On Fri, 9 Sep 2005 17:01:30 -0400, "Glen M. Sizemore"
<gmsizemore2[at]yahoo.com> wrote:

- quote -

[Note: I "corrected" your top-posting]

Rich Murray has been publishing these extremely long and tedious
anti-aspartame notices for years, now. In times past, the
anti-aspartame group really was quite a nuisance in this
(bionet.neuroscience) newsgroup. Now, it is at least somewhat
subdued. I simply wish it to be eliminated completely.

This is written as I sit sipping my diet soda. I notice that the one
I now drink is sweetened with acesulfane and sucralose. The only
reason I switched from the type with aspartame is to eliminate the
caffeine which, my doctor assures me, is not good for my health. That
did concern me. The methanol derived from aspartame, plus the
phenylalanine and aspartate, absolutely did not.

This is somewhat uncharacteristic of you, Dr. Norman. Just out of
curiousity, why that post in particular?


"r norman" <NotMyRealEmail[at]_comcast.net> wrote in message
news:11g3i1hfdgmqm889rnson2m4flks1cfmqa[at]4ax.com...
- quote -

On 9 Sep 2005 09:02:41 -0700, "TC" <tunderbar[at]hotmail.com> wrote:

- quote -

Shorten the entire post. In fact, shorten it to zero lines then
refrain from posting it!

shorten the subject line

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

http://groups.yahoo.com/group/aspartameNM/message/1213
aspartame (methanol, phenylalanine, aspartic acid) effects, detailed expert
studies in 2005 Aug and 1998 July, Tsakiris S, Schulpis KH, Karikas GA,
Kokotos G, Reclos RJ, et al, Aghia Sophia Children's Hospital, Athens,
Greece: Murray 2005.09.09

Rich Murray, MA Room For All rmforall[at]comcast.net
505-501-2298 1943 Otowi Road Santa Fe, New Mexico 87505
http://groups.yahoo.com/group/aspartameNM/messages
group with 148 members, 1,213 posts in a public, searchable archive

[ The lowest dose level tested, 34 mg aspartame per kg body weight, well
below the FDA daily human limit of 50 mg/kg, 16 12-oz cans,
caused enzyme activity reduction by -33%.

However, a missed opportunity in both studies is that the inevitable,
extremely and cumulatively toxic products of methanol in the human body,
formaldehyde and formic acid, which are responsible for the toxicity of
methanol, were not independently tested.

" It is concluded that low concentrations of ASP metabolites had no effect
on the membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably decreased the
membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. " ]

Pharmacol Res. 2005 Aug 26; [Epub ahead of print]
The effect of aspartame metabolites on human erythrocyte membrane
acetylcholinesterase activity.
Tsakiris S,
Giannoulia-Karantana A,
Simintzi I,
Schulpis KH.
Department of Experimental Physiology, Medical School, University of Athens,
P.O. Box 65257, GR-154 01 Athens, Greece.

Stylianos Tsakiris. stsakir[at]cc.uoa.gr

Giannoulia-Karantana A. First Department of Pediatrics, Aghia Sophia
Children's Hospital, University of Athens, Greece.

Kleopatra H. Schulpis, MD, PhD. Institute of Child Health, Aghia Sophia
Children's Hospital, GR-11527 Athens (Greece)
Tel. +30 1 7708291, Fax +30 1 7700111 inchildh[at]otenet.gr ;

[ Papoutsakis T. tina.papoutsakis[at]hua.gr

Papadopoulos G. Department of Biochemistry and Biotechnology, University of
Thessaly, Ploutonos 26,
41221 Larisa, Greece papg[at]chem.auth.gr ]

Abstract:

Studies have implicated aspartame (ASP) with neurological problems. The aim
of this study was to evaluate acetylcholinesterase (AChE) activity in human
erythrocyte membranes
after incubation with the sum of ASP metabolites,
phenylalanine (Phe),
methanol (met) and
aspartic acid (aspt),
or with each one separately.

Erythrocyte membranes were obtained from 12 healthy individuals and were
incubated with ASP hydrolysis products for 1h at 37 degrees C. AChE was
measured spectrophotometrically.

Incubation of membranes with ASP metabolites corresponding
with 34 mg/kg, 150 mg/kg or 200 mg/kg of ASP consumption resulted in an
enzyme activity reduction by -33%, -41%, and -57%, respectively.

Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased the enzyme
activity by -20%, -32% or -40%, respectively.

Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited membrane AChE
acitivity by -20%, -35%, and -47%, respectively.

Phe concentrations 0.14 mM, 0.35 mM or 0.50 mM reduced the enzyme activity
by -11%, -33%, and -35%, respectively.

Aspt or Phe concentrations 0.82 mM or 0.07 mM, respectively,
did not alter the membrane AChE activity.

It is concluded that low concentrations of ASP metabolites had no effect on
the membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably decreased the
membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. PMID: 16129618
************************************************** ****


http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA: Karikas July
1998: Murray 2003.01.05

Karikas (1998):
"In conclusion, these in vitro findings are of interest because
a widely used compound such as ASP along with its
metabolites gave a measurable molecular interaction with DNA."

This study tests aspartame directly reacting with DNA, and finds very
troubling results.
Karikas also tested the two aspartame components,
aspartic acid and phenylalanine, finding substantial binding with DNA.
A month earlier, the Trocho study found that formaldehyde from the
methanol component of aspartame also binds with DNA when fed to rats.

So, all three components of aspartame,
quickly decomposed in the GI tract,
methanol (11%), aspartic acid (39%), and phenylalanine (50%),
lead to binding with DNA,
the probable results including cell malfunction and death, mutations,
spontaneous abortions, birth defects, cancers, and chronic complex symptoms
for long-term heavy users, over 2 L daily of diet soda
(six 12-oz cans).

It is high time for definitive, independently funded studies on the
mutagenic properties of aspartame and its problematic metabolites in
humans.

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

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 2002.05.30 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: 2002.02.09
************************************************** *********

"Measurement of Molecular Interaction of Aspartame and Its
Metabolites with DNA"
Clinical Biochemistry, 31 (5); 405-7, July 1998
Manuscript received July 15 1997;
revised and accepted March 16, 1998.
copyright 1998 The Canadian Society of Clinical Chemists
0009-9120/98

George A. Karikas, Pharm D, MD, Lab. of Organic Chemistry,
U. of Athens, Panepistimiopolis, Athens 15771 Greece

George Kokotos, PhD, Assc. Prof., Lab of Organic Chemistry
http://www.chem.uoa.gr/personel/Labo...VS/kokotos.htm

gkokotos[at]cc.uoa.gr ++301-7274462 fax ++301-7249101

Kleopatra H. Schulpis, MD, PhD
Pharmacokinetics and Parental Nutrition Unit
Institute of Child Health
Aghia Sophia Children's Hospital inchildh[at]otenet.gr
Thivon & Levadias Street GR-11527 Athens, Greece
(+30 1) 7467 000 fax: (+30 1) 7798 088
http://www.teleremedy.gr/Pages/Membe...phia/aghia.htm

George J. Reclos, PhD R&D Diagnostics, Ltd
41, Eleftheriou Venizelou street, GR 15561, Holargos, Greece.
+30-1-6537307 fax: +30-1-6537357 & 6548284
reklos[at]otenet.gr ; reklos[at]mailbox.gr ; reklos[at]rddiagnostics.com
http://www.rddiagnostics.com/
http://www.RdDiagnostics.com/cv/page4.html
Dr. George J. Reclos Curriculum Vitae

[ current addresses ]
Reclos GJ mail[at]rddiagnostics.com ; reklos[at]otenet.gr
Laboratory of Organic Chemistry, Department of Chemistry, University of
Athens, Panepistimiopolis, Athens 15771, Greece.

Kokotos G. gkokotos[at]cc.uoa.gr
Dr. George Kokotos, Laboratory of Organic Chemistry, Department of
Chemistry, University ofAthens, Panepistimiopolis, Athens 15771, Greece.
Tel. 7274462, Fax: 7249101 E-mail: gkokotos[at]atlas.uoa.gr
http://www.chem.uoa.gr/Personel/Labo...rganic%20Chem/
CVS/kokotos.htm

George A. Karikas. Department of Clinical Biochemistry, Aghia Sophia
Children's Hospital, 11527 Athens, Greece;

[ Notes by Rich Murray are in square brackets. ]

Abstract:

Following amide and ester hydrolysis ASP is metabolized to
aspartic acid (Asp), methanol and phenylalanine (Phe) with
serum levels of all three metabolites increasing after
ingestion of modest amounts (1,2).

Increases of serum Phe levels have been of concern because of the
pivotal role played by Phe in the transport of precursors of
monoamide neurotransmitters into the brain.
Additionally, Phe is a diagnostic tool for phenylketonuria, an inborn error
of metabolism (3).

Some findings have speculated that ASP molecule might
possess mutagenic potential effect...a promising candidate
to explain the increase in incident and degree of
malignancy of brain tumors (2,4).

In an attempt to reassess by in vitro experiments the
possible carcinogenic potential of ASP,
we measured its direct molecular interaction with DNA by using a rapid
reversed phase high-performance liquid chromatography
(HPLC) method (5-7),
which has showed a good correlation with brine shrimp toxicity and tumor
inhibition tests (5).
Asp and Phe were also tested by the same method.
Additionally, a number of synthetic Phe analogues were used in order to
investigate the mechanism of ASP binding to DNA....

Doxorubicin (Doxo) from Farmacia (1.0 mg/mL) was used
as a typical intercalating agent with major binding (100%) capability...

The column was equilibrated with a H20:MeOH (80:20) solution.
Test samples and DNA solutions were then introduced in a
ratio (1:1, v/v) into the sample loop (20 microL) without incubation.
The flow rate was maintained at 1 mL/min and the
free DNA eluted from the column in approximately 1 min.
After the appearance of DNA peak, the column was later
washed with MeOH for 20 min to elute the sample mixture.
All samples were tested in triplicate.

ASP and Doxo were tested at three final concentrations
(0.12, 0.25, 0.5 mg/mL) versus DNA at a final
concentration of 0.05 mg/mL.

According to our method a fixed amount of ligand
is added to the elution solvent of the HPLC system
and a known quantify of DNA is then injected.
This results in a residual DNA peak (% DNA peak size
exclusion) where the exclusion of the peak is
proportional to the amount of bound ligand....

Table 1
Molecular Effect of Doxo and ASP on DNA

Compound (mg/mL) % DNA Peak Exclusion (% DNA Bonding)

DNA 0.05 + Doxo 0.12 45.8+- 5.4
DNA 0.05 + Doxo 0.25 100
DNA 0.05 + Doxo 0.50 100

DNA 0.05 + ASP 0.12 11.3+- 3.4
DNA 0.05 + ASP 0.25 39.8+- 6.1
DNA 0.25 + ASP 0.50 65.5+- 10.1

[ So, doubling the amount of ligand roughly
doubles the % DNA bound, until 100% saturation
of the DNA. ]

A moderate DNA molecular interaction, expressed as
almost 40% (39.8+- 6.1) DNA peak exclusion
was observed when ASP was tested with DNA
(0.05 mg/mL) at a final concentration of of 0.25 mg/mL.

Analogous effect was exhibited by Phe (31.6+- 8.5%) at a final
concentration of 0.25 mg/mL, whereas a 65.5+- 10.1% DNA peak exclusion was
observed when ASP reached the final concentration of 0.50 mg/mL.

Doxo performed a complete molecular DNA effect
(intercalation plus ionic interaction) (100% DNA
peak size exclusion) at concentration of 0.25 and
0.50 mag/mL.

Table 2
Molecular Effect of Phe and Related Compounds on DNA

Compound (mg/mL) % DNA Peak Exclusion (% DNA binding)

DNA 0.05 + Phe 0.25 31.6+- 8.5
DNA 0.05 + Asp 0.25 39.3+- 4.2
DNA 0.05 + Ala 0.25 12.3+- 4.1
DNA 0.05 + Z-Phe 0.25 0
DNA 0.05 + I 0.25 100

Phe L-phenylalanine
Asp L-aspartic acid
Ala L-alanine
Z-Phe benzyloxycarbonyl-L phenylalanine
I 3-phenyl-1,2-propanediamine

A moderate DNA exclusion (39.3+- 4.2%) was found
when L-Asp (conc. 0.25 mg/mL) was tested with
DNA (0.05 mg/mL),
whereas Ala performed only a mild effect on DNA (12.3+- 4.1%) at the same
concentration.

Benzyloxycarbonyl-L-Phe gave no measureable interactions.
On the contrary, the synthetic analogue 3-phenyl-1,2-propanediamine
exhibited complete DNA peak exclusion (100%).

In general, there are three major classes of clinically
important DNA interactive substances:
the alkylators, which react covalently with DNA base,
the DNA strand breakers, which generate reactive radicals
that produce cleavage of the polynucleotide strands, and
the compounds that interact reversibly with DNA (10,11).

Intercalators and cationic polyamines exhibiting
electrostatic interactions are included in the third class...

The ionized amino group was close to the
deoxyribose phosphate chain suggesting that a
strong electrostatic interaction could take place between
the drug and the negatively charged DNA phosphate away
from the interaction site (10).
Such phenomena were successfully detected in previous experiments by using
cationic polyamines (6) and DNA photochemical adducts
(7) as well as in the present study expressed in the
% DNA peak exclusion.

Therefore, ASP along with Phe and Asp exhibited relative binding effect on
DNA due to the presence of their amino groups.

The amino acid Ala, which does not contain the aromatic ring of the Phe side
chain gave a small measureable % DNA peak exclusion due to the presence of
the amino group,
whereas no DNA peak exclusion was observed with benzyloxycarbonyl-L-Phe, a
protected amino group Phe analogue.

However, the Phe derivative 3-phenyl-1,2-propanediamine,
where the carbonyl group of Phe has been substituted by an additional amino
group showed a considerable increase of % DNA peak exclusion compared to
that caused by Phe (100% and 31.6% respectively).

This result is obviously related to the presence of the two amino groups
which is in full agreement with previous data (6).

Consequently, the potency of the phenomenon attributed to
ionic interactions is increased when the number of amino
groups increases (Table 2).

Apart from the ionic effect, a possible partial intercalation of the Phe
aromatic ring into the base pairs of DNA is reinforced by recent
findings showing that the Phe residues of TATA box binding protein
interacts with the T-A base pair by Van der Walls contacts (12).

Although Shephard et al (13) found no detectable mutagenicity
of ASP and Phe by using other methods,
structural modification of DNA through covalent and noncovalent interactions
have significant functional consequences such as replication errors, which
could be among the events that start the cellular
processes ultimately yielding malignant tumors (14).

The hypothesis that structural transitions and condensations
in specific DNA sequences caused by polyamines may also
be related to nucleosome formations and the condensation
of DNA into chromatin is gaining experimental support.

In conclusion, these in vitro findings are of interest because
a widely used compound such as ASP along with its
metabolites gave a measurable molecular interaction with DNA.

These DNA effects are evaluated for the first time with a
considerable reproducibility and can serve as a useful
prescreen assay.

1. Partridge WM.
The safety of aspartame.
JAMA 1986; 256: 2678 (letter)

2. Janssen PJ, Heijden CA.
Aspartame: review of recent experimental and observational data.
Toxicology 1986; 50: 1-26.

3. Michals K, Azen C, Acosta P.
Blood Phenylalanine levels and intelligence
of 10 year old children with Phenylketonuria.
J Am Diet Assoc 1988; 88: 1226-9.

4. Olney JW, Farber NB, Spitznagel E, Robins LN.
Increasing brain tumor rates: Is there a link to aspartame?
J Neuropathol Exp Neurol 1996 55/11: 115-23.

5. Gupta MP, Monge A, Karikas GA, et al.
Screening of panamanian medicinal plants
for brine shrimp toxicity, grown gall, tumor inhibition,
cytotoxicity and DNA intercalation.
Int J Pharmacognosy 1996; 34: 19-27.

6. Karikas GA, Constantinou V, Kokotos G.
An HPLC method for the measurement of polyamines
and lipidic amines binding to DNA.
J Liquid Chromatography 1997; 20(11): 1789-96.

7. Karikas GA, Schulpis KH, Kokotos G,
Michas T, Georgala S.
Stoichiometric measurement of DNA damage
caused by 8-Methyl-Psoralen and UVA.
Clin Biochemistry 1997; 30(5): 439-42.

8. Aposhian HV, Kornberg A
Enzymatic synthesis of Deoxyribonucleic acid.
J. Biol Chem 1962; 237: 519-25.

9. Kokotos G, Constantinou V,
Modifid amino acids and peptides.
Part 2. A convenient conversion of amino and
peptide alcohols into amines.
J Chem Res (S) 1992; 391, and
J Chem Res (M) 1992; 3117-32.

10. Silverman RB.
The organic chemistry of drug design and drug action.
DNA 1992; 236-43.

11. Blackburn GM, Gait MJ, eds.
Reversible interactions of nucleic acids with small molecules.
In: Nucleic acids in chemistry and biology. Pp. 297-336.
Oxford: IRL Press, 1990.

12. Burley SK.
The TATA box binding protein.
Curr Opin Struct Biol 1996; 6: 69-75.

13. Shephard SE, Wakabayashi K, Nagao M.
Mutagenic activity of peptides and the artifical
sweetener aspartame after nitrosation.
Food Chem Toxicol 1993; 31/5: 325-9.

14. Wallace S, Van Heuten B, Kow YW.
DNA damage effecting DNA structure and
protein recognitions.
Ann NY Acad Sci 1994; 726: 18.
************************************************** **********************

[ This paper demonstrates the details of their current competence. ]

http://jcem.endojournals.org/cgi/content/full/89/8/3983 free full text

The Journal of Clinical Endocrinology & Metabolism
Vol. 89, No. 8 3983-3987
Copyright © 2004 by The Endocrine Society

Morning Preprandial Plasma Ghrelin and Catecholamine Concentrations in
Patients with Phenylketonuria and Normal Controls: Evidence for
Catecholamine-Mediated Ghrelin Regulation

Kleopatra H. Schulpis,
Ioannis Papassotiriou, biochem[at]paidon-agiasofia.gr
Maria Vounatsou,
George A. Karikas,
Stylianos Tsakiris and
George P. Chrousos

Institute of Child Health (K.H.S.), 11527 Athens, Greece;

Department of Clinical Biochemistry, Aghia Sophia Children's Hospital (I.P.,
M.V., G.A.K.), 11527 Athens, Greece;

Blood Transfusion Service, Henri Dunant Hospital (M.V.), 11527 Athens,
Greece; and

Departments of Experimental Physiology (S.T.) and

Pediatrics (G.P.C.), Athens University Medical School, 11527 Athens, Greece

Address all correspondence and requests for reprints to:
Dr. I. Papassotiriou, Department of Clinical Biochemistry, Aghia Sophia
Children's Hospital, 11527 Athens, Greece.
E-mail: biochem[at]paidon-agiasofia.gr

Abstract
Introduction
Subjects and Methods
Results
Discussion
References

Abstract

Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the
conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased
production of noradrenaline, adrenaline, and dopamine.

Poor diet control results in high plasma Phe and low plasma Tyr and
catecholamine concentrations.
Ghrelin, a recently described gastrointestinal hormone that is elevated in
the fasting state and low in the fed state, is considered a major
appetite-stimulating hormone, possibly involved in the generation of obesity
and insulin resistance.

We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled
and 15 poorly controlled PKU patients and 20 age- and body mass index
(BMI)-matched healthy children (controls) and correlated its concentrations
with those of Phe and catecholamines as well as with their BMI and 24-h
nutrient intake.

Plasma ghrelin levels were measured by RIA, plasma catecholamine
concentrations were determined by HPLC with electrochemical detection, and
Phe and Tyr levels were measured in an amino acid analyzer.

The ghrelin concentration (744 ± 25 ng/liter) in diet-controlled patients
did not differ from that in controls (802 ± 26 ng/liter; P > 0.05).

On the contrary, the ghrelin concentration was significantly reduced in
poorly controlled patients (353 ± 23 ng/liter; P < 0.0001).

Ghrelin correlated negatively with Phe in all three groups,
whereas it correlated positively with catecholamine levels and energy intake
and negatively with BMI only in diet-controlled patients and controls.

We conclude that ghrelin secretion may receive positive direct or indirect
input from catecholamines.
The absence of a correlation between ghrelin and catecholamines, energy
intake, or BMI in PKU patients on an inadequate diet may be due to
dysregulation of their neuroendocrine system and might be affected by high
Phe levels in the stomach and/or central nervous system.

Introduction

CLASSIC PHENYLKETONURIA (PKU)
is an inborn error of metabolism in which the
aromatic amino acid phenylalanine (Phe) cannot be converted to tyrosine
(Tyr) (1, 2).

PKU is successfully treated with a low Phe diet started as soon as possible,
in the first days of life.

Many PKU patients, however, do not adhere strictly to this diet,
and this results in high plasma levels of Phe interfering with the
conversion of Tyr to the catecholamine neurotransmitters
noradrenaline (NA), adrenaline (A) and dopamine (DA) (3), and
low plasma NA, A, and DA concentrations (4, 5).

Poorly controlled patients with PKU have significantly elevated
concentrations of plasma leptin,
the adipose tissue hormone that plays a role in inhibiting food intake and
stimulating the basal metabolic rate (6).

Because the secretion of this adipokine is normally inhibited by NA and/or A
via ß-adrenergic receptors on fat cells,
the decreased catecholamine levels of poorly controlled PKU patients appear
to result in disinhibition of plasma leptin concentrations (6).

Ghrelin is the endogenous ligand for the GH secretagogue receptor,
a G protein-coupled receptor expressed in the hypothalamus, pituitary, and
pancreas (7).

Ghrelin was recently isolated from the stomach,
where its concentrations are quite high (8),
although lower amounts were also found in hypothalamic arcuate nucleus
neurons as well as in the pituitary, kidney, placenta, bowel, and pancreas
(9, 10).

Ghrelin concentrations are generally negatively correlated with the levels
of leptin, and accordingly, this gastric hormone is,
respectively, stimulated or inhibited by fasting and food intake.

Furthermore, ghrelin diametrically opposes the actions of leptin,
stimulating food intake, inhibiting metabolic rate, and increasing body
weight in experimental animals (11).

The end products of the sympathetic system, especially NA, play a major role
in the regulation of appetite, energy expenditure, and the secretion of
adipokines such as leptin.

We hypothesized that the secretion of ghrelin might be regulated by
catecholamines in a fashion opposite that of leptin, and that an inborn
error of metabolism, such as in PKU, characterized by decreased
catecholamine production might reveal such regulation.

The aim of this study was to evaluate the secretion of ghrelin in PKU
patients under excellent or poor dietary control and to correlate its
concentrations with those of Phe and the catecholamines as well as with the
24-h nutrient intake and body mass index (BMI) of these subjects.

Subjects and Methods

Patients and controls

The study population consisted of 29 PKU patients
who were divided into two groups according to their mean annual morning
preprandial plasma Phe (Phe mean) concentrations and
20 appropriately matched control children (Table 1):
group A (n = 14) included patients who adhered strictly to their special
diet (mean annual Phe, 127.0 ± 72.6 µmol/liter),
whereas group B included 15 PKU patients who were on a "loose" diet and had
grossly elevated mean annual Phe levels (1234.2 ± 157.3 µmol/liter).

All patients were initially detected by neonatal screening and placed on a
special diet after a tetrahydropterin (BH4) loading test and
dihydropteridine reductase evaluation confirmed the diagnosis of PKU.

Their daily protein intake was largely replaced by PKU2 (Milupa AG, Milupa
GmbH, Friedrichdorf, Germany), which is a Phe-free mixture of amino acids.

Group C was comprised of 20 healthy children of similar age to the PKU
patients.
Both patients and controls were prepubertal.
All PKU patients and control children were admitted to a day clinic for
evaluation and blood sampling.
The daily nutrient intake of each child was calculated by a 24-h dietary
recall of the day preceding admission according to a coded list (12). These
subjects and their plasma leptin concentrations were previously reported
(6).

View this table:
[in this window]
[in a new window]
TABLE 1. Clinical profile of PKU patients and controls

Samples

The study was approved by the Aghia Sophia Children's Hospital ethics
committee, and written consent was obtained from the parents of the children
who participated in this study.
All blood samples (5.0 ml) were drawn from an antecubital vein at the same
time of the day (0900 h) after a 10-h overnight fasting and after a 1- to
2-h period in the day clinic area to allow acclimatization to the
environment and staff.

Methods

Height (centimeters) was measured on a portable stadiometer, calibrated with
a machine meter rod, and
weight (kilograms) was evaluated with an electronic scale.
Genital or breast development was graded according to Tanner, with
testicular volume (milliliters) defined by comparison with a Prader
orchidometer.
BMI was calculated and expressed as kilograms per meter squared (13).
Plasma catecholamine (NA, A, and DA) levels were measured by reverse phase
HPLC with electrochemical detection (14).
The interassay coefficients of variation (CVs) for NA, A, and DA were 3.2%,
2.9%, and 3.4%, respectively.
Plasma ghrelin levels were measured using a commercial RIA kit (Phoenix
Pharmaceuticals, Belmont CA) that uses 125I-labeled bioactive ghrelin as a
tracer molecule and a rabbit polyclonal antibody against full-length
octanoylated human ghrelin.
This assay recognizes both active and inactive forms of ghrelin.
The sensitivity of the assay was 10 pmol/liter, the intraassay CV was 5.5%,
and the interassay CV was 2.1% (15).

Quantitative analysis of serum amino acids, including Phe and Tyr, was
carried out using an automatic amino acid analyzer (LC 5001, Biotronik,
Berlin, Germany).
Results were calculated using nor-leucine as an internal standard.
The CVs for Tyr and Phe were 2.1% and 2.3%, respectively.

Data analyses

Data are expressed as the mean ± SD or the mean ± SEM as indicated.
Data were analyzed by ANOVA, followed by Bonferroni-corrected
t test or a post hoc test (Tukey's), as indicated.
The correlation coefficient r between the parameters tested was computed
using least squares regression analysis.
The P values reported are two-tailed.
All statistical procedures were performed using the STATGRAFICS PLUS version
5.1 for Windows
(Graphic Software System; Manugistics Inc., Rockville, MD),
whereas the regression plot and box plots were prepared using the Sigma-Plot
software version 8.0 program.

Results

Age, height, weight, and BMI did not differ among the three groups studied
(Table 1).
Twenty-four-hour energy intake, total protein, and carbohydrates also did
not differ among the three groups; however, saturated and polyunsaturated
fat intake values were different (Table 2).

Statistically significant differences in total fat, monounsaturated fat, and
fiber intake were found between groups A and B as well as between groups A
and C.

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TABLE 2. Estimated 24-h nutrient intake for PKU patients and controls

Plasma Phe was significantly different among the three groups, whereas Tyr
levels were significantly reduced in group B compared with those in group A
and controls (Table 3).
On the contrary, plasma ghrelin (Fig. 1) as well as DA and NA did not differ
between group A and controls,
whereas the concentrations of these hormones were significantly different
between the two groups of PKU patients and between group B and controls.
Plasma A levels were significantly higher in group A than in group B and
slightly higher (P = 0.04) than those in controls.

View this table:
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[in a new window]
TABLE 3. Biochemical data in PKU patients and controls

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FIG. 1. Morning preprandial plasma ghrelin concentrations (median ± SD) in
patients with PKU and matched normal controls.
Group A, PKU patients well controlled on a strict diet;
group B, PKU patients poorly controlled on a loose diet;
group C, controls.

Plasma ghrelin concentrations correlated negatively with Phe (Fig. 2) and
BMI in all three groups.
On the contrary, the hormone correlated positively with the 24-h energy
intake, all three catecholamines, and Tyr only in group A and controls
(Table 4).
No correlation was found between plasma ghrelin concentrations and the above
parameters in group B of patients who were poorly controlled by diet.

View larger version (15K):
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[in a new window]
FIG. 2. Correlations between plasma Phe and ghrelin concentrations in
patients with PKU and matched normal controls. Group A, PKU patients well
controlled on a strict diet; group B, PKU patients poorly controlled on a
loose diet; group C, controls.

View this table:
[in this window]
[in a new window]
TABLE 4. Correlation coefficients between ghrelin and plasma amino acids
or catecholamines and 24-h nutrient intake or BMI in PKU patients and
controls

The plasma ghrelin levels correlated negatively with the leptin levels of
the same patients measured and reported previously in group A and controls,
but not in group C (6).

Discussion

Energy intake and body weight are tightly regulated at a remarkably
consistent set-point by control systems in the hypothalamus and elsewhere in
the central nervous system, receiving feedback from diverse peripheral
signals (16).

In addition, it is now recognized that there are many central and peripheral
factors involved in energy homeostasis, and it is expected that the
understanding of these mechanisms should lead to effective treatment for the
control of body weight (17).

Thus, all nutrients inhibit ghrelin secretion equally and can do this by
administration via both the luminal and systemic routes (18).

As expected, in this study, ghrelin levels positively correlated with energy
intake and negatively with BMI in the diet-controlled patients of group A
and controls, but not in the poorly controlled patients of group B.

In our previous study (6), leptin, which signals the state of fat stores to
the brain and inhibits food intake and further fat accumulation (19),
correlated negatively with 24-h energy intake and BMI only in PKU patients
who were well controlled on a strict diet.

We suggested that the diminished concentrations of the catecholamines NA and
A in these patients might have disinhibited leptin secretion and hence
increased their plasma leptin concentrations.

The same rationale could be applied for ghrelin to explain the diametrically
opposite relations of this hormone with the catecholamines; only in this
instance these hormones appear stimulatory.

Increased Phe concentrations, as we found in the poorly controlled PKU
patients in group B, decrease the availability of the catecholamine
precursor Tyr for catecholamine biosynthesis,
which was indeed low in these patients, and might be the primary cause of
their catecholamine depletion in the central nervous system and periphery
(13, 20).

Because the hypothalamus and brainstem lie inside the blood-brain barrier,
movement of large neutral amino acids, including Phe and Tyr, across this
barrier is mediated by a common high affinity transport system (21).

In group B patients, the large excess of Phe may saturate this carrier
system and thus block other amino acids, such as Tyr,
from entering the brain and be available for the synthesis of
catecholamines,
leading to major brain dysfunction and decreased peripheral secretion of NA
by the systemic sympathetic system (21, 22).

Also, it is likely that the decreased Tyr concentrations in the plasma of
PKU patients (group B) result in decreased uptake by chromaffin cells of the
adrenal medulla,
leading to low production of A, as found in the blood of these patients.
We know very little about the neural and hormonal regulation of ghrelin
secretion by the stomach.

Because food intake and energy expenditure are both regulated by the
catecholamines NA and A,
it is obvious that these biogenic amines might also affect the production of
ghrelin (9, 22, 23).

This suggestion is supported by the positive correlations found between
ghrelin and catecholamines in patients on a strict diet (group A) and in
healthy children (controls) and
by the general decrease in ghrelin secretion in poorly controlled PKU
children.

Additionally, high levels of Phe may directly affect the arcuate
hypothalamic nucleus, pituitary, and/or stomach (7, 9, 14, 22), resulting in
an inhibition of ghrelin production,
as shown by the significant negative correlations between ghrelin and Phe in
all three groups.

With regard to the healthy group of children, the small number of
participants used suggests that further investigations are warranted.

Phe significantly decreases rat brain acetylcholinesterase activity in
vitro, potentially resulting in increased cholinergic activity (24).

Similarly, erythrocyte membrane acetylcholinesterase activity in poorly
controlled PKU patients is markedly inhibited (25).

Moreover, an increase in the Phe concentration appears to stimulate the
production of GTP-cyclohydrolase-stimulating protein,
which increases de novo the synthesis of tetrahydrobiopterin, a natural
cofactor of Phe hydroxylase,
which has direct acetylcholine-releasing action in the rat brain in vivo
(26).

The stomach is the major source of circulating ghrelin in humans (27), and
high Phe-induced dysregulation of the gastric cholinergic system in poorly
controlled PKU patients may result in decreased secretion of ghrelin (24,
25, 26).

The latter hypothesis could be tested by measuring plasma ghrelin levels
pre- and postloading with Phe (L-Phe, 100 mg/kg, orally) in healthy and
gastrectomized patients (27).

These and previously reported data (6) in children with PKU show marked
dysregulation in two major hormones regulating appetite, energy expenditure,
and body weight, namely ghrelin and leptin, in poorly controlled patients.

Yet, despite the gross change in the ratio of the concentrations of these
hormones, poorly controlled PKU patients retain the ability to maintain a
stable body weight regulatory set-point.

This is in contradistinction with data from experimental animals,
in which this set-point can be easily reset by administration of ghrelin or
leptin and in concert with data from human adults.

These findings together suggest that the regulation of body weight stability
in humans contains many redundancies that are difficult to overcome with
disturbance of one single hormone.

Acknowledgments

We are grateful to Ms. Anna Stamatis for typing the manuscript.

Footnotes

Abbreviations:
A, Adrenaline;
BMI, body mass index;
CV, coefficient of variation;
DA, dopamine;
NA, noradrenaline;
Phe, phenylalanine;
PKU, phenylketonuria;
Tyr, tyrosine.
Received February 18, 2004.
Accepted May 14, 2004.

References

Scriver C, Kaufman S, Eisensmith R, Woo S 2000 The hyperphenylalaninemias.
In: Scriver C, Beaudet A, Sly W, Valle D, eds. The metabolic and molecular
bases of inherited disease, 8th ed. New York: McGraw-Hill; 1775-1875

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U, Constantopoulos A 1998 Elevated serum prolactin concentrations in
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concentrations in phenylketonuric patients. Horm Res 53:
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natural endogenous ligand for the growth hormone secretagogue receptor.
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Horvath TL, Diano S, Sotonyl P, Heiman M, Tschop M 2001 Minireview: ghrelin
and the regulation of energy balance a hypothalamic perspective.
Endocrinology 142: 4163-4169[Abstract/Free Full Text]

Broglio F, Arvat E, Benso A, Gottero C, Prodam F, Grottoli S, Papotti M,
Muccioli G, van der Lely AJ, Deghenghi R, Ghigo E2002 Endocrine activities
of cortistatin-14 and its interaction with GHRH and ghrelin in humans. J
Clin Endocrinol Metab 87: 3783-3790

Camina GP, Carreira MC, Micic D, Pombo M, Kelestimur F, Dieguez C, Casanueva
FF 2003 Regulation of ghrelin secretion and action. Endocrine 22:
5-12[CrossRef][Medline]

Paul AA. Southgata GA, Russel J 1980 The composition of the food. London:
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De Onis M, Habicht JP 1996 Anthropometric reference data for international
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Candito M, Albentini M, Politano S, Deville A, Mariani R, Chambon P 1993
Plasma catecholamine levels in children. J Chromatogr 17: 304-307

Wren AM, Seal LG, Cohen MLA, Brynes AE, Frost GS, Murphy KG, Dhillo WS,
Gatel MA, Bloom SR 1995 Ghrelin enhances appetite and increases food intake
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Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG 2000 Central nervous
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Gale SM, Castracane VD, Mantzoros CS 2004 Energy homeostasis, obesity and
eating disorders: recent advances in endocrinology. J Nutr 134:
295-298[Abstract/Free Full Text]

Gomez G, Englander EW, Greeley Jr GH 2004 Nutrient inhibition of ghrelin
secretion in the fasted rat. Regul Pept 117: 33-36[CrossRef][Medline]

Mantzoros CS, Moschos SJ 1998 Leptin in search of role(s) in human
physiology and pathophysiology. Clin Endocrinol (Oxf) 49:
551-567[CrossRef][Medline]

Carlson H, Hyman D, Blitzer M 1990 Evidence for an intracranial action of
phenylalanine in stimulation of prolactin secretion: interaction of large
neutral amino acids. J Clin Endocrinol Metab 70: 814-816[Abstract]

Koch R, Moats R, Guttler F, Guldberg P, Nelson M 2000 Blood-brain
phenylalanine relationships in persons with phenylketonuria. Pediatrics 106:
1093-1096[Abstract/Free Full Text]

Curtius H, Wiederwieser C, Viscontini G, Leimbachter M, Wegman H, Schmidt H
1981 Serotonin and dopamine synthesis in phenylketonuria. Adv Exp Med Biol
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Quigada M, Illner P, Krulich L, McCann S 1974 The effect of catecholamines
on hormone release from anterior pituitaries and ventral hypothalamus
incubated in vitro. Neuroendocrinology 13: 151-154

Tsakiris S, Krontiri T, Schulpis KH, Stavridis J 1998 The phenylalanine
effect on rat brain acetylcholinesterase and Na+K+ATPase. Z Naturforsch C
53: 163-167[Medline]

Schulpis KH, Karikas GA, Tjamouranis H, Michelakakis H, Tsakiris S 2002
Acetylcholinesterase activity and biogenic amines in phenylketonuria. Clin
Chem 48: 794-796

Ohue T, Koshimura K, Lee K, Watanabe Y, Miwa S 1991 A novel action of
6R-L-erythro-5,6,7,8 tetrahydropterin, a cofactor of hydroxylases of
phenylalanine, tyrosine and tryptophane enhancement of acetylcholine release
in vivo in the rat brain. Neurosci Lett 128: 93-96[CrossRef][Medline]

Ariyasu H, Tanaka K, Tagami T, Ogawa Y, Hosoda K, Akamizu T 2001 Stomach is
a major source of circulating ghrelin and feeding state determines plasma
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5743-5757

EndocrinologyEndocrine Reviews
J. Clin. End. & Metab.
Molecular Endocrinology
Recent Prog. Horm. Res.
All Endocrine Journals
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http://groups.yahoo.com/group/aspartameNM/message/1186
aspartame induces lymphomas and leukaemias in rats, free full plain text, M
Soffritti, F Belpoggi, DD Esposti, L Lambertini, 2005 April, 2005.07.14:
main results agree with their previous methanol and formaldehyde studies,
Murray 2005.07.19

http://groups.yahoo.com/group/aspartameNM/message/1185
Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at
human use levels causes cancer (methanol, formaldehyde, formic acid), M
Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray
2005.07.15

http://groups.yahoo.com/group/aspartameNM/message/1189
Michael F Jacobson of CSPI now and in 1985 re aspartame toxicity, letter to
FDA Commissioner Lester Crawford; California OEHHA aspartame critique
2004.03.12; Center for Consumer Freedom denounces CSPI: Murray 2004.07.27


http://www.ramazzini.it/fondazione/d...ameGEO2005.pdf

" In rodents and humans,
APM is metabolised in the gastrointestinal tract
into three constituents:
aspartic acid, phenylalanine and methanol 3. "

" These experiments demonstrate that the increase in
lymphomas and leukaemias,
observed in the APM study,
could be related to methanol, a metabolite of APM,
which is metabolised to formaldehyde and then to formic acid,
both in humans and rats 3. "

" Yellowing of the coat was observed in animals exposed to APM, mainly at
the highest concentrations.

This change was previously observed in our laboratory in rats exposed
to formaldehyde administered with drinking water 9. "


1. The total number of rats was 1800. 1500 were given aspartame.

2. 44 [ 14.7 % ] of the 300 control rats, given no aspartame, developed
lymphomas and leukemias (hemolymphoreticular neoplasias ), and none had
malignant brain tumors.

Of 1500 rats given aspartame, 294 [ 19.6 % ] had lymphomas and leukemias
(hemolymphoreticular neoplasias), and 12 [ 0.8 % ] had malignant brain
tumors.

In their previous methanol study, reported Dec 2002, of 200 + 100 = 300
control rats, given no methanol, there were 41+ 15 = 56 [ 18.7% ]
lymphomas and leukemias (hemolymphoreticular neoplasias), while of 600 +
100 = 700 rats given methanol, there were 187 + 15 = 202 with the same
cancers [ 28.9 % ]. They added 100 rats given 15 ppm methanol to their
Table 3 summarizing the formaldehyde data in their formaldehyde study, in
which their 200 control rats had 15 of these cancers.

In their previous formaldehyde study, reported Dec 2002, 200 control rats,
given no formaldehyde, had 15 [ 7.5 %] lymphomas and leukemias
(hemolymphoreticular neoplasias), while of the 600 rats given formaldehyde,
121 [ 20.3 % ] had these cancers.

Probably, other factors, such as viruses, bacteria, molds, or toxic
chemicals in the air, water, and food, also facilitate these cancers.

http://www.ramazzini.it/eng/fondazio...gli.asp?id=210



http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame...2-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

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

Gold points out that industry methanol assays were too insensitive to
properly measure blood methanol levels. ]

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). If 30% of
the methanol is turned into formaldehyde, the amount of formaldehyde is 18
times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2
L water.

http://groups.yahoo.com/group/aspartameNM/message/835
ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
Murray 2002.05.30 rmforall

Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
both ordinary amino acids, bound loosely together by methanol (wood alcohol,
11%). The readily released methanol from aspartame is within hours turned
by the liver into formaldehyde and then formic acid, both potent, cumulative
toxins.


http://groups.yahoo.com/group/aspartameNM/message/1182
Joining together: short review: research on aspartame (methanol,
formaldehyde, formic acid) toxicity: Murray 2005.07.08 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1071
research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray
2004.04.29 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition: Bouchard M et al, full
plain text, 2001: substantial sources are degradation of fruit pectins,
liquors, aspartame, smoke: Murray 2005.04.02 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1131
genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text,
Rencuzogullari E et al, Cukurova University, Adana, Turkey 2004 Aug: Murray
2004.11.06 rmforall

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 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
Belsito, Nov 2003: Murray 2004.03.30 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[at]drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehy..._toxicity.html full text

http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol
98 mg/L [ becomes formaldehyde in body ]: EU Scientific Committee on Foods
2001.07.12: Murray 2004.01.22 rmforall


http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text Trocho & Alemany 1998.06.26: Murray 2002.12.22

Trocho & Alameny (1998):
"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."

Here is research in 1998 at a very low level of aspartame
ingestion, 10 mg/kg, for rats, which have a much greater tolerance for
aspartame than humans. The same toxicity level for humans would be
about 1 mg/kg. Many headache studies in humans used doses of about 30
mg/kg daily. A daily dose of 1120 mg aspartame, about 2 L diet soda,
used in many experimental tests on humans, is 19 mg/kg and supplies 123
mg methanol into the body, 2 mg/kg for a 60 kg body. Many cases report
typical serious symptoms at this level. This report shows that
aspartame causes binding of methanol's product, formaldehyde, a potent,
cumulative toxin, into tissues.

http://ww.presidiotex.com/barcelona/index.html full text & graphs

Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, X. Remesar, Dr. Jose Antonio Fernandez-Lopez,
Dr. Marià Alemany Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain. 34-934021521 fax 34-934021559
Avinguda Diagonal, 645; 08028 Barcelona, Spain.
Maria Alemany, PhD (male) alemany[at]porthos.bio.ub.es
http://www.bq.ub.es/grupno/grup-no.html
************************************************** ********