Margaret Hamburg, M.D.

Commissioner, F.D.A.

5600 Fishers Lane

Rockville, Maryland 20857

Dear Dr. Hamburg:

I would like to urgently request that the F.D.A. re-visit the approval of aspartame.

This is an issue which I have been involved with for the past 25 years - initially because of the adverse effects experienced by one of my patients. I had been treating a then 54 year old woman with imipramine because of recurrent major depressive episodes. Previous psychoanalytically based therapy had proven ineffective, but she responded dramatically to 150mg of imipramine per day. She had done well for 11 years on this medication, but was then suddenly hospitalized with a grand mal seizure and subsequent manic episode.

One could postulate that she was bipolar and the imipramine had triggered the mania, but she had been on the same medication for a total of 11 years, and for the previous 5 years at the same 150mg per day dose. Neither the seizure nor her mania were consistent with what we know about the clinical course of bipolar disorder or epilepsy. Careful history revealed that the only change in her life was a recent decision to switch from the sugar which she had always used to sweeten her iced tea to a newly marketed product with aspartame. I reasoned that the aspartame could have altered the catecholamine/indoleamine balance and thus account for her clinical difficulties.

After the publication of this case report many patients with unexplained seizures or puzzling psychiatric presentations were referred to me. I became increasingly convinced that aspartame could trigger seizure activity and mimic or exacerbate a variety of psychiatric disorders. I presented a paper based on those patients at a 1987 MIT sponsored conference on dietary phenylalanine and brain function.

Industry sponsored criticism was made that my conclusions regarding aspartame's toxicity could not be accepted as valid because my case reports were "merely anecdotal" and not based on double-blind research. Although I personally believe that case reports are undervalued in modern medical literature, I was so convinced of aspartame's toxicity, and the need to have it's hazards more widely appreciated in the medical community, that I did undertake a double-blind study.

That study was published in Biological Psychiatry in 1993 (a copy of the paper is enclosed). It demonstrated that individuals with mood disorders are particularly sensitive to aspartame and experienced an accentuation of depression and multiple physical symptoms. I had expected that the difficulties experienced by patients receiving aspartame would be fairly subtle (the dose of 30mg/kg/day was well below the 50mg/kg/day that the F.D.A. considered "safe"). I was not prepared for the severity of the reactions and for obvious ethical reasons cannot perform any further human studies with aspartame.

Two years after the publication of that study I was contacted by a producer for "60 Minutes" and asked if I would be willing to be interviewed by Mike Wallace for a segment on aspartame. During that interview Mike challenged me on my assertion that there were major problems with this sweetener in view of the fact that the bulk of the medical literature attested to it's safety.

I responded that one had to look carefully at study funding - that virtually all of the studies claiming safety were funded by the industry, whereas independently funded studies invariably identified one or more problems. When he challenged me to prove this I prepared a chart correlating study outcome and funding source. This chart was aired on the 60 Minutes segment, and is enclosed, with further discussion of this entire issue.

Although for obvious ethical reasons I cannot perform further human studies with aspartame, as a busy clinician I continue to see the multiple neurological and psychiatric consequences of aspartame use. It can lower seizure threshold and lead to an incorrect diagnosis of epilepsy, with subsequent inappropriate prescription of anticonvulsants. It can mimic or exacerbate symptoms of MS, it can paradoxically produce carbohydrate craving and weight gain. The world-wide epidemic of obesity and type 2 diabetes obviously has multiple causes, but I am convinced aspartame is a major factor.

On a daily basis I see how it can both produce and aggravate depression, in certain patients it can trigger manic episodes, it can produce or aggravate panic attacks. Some of my patients have experienced a complete cessation of panic attacks and needed no further treatment after they totally eliminated aspartame from their diet. Certain schizophrenic patients have experienced fewer auditory hallucinations and needed less antipsychotic medication after the elimination of aspartame consumption.

Thank you Dr. Hamburg for your attention to this urgent public health problem.

Yours sincerely,

Ralph G. Walton, M.D.

Former Professor and Chairman,

Department of Psychiatry,

Northeastern Ohio Universities College of Medicine