X-Message-Number: 16714
Date: Tue, 26 Jun 2001 14:29:33 EDT
Subject: (no subject)

Thanks for your input Doug. It is said all highly active drugs go through 
three phases: 1) The panacea phase; it's miracle, cures everything and can do 
no harm. 2) The demonization phase; it has terrible side effects, causes more 
problems than it cures, and is overpriced. 3) Finally, the Perfectly 
Pedestrian Pharmaceutical Phase wherein physicians and patients adjust to the 
benefits and shortcomings of the drug in a more or less realistic way. This 
will probably happen with statins.

Perhaps Doug is right that in Canada you have to have an MI before they are 
prescribed. But this is not the case in US. The current NIH and AHA blood 
lipid guidelines are all that is needed. If you are not in an HMO or are 
willing to pay for you own drugs and you show up with the raft of compelling 
papers from the NEMJ, Stroke, The Lancet, and too many others to name, you'll 
get a prescription. I did and I got my insurance to pay for it. I wish I 
could have taken Prevachol, and may try it again; in my case it seems that 
Captopril is a major driver of the itching when taken with a statin and I've 
switched back to enalapril. In the meantime, I'll have to be happy with a 50% 
drop in LDL and a massive improvement in LDL/HDL ratio.

I think it is very important to point out that the statins are working by 
mechanisms other than lowering cholesterol. These drugs are potent 
antiinflammatories and appear to affect Nf kappa B expression and impact 
multiple other genes. 

I suspect their effect in Alzheimer's, if it proves out, will be due to a 
direct effect on the CNS unrelated to cholesterol and that the same will be 
true of osteoporosis and Type II diabetes. They were candidates in my mind 
for use as pretreatment in cerebral resuscitation and I would tentatively 
recommend that terminal cryonics patients start and continue statin therapy 
where not contraindicated. The statins appear to be more effective at 
inhibiting CNS inflammation than my pet drug Dapsone; an antileprosy drug 
with potent CNS protective effects. They are also less toxic and more 
available. If I ever to get where I can do research again, I have a good 
small animal model validated to evaluate these kinds of interventions.

John Bull has asked to reprint this article in THE IMMORTALIST. You may want 
to amplify and add to it and tip in references and come on as a coauthor. I 
think that intelligent application of these drugs could prolong both the 
quality and the quantity of a lot of lives. The important thing here is that 
the statistical base is large, it is in HUMANS and it mostly RCT or very good 
retrospective studies. It seems clear that for the past decade the statins 
are really squaring the curve. That's a wonderful piece of luck, because 
everybody knows that if that were the purpose of the statins they would be in 
FDA Hell till we were all dead.

I'd also caution people that taking supplements has very little comparable 
evidence that they work, and growing evidence that most don't -- or can even 
hurt you. I became very suspicious of Vitamin C about 10 years ago and cut it 
out of the cryonics protocols. Every ischemic animal that got ascorbate had 
markedly greater injury after ischemia -- usually not recovering any level of 
consciousness even with less than 10 minutes of insult time. Recently the 
Aerospace study on carotid artery intimal thickening in people supplementing 
with ascorbate, and the recent in vivo studies showing increased radical 
production and mutation seem to bear out our earlier experience. Perhaps if 
supplementation is more aggressive with other antioxidants this negative 
effect could be avoided. However, until this is demonstrated I'd hold C 
intake to no more than 250 mg/day/adult. It is just too potent a driver of 
the Fenton reaction and there is plenty of free iron to catalyze this nasty 
radical cascade.

Mike Darwin

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