides.
Argirova MD Argirov OK.
Department of Chemistry and Biochemistry. Medical Institute, 15a Vassil
Aprilov St, 4002 Plovdiv, Bulgaria. margirova@...

The effects of three dipeptides L-phenylalanyl-glybine,
glycyl-L-phenylalanine,and aspartame (L-aspartyl-L-phenylalanine, methyl
ester) as inhibitors of the ascorbic acid-induced modifications in lens
proteins were studied.

Their efficiency was compared to that of two known inhibitors--
aminoguanidine and carnosine.

The tested dipeptides diminished protein carbonyl content by 32-58% and
most moderated the formation of chromophores, as measured by the
absorbency at 325 nm of the glycated proteins.

The appearance of non-tryptophan fluorescence (excitation 340
nm/emission 410 nm) was observed for proteins glycated with ascorbic
acid.

All of the dipeptides examined, as well as aminoguanidine, decreased
this glycation-related fluorescence.

The potential inhibitors prevented the intensive formation of very high
molecular weight aggregates.

A competitive mechanism of their inhibitory effect was proposed, based
on the reactivity of individual substances toward ascorbic acid.

These findings indicate that they have a potential for use as
alternatives for aminoguanidine as an anti-glycation agent.
PMID: 12675499
************************************************************************

Biochim Biophys Acta 2003 Mar 17;1620(1-3):235-44
Isolation and characterization of a new advanced glycation endproduct of
dehydroascorbic acid and lysine.
Argirov OK, Lin B, Olesen P, Ortwerth BJ.
Mason Eye Institute, University of Missouri-Columbia
404 Portland Street, 65201, Columbia, MO, USA

Proteins are subject of posttranslational modification by sugars and
their degradation products in vivo.

The process is often referred as glycation. L-Dehydroascorbic acid
(DHA), an oxidation product of L-ascorbic acid (vitamin C), is known as
a potent glycation agent.

A new product of modification of lysine varepsilon -amino group by DHA
was discovered as a result of the interaction between Boc-Lys and
dehydroascorbic acid.

The chromatographic and spectral analyses revealed that the structure of
the product was
1-(5-ammonio-5-carboxypentyl)-3-oxido-4-(hydroxymethyl)pyridinium.

The same compound was isolated from DHA modified calf lens protein after
hydrolysis and chromatographic separation.

The study confirmed that L-erythrulose is an important intermediate of
modification of proteins by DHA.

The structure of the reported product and in vitro experiments suggested
that L-erythrulose could further transform to L-threose, L-erythrose and
glycolaldehyde under conditions similar to physiological.

The present study revealed that the modification of varepsilon -amino
groups of lysine residues by DHA is a complex process and could involve
a number of reactive carbonyl species. PMID: 12595094
************************************************************************

http://www.missouri.edu/index.cfm
Paul R. Olesen OlesenPR@...
Title: Senior Research Specialist
Department: Ophthalmology
Office Phone: (573) 882-6093
Office Address: DC350.00 Mason Eye Res E Columbia, MO 65211

Beryl J. Ortwerth OrtwerthB@...
Title: Professor Emeritus of Ophthalmology & Biochemistry
Department: Ophthalmology
Office Phone: (573) 882-6092
Office Address: C112 Eye Inst East Columbia, MO 65211
************************************************************************

Free Radic Res 2002 Dec;36(12):1251-9
Glycated proteins can enhance photooxidative stress in aged and diabetic
lenses.
Argirova MD, Breipohl W.
Department for Experimental Ophthalmology, University of Bonn, Abbestr.
2, 53105 Bonn, Germany. margirova@...

This study intends to clarify the ability of different
carbonyl-containing lens metabolites to form advanced glycation end
products, which possess photosensitizer activity and to investigate
whether these modified proteins could be implicated in lens photodamage.

Calf lens protein was experimentally glycated with either methylglyoxal,
glyoxal, ascorbic acid, or fructose to obtain models of aged and
diabetic cataractous lenses.

Being exposed to 200J/cm2 UVA radiation the model glycated proteins
produced 2-3-fold more singlet oxygen compared to the unmodified protein
and the superoxide radical formation was 30-80% higher than by the
native protein.

Ascorbylated proteins demonstrated the highest photosensitizer activity.

Biological responses of glycation-related photosensitizers were studied
on cultured lens epithelial cells irradiated with 40J/cm2 UVA.

Tissue culture studies revealed a significant increase in thiobarbituric
acid reactive substances in the culture medium of lens epithelial cells
after irradiation and treatment with glycated proteins.

Lens proteins had a protective effect against UVA induced cytotoxicity,
however, this protective effect decreased with the increasing
photosensitizer activity of experimentally glycated proteins.

The documented glycation-related photosensitization could explain the
accelerated pathogenic changes in human lens at advanced age and under
diabetic conditions. PMID: 12607815
************************************************************************

http://www.uia.ac.be/ects/Ophthalmo.htm
Prof. W. Breipohl (Exptl. Ophthalmology) breipohl@...
European Office in the Dean of Medical Education Unit, Faculty of
Medicine, R.F.W.-University Bonn, 53105 Bonn, Germany.
************************************************************************

Biochem J 2002 May 15;364(Pt 1):1-14
Assay of advanced glycation endproducts (AGEs): surveying AGEs by
chromatographic assay with derivatization by
6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to
Nepsilon-carboxymethyl-lysine- and
Nepsilon-(1-carboxyethyl)lysine-modified albumin.
Ahmed N, Argirov OK, Minhas HS, Cordeiro CA, Thornalley PJ.
Department of Biological Sciences, University of Essex, Central Campus,
Wivenhoe Park, Colchester, Essex CO4 3SQ, U.K.

Glycation of proteins leads to the formation of early glycation adducts
(fructosamine derivatives) and advanced glycation endproducts (AGEs).

Formation of AGEs has been linked to the development of cataract,
diabetic complications, uraemia, Alzheimer's disease and other
disorders.

AGEs are a group of compounds of diverse molecular structure
and biological function.

To characterize AGE-modified proteins used in studies of structural and
functional effects of glycation, an assay was developed that surveys the
content of early and advanced glycation adducts in proteins.

The assay procedure involved enzymic hydrolysis of protein substrate,
derivatization of the hydrolysate with
6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and HPLC of the
resulting adducts with fluorimetric detection.

Structural isomers of methylglyoxal-derived hydroimidazolone,
glyoxal-derived hydroimidazolone, 3-deoxyglucosone-derived
hydroimidazolone and
N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)\
-ornithine
(THP) were determined for the first time.

AGEs with intrinsic fluorescence (argpyrimidine, pentosidine) were
assayed without derivatization.

Limits of detection were 2-17 pmol and levels of recovery were 50-99%,
depending on the analyte.

The AQC assay resolved structural and epimeric isomers of
methylglyoxal-derived hydroimidazolones and THP.

Hydroimidazolones, THP and argpyrimidine were AGEs of
short-to-intermediate stability under physiological conditions, with
half-lives of 1-2 weeks.

Their measurement provides further insight into the glycation process.

The assay was applied to the characterization of human serum albumin
minimally and highly modified by N(epsilon)-carboxymethyl-lysine and
N(epsilon)-(1-carboxyethyl)-lysine. PMID: 11988070
************************************************************************

http://www.essex.ac.uk/bs/staff/thornalley/index.htm
Prof. Paul J. Thornalley
Director of the Disease Medchanisms and Therapeutics Research Group
Department of Biological Sciences, University of Essex,
Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U.K.
Tel/fax 0044 1206 873010 Mobile 0044 7884331407

Paul J. Thornalley, Professor of Disease Mechanisms and Therapeutics,
Department of Biological Sciences, University of Essex, Central Campus,
Wivenhoe Park, Colchester, Essex CO4 3SQ, U.K.
e-mail thorp@...
Tel or Fax (0) 1206 873010 (office) Mobile (0)7884331407
Tel (0)1206 872537 or 872531 or 873354 (lab)

http://www.essex.ac.uk/bs/staff/thornalley/Meeting0703.htm
Colloquium: The enzymatic defence against glycation in health, disease
and therapeutics
Biochemical Society Meeting, University of Essex, 2nd – 4th July 2003,
Colchester, Essex, U.K.

http://www.essex.ac.uk/bs/staff/thornalley/nahmed/nahmed.html
Naila Ahmed <nahmed@...>

http://www.orgchm.bas.bg/
Institute of Organic Chemistry with Centre of Phytochemistry BAS
************************************************************************

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

http://groups.yahoo.com/group/aspartameNM/message/984
aspartame review: methanol, formaldehyde, formic acid toxicity:
Murray 4.8.3 rmforall

http://groups.yahoo.com/group/aspartameNM/messages
for 986 posts in a public searchable archive

http://groups.yahoo.com/group/aspartame/ 633 member group

http://groups.yahoo.com/group/aspartameNM/message/985
details on EU Environment Committee vote 2.19.3 to reevaluate aspartame
and stevia and limit cyclamate-- EU vote April 9: Murray 4.8.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/968
EU MEPs vote to re-evaluate aspartame and stevia:
Martini: Murray 2.21.3 rmforall

http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame (12.4.2): 59 pages, 230 references

http://groups.yahoo.com/group/aspartameNM/message/910
formaldehyde & formic acid from methanol in aspartame:
Murray: 12.9.2 rmforall

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans) is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time become carbon dioxide and water-- 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.
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in
drinking water.

Bear in mind that the EPA limit for formaldehyde in
drinking water is 1 ppm,
or 2 mg daily for a typical daily consumption of 2 L of water.

http://groups.yahoo.com/group/aspartameNM/message/835
RTM: ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999
5.30.2 rmforall

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and
leading to vision and eye problems and even seizures. In many cases
there is addiction. Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

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: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/946
Functional Therapeutics in Neurodegenerative Disease Part 1/2:
Perlmutter 7.15.99: Murray 1.10.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 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 1.1.3 rmforall
[Also borderline evidence, in this pilot study of 39 food additives,
using a test group of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 1.27.3 rmforall [A detailed look at the data]

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 1.5.3 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@...

http://groups.yahoo.com/group/aspartameNM/message/960
aspartame & MSG: possible role in autoimmune hepatitis:
Prandota Jan 2003: Murray 1.15.3 rmforall

http://www.dorway.com/tldaddic.html 5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan; HJRobertsMD@...
http://www.sunsentpress.com/ sunsentpress@...
Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax

http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text "Aspartame Disease: An Ignored Epidemic"
published May 30 2001 $ 85.00 postpaid data from 1200 cases
available at http://www.amazon.com
over 600 references from standard medical research
************************************************************************