From: Rich Murray [rmforall@att.net]
Sent: Monday, August 05, 2002 2:39 AM
To: fdadockets@oc.fda.gov
Subject: RTM: FDA: (Section C) Drake: aspartame & panic attacks 9.13.86
10.30.99 rmforall


RTM: FDA: (Section C) Drake:
aspartame & panic attacks 9.13.86 10.30.99 rmforall

http://groups.yahoo.com/group/aspartameNM/message/32

http://www.dorway.com/drake.html

Letters to the Editor  The Lancet  September 13, 1986

PANIC ATTACKS AND EXCESSIVE ASPARTAME INGESTION

           Sir,--The artificial sweetener aspartame has been alleged
to cause seizures(1) and neuropsychiatric symptoms(2) in large doses.
I have observed the precipitation by aspartame abuse of panic attacks
in a previously symptomless patient with mitral valve prolapse, the
association of which with anxiety disorder and panic attacks is
controversial.(3) The effects of aspartame on brain amines(4, 5)
support the role of catecholamines in panic attacks and suggest that
persons with mitral valve prolapse may have an exaggerated sensitivity
to aspartame excess.
           A 33-year-old cook had been found incidentally to have a
mid-systolic click and murmur.  She had smoked two packs of cigarettes
per day for several years, and daily consumed one or two cups of coffee
and six to twelve cans of diet cola sweetened with aspartame. When she
was transferred to a different and very hot kitchen her consumption of
diet cola went up to about twenty cans per day. Within a week she began
to feel persistently "shaky" at home and at work, and then had paroxysms

of dizziness, diaphoresis, chest tightness, dyspnoea, claustrophobia,
and the intense feeling that "something was about to happen" to her or
that she "would die any minute." Physical examination was normal except
for click and murmur, and neurological examination was intact.
Laboratory studies, including thyroid function tests, electrocardiogram,

and electroencephalogram, were normal. A two-dimensional echocardiogram
confirmed mitral valve prolapse.
           She decreased her smoking by half and stopped drinking
coffee, but the attacks continued daily until she reduced her intake of
diet cola to two or three cans per day, at which time they subsided. She

could not maintain this moderate consumption, however, and after one
week rapidly returned to her former level of intake, whereupon the daily

attacks returned.
           She changed to several brands of diet soft drink which
contained no caffeine but the symptoms persisted. With the aid of a
behaviour modification programme she was able to reduce her daily
consumption of such beverages to two or three cans, and has
subsequently had relief from her symptoms.
           This patient had asymptomatic mitral valve prolapse but
experienced typical panic attacks when consuming excessive amounts of
aspartame-sweetened soft drinks, the attacks subsiding when she reduced
her aspartame consumption. She also smoked and drank coffee, so nicotine

and caffeine may have played a part, but moderation of these was not
effective, while attacks subsided with reduction of cola intake. Her
panic attacks may well have been predisposed by mitral valve prolapse
and precipitated by aspartame excess, which suggests that people with
mitral valve prolapse may have an exaggerated susceptibility to
aspartame and possibly to other stimulants as well. Wurtman reported
three patients, consuming more than a gallon of aspartame-sweetened tea
daily, who experienced generalized seizures, although at least one
patient was significantly hyponatraemic and may have had seizures on
that basis. A seizure followed by mania was described in a patient with
bipolar affective disorder who consumed a gallon of aspartame-sweetened
tea per week; the role of the patient's underlying affective disorder,
as well as psychotropic medications, is not clear. Administration of
aspartame and carbohydrate increases brain tyramine content and
suppresses the postprandial increase of tryptophan; this might have a
catecholamine-augmenting and stimulant effect, as could the large
increase in phenylalanine shown in rat brain after an aspartame load.
It is unclear how this might cause seizures, but the precipitation of
cardiovascular and psychological features of anxiety is consistent
with evidence that catecholamines play a part in pathogenesis of panic
attacks and that adrenergic blockade is useful in their treatment.
Mitral valve prolapse and panic symptoms are both common and may
overlap, but patients with mitral valve prolapse may be predisposed
to panic symptoms under the influence of stimulants and adrenergic
agonists and so may be unusually susceptible to the effects of
excessive aspartame. There is no evidence that aspartame is harmful
in usual amounts, but perhaps patients with mitral valve prolapse
should be cautioned against immoderate use.
           Simultaneous consumption of large amounts of carbohydrates
and aspartame, a common  practice in snack eating today, should also
be avoided.

           Department of Neurology and Psychiatry,
           Ohio State University Medical Center,
           Columbus, Ohio 43210, USA

Miles E. Drake, MD

Director of EEG and Evoked Potential
Laboratory; Codirector of Comprehensive
Epilepsy Program; Associate Professor of
Neurology   Phone (614) 293-6195

Training            Duke University, 1977
Specialty Training  Duke University
Research Interests  management of intractable epilepsy,
                    neurobehavioral consequences of epilepsy,
                    neurophysiological aspects of hysteria and
                    other psychiatric disorders

Clinical Interests  EEG, epilepsy, clinical evoked potentials
OSU Appointment   1982
Department(s)     Neurology

(1) Wurtman R J  Aspartame: possible effect on seizure susceptibility.
Lancet, 1985; iii: 1060.

(2) Walton R G Seizure and mania after high intake of aspartame.
Psychosomatics, 1986; 27: 218-20.

(3) Boudoulas H, King B D, Wooley,C F  MVP: a marker for anxiety
or overlapping phenomenon? Psychopathology, 1984; 17(suppl 1): 98-106.

(4) Stegink L D, Filer L J, Baker G L  Effect of aspartame
loading upon plasma and erythrocyte amino acid levels in PKU
heterozygotes and normal adult subjects. J Nutr, 1979; 109: 708-17.

(5) Wurtman R J  Neurochemical changes following high-dose aspartame
with dietary carbohydrates. N Engl J Med, 1983: 309: 429-30.
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Rich Murray, MA    Room For All    rmforall@att.net
1943 Otowi Road, Santa Fe  NM  USA  87505   505-986-9103

http://groups.yahoo.com/group/aspartameNM/messages  for 862  posts
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http://groups.yahoo.com/group/aspartameNM/message/860
RTM: FDA: objections to neotame approval  (Section A) 8.4.2 rmforall
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