User talk:Glynwiki/Cholesterol Depletion

This article is under development to look at the growing volume of research in lipdology reporting the effects of cholesterol depletion with the long term use of hmg coa reductase medications. The inhibition of de-novo cholesterol is associated with failure of cholesterol-rich lipid rafts in processes such as exocytosis and endocytosis As an example depletion of cholesterol in lipid membranes and failing exocytosis include:
 * Increased incidence of Diabetes

It does appear to present medicine with a huge paradigm shift in their thinking about cholesterol. The paradigm shift has been underway in lipidology and bio-sciences since the lipid raft hypothesis in 1997. Glynwiki (talk) 17:36, 2 June 2009 (UTC)

Note to JFW
= Mevalonate Inhibition ==

Thanks for your interest in this topic. I note your interest in statin therapies and the huge amount you have published on this matter and whilst my work acknowledges the cardiovascular importance of this medication we must look at the detail of its action within the mevalonate metabolic pathway along with squalene epoxidase inhibitors. Some very powerful medical opportunities for such drugs are being overlooked because their role in cardiology is dominant. E.g if the immunomodulatory use of statins might benefit mankind in a flu epidemic (cytokine storm) etc. We do need to assemble a table of mevalonate implication from all inhibitors operating in this area. Caution over dose and selection for statin therapy might benefit pharmaceutical reputation which is looking very unbalanced at the moment? Do we find any common grounds here? Thanks for looking at this.Glynwiki (talk) 16:33, 1 June 2009 (UTC)


 * The whole concept of "mevalonate inhibition" is based on original research. Studies that show the benefits of statins in non-CVD settings (e.g. sepsis in renal failure patients) should be discussed on the statin page because there is no direct evidence that this effect is even achieved as a result of mevalonate inhibition. JFW | T@lk  20:35, 1 June 2009 (UTC)

Thanks re: context and contributor bias guidance
Thanks for your guidance on this matter, and I am considering an improved context and style of contribution if that becomes a wider consensus. I do acknowledge the undoubted success of statins in addressing cardiovascular issues. I took simvastatin and experienced its non-cardiological effects in a preventative context - based on a blood plasma cholesterol test in 2004. Being very aware that personal experience can create bias, I set about reading up on the subject (largely via PUBMED). I first studied the mevalonate metabolic pathway in my undergraduate biochemistry course in 1969, and that knowledge did save me in the 2004 incident. I do see the broader and complex context of my personal experience of simvastatin.

Cholesterol Lowering Therapies and Cell Membranes
Realising that the lipid raft hypothesis had by 1997 created a huge paradigm shift in the functional understanding of cholesterol and the work of FW Pfriger was fleshing out some interesting perspectives on the memory issues, I have been reading avidly to undrstand the bigger picture. I do not want to bring the consequences of the biosciences paradigm shift into conflict with the cardiovascular debate, but the cardiovascular success is in danger of overshooting and destroying the benefits by excluding the implications of lipid raft developments. Last year I decided I was ready and to write a biochemical review paper on the matter. That paper in now in press for publication this summer. My medical mentors persuaded to redraft for a clinical perspective. My paper "Cholesterol Lowering Therapies and Cell Membranes" acknowledges cardiovascular success but also reviews non-cardiovascular clinical issues of the broadening criteria and lengthening usage of cholesterol reduction therapy. It concludes by making a case for more research into long term effects of statins. Quality and Disability adjusted life years are important measures in the assessment of medical outcomes. A hard lesson for me has been the encounters with a very biased and vociferous attacks on the implcations of the lipid raft research - but paradigm shifts have never been easy. I have been assured that although your opinions on this matter may not align well with mine we do share a common interest in presenting a balanced and factual review of current knowledge on the hard won benefits and longer term risk profile of these powerful medicine. I hope we can agree a mutually beneficial way to resolve this issue between us and.... Thanks - I do value your time and guidance. Glynwiki (talk) 06:11, 3 June 2009 (UTC)