From: bhjelle@carina.unm.edu ()
Subject: Re: FDA/ Amino Acids/ Smart Drugs
Date: Tue, 15 Sep 92 19:55:54 GMT
Organization: University of New Mexico, Albuquerque
Keywords: amino acids   FDA   alternative approaches

In article <1992Sep15.054031.0231707@locus.com> yazz@locus.com (Bob Yazz) writes:
>dyer@spdcc.com (Steve Dyer) writes:
>
[Herman Rubin]
>| Since it seems that EMS was caused not by tryptophan, but by a contaminant,
>| and since that contaminant is now tested for, why is it still off the market?
>
>| Because, we don't know for sure it was caused by the contaminant, nor is the
>| contamination situation as cut and dried as it's sometimes described to be.
>| It may well be that high dose tryptophan taken as a single entity (i.e.,
>| not as part of your food) can cause EMS in susceptible individuals.
>
>There is no doubt that it's the contaminant, not the tryptophan, causing
>EMS.  I've followed the literature very closely since the beginning
>on this one.  I've also followed other sources, but I base my certainty
>on journal articles.

While there is a lot of reason to suspect that
contaminants are much more potent at causing EMS than tryptophan,
it is still far from conclusively demonstrated that peak E alone,
or even contaminants alone, cause EMS. The linkage between peak E
and EMS was based upon the nearly universal finding of peak E among
those lots of tryptophan prepared after Denko changed its manu-
facturing process (a change that was associated with the 1989
EMS epidemic). However, it is naive to assume that that
*association* proves causality. If so, why are there at least 9
cases of tryptophan-associated eosinophilic 
fasciitis that occurred before the 1989 manufacturing
change (Arthritis Rheum 1992;35:299)?

>NIH researchers can cause EMS in rats every time with the contaminant
>and they can't cause it at all with even ridiculous doses of tryptophan.
>There's no scientific mystery about it -- only a bureaucratic one.

Peak E does cause  a syndrome distantly related to EMS in Lewis
rats. But a better candidate, phenylamino-L-aniline, was recently
identified among the ~60 contaminants in L-tryptophan. This agent
is similar to that causing an outbreak of EMS in Spain in 1981
associated with cooking oil (Nature 1992;358:96).

>Even before this confirming, reproducible  evidence, the epidemiology made
>it pretty obvious that the problem was caused by a contaminant.  And I'm
>aware of no other country where tryptophan is controlled as a prescription
>drug that has pulled the stuff from the market, either.

We still don't really know what the contaminant(s) was (were). We thus
don't know that they are gone. See above -old tryptophan lots
caused EMS before peak E or other contaminants were identified.

>Now, before it was known what was happening, people were DYING of EMS.
>I have no problem with the FDA pulling a product off the market when
>it's making people sick and killing them.
>
>But that's all over now.  Frankly, once contaminated tryptophan was
>discovered, the scientific mystery was not a difficult one to solve.
>
Well, you have more confidence in the data than FDA does. Sam Page
at FDA recently said "We're looking at an enormously complex
inflammatory disease process" that "is not due to a single cause
or the effect of a single contaminant". 

Could it be that FDA knows more about this than Bob Yazz?

Brian
From: sude@hpbbi4.BBN.HP.COM (#Susanne Denninger)
Date: Mon, 14 Sep 1992 08:21:50 GMT
Subject: Sleeping Problem
Organization: Hewlett-Packard GmbH