From: [email protected] (Steven B. Harris )
Subject: Re: melatonin - how is it made?
Date: 02 Aug 1995

In <[email protected]> [email protected] (Christina Mercier)
writes:


>Yet another question about melatonin.
>
>Does anyone know how it is made?  If it is a human hormone,
>how is it extracted? or is it manufactured?


It's manufactured.  It's fairly simple chemical, a derivitive of the
amino acid tryptophan.  That's how the body makes it, and I imagine
that's how it's made commercially also-- out of tryptophan.

                                      Steve Harris, M.D.

From: [email protected] (Steven B. Harris )
Subject: Re: melatonin - how is it made?
Date: 03 Aug 1995

In <[email protected]> [email protected] (Dr Ray)
writes:

>In <[email protected]> [email protected] (Steven B.
>Harris ) writes:
>
>>In <[email protected]> [email protected] (Christina Mercier)
>>writes:
>>
>>>Yet another question about melatonin.
>>>
>>>Does anyone know how it is made?  If it is a human hormone,
>>>how is it extracted? or is it manufactured?
>>
>>>It's manufactured.  It's fairly simple chemical, a derivitive of the
>>amino acid tryptophan.  That's how the body makes it, and I imagine
>>that's how it's made commercially also-- out of tryptophan.
>>
>>                                      Steve Harris, M.D.
>
>	I called and asked Genzyme, one of the two main melatonin
>manufacturers in this country, on how it is made. They said they make it
>completely synthetically, without the fermentation process that led to
>the tryptophan contamination a few years ago.
>	They were not willing to share with me on what the primary
>molecule was that they started with in order to get to melatonin.
>	Ray Sahelian, M.D., author, Melatonin: Nature's Sleeping Pill.



If they weren't willing to do that, then I expect they are lying SOBs,
and they do start with tryptophan, or at least a chemical which is
derived from tryptophan.  Tryptophan is simply too easy a route into
substituted indole ring chemicals to be ignored as a starting reagent--
history of contamination or not.


                                      Steve Harris, M.D.

From: [email protected] (Steven B. Harris )
Subject: Re: Is it Melatonin, Elavil or what?
Date: 07 Oct 1995
Newsgroups: misc.health.alternative

In <[email protected]> [email protected] (hardware)
writes:

>There was a report on this board that a an Elavil user suffered a
>"coma-like sleep so deep that I was scared I'd die and never wake up and
>the second and third nights were almost as bad.  I also had vivid,
>horrible nightmares."  The same individual switched to Melatonin and had
>the exact same problem.
>
>You wonder if the Melatonin manufacturer actually used Elavil instead of
>Melatonin perhaps because it was cheaper or more readily available. This
>is kind of scary because you're not sure what's in the pill.  I wonder if
>other users who suffered adverse reactions to Melatonin reported a much
>better reaction after they switched brands?
>
>Has anyone used Horizon brand Melatonin manufactured by Horizon Natural
>Products of Santa Cruz, CA?  What brands of Melatonin would our readers
>recommend?
>
>The bottom line: "Is it Melatonin, Elavil, or what?"




   I recommend "Sweet Dreams" melatonin made by Emerald phamaceuticals.
1-800-775-1112.  I don't have any financial interest in this company,
but I know the owners and have been through their lab.  They took extra
care to get very high purity melatonin for the product (99.8%), and
this is one of the best in the business (they also tested a bunch of
other products on the market by high performance liquid chromatography
to demonstrate this).  The Emerald tests also showed that the melatonin
available from the Life Extension Foundation (yes, John Hammel's
outfit) was also very pure, and the other winner on the market in this
regard.  You can get melatonin from the LEF by calling 1-800-FOR-LIFE.
Don't get your melatonin from any kind of pineal extract preparation.
Not only don't these contain appreciable melatonin, but you never know
what strange viruses (prions) you're going to get from cow brain
extracts.  If you know anything about mad cow disease and spongiform
encephalopathy, the idea of pineal extract melatonin should make you
shiver.

                                       Steve Harris, M.D.

Warning: melatonin should not be used by women attempting to concieve,
or by preganant or nursing women, or by children.  There are
theoretical problems also for people with autoimmune disorders and
people with depression.  And don't exceed 5 mg a night.  2.5 is plenty
for most people.  So far as I know, sublingual holds no advantages over
any other form.

From: [email protected](Steven B. Harris)
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 05 Aug 1998
Newsgroups: rec.drugs.smart,sci.med.nutrition

In <[email protected]> [email protected] (Alan Pollock)
writes:

>sextoy ([email protected]) wrote:
>>Well, the 3 mg dose they suggest on the label is just
>>paranoid nonsense.  And I respectfully suggest that anyone
>>who has their regularly sleep induced with 500 mcg is very
>>susceptible to placebo.  Get a copy of Tikhal, by Shulgin
>>and Shulgin.
>>
>>Nightly doses of up to 80 mg have been used by some with no
>>ill effects.
>>
>>If 20 mg works for you, don't worry about it.  The 3 mg was
>>just some nonsense dreamed up by an empty-headed FDA bean
>>counter.
>>
>>Borow wrote in message
>><[email protected]>...
>>>Hi,
>>>
>>>Some of you surely have experience with melatonin. I tried 3-6 mg to
>>>solve sleeping problems but I felt no effect. So I raised the dose up
>>>to 20mg. That made my sleep deeper and my dreams more intensive. Does
>>>anybody know if there is a critical dose of melatonin or can I take
>>>20mg or more without any problems ?
>>
>>
>>
>
>I suggest that perhaps you're not getting enough sleep when you flatly
>state that anyone getting an effect from 500mcg of melatonin is under a
>placebo effect. Nex



   Since 500 mcg is more than your body normally produces, and causes
higher blood levels than you usually get from a normal pineal, I second
your thought.

   As for Sulgin and Shulgin, PIHKAL I know ("Phenylethylamines I Have
Known And Loved").  But Tikhal?  Either a Hebrew sequel, or else this
guy really doesn't get enough sleep.

                                         Doc Harris

From: [email protected](Steven B. Harris)
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 06 Aug 1998
Newsgroups: rec.drugs.smart,sci.med.nutrition

In <[email protected]> David Bozzi
<[email protected]> writes:

>Steven B. Harris wrote:  (on melatonin)
>
>>    Since 500 mcg is more than your body normally produces,
>
>At what age?Melatonin levels begin declining at about age 20.
>From there you're at about 50% at age 25.
>Age 40: 20%
>Age 70: 10%



   Where are you getting these numbers?  I've not seen anything more
than 50% decline with aging in melatonin.  Citation, please?  And no
books-- I want primary literature.  There are a lot of nutty books out
there.

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition,sci.life-extension,sci.med
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 6 Aug 1998 16:22:06 GMT

In <[email protected]> David Bozzi
<[email protected]> writes:

>Steven B. Harris wrote:
>
>>    Where are you getting these numbers?  I've not seen anything more
>> than 50% decline with aging in melatonin.
>
>Will you kindly reveal the source of *your* numbers?In any event,  you
>at least acknowledge the fact of a sharp decline of  melatonin with
>aging.


Comment:

   Whether the decline is sharp or not sort of depends on what you look
at.  One recent study has found that older people secrete the same
total amount of metatonin, but at different times and in different
patterns.  Because of this, if you think melatonin is doing something
by mass-action (as in the free radical theory), then it's not a good
candidate for an "aging hormone."


Biol Signals 1997 Jul;6(4-6):301-306
Differential pattern of the circadian rhythm of serum melatonin in
young and elderly healthy subjects.

Ohashi Y, Okamoto N, Uchida K, Iyo M, Mori N, Morita Y

Department of Psychiatry and Neurology, Hamamatsu University School of
Medicine, Japan. [email protected]

The daily profile of serum level of melatonin was studied in 10 young
and 13 elderly subjects. All of the subjects were physically and
psychiatrically healthy and did not have any clinical symptoms related
to rhythm disturbance. Blood samples were taken every 3 h for 1 day and
serum melatonin levels were determined by RIA. All except for 1 of the
elderly subjects exhibited a clear circadian rhythm of serum melatonin
level with a nocturnal peak. In both subject groups, the melatonin
rhythm showed significant diurnal variation. There was no significant
difference in the total melatonin level per day between young and
elderly groups, suggesting that there was no influence of
aging on daily total melatonin secretion. However, there was a marked
difference in the features of the melatonin rhythm between the two
groups, i.e., a rapid decline of the melatonin level from the nocturnal
peak in the elderly group, suggesting that the off-set time of
melatonin secretion advances with aging. Our findings suggest that the
pattern of melatonin rhythm alters significantly without clear clinical
symptoms in the process of senescence.

PMID: 9500669, UI: 98160305



   The following study, which found a drop in early nightime melatonin
from 62 nmol/L to 29 nmol/L from age 15-20 to age 70-90 (this is the
paper I was thinking of).  However, this paper did not look at all
times in the night, and would have missed the peak time-shift found in
the above study.  Suffice to say that NONE of the latest data confirm
what Reiter says, or the data in the graph on page 20 of his book.
THAT graph is unreferenced, and occurs between references 13 and 14 for
the chapter, which clearly have nothing to do with it.  So I don't know
WHERE it comes from.  And I don't care WHO Reiter is, his stature
doesn't give him the right to put unreferenced data in his books
without getting skepticism.  I frankly think he's wrong.  Pierpaoli, in
HIS book on melatonin (pg 202) give the 50% number, and I at least can
guess where he gets HIS numbers (though he has no reference, either).
Sloppy.  Pierpaoli, BTW, is as big a name in the field as Reiter is, if
that means anything to you (it doesn't to me-- I want to see the DATA).



---------

J Clin Endocrinol Metab 1988 Mar;66(3):648-652
Alterations in nocturnal serum melatonin levels in humans with growth
and aging.

Waldhauser F, Weiszenbacher G, Tatzer E, Gisinger B, Waldhauser M,
Schemper M, Frisch H

Department of Pediatrics, University of Vienna, Austria.

The available data on potential alterations in serum melatonin (MLT)
levels during a human lifetime are fragmentary and inconsistent. We,
therefore, measured day- and nighttime serum MLT concentrations in 367
subjects (210 males and 157 females), aged 3 days to 90 yr. Blood
samples were collected between 0730 and 1000 h and between 2300 and
0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum
MLT concentration was low during the first 6 months of life, i.e. 27.3
+/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a
peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43
+/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL;
(0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the
following decades serum MLT declined moderately until old age (70-90 yr
of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic
MLT decline follows 2 exponential functions with different slopes (from
age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from
age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The
decrease in nocturnal serum MLT in children and adolescents (1-20 yr)
correlated with the increase in body weight (r = -0.54; P less than
0.001) and body surface area (r = -0.71; P less than 0.001). At a
later age (20-90 yr) there was no correlation among these variables.
Daytime serum MLT levels were low and no age-related alterations were
found. This study revealed major age-related alterations in nocturnal
serum MLT levels. The negative correlation between serum MLT and body
weight in childhood and adolescence is evidence that expansion of body
size is responsible for the huge MLT decrease during that period. The
moderate decline at older ages must derive from other factors.

PMID: 3350912, UI: 88169956





>> Citation, please?  And no
>> books-- I want primary literature.
>

Bozi:
>Dr. Russell Reiter,professor of neuroendocrinology at the University of
>Texas Health Sciences Center at San Antonio, one of the world's leading
>melatonin researchers. Authored over 700 scientific papers on melatonin
>and made some of the most significant discoveries in the field, including
>the 1993 discovery that melatonin is the body's most potent antioxidant.
>Colleagues have labeled him the "the godfather of melatonin research."
>(perhaps you've heard of him?)

Comment:

    This is the kind of garbage statement we get on usenet.  Yeah, I've
heard of him.  So what?


>Regardless, no one with a shred of credibility disputes the fact
>that there is a sharp and dramatic decline of peak nighttime levels of
>melatonin with usual aging.


    You don't know what you are talking about.  I would not call 50%
change in peak at one particular time "dramatic", especially when the
peak is shifted in time, and total amount of hormone secreted in not
changed.


>And egomaniacs who find 'being right' is more important than discovering
>truth.(even at the expense of public health)


    Which egomaniacs are those?  If you're really interested in public
health, you're interested in being "right" about what you say.  The one
follows the other, does it not?



>We all have the right to question anything we please, but considering all
>of that, one must seriously question the motive behind one questioning
>someones' rationale in taking a dose more or equivalent to 500mcg. of
>melatonin. (as you did)

Comment:
    Oh, I work for the pharmaceutical companies, who secretly pay me to
pooh-pooh the geniuses here who are advocating that people take
artificial control of their own endocrine systems by buying stuff in
healthfood stores recommended by credential-free enthusiasts on usenet.


>Cast all the doubts you please, but wouldn't you rather reserve your
>right to question something perhaps, unreasonable?


    And now I'm being unreasonable.  Okay, now you back up YOUR views.
And I want something better than an unreferenced graph in a popular
book.


>How much melatonin are *you* taking?


   0.5 to 1 mg, when I can't sleep.  Which isn't all the time.  But I
monitor my own blood levels, and I'm familiar with the primary
literature.  And I dare say I'm a little better qualified to be giving
advice on the subject than you are.  If you will get your friend doctor
Reiter on this newsgroup, I'll be glad to discuss the subject with him.
Perhaps he can explain where his strange data come from.

                                    Steve Harris, M.D.

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 7 Aug 1998 04:11:44 GMT

In <[email protected]> "sextoy" <[email protected]>
writes:

>If using it for insomnia, blood levels of melatonin are
>irrelevant because it has to cross the blood-brain barrier
>to have an effect.

    It must cross the blood brain barrier to have an effect, even if
made in the pituitary.  Before you call me a "mock doctor" get your
facts right.  I've done research on melatonin in an animal model for
years, and have seen it do things under certain drug delivery
circumstances you won't read about in ANY literature.  What have YOU
done with it?


                                   Steve Harris, M.D.

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition,sci.life-extension,sci.med
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 7 Aug 1998 04:25:47 GMT

In <[email protected]> David Bozzi
<[email protected]> writes:

     Hey, David, you wrote a bunch of stuff below, and not a word of it
is on-subject.  I would check your debating skills.  Or really,
thinking skills.




>Steven B. Harris wrote:
>
>>     And now I'm being unreasonable.  Okay, now you back up YOUR views.
>> And I want something better than an unreferenced graph in a popular
>> book.
>
>You want? Yes sir! Right away. But... I honestly I can't take you
>seriously.The data base is loaded with stuff that you wrote that says you
>are not worth responding to, such as:


    <Irrelevent stuff snipped.>


>(shrug) Oh well.
>
>> >How much melatonin are *you* taking?
>>
>>    0.5 to 1 mg, when I can't sleep.  Which isn't all the time.
>
>More than *twice* the amount you cautioned against taking. (shrug)


Comment:

  Take that much to get me to normal ranges.



>>  But I
>> monitor my own blood levels, and I'm familiar with the primary
>> literature.  And I dare say I'm a little better qualified to be giving
>> advice on the subject than you are.
>
>You're the man. All we've got is you and the science, and the opinions of
>real geniuses of the caliber, as say Dr. Michael Colgan.


    Not sure if you're trying to be funny or not.  Colgan is the guy
who convinced me to start taking vitamins, many years ago (let's see--
1982).  I've read his stuff since, and even met him.  He's an ordinary
guy, not a genius.  I've seen no evidence he knows more about the
subject than I do, by now.  Sorry.



> In the end I'm
>certain we will all make up our own minds.
>
>>  If you will get your friend doctor
>> Reiter on this newsgroup, I'll be glad to discuss the subject with him.
>> Perhaps he can explain where his strange data come from.
>
>Well actually I'm pretty sure he's busy with his career.(as opposed to
>sending thousands of posts to usenet in the last 6 months.)


Comment:

   He's busy making money.  I'm busy trying to change the world.  No
doubt when I get to be his age, I'll be less idealistic.





>If you're really interested in preventing the decline of credibility
>regarding your profession,
>I suggest you consider refraining from putting the letters 'M' and 'D'
>after your name.


      That's your problem, not mine.  Spending 10 years of your life
studying disease, and another 4 studying experimental nutrition, does
change thinking.  The M.D. doesn't show how much, but it's a good
marker for the fact that you've put in the time.  As far as YOU go, all
we know is that you've read a book.  So frigging what?



>I will add that you do have a purpose.  You help people to appreciate
>the light. (Though probably not in the way that you'd like to think.)
>You see,
>folks wouldn't appreciate the light so much without the darkness.


    And YOU'RE the light?  ROFLMAO

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 7 Aug 1998 18:36:14 GMT

In <[email protected]> "sextoy" <[email protected]>
writes:


>Steven B. Harris wrote
>>I've done research on melatonin in an animal model for
>>years, and have seen it do things under certain drug delivery
>>circumstances you won't read about in ANY literature.
>>What have YOU done with it?
>
>
>Interesting.  You've done research "for years" and you've
>seen "it do things" that won't be reported in "ANY
>literature."   Pray tell--Why so?  Are the forces of evil
>censoring your publications?

    Time and money and competing demands (teaching loads, patient care,
etc, etc).  You'll see this stuff in the next couple of years.


>Since you ask.  What I'VE done with it is use 9-12 mg
>p.o.for occasional insomnia.  It works.  My age and weight
>are typical of Standard Man.


    That's nice.  Trying disolving 100 mg of it in a micellized vehicle
and giving it to yourself IV.  You'll see melatonin forever more in a
new light.

                                        Steve

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition
Subject: Re: Dangerous dose of melatonin (up to 80 mg should be fine)
Date: 8 Aug 1998 01:00:01 GMT

In <[email protected]> "sextoy" <[email protected]>
writes:

>Steven B. Harris
>>That's nice.  Trying disolving 100 mg of it in a micellized vehicle
>>and giving it to yourself IV.  You'll see melatonin forever more in a
>>new light.
>
>
>So, Dr. Harris, M.D., that's your medical tip for me?  Is
>that your "prescription"?
>
>Better Watch Your ASS giving out advice like that if you're
>a licensed doctor!



    In case you didn't notice, you and I don't have a doctor-patient
relationship.  My license is in no danger.  And if you're intellient
enough to write as you do, yet follow a suggestion such as the above
while claiming you didn't realize it was made rhetorically and
speciously, I imagine any jury will figure you deserve what's coming to
you.  Which, BTW, will consist more of extreme unpleasantness than
danger.

                                     Steve Harris, M.D.

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition,sci.life-extension,sci.med
Subject: Re: Dangerous dose of melatonin
Date: 12 Aug 1998 16:17:46 GMT

In <[email protected]> [email protected] writes:

>Melatonin has also been found to be a direct vasoconstrictor of rat
>cerebral vessels (Am J Physiol 273:H1530 (97)), so that stroke might be
>a side effect if given in high enough dose.  Although stroke has not
>been reported yet, I would not want to be the first victim.


   It's a pretty good free radical scavenger.  Vasoconstriction is no
doubt due to its sopping up of the natural vasodilator radical nitric
oxide (NO).   This is, of course, a mixed blessing.  Sometimes you have
too much NO, sometimes not enough.  As with most free radicals, it's
not like you can just go around stamping them out wherever you find
them.
                                     Steve Harris, M.D.

From: [email protected](Steven B. Harris)
Newsgroups: rec.drugs.smart,sci.med.nutrition,sci.life-extension,sci.med
Subject: Re: Dangerous dose of melatonin
Date: 14 Aug 1998 02:30:10 GMT

In <[email protected]> [email protected] writes:
>
>In article <[email protected]>,
>  [email protected](Steven B. Harris) wrote:
>> In <[email protected]> [email protected] writes:
>>
>> >Melatonin has also been found to be a direct vasoconstrictor of rat
>> >cerebral vessels (Am J Physiol 273:H1530 (97)), so that stroke might be
>> >a side effect if given in high enough dose.  Although stroke has not
>> >been reported yet, I would not want to be the first victim.
>>
>>    It's a pretty good free radical scavenger.  Vasoconstriction is no
>> doubt due to its sopping up of the natural vasodilator radical nitric
>> oxide (NO).
>
>Actually, the experiment cited above ruled that out as an explanation for its
>effect. (NG-nitro-L-arginine methyl ester did not affect melatonin-induced
>vasoconstriction.)  The data pointed to melatonin's vasoconstrictive effect
>being via the potassium channels.


   Very interesting!