Onibasu.com

Re: Andy: another technical question

  • Subject: Re: Andy: another technical question
  • Date: Sun, 26 Sep 2004 13:06:44 -0700
  • Yahoo! Message Number: 120554
  • Onibasu Link: http://onibasu.com/archives/am/120554.html

Andy,

Thanks a lot for your answer!

can I ask another stupid question? This time about chemistry. I went to
http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

to see what alpha lypoic acid looks like and found not one, but several:
1) DL alpha lipoic acid = Thioctic acid dl-form
RN: 1077-28-7
has no SH group, but a disulphide bond

2) (+) alpha lipoic acid -
Thioctic acid d-form
RN: 1200-22-2
also has no SH group, but a disulphide bond

3) (-) alpha lipoic acid
(-)-alpha-Lipoic acid
RN: 127254-35-7
(no structure)

4) lipoic acid
Thioctic acid [JAN]
RN: 62-46-4
also has no SH group, but a disulphide bond

So the question is:
which one of them is the ALA we use, and do 2 connected S-s (disulphide
bond) under some conditions break the bond, acquire an H each and turn into
two SH groups?

Sorry to waste your time on such questions, probably it is organic chemistry
101, but I don't know where to look it up. Thanks a lot!

Elena
----- Original Message -----
From: "andrewhallcutler" <AndyCutler>
To: <Autism-Mercury@yahoogroups.com>
Sent: Saturday, September 25, 2004 11:28 PM
Subject: [Autism-Mercury] Andy: technical question Re: Don't poison kids
with TTFD, use Benfotiamine instead

Andy,

As far as I can understand the matter I agree with your discussion, but
there is one thing I do not understand: why your null hypothesis is
that if
nothing influences there will be 50% cases of larger excretion and other
50%
of lesser? If the amount of excretion of the metal X normally fluctuates
don't we need to measure if many times before the experiment starts and
figure out how it works normally to be able to use that as null
hypothesis?

Metal excretion does vary from day to day. Also there are measurement
errors inherent in sample collection.

The intellectually simpler case is that you do a very large number of
24 hour urine collections and get a very accurate average excretion.
Then if you meausre after giving a placebo, it will be half over the
average, half under.

While it takes some thought, if you do NOT have a good average, but
simply take 2 measurements before and after it is also true that it is
50/50 whether it is higher or lower after than before.

Maybe under normal conditions (withouth the application of the
influencing
factor in question) the excretion goes up in one case out of ten and
down in
one case out of ten, or something. Can we formulate a null hypothesis
without such measurements and calculations?

Yes. It does require some assumptions about what is going on, but they
aren't really ASSUMPTIONS in the sense that similar measurements have
been done a very large number of times on human beings, e. g. serial 24
hour urine analyses.

Also because we are only considering greater or less than rather than a
ratio or any such, if you do assume urine collection errors are small
then the form of the probability distribution of daily urine metal
levels is completely irrelevant. This again makes it very much simpler
to think through.

So for each individual you take the measurement X, urine element thus
and such and the measurement X', urine element thus and such again but
with some agent you are testing for being active.

You ask the binary question, is X' greater than X? Yes or no.

If the agent is inactive, the probability of X' > X is P = 50%.

If the agent is active, the probability of X' > X is P > 50%.

All you need to do is determine the confidence interval for P. If this
interval includes 50% you have not excluded the null hypothesis to the
relevant probability (typically the 95% confidence interval is used).
If the confidence interval does not include much in the way of P > 50%
it seems quite unlikely that the stuff is a chelator. If the
confidence interval lies entirely above P = 50% then the material
increases excretion. If the confidence interval actually is entirely
below P = 50% then the stuff reduces excretion.

One may make reference to standard statistical tables to see that for
10 trials having 0 or 1 show up with X' > X means P is below 50% at the
95% confidence limit, and for 9 or 10 with X' > X P is greater than
50%, while for 2-8 trials where X' > X the null hypothesis is not
excluded. For 99% confidence the numbers where the null hypothesis may
be excluded are either all X' > X or all X' < X.

Another view is to say that since statistics suck for 10 person trials
(that is you have a hard time excluding the null hypothesis), and since
chelators tend to not be all that specific, you could consider it 100
trials, 10 elements for 10 people. In this situation, the null
hypothesis is not excluded (at the 95% confidence limit) if between 39
and 60% of the X' are > X.

The Lonsdale abstract Teresa posted that started this discussion
suggests at best the null hypothesis wasn't excluded versus TTFD
enhancing excretion, and possibly that in fact the null hypothesis WAS
excluded versus TTFD lessening excretion!

Andy . . . .. . .

Not that it is relevant to the topic of TTFD not being a chelator, but I
am
just interested.

Elena


----- Original Message -----
From: "andrewhallcutler" <AndyCutler>
To: <Autism-Mercury@yahoogroups.com>
Sent: Wednesday, July 21, 2004 1:23 PM
Subject: [Autism-Mercury] Re: Don't poison kids with TTFD, use
Benfotiamine
instead


Diane wrote:

What is TTFD?


1: Neuro Endocrinol Lett. 2002 Aug;23(4):303-8.

Treatment of autism spectrum children with thiamine
tetrahydrofurfuryl
disulfide: a pilot study.

Lonsdale D, Shamberger RJ, Audhya T.

Preventive Medicine Group, 24700 Center Ridge Road, Westlake, OH
44145,
USA.
dlonsdale

OBJECTIVES: In a Pilot Study, the clinical and biochemical effects
of
thiamine
tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children
were
investigated. SUBJECTS AND METHODS: Ten children were studied.

Big study group!

Diagnosis was
confirmed through the use of form E2, a computer assessed symptom
score.
For
practical reasons, TTFD was administered twice daily for two months
in
the form
of rectal suppositories,

Currently it is used transdermally.

each containing 50 mg of TTFD.

Currently dramatically more is used, and in fact the use of wildly
excessive amounts of it is part of the problem. However I do have
serious adverse reaction reports from using similar amounts.

Symptomatic responses
were determined through the use of the computer assessed Autism
Treatment
Evaluation Checklist (ATEC) forms. The erythrocyte transketolase
(TKA)
and
thiamine pyrophosphate effect (TPPE), were measured at outset and on
completion
of the study to document intracellular thiamine deficiency. Urines
from
patients
were examined at outset, after 30 days and after 60 days of
treatment
and the
concentrations of SH-reactive metals, total protein, sulfate,
sulfite,
thiosulfate and thiocyanate were determined. The concentrations of
metals in
hair were also determined. RESULTS: At the beginning of the study
thiamine
deficiency was observed in 3 out of the 10 patients. Out of 10
patients,
6 had
initial urine samples containing arsenic in greater concentration
than
healthy
controls.

This is not statistically significant. It is like saying I flipped a
coin 10 times and got heads 6 times. I'm surprised the reviewers
didn't object to this.

Traces of mercury were seen in urines from all of these autistic
children.

And if they checked probably all of the controls too. With modern
instruments you find it in most everryone.

Following administration of TTFD an increase in cadmium was seen in 2
children and in lead in one child.

Not statistically significant, in fact probably this IS statistically
significant with TTFD reducing excretion and causing retention.

Day to day variations in the output of the toxics occur, so if you do
10 before and afters, on average you'll see 5 higher after and 5 lower
after.

In fact, at the 95% confidence level this shows that TTFD decreases
lead excretion (I assume that since it does not increase it, it did
decrease).

At the 95% confidence level it is impossible to tell if TTFD has any
effect on arsenic excretion or not. However there is 89% confidence
that TTFD also reduced arsenic excretion.

Nickel was increased in the urine of one
patient during treatment.

At the 95% confidence limit, this shows again that TTFD REDUCS nickel
excretion.

Sulfur metabolites in urine did not differ from those
measured in healthy children.

This shows that TTFD had no effect on sulfur metabolism.

CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide
appears to have a beneficial clinical effect on some autistic
children,
since 8
of the 10 children improved clinically.

I gather this means that 8 out of 10 ATEC scores improved. I
understand that 2 children dropped out of the study, consistent with
the 20% adverse reaction rate observed and reported by parents.

We obtained evidence of an association
of this increasingly occurring disease with presence of urinary
SH-reactive
metals, arsenic in particular.

This is clearly an incorrect conclusion based on information presented
by the author claiming it in the abstract above.

The abstract suggests but does not say that there was some evidence of
thiamine deficiency being corrected. Assuming that this is so and was
statistically significant, the message is clear:

Thiamine helps address thiamine deficiency, so any form can be used.
Since TTFD is demonstrated to be dangerous one should try regular
thiamein several times a day first, and if that doesn't work, then use
benfotiamine.

Lonsdale et al. have conclusively demonstrated that TTFD does not have
any benefit beyond addressing thiamine deficiency, so use of TTFD as
opposed to any other particular form of thiamine is not required.

Andy . . . . . . . . . . .

PS Anyone with a modest technical background (and a significant number
of liberal arts types too) can easily learn to use the tables for
confidence limits, etc. found in most statistical manuals. It isn't
something magic that requires a supercomputer, nor is it something so
newfangled that few people can understand it. It was old hat when the
table I am using was published in 1960.





=======================================================
Statements posted on this list are for information only,
and should NOT be taken as medical advice. If you need
medical advice, you should seek it from those who are
authorized to give medical advice: doctors.

Post message: Autism-Mercury@yahoogroups.com
Subscribe: Autism-Mercury-subscribe@yahoogroups.com
Unsubscribe: Autism-Mercury-unsubscribe@yahoogroups.com
Shortcut URL: http://onibasu.com/archives/am/date_index_1.html
Answers to common questions:

http://onibasu.com/archives/am/date_index_1.html/files/Mercury-Autism%20FAQ



Onibasu Link: http://onibasu.com/archives/am/120554.html

Recent Blogs »

Tips!

We now support Yahoo! message number portability. Tell me more »

Do you want to see your Yahoo! group archived in Onibasu? Click here for more details.