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home:othertreatments:statins [02.23.2019] – [Read more] sallieqhome:othertreatments:statins [09.14.2022] (current) – external edit 127.0.0.1
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 Statins interfere with the actions of Olmesartan, as they are a very similar molecule, and compete with Olmesartan for many of Olmesartan's molecular binding sites. The actions of statins on the Nuclear Receptors are therefore competitive with Olmesartan, as they reduce or negate Olmesartan's therapeutic activities. Statins interfere with the actions of Olmesartan, as they are a very similar molecule, and compete with Olmesartan for many of Olmesartan's molecular binding sites. The actions of statins on the Nuclear Receptors are therefore competitive with Olmesartan, as they reduce or negate Olmesartan's therapeutic activities.
  
-As the 2008 ENHANCE trial illustrates, while high cholesterol is //correlated// with increased incidence of diseases, lowering cholesterol does not appear to improve human health.(({{pubmed>long:18376000}})) Indeed, there is some evidence this type of intervention does the opposite.(({{pubmed>long:14631060}}))+As the 2008 ENHANCE trial illustrates, while high cholesterol is //correlated// with increased incidence of diseases, lowering cholesterol does not appear to improve human health.(({{pmid>long:18376000}})) Indeed, there is some evidence this type of intervention does the opposite.(({{pmid>long:14631060}}))
  
  
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 ====Other cholesterol drugs==== ====Other cholesterol drugs====
 The following is a list of common non-statin cholesterol-lowering drugs: The following is a list of common non-statin cholesterol-lowering drugs:
-  * cholestyramine (Questran) – Part of another treatment protocol, cholestyramine is touted to relieve symptoms supposedly caused by the release of toxins as the Lyme spirochete is killed. However, cholestyramine is [[http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=Que1366.html&contentName=Questran&contentId=484|known to interfere]] with the action of tetracycline, an antibiotic in the same class – the tetracycline family of antibiotics – used by many of the MP antibiotics.+  * cholestyramine (Questran) – Part of another treatment protocol, cholestyramine is touted to relieve symptoms supposedly caused by the release of toxins as the Lyme spirochete is killed. However, cholestyramine is [[https://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=Que1366.html&contentName=Questran&contentId=484|known to interfere]] with the action of tetracycline, an antibiotic in the same class – the tetracycline family of antibiotics – used by many of the MP antibiotics.
   * gemfibrozil (Lopid, Gemcor)   * gemfibrozil (Lopid, Gemcor)
   * Omacor   * Omacor
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 Large numbers of patients at risk for cardiovascular disease or stroke are prescribed statins – drugs that are marketed as improving health by lowering cholesterol. There’s no question that statins can effectively lower cholesterol. But, does lowering cholesterol actually benefit patients with coronary artery disease, and more importantly, are the effects of statins on patients with heart disease even related to their ability to lower cholesterol? Large numbers of patients at risk for cardiovascular disease or stroke are prescribed statins – drugs that are marketed as improving health by lowering cholesterol. There’s no question that statins can effectively lower cholesterol. But, does lowering cholesterol actually benefit patients with coronary artery disease, and more importantly, are the effects of statins on patients with heart disease even related to their ability to lower cholesterol?
  
-<blockquote>The fact that statin treatment lowers both total and cardiovascular mortality in high-risk individuals is taken as evidence that cholesterol lowering is effective. However, statins are just as effective whether cholesterol is lowered by a small amount (as in the unsuccessful non-statin trials) or by more than 40%. In addition, statin treatment is effective whether the initial LDL-C is high or low.(({{pubmed>long:9576424}})) (({{pubmed>long:11277825}})) If high LDL-C were causal, the greatest effect should have been seen in patients with the highest LDL-C, and in patients whose LDL-C was lowered the most, but this is not the case. Lack of dose-response cannot be attributed to the knowledge that the statins have other effects on plaque stabilization, as this would not have masked the effect of cholesterol-lowering, considering the pronounced lowering that was achieved. +<blockquote>The fact that statin treatment lowers both total and cardiovascular mortality in high-risk individuals is taken as evidence that cholesterol lowering is effective. However, statins are just as effective whether cholesterol is lowered by a small amount (as in the unsuccessful non-statin trials) or by more than 40%. In addition, statin treatment is effective whether the initial LDL-C is high or low.(({{pmid>long:9576424}})) (({{pmid>long:11277825}})) If high LDL-C were causal, the greatest effect should have been seen in patients with the highest LDL-C, and in patients whose LDL-C was lowered the most, but this is not the case. Lack of dose-response cannot be attributed to the knowledge that the statins have other effects on plaque stabilization, as this would not have masked the effect of cholesterol-lowering, considering the pronounced lowering that was achieved. 
  
-//**U. Ravnskov**// (({{pubmed>long:14631060}}))</blockquote>+//**U. Ravnskov**// (({{pmid>long:14631060}}))</blockquote>
  
-Ravnskov compares two separate trials of a single statin, simvastatin: a 2002 trial (nicknamed HPS)(({{pubmed>long:12114036}}))  and a 1994 study (nicknamed 4S)(({{pubmed>long:7968073}})). The 4S research team reported a three times greater risk of coronary death in the HPS trial, even though patients' total cholesterol in the 4S trial was decreased to a much lower extent.(({{pubmed>long:14631060}}))+Ravnskov compares two separate trials of a single statin, simvastatin: a 2002 trial (nicknamed HPS)(({{pmid>long:12114036}}))  and a 1994 study (nicknamed 4S)(({{pmid>long:7968073}})). The 4S research team reported a three times greater risk of coronary death in the HPS trial, even though patients' total cholesterol in the 4S trial was decreased to a much lower extent.(({{pmid>long:14631060}}))
  
-A seminal study called the ENHANCE trial was published in 2008. The trial tested the effects of a new cholesterol-lowering medication called Zetia (which, as opposed to the statins, works by decreasing cholesterol absorption in the intestine) on patients with cardiovascular disease. It found that Vytorin, a combination pill containing both Zetia and the statin Zocor (simvastatin), proved better than the statin alone at reducing levels of cholesterol. However, ENHANCE collaborators reported that Vytorin resulted in //growth// of plaque.(({{pubmed>long:18376000}}))+A seminal study called the ENHANCE trial was published in 2008. The trial tested the effects of a new cholesterol-lowering medication called Zetia (which, as opposed to the statins, works by decreasing cholesterol absorption in the intestine) on patients with cardiovascular disease. It found that Vytorin, a combination pill containing both Zetia and the statin Zocor (simvastatin), proved better than the statin alone at reducing levels of cholesterol. However, ENHANCE collaborators reported that Vytorin resulted in //growth// of plaque.(({{pmid>long:18376000}}))
  
-All together, this evidence suggests statins' ability to (slightly) improve health outcomes is independent of their ability to lower cholesterol.(({{pubmed>long:12562541}})) +All together, this evidence suggests statins' ability to (slightly) improve health outcomes is independent of their ability to lower cholesterol.(({{pmid>long:12562541}})) 
  
  
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 <blockquote>Statins have been demonstrated to increase CYP3A expression in vitro, most likely because they are ligands to nuclear receptors (pregnane X receptor and constitutive androsterone receptor) that form heterodimers with retinoid X receptors and bind to responsive elements in the CYP3A4 and CYP3A5 promoter regions. <blockquote>Statins have been demonstrated to increase CYP3A expression in vitro, most likely because they are ligands to nuclear receptors (pregnane X receptor and constitutive androsterone receptor) that form heterodimers with retinoid X receptors and bind to responsive elements in the CYP3A4 and CYP3A5 promoter regions.
  
-//**M.A. Willrich**// (({{pubmed>long:19530969}}))+//**M.A. Willrich**// (({{pmid>long:19530969}}))
 </blockquote> </blockquote>
  
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 ===== Immunopathological effects of statins? ===== ===== Immunopathological effects of statins? =====
  
-According to the reports from the statin trials, all of which have been sponsored by the drug companies, side effects are mild and rare, but underreporting is prevalent. According to drug companies, muscular symptoms occur in less than one percent of patients taking statins, however researchers independent of drug companies have found the frequency to be 64%(({{pubmed>long:16386629}})) and 75%.(({{pubmed>long:16873939}})) In the IDEAL trial, almost 90% of participants in both groups had side effects, and in almost half of them they were recorded as serious.(({{pubmed>long:16740566}})) The following adverse effects for statins have been noted in the medical literature: +According to the reports from the statin trials, all of which have been sponsored by the drug companies, side effects are mild and rare, but underreporting is prevalent. According to drug companies, muscular symptoms occur in less than one percent of patients taking statins, however researchers independent of drug companies have found the frequency to be 64%(({{pmid>long:16386629}})) and 75%.(({{pmid>long:16873939}})) In the IDEAL trial, almost 90% of participants in both groups had side effects, and in almost half of them they were recorded as serious.(({{pmid>long:16740566}})) The following adverse effects for statins have been noted in the medical literature: 
-  * **increased incidence of lupus and pneumonia**(({{pubmed>long:11936540}})) – Note the similarity between "statin-induced lupus" and "[[home:mp:allergies|minocycline-induced lupus]]."(({{pubmed>long:17366961}}))+  * **increased incidence of lupus and pneumonia**(({{pmid>long:11936540}})) – Note the similarity between "statin-induced lupus" and "[[home:mp:allergies|minocycline-induced lupus]]."(({{pmid>long:17366961}}))
   * **dyspnea (pain while breathing)** – Those with pulmonary involvement such as sarcoidosis patients sometimes confuse their disease symptoms with the side effects of statins.   * **dyspnea (pain while breathing)** – Those with pulmonary involvement such as sarcoidosis patients sometimes confuse their disease symptoms with the side effects of statins.
-  * **muscle pain**(({{pubmed>long:12622602}})) (({{pubmed>long:15006590}})) +  * **muscle pain**(({{pmid>long:12622602}})) (({{pmid>long:15006590}})) 
-  * **renal dysfunction** — Statins appear to be able to cause proteinuria through tubular inhibition of active transport of small molecular weight proteins.(({{pubmed>long:15339975}})) (({{pubmed>long:15073451}}))  +  * **renal dysfunction** — Statins appear to be able to cause proteinuria through tubular inhibition of active transport of small molecular weight proteins.(({{pmid>long:15339975}})) (({{pmid>long:15073451}}))  
-  * **tendon complications**(({{pubmed>long:17599460}})) +  * **tendon complications**(({{pmid>long:17599460}})) 
-  * **cognitive dysfunction** – A 2008 survey of statin patients found that 75% experienced cognitive dysfunction determined to be probably or definitely related to statin therapy. Of 143 patients who reported stopping statin therapy, 90% reported improvement in cognitive problems, sometimes within days of statin discontinuation with a median time to recovery of 2.5 weeks. In some patients, a diagnosis of dementia or Alzheimer's disease reportedly was reversed. Severity of cognitive problems were clearly related to statin potency.(({{pubmed>long:19558254}}))  +  * **cognitive dysfunction** – A 2008 survey of statin patients found that 75% experienced cognitive dysfunction determined to be probably or definitely related to statin therapy. Of 143 patients who reported stopping statin therapy, 90% reported improvement in cognitive problems, sometimes within days of statin discontinuation with a median time to recovery of 2.5 weeks. In some patients, a diagnosis of dementia or Alzheimer's disease reportedly was reversed. Severity of cognitive problems were clearly related to statin potency.(({{pmid>long:19558254}}))  
-  * **fatigue** – Almost half of participants in a 2012 study reported a significant increase in fatigue while taking statins.(({{pubmed>long:22688574}}))+  * **fatigue** – Almost half of participants in a 2012 study reported a significant increase in fatigue while taking statins.(({{pmid>long:22688574}}))
      
  
-As discussed in the previous section, it may be that their effect on nuclear receptors explain how some statins increase patients' disease symptoms. Indeed, a 2009 //Pathology// paper described antimicrobial activity of atorvastatin and rosuvastatin.(({{pubmed>long:20001351}})) Some of the observed side effects of statins may be immunopathological in nature. One study reports both bactericidal and inflammatory response changes in macrophage activity from simvastatin. (({{pubmed>long:19892847}})) It is possible that statins have similar immune-activating properties to the main drug for the Marshall Protocol, olmesartan, which causes an increase in disease symptoms following bacterial death.+As discussed in the previous section, it may be that their effect on nuclear receptors explain how some statins increase patients' disease symptoms. Indeed, a 2009 //Pathology// paper described antimicrobial activity of atorvastatin and rosuvastatin.(({{pmid>long:20001351}})) Some of the observed side effects of statins may be immunopathological in nature. One study reports both bactericidal and inflammatory response changes in macrophage activity from simvastatin. (({{pmid>long:19892847}})) It is possible that statins have similar immune-activating properties to the main drug for the Marshall Protocol, olmesartan, which causes an increase in disease symptoms following bacterial death.
  
-However, olmesartan has several advantages over the statins including a [[home:protocol:olmesartan:safety|superior safety profile]],(({{pubmed>long:11361048}})) demonstrated ability to decrease plaque formation,(({{pubmed>long:19124398}})) and renoprotective properties.(({{pubmed>long:17130263}})) +However, olmesartan has several advantages over the statins including a [[home:protocol:olmesartan:safety|superior safety profile]],(({{pmid>long:11361048}})) demonstrated ability to decrease plaque formation,(({{pmid>long:19124398}})) and renoprotective properties.(({{pmid>long:17130263}})) 
  
-In any case, researchers tend not to study or discuss what may be statins' primary mechanism of action: its effect on immune function. Nor, is their an earnest exploration of how modulating immune activity against chronic microbes(({{pubmed>long:11036910}})) affects the course of human disease.+In any case, researchers tend not to study or discuss what may be statins' primary mechanism of action: its effect on immune function. Nor, is their an earnest exploration of how modulating immune activity against chronic microbes(({{pmid>long:11036910}})) affects the course of human disease.
 ===== Contraindications of statins ===== ===== Contraindications of statins =====
  
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 ===== Statins are over-prescribed ===== ===== Statins are over-prescribed =====
  
-For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial. However, 75% of patients who take statins are not in this category.(({{pubmed>long:17240267}})) +For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial. However, 75% of patients who take statins are not in this category.(({{pmid>long:17240267}})) 
  
-For patients who are healthy, there is marginal evidence that statins prevent heart attacks or strokes.(({{pubmed>long:17240267}})) One meta-analysis (which was itself compromised almost entirely of industry-funded studies) showed that in healthy patients, there was only a 0.6% reduction in mortality. In other words, physicians would need to treat between 100 and 450 patients with a statin for more than four years to prevent one death.(({{pubmed>long:19841451}})) +For patients who are healthy, there is marginal evidence that statins prevent heart attacks or strokes.(({{pmid>long:17240267}})) One meta-analysis (which was itself compromised almost entirely of industry-funded studies) showed that in healthy patients, there was only a 0.6% reduction in mortality. In other words, physicians would need to treat between 100 and 450 patients with a statin for more than four years to prevent one death.(({{pmid>long:19841451}})) 
  
 Certainly, one of the motivations to demonstrate statins' value as a preventative therapy is financial. The best-selling drug in the world is Lipitor (atorvastatin), which is manufactured by Pfizer. Certainly, one of the motivations to demonstrate statins' value as a preventative therapy is financial. The best-selling drug in the world is Lipitor (atorvastatin), which is manufactured by Pfizer.
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-//**John Abramson, M.D.,** [[http://www.boston.com/yourlife/health/blog/2007/01/statins_overpre_1.html|Harvard Medical School]]// +//**John Abramson, M.D.,** [[https://www.boston.com/yourlife/health/blog/2007/01/statins_overpre_1.html|Harvard Medical School]]// 
 </blockquote> </blockquote>
  
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 ===== Vitamin D ===== ===== Vitamin D =====
  
-A 2012 randomized, placebo-controlled trial gave 120 adults with levels of 25-D below 20 ng/mL and elevated risk for cardiovascular disease either 50,000 IU of vitamin D3 weekly for 8 weeks or placebo. The study found a significant and undesired increase in LDL cholesterol.(({{pubmed>long:22947589}}))+A 2012 randomized, placebo-controlled trial gave 120 adults with levels of 25-D below 20 ng/mL and elevated risk for cardiovascular disease either 50,000 IU of vitamin D3 weekly for 8 weeks or placebo. The study found a significant and undesired increase in LDL cholesterol.(({{pmid>long:22947589}}))
  
  
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 ===== Read more ===== ===== Read more =====
  
-  * [[http://www.fathead-movie.com/index.php/2011/01/20/bad-news-for-statins-is-good-news/|Bad News For Statins Is Good News]] – blog post explaining how evidence does not support the use of statins in patients without cardiovascular disease +  * [[https://www.fathead-movie.com/index.php/2011/01/20/bad-news-for-statins-is-good-news/|Bad News For Statins Is Good News]] – blog post explaining how evidence does not support the use of statins in patients without cardiovascular disease 
-  * [[http://www.joimr.org/JOIMR_Vol7_No1_Dec2009.pdf|Jeff Cable:Adverse Events of Statins]]+  * [[https://www.joimr.org/JOIMR_Vol7_No1_Dec2009.pdf|Jeff Cable:Adverse Events of Statins]]
  
  
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 {{tag>non-MP_therapies}} {{tag>non-MP_therapies}}
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
  
-del  broke  * [[http://www.youtube.com/watch?v=rDVf-00w5gk|The Heart of the Matter]] - excellent documentary with interviews of experienced cardiologists explaining the evidence against the cholesterol hypothesis.+del  broke  * [[https://www.youtube.com/watch?v=rDVf-00w5gk|The Heart of the Matter]] - excellent documentary with interviews of experienced cardiologists explaining the evidence against the cholesterol hypothesis.
  
  
   * Legacy content   * Legacy content
-    * http://www.marshallprotocol.com/forum32/1198.html#p84709 +    * https://www.marshallprotocol.com/forum32/1198.html#p84709 
-    * http://www.marshallprotocol.com/view_topic.php?id=1198&forum_id=32&jump_to=84711#p84711 +    * https://www.marshallprotocol.com/view_topic.php?id=1198&forum_id=32&jump_to=84711#p84711 
-    * http://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=66100#p66100 +    * https://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=66100#p66100 
-    * http://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=66100#p66100 +    * https://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=66100#p66100 
-    * http://www.marshallprotocol.com/view_topic.php?id=1078&forum_id=32&jump_to=45902#p45902+    * https://www.marshallprotocol.com/view_topic.php?id=1078&forum_id=32&jump_to=45902#p45902
  
  
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 PMID: 21075355 PMID: 21075355
  
-http://www.eurekalert.org/pub_releases/2010-11/uoc--csb111210.php+https://www.eurekalert.org/pub_releases/2010-11/uoc--csb111210.php
  
-http://news.oneindia.in/2010/11/18/cholesterollowering-statins-killbacteria.html+https://news.oneindia.in/2010/11/18/cholesterollowering-statins-killbacteria.html
 </blockquote> </blockquote>
  
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 © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
 PMID: 22432744</blockquote> PMID: 22432744</blockquote>
-===== References ======+===== References ======</nodisp> 
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