bionet.neuroscience.not.aspartame

[Mark Gold]

>From: grovesa at starbase1.caltech.edu (Andrew K. Groves)
>Newsgroups: bionet.neuroscience
>Subject: Re: bionet.neuroscience.not.aspartame
>Date: Thu, 24 Aug 1995 22:14:19 -0700
>
>Are there any studies that show demyelinating conditions (such as EAE) in
>lab animals treated with aspartame? I checked my literature database back
>to 1982, and could find none.

Andy,

I do not think it is being claimed that aspartame leads to demyelination
and MS symptoms.  I believe that there are a significant number of people
who experience symtpoms similar to that found in MS after medium or long-
term use of aspartame.

>Interestingly, I came across a fair number of papers on aspartame as I was
>scanning. Two papers I found showed that aspartame does not increase brain
>amino acid levels any more than sucrose does.

I believe that you are referring to the industry's wishful thinking on
this issue.  The phenylalanine from aspartame spikes the plasma 
phenylalanine to extremely high levels after ingesting an amount of 
aspartame that some people could obtain from one Super Big Gulp of diet soda.
The other Large Neutral Amino Acids (LNAAs) do not change much.  The plasma
phenylalanine/LNAA rises significantly.

When ingesting a large dose of sucrose, the LNAA levels in the plasma goes
down significantly.  The plasma phenylalanine goes down slightly less
than some of the other LNAAs and therefore the plasma phenylalanine/LNAA
level rises.  Not only is there an enormous difference in the plasma 
level of phenylalanine after aspartame ingestion as compared to sucrose, 
but the plasma phenylalanine/LNAA levels are different as well.

Some industry experiments avoid showing the significant different by
testing a small number of people for a single day and only presenting
average values for each time period (e.g., Pharmacology 1991;43:210-219),
but industry studies which are longer and have more subjects show the 
difference of plasma phenylalanine/LNAA levels even though average values 
were still presented (e.g., New England Journal of Medicine 
1994;300:301-307).

The biochemical changes that occur after carbohydrate ingestion is
quite different than what occurs after aspartame ingestion.
Industry researchers are grasping at any similarity between
the biochemicals changes that occur after aspartame ingestion and the 
changes that occur after ingestion of food.  Animal experiments have 
already shown that aspartame can lead to changes in brain 
neurotransmission.  Long-term aspartame ingestion may lead to similar 
changes.  The large number of case histories showing behavior and mood 
changes certainly should cause any researcher to be concerned.

>Further to your report of
>airline pilots, I also found two studies that examined the effect of
>aspartame and alcohol on pilot cognitive function. Aspartame had no
>effect.

This is more industry nonsense.  (I'm referring to the studies, not 
your post.)  

The first "study" was particularly abyssmal (Aviation, Space, and 
Environmental Medicine, 1991; 62:648-653).  The study was based on the 
hypothesis that an acute dose of aspartame, particularly the 
phenylalanine part, leads to cognitive performance deficits in pilots.
The 12 pilots tested had similar test results for both aspartame and placebo.

Major flaws
-----------
1.  The study was only a *single* dose study.  No one is suggesting
    that a single dose of aspartame in a lifetime is going to lead
    to major brain chemistry changes.  Unfortunately, many industry
    experiments are worthless single-day studies when the major
    concern is the ingestion of aspartame for months and years. 
    This is especially the case when considering the phenylalanine
    from aspartame since it is believed by some researchers to cause
    a gradual change in brain chemistry.

2.  The aspartame was given in capsules.  This was a particularly
    bad mistake.  Stegink (Metabolism, 36:507-512) showed that between
    ingesting aspartame in liquid form and in capsules.  The plasma 
    phenylalanine spikes to extremely high levels when ingesting 
    aspartame in liquids, but the spike is much lower when ingested in
    capsules.  If the concern is plasma phenylalanine levels, this
    mistake, by itself, renders this test questionable at best and 
    probably worthless.

3.  The tests given the pilots started 45 minutes after aspartame capsule 
    ingestion.  The Stegink experiment cited above shows that plasma 
    phenylalanine levels do not peak (using capsules) until 123 minutes 
    (average) and it takes as much as 240 minutes until it peaks in some 
    persons.  In addition, simply because the plasma phenylalanine level
    has peak, does not mean that enough time has passed for a) small 
    changes in brain chemistry to take place and b) slight changes in 
    neurotransmission (from the single dose of aspartame).

4.  Substances were given with aspartame that are likely to reduce any 
    possible biochemical changes and toxicity from the aspartate and the 
    methanol.

The second study (Aviation, Space, and Environmental Medicine, 1994; 
65:7-15) suffered from all of the same major flaws as listed above except 
that it last nine days instead of one day -- still a ridiculously short 
time when testing effects of gradual changes of brain chemistry in 
healthy subjects.

>Several studies showed no correlation between aspartame intake and
>seizures in children (or in susceptible adults) or increased activity in
>children diagnosed with attention deficit disorder. 

Here is an excerpt from a document I wrote which discusses the 
aspartame research:

---------
In 1992, an independent researcher, Camfield (Neurology;42:1000),
showed that children with a history of seizures who ingested a single
dose of aspartame had abnormal EEG spike waves. This was the first 
independent scientific test of aspartame and seizures and beyond the 
hundreds of case histories of seizures due to aspartame it raised 
additional red flags.

Monsanto/NutraSweet was quick to respond with a series of 
seriously flawed studies intended to "prove" that aspartame does not 
cause seizures.

1. Shaywitz (Ann Neurol 1994;35:98-103) studied 9 children (ages
   5-13) who had clinical evidence of seizure disorders for 7
   days. He claimed that no seizures were noted nor were there
   unusual EEG measurements.

   Selected Flaws
   -------------
   a. The aspartame was encapsuled which significantly
      lessens the plasma spikes of the amino acids. It's
      difficult to believe that the investigators were not
      aware of this fact. It also appears that the
      aspartame was taken near mealtime (breakfast) which
      would further cut down on the plasma amino acid spike
      and the methanol toxicity.
   b. The aspartame was fresh and did not include the
      numerous breakdown products found in real-world
      aspartame-containing products.
   c. The dosage was less than 1/2 the amount that Frey
      (J Toxicol & Environ Health 1976; 2:401-415)
      found that children of that age can ingest
      when aspartame products are freely available. It was
      less than 2/3 of the Acceptable Daily Intake (ADI)
      and less than 1/3 of what they should test (i.e.,
      double the ADI). They base their reasoning on the
      laughable food survey results discussed earlier in
      this document.
   d. Eight or all nine of the subjects were on
      antiepileptic medication at the time of the study.
      This probably helped to prevent seizures and abnormal
      EEG readings.
   e. A 14-day study is hardly long enough to see seizures
      develop. Some people are on real-world aspartame
      products for months or years before that get regular
      seizures.

2. Rowen (Epilepsia 36:270-275, 1995) used a single dose
   of aspartame to test 15 adults and 2 children who had a
   claimed that aspartame caused seizures. He claimed that
   no clinical seizures were experienced nor were there any
   statistically significant differences in EEG measurements.

   Selected Flaws
   --------------
   a. The aspartame was encapsuled which significantly
      lessens the plasma spikes of the amino acids. It's
      difficult to believe that the investigators were not
      aware of this fact. Two of the three aspartame doses
      were administered during meals which would further
      cut down on the plasma amino acid spike and the
      methanol toxicity.
   b. The aspartame was fresh and did not include the
      numerous breakdown products found in real-world
      aspartame-containing products.
   c. Sixteen of the 17 subjects were on antiepileptic
      drugs which may have helped to prevent seizures or
      abnormal EEGs (especially since they hadn't taken
      aspartame 7 days before the study started and didn't
      take real-world aspartame on the study).
   d. This was a one day experiment! Much too short to
      determine anything.
   e. The investigators imply that their difficulty finding
      their goal of 60 subjects suggests that seizures
      linked to aspartame are rare. This is a ridiculous
      assumption as there are hundreds of cases registered
      with the FDA (1993) and countless others reported to
      independent parties (e.g., Mary Stoddard, Richard Wurtman,
      etc.). There are likely many times more than this that go
      unreported or undiagnosed. Their inability to find subjects
      is probably related to 1) inadequate recruitment methods
      as described by Kulczycki (J Allergy & Clin Immun, Feb 1995,
      page 639-640); and 2) people being extremely unwilling to
      provoke seizures in the interest of "science."

It is unlikley that Camfield's small, idependent study
showing abnormal spike waves in children who ingest
aspartame and the hundreds (if not thousands) of *reported*
case histories of aspartame-caused seizures can hold up under the
barrage of flawed NutraSweet-funded studies on seizures as
shown above.

>The best claim that the studies that I scanned could make is that *certain
>groups* within a population may have some sensitivity to aspartame. For
>example, in one study of patients who attributed their headaches to
>aspartame, only a subset of these patients showed sensitivity to aspartame
>in a double blind study.

This was an *independent* study testing for one particular acute 
reaction.  This says nothing about the danger of chronic health 
problems caused or contributed to by long-term aspartame ingestion.  
You should note that the industry study showing no increase in 
headaches was another one or their one-day "studies."

>However, the concluding sentence in another paper
>read
>
>"In summary, we found that it is difficult to recruit study subjects with a
>    history of hypersensitivity reactions to aspartame and that subjects who
>    believed themselves allergic to aspartame did not have reproducible
>    reactions."

This industry-connected study by Garriga (J Allergy Clin Immunol 
1991; 87:821-7), suffered from a number of possible recruiting 
problems.  One is that the study was initiated in 1986, not long 
after aspartame began to be sold in carbonated beverages.  In 1987, 
there were 600 products with aspartame, now there are over 5000 
products with aspartame.  It would be much easier now to find such 
reactors as it was back then.

The researchers were looking for persons with immediate allergic 
reactions to aspartame and not individual who have food intollerance 
(or toxicity) reactions that are often delay from 2 to 48 hours.  
There is nothing wrong with limiting the group to this specific 
population.  Since delayed reactions to aspartame appear to be quite 
common, it would be innappropriate to imply that the difficulty in 
finding "hypersensitive" individual means that aspartame reactions are 
rare.

There was no information provided as to how large the ad in the 
Volunteer/Health section of the Washington Post was.  If it was a 
small ad, it might not have been seen by many peopel.  After a direct 
television appeal in 1986, Kulczycki (J Allergy Clin Immun, Feb 1995,
page 639-640) was contacted by 88 individuals from the St. Louis area.

Only three persons in this experiment were tested in a double-blind 
manner.  One person reacted repeatedly to a small dose of a real-
world aspartame-containing product (one diet soda).

>I am not suggesting for a moment that aspartame is perfectly safe in all
>humans at all doses, but the brief scan through the literature over the
>last 7 years would suggest that at best, only a small group of people
>demonstrate any sensitivity to aspartame in controlled conditions. And
>that, really, is the key word. The key is to distinguish between anecdotal
>attribution of a reaction to aspartame, and a controlled test of such a
>reaction.

I disagree.  I believe that the most important key is to distinguish 
between the industry studies which are almost always flawed to the point 
of being worthless and the independent studies which usually show 
adverse reactions caused by aspartame.  And whatever you do, watch 
out for the industry "reviews" which are just one convincing-sounding 
mis-statement after another.

Best regards,

                        - Mark
                     mgold at tiac.net