LIPITOR,® THIEF OF MEMORY Dr.Graveline has unraveled the impact of statins
on the immune system . The implications of this are huge. This is a must read
even though it is a bit technical for some (gets easier to understand as you
read). His comments could just as easily be applied to many other drugs.
"Tossing the statin sledgehammer into this system is perhaps quite comparable in effect to the rampages of "a bull in a China shop" and it is far too soon to tell about most malignant changes...
...statin's effect is based upon interference with our most basic immuno defense system. The potential consequences are frightening."
Unlike foods/nutrients most drugs muck around with some very intricate biochemical pathways and frequently mask, not cure as many pretend, the effects of a disease at the expense of creating another.
Some examples are: Tomoxifin and Roloxifin, which are second generation anti-estrogen medications which supposedly prevent breast cancer at the expense of upping the chances of endometrial cancer and pulmonary embolus (twofold increase in embolic event).
"The thiazolidinediones used to control Type II Diabetes are famous for causing liver cancer. One of them, Rezulin, was approved in the USA through devious political infighting, but failed to get approval in the UK because it was known to cause liver cancer.... As of April 2000, lawsuits commenced to clarify this situation (Law Offices of Charles H. Johnson & Associates (telephone 1 800 535 5727, toll free in North America)"...
Extracted from: Our Deadly Diabetes Deception
The drug companies, in many instances, knowing release drugs that are harmful. Like professional criminals their motto is "not guilty unless caught" As the probability of being caught is very low and the cultivated public trust not to mention the profits so high they continue to gamble with our health!
Statins And Our Immune System
The pharmaceutical industry has long been attempting to develop a means by which interference with cholesterol production might be achieved farther along the biosynthetic pathway, beyond the point where vital intermediary products such as ubiquinones and dolichols originate. Thus far, their quest has failed. There is reason to believe that such biochemical maneuvering, even if successful for restoring such products may be completely inadequate to address the full spectrum of physiological consequences from statin drug use. Certainly any hormonal consequence from inadequate cholesterol availability, such as testosterone and progesterone deficiency, would remain an issue. And, as Pfreiger has so brilliantly demonstrated, impairment of synapse formation and function in our brain cells from deficient cholesterol manufacture would continue unabated, resulting in the incredible spectrum of cognitive dysfunction. Even if the clever and dedicated researchers of the pharmaceutical industry finally discover a way around these two, very substantial side effects, even greater hurdles exist from our recent evidence that statins work not by cholesterol manipulation but by some basic anti-inflammatory role.
Key to this is a substance known as nuclear factor kappa B. All statins inhibit this vital step in our immune system's ability to defend us from alien forces. Whether by being the recipient of a donor kidney or under attack by bacteria or viruses, our immune system has evolved a defensive strategy in which suppression of inflammation, triggered by nuclear factor kappa B, plays a vital role. Such stimulants to inflammation include the foreign by-products of arterial inflammation and damage. Statin drugs are known to suppress this nuclear factor kappa B (NF-kB) response and thereby open a veritable Pandora's box of unpredictable consequences.
At best, our HMG Co-A reductase inhibitors are blunt instruments and our immuno-defense system is both delicate and complex. During eons of coexistence of our complex multicellular life forms in the midst of competing, simpler unicellular organisms, there have developed many different forms of defensive and offensive strategy - all dealing with the needs of one or the other of these duelling organisms to gain a survival advantage. We have had 3.5 billion years to work out our defense systems against widely diverse challenges and NF-kB is key to all of them. If we thought the complexity of cholesterol manufacture by our body is complex, it's child's play compared to what is involved in anti-infection and immuno-modulation. Now, throw in a statin and try to predict the consequences.
NF-kB in its several forms is known to molecular biologists as a transcription factor and my bringing more than a smattering of this complex subject to your attention would risk losing you from terminal boredom, so skim the following very lightly. I warmed you this is challenging - how could a history of a 3.5 billion year war be otherwise? NF-kB resides in the cytoplasm of each cell in five different forms known to our molecular biologists as family. The offspring of these family members, known as dimers, remain held in check in the cytoplasm by certain inhibitory proteins until a release signal is received, allowing our now activated NF-kB to enter the nucleus of the cell. It is there, in the nucleus, that it completes its mission in life to stimulate genes and manufacture proteins necessary for such diverse tasks as monocyte adhesion, macrophage recruitment, smooth muscle migration and platelet activation, key elements of our defensive inflammatory response.
With so many steps involved, a good strategist could predict many different forms of assault by dedicated viruses, bacteria and other forms of single celled life, for this war is basically that of the monocellular rulers originally dominating life on our planet against we multicellular usurpers. Therefore it should come as no surprise that some of these defenders have managed to gain an advantage over us, their adversary, by inhibiting NF-kB while others succeed by enhancing NF-kB. Others manage both sides of the coin. E. coli, one of our most common infectious agents, prevents NF-kB from entering the nucleus, thereby enabling this ubiquitous organism freer access to our bladder walls and urethras. Through a similar process of checkmate, another common bacteria, Salmonella, inhibits our anti-inflammatory response sufficiently long to allow bacterial colonization of the lining of the gut, giving a decided advantage to "their" side. On the other hand, some Chlamydia organisms, warring against the urogenital systems of both men and women, have evolved a distinct advantage by enhancing our NF-kB, thereby assuring increased survival of infected cells in our urinary and reproductive systems. On a far more serious note, the very common Epstein-Barr virus causing infectious mononucleosis uses NF-kB inhibition to help destroy our protective "T "cells as part of our common teenage "mono" presentation but when it decides to go on a malignant rampage, triggering nasopharyngeal carcinoma and Burkitt's lymphoma, it does so through sustained NF-kB activation. The list goes on and on with other microorganisms and foreign antigens of all kinds, numbering thousands of variations of these basic themes.
So now let us return to statin drugs and their now well-established effect of inhibition of NF-kB. What does this really mean in our ancient struggle with disease organisms and our immune system's competence? It means while taking statins we are likely to be far more susceptible to certain common infectious agents but at the same time may be somewhat more resistive to others. In the case of the Epstein Barr virus, perhaps we will see more " mono" but, fortunately, less nasopharyngeal carcinoma and Burkitt's lymphoma. But the reality is that we do not as yet know because this new statin role of NF-kB inhibition has only just been recognized. The potential for increased risk of both infectious disease and malignancy is there, for both depend upon our immune system's competence. Tossing the statin sledgehammer into this system is perhaps quite comparable in effect to the rampages of "a bull in a China shop" and it is far too soon to tell about most malignant changes. The implications of the very recent drug company promotion of statin drugs for organ transplant recipients and as adjunctive therapy in the treatment of auto-immune diseases are sobering, indeed, for these drugs can only work in this capacity at the risk of causing mischief elsewhere. One must admire the drug companies' ability for "positive spin" on a very alarming proposition, or is it arrogance? One cannot have the one without the other. The sense of cynicism here is overwhelming to me.
Increased cancer deaths among recipients of statin drugs already are being observed. Ravnskov has reported of the recent PROSPER trial that statin therapy increased the incidence of cancer deaths, completely offsetting the slight decrease in deaths from cardiovascular disease. As Dr. Paul Roach predicted in his Weston Price Foundation presentation of May 2003, the Japan Lipid Intervention trial observed excess deaths from malignancy in their so-called statin "hyper-responder" group. Of the 12 cancer deaths reported in this group, whose cholesterols plummeted deeply with statin use, four were from gastric cancer and two were from lung cancer. Although other factors may have played a role, this heightened cancer risk may well be based on loss of immuno-resistance secondary to NF-kB inhibition.
How strange it is that a class of drugs developed solely for the purpose to interfering with the biosynthesis of cholesterol has now been shown to reduce cardiovascular risk by an anti-inflammatory role completely unrelated to cholesterol manipulation. Generally speaking this should be a welcome observation, for atherosclerosis with all of its consequences is based primarily upon inflammation within the arterial walls. Now, however, any optimism we might have had is thoroughly tempered by our growing realization that statin's effect is based upon interference with our most basic immuno defense system. The potential consequences are frightening.
Duane Graveline MD MPH
References to NF-kappaB paper follow:
1. Pfrieger F.Brain researcher discovers bright side of ill-famed molecule. Science, 9 November, 2001
2. Huang KC and others. HMG-CoA reductase inhibitors inhibit inducible nitric oxide synthase gene expression in macrophages. J Biomed Sci.10(4):396-405, 2003
3. Zelvyte I and others. Modulation of inflammatory mediators and PPARgamma and NF appaB expression by pravastatin in response to lipoproteins in human monocytes in vitro.45(2):147-54, 2002
4. Zheng Y and others. Combined deficiency of P50 and cRel in CD4+ T cells reveals an essential requirement for nuclear factor - kappa B in regulating mature T cell survival and in vivo function. J Exp Med. 197(7):861-74. 2003
5. Knight JA. Reiew: Free radicals, anti-oxidants and the immune system. Ann Clin Lab Sci. 30(2):145-58, 2000
6. Barnes PJ and Karin M. Nuclear Factor kappa B - a pivotal transcription factor in chronic inflammatory diseases. NEJM. 15:1066-71, 1997
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