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aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

[Continued from Part 1/2]
Results: [ Table I: [Omitted] Plasma parameters in rats acutely or
chronically treated with oral aspartame, page 341 ]

Table 1 shows the blood chemistry of the rats used. Aspartame
administration, either chronic or acute (NC, NA groups), did not result
in significant changes in plasma composition of the rats. In the
cirrhotic rats, groups CC and CA, the plasma chemistry was deeply
altered. The liver cytology (data not presented) together with altered
transaminase levels and plasma chemistry showed that the CC and CA rats
were affected by liver cirrhosis. The rats with cirrhosis showed lower
urea, albumin and, especially, triacylglycerol levels than the controls.
Aspartame administration resulted in no changes in plasma chemistry in
normal rats.

Figure 1 [Omitted] shows the radioactivity found in several tissues of
rats receiving a single oral dose of labelled aspartame. Liver, blood
plasma and kidneys showed the higher radioactivity levels, in the range
of 0.1-0.4% in each gram of fresh tissue of the dose administered.

Since the dose given to each rat was 10 mg, of which a 10.5%
corresponded to methanol (i.e. 1 mg), 1/1000th of the dose given was
just 1 µg, which means that 0.1% of the dose per gram of tissue was
equivalent to 1 µg of methanol/formic acid/formaldehyde (= 31 mnol = 1
ppm). Liver, thus, contained between 1 and 3.7 ppm of label, while
plasma and kidneys maintained very stable levels of about 2 ppm,
following administration of a single dose.

Chronic administration of aspartame (NC group) resulted in a higher
yield of label after the last administration, as observed when comparing
the data for 6 hours, ranging from 130-140% of the value obtained in the
single NA group.

A fairly conservative estimate may indicate that the daily incorporation
of aspartame carbon was in the range between 2 and 4 ppm for liver
tissue, i.e. after 11 days, the accumulation may be up to 30 ppm.

In the cirrhotic rats, the pattern of label distribution was quite
similar to that of healthy rats. In general, the amount of radioactivity
in liver and kidney was lower, but higher in WAT than in normal-liver
rats.

The counting of radioactivity in plasma after acid precipitation of
protein (which would set free formic acid and methanol, but not
formaldehyde) gave a yield of less than 2% of total label in the
supernatant, i.e. practically all the radioactivity in the plasma at 6
hours was bound to protein.

The same experiment done with liver gave a yield of 20-23 % of the label
in the supernatant, the rest bound to protein and nucleic acids. The
form of the time-course of label present in liver agrees with this
finding, since there is a certain decay of label present in that organ
with time from a peak at 60 min. This same pattern can be found in
several other tissues (brown adipose tissue, muscle, brain and eye), but
in the end, a significant part of the label can be assumed to be
retained bound to protein.

The specific radioactivity of liver RNA, DNA and protein in the rats
treated with very high specific activity labelled aspartame are
presented in Table 2. [Omitted] Despite considerable variability in the
individual data, RNA showed lower specific activity than DNA and protein
had the higher values per mg. The data are also expressed as a ratio of
altered versus total structural unit (nucleotide/amino-acid), i.e. units
incorporating one of the labelled carbons derived from aspartame versus
total nucleotides or amino acids. This ratio was obtained by dividing
the specific activity found by that of the aspartame in the gavage. The
ratios obtained show that the uniformity between protein and DNA was
higher than when expressed per unit of weight. Cirrhotic rats showed
high liver specific activities, in the same general range as the normal
rats did.

Roughly, the liver contained about one quarter of its label in
"soluble" form, 2/3 in protein and less than 10% in nucleic acids, with
a higher share in DNA than in RNA.

Figure 2 [Omitted] depicts the distribution of label in two thin layer
chromatograms, the first showing the label distribution of DNA
hydrolysates, from the rats receiving high specific activity aspartame,
and the second, run under the same conditions, depicts the location of
labelled adenine, guanine and thymine spots. In the DNA hydrolysate,
the radioactivity present in the adenine, guanine and thymine spots was
nil, since the label was present in another different and distinct spot,
which was assumed to correspond to the adduct products of
methanol-derived carbon and DNA constitutive bases. The Rf values for
the bases and the adduct were quite different: adduct 0.05/0.0 (first
run/second run), guanine 0.10/0.22, adenine 0.40/0.43, thymine
0.57/0.49.

The separation through HPLC of the labelled fractions in the DNA
hydrolysate resulted in three main peaks, eluting at 7.65, 11.94 and
12.86 min. Thymine eluted at 8.95 min, guanine at 9.42 min and adenine
at 12.28 min under the same conditions.

Figure 3 [Omited] shows the distribution of radioactivity in three thin
layer chromatography plates. The first plate shows the label
distribution obtained after processing the product of plasma protein
hydrolysis from rats treated with high specific activity labelled
aspartame.

The second plate shows the results of an albumin sample exposed to
labelled formaldehyde and ran in parallel with the other samples.

The third plate contains the spot of DNP-methionine. The Rf values for
the radioactive spots were: in vivo labelled plasma protein 0.24/0.86
(first run/second run), in vitro labelled albumin: three spots,
A 0.02/0.0, B 0.38/0.0 and C 0.38/0.88, DNP-methionine 0.44/0.51.

The plates were considerably loaded with sample in order to obtain a
minimal radioactivity recording. This resulted in long "tails" and
blurred spots. In any case, there was a fair coincidence in one of the
spots of in vitro labelled albumin (C) with that observed in the in vivo
labelled plasma proteins. The methionine spot was quite different from
this one. In addition, the radioactive spot of exposed rat protein (and
those of formaldehyde-labelled plasma proteins) were not coincident with
any of the standard protein amino acids.

[Page 343] FIGURE 1 [Omitted]: Time course of label presence in several
tissues of rats receiving a dose of labelled aspartame.

[Page 344] TABLE II [Omitted]:
Specific activity of liver RNA, DNA, and protein in rats receiving high
specific activity gavage of labelled protein.

FIGURE 2 [Omitted]: Distribution of radioactivity in the nucleotides
resulting from the hydrolysis of DNA of rates treated with labelled
aspartame.
Thin layer chromatograms on cellulose plates showing: the result of the
hydrolysis of DNA from rats receiving a high specific activity gavage of
aspartame (chromatogram in the left; 25 Bq, 4 days exposure) and
standards for adenine A, guanine G and thymine T (chromatogram in the
right; 220 Bq each, 1 day exposure)

[Page 345] FIGURE 3 [Omitted]:
Distribution of radioactivity in the DNP-amino acids resulting from the
hydrolysis of plasma proteins of rats treated with labelled aspartame.
Bidimensional thin layer chromatograms on silicagel plates showing: the
spot obtained from hydrolysed plasma proteins of rats treated with
labelled aspartame after hydrolysis and derivatization (chromatogram in
the left, total about 50 Bq, 4 days exposure), the spots obtained
exposing in vitro albumin to labelled formaldehyde, after hydrolysis
and derivatization (chromatogram in the center, total about 110 Bq,
4 days exposure) and the spot for labelled DNP-methionine (chromatogram
in the right, 180 Bq, 1 day exposure).

Discussion:
The lower incorporation of methanol label in most tissues of
cirrhotic rats, compared with controls, may be the consequence of
reduced liver uptake of substrates, but also the result of a reduced
overall metabolic activity in the damaged liver of the rats (44). These
effects are clearly reflected by their stunted growth and high mortality
rate during the intoxication process, of about 50% of the rats (36).

The relative insignificance of the differences between the normal and
cirrhotic groups indicates that the liver is not essential in the
process of transfer of aspartame carbon to tissue proteins, i.e. that
there is not a direct relationship between the ability to process
alcohols and the retention of methanol carbon, bound to tissue
components.

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. In all groups studied, the label
bound found in plasma and tissues corresponds to that injected with
aspartame, since there is no other source of radioactivity available.

The lack of changes in plasma radioactivity from 1 to 24 h suggests that
the half-life of this newly added carbon was quite long, thus precluding
the possibility that the label detected would simply correspond to
unattached methanol.

The label bound to plasma proteins was not aspartame either, since the
latter is a non-reactive molecular species fully hydrolysed in the
intestine (1-2); the peptide never arrived to be in contact with the rat
tissues or its components.

We were not able to reproduce any direct labelling of protein exposed
either to aspartame, methanol nor formic acid.

Most of the label found in the tissues is the result of the formation of
formaldehyde or (in smaller proportion in any case, because of its lower
reactivity) formate adducts.

Methanol is highly volatile and, eventually, its radioactivity could
hardly be taken into account, since the counting method already
eliminates this possibility. In addition, the stabilized maintenance of
the plasma radioactivity levels could not belong to formate nor
methanol, since these unattached substrates are easily taken up and
oxidized by tissues, filtered by the kidneys or even lost through
respiration as occurs with short chain volatile alcohols.

The shape of the time-course graph representing the changes in tissue
label supports the hypothesis assuming that the label is firmly bound at
least for 6 hours after administration of aspartame. This behavior is
also found in formaldehyde-protein adducts (31), long lived species
difficult to eliminate, in which the protein is denatured and its
original function altered.

The transfer of "one-carbon" units from aspartame to plasma and tissue
proteins has been known for a time (35). Its nature, and the mechanism
of attachment, however, were assumed to be due to the incorporation of
the methanol carbon to normal amino acid structures (essentially forming
the methyl group of methionine) through the "one-carbon"
tetrahydrofolate and S-adenosyl-methionine pathways (35).

The lack of radioactivity in the methionine spot from aspartame-treated
labelled rat proteins, however, shows that this assumption could no
longer be maintained.

The findings of other- different -labelled DNP-derivatized amino acid(s)
in the exposed protein hydrolysates confirms that the label was not
caried into protein through the one-carbon pool metabolism labelling of
methionine, i.e. prior to the synthesis of the protein.

The coincidence of this labelled DNP-amino acid residue with that
obtained from protein experimentally exposed to formaldehyde confirms
that the label fixed to rat proteins after labelled aspartame exposure
was derived from formaldehyde adducts, and definitely proves that the
label in tissue proteins does not correspond to methionine.

This agrees with the incorporation of the label into the fully
synthesized protein at a remarkably uniform rate of label distribution
between different molecular species in spite of their eventually
different turnover (synthesis) rates.

The analysis of label distribution in the nucleic acids shows a
remarkable uniformity in the specific activities of DNA and proteins,
with RNA showing somewhat lower values in the same range. This
distribution is in agreement with a fairly uniform exposure to the same
reacting species, and could not be explained through incorporation of
one-carbon pathways into molecules which show widely different
half-lives, as is the case with the highly recycled RNA and some
proteins and long-lived DNA and proteins.

The finding of large amounts of label in DNA, higher than in RNA, could
be only explained through direct reaction, since its slow turnover would
require inordinately long exposure times to achieve the observed
specific activities.

The additional existence of different labelled bases, probably formed by
the binding of formaldehyde and the "normal" bases not coinciding with
any of the other bases. The thin layer chromatograms show a single
spot, resolved in at least three peaks, none of which coincided with
adenine, guanine nor thymine. The lack of label in these spots is
incompatible with the "one-carbon" pathways hypothesis of label
incorporation, since two "1C" units are needed for the synthesis of
adenine and guanine and one for that of thymine.

The presence of label in other different molecules strongly supports the
adduct formation postulate, attributing to formaldehyde the main
responsibility for the appearance of apartame-methanol label in tissue
components.

The evidence presented, then, proves that a significant portion of the
methanol carbon of aspartame finds its way into adducts of proteins and
nucleic acids under the conditions tested, both in normal and cirrhotic
rats. The results presented show that the carbon adducts of protein and
DNA could have generated only from aspartame methanol, since all the
other biochemical forms in which this carbon may be found could not
produce adducts with protein and nucleic acids.

The doses of aspartame given to the rats in this experiment were high,
higher at least than that any human may receive daily with normal
consumption of the additive-- in the range of 2-6 mg/kg-day
(46)--, but were similar to those used in comparable tests on rodents
in which no ill-effects were detected. These doses were in the same
range as the ADI for humans established for Canada and the EC
(40 mg/kg-day) (46). The dose administered was also lower than that
used for toxicity studies, which have shown that even at very high doses
aspartame does not produce immediately appreciable harm (17).

Most of these studies, however, refer to direct acute toxicity effects,
which were not observed either in the rats used in the present study
(except, perhaps, for softer droppings in those subjected to the chronic
treatment with aspartame gavages).

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 need 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.

Acknowledgements:
This research was carried out within a general study of artificial
sweeteners' toxicity supported through the Bosch & Gimpera Foundation,
Barcelona. Thanks are given to Robin Rycroft, from the Languages
Advisory Service of the University of Barcelona, for revision of the
manuscript.

References:
1. S.L. BURGERT, D.W. ANDERSEN, L.D. STEGINK, H. TAKEUCHI and H.P.
SCHEDL. Metabolism 40, 612-618 (1991)
2. N.M. HOOPER, R.J. HESP and S. TICKER. Biochem. J. 298, 635-639
(1994).
3. W.E. LIPTON, Y.N. LI, M.K. YOUNOSZAI and L.D. STEGINK. Metabolism
40, 1337-1345 (1991).
4. M. KOIVUSALO. International Encyclopedia of Pharmcology and
Therapeutics. J. Tremoličres (Ed.) Vol. 2 Sect. 20, 564-605. Pergamon
Press, New York, (1970).
5. S.K. VAN DEN EEDEN, T.D. KOEPSELL, W.T. LONGSTRETH, G. VANBELLE,
J.R. DALING and B. MCKNIGHT. Neurology 44, 1787-1793 (1994).
6. R.J. WURTMAN. New Eng. J. Med. 309, 429-430 (1983).
7. M.M. GARRIGA, C. BERKEBILE and D.D. METCALFE. J. Allerg. Clin.
Immunol. 87, 821-827 (1991).
8. R. GEHA, C.E. BUCKLEY, P. GREENBERGER, R. PATTERSON, S. POLMAR,
A. SAXON, A. ROHR, W. YANG and M. DROUIN. Clin. Experiment. Allergy 24,
175 (1994).
9. A. KOESTNER. Aspartame, Physiology and Biochemistry. L.D. Stegink
and L.J. Filer (Eds.), 447-457. Marcel Dekker, New York (1984).
10. H.J. ROBERTS. Clin. Res. 38, A798 (1990).
11. S. SARAVIS, R. SCHACHAR, S. ZLOTKIN, L.A. LEITER and G.H.
ANDERSON. Pediatrics 86, 75-83 (1990).
12. H.A. TILSON, J.S. HONG and T.J. SOBOTKA. Neurotoxicol. Teratol. 1,
27-35 (1991).
13. L. TOLLEFSON and R.J. BARNARD. J. Am. Diet. Assn. 92, 598-601
(1992).
14. P.A. SPIERS, D.L. SCHOMER, R.J. WURTMAN, L. SABOUNJIAN, A. REINER,
D. MYERS and J. WURTMAN. J. Clin. Exp. Neuropsychol. 15, 407 1993.
15. R.G. WALTON, R. HUDAK and R.J. GREENWAITE. Biol. Psychiat. 34,
13-17 (1993).
16. A. LAJTHA, M.A. REILLY. and D.S. DUNLOP. J. Nutr. Biochem. 5,
266-283 (1994).
17. L.D. STEGINK. Am. J. Clin. Nutr. 46, 204-215 (1987).
18. K.P. PORIKOS and T.B, VAN ITALLIE. Aspartame, Physiology and
Biochemistry. L.D. Stegink and L.J. Filer (Eds.), 273-286. Marcel
Dekker, New York (1984).
19. D.A. BOOTH. Developments in Sweeteners. T.H. Grenby (Ed.), Vol.3,
287-316. Elsevier, London (1987).
20. T.R. TEPHLY and K.E. MCMARTIN. Aspartame: Physiology and
Biochemistry. L.D. Stegink and L.J. Filer(Eds.), 111-140. Marcel Dekker,
New York (1984).
21. J.T. EELLS, C. RAJANI, T.G. MURRAY, M. LEWANDOWSKI and J.M. BURKE.
Invest. Ophthalmol. Vis. Sci. 31, 143 (1990).
22. L.J. FREDERICK, P.A. SCHULTE and A. APOL. Am. Ind. Hyg. Assoc. 45,
51-55 (1984).
23. K.E. MCMARTIN, A.B. MAKAR, G. MARTIN-AMAT, M. PALESE and T.R.
TEPHLY. Biochem. Med. 13, 319-333 (1975).
24. J.T. EELLS, K.A. BLACK, C.E. TEDFORD and T.R. TEPHLY. J. Pharmacol.
Exp. Ther. 227, 349-353 (1983).
25. K.A. BLACK, T.J. EELLS, P.E. NOKES, C.A. HAWTREY and T.R. TEPHLY.
Proc. Nat. Acad. Sci. USA 82, 3854-3858 (1985).
26. C.S. LIEBER and L.M. DE CARLI. Science 162, 917-918 (1968).
27. C.D. BENTON and F.P. CALHOUN. Trans. Am. Acad. Ophthalmol. 56,
875-883 (1952).
28. J.T. EELLS. J. Pharmaeol. Exp. Ther. 257, 56-63 (1991).
29. N.H RASKIN and L. SOKOLOFF. J. Neurochem. 19, 273-282 (1972).
30. P. JULIŔ, J. FARRÉS and X. PARÉS. Biochem. J. 213, 547-550 (1983).
31. R.H. HASCHEMEYER and A.E.V. HASCHEMEYER. Proteins. 11-30. John
Wiley & Sons, New York (1973).
32. D.E. METZLER. Biochemistry, 90-107. Academic Press, New York.
(1977).
33. H.D. HECK, M. CASANOVA and T.B. STARR. Crit. Rev. Toxicol. 20,
397-426 (1990).
34. A. BLAIR, R. SARACCI, P.A. STEWART, R.B. HAYES and C. SHY. Scad. J.
Work Environ. Hlth. 16, 381-393 (1990).
35. J.A. OPPERMANN, E. MULDOON and R.E. RANNEY. J. Nutr. 103, 1454-1459
(1973).
36. F. BLONDÉ-CYNOBER, F. PLASSART, C. REY, C. COUDRAY-LUCAS, N.
MOUKARBEL, R. POUPON, J. GIBONDEAU and L. CYNOBER. Ann. Nutr. Metab.
38, 238-248 (1994).
37. K.G. ISHAK, H.J. ZIMMERMAN and B. RAY. Alcoholism 15 45-66 (1991).
38. S.R. GALLAGHER. Current Protocols in Molecular Biology. Vol. 3
A.3D.1-A.3D.8. Wiley, Boston (1996).
39. M.M. BRADFORD. Anal.Biochem. 72, 248-254 (1976).
40. A. BENDICH. Meth. Enzymol. 3, 715-723 (1956).
41. A.H. VAN GENNIP, N.G.G.M. ABELING and D. DE KORTE. Handbook of
TLC. J. Sherma and B. Fried (Eds.). Vol. 55, 863-906. Chromatographic
Science Series (1990).
42. G. ALLEN. Laboratory Techniques in Biochemistry and Molecular
Biology. R.H. Burdan and P.W. van Knippenberg (Eds.)Vol. 9, 40-42.
Elsevier, Amsterdam (1989).
43. P. ROCA, A. PALOU and M. ALEMANY. J. Biochem. Biophys. Meth. 8,
63-67 (1983).
44. F. MION, A. GÉLOEN, E. AGOSTO and Y. MINAIRE. Hepatology 23,
582-588 (1996).
45. C. ADÁN, A. ARDÉVOL, X. REMESAR, M. ALEMANY and J.A.
FERNÁNDEZ-LÓPEZ. Arch. Int. Physiol. Biochim. Biophys. 102, 55-59
(1994).
46. H.H. BUTCHKO and F.N. KOTSONIS. Nutr. Toxicol. 11, 235-250 (1994).
47. T.D. STERLING and J.J. WEINHAM. Exp. Pathol. 37, 128-132 (1989).
48. J.W. OLNEY, N.B. FARBER, E. SPITZNAGEL and L.N. ROBINS. J.
Neuropathol. Exp. Neurol. 55, 1115-1123 (1996).
49. L. BRETHERICK (Ed.) Hazards in the chemical laboratory. 3rd. ed.,
339. Royal Society of Chemistry, London (1981).
50. T.J. MAHER and R.J. WURTMAN. Hlth. Perspect. 75, 53-57 (1987).
************************************************************************

http://groups.yahoo.com/group/aspartameNM/message/912
aspartame: methanol, formaldehyde, formic acid toxicity:
brief review: Murray 12.19.2 rmforall

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/860
RTM: FDA: objections to neotame approval 8.3.2 rmforall 38 pages

http://groups.yahoo.com/group/aspartameNM/message/868
Murray: submit complaints and papers to FDA Docket 02P-0317
by Jan 12 2003: Recall Aspartame as a Neurotoxic Drug 9.20.2 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
http://www.aspartameispoison.com/contents.html 34 chapters

Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
Palm Beach Institute for Medical Research, Inc.
P.O. Box 17799, West Palm Beach, FL 33416
fax 561-547-8008 dr.roberts@...
aspartame disease pages 627-685, 778-780 .

http://groups.yahoo.com/group/aspartameNM/message/859
RTM: Roberts: the life work of a brilliant clinician:
aspartame toxicity 8.2.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/790
RTM: Moseley:
review Roberts "Aspartame Disease: An Ignored Epidemic" 2.7.2 rmforall

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@...

http://groups.yahoo.com/group/aspartameNM/message/855
RTM: Blumenthall & Vance:
aspartame chewing gum headaches Nov 1997 7.28.2 rmforall
Harvey J. Blumenthal, MD, Dwight A Vance, RPh
Chewing Gum Headaches.
Headache 1997 Nov-Dec; 37(10): 665-6.
Department of Neurology, University of Oklahoma College of Medicine,
Tulsa, USA. neurotulsa@...
Aspartame, a popular dietetic sweetener, may provoke headache in some
susceptible individuals. Herein, we describe three cases of young women
with migraine who reported their headaches could be provoked by chewing
gum sweetened with aspartame. [6-8 mg aspartame per stick chewing gum]

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/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

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/645
Rich Murray: 18 recent formaldehyde toxicity [Comet assay] abstracts
6.25.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/857
RTM: www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research 7.31.2 rmforall

http://www.dorway.com David O. Rietz over 12,000 print pages
Mission-Possible-USA Betty Martini 770-242-2599
Bettym19@... dorietz@...
http://www.dorway.com/asprlink.html many links
http://www.dorway.com/nslawsuit.txt Jeff Martin, Attorney
http://www.dorway.com/upipart1.txt
UPI reporter Gregory Gordon: 96K 3-part expose Oct 1987
http://www.dorway.com/doctors.txt
What many informed doctors are saying/have said about aspartame

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"

Aspartame Consumer Safety Network and Pilot Hotline [1987-2001]
Mary Nash Stoddard, Founder & President
P.O. Box 780634 Dallas, TX 75378 .
214-352-4268 marystod@...
http://web2.airmail.net/marystod/index.html
http://web2.airmail.net/marystod/espanol.htm
Toxicology Sourcebook: "Deadly Deception: Story of Aspartame"

http://groups.yahoo.com/group/aspartameNM/message/858
RTM: Samuels: Strong: Roberts: Gold: flaws in double-blind studies re
aspartame and MSG toxicity 8.1.2 rmforall

"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished: http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100%) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91%)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240 Youngstown,
OH 44501 330-740-3621 rwalton193@...
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://google.com gives 133,000 websites for "aspartame" , while
http://groups.google.com/ finds on 700 MB of posts from 20-years of
Usenet groups, 75,700 posts, and
http://www.AllTheWeb.com gives 261,750, the top three being leading and
very well informed volunteer anti-aspartame sites.
http://teoma.com/index.asp gives 34,100 websites.
http://www.ncbi.nlm.nih.gov/PubMed/ lists 719 aspartame items.
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Serious symptom syndrome summary:
Aspartame (NutraSweet, Equal, Canderel, Benevia) is reported by
scientific studies and case histories to be toxic: * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, or numbness) * fever, fatigue
* "mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech,
ringing in ears, sexual problems, poor vision, hearing, or taste
* red face, itching, rashes, burning eyes or throat,
dry mouth or eyes, mouth sores * hair loss
* obesity, bloating, edema, anorexia,
poor or excessive hunger or thirst * breathing problems
* nausea, diarrhea or constipation * coldness * sweating
* racing heart, high blood pressure, erratic blood sugar levels
* seizures * birth defects * brain cancers * addiction
* aggrivates diabetes, autism, ADHD, allergies,
and interstitial cystitis (bladder pain)
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http://members.tripod.com/~mission_possible/scotland_branch.html
http://www.aspartame.ca/ Canada
http://www.geocities.com/HotSprings/4578/ Canada
http://www.cybernaute.com/earthconcert2000/AspartaMalcache.htm
http://www.reseauproteus.net/therapies/nutritio/aspartame.htm
http://ww2.grn.es/avalls/aspa1.htm Spain
http://www.geocities.com/HotSprings/Falls/8669/ Brazil
http://www.phd.com.br/aspartame.htm
http://hem.passagen.se/mission.possible.sweden/
http://home.online.no/~dusan/foods/aspartame.html Norway
http://www.aspartaam.nl/info/product.html Holland, in Dutch
http://www.laleva.org/ Italy
http://www.laleva.org/alimenti/dorwayaspartame.html
http://users.westnet.gr/~cgian/aspartame.htm Greece
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