Life extension and this newsgroup
Brian Manning Delaney
Tom Matthews wrote:
[....]
>> > In particular, some posters have stated
>> > the *I* was most likely shortening my life,
>> > causing liver damage, etc. by doing so.
>>
>> For the record, I think it's very unlikely that you're
>> shortening the life you would live with no supplementation
>> at all, and, further, believe that the risks aren't
>> primarily about liver damage.
>
> But I remember you appearing to agree with Mark
> Thorson on a sci.med.nutrition thread concerning
> the potiential state of my liver.
Hmm.. I don't think so. If I did so, I retract it (not that
I think your liver is in good shape; rather, I wouldn't
argue it's in bad shape).
I, Brian, wrote:
>> The point is that
>> we need studies of the supplements in combination.
Let me add what I normally add here: we need studies of the
supplements in combination, OR a radically improved
knowledge of human physiology, improved in such a way that
we can deduce what effect supplements in combination would
have. The studies are much, much easier to pull together
quickly, that's why I usually stress the direct empirical
evidence approach to questions like these.
>> You've pointed to some studies that look at pairs of
>> high-dose vitamins, and in a few cases, more than two or
>> three vitamins (but not in mega-doses). This is a beginning,
>> but doesn't bear more than minimally on the question of 1)
>> mega-doses of 2) dozens of different supplements. (One
>> exception, the A, B6, C and E plus zinc mega-dose study. But
>> this was a study of people who HAVE cancer, AND are
>> receiving BCG immunotherapy. Why should the study have
>> anything to do with the vast majority of people taking
>> multi- mega-supplements?)
>
> This is a reasonable question and, in fact, in
> most of the studies which I cited and for others
> which can be found, the nutrients, multiple or
> not, were being taken in an attempt to
> ameliorate some disease process. My view of this
> is that any combination of vitamins which does
> ameliorate some disease process is quite likely (not
> necessarily, but reasonably likely) to be
> beneficial to those which do not have that
> disease process either to prevent them from
> getting that specific disease or for other
> general health purposes.
I disagree very strongly with this view, especially if you
expand it to include more than just vitamins. One obvious
example where this is false is where a disease is caused by
a deficiency of a vitamin (most vitamins). Giving someone
more than enough B-12 to prevent the B-12 deficiency
associated diseases isn't going to improve their health
beyond the improvement that would come with the amelioration
of existing deficiency conditions (if there had been a
deficiency). Thinking otherwise is the classic 1970's
life-extensionist fallacy: less than "normal" is bad,
therefore more than normal is good. It's not true (the whole
statement).
>> At this point, one way we can try to advance this discussion
>> is with more specifics. Something I would love to see -- as
>> would most people reading this group, if the email pulse is
>> representative -- is a detailed justification of The Life
>> Extension Foundation's Life-Extension Mix (TM): "clear
>> supporting documentation." This would be very helpful.
> ... First, I will query LEF about who and how
> the decisions are made. And secondly I will
> start producing abstracts supporting ingredients,
> ratios, etc in the mix. This will be a long but
> worthwhile and interesting exercise. Who knows,
> the result may be a still superior mix which we
> will all understand the reasons for.
That would be great. I wouldn't, though, expect you to put
any time into posting abstracts supporting well-known
nutrients taken in isolation, since that would be a huge
undertaking. (Take "well-known" as you want; you'll probably
be right enough.)
>> There are a lot of ingredients in LEM, but for the
>> well-known ones, I wouldn't expect citations of studies. I
>> mean a justification for LEM geared towards people who know
>> the life-ext. literature well. We know vitamin E reduces
>> risk of heart disease, probably cancer, possibly
>> Alzheimer's, etc., etc. I just mean: 1) justification for
>> the less well-known nutrients, and 2) justification of the
>> doses,
> Yes, we can approach it that way.
>> and 3) justification for the claim of efficacy of the
>> substances in combination.
> I don't understand you again here. You know that
> we will "not" find any such studies in general.
We've run into this problem before, the problem of
understanding what we mean by "justification," or even
"reasons." Justification doesn't require a strictly
empirical approach; indeed, such an approach is impossible
(deduction and interpretation are both always required).
I just mean an answer to the question: What are the reasons
for thinking that evidence of the efficacy of the substances
that comes from studies of their use in isolation (or pairs
or other small numbers of them) still operates when all
these substances are used in combination? (You know,
"justify": to make "justus," to make just, right. The _quid
juris_ question, etc.)
The answer I'd expect would be, perhaps, of the form: "Well,
we have studies in humans with vitamin E, beta carotene, and
selenium, and the results were positive. Now, we add vitamin
C into the mix, and we believe this is good because vitamin
C works on system Z, and E and the others work on W, X, Y,
respectively, and we believe these systems are sufficiently
independent, in the following ways, for the following
reasons.... Onto gingko: Gingko effects blood vessel wall
health in a way that would not be interfered with by
vitamins C or E or...."
Something like that.
> That best that we can hope to do is to find
> studies that each nutrient has a key biochemical
> role which can be enhanced by supplementing it
> and that the biochemical mechanisms of two
> nutrients are sufficiently independent that it
> is reasonable that the effects will be nearly
> additive. Is not this sufficient to justify "the
> claim of efficacy of the substances in
> combination"?
It might well be, but I'd have to see the details -- above
all, the reasons for believing that the nutrients' modes of
action are independent.
>> >> One practical conclusion: let's support research into this
>> >> and related questions.
>> [....]
>>
>> > You certainly haven't got any arguement from me
>> > about this. However, I believe that
>> > practicalities of the research situation and the
>> > enormous complexity of the task...
>>
>> I don't know what you mean here. Give lab animals or people
>> LEM and follow them for a few years. What's the prob with
>> that?
>
> Of course, this would be possible, but only LEF
> would be willing to finance it. I meant general
> studies of general multiple combinations of
> vitamins by disinterested scientists.
Last time I talked with Saul Kent about this (two or three
years ago), he said LEF was indeed willing to finance this.
>> > ...and possibly
>> > the lack of proper (ie meaningful) animal models
>> > for such a process are going to prevent this
>> > from happening.
>>
>> How so? You continually cite studies using standard lab
>> rodents to support other claims you've made.
>
> Actually, I believe that you are mistaken. I
> don't do that very much. I generally look only
> for human studies. Only when I can't find any do
> I look at animal studies for some evidence. That
> one of the problems that I have with the studies
> about CR. Animal studies for CR certainly give
> better life-extension results than do animal or
> human studies for supplementation. However, if
> one restricts oneself to only human studies,
> there is far more health beneficial evidence for
> supplementation that there is for CR.
Oh, I disagree, but we can get into that later, after more
of a breather from the last round.
>> I await the rationale for the Life Extension Mix.
>
>It's going to take some time.
Understood.
<> Non-Science Issue.
>Brian Manning Delaney wrote:
>> Tom Matthews wrote:
>> > Brian, when I reply to a post, I don't reply
>> > just to the one thing that was being said in
>> > that message but to the sum total of what that
>> > person and others have been saying about the
>> > issue in many messages. My purpose in posting is
>> > generally *never* to make points *against* or
>> > even *related* to another poster, but instead to
>> > convey information, analysis and other correct
>> > ways of thinking about the subject at hand.
>
>> I think this is ultimately incoherent, but that's a
>> philosophical question, which I'm content not to pursue. In
>> any event, your view is noted.
>
> Thanks for your tact here. But I believe it is
> not a philosophical question but more of a
> question of fidelity and comprehensibility of
> information.
I just meant that the idea that information is neither for
nor against is incoherent. But maybe you just mean that your
for's and against's shouldn't be taken to be about
particular Usenet posters, but about larger positions in
general. If so, that's certainly not incoherent.
-Brian.
--
Brian Manning Delaney
My email address is here:
http://xyz.uchicago.edu/users/bmdelane/email.htm
[Wrists: "Leave unambiguous typos."]
Note: All statements in this article are in jest; they
are not statements of fact.
"Mein Genie ist in meinen Nuestern." -Nietzsche.
** Please do not CC your Usenet articles to me. I'll find
them.
Tom Matthews
Brian Manning Delaney wrote:
-> >> You've pointed to some studies that look at pairs of
-> >> high-dose vitamins, and in a few cases, more than two or
-> >> three vitamins (but not in mega-doses). This is a beginning,
-> >> but doesn't bear more than minimally on the question of 1)
-> >> mega-doses of 2) dozens of different supplements. (One
-> >> exception, the A, B6, C and E plus zinc mega-dose study. But
-> >> this was a study of people who HAVE cancer, AND are
-> >> receiving BCG immunotherapy. Why should the study have
-> >> anything to do with the vast majority of people taking
-> >> multi- mega-supplements?)
-
-> > This is a reasonable question and, in fact, in
-> > most of the studies which I cited and for others
-> > which can be found, the nutrients, multiple or
-> > not, were being taken in an attempt to
-> > ameliorate some disease process. My view of this
-> > is that any combination of vitamins which does
-> > ameliorate some disease process is quite likely (not
-> > necessarily, but reasonably likely) to be
-> > beneficial to those which do not have that
-> > disease process either to prevent them from
-> > getting that specific disease or for other
-> > general health purposes.
> I disagree very strongly with this view, especially if you
> expand it to include more than just vitamins.
Well we do need a common term which stands for all the things, possibly
excepting hormones, which one normally supplements. My preferred term is
"nutrient", but I realize that's actually too broad since is includes
all foods as well. But then often, foods too are taken in concentrated
supplemental pill form. I will try to stick to just using the term
"nutrient" unless I specifically mean the defined vitamins.
> One obvious
> example where this is false is where a disease is caused by
> a deficiency of a vitamin (most vitamins). Giving someone
> more than enough B-12 to prevent the B-12 deficiency
> associated diseases isn't going to improve their health
> beyond the improvement that would come with the amelioration
> of existing deficiency conditions (if there had been a
> deficiency). Thinking otherwise is the classic 1970's
> life-extensionist fallacy: less than "normal" is bad,
> therefore more than normal is good. It's not true (the whole
> statement).
Well, I understand what you are saying and you are right that in certain
cases, more will not be better and in fact may be worse. However, with
respect to vitamin deficiency conditions, I believe that you are wrong.
It doesn't make sense that the amount necessary to stop the deficiency
symptoms will also be the optimal amount to stop various unseen, hard to
detect, subclinial physiological or biochemical "weaknesses" which a
higher, "optimal" amount would overcome. So what I am saying is that in
general more beyond the RDA *will* be better up to the point at which it
gets worse. I believe that the point at which raising a particular
vitamin dosage starts to have detrimental effects depends strongly on
the dosages of other certain other nutrients which are related to it.
As for the "classic 1970's life-extension fallacy", it is always easy
for those who weren't mature (or even born) at a certain time in the
past to look back and see the era in a stereotyped way. However, I
believe there were lots of people around then who also did not simply
think that more was always better. At least, I know I didn't. The people
of the past were not as dumb as history generally paints them to be. And
the people of the present aren't that much more brilliant either, they
simply have a little more research knowledge to work from.
But, Brian, this is where you seem to keep changing your tune
(seriously, no offense intended, I am honestly very confused as to what
you will or will not accept). When I and others have before suggested
that we can effectively make the kind of reasoning which you just
illustrated to make decisions, you have continually stated that we can't
or that such arguments aren't nearly as strong as we thing they are. At
least, that is how what you have been saying appears to me. This type of
reasoning you have just described is precisely what I say we *can* use
to make good decisions for multiple combinations from the limited single
studies and the knowledge of biochemical/physiological mechanisms which
we have.
> > That best that we can hope to do is to find
> > studies that each nutrient has a key biochemical
> > role which can be enhanced by supplementing it
> > and that the biochemical mechanisms of two
> > nutrients are sufficiently independent that it
> > is reasonable that the effects will be nearly
> > additive. Is not this sufficient to justify "the
> > claim of efficacy of the substances in
> > combination"?
> It might well be, but I'd have to see the details -- above
> all, the reasons for believing that the nutrients' modes of
> action are independent.
Well, we seem to getting somewhere here!
> >> >> One practical conclusion: let's support research into this
> >> >> and related questions.
> >> > You certainly haven't got any arguement from me
Ok. Thanks for your forbearance, that's an admirable quality.
That's precisely what I meant!
Hey! maybe we are starting to understand each other :-)
--Tom
Tom Matthews
All personal comments do not represent the views of anyone from:
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-841-5433
A non-profit membership organization dedicated to the extension of the
healthy human lifespan through ground breaking research, innovative
ideas and practical methods.
Tom Matthews
In response to my forwarding of Brian Delaney's message re suppor for
multiple supplement use and testing the Life Extension Mix formulation
to Bill Faloon and Saul Kent founders of LEF, I received the following
replies:
From Bill Faloon:
>Dear Tom,
>
>Please be advised that the original Life Extension Mix formula was based on
>the recommendations made by Durk Pearson and Sandy Shaw in the 1982 book
>Life Extension.
>
>Since then, new evidence has prompted us to change the formula eleven times
>to reflect new research data.
>
>We extrapolate from animal studies and human epidemiological studies when
>determining the potency of any single ingredient in the formula.
>
>We could fund studies using Life Extension Mix, but the objective of our
>studies is to find new methods of extending lifespan. Life Extension Mix
>relies on existing research showing disease risk reduction when the
>nutrients contained in the formula are consummed on a regular basis. The
>aging process meanwhile continues unabated.
>
>As our research budget expands, we intend to do a lifespan study on Life
>Extension Mix, but for now, we have thousands of published studies backing
>up the individual ingredients in the product.
>
>We need to go well beyond the efficacy of the Life Extension Mix
>ingredients if we are to significantly increase lifespan.
And from Saul Kent:
> Tom. Yes, Bill knows the most about the rationale for the LE Mix
>formula. We pay far more attention to research in formulating and
>re-formulating LE Mix than most other companies do for their
>multi-nutrient formulas.
> The reason we didn't include LE Mix in the lifespan studies is because
>we were looking to test substances we thought had the best chance of
>extending maximum lifespan based on the most commonly advanced theories
>of aging. Traditionally, such studies include only a single agent. In our
>studies, we have several groups where there is a combination of agents.
>This is highly unusual in itself. A 52-ingredient formula such as Life
>Extension Mix would have many confounding variables. I think it is highly
>unlikely that *any* of these studies will lead to a significant extension
>of maximum lifespan, however, if one of them does, it will be a monumental
>discovery. My assumption is that we will have to do a great many lifespan
>studies over many years to find something that can extend maximum lifespan,
>unless and until we have better clues from basic research about agents most
>likely to extend maximum lifespan.
>
> We do have about 15 years of extensive human use of LE Mix, with
>considerable anecdotal evidence for its benefits and little or no evidence
>of adverse side effects.
> A clinical study will soon begin among union members in the Boston
>area in conjunction with an HMO and Tufts Medical School to assess the
>affects of a multi-nutrient supplement similar (but not identical to) Life
>Extension Mix. This should provide more controlled evidence in a couple of
>years.
Here are the nutrients and combinations for which the Life Extension
Foundation currently has lifespan studies underway.
For details, see the August 1997 issue of Life Extension Magazine at
http://www.lef.org
By Richard Weindruch at the University of Wisconsin at Madison
1. Alpha lipoic acid
2. Alpha lipoic acid & procysteine & vitamin E & lycopene
3. Coenzyme Q10
4. Coenzyme Q10 & acetyl-l-carntine and alpha lipoic acid & NADH
Conrols:
5. 40% Calorie restricted
6. ad libitum, no supplements
By Stephen R Spindler at the University of California at Riverside
1. Pregnenolone
2. Pregnenolone & melatonin
3. Aminoguanidine
4. Aminoguanidine & alpha lipoic acid
5. aminoguanidine & alpha lipoic acid & pregnenolone & coenzyme Q10
Controls:
6. ad libitum, no supplements
I would like to add that my current supplement regimen already includes
everything being tested here except "procysteine" (I take n-acetyl
cysteine instead). And I am moderately calorie restricted as well.
From the same issue of Life Extension Magazine:
Strategies Tested in Mice, Rats, and Hampsters for effects on Lifespan
Type of Intervention Reference
Nutritional:
-Caloric restriction Weindruch and Walford 1988; Weindruch 1996
-Protein level Nakagawa et al 1974; Feldman et al 1982
-Fat level French et al 1953; Birt et al 1982
-Carbohydrate level Dalderup and Visser 1969
-Source of protein, Fat Iwasaki et al 1988a; Kaunitz & Johnson 1975
or carbohydrate Durand et al 1968; Murtagh-Mark et al 1995
-Vitamin level (overall) Kokkonen and Barrows 1985
-Vitamin E Blackett and Hall 1981
-Mineral level (overall) Iwasaki et al 1988b
-Selenium Schroder and Mitchner 1971
-Self-selection among Ross et al 1976
different diets
Drugs, Hormones, and Metabolic Factors:
-Antioxidants Harman 1968; Khon 1971
-Melatonin Pierpaoli and Regelson 1994
-Centrophenoxine Hochschild 1973
-L-dopa Cotzias et al 1977
-Gerovital H3 Verzar 1959
-Beta-aminopropionitrile (BAPN) LaBella and Viven 1975
-Anterior pituitary Robertson and Ray 1919
-Prednisolone Bellamy 1968 "Surgery"
-Removal of pituitary gland Everitt et al 1980
-Immunologic reconstruction Walford et al 1977
-Parabiosis Ludwig and Elashoff 1972
-Castration (males) Drori and Folman 1976
Exercise: Holloszy et al 1985
Ambient temperature: Kibler and Johnson 1966
I would like to add that I have *not* done ALL the things from this long
list, and don't intend too! :-)
Tom Matthews
Here is another reference I just turned up, showing an additive, if not
synergistic, effect of multiple supplements.
Anticancer Res 1997 Mar;17(2A):1099-1106
Effects of conjugated dienoic derivatives of linoleic acid and
beta-carotene in modulating lymphocyte and macrophage function.
"When present together, CLA and beta-carotene interacted in an additive
manner to further enhance lymphocyte cytotoxicity and spontaneous
lymphocyte proliferation. In addition, beta-carotene was able to negate
the inhibitory action of CLA on the phagocytic activity of macrophages.
Also, CLA and beta-carotene together seemed to suppress mitogen-induced
lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
concert, act to modulate different aspects of cellular host defense."
Brian Manning Delaney
<> Terminology
Tom Matthews wrote:
: Well we do need a common term which stands for
: all the things, possibly excepting hormones,
: which one normally supplements. My preferred
: term is "nutrient", but I realize that's
: actually too broad since is includes all foods
: as well. But then often, foods too are taken in
: concentrated supplemental pill form. I will try
: to stick to just using the term "nutrient"
: unless I specifically mean the defined vitamins.
"Nutrient" is a good general term (I think it ultimately
comes from the Latin _nutrire_, to feed, which is, in a
sense, all we're talking about here), but it's not great,
since it presupposes that the substances in question
actually do nourish. Maybe "purported nutrients" or
something like that would be better. I prefer "substance."
But I'll know what you mean when you say nutrient.
<> Miscellaneous.
[....]
: > > My view of this
: > > is that any combination of vitamins which does
: > > ameliorate some disease process is quite likely (not
: > > necessarily, but reasonably likely) to be
: > > beneficial to those which do not have that
: > > disease process either to prevent them from
: > > getting that specific disease or for other
: > > general health purposes.
:
:
: Brian Manning Delaney wrote:
: > I disagree very strongly with this view, especially if
you
: > expand it to include more than just vitamins.
: >
: > One obvious
: > example where this is false is where a disease is caused
by
: > a deficiency of a vitamin (most vitamins). Giving
someone
: > more than enough B-12 to prevent the B-12 deficiency
: > associated diseases isn't going to improve their health
: > beyond the improvement that would come with the
amelioration
: > of existing deficiency conditions (if there had been a
: > deficiency). Thinking otherwise is the classic 1970's
: > life-extensionist fallacy: less than "normal" is bad,
: > therefore more than normal is good. It's not true (the
whole
: > statement).
:
: Well, I understand what you are saying and you
: are right that in certain cases, more will not
: be better and in fact may be worse....
That's not what I'm getting at. I put in the parenthetical
comment to stress that I'm disagreeing with a particular
line of reasoning which argues: IF less is bad, THEN more is
good (more is better than normal; normal =
"deficiency"-avoidance levels). I believe that more is
indeed good, very good, in particular cases. Example:
there's evidence that folic acid far above levels that
prevent anemia is beneficial. But we don't know if the extra
folic acid is beneficial in ways that have much to do with
its RDA-level functioning. It might not be at all. (There
are many other exs.; vitamin C is also a good case.)
Does B-12 beyond RDA levels do anything special? Vitamin K?
Copper? Manganese? Iodine?, etc.
: ... However,
: with respect to vitamin deficiency conditions, I
: believe that you are wrong. It doesn't make
: sense that the amount necessary to stop the
: deficiency symptoms will also be the optimal
: amount to stop various unseen, hard to detect,
: subclinial physiological or biochemical "weaknesses"
: which a higher, "optimal" amount would overcome.
Substances ("nutrients") do _qualitatively_ different things
at different doses. Claims about zinc are an instance of the
1970's life-extensionist fallacy: zinc is needed for proper
immune function, THEREFORE more zinc gives even BETTER
immunity. This is wrong (both the full statement, AND the
idea itself that more than RDA zinc improves immunity, as
far as research currently shows -- there may be exceptions
-- the elderly, for ex.).
Extra zinc, may, under certain conditions, be useful for
certain disease conditions, but thoughts and experiments
about this should be -- or, certainly, shouldn't not at all
be -- decoupled from what we know of its RDA-level role.
: As for the "classic 1970's life-extension fallacy",
: it is always easy for those who weren't mature (or
: even born) at a certain time in the past to look
: back and see the era in a stereotyped way.
: However, I believe there were lots of people
: around then who also did not simply think that
: more was always better. At least, I know I didn't.
Absolutely. I'm referring only to what appeared in a lot of
pop books, and to that which was believed by a lot of people
in general.
[....]
: > >> and 3) justification for the claim of efficacy of the
I think reasoning of this form -- reasoning that purports to
work like computer drug-testing models -- tends to be weak.
Sometimes it's all we have to go on, though. Either way,
what I said was "The answer I'd expect would be, perhaps, of
the form:...." I didn't say that would be a good answer. But
it appears to be all you and The Life Extension Foundation
have. This is understandable, since the direct empirical
studies haven't been done.
I can't pass any final judgements on the reasoning until I
get details.
(Ah, just noticed your recent posts -- more on those soon.)
Best,
Mark Thorson
In article <348226...@netcom.ca>, Tom Matthews <tma...@netcom.ca> wrote:
>
>"When present together, CLA and beta-carotene interacted in an additive
>manner to further enhance lymphocyte cytotoxicity and spontaneous
>lymphocyte proliferation. In addition, beta-carotene was able to negate
>the inhibitory action of CLA on the phagocytic activity of macrophages.
>Also, CLA and beta-carotene together seemed to suppress mitogen-induced
>lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
>concert, act to modulate different aspects of cellular host defense."
So one nutrient suppresses the immune response, while another
mitigates the suppression. How do you know how much of either
to take, or even whether you should take either one at all?
People who wouldn't even consider taking a screwdriver and
adjusting the carburator of their car should be screwing
around with their immune system?
Oh, but hey, I NEED my car.
Brian Manning Delaney
Tom Matthews wrote:
:
: In response to my forwarding of Brian Delaney's
: message re suppor for multiple supplement use
: and testing the Life Extension Mix formulation
: to Bill Faloon and Saul Kent founders of LEF,
: I received the following replies:
:
: From Bill Faloon:
:
: >Dear Tom,
: >
: >Please be advised that the original Life Extension
: >Mix formula was based on the recommendations
: >made by Durk Pearson and Sandy Shaw in the 1982 book
: >Life Extension.
[....]
: >We extrapolate from animal studies and human
: >epidemiological studies when determining the
: >potency of any single ingredient in the formula.
[....]
: >As our research budget expands, we intend to do
: >a lifespan study on Life
: >Extension Mix, but for now, we have thousands
: >of published studies backing
: >up the individual ingredients in the product.
: And from Saul Kent:
:
[....]
: > We do have about 15 years of extensive
: >human use of LE Mix, with considerable anecdotal
: >evidence for its benefits and little or no evidence
: >of adverse side effects.
Tom, the info in your post from Saul and Bill is probably
useful to many people reading this, so thanks for passing it
on. But I still don't see an answer for the third of my
requested justifications -- the three being, again:
1) justification for the less well-known nutrients
2) justification of the doses
3) justification for the claim of efficacy of
the substances in combination.
except for the evidence Saul pointed to: the 15 years of
anecdotal evidence. Anecdotal evidence is not worthless in
my view, but I'd like to see something of what I was
expecting -- detailed thought about likely or possible
interactions among the various components of LEM.
Here's another thought. We might be able to make the
evidence stronger than merely anecdotal. Wait, I'll put this
in a different post. (I'll post this other post only to
sci.life-extension, for those reading in a cross-posted
group.)
But I do want to see some details on the question of
interaction of the components of the Mix.
Tom Matthews
Brian Manning Delaney wrote:
> I believe that more is
> indeed good, very good, in particular cases. Example:
> there's evidence that folic acid far above levels that
> prevent anemia is beneficial. But we don't know if the extra
> folic acid is beneficial in ways that have much to do with
> its RDA-level functioning. It might not be at all. (There
> are many other exs.; vitamin C is also a good case.)
Well I agree with you here, but all this suggests to me is that the RDA
deficiency disease caused by the lack of a vitamin is a very poor
indicator of its many possible biochemical uses and, therefore, of its
potential for benefiting (or harming) health. Vitamin E in its various
forms in another good example. From the studies that have been done it
appears as if E succinate should be classified as a separate nutrient to
unesterfied tocopherol or tocopherol acetate.
RDA levels should simply be viewed as what they are the level above
which most people do not get the specific deficiency disease. But we do
not take more than the RDA of say, Vitamin C so that we will get a
"negative amount" of scurvy, we take it because it has other major
benefits, the harmfulness of which is not so simple to detect and
classify as is scruvy. I would suggest that this potential for action at
many levels, in many biochemical ways and at many physiological sites is
probably the norm for most nutrients. In fact, a nutrient may even have
different U-shaped dose/response curves for each of its different
biochemical uses and these dose/response curves may vary quite a lot
between genetically determined biochemical variations of different
individuals. I have never said that working out optimal doses would be
easy!
=
> Does B-12 beyond RDA levels do anything special?
Yes, when combined with folate. As well as possibly being necessary.
Call for endorsement of a petition to the Food and Drug Administration
to always add vitamin B-12 to any
folate fortification or supplement. (Herbert V; Am J Clin
Nutr, 1997 Feb)
> Vitamin K?
Yes, if you are newborn at risk for hemorrhagic disease. =
Prevention of vitamin K deficiency bleeding: efficacy of different
multiple oral dose schedules of vitamin K.
(Cornelissen M; Eur J Pediatr, 1997 Feb)
Both more often (for those with a tendency to blood clots) it may be
harmful, although more supplemented generally just gets excreted.
>Copper?
Yes, if you are taking lots of zinc, ascorbate or cysteine, but
generally extra copper is a free radical producer almost as bad as iron.
The resistance of low density lipoprotein to oxidation promoted by
copper and its use as an index of
antioxidant therapy. (O'Leary VJ; Atherosclerosis, 1996 Jan
26)
>Manganese?
Yes, it you have AIDS:
Effects of manganese salts on the AIDS-related pathogen, Cryptosporidium
parvum in vitro and in vivo.
(Nesterenko MV; Biol Trace Elem Res, 1997 Mar)
Or if you are eating lots of fat and iron:
Increasing dietary lipid and iron content decreases manganese superoxide
dismutase activity in colonic
mucosa. (Kuratko CN; Nutr Cancer, 1997)
> Iodine?
It may lower calcium and magnesium excretion
[Changes in urinary calcium and magnesium levels during supplementation
with iodine and selenium]
(Simeckov=E1 A; Vnitr Lek, 1996 Nov)
The main point, however, that I would make with all of your examples
(except K and copper), is that quite a lot more than the RDA has well
been shown to be not harmful. Therefore, I believe that it would be
reasonable (because is might be beneficial and is highly unlikely to be
harmful) to take an amount more than the RDA but still substantially
less than any know toxic amount, possibly even many times more if there
is no known toxicity at all. =
> : ... However,
> : with respect to vitamin deficiency conditions, I
> : believe that you are wrong. It doesn't make
> : sense that the amount necessary to stop the
> : deficiency symptoms will also be the optimal
> : amount to stop various unseen, hard to detect,
> : subclinial physiological or biochemical "weaknesses"
> : which a higher, "optimal" amount would overcome.
> =
> Substances ("nutrients") do _qualitatively_ different things
> at different doses.
I don't disagree with this. I said the same thing above.
> Claims about zinc are an instance of the
> 1970's life-extensionist fallacy: zinc is needed for proper
> immune function, THEREFORE more zinc gives even BETTER
> immunity. This is wrong (both the full statement, AND the
> idea itself that more than RDA zinc improves immunity, as
> far as research currently shows -- there may be exceptions
> -- the elderly, for ex.).
Don't forget the RDA (12-15mg) is the amount necessary to stop the
deficiency disease (poor wound healing, lowered immunity and retarded
growth in children) in *most* people. To be safe, I think it would be
wise to take a bit more, say 30mg, since the toxic dose is a few hunderd
mg (and then you will know it form having cramps or vomiting) it would
be wise to keep the dose below 100mg and if you are about 30mg you
should take extra copper and make sure you have adequate calcium.
Anyway, again zinc as with so many other nutrients has more uses than
just one (immunity enhancement). Here's as study which showed great
benefit from supplementing with 25mg daily.
Zinc supplementation and plasma lipid peroxides in an elderly
population. (Fortes C; Eur J Clin Nutr, 1997
Feb)
Furthermore, here's an abstract which suggests to me that additional
zinc beyond the RDA may well increase immunity also.
Competitive reverse transcriptase-polymerase chain reaction shows that
dietary zinc supplementation in
humans increases monocyte metallothionein mRNA levels.
(Sullivan VK; J Nutr, 1997 May)
=
> Extra zinc, may, under certain conditions, be useful for
> certain disease conditions, but thoughts and experiments
> about this should be -- or, certainly, shouldn't not at all
> be -- decoupled from what we know of its RDA-level role.
Quite so. The RDA is only one facit of its potential. It is especially
true with nutrients such as zinc, where there is no clear-cut single RDA
deficiency disease, that there are many clear possibilities for benefit
by taking more than the RDA. =
More later,
--Tom =
Tom Matthews
=
All personal comments do not represent the views of anyone from:
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-841-5433 =
A non-profit membership organization dedicated to the extension of the =
healthy human lifespan through ground breaking research, innovative =
ideas and practical methods.
Tom Matthews
Mark Thorson wrote:
>
> In article <348226...@netcom.ca>, Tom Matthews <tma...@netcom.ca> wrote:
> >
> >"When present together, CLA and beta-carotene interacted in an additive
> >manner to further enhance lymphocyte cytotoxicity and spontaneous
> >lymphocyte proliferation. In addition, beta-carotene was able to negate
> >the inhibitory action of CLA on the phagocytic activity of macrophages.
> >Also, CLA and beta-carotene together seemed to suppress mitogen-induced
> >lymphocyte proliferation. Therefore, CLA and beta-carotene; alone and in
> >concert, act to modulate different aspects of cellular host defense."
>
> So one nutrient suppresses the immune response, while another
> mitigates the suppression. How do you know how much of either
> to take, or even whether you should take either one at all?
Mark, you seem to be under the misguided impression that the immune
system is all good. That any lowering or modifying of it in any way must
be bad. This is far from the truth as shown buy the many forms of
autoimmune diseases which are around us (which properly looked at are
*distorted* immune systems rather than just too much generally
immunity). Furthermore, as a science news article that I was just
reading today pointed out the immune system and markers of the potential
problem are now clearly implicated in atheroscelosis many years prior to
what were thought to be the standard risk factors. Both CLA and
beta-carotene (make sure to take lots of other carotenoids as well) have
been shown to be highly beneficial for various things. The study that I
cited simply showed that there effect was additive for one particular
purpose. That's all that I was using it to illustrate.
> People who wouldn't even consider taking a screwdriver and
> adjusting the carburator of their car should be screwing
> around with their immune system?
Actually, I don't think that you adjust carburetor much with
screwdrivers these days. But in any case, if you are well read and
knowledgeable about the literature of supplements, or rely on someone
who is, then you are just as much able to make good decisions about your
nutritional health as you would be about your carburetor once you had
study the mechanics manual on the car. And instead of just decreasing
your need to take a bus, you make be preventing cancer or heart disease!
> Oh, but hey, I NEED my car.
But you *don't* need your health, right?
Tom Matthews
Brian Manning Delaney wrote:
> Tom, the info in your post from Saul and Bill is probably
> useful to many people reading this, so thanks for passing it
> on. But I still don't see an answer for the third of my
> requested justifications -- the three being, again:
>
> 1) justification for the less well-known nutrients
> 2) justification of the doses
> 3) justification for the claim of efficacy of
> the substances in combination.
>
> except for the evidence Saul pointed to: the 15 years of
> anecdotal evidence. Anecdotal evidence is not worthless in
> my view, but I'd like to see something of what I was
> expecting -- detailed thought about likely or possible
> interactions among the various components of LEM.
>
> Here's another thought. We might be able to make the
> evidence stronger than merely anecdotal. Wait, I'll put this
> in a different post. (I'll post this other post only to
> sci.life-extension, for those reading in a cross-posted
> group.)
>
> But I do want to see some details on the question of
> interaction of the components of the Mix.
Brian, I agree with you that it would be very nice to have multiple
supplement studies. However, I still don't understand what your problem
is with accepting that unless two beneficial nutrients are clearly
operating in the same manner, their results would most likely be
additive or close to it. Again, it seems to me that the onus is on you
or anyone else to show that they would *not* be additive, somewhat at
least.
We have already begun it with serveral nutrients, so I will try to find
the time to go through everything which is in Life Extension Mix and see
that every pair of ingredients either enhances or do not interfer with
each other's actions to the extent which I can find references. But
again I really believe it should be up to you and others who raise the
question of potential reduction of individual benefits (or even harm)
when several nutrients are taken together to bring forth the evidence to
support your suggestions.
Frankly, I am getting a bit tired of doing all the work :-)
Tom Stone
In article <34840D...@netcom.ca>, Tom Matthews <tma...@netcom.ca> writes:
|> Brian Manning Delaney wrote:
|> > Claims about zinc are an instance of the
|> > 1970's life-extensionist fallacy: zinc is needed for proper
|> > immune function, THEREFORE more zinc gives even BETTER
|> > immunity. This is wrong (both the full statement, AND the
|> > idea itself that more than RDA zinc improves immunity, as
|> > far as research currently shows -- there may be exceptions
|> > -- the elderly, for ex.).
|>
|> Don't forget the RDA (12-15mg) is the amount necessary to stop the
|> deficiency disease (poor wound healing, lowered immunity and retarded
|> growth in children) in *most* people. To be safe, I think it would be
|> wise to take a bit more, say 30mg, since the toxic dose is a few hunderd
|> mg (and then you will know it form having cramps or vomiting) it would
|> be wise to keep the dose below 100mg and if you are about 30mg you
|> should take extra copper and make sure you have adequate calcium.
Tom,
According to "Modern Nutrition in Health and Disease" 8th ed., zinc
dosages in excess of 150mg generally interfere with copper absorption
and place people at risk of developing a copper deficiency. It further
states that this effect has been seen at dosage levels as low as
28 mg. It doesn't mention whether this effect can be countered via
additional copper supplementation.
Keep in mind that they are discussing total intake, not just supplemental
intake. I generally recommend that people not supplement any more
than the RDA for zinc since this level of supplementation will generally
yield a total intake of 25-30 mg.
When people take supplements, it is important that they keep in mind that
they are taking something IN ADDITION TO their normal diet. Many people
forget to calculate their dietary intake before deciding on a supplementation
regimen. Take magnesium for instance. RDA 400 mg, average dietary
intake is 300 mg, so the AVERAGE person only really needs to supplement
with 100 mg. If they supplement with more than that, they need to account
for the 300 mg dietary intake when determining their dosage level.
Regards,
Tom Stone
--
Any opinions expressed are strictly my own.
tstone@(~remove~)nortel.ca <Literasy Ain't Everthing>
Steven B. Harris
>Mark Thorson wrote:
>> People who wouldn't even consider taking a screwdriver and
>> adjusting the carburator of their car should be screwing
>> around with their immune system?
That gave me a smile, but the truth is, you can hardly avoid it. It
happens when you eat this vs that, when you run and don't walk, when
you stay in bed too long or not long enough, when you prevaricate and
procrastinate and otherwise put yourself under stress; when you take a
really long hot bath, when you kiss this girl and not that one, and so
on and so on and so on. Vitamins and rain and sunshine and pollen all
have their input. And pesticides and industrial wastes and the sound
of music.
You want to stick that screw driver in at random and let the world do
the same? Or do you want to have at least little bit of method to what
happens? You didn't come from the factory with a sealed and perfectly
adjusted unit, you know, and a little sign saying that tampering by
owner nulls warrantee. I hate to burst your bubble, but there ain't no
warrantee. The unit isn't sealed. Tampering by owner and everybody
else is expected, unavoidable, and probably necessary for the best
health.
Steve Harris, M.D.
Steven B. Harris
In <661dbg$l...@bcrkh13.bnr.ca> tst...@nortel.ca (Tom Stone) writes:
>
>
>In article <34840D...@netcom.ca>, Tom Matthews <tma...@netcom.ca>
writes:
>|> Brian Manning Delaney wrote:
>|> > 1970's life-extensionist fallacy: zinc is needed for proper
>|> > immune function, THEREFORE more zinc gives even BETTER
>|> > immunity. This is wrong (both the full statement, AND the
>|> > idea itself that more than RDA zinc improves immunity, as
>|> > far as research currently shows -- there may be exceptions
>|> > -- the elderly, for ex.).
>|>
>|> Don't forget the RDA (12-15mg) is the amount necessary to stop the
>|> deficiency disease (poor wound healing, lowered immunity and
retarded
>|> growth in children) in *most* people. To be safe, I think it would
be
>|> wise to take a bit more, say 30mg, since the toxic dose is a few
hunderd
>|> mg (and then you will know it form having cramps or vomiting) it
would
>|> be wise to keep the dose below 100mg and if you are about 30mg you
>|> should take extra copper and make sure you have adequate calcium.
>
>
>According to "Modern Nutrition in Health and Disease" 8th ed., zinc
>dosages in excess of 150mg generally interfere with copper absorption
>and place people at risk of developing a copper deficiency. It
further
>states that this effect has been seen at dosage levels as low as
>28 mg. It doesn't mention whether this effect can be countered via
>additional copper supplementation.
>
>Keep in mind that they are discussing total intake, not just
supplemental
>intake. I generally recommend that people not supplement any more
>than the RDA for zinc since this level of supplementation will
generally
>yield a total intake of 25-30 mg.
Agree completely. And it probably helps to take that RDA of zinc with
your RDA of molybdenum, and take your RDA of copper at some other meal.
Steve Harris, M.D.
Tom Matthews
Steven B. Harris wrote:
>
> In <661dbg$l...@bcrkh13.bnr.ca> tst...@nortel.ca (Tom Stone) writes:
> >
> >
> >In article <34840D...@netcom.ca>, Tom Matthews <tma...@netcom.ca>
> writes:
> >|> Brian Manning Delaney wrote:
> >|> > 1970's life-extensionist fallacy: zinc is needed for proper
> >|> > immune function, THEREFORE more zinc gives even BETTER
> >|> > immunity. This is wrong (both the full statement, AND the
> >|> > idea itself that more than RDA zinc improves immunity, as
> >|> > far as research currently shows -- there may be exceptions
> >|> > -- the elderly, for ex.).
> >|>
> >|> Don't forget the RDA (12-15mg) is the amount necessary to stop the
> >|> deficiency disease (poor wound healing, lowered immunity and
> retarded
> >|> growth in children) in *most* people. To be safe, I think it would
> be
> >|> wise to take a bit more, say 30mg, since the toxic dose is a few
> hunderd
> >|> mg (and then you will know it form having cramps or vomiting) it
> would
> >|> be wise to keep the dose below 100mg and if you are about 30mg you
> >|> should take extra copper and make sure you have adequate calcium.
> >
> >
> >According to "Modern Nutrition in Health and Disease" 8th ed., zinc
> >dosages in excess of 150mg generally interfere with copper absorption
> >and place people at risk of developing a copper deficiency. It
> further
> >states that this effect has been seen at dosage levels as low as
> >28 mg. It doesn't mention whether this effect can be countered via
> >additional copper supplementation.
> >
> >Keep in mind that they are discussing total intake, not just
> supplemental
> >intake. I generally recommend that people not supplement any more
> >than the RDA for zinc since this level of supplementation will
> generally
> >yield a total intake of 25-30 mg.
>
> Agree completely. And it probably helps to take that RDA of zinc with
> your RDA of molybdenum, and take your RDA of copper at some other meal.
Steve, I wonder if your last suggestion in valid. The mechanism by which
zinc inhibits copper absorption is by the stimulation of of the
synthesis of thionein in the intestinal lumen cells and elsewhere.
Thionein is a protein which binds to many metals but with a higher
affinity for copper than to zinc (or almost any other metal). Therefore,
it would appear to me that as long as the extra zinc is in the diet (and
increasing the thionein synthesis) even a later dose of copper would
still be just as easily bound to the thionein displacing the zinc that
it was holding. However, if the copper is already bound to something
which enhances its absorptions (see list below) then that may not happen
to such a great extent.
However, I still believe that extra zine may be beneficial and that an
decreased copper absorption can be offset. In defense of my position, I
offer the following items:
J Appl Physiol 1994 Jun;76(6):2298-2303
Exercise-induced changes in immune function: effects of zinc
supplementation.
Singh A, Failla ML, Deuster PA
To examine the effect of zinc (Zn) supplementation on exercise-induced
changes in immune function, five male runners were randomly assigned in
a double-blind crossover design to take a supplement (S; 25 mg of Zn and
1.5 mg of copper) or placebo (P) twice daily for 6 days. On morning 4 of
each phase, 1 h after taking S or P, subjects ran on a treadmill at
70-75% of maximal oxygen uptake until exhaustion (approximately 2 h).
Blood samples were obtained before (Pre), immediately after (Post), and
1 (Rec1) and 2 (Rec2) days after the run. [3H]thymidine incorporation by
mitogen-treated mononuclear cell cultures was significantly lower (P <
0.05) Post than Pre, Rec1, or Rec2 for both S and P. Respiratory burst
activity of isolated neutrophils was enhanced after exercise with P but
not with S (P: Pre 12.0 +/- 1.1 vs. Post 17.6 +/- 2.3 nmol O2-/10(6)
cells; S: Pre 11.7 +/- 0.3 vs. Post 12.1 +/- 1.2 nmol O2-/10(6) cells).
Thus supplemental Zn blocked the exercise-induced increase in reactive
oxygen species. Whether this antioxidant effect of Zn will benefit
individuals exposed to
chronic physical stress remains to be determined.
This suggests to me that zinc at a small excess of RDA was beneficial
(probably caused more SOD to be produced), at least for those who
exercise.
Toxicology 1981;19(3):247-254
The influence of high dietary zinc on tissue disposition and urinary
excretion of cadmium, zinc, copper and iron after repeated parenteral
administration of cadmium to rats.
Bonner FW, King LJ, Parke DV
The administration of a high dietary supplement of zinc sulphate (2000
ppm) to rats for 28 days produced no effect upon growth rate of the
animals but caused in increased food intake. The supplement had no
effect upon the reduction of growth rate caused by the daily injection
of cadmium chloride (1.5 mg/kg). Zinc-supplemented animals showed an
increased accumulation of zinc in the liver and kidney, plasma zinc
levels were significantly increased and there was an elevated excretion
of zinc in the urine compared to control animals. Cadmium-treated,
zinc-supplemented animals had a higher concentration of cadmium in the
liver compared to animals treated only with cadmium. The high dietary
zinc did not interfere with tissue or plasma concentration of copper and
iron, nor did it influence the cadmium-induced changes in these metals.
There was some indication however of a decreased urinary excretion of
copper.
Maybe the cadmium has something to do with it, but this high zinc
supplement (maybe Steve can tell us what the human equivalent amount of
2000ppm for a rat) did not appear to decrease plasma copper and even
decreased urinary excretion (or course it may have increased fecal
excretion which they did not measure, at least according to the
abstract).
Furthermore, it should be noted that while many studies have shown
reduced copper absorbtion when increased zinc was taken, I could not
find one which increased copper at the same time let alone one which
increased the things that aid copper absorption such as amino acids
(especially histidine), citrate and gluconate, and fructose.
In summary, I believe that there is some evidence that zinc
supplementation moderately above RDA levels can be beneficial and little
evidence to suggest that by taking the right steps (supplementation
correspondingly increased or increased absorptions aids), copper status
need suffer.
Obviously, there are more studies needed to settle these questions. When
I look at the studies which have been undertaken, it always appears to
me that those designing the studies, almost on purpose, left out the
factors which might have helped the study show a positive effect from
supplementation above RDA levels. Maybe I'm just paranoid :)
--Tom
Tom Matthews
All personal comments do not represent the views of anyone from:
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-841-5433
A non-profit membership organization dedicated to the extension of the
healthy human lifespan through ground breaking research, innovative
ideas and practical methods.
increase lifespan
> [Wrists: "Leave unambiguous typos."]
> Note: All statements in this article are in jest; they
> are not statements of fact.
> "Mein Genie ist in meinen Nuestern." -Nietzsche.
> ** Please do not CC your Usenet articles to me. I'll find
> them.
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