In article ,
"Ed Huntress" wrote:

"Joseph Gwinn" wrote in message
...

snip


Estrogen production in fat is well established it seems. Google is your
friend. Here is one article:
http://www.cancerportfolio.org/abstract.jsp?SID=159653&ProjectID=312260

That's about post-menopausal women, Joe. As far as I've ever heard, estrogen
in girls and young women is produced by the ovaries. And we're talking here
about precocious development of sexual characteristics in girls.

Umm. Yes, but I have to believe that estrogen production in fat didn't
just start at age 50. I imagine a little more research would buttress
the point.


But there are a lot of endocrine functions associated with adipose tissue,
and I'm sure there's more to it than I had to study. I was studying
metabolic syndrome. Among the complex of endocrine functions that go on
within adipose tissue, the studies I've worked with focus on their mediating
functions in the production of hormones secreted in other glands (insulin in
the pancreas; estrogen in the ovaries; etc.).

Another layer of complexity emerges.


The endocrine function of adipose tissue is just as marked in men,
though.
And it's focused on intra-abdominal adipose tissue, rather than
subcutaneous
fat. Young girls usually have mostly subcutaneous fat unless they're
really
obese. Please don't ask me how I know this. d8-)

Hmm. I know what you want us to think, but really is it that you were
doing autopsies on them? How else could you know the amount of visceral
fat?

CT scans. I've had to look at dozens of them, which is a little
disconcerting as you're looking at a computer image of what amounts to a
human steak, well-marbled. d8-(

The visceral, or intra-abdominal fat shows up as fat accumulations between
the internal organs, rather than under the skin, as with subcutaneous fat.

Does not sound like fun at all.


Well, which reaction is the cautious one? The one that recognizes a
marked
correlation and discourages the use of hormones in beef, or the one that
worries we may be overreacting, and that encourages waiting until we can
prove the causative pattern before doing anything? Medicine, out of
necessity, considers the first reaction to be the conservative reaction.
The
second one is conservative only if the business interests involved are
your
primary concern.

The caution is about jumping to conclusions. Aside from accusations of
evil motive, there is lots of experience that would make one hold back,
waiting for the smoke to clear.

Hormone use in beef cattle and other meat animals has been studied for 50
years or more, and it has been a political football for at least that long.
Our chances of sorting out the facts at this point are pretty slim, beyond
the fact that the types of research conducted in the past relate to fairly
controlled use of hormones and to relatively insensitive measures of the
effects in humans. The levels of proof demanded by the FDA today for drugs
for human use, for example, tend to pay more attention to outliers and to
potential misuse, such as a feedlot operator who gets a little too frisky in
the use of steroids in cattle.

Yep.


But I'm less interested in the scientific argument, which we can't settle
here, than in what you're implying about the burden of proof. Are you
suggesting that when the data is inconclusive, we should allow the use of a
drug or food additive until the mechanism of action can be proven to have
harmful effects?

Almost. Given the large uncertainties, it has to take real proof of
harm (even if the exact mechanism isn't known) before we forbid
something. And inconclusive data is just that - inconclusive.


Regarding "evil motive," the issue is marketing and the inescapable
structure of incentives in business, and their inappropriateness to
something like pharmaceuticals, not evil intent. Marketing drugs is what I
did, and I often was given explicit instructions about what to emphasize and
what to soft-pedal. That's the way the pharmaceutical industry works. It's a
business, not a philanthropy, and the object is to sell as many drugs as you
can at the highest price you can get. The ethical conflict that often leads
to is rampant in both food and drug production and sales.

Sure. But we know that. This is why proof is needed, but it cuts both
ways.


The story about rimonabant is a good example. I wrote literature about that
drug that was intended to educate doctors, public health officials, and
corporate benefits managers about the health benefits of the drug, which are
quite real. What I didn't know, because the research on it was not yet
published and was known primarily by the manufacturer -- they didn't even
tell us about it -- is that there have been incidences of depression and
even suicide among some users of the drug. It could be argued that the data
is inconclusive, which I believe is true. But the way it was handled kept
any mention of that problem out of the marketing literature. Fortunately the
FDA regulations on reporting required that they inform the FDA about it. The
FDA denied approval of the drug pending further studies, which will take
roughly three years to complete.

"Jumping to conclusions" is what the FDA and other regulatory bodies around
the world do every day. That's their job and their responsibility. That's
exactly what we *want* them to do. They have to be both suspicious and
cautious. Protecting the public's health requires caution in the use of
agents, whether they're drugs in humans or chemicals in food, based on
correlations that usually are uncertain at the time when an appearance of
risk appears in preliminary studies. The burden of proof is, and must be, on
the sellers of those agents to prove they're safe, not the other way around.
And when medical science advances and makes more sensitive proofs available,
those drugs and food additives may have to prove themselves once again.

This is a whole other thread. The FDA is trying to find drugs that are
at once are effective, are totally safe, and have zero side effects.
Impossible, but Congress keeps trying.


There should be no grandfather clauses for food or drugs.

Be careful what you pray for. Do you think garlic and jalapeños could
ever be approved today? Fortunately, they have been around for
centuries to millennia, so they are grandfathered, if only because any
regulator that tried to outlaw them would be laughed off the planet.

A good example is the FDA trying to deal with German beer (unpasturized)
and especially French raw-milk cheese (ditto). The fact that ~120
million people are none the worse for it doesn't seem to matter.

Which reminds me of a war story. In the 1970s I worked with an ex-Army
guy who had been stationed in West Germany. The US Army warned their
soldiers against eating the local German food, and my coworker followed
this advice until one day he was driving and went by a line of young
German boys walking to school, each with a lunchbox and a bottle of
beer. And these boys looked rosy-cheeked *healthy*. What can the Army
be thinking? Coworker stopped listening to the Army, and went native.


The classic example is the true statement that there is a positive
and
significant correlation between ice cream sales and automobile
accident
rate - they rise and fall together. So, to save lives we should
forbid
the sale of ice cream?

You really have to read the clinical studies to understand most
medical
science research. This is not logic class. It's medical research, and
it
has
to march to different drummer than physical science, out of necessity.

I have read many of them. I've subscribed to the New England Journal
of
Medicine for many years, and I designed instruments for pharmacological
research in the 1970s.

Well, then, you know how rare it is, in endocrinology or other fields
that
involve complexes of phenomena, to see any sure claim of causation. In
your
reading about adipose tissue and endocrine functions, how often do you
see
anything that says "and this causes this"? Not often, I'm sure.

Right. But the point is that this is *very* complex and ill-understood,
so it's unlikely that we really have the slightest idea what's really
going on.

It is complex. Studying the mediative pathways in endocrine functions is one
of the bleeding edges of medical research. You and I are unlikely to be able
to sort them out, although, as with global warming, the preponderance of
historical studies fall on one side -- the side that says hormones in beef
are OK, in this case.

Right. If it were really that dangerous, we would have the piles of
dead bodies to prove it.


I remain suspicious because I've seen the effects of business incentives,
which are normal and healthy in non-health-related cases, as they operate in
the food and drug industries. They don't work in the favor of consumers,
IMO. And specific studies continue to raise a red flag here and there.

Yes, companies are biased towards their economic interests. That's why
they have to be made to prove their case. But again, it cuts both ways,
and long-term successful use is a very powerful argument, and very much
puts the burden of proof on the latecomer claiming heretofor unknown
great danger.

More generally, we always have conflicting agendas, and one can always
accuse the proponents of the sides of bias and conflict-of-interest and
general evil. It may even be true. But this will never change, so we
have to deal with it.


It *will* be sorted out, because there is a billion-dollar
business awaiting the evil company that figures it out. And likely a
Nobel Prize or two.

When you figure out how it would be in the financial interest of a company
to show that hormones in beef are bad for our health, let us know. The
opposite is true in the extreme. And that's the way the whole pharma
industry operates: there is no incentive and no money for studies that show
a drug is bad for you. The incentive is almost exclusively to try to show
that they're good.

No, I was talking about the whole endrocrine system involving weight
control, diabetes, estrogen, et al. There is a fortune to be made here,
and someone will crack that nut. The motive is there.

And one perhaps unintended consequence is that we would find out for
sure if extra hormones in beef mattered, and why. And how.


Excuse me for trimming the rest of this message off, but I think we're
repeating ourselves. And we probably don't disagree very much, anyway. I
recognize what you're saying about the people who keep warning that the sky
is falling, on this as well as many other issues. I just happen to apply a
different standard of proof to matters of the things we put in our bodies.

OK. Why would bodies be different? It's the same scare tactics.


I hope we didn't make too many people fall asleep here. g

It *is* an occupational hazard.


But I have to ask: Why is ice cream sales correlated with highway
accident rate? It is true; the question is why.

Joe Gwinn