In article ,
"Ed Huntress" wrote:

"Joseph Gwinn" wrote in message
...
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.

Imagine all you want. The road to perdition is paved with failed
speculations about the endocrine system. d8-)

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.

That ain't the half of it, pard':

"Regardless of their origin, neuroactive steroids are capable of modifying
neural activities by modulating different types of membrane receptors.
Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic
enzymes are found in the central nervous system. Classical steroid receptors
are localized in the cytoplasm, they exert regulatory actions on the genome,
and their activation causes medium- and long-term effects. Non-classical
receptors are located within the membrane and act as mediators of short-term
effects. Other important players are co-repressors and co-activators that
can interfere with or enhance the activity of steroid receptors."

And so on.

It even makes sense.


snip


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.

"Real proof of harm" is in the eye of the beholder, if you're allowing that
the mechanism may not be known. Overall, I think the FDA has it about right.

To the degree permitted by Congressional politics.


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.

There is no civilized country in the world that allows drugs to be sold
until there is proof they are harmful. ALL of the burden of proof is on the
manufacturer. And rightly so.

There is the sticky problem of unregulated "natural supplements" and such.
They kill a few people every year. The loophole will eventually be closed.

Maybe. Depends on the kill rate.


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.

That's not the value system they use. They weigh the *significance* of the
"effectiveness," and both the nature and incidence of adverse effects is
weighed, as well. It was the former that bit rimonabant in the rear.

Without going into detail, the FDA will tolerate very few dangerous side
effects on a weight-loss drug. But they will tolerate a 5% death rate or
even higher for a terminal cancer drug that extends lives by only a few
months in patients who are otherwise virtually sure to die in weeks.

There should be no grandfather clauses for food or drugs.

Be careful what you pray for.

Well, it's not something you have to pray for. Several drugs have been
pulled off the market by the FDA years later, even after their patents
expired and they went generic, as new research uncovered newly discovered
hazards.

Do you think garlic and jalapeños could
ever be approved today?

Sure. The whole scheme on foods is different. There, the point is freedom
from infectuous diseases.

Right now, there are health-department warnings on such things as eating
large quantities of fish that live in PCB-infested waters and are high on
the food chain. There are some fish that can't be sold. So there are food
regulations that come about despite the fact that people ate those things
for centuries or more.

I think the theory is that PCBs have not been around for centuries.
Mercury in fish may be a better example.


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.

This is not a real issue. If someone discovered that they kill people, that
would be a different matter.


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.

If they caused an epidemic of listeriosis, like some cheese made from
unpasteurized milk did a few years ago, they'd be yanked as fast as
possible.

Drinking raw milk is one thing, eating cheese is quite another. That
was the point.


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.

I have no idea what the army is thinking, at any time and about most
subjects. Maybe there was a reason for the caution and maybe there wasn't. I
find it doubtful that the army was telling those soldiers not to drink beer,
but who knows.

As I recall the story, it was the food that was advised against. But
foolishly.


As for the rosy cheeks on those kids, vascular dilation in the cheeks is
common to people of northern European descent when they drink a lot of
alcohol. The kids were probably half in the bag. d8-)

Nah. They are German; were raised on the stuff. No effect.


snip
.

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.

Or kiddies with tits, which seems to be a trend, and the thing that started
this discussion.

To use this, you have to show that the prevalence of kids with tits (or
any other oddity) is a factor larger than now. A percentage won't do,
as the probability of random false positives is too great.


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.

Sure.


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.

That's why we have an FDA and a National Academy of Sciences who don't run
for political office.

True, but they have their own politics. We just hope that it's neutral
with respect to the question at hand.


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.

Human bodies would be different from, say, cows, because the object is to
avoid human mortality and morbidity. That's why the whole discussion
started. Tits on kids is morbidity.

The politics of scaring people is the same, and the cows are not the
guilty parties. That is my point.


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.

Do you mean by time of year? We drive more in the summertime, especially
when it's hot enough for ice cream and to go to the beach.

Bingo! It's a very good example.

Joe Gwinn