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LDL, the blood transport for cholesterol & fats

Statins a 6 Page Critical Review   6/12/2022 http://healthfully.org/rc/id6.html  

36 NEGATIVE EFFECTS:  One, Erectile dysfunction, it lowers testosterone , and  nitrous oxide thus causes erectile dysfunction (ED); a similar effect upon women for the steroids are synthesized from cholesterol.  Since both estradiol and testosterone are essential for optimal health, the lower of both promotes much more than the ischemic events they are taken to prevent.  Two, COX-2 inhibitor, just like Vioxx, which increased heart attacks (MIs) over 300%[1].  The American Heart Association warns: “accumulated evidence that non-steroidal, anti-inflammatory drugs [COX inhibitors], with the exception of aspirin; they increase  the risks for heart attack and stroke”--promote atherogenesis. Three, blocks production of Q10, which enters LDL and inhibits oxidative damage that causes atherogenesis, and.  Four, Plaque instability:  “Vulnerability of plaques to rupture and thrombosis is of greater clinical relevance than the degree of stenosis they cause” (Corti et al., 2003).  “Statins affect plaque stability in a variety of ways.  The meta-lop-proteinases degrade extra-cellular matrix components and thus “weaken the fibrous cap and destabilize the lesions” -- Goodman and Gilman pharmacology, 11^th Ed, p 950.  Rupture of plaque causes over 80% of MIs.  Statins inhibit secretion MMP-1, 3, & 9 from SMC, and microphages make plaque less stable.   Five, reduction in ATP:  Q10 is needed for the conversion of APD to ATP (adenosine-5-triphosphate), the source of energy for muscles contraction.  “ATP is often called the ‘molecular unit of currency’ of intracellular energy transfer including muscle contraction and for chemical reactions.  ATP transports chemical energy within cells for metabolism”--Wikipedia.  “ATP is essential for normal heart muscle function, metabolism of cellular components and other activities in cell life.” reduction of 40% in CoQ10 is accepted.[2]  Six, The heart muscle under stress needs more ATP, not less.  This is why pharma excludes the elderly and those with coronary heart failure (CHF) from trials.   Thus, “the mean age of ME/CFS patients dying from CHF [coronary heart failure] are 2.5 years younger than the control group.”  CHF death rate  has tripled since 1989.  In a review of statins on depletion of Q10 concludes:  “As the potency of statin drugs increases and as the target LDL cholesterol level decreases, the severity of Q10 depletion increases and heart-muscle function declines. This tragic scenario may very well be prevented by using supplemental Q10 with all HMG CoA reductase inhibitors [statins]” and, and. Thus “Lower cholesterol, poorer outcome in CHF patients.”  Pharma ignores Q10 side effect.  Seven, All Statins inhibit the rate controlling enzyme HMGCR of the mevalonate pathway.  “This pathway generates a range of other products in addition to cholesterol, including coenzyme Q10, heme-A, [dolichol], the production of dimethylallyl pyrophosphate (DMAP),  &  isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse  as terpenoid synthesis, protein prenylation and isoprenylated proteins  which have pivotal roles in cell biology and human physiology and potential relevance to benefits as well as risks of statins.  Drugs, such as the statins, stop the production of mevalonate by inhibiting HMG-CoA reductase” Wiki.  “The Mevalonate pathway is important for, cell membrane maintenance,  hormones, protein anchoring, and N-glycosylation.  It is also a part of steroid biosynthesis” Wiki.  “Dolichols are isoprenoids  synthesized from mevalonate. They are vital to the process of Glycoprotein formation in the endoplasmic reticulum of cells. In this capacity it is critical to the formation of the Glycoproteins involved in neuro-peptides, cell identification, cell messaging and Immune defense.  Reduced bioavailability of dolichols can affect every cellular process in the body” Wiki.  And this is only a partial list.  Eight, Cholesterol is essential for life.  “It is the precursor for the biosynthesis of steroid hormones, bile acids, vitamin D, and is an essential component of cell membranes for proper permeability.  Effects include pancreatic and hepatic dysfunction, ED, diabetes[3], muscle weakness and myopathy (muscle disease). The myelin is a cholesterol base coating around nerve cells[4]” (Wiki).  Nine, Cognitive, the reduction Q10 & cholesterol for the myelin sheath causes cognitive decline--especially in the elderly where it often leads to an incorrect diagnosis of Alzheimer’s disease (AD)and of neuropathy.  Ten, Causes Parkinson’s  and Alzheimer’s diseases.  These conditions are associated with low level of cholesterol—at Uffe p 56.   In addition, I view the accumulation of amyloid and tau proteins, which are toxic to the brain and found in excess in all AD patients is a result of lowered brain metabolism that diminishes the rate of the removal of those proteins.  Lower ATP thus is causative of AD.  Eleven Causes cancer a confirmation of earlier animal studies—summary of cancers, 25% increase and.  Twelve  Stimulates atherosclerosis and heart disease by blocking the vital CoQ10, heme A, vitamin K2 (the cofactor for matrix Gla-protein activation) and biosynthesis of selenium containing proteins, one of which is vital glutathione peroxidase—at 2015.  This article states that “statins stimulate atherosclerosis and heart failure”, and then provides the mechanisms.  Thirteen Causes Interstitial lung disease is similar to emphysema in that it is a progressive condition that affects alveolar epithelium and other tissues.  Of FDA reported side effects, it is 1/40^th.  Fourteen, at ten years statins doubles the rate in women, at.  Fifteen,  diabetes is 46% more common, a 5.9 year study found at  Diabetes doubles to triples the mortality rate.  The number for senior must be at least twice that given their prevalence of insulin resistance for which type-2 diabetes in an advance from of (see work of Dr. Joseph Kraft).  See appendix for how statins cause diabetes.  Women ae at much higher rate on statins.  Sixteen Polyneuropathy, damage affecting peripheral nerves, features weakness, numbness, pain, etc. is 26 times more common after 2 years on statins compared to general matched population—at.  Seventeen Side effects account for the poor compliance in the elderly (75% stop within 2 years).  Poor compliance also occurs with elite athletes (see 1^st pg.).  Eighteen “Statins inhibit the synthesis of vitamin K₂, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification.”  This accumulation of calcium is causal for atherosclerosis—one test for AS is the calcium score.  Nineteen “Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress” at 2015.  The reduction in glutathione entails increased oxidative damage, thus statins are causal for all the conditions associated with oxidative stress—quite a long list, see RAGE & diseases.  Twenty  “An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency” at 2015.  Twenty one “Statins inhibit the synthesis of vitamin K₂, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification.”  Calcification is the major causes of the stiffness of arteries in atherosclerosis. This article by 7 Japanese professors is titled Statins stimulate atherosclerosis and heart failure:  pharmacological mechanisms. Twenty-two, reduced production of heme A.  In the important respiratory protein cytochrome c oxidase, heme A plays an important role in the oxygen center.  Lowering heme, A production through the melavonate pathway has many adverse effects.  Twenty-three Adversely effects the mitochondria by lowering the level of CoQ10 which among its other functions acts as an antioxidant protecting the  membrane and mtDNA.  Twenty-four Statin administration cause deficiency in selenium which is causal for myopathy.  Twenty-five treating the wrong cause, cholesterol, entails failure to research for and develop effective treatments for CVD.  The major causes have, pathogens in the artery walls; thus statins are ineffective.  Three out of 4 major studies of secondary prevention (ALL-HAT, ASCOT, & PROSPER) failed to find life extension from statins (Table 42-78, Braunwald’s Supra, p 1085).  This consistent failure even though scientific fraud (politely called Positive bias) is their business norm.  Such negative results explain why pharma uses surrogate endpoint of lower cholesterol instead of lives saved.  This table stands in opposition to the “safe & effective” claim (p 2286), which is pharma’s mantra, a mantra supported by their marketing studies and guidelines. Junk science is the norm (p 3) on TNT trial.  Twenty-six  Primary prevention of high risk patient is of no benefit huge meta-study found, in JAMA.  Twenty-seven fails to extend life of those with familial hypercholesterolemia (those with extremely high cholesterol)[5] at.  Twenty-eight Liver functions are worse and a few cases of liver failure (rhabdomyolysis), at.  Twenty-nine, with long-term usage study (8.4 years) a 30% increase in acute kidney injury at Feb 2016.   Thirty, drug interaction with serious side effects are common, considering that over half of senior in their 6^th decade have taken statins, and seniors average age 72 average 6 drugs according to a hospital emergency admission study (polypharmacy); 36 drug interactions.  Thirty-one, both low-fat diet and statin drug treatment increase susceptibility to Alzheimer’s,” 2009 seminal.  To this I hold that the reduced production of ATP results in a reduced rate of removal of tau protein, beta amyloid, and misfolded alpha synuclein which is causal for Lewy body dementia and Parkinson’s disease.   Thirty-two, statins in blocking HMG-CoA by 40% reduce the production of beta hydroxybutyrate by that amount, a brain derived neurotropic factor (BDNF), and thus blocks a major compound which promote a healthy brain.  HMG-CoA is converted to BDNF in 2 steps.  Statins thereby promote dementia.   Thirty-three, dose increasing side effects are the norm.  A study of 50 consecutive heart patients taken off statin and given CoQ10, the report on initial visit:  (fatigue 84% to 12% at one year, myalgia 64% to 6%, dyspnea 58% to 12%, memory loss 8% to 4%, Swedish journal, 05.  Thirty-four weight gain:  Since statins through the lower of CoQ10 lowers the product of the energy molecule ATP it must lower the rate of metabolism and if all others things don’t change (such as appetite reduction from nausea) then statins must promote sedentary lifestyle through reduced rate of metabolism.  Thirty-five, Cumulative effect: many of the effects are a result of promotion of mitochondrial dysfunction and lower CoQ10, which cause a lower production of ATP; this causes the large variety of side effects known as conditions associated with the western diet (CAWD) which is driven by the lower production of ATP.  Thus, all of the long list of conditions of CAWD are increased by use of a statin.   Thirty six, Anti-inflammatory effect:  is a response to a positive-healing process, therefore reducing the response increase the virulence of pathogenic causes and slows the repair processes.  Lowering inflammation compromises the immune system.  For this reason statins effect upon prostaglandins statins like the NSAIDs doesn’t inhibit atherogenesis, an inflammatory process—see Vioxx, and. 

36 NEGATIVE EFFECTS:  One, Erectile dysfunction, it lowers testosterone , and  nitrous oxide thus causes erectile dysfunction (ED); a similar effect upon women for the steroids are synthesized from cholesterol.  Since both estradiol and testosterone are essential for optimal health, the lower of both promotes much more than the ischemic events they are taken to prevent.  Two, COX-2 inhibitor, just like Vioxx, which increased heart attacks (MIs) over 300%[1].  The American Heart Association warns: “accumulated evidence that non-steroidal, anti-inflammatory drugs [COX inhibitors], with the exception of aspirin; they increase  the risks for heart attack and stroke”--promote atherogenesis. Three, blocks production of Q10, which enters LDL and inhibits oxidative damage that causes atherogenesis, and.  Four, Plaque instability:  “Vulnerability of plaques to rupture and thrombosis is of greater clinical relevance than the degree of stenosis they cause” (Corti et al., 2003).  “Statins affect plaque stability in a variety of ways.  The meta-lop-proteinases degrade extra-cellular matrix components and thus “weaken the fibrous cap and destabilize the lesions” -- Goodman and Gilman pharmacology, 11^th Ed, p 950.  Rupture of plaque causes over 80% of MIs.  Statins inhibit secretion MMP-1, 3, & 9 from SMC, and microphages make plaque less stable.   Five, reduction in ATP:  Q10 is needed for the conversion of APD to ATP (adenosine-5-triphosphate), the source of energy for muscles contraction.  “ATP is often called the ‘molecular unit of currency’ of intracellular energy transfer including muscle contraction and for chemical reactions.  ATP transports chemical energy within cells for metabolism”--Wikipedia.  “ATP is essential for normal heart muscle function, metabolism of cellular components and other activities in cell life.” reduction of 40% in CoQ10 is accepted.[2]  Six, The heart muscle under stress needs more ATP, not less.  This is why pharma excludes the elderly and those with coronary heart failure (CHF) from trials.   Thus, “the mean age of ME/CFS patients dying from CHF [coronary heart failure] are 2.5 years younger than the control group.”  CHF death rate  has tripled since 1989.  In a review of statins on depletion of Q10 concludes:  “As the potency of statin drugs increases and as the target LDL cholesterol level decreases, the severity of Q10 depletion increases and heart-muscle function declines. This tragic scenario may very well be prevented by using supplemental Q10 with all HMG CoA reductase inhibitors [statins]” and, and. Thus “Lower cholesterol, poorer outcome in CHF patients.”  Pharma ignores Q10 side effect.  Seven, All Statins inhibit the rate controlling enzyme HMGCR of the mevalonate pathway.  “This pathway generates a range of other products in addition to cholesterol, including coenzyme Q10, heme-A, [dolichol], the production of dimethylallyl pyrophosphate (DMAP),  &  isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse  as terpenoid synthesis, protein prenylation and isoprenylated proteins  which have pivotal roles in cell biology and human physiology and potential relevance to benefits as well as risks of statins.  Drugs, such as the statins, stop the production of mevalonate by inhibiting HMG-CoA reductase” Wiki.  “The Mevalonate pathway is important for, cell membrane maintenance,  hormones, protein anchoring, and N-glycosylation.  It is also a part of steroid biosynthesis” Wiki.  “Dolichols are isoprenoids  synthesized from mevalonate. They are vital to the process of Glycoprotein formation in the endoplasmic reticulum of cells. In this capacity it is critical to the formation of the Glycoproteins involved in neuro-peptides, cell identification, cell messaging and Immune defense.  Reduced bioavailability of dolichols can affect every cellular process in the body” Wiki.  And this is only a partial list.  Eight, Cholesterol is essential for life.  “It is the precursor for the biosynthesis of steroid hormones, bile acids, vitamin D, and is an essential component of cell membranes for proper permeability.  Effects include pancreatic and hepatic dysfunction, ED, diabetes[3], muscle weakness and myopathy (muscle disease). The myelin is a cholesterol base coating around nerve cells[4]” (Wiki).  Nine, Cognitive, the reduction Q10 & cholesterol for the myelin sheath causes cognitive decline--especially in the elderly where it often leads to an incorrect diagnosis of Alzheimer’s disease (AD)and of neuropathy.  Ten, Causes Parkinson’s  and Alzheimer’s diseases.  These conditions are associated with low level of cholesterol—at Uffe p 56.   In addition, I view the accumulation of amyloid and tau proteins, which are toxic to the brain and found in excess in all AD patients is a result of lowered brain metabolism that diminishes the rate of the removal of those proteins.  Lower ATP thus is causative of AD.  Eleven Causes cancer a confirmation of earlier animal studies—summary of cancers, 25% increase and.  Twelve  Stimulates atherosclerosis and heart disease by blocking the vital CoQ10, heme A, vitamin K2 (the cofactor for matrix Gla-protein activation) and biosynthesis of selenium containing proteins, one of which is vital glutathione peroxidase—at 2015.  This article states that “statins stimulate atherosclerosis and heart failure”, and then provides the mechanisms.  Thirteen Causes Interstitial lung disease is similar to emphysema in that it is a progressive condition that affects alveolar epithelium and other tissues.  Of FDA reported side effects, it is 1/40^th.  Fourteen, at ten years statins doubles the rate in women, at.  Fifteen,  diabetes is 46% more common, a 5.9 year study found at  Diabetes doubles to triples the mortality rate.  The number for senior must be at least twice that given their prevalence of insulin resistance for which type-2 diabetes in an advance from of (see work of Dr. Joseph Kraft).  See appendix for how statins cause diabetes.  Women ae at much higher rate on statins.  Sixteen Polyneuropathy, damage affecting peripheral nerves, features weakness, numbness, pain, etc. is 26 times more common after 2 years on statins compared to general matched population—at.  Seventeen Side effects account for the poor compliance in the elderly (75% stop within 2 years).  Poor compliance also occurs with elite athletes (see 1^st pg.).  Eighteen “Statins inhibit the synthesis of vitamin K₂, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification.”  This accumulation of calcium is causal for atherosclerosis—one test for AS is the calcium score.  Nineteen “Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress” at 2015.  The reduction in glutathione entails increased oxidative damage, thus statins are causal for all the conditions associated with oxidative stress—quite a long list, see RAGE & diseases.  Twenty  “An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency” at 2015.  Twenty one “Statins inhibit the synthesis of vitamin K₂, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification.”  Calcification is the major causes of the stiffness of arteries in atherosclerosis. This article by 7 Japanese professors is titled Statins stimulate atherosclerosis and heart failure:  pharmacological mechanisms. Twenty-two, reduced production of heme A.  In the important respiratory protein cytochrome c oxidase, heme A plays an important role in the oxygen center.  Lowering heme, A production through the melavonate pathway has many adverse effects.  Twenty-three Adversely effects the mitochondria by lowering the level of CoQ10 which among its other functions acts as an antioxidant protecting the  membrane and mtDNA.  Twenty-four Statin administration cause deficiency in selenium which is causal for myopathy.  Twenty-five treating the wrong cause, cholesterol, entails failure to research for and develop effective treatments for CVD.  The major causes have, pathogens in the artery walls; thus statins are ineffective.  Three out of 4 major studies of secondary prevention (ALL-HAT, ASCOT, & PROSPER) failed to find life extension from statins (Table 42-78, Braunwald’s Supra, p 1085).  This consistent failure even though scientific fraud (politely called Positive bias) is their business norm.  Such negative results explain why pharma uses surrogate endpoint of lower cholesterol instead of lives saved.  This table stands in opposition to the “safe & effective” claim (p 2286), which is pharma’s mantra, a mantra supported by their marketing studies and guidelines. Junk science is the norm (p 3) on TNT trial.  Twenty-six  Primary prevention of high risk patient is of no benefit huge meta-study found, in JAMA.  Twenty-seven fails to extend life of those with familial hypercholesterolemia (those with extremely high cholesterol)[5] at.  Twenty-eight Liver functions are worse and a few cases of liver failure (rhabdomyolysis), at.  Twenty-nine, with long-term usage study (8.4 years) a 30% increase in acute kidney injury at Feb 2016.   Thirty, drug interaction with serious side effects are common, considering that over half of senior in their 6^th decade have taken statins, and seniors average age 72 average 6 drugs according to a hospital emergency admission study (polypharmacy); 36 drug interactions.  Thirty-one, both low-fat diet and statin drug treatment increase susceptibility to Alzheimer’s,” 2009 seminal.  To this I hold that the reduced production of ATP results in a reduced rate of removal of tau protein, beta amyloid, and misfolded alpha synuclein which is causal for Lewy body dementia and Parkinson’s disease.  Cholesterol is a signal molecule which prevents the clustering of lipids, that function is compromised by statins.  Thirty-two, statins in blocking HMG-CoA by 40% reduce the production of beta hydroxybutyrate by that amount, a brain derived neurotropic factor (BDNF), and thus blocks a major compound which promote a healthy brain.  HMG-CoA is converted to BDNF in 2 steps.  Statins thereby promote dementia.   Thirty-three, dose increasing side effects are the norm.  A study of 50 consecutive heart patients taken off statin and given CoQ10, the report on initial visit:  (fatigue 84% to 12% at one year, myalgia 64% to 6%, dyspnea 58% to 12%, memory loss 8% to 4%, Swedish journal, 05.  Thirty-four weight gain:  Since statins through the lower of CoQ10 lowers the product of the energy molecule ATP it must lower the rate of metabolism and if all others things don’t change (such as appetite reduction from nausea) then statins must promote sedentary lifestyle through reduced rate of metabolism.  Thirty-five, Cumulative effect: many of the effects are a result of promotion of mitochondrial dysfunction and lower CoQ10, which cause a lower production of ATP; this causes the large variety of side effects known as conditions associated with the western diet (CAWD) which is driven by the lower production of ATP.  Thus, all of the long list of conditions of CAWD are increased by use of a statin.   Thirty six, Anti-inflammatory effect:  is a response to a positive-healing process, therefore reducing the response increase the virulence of pathogenic causes and slows the repair processes.  Lowering inflammation compromises the immune system.  For this reason statins effect upon prostaglandins statins like the NSAIDs doesn’t inhibit atherogenesis, an inflammatory process—see Vioxx, and. 

One  POSITIVE EFFECTS:  12) Statins, like aspirin, reduce clotting and thus the risk for thrombosis.  Statins “down-regulate transcriptional activities of NF-kappa B, AP-1, and HIF-1a with coordinate reduction in expression of pro-thrombotic and inflammatory cytokines” at 2006.  But rather than promote as an anti-inflammatory drug, and thereby thus by extension aspirin, pharma pitches only lowering total cholesterol.[6]  Pharma is against aspirin because aspirin lowers significantly lowers the risk for CVD, dementia, and cancer.