[Neuroscience] 21 years of aspartame (methanol, formaldehyde) toxicity from daily Baclofen Schwarz Pharma, Kemstro orally dissolving tablets): FDA info: MaryChris: Greg: Murray 2005.07.07

Rich Murray rmforall at att.net
Fri Jul 8 01:00:19 EST 2005


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

http://groups.yahoo.com/group/aspartameNM/message/1180
21 years of aspartame (methanol, formaldehyde) toxicity from daily Baclofen
(Schwarz Pharma, Kemstro orally dissolving tablets): FDA info: MaryChris:
Greg: Murray 2005.07.07

[ These three items are slightly edited for clarity, with more spacing.
Comments by Rich Murray are in square brackets.  I am sending this to the
Board of Schwarz Pharma, hoping to elicit a creative response that will
enormously benefit the citizens of our world. ]

From: <MaryChrisW at aol.com>
To: <gregdude63 at hotmail.com>; <aspartame at yahoogroups.com>
Subject: Re: [Aspartame Support] new to group and can't sleep
Date: Thursday, July 07, 2005 10:42 AM

When I first started reading Greg's post, I thought I was reading my own
story.  I, too, am 42.  Over the last 5 years my symptoms increased from
abdominal  pain, to numbness in face and belly, to memory loss, to ringing
ears-- to now numbness in my lower extremities.

I read about aspartame poisoning and  said, THIS IS ME!  Yet I never
consumed diet pop and ate whole foods. I finally did some digging last night
on the medication I've been prescribed (and taking  daily for 21 years) and
sure enough, Aspartame. I was devastated and yet finally  I feel I have an
answer for years of increased suffering and negative test  results.
Unfortunately-- or ironically? -- the drug (Baclofen) is not something you
can stop cold turkey. There are all kinds of warnings.

I'm supposed to contact my doctor who -- after years of finding nothing
wrong with me despite my  weighing 82 pounds -- treats me like a headcase
rather than a medical case. I can just imagine  his reaction if I suggest
aspartame is to blame for  anything.

Mary


From: "gregdude1763" <gregdude63 at hotmail.com>
To: <aspartame at yahoogroups.com>
Subject: [Aspartame Support] new to group and can't sleep
Date: Thursday, July 07, 2005 9:28 AM

Hello,

My name is Greg and I am 42 years old.  I've been following this
group off and on for a few years, but lately very much off.  About 3
years ago I started having (more like noticing) symptoms such as
headaches, depression, blurry vision, muscle sorness, short term
memory loss, ringing ears, etc.  I found this site then and totally
was amazed and shocked that these problems could be related to
aspartame.  And I knew it was possible since I was drinking about a
6 pack a day of diet coke!

Anyway, I managed to get off the diet soda for a while and felt much better.
But after a while, I would inevitably gravitate back to the soda...
drink tons of it daily, then
get off of it a while and feel better...then start the cycle all
over again. After a while, I just started ignoring the symptoms and
now for the last couple of years I have been back guzzling diet
sodas.  I really think I have a problem...I know the stuff is bad
for me, but I just can't seem to quit...I don't know why!  At work,
for instance, I love the fresh taste of cool bottled water...but
here I go to the vending machine for a diet coke!

Anyway, why I am finally asking for encouragement
(which I should have done 3 years ago),
is I'm having slightly worsening headaches, muscle soreness
(exercise seems to be helping lately with that), blurred vision in
my right eye, loud ringing in ears and, the most disturbing and what
I'd like to ask about...is sleep apnea (spelling?).  This has been
getting progressively worse, until the last few nites I jump out of
bed just after falling asleep trying to catch my breath.  I
literally feel like I am dying.  It is very scary. It's like there
is some sort of blockage in my throat, or it's constricted in some
way...I don't know. That's why I am up now writing this at nearly 3
am.  Anyway, I have to go for a check up to see what could be
causing this...but is it possible these symptoms could be caused by
acute aspartame poisening?  Even if not, this has got me so scared
that I am determined to drop the aspertame for good, and I know my
other symptoms will go away, and maybe it is contributing to the
apnea in some way.

Thanks for listening...and I look forward to reporting back on my
progress as I try and detox myself from this retched poison.  The
fist step though, is to get off the stuff cold turkey...which I
have'nt been able to do. Take it a day at a time as they say. Wish
me luck...I will need it.

Greg
************************************************************


"During the last few years SCHWARZ PHARMA has been able to create and move
forward an impressive development portfolio in neurology and urology through
its Search and Development strategy.

SCHWARZ PHARMA is advancing the development of innovative drugs for the
treatment of Parkinson's disease, Restless Legs Syndrome (RLS), epilepsy,
neuropathic pain, overactive bladder syndrome and others."

[ Aspartame reactors commonly report aggravation of all the above
neurological syndromes. ]

SCHWARZ PHARMA AG
Alfred-Nobel-Straße 10   Monheim, Germany
Tel +49 2173 48 - 0  Fax +49 2173 48 -1608   info at schwarzpharma.com

Schwartz Pharma, Inc.
P.O.Box 2038  Milwaukee, WI 53201
(800) 558-5114   (262) 238-9994   Fax: 262-238-0311
dbrennan at schwarzusa.com  mleister at schwarzusa.com

 Donna K. Multhauf     Director, Regulatory Affairs and Quality Assurance

PO. Box 2038 l Milwaukee, WI 53201-2508 l     6140 West Executive Dr. l
Mequon, WI 53092-4467
Telephone 262-238-9994  Tollfree 800-558-5114    Fax 262-238-0311
www.schwarzusa.com

twillard at schwarzusa.com; kveiting at schwarzusa.com;
patrick.schwarz-schuette at schwarzpharma.com;
detlef.thielgen at schwarzpharma.com; juergen.baumann at schwarzpharma.com;
iris.loew-friedrich at schwarzpharma.com
************************************************************

http://www.fda.gov/cder/foi/label/2003/21589_kemstro_lbl.pdf

"Phenylketonurics

Phenylketonuric patients should be informed that KEMSTRO. contains
phenylalanine 3.9 mg per 10 mg orally disintegrating tablet and 7.9 mg per
20 mg orally disintegrating tablet."

[ Since phenylalanine is 50% of aspartame, the aspartame dose is 7.8 and
15.8 mg for these two dose levels of a medicine that dissolves in the mouth
at a level that has been observed to trigger toxic symptoms for aspartame
reactors.

The 20 mg pill is about the same dose, 15.8 mg aspartame, as three sticks of
chewing gum, 6-8 mg aspartame each, nearly half of a packet of Equal
tabletop sweetener, 37 mg aspartame.

Aspartame reactors often react immediately and severely to such small doses,
even without knowing they were exposed.

The maximum daily Kemstro dose is 80 mg, with 63.2 mg aspartame, about 10
sticks of gum, nearly 2 packets of Equal, about a third of a 12-oz can of
diet soda.

The maximum methanol dose, 11% of the aspartame, is thus 7.0 mg, of which a
large fraction is quickly converted into formaldehyde and then formic acid,
both dire, potent, cumulative toxins.  The USA EPA limit for formaldehyde in
drinking water is 1 ppm, which is 2 mg daily for the average use of 2 L
daily drinking water.  The state limit in California is three times more
stringent, and in Maryland, ten times.  So there is remarkable lack of
consensus and clarity about  safety levels for ingested formaldehyde at low
levels for years. ]

"KEMSTRO. is useful for the alleviation of signs and symptoms of spasticity
resulting from multiple sclerosis, particularly for the relief of flexor
spasms and concomitant pain, clonus, and muscular rigidity.'

[ Aspartame reactors often report headache and many other body pains,
including aching joints, muscle cramps and spasms, burning sensations, and
numbness, as well as fatigue, depression, irritability, visual and eye
problems, poor memory, "brain fog", poor coordination, and so are often
misdiagnosed as having multiple sclerosis. ]

"CONTRAINDICATIONS

KEMSTRO. is contraindicated in patients who are hypersensitive to any
component of this product."

"In patients with epilepsy, the clinical state and electroencephalogram
should be monitored at regular intervals, since deterioration in seizure
control and EEG have been reported occasionally in patients taking
baclofen."

[ Hypersensitity, irregular EEGs, and ideopathic seizures are widely
reported by aspartame reactors.
Formaldehyde, according to Prof. Martin L. Pall, is a major trigger for
Multiple Chemical Sensitivity and many similar syndromes. ]

"The central nervous system depressant effects of baclofen may be additive
to those of alcohol and other CNS depressants.'

[ Dark wines and liquors have about twice the methanol level of the same
volume of diet soda.  Experts state that the main cause of the dreadful
symptoms of "morning after" hangover are due to formaldehyde produced by the
body from methanol.  That is why gin and vodka, with little methanol
impurity, are well known for not causing hangovers.  However, about a
quarter to a half of those who get inebriated do not get hangovers, so there
are huge individual differences.

In ADVERSE REACTIONS, the long list will be a very familiar litany of
problems recognizable by aspartame reactors and their informed physicians. ]


NDA 21-589  Page 5

KEMSTRO.
(baclofen orally disintegrating tablets)

Rx Only

DESCRIPTION

KEMSTRO. (baclofen orally disintegrating tablets) is a muscle relaxant and
antispastic.
Baclofen USP is a white to off-white, odorless or practically odorless
crystalline powder.
It is slightly soluble in water, very slightly soluble in methanol, and
insoluble in chloroform.
Its chemical name is 4-amino-3-(4-chlorophenyl)-butanoic acid.
The molecular weight of baclofen is 213.66
and the empirical formula is C10H12C1NO2.
The structural formula is represented below:

KEMSTRO. is available as 10 mg and 20 mg orally disintegrating tablets.
Each orally disintegrating tablet also contains as inactive ingredients:
aspartame,
colloidal silicon dioxide,
crospovidone,
magnesium stearate,
mannitol,
microcrystalline cellulose,
natural and artificial orange flavor and
povidone.

CLINICAL PHARMACOLOGY

The precise mechanism of action of baclofen is not fully known.
Baclofen is capable of inhibiting both monosynaptic and polysynaptic
reflexes at the spinal level,
possibly by hyperpolarization of afferent terminals,
although actions at supraspinal sites may also occur
and contribute to its clinical effect.

Although baclofen is an analog of the putative inhibitory neurotransmitter
gamma-amino-butyric acid (GABA),
there is no conclusive evidence that actions on GABA systems are involved in
the production of its clinical effects.
In studies with animals, baclofen has been shown to have general CNS
depressant properties as indicated by the production of sedation with
tolerance, somnolence, ataxia, and respiratory and cardiovascular
depression.

NDA 21-589  Page 6

Pharmacokinetics

Absorption

Baclofen is rapidly and extensively absorbed.
Absorption may be dose-dependent,
being reduced with increasing doses.
KEMSTROT given with or without water is bioequivalent to the baclofen
conventional tablet.
Thus KEMSTROT can be placed on the tongue until it disintegrates and then be
swallowed with or without water.
Following a single 20 mg oral dose of KEMSTRO., the peak
plasma concentration was reached about 1½ hours after administration.

Distribution

The apparent volume of distribution is 59 liters.
Baclofen does not readily cross the blood-brain barrier.
Plasma protein binding is approximately 30%.

Metabolism

In a study using radiolabeled baclofen, approximately 85% of the dose was
excreted unchanged in the urine and feces.
About 15% of the dose was metabolized, primarily by deamination.
The ã-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid,
is formed after deamination of baclofen.

Excretion

Baclofen is rapidly and extensively eliminated.
There is a relatively large intersubject variation in elimination.
Baclofen is excreted primarily by the kidney as unchanged drug;
70 - 80% of a dose appears in the urine as unchanged drug.
The remainder is excreted as unchanged drug in the feces or as metabolites
in the urine and feces.
Excretion is complete within 72 hours after administration.
The elimination half-life of KEMSTRO. is approximately 5½ hours.
Total systemic clearance is 180 mL/min and renal clearance is 103 mL/min.

Special Populations

Elderly

The pharmacokinetics of baclofen tablets were evaluated in elderly patients
(69-81 years) and in
healthy younger subjects (23-53 years) after a single 10 mg dose.
The Cmax was lower (119 ng/mL vs. 178 ng/mL)
and the Tmax was longer (3 hours vs. 1 hour)
in the elderly patients compared to the younger subjects.
The AUCs were similar in the two groups.
In this study, the elimination half-life was slightly prolonged in the
elderly patients compared to the younger subjects,
4.43 hours vs. 3.75 hours, respectively.

INDICATIONS AND USAGE

KEMSTRO. is useful for the alleviation of signs and symptoms of spasticity
resulting from multiple sclerosis, particularly for the relief of flexor
spasms and concomitant pain, clonus, and muscular rigidity.

NDA 21-589  Page 7

Patients should have reversible spasticity so that treatment with KEMSTRO.
will aid in restoring residual function.
KEMSTRO. may also be of some value in patients with spinal cord injuries and
other spinal cord diseases.
KEMSTRO. is not indicated in the treatment of skeletal muscle spasm
resulting from rheumatic disorders.
The efficacy of KEMSTRO. in stroke, cerebral palsy, and Parkinson's disease
has not been established and, therefore, it is not recommended for these
conditions.

CONTRAINDICATIONS

KEMSTRO. is contraindicated in patients who are hypersensitive to any
component of this product.

WARNINGS

Abrupt Drug Withdrawal

Hallucinations and seizures have occurred on abrupt withdrawal of baclofen.
Therefore, except for serious adverse reactions,
the dose should be reduced slowly when the drug is discontinued.

Impaired Renal Function

Because baclofen is primarily excreted unchanged by the kidneys,
it should be given with caution and it may be necessary to reduce the dosage
in patients with impaired renal function.

Stroke

Baclofen has not significantly benefited patients with stroke. These
patients have also shown poor tolerability to the drug.

PRECAUTIONS

General

Baclofen should be used with caution where spasticity is utilized to sustain
upright posture and balance in locomotion or whenever spasticity is utilized
to obtain increased function.

In patients with epilepsy, the clinical state and electroencephalogram
should be monitored at regular intervals, since deterioration in seizure
control and EEG have been reported occasionally in patients taking baclofen.

Information for Patients

Because of the possibility of sedation,
patients should be cautioned regarding the operation of automobiles or other
dangerous machinery, and activities made hazardous by decreased alertness.
Patients should also be cautioned that the central nervous system depressant
effects of baclofen may be additive to those of alcohol and other CNS
depressants.

Phenylketonurics

Phenylketonuric patients should be informed that KEMSTRO. contains
phenylalanine 3.9 mg per 10 mg orally disintegrating tablet and 7.9 mg per
20 mg orally disintegrating tablet.

NDA 21-589 Page 8

Drug Interactions

The central nervous system depressant effects of baclofen may be additive to
those of alcohol and other CNS depressants.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A dose-related increase in incidence of ovarian cysts and a less marked
increase in enlarged and/or hemorrhagic adrenal glands was observed in
female rats treated chronically with baclofen.

Ovarian cysts have been found by palpation in about 4% of the multiple
sclerosis patients that were treated with baclofen for up to one year.
In most cases these cysts disappeared spontaneously while patients continued
to receive the drug.
Ovarian cysts are estimated to occur spontaneously in approximately 1% to 5%
of the normal female population.

Pregnancy

Pregnancy Category C.

Baclofen has been shown to increase the incidence of omphaloceles (ventral
hernias) in fetuses of rats given approximately 13 times the maximum dose
recommended for human use,
at a dose which caused significant reductions in food intake and weight gain
in dams.
This abnormality was not seen in mice or rabbits.
There was also an increased incidence of incomplete sternebral ossification
in fetuses of rats given approximately 13 times the maximum recommended
human dose,
and an increased incidence of unossified phalangeal nuclei of forelimbs and
hindlimbs in fetuses of rabbits given approximately 7 times the maximum
recommended human dose.
In mice, no teratogenic effects were observed,
although reductions in mean fetal weight with consequent delays in skeletal
ossification were present when dams were given 17 or 34 times the human
daily dose.
There are no adequate and well-controlled studies in pregnant women.

KEMSTRO. should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk,
caution should be exercised when KEMSTRO. is administered to a nursing
woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not
been established.

Geriatric Use

Clinical studies of baclofen did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger
subjects.
In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk
of toxic reactions to this drug may be greater in patients with impaired
renal function.
Because elderly patients are more likely to have decreased renal function,
care should be taken in dose selection, and it may be useful to monitor
renal function.
Sedating drugs may cause confusion and over-sedation in the elderly; elderly
patients generally should be started on low doses of KEMSTRO. and observed
closely.

NDA 21-589  Page 9

ADVERSE REACTIONS

The most common adverse reaction during treatment with baclofen is transient
drowsiness (10-63%).
In one controlled study of 175 patients, transient drowsiness was observed
in 63% of those receiving baclofen tablets compared to 36% of those in the
placebo group.

Other common adverse reactions are dizziness (5-15%), weakness (5-15%) and
fatigue (2-4%).

Others reported:

Neuropsychiatric:

Confusion (1-11%),
headache (4-8%),
insomnia (2-7%);
and, rarely, euphoria, excitement, depression, hallucinations, paresthesia,
muscle pain, tinnitus, slurred speech, coordination disorder, tremor,
rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis,
mydriasis, diplopia, dysarthria, epileptic seizure.

Cardiovascular:

Hypotension (0-9%).
Rare instances of dyspnea, palpitation, chest pain, syncope.

Gastrointestinal:

Nausea (4-12%),
constipation (2-6%);
and, rarely, dry mouth, anorexia, taste disorder, abdominal pain, vomiting,
diarrhea, and positive test for occult blood in stool.

Genitourinary:

Urinary frequency (2-6%); and, rarely, enuresis, urinary retention, dysuria,
impotence, inability to ejaculate, nocturia, hematuria.

Other:

Instances of rash, pruritus, ankle edema, excessive perspiration, weight
gain, nasal congestion.
Some of the CNS and genitourinary symptoms may be related to the underlying
disease rather than to drug therapy.
The following laboratory tests have been found to be abnormal in a few
patients
receiving baclofen:
increased SGOT,
elevated alkaline phosphatase,
and elevation of blood sugar.
The adverse experience profile seen with KEMSTROT was similar to that seen
with baclofen tablets.

OVERDOSAGE

Signs and Symptoms

Vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma,
respiratory depression, and seizures.

Treatment

In the alert patient, empty the stomach promptly by induced emesis followed
by lavage.
In the obtunded patient, secure the airway with a cuffed endotracheal tube
before beginning lavage (do not induce emesis).
Maintain adequate respiratory exchange,
do not use respiratory stimulants.
It is unknown what effect hemodialysis or peritoneal dialysis has on the
serum concentration of baclofen.

DOSAGE AND ADMINISTRATION

The determination of optimal dosage requires individual titration.
Start therapy at a low dosage and increase gradually until optimum effect is
achieved (usually between 40-80 mg daily).

The following dosage titration schedule is suggested:
5 mg three times a day for 3 days
10 mg three times a day for 3 days
15 mg three times a day for 3 days
20 mg three times a day for 3 days

NDA 21-589  Page 10

Thereafter additional increases may be necessary but the total daily dose
should not exceed a maximum of 80 mg daily (20 mg four times a day).

The lowest dose compatible with an optimal response is recommended. If
benefits are not evident after a reasonable trial period, patients should be
slowly withdrawn from the drug (see WARNINGS, brupt Drug Withdrawal).

Administration

Using dry hands, the patient should be instructed to place the tablet on the
tongue, where it will disintegrate and can then be swallowed with or without
water.

Patients with Renal Impairment

Because baclofen is primarily excreted unchanged by the kidneys,
it should be given with caution and it may be necessary to reduce the dosage
in patients with impaired renal function.

HOW SUPPLIED

KEMSTRO. (baclofen orally disintegrating tablets) 10 mg are white, round,
orange-flavored, scored and engraved "10" on the unscored side and "SP"
above and "351" below the score on the other side.

They are supplied as follows:
Bottles of 100 NDC 0091-3351-01

KEMSTRO. (baclofen orally disintegrating tablets) 20 mg are white, round,
orange-flavored, scored and engraved "20" on the unscored side and "SP"
above and "352" below the score on the other side.

They are supplied as follows:
Bottles of 100 NDC 0091-3352-01

Dispense in a tight container as defined in the USP/NF with a
child-resistant closure.

Store at controlled room temperature 20° - 25°C (68° - 77°F);
excursions permitted between 15° - 30°C (59° - 86°F).  Protect from
moisture.

Manufactured for:
SCHWARZ PHARMA Milwaukee, WI 53201, USA
By: CIMA. Eden Prairie, MN 55344, USA
KEMSTRO. uses CIMA U.S. Patent Nos. 6,024,981 and 6,221,392.
************************************************************

Rich Murray, MA  Room For All  rmforall at comcast.net  505-501-2298
1943 Otowi Road    Santa Fe, New Mexico 87505   USA
http://groups.yahoo.com/group/aspartameNM/messages
group with 185 members, 1,181 posts in a public, searchable archive

http://groups.yahoo.com/group/aspartameNM/message/1165
short review: research on aspartame (methanol, formaldehyde, formic acid)
toxicity: Murray 2005.07.06 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

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/846
aspartame in Merck Maxalt-MLT worsens migraine,
AstraZeneca Zomig, Eli Lilly Zyprexa,
J&J Merck Pepcid AC (Famotidine 10mg) Chewable Tab,
Pfizer Cool Mint Listerine Pocketpaks: Murray 2002.07.16 rmforall

Migraine MLT-Down: an unusual presentation of migraine
in patients with aspartame-triggered headaches.
Newman LC, Lipton RB  Headache 2001 Oct; 41(9): 899-901.
[ Merck 10-mg Maxalt-MLT, for migraine, has 3.75 mg aspartame,
while 12 oz diet soda has 200 mg. ]
Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY
Department of Neurology   newmanache at aol.com
Albert Einstein College of Medicine, Bronx, NY
Innovative Medical Research   RLipton at IMRInc.com

http://groups.yahoo.com/group/aspartameNM/message/855
Blumenthall & Vance: aspartame chewing gum headaches Nov 1997:
Murray 2002.07.28 rmforall

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

http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17 rmforall
Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
for two to 17 years are described.
All had undergone multiple treatment
modalities with limited success. All had complete, or nearly complete,
resolution of their symptoms within months after eliminating monosodium
glutamate (MSG) or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG is ingested.

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



Aspartame (NutraSweet, Equal, Canderel, E951), after eight years of
controversy, was suddenly and capriciously approved by a new FDA
commissioner,  Arthur Hull Hayes, Jr,  just appointed by President Reagan, a
pharmacologist who had been in office less than three months and had little
background in food additives, in July 1981, overturning the vote of his own
Scientific Board of Inquiry.

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.

A team in a Searle Co. lab, led by J.A. Oppermann, proved that 30% of the
methanol in aspartame fed to rats remained, indubitably as toxic products of
formaldehyde and formic acid in all tissues (1973, 1976).

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 rmforall

This was confirmed by an expert team at the University of Barcelona (Trocho,
Alemany et al, 1998):
"...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...These are indeed extremely high levels for
adducts of formaldehyde, a substance responsible for chronic deleterious
effects (33), that has also been considered carcinogenic (33,47)."

http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
carcinogenicity results Dec 2002: Soffritti: Murray 2003.08.03 rmforall

p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
tract to become free methyl alcohol, which is metabolized in the liver to
formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level methanol
exposure. CIIT Act. 14: 1-7.
Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.   M. Soffritti et al.  Cancer
Research Center, European Ramazzini Foundation for Oncology and
Environmental Sciences, Bologna, Italy. crcfr at tin.it

http://groups.yahoo.com/group/aspartameNM/message/1077
eight depressed people react strongly to aspartame, Prof. Ralph G. Walton,
MD, 1993 double-blind study, full text: Murray 2004.04.26 rmforall
Despite the very small number of subjects, the results were dramatic and
statistically significant.  The eight depressed patients reported with
aspartame, compared to placebo, much higher levels of nervousness, trouble
remembering, nausea, depression, temper, and malaise.

Many scientific studies and case histories report:  * headaches  * many body
and joint pains (or burning, tingling, tremors, twitching, spasms, cramps,
stiffness, numbness, difficulty swallowing)  *  fever, fatigue, swollen
glands  * "mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech, sexual
problems,  poor vision, hearing (deafness, tinnitus), or taste  * red face,
itching, rashes, allergic dermatitis, hair loss, burning eyes or throat, dry
eyes or mouth, mouth sores, burning tongue  * obesity, bloating, edema,
anorexia, poor appetite or excessive hunger or thirst    * breathing
problems, shortness of breath * nausea, diarrhea or constipation  * coldness
* sweating  * racing heart, low or high blood pressure, erratic blood sugar
levels  * hypothryroidism or hyperthyroidism  * seizures  * birth defects
*  brain cancers  * addiction  * aggrivates diabetes, autism, allergies,
lupus, ADHD, fibromyalgia, chronic fatigue syndrome, multiple chemical
sensitivity, multiple sclerosis, pseudotumor cerebri and interstitial
cystitis (bladder pain).

http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
Turner: Murray 2002.12.23 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission Scientific Committee
on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

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

http://groups.yahoo.com/group/aspartameNM/message/1155
continuing aspartame debate in British Medical Journal, John Biffra, Bob
Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1065
politicians and celebrities hooked on diet sodas (aspartame): Murray
2004.03.24 rmforall

http://google.com  gives 585,000 websites for "aspartame" , with the top 7
of 10 listings being anti-aspartame, while
http://www.ncbi.nlm.nih.gov/PubMed   lists 786 aspartame items.
************************************************************

Additional material:

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

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity:  Thrasher & Kilburn: Shaham: EPA: Gold:
Wilson: CIIN: Murray 2002.12.12 rmforall

Thrasher (2001): "The major difference is that the Japanese demonstrated
the incorporation of FA and its metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.  toxicology at drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html   full text

http://www.drthrasher.org/formaldehyde_1990.html  full text   Jack Dwayne
Thrasher, Alan Broughton, Roberta Madison. Immune activation and
autoantibodies in humans with long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.  "Immune activation,
autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term
formaldehyde inhalation."  PMID: 2400243


http://groups.yahoo.com/group/aspartameNM/message/864
Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats: Murray 2002.09.08 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ].  Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."

In the same report, Schiffman concludes on page S49, not citing any
research after 1997, "Thus, the weight of the scientific evidence
indicates that aspartame does not cause headache."
Dr. Susan S. Schiffman, Dept. of Psychiatry, Duke University
sss at acpub.duke.edu    919-684-3303, 660-5657

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 2002.12.09 rmforall

Finally, an intripid and much published team in Japan has found DNA damage
in 8 tissues from single non-lethal doses of aspartame (near-significant
high levels of DNA damage in 5 tissues) and many other additives in groups
of just 4 mice:

Mutat Res 2002 Aug 26; 519(1-2): 103-19
The comet assay with 8 mouse organs: results with 39 currently used food
additives.
Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K,
Taniguchi K, Tsuda S.
Laboratory of Genotoxicity, Faculty of Chemical and Biological
Engineering, Hachinohe National College of Technology,
Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
yfsasaki-c at hachinohe-ct.ac.jp  s.tsuda at iwate-u.ac.jp

We determined the genotoxicity of 39 chemicals currently in use as food
additives.
They fell into six categories-dyes, color fixatives and
preservatives, preservatives, antioxidants, fungicides, and sweeteners.

We tested groups of four male ddY mice once orally with each additive at
up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet
assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung,
brain, and bone marrow 3 and 24 h after treatment.

Of all the additives, dyes were the most genotoxic.
Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and
Rose Bengal induced dose-related DNA damage
in the glandular stomach, colon and/or urinary bladder.
All seven dyes induced DNA damage in the gastrointestinal organs at a low
dose (10 or 100mg/kg).

Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced
DNA damage in the colon at close to the acceptable daily intakes (ADIs).

Two antioxidants (butylated hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
o-phenylphenol, and thiabendazole), and four sweeteners (sodium
cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA
damage in gastrointestinal organs.

Based on these results, we believe that more extensive assessment of
food additives in current use is warranted.  PMID: 12160896

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 2002.12.31 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S  Aug 2002: Murray 2003.01.01 rmforall
[ Also borderline evidence, in this pilot study of 39 food additives,
using test groups of 4 mice, for DNA damage from for stomach, colon,
liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
a very high dose.]

http://groups.yahoo.com/group/aspartameNM/message/961
genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
Murray 2003.01.27 rmforall   [A detailed look at the data]     ]

http://groups.yahoo.com/group/aspartameNM/message/857
www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31 rmforall

http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold:  flaws in double-blind studies re
aspartame and MSG toxicity: Murray 2002.08.01 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 at aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

http://groups.yahoo.com/group/aspartameNM/message/622
Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity: Murray 2001.06.04 rmforall   four double-blind studies

Headache 1988 Feb; 28(1): 10-4
The effect of aspartame on migraine headache.
Koehler SM, Glaros A     PMID: 3277925, UI: 88138777
Shirley  M. Koehler, PhD   904-858-7651   skoehler at brookshealth.org
http://www.med.umich.edu/abcn/alpha/alpha-K.html#Koehler
Alan Glaros  glarosa at umkc.edu  816-235-2074

They conducted a double-blind study of patients, ages 18-55, who had
a medical diagnosis of classical migraines (normally having 1-3
migraines in 4-weeks), who were not on medications (other than
analgesics), and who suspected that aspartame had a negative effect on
their migraine headaches. The subjects were given 1200 mg daily,
aspartame or placebo, for four weeks, about 17 mg/kg.  The placebo
group had no increase in headaches.  Approximately half of the subjects
(5 of 11) who took aspartame had a large, statistically significant
(p = 0.02), increase in migraine headache frequency, but not in
intensity or duration, compared to baseline or placebo.  Only 11 of
25 subjects completed the program: 8 dropped out, 4 began new
medications, 2 had incomplete records.  They were at home.
Since 1/3 of the subjects dropped out, they may have been choosing
to avoid headaches-- were they unpaid?  To achieve statistical
signifance with only 11 subjects hints that the incidence rate from
aspartame is very high, about 1/2,  for migraine cases who believe
that they are hurt by aspartame.

http://groups.yahoo.com/group/aspartameNM/message/1077
eight depressed people react strongly to aspartame, Prof. Ralph G. Walton,
MD, 1993 double-blind study, full text: Murray 2004.04.26 rmforall

Walton, RG, "Adverse reactions to aspartame: double-blind challenge in
patients from a vulnerable population," 1993,  with Robert Hudak and
Ruth J. Green-Waite,  Biological Psychiatry, 34 (1), 13-17.
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 at aol.com
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm

Eight depressed patients, ages 24-60, and five non-depressed controls,
ages 24-56, employed at the hospital, were given for 7 days either
aspartame or a placebo, and then after a 3 day break, given the
opposite.  Each got 2100 mg  aspartame daily, 30 mg/kg bodyweight,
equal to 10-12 cans of diet soda daily, about a gallon.  Despite the
very small number of subjects, the results were dramatic and
statistically significant.  The eight depressed patients reported with
aspartame, compared to placebo, much higher levels of nervousness,
trouble remembering, nausea, depression, temper, and malaise. (For each
symptom, p<0.01)  The five normals did not report strong enough
differences between aspartame and placebo to be significant.
Initially, the study was to be on a group of 40, but was halted by the
Institutional Review Board because of severe reactions among 3 of the
depressed patients.

Again, statistical significance with only 8 depressed patients:
"In this study, patients most often began to report significant
symptoms after day 2 or 3."  The incidence rate is very high,
indeed, about 1/3.  The most common symptoms are entirely typical
of thousands of case histories.

Stephen K. Van Den Eeden, T.D. Koepsell, W.T. Longstreth, Jr,
G. van Belle, J.R. Daling, B. McKnight, "Aspartame ingestion and
headaches: a randomized crossover trial," 1994, Neurology, 44, 1787-93
Steven K. Van Den Eeden,PhD  550-450-2202  skv at dor.kaiser.org
Division of Research, Kaiser Permanente Medical Care Program
3505 Broadway, Oakland, CA 94611-5714
http://www.dor.kaiser.org/dorhtml/investigators/Stephen_Van_Den_Eeden.html

In their introduction, they comment:

"In addition, the FDA had received over 5,000 complaints as of July,
1991 in a passive surveillance system to monitor adverse side effects.
(17)  Neurologic problems constitute the primary complaints in these
and several other case series, with headaches accounting for
18 to 45 %,depending on the case series reported. (17-19)"

Subjects, ages 18-57, were recruited who believed they got headaches
from aspartame, but were otherwise mentally and physically healthy.
They were paid $ 15 total, and were at home. Of the 44 subjects, 32
contributed data to the 38-day trials: a week of inert placebo, a week
of either aspartame or placebo, followed by a week of the opposite, and
then this two-week cycle repeated.  The daily dose was about 30 mg/kg.
"The proportion of days subjects reported having a headache was
higher during aspartame treatment compared with placebo treatment
(aspartame = 0.33, placebo = 0.24; p = 0.04) (table 5)".
Of the 12 subjects not included in the data, 7 reported adverse
symptoms before withdrawing.

Again, statistical significance with a moderate number of healthy
subjects, willing to be recruited by a newspaper ad, who believed
aspartame hurt them.  The number of headaches for each subject
for each treatment week are given: it appears that 4 subjects
had the strongest increase in headaches from the run-in week
or placebo week to their first week on aspartame, jumping from 0 to 5,
1 to 6, 1 to 4, 0 to 5 headaches per week.  So, about 4 of the 44
healthy people recruited for the study, who believed aspartame hurt
them, had a stong increase in headaches from the first week of daily
asparame exposure, while 7 reported adverse symptoms before leaving,
a total of 11 out of 44, an incidence ratio of 1/4.

This is sky high, if we consider that, if the incidence ratio for the
about two hundred million users in the USA is 1 of 100, that is 2
million cases.  It is plausible that the incidence ratio lies between 1
and 10 out of 100 for continuous daily exposure.  These three flames
should have set off alarm bells, with extensive follow-up studies and
much more careful study of thousands of case histories.  But these
little flares were adroitly smothered by thick blankets of industry
funded fluff:

http://groups.yahoo.com/group/aspartameNM/message/623
Simmons: Gold: Schiffman: Spiers:
aspartame toxicity: Murray 2001.06.04 rmforall    two double-blind studies
*************************************************************

 5. Robert Hickey  Aug 24 2001, 11:30 am
Newsgroups: alt.support.mult-sclerosis
From: Robert Hickey rob... at bellsouth.net
Date: Fri, 24 Aug 2001 10:35:00 -0500
Subject: Re: Baclofen?

jp wrote:

> what are some other side effects of thsi drug? My neuro said i should be
> on
> it..don't know why..i get a little cramping and tightness but nothing
> major.

My only experiences with Baclofen made we unacceptably weak. I took it
*many* years ago when I was just recently diagnosed (what was the doc
thinking? I was about 98% "normal" and had no walking problems) and I
got around fine. After taking Baclofen for a few days (and at a rather
small dose) I found myself walking worse than before I took it. I also
couldn't stand for very long and felt a bit groggy. I don't like or use
Baclofen. It really disagrees with me.


  6. John O'Brien  Aug 25 2001, 1:05 pm
Newsgroups: alt.support.mult-sclerosis
From: "John O'Brien" obri... at sky.net
Date: Sat, 25 Aug 2001 12:02:07 -0500
Local: Sat, Aug 25 2001 1:02 pm
Subject: Re: Baclofen?

I also echo Robert's experience with Baclofen.  I think it's
the worst thing that can happen to "us".  Shame on the neurologists for
using it.  It put me in a wheelchair for a couple years till I figured out
what was happening to me.
John
************************************************************* 




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