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Aspirin (ASA, acetylsalicylic acid)

These numbers above are low: First, the population that is taking aspirin includes those who are taking low dose, which has been available since the 1970s as too enteric coated, and the cancer protection is near zero because of their tolerance to the low dose and poor and delayed absorption of the coated aspirin.  Second those who take aspirin are a select population whose health is poorer than those not taking aspirin; thus, to compare their risk to the general population under-estimates aspirin’s benefits.  . Moreover, the sick and elderly would have less a response to aspirin.  Many of them have arthritic pains, it is a sign of a fundamental dysfunction on a cellular level because of mitochondrial dysfunction, which puts then at higher risk for all sorts of conditions including cancer, and they are sedentary, and such a population of aspirin users are less like to take hormone replacement, exercise, eat a low sugar diet. The risks would be less if they were a healthier population to start with.  Finally, reduction depends on duration thus 10  years is better than 5.

This seems like a drug marketing hype, all those claims, but it isn’t.  High dose aspirin lowers significantly serum glucose and thereby reduces the percentage of dysfunctional mitochondria in cells and thus increases the production of the energy molecule ATP.  Every cells and tissue gradually benefit from the normal amount of ATP.  insulin resistance will diminish and rate of autophagy (healing) increase. 

So why doesn’t every-one know of these benefits above, and why don’t doctors recommend a 325 mgs of uncoated aspirin daily?   The short answer is corporatization of medicine which includes medical education and regulatory capture.  Pharma profits much more from illness than it does from creating wellness.  As Harvard Prof. Marcia Angell, MD. and former Editor-in-Chief of the NEJM:  “If we had set out to design the worst system that we could imagine, we couldn’t have imagined on as bad as we have” her video.  A chorus of professional critics confirm her dismal assessment, but you won’t hear them in corporate media. As a social animal physicians and the public have become true believers.   

The evidence for an even longer list of benefits is in the next section.  These benefits explain pharma’s multifaceted attack, which includes use of too low a dose (125 mg), coated aspirin, which takes 5-8 hours to dissolve.  Tolerance develops with low does and coated aspirin only half is absorbed because it has passed the part of the small intestines where most would be absorbed, and it takes too long for pain reduction.  The scare about ulcers & Reyes syndrome (an extremely rare condition in children) is explained below. Pharma’s assault has turned the #1 NSAID, the first recommended treatment for arthritis and moderate pain into the 7^th, as of 2012. 

Besides ignoring its benefits, no mention is made that aspirin in its bioactive form of salicylic acid is found in plants as part of their immune system—yes, plants are attacked by viruses, fungi, and bacteria, and aspirin is protective for plants and mammals.  There is no mention that we get a moderate amount of aspirin in our diet depending on amount of vegetables eaten, or that the body synthesizes aspirin for its anti-pathogen properties—all this is confirmed in a pod cast by Scientific American.  If it was used as a co-enzyme in an essential pathway it would be classified as a vitamin, but it is used in non-vital ways that reduce risk for most of the age-related conditions for those on the western high sugar diet.  The reduction in sales of aspirin is contributory to many of our illnesses, since its use has been replaced by naproxen, acetaminophen, and other NSAIDs which promote significantly an assortment of ailments, including the big one cardiovascular disease.  Aspirin clearly should be our first choice among supplements.  Supplements because it is part of our diet like vitamins, CoQ10, and minerals.  Doe spin’s modus operandi see  ria (below).    “Aspirin elevated ATP levels” at 2002, and ATP made in the mitochondria is the energy molecule that powers  the repair-& replacements.         

The recorded history of aspirin starts with the ancient Egyptians.  The Greeks used an extract of willow bark and leaves which contain the plant hormone salicylic acid.  “Salicylic acid (SA) plays a key role in the establishment of resistance to microbial pathogens in many plants” at.   (ASA is rapidly hydrolyzed in the stomach to salicylic acid, its active form.)  Hippocrates, the Greek physician, 420 BC wrote of its use to relieve extra for pain & fever.  The Romans Pliny the Elder, and later Galen added its use as skin ulcer treatment.  The drug remained thereafter in the European pharmacopeia, and became widely used to treat malaria by the 1760s.  In 1853 a German chemist modified bitter salicylic acid (SA) to the less caustic ASA by adding an acetate group, and in 1899 the German dye and drug company Bayer marketed it as aspirin. 

“For almost 100 years the salicylates [aspirin family of drugs] have retained their preeminent position” Goodman and Gilman Pharmacology, 11^th Ed, 2006, p. 692.  “It is the standard against which all rheumatoid arthritis medication should be measured” supra 690.  3.5 gram is the recommended dose--Merck Manual 1987, p. 960, and same in earlier editions.  In 1958 production peaked at 20,000 tons (3 lb. per person).  In the late 50s aspirin’s share of sales fell to the heavily-marketed newer NSAIDs.  Following the 1973 discovery that aspirin reduces the incidence of heart attacks (MIs) by reducing blood clotting (thrombi) that completes occlusion of a coronary artery when plaque is leaked.  By the 1980s it regained its number 1 position, but much of the sales was for too low a dose for prevent of cancer, MIs, CVD, etc.  “Even at 1300 mg/d, [long-term] 8% of subjects were resistant” AHA to its anticoagulant action (MI protection).  Its biological half-life is dose dependent---2-3 hours for low dose and up to 15-30 hours for large doses. About 80 to 90% of aspirin is bound (inactive) to albumin protein where it is gradually released; while the rest remains in active, ionized unbound state.   From 80 to 100% is excreted in the urine, sweat, saliva, and feces.   It has now slipped to 6^th in NSAID sales in 2010, and on my bottle are 15 lines of FDA warnings for stomach bleeding and in children Reyes syndrome.  Is the old wisdom and research false?  Or is it another example of tobacco science used to promote illnesses? 

Pharma had by late 1980s gained control of research and production of information.  Aspirin the drug of choice by your parents and grandparents was “shown” to be unsafe in published tobacco studies.  Pharma drummed into the publics and physicians’ heads that aspirin is ineffective & frequently causes stomach bleeds, ulcers, and Reyes Syndrome in children.  Capitalism places profits before people, and the pharmaceutical industry profits from illness.  This 1.2-trillion-dollar industry can do pretty much what it wants in our pro-business world.  But the older record has not been erased, just ignored.  In the 11^th Edition of Goodman and Gilman supra 690, “many clinicians favor the use of other NSAIDs perceived to have better gastrointestinal tolerability, even though this perception remains unproven by convincing clinical trials”—ASA's low rate of ulcers.  Ulcers is only one prong of pharma’s attack on a drug which is cheap and prevents illnesses.  Another approach is to change the dose.  To assure that it isn’t effective for pain they have cut the dose from 1 gram (2 tablets) to start to 325 mgs.  And by enteric coating the aspirin takes too long to be absorbed to relieve pain. And the peak serum level is one-half of the uncoated aspirin.  And they encourage through the fear of heartburn and ulcer that it be taken with food—further delaying absorption.  “Compared to an uncoated aspirin the start of absorption with food averaged 0.8 hours, the enteric start averaged 5.9 hours.  For after feeding the time for peak serum concentration was 2.7 hours, but for the enteric it was 8.9 hours” at 1987.   It is most commonly prescribed for heart attacks based on the Doctor’s Study in the early 80s using uncoated 325 mgs.  It works by inhibiting the second prong of a heart attack:  platelets form a blood clot to completely occlude a partially blocked coronary artery.  As for Reyes syndrome, diagnosis was based on symptoms, when genetic testing was introduced the number affected dropped to 2 per year.  The coated aspirin is modified in the large intestine to the less active salicylic acid.  “Aspirin irreversibly acetylates the platelet enzyme cyclo-oxygenase and in this way, interrupts the prostaglandin pathway and prevents the biosynthesis.... however, enteric-coated ASA preparations can be deacetylated in the gut [where it dissolves] and hence might lack antiplatelet activity….” at 1984.  And to prevent a future generation of users, pharma and later the FDA warned parents about Reyes syndrome in children.  Diagnosis was based upon symptoms.  However, when a test for Reyes syndrome was developed in the early 90s, and the cases dramatically dropped, but pharma and the FDA warnings were changed.   “Between 1980 and 1997, the number of reported cases of Reye’s syndrome decreased from 555 cases in 1980 to about 2 cases per year since 1994… when genetic testing for inborn errors of metabolism…” Moreover a mechanism of cause is lacking:  “in 93% of the cases a viral infection had occurred in the preceding three-week period… and no animal model of Reye’s syndrome has been developed with aspirin” Wiki 2008. This 2008 passage has since been removed by friends of pharma.   And only 55% salicylate detected, 73% viral infection, yet the FDA’s warning remains on bottles of aspirin against its usage for those under 19, plus gastro-intestinal irritation and bleeding, thus getting parents and their children onto other NSAIDs, all of which increase the risk of MIs and lack protections listed below.  The rise in heart attacks, arthritis, Alzheimer’s disease, ALS, Parkinson’s, and cancer in part results from the reduction in the use of aspirin (the main cause high carb & fructose diet).  Nearly everyone dies earlier thanks to pharma’s and food manufacturers’ corporate tobacco ethics—profits before people, tobacco ethics.  This is the business model for pharma, and my website has many more examples.  And I stand on the shoulders of others.  For a partial list of them and their efforts, go to /rg to watch them on YouTube where there is a page of over 300 lectures and documentaries with links, and also a list of their books.  At /rep  and /rmbp are some of their peer reviewed journals articles.  The only conclusion I and others have drawn is that pharma profits from illness.  And as Prof. Ben Goldacre put it in his Bad Pharma “The devil is in the details.”  Below are the details of the benefits, and the alternatives that promote illness.    

Relying on Wikipedia the list of side effects for aspirin, my parent and grandparents, relatives, neighbors were very fortunate not have conditions now attributed to aspirin, and the doctors must have had mass delusion.  Listed are heart burn, ulcers, Reyes syndrome, and AERD (aspirin exacerbated respiratory disease).   Aspirin exacerbates gout, and cause tinnitus, and skin rash.   And there is FDA warning about a high rate of allergic reaction. 

Autophagy and age related conditions (AGES): The gift that gives (to pharma) is our western high sugar diet, the fructose half of sucrose is a reactive sugar which through a process of glycation  bonds to proteins that are imported from the cytosol into the mitochondria, where the glycated amino acids undergo further reactions which damages the systems within the mitochondria including their DNA.  Mitochondria are created from imported proteins and fatty acids, thus an abnormally high amount of glycated fats and proteins results in diminished functions of the mitochondria.  Since mitochondria supplies nearly all of the energy molecule ATP from ADP and AMP, through metabolism of pyruvate and acetyl-CoA derived from glucose and fatty acids, the damage to the mitochondria (mitochondrial dysfunction) adversely affects nearly every process in the cell.  Of pathogenic significance is the delayed replacement of collagen, sensitivity to uric acid, elevated insulin (insulin resistance) and the down regulation of the cellular repair-replacement system that occur during autophagy, which are downregulated when ATP is low and insulin resistance.  Aspirin reduces the rate of glycation by reducing blood glucose, which ultimately reduces insulin resistance and thereby increasing the rate of clearance of glucose and fructose, and thereby glycation  The main cause of AGES is glycation and fatty liver causing insulin resistance from excess fructose--see AEGs.  “Aspirin has been shown to be a powerful inhibitor of post-Amadori Maillard reactions” at 2001.  This article describes how aspirin protects the ubiquitous collagen (connective tissues) from damage by reactive chemicals produced by metabolism of carbohydrates and fats and by the reactive sugar fructose by glycation (Maillard reaction), also.  This is the modus operandi (preventing glycation) is the main way that aspirin lowers the risk for so many different conditions listed below:  every system is working better because of healthier mitochondria. Healthier mitochondria through increased ATP increases autophagy.  “Aspiring triggers cardo-protective mitophagy in mice and nematodes.... induction of autophagy by salicylate” at 2018.  Autophagy is an umbrella term for the various cellular ways in which structures are repaired, or if sufficiently compromised orderly dismantled.  Under autophagy’s umbrella are mitophagy (orderly dismantling of mitochondria) and apoptosis (the orderly dismantling of cells) for their replacement.  The benefits generated through the upregulation of autophagy, like with the male and female sex hormones, is long, both hormones and aspirin improve mitochondrial functions especially its ATP production. 

All NSAIDs (but aspirin) long-term greatly increases risk of MI--American Heart association warning also in journal sources by causing cardiovascular disease through inhibition of COX-2; but only high dose aspirin protects--by 50%.

ALZHEIMER’S & ALS reduced 60% by COX-2 inhibition--Neurology, 997; 48: 626-632, ALS,  Swedish twin matching study, shows low dose and other NSAIDs don’t. “Aspirin (the quintessential acylating pharmacon) can inhibit the amyloidogenesis of superoxide dismutase (SOD1)…. therapies for diseases linked to protein self-assembly” 2015 , and by inhibiting excitatory function of glutamate, Science 1996.  Note:  testosterone and estradiol also greatly reduce risk.   Chronic use of aspirin inhibits beta amyloid-aggregation [the physical sign of Alzheimer’s], at 2001, by 2x Science 1996. “Current knowledge and clinical data indicate that aspirin can be an attractive addition to treatment regiments for neurodegenerative diseases”. 2016, and mechanism 2002.

Antioxidant effects:  Salicylic acid’s [SA, active form of aspirin] immune action is through “catalase a common enzyme found in nearly all living organisms exposed to oxygen….  It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS)… one catalase molecule can convert approximately 5 million molecules of hydrogen peroxide to water and oxygen each second… also catalyze various metabolites and toxins,” Wiki.  “SA could also protect plant and mammalian catalases against inactivation by H₂O₂ in vitro “, at.  ASA inhibits lipid peroxidation, DNA damage, NF-kapa B activation and TNF-alpha production at 1999.  ROS are the major cause of age related degenerative diseases.   For example ASA protect fibrinogen.   “In cultured endothelial cells derived from human umbilical vein, aspirin (30–300 μM) increased heme oxygenase-1 (HO-1) protein levels in a concentration-dependent fashion up to fivefold over basal levels…. Pretreatment with aspirin or bilirubin at low micro-molar concentrations protected endothelial cells [on endothelial damage and Wiki]] from hydrogen peroxide-mediated toxicity…. a novel mechanism by which aspirin prevents cellular injury under inflammatory conditions and in cardiovascular disease.” at 2003.  This effect was not demonstrated with other NSAIDs.  “The potent antioxidant property of gentisic acid [ASA metabolite] may partly account for the anti-atherogenic effects of aspirin”, at 2005.    This affects has shown to protect numerous tissues/organs such as eye lens, preventing cataracts at 1988. Aspirin protects against the reactive oxygen species produced by sugars and their metabolites (a process known as glycation).  In my own case I have inherited a gene for hemochromatosis from my father, and thus absorb a higher than normal rate of iron.  Excessive iron forms crystal that cause reactive oxygen a cause for many serious conditions.  Aspirin increases the production of ferritin which stores iron, and thus prevents the formation of iron crystal precipitates—at 1998. 

Anti-inflammatory  “Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS [acute respiratory distress syndrome]” Critical Care 2015.  The effect is “not by direct inhibition of COX like most other non-steroidal anti-inflammatory drugs  (NSAIDs) but instead by suppression of the expression of the enzyme (via a yet-unelucidated mechanism)” Wiki, thus unlike the other NSAID which increase the risk of heart attack by 50% or more, aspirin lowers the risk.  “These findings provide direct in vivo evidence for an anti-inflammatory action for both aspirin-triggered LXA₄ and LXA₄ stable analogues and their site of action in vivo, at 1987. Aspirin attenuates beta-caternin/TCF 4 signaling, at 2001.  Also inhibits IKK-beta, which prevents activation of NF-kapaB that downregulates genes involved in the inflammatory response—Nature 1998.  Note, Peter Gotzsche expresses doubt of NSAIDs ability to reduce inflammation, and the evidence in support, measurements of finger diameter is hardly science.  For other NSAIDS, I doubt there is a net benefit from partially block the immune functions of inflammation and fever.  Nature didn’t evolve these highly-preserved mechanism to reduce survival. Aspirin fine tunes these immune responses unlike the other NSAIDs, and thereby prevents the damage caused in the acute phase.  It wide availability through plant sources for plant biological functions explains its salubrious functions in mammals.  

Antimicrobial:  Given that pathogens play the major role in cardiovascular disease, safe antimicrobial agents ought to be widely researched.  The lead  starts with plants:  because of salicylic acid ability to inhibit many plant pathogens, this brother of aspirin is produced in many plants, and thus unlike other NSAIDS animals have developed uses for this commonly supplied chemical, Plant Journal 1992, and book 2000.   “Aspirin-triggered lipoxin enhances macrophage [large immune cells] phagocytosis of bacteria [engulfing bacteria] while inhibiting inflammatory cytokine production” 2011.  Inhibits growth of H. pylori, BMJ Gut, 2017, and clinical trial 2017.  “The aspirin N‐mustard agent expressed strong antibacterial activity against a penicillin‐resistant bacteria and first‐order alkylation kinetics” biotechnology 2003.  Like so much of our profits first world, the trail is thin.

Apoptosis:  is the system whereby significantly dysfunction cells are systematically dismantle for reproeessing of molecules.  The process removes precancerous cells, benign tumors, and the likes.  Aspirin through the release of cytochrome c from the mitochondria turns up apoptosis--see cancer below.   

Atherogenesis slowed:  “strong evidence that atherosclerosis is slowed down in a dose term” by 47%, stopped, also. Mechanisms: By NO endothelial cells oxidative damage, inhibits leukocyte attacks, cytokinies,  CD36, FFA & diabetes.  For papers on developing the use of aspirin for atherosclerosis and for cancer, and limited value of chemotherapy.

Autophagy, is the healing process which aspirin turns up,  I hold the main way is through reducing insulin resistance and mitochondrial dysfunction, which I develop at http://healthfully.org/rmb/ and elsewhere. Other ways of turning up autophagy is through being a fasting mimic, 2018 and 2018 full. This promotes apoptosis of cancer cells, and tissue healing.. I hold that this is down stream of its upregulation of glucose and decreased mitochondrial dysfunction. 

BREAST CANCER SURVIVAL (long), UP 67% compared to no aspirin use stages 1-3; by necrosis factor TNF, and. Mechanism: COX-2 which increases prostaglandin which correlates to metastasis and carcinogenesis, which aspirin blocks.     

CANCERS VARIOUS TISSUES RISK: reduction of “63% colon, 39% breast, 36% lung, and 39% prostate cancer. Significant risk reductions were also observed for esophageal 73%, stomach 62%, and ovarian cancer 47%” also, and.  Epidemiologic studies of malignant melanoma, Hodgkin's disease, and adult leukemia also found that NSAIDs are protective; melanoma 55%.  Other studies have shown that aspirin promotes the death of abnormal cells through the natural mechanism of apoptosis by stimulating tumor necrosis factor NF-B, by p38 & JNK, mechanism.  Long term, but low dose is insufficient.  These numbers are low, allow me to explain.  First, the population that is taking aspirin includes those who are taking low dose, which has been available since the 1980s, thus the cancer protection is near zero because of their tolerance.  Second those who take aspirin are a select population whose health is poorer than those not taking aspirin.  Many of the have arthritic pain, a sign of a fundamental dysfunction on a cellular level because of mitochondrial dysfunction, which puts that at higher risk for all sorts of conditions including cancer, and they are sedentary, and such a population of aspirin users are less like to take hormone replacement. The risks would be less if they were a healthier population to start with. Various mechanism why ASA use for cancer therapy, FULL 2011.1993 colon study.

Cognitive decline following surgery prevented with aspirin: “ Hospitalization for major surgery or critical illness often associates with cognitive decline. Inflammation and dysregulation of the innate immune system can exert broad effects in the periphery and central nervous system (CNS). . . Systemic prophylaxis with aspirin-triggered resolvin D1 (AT-RvD1: 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, as little as 100 ng dose per mouse) improved memory decline following surgery and abolished signs of synaptic dysfunction.” 2013  

Diabetes treatment of type 2 (T2D) with high dose aspirin or other salicylates has a positive effect upon obesity and diet induced insulin resistance; thus by improving the function of insulin it lowers serum glucose level through improved in glucose metabolism.  Going back over a century salicylates (aspirins) were used to treat T2D.  Noting that “rheumatic fever and diabetes rarely coexist,… an intensive 2-week course of aspirin [5 gm daily] abolished glycosuria and lowered the fasting blood sugar to normal… to moderately severe diabetics” BMJ-1953 also 2001, and review.  On low carb diet to treat T2D and treat non-alcoholic fatty liver disease and reverse Insulin resistance—see diet articles at id.14 & id 15.

Drug safer, “The prevalence of asthma, atopic eczema, and allergic rhinitis has increased over the last three decades” cause the increase use of acetaminophen replacing aspirin, at 1998,

Endothelial cells play a key role in modulating functions of the tissues they form the outer layer.  Aspirins through modulating mitochondrial functions improves endothelial cell functions, 2002.

Fibrosis of lungs and other tissues (fibrotic scarring):  Fibrosis is a condition that can affect lungs, liver brain (glia scar) heart and other tissue types.  Reduces paraquat-induced lung toxicity, 2019, risk for fibrosis in patient with NAFLD (fatty liver) 2019.and lower risk of liver fibrosis 2016, and lowers rate of progression to NASH, 2019.  “Aspirin is a cardioprotective drug with anti-cardiac fibrosis action in vivo” 2017.  “Aspirin inhibits endometrial fibrosis by suppressing TGF-beta1….” 2020.  Cystic fibrosis, 1999.  “Aspirin inhibits NF-kapa-B and protects from angiostein II induced organ damage… explains utility of high dose aspirin.” 2001

Gout  aspirin in a high does is a uricosuric drug, increases the secretion of uric acid in the urine; it thereby lowers the formation of uric acid crystals that cause gout, kidney damage, and endothelial dysfunction, which is one reason aspirin slows atherogenesis—see SCAm 1991. Also in Alexander Haig’s 1894 book on hyperuricemia, salicylates were used for treatment.  Because of the glucose and fructose lowering effect, the production of uric acid is reduced by a reduction in the IMP pathway stimulated by fructose caused by the depletion of NADP. 

Heart attack deaths lowered 51% for higher dose; it prevents aspirin resistance, and.  A heart attack is a two-step process, first immature plaque leaks and partially blocks a coronary artery, then platelets aggregate and form around the partial blockage, and totally obstruct the flow of blow.  Aspirin irreversible blocks platelet aggregation.  This is the immediate protective effect of aspirin.  For unstable angina, a 236% reduction in death, cardiac event 52% meta-study; previous MI 2 studies by 44%.  Method by artery infection.  “Reduction of stroke & death of 25% to 42% using 900 to 1300 mg aspirin daily” AHA.   Statins block aspirin.  As a powerful antioxidant ASA protect fibrinogen from oxidation a key clotting factor, thus thereby reducing the risk of/extent of a clot forming during a MI or other ischemic event, at 1998.  ASA stops atherosclerosis summary.  Enteric coated aspirin has the acetate group removed in the large intestines where it dissolves and this prevents the “deacetylated prevents antiplatelet activity, 1984. Protects endothelial cells, 2020.  

Immune system functions:  “aspirin improve immunoregulatory potential and modulates the innate and adaptive immune responses.”  Upregulates immunomodulatory relation of aspirin to different immune cells, 2012.

Metabolic syndrome is a family of conditions causal for MI that results from the high carbohydrate with sugars western diet, see CVD.  An experiment in fructose fed rats that were after 6 weeks given aspirin at an equivalent to our 975 mgs.  Aspirin reversed all of the signs of metabolic syndrome:  hypertension, promoted vascular remodeling, reverse insulin resistance, and prevention of oxidative stress which is causal for endothelial dysfunction, at 2008, 2001 for mechanism.

Mental Illness:  There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD)… new therapy for a range of neuropsychiatric disorders, FULL 2013.  See above “Alzheimer’s ALS” risk reduction by ASA. 

Mitochondria dysfunction (MTD) has multiple pathogenic effects of which probably all the risk can be reduced with regular high dose aspirin.  The main reason is that MD is caused by excess fructose on the Western diet, the conditions of affluence.  Excessive fructose glycates with proteins, amino acids and other compounds produced in the endothelium reticulum that are transported to the mitochondria.  The results of MTD are insulin resistance whose extreme form is type-2 diabetes.  By lowering serum glucose, aspirin reduces the pathogenic effects of fructose.  Fructose is metabolized in the liver after glucose.  By lowering blood level of glucose, and thus cellular level of glucose the higher dose of aspirin lowers insulin resistance significantly and thereby the degree of MD, and thus its pathogenic consequences.  This is a slow process of promoting lower blood and cellular glucose and thereby reducing the percentage of dysfunctional mitochondria.  This is a brief incomplete summary as to why aspirin has so many varied salubrious effects.  With increased ATP production in the mitochondria comes in a positive circle the increased rate of repair and replacement of dysfunctional mitochondria 2013  One example mention in this paper is  in reducing the risk of cancer, since the signaling for apoptosis of abnormal cells is initiated because of signaling by the mitochondria.  This function is affected by the state of the 100 or more mitochondria in most cell types.  This process of apoptosis prevents cells from becoming pre-malignant.  Much like a vitamin, but unlike a vitamin aspirin is not an essential cofactor in a vital process, thus it is like B4, B8, B10, B11, B13, B14, B15, myo-inositol, beta carnitine, and others other compounds that were classified as a vitamin or proposed--all failed the standard.  Aspirin MTD effect comes from lowering of blood glucose and thus glycation.  Fructose in excess is a slow acting poison.  The development of these conditions is because of mitochondrial dysfunctions with diabetics having a greater percentage of dysfunction mitochondria.  More direct evidence is the increase in fatty acid oxidation by the mitochondria and 1993, and restores ATP level.

Multiple sclerosis (MS): Aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects,” 2005. “Aspirin should slow or prevent the demyelination of neuron in MS patients by increasing the expression of cilary neurotrophic factor, “There are several advantages of aspirin over other available therapies for MS,” full 2013; and for a review of 11 different effects of aspirin on MS with links, 2015, and profoundly affect mitochondrial metabolism and energy utilization” 2012.  

Oxidative stress is reduced by aspirin through the mitochondria-lysosome axis.  “Preincubation with aspirin (3–30 μM) protected endothelial cells from hydrogen peroxide-induced toxicity and increased viability in a concentration-dependent fashion by up to 64% of control,” 1997, and much more..

Osteoarthritis (OA) a degenerative joint disease involving degradation of joints including articular cartilage  and  subchondral bone, for which aspirin promotes healing & relieves pain, and “is the drug of choice” Merck supra 973. “Aspirin can inhibit osteoclast differentiation and bone resorption activity in a dose-dependent manner, thus exerting its anti-osteoporosis effect” at 2013, also, and,  and.  ASA has positive effect on bone remodeling.

Pulmonary embolism following high-risk surgery, 6% versus 15.4% placebo--p 231, similar with 1,200 mg, and, and 3 gm.

Rheumatoid arthritis (RA) an autoimmune disease causes inflammation and joint pain.  Merck Manual 1987, p. 960, recommends a dose “from 3 to 7.5 gm, the average 4.5 gm” for RA.  Goodman & Gilman supra, aspirin is “the gold standard” for RA.”  As anti-inflammatory drug slows the auto immune attack, reduces pain, at while also lowering the risk for CDV. 

Stroke neuroprotection:  “Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects. The aim of this study was to elucidate its direct neuroprotective effects....  Aspirin inhibited OGD-induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition of the transcription factor nuclear factor-κB (which are >1 mmol/L), an effect that correlated with the inhibition caused by aspirin on glutamate release” Stroke Journal 2002,and 2002, and Science 1995, similar Neuochemistry 2008 and “Aspirin also inhibited ischaemia-induced decrease in brain ATP levels.” “The neurotoxic effects of the dopamine‐selective neurotoxin MPTP (15 mg/kg, s.c.), in mice, were totally prevented by systemic administration of salicylate”, at 2002. Neuroprotective effects of aspirin. . . useful in the management of patients with high risk of ischemic events; and promotes superior healing following a stroke at 2002, and “significant reduction in infarct volume” at Dec 2001

Longevity:  A series of experiments have shown that aspirin extends median life in C. elegans by 25%--not maximum lifespan.  Several mechanisms have been uncovered and published in numerous journal articles:  1) effect on inulin like signal through transcription factors DAF16/FOXO genes, 2) increases catalase and SOD transcripts, and 3) acetylating about 20% of mitochondrial proteins, and slightly less non-mitochondrial protein.  Median extension also was found in mice.  By using the flat worm gains from neuro and MI protection are not present—YouTube, 35 min.   

NOTES:  bleeds stomach & stroke:  the typical response of a physician or nurse to a GI bleed is to blame aspirin and ignore other medications.  The lifetime risk of an ulcer goes from 2% to 4% with a daily dose of 1000 mg.  The stomach and intestine lining are protected by a mucus membrane.  The Helicobacter pylori bacteria causes 80% of GI ulcers by boring under the mucus membrane.  This permits the stomach’s hydrochloric acid (HCl), digestive bile and drugs to irritate the lining.  However, digestive bile excreted into the duodenum is basic and neutralize hydrochloric acid and aspirin. There are four times as many ulcers in the duodenum than the stomach, thus aspirin is minor causal factor.  At 5 years a 22% increase for 325 mg aspirin (169 ulcers aspirin vs. 138 placebo). The rare hemorrhagic stroke (1/7) is offset “[net] reduction of [stroke] 25% to 42% using 900 to 1300 mg aspirin daily” AHA.  Tums is best antacid; avoid PPIs,        

Anticoagulant drugs Warfarin (Coumadin), Plavix, and other have a much higher risk of serious bleeding episodes.  Warfarin accounts for an estimated 33,000 hospital admission for hemorrhaging.  Standard treatment for arrhythmia (fibrillation) includes an anticoagulant for life, but the vast majority of cases the risk rewards don’t justify the use (the risk of bleeding increases over the years).  And there are other side effects, including large red blotches under the skin.  Journal articles down-play bleeding by counting only 2 or more pints of blood.  Except for Warfarin there is no antidote for bleeding, thus pharma’s prescription choice causes far more deaths.  Greater protection comes from aspirin the Cochrane Review, and the AHA agreed.  Aspirin in the medicinal dose of 325-975 mg is a healthier and safer choice.

For pain and inflammation:   By Pharma exaggerating the risks and ignoring benefits, physicians believe there are better alternatives for pain such as Celebrex, a blockbuster which triples MI risk—band in EU & Canada.  Pharma 30 years ago dropped the dosage to the less effective 325 mg thereby causing users to switch to heavily advertised alternatives Advil, Tylenol, and Aleve.  The once standard 1,000 mgs to start and 500 mg is dose comparable to Advil & Alive.  Studies justify the higher dose of 900-1,300 mg.  Enteric coated takes hours to dissolve, thus not for prompt relief, not for pain and 8.9 hrs. with food.  There is no advantage from adding an NSAID to an opioid analgesic, except for inflammation.         

Aspirin (salicylic acid)[1] is natural:  These benefits occur because aspirin (salicylic acid) has evolved salubrious biological functions.  Plants make salicylic acid to fight infects and so do mammals including humans—see, and.  “A ¹³C₆ benzoic acid load ingested by six volunteers led, between 8 and 16 h, to a median 33.9% labeling of urinary salicyluric acid. The overall contribution of benzoic acid (and its salts) to the turnover of circulating SA [salicylic acid] thus requires further assessment” Nov 2008.  The production of salicyluric acid is an excretion for of salicylic acid, thus the benzoic acid has been converted.  This shows a conversion of benzoic acid into the active form of salicylic acid.  Given the complex of mammals’ biological systems, like with so many other hormones and simple compounds, mammals have evolved multiple functions for salicylic acid.  Because it is found in most of the plants we eat as part of their immune system, mammals evolved similar functions for salicylic acid as it has for vitamins; it is thus quite safe.  The claim for “aspirin intolerance” is based up the development of hives within 3 hours of taking aspirin; however, given the long list of causes for hives, the belief pharma has drummed into to doctors and nurses of aspirin’s role, rather than their patented drugs, the manifestation of intolerance is grossly over reported.  Moreover, salicylic acid is common to plants, thus such reaction given long-term dietary exposure makes this claim even more suspect.   

Fat soluble form has better effects “Prior to the synthesis of new aspirin derivatives, we assessed whether generic aspirin can be incorporated in the hydrophobic core of biodegradable polymeric NPs. As we would like to target conditions such as mitochondrial dysfunctions associated with oxidative stress, impaired Ca²⁺ signaling, inflammatory processes demonstrated by brain cells during neurodegenerative processes, we selected a biodegradable poly(lactic-co-glycolic acid)-block-polyethyleneglycol (PLGA-b-PEG) polymer functionalized with a terminal triphenylphosphonium cation (TPP) with significant mitochondrial association properties.” 2016

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Aspirin:  In the 1950s, when I was growing up, aspirin was the dominant over-the-counter drug for mild pain, arthritis, anti-inflammatory, and colds.  It came in 500 mgs, and the initial dose was 2, followed by 1 every 3 hours, or as needed.  The standard daily usage for arthritic and joint pain, and chronic lower back pain was 2.5 grams per day, with 7.5 grams as the upper limit—this continued to be recommended by doctors until the 1990s.  Annual production reached a peak in the U.S. of 20,000 tons in 1958.  Nothing has changes since the 1960s as to its risk factors, and several major benefits were added including those of reduction of heart attacks, cancer prevention, and increased cancer survival, yet its sales have decline until now it is 8^th among over-the counter pain medications.  Given that the American Heart Association warns that all NSAIDs[1] but aspirin increases significantly the risk of heart attack, this is proof of their affect of pharma upon doctors and the public.  Among it significant benefits are prevention of hardening of the arteries, cancer, Alzheimer’s disease, and thrombosis especially those which result in heart attacks and strokes.  Aspirin reduces the yearly risk of the top three killers.  Because of its anti-inflammatory action, “It is the standard against which all rheumatoid arthritis medication should be measured” Goodman & Gilman 11^th Ed, 2006.  Promotes healing of osteoarthritis and is drug of choice Merck 15^th Ed. p 973.  Aspirin’s anti-inflammatory action & prevention of oxidative damage prevents hardening of the arteries, which is essentially an inflammatory process to oxidized LDL (see hardening of the arteries below).  Aspirin also promotes the death of abnormal cells by stimulating the body’s mechanism for destruction of abnormal cells (necrosis factor) including trauma damaged cells and precancerous tumors cells.  By doing so it both prevents most cancers and promotes survival   For example, with breast cancer the rate is reduced over 40% and survival of stages I, II & III increased over 60% (doesn’t affect metastatic cancers.  Pharma thus attacks the usage aspirin because it would drastically reduce the sales of nearly half their blockbusters.  Besides ignoring aspirin’s benefits, pharma has blown out of proportion its health risks.   Doctors automatically blame all major & minor bleeding episodes on aspirin, though scientific studies shown to increase risk about 4% for an ulcer over 5 years.  They fail to consider the concurrent drugs and Helicobacter pylori bacteria as causes.  Goodman and Gilman supra, comment that “many clinicians favor the use of other NSAIDs perceived to have better gastrointestinal tolerability, even though this perception remains unproven by convincing clinical trial”.  And to prevent the next generation pharma and the FDA warn about Reyes Syndrome.  Once diagnosed based on symptom with 555 cases in 1980, it dropped to two cases in 1994 with the advent of genetic testing for a metabolic syndrome.  This drop in frequency is ignored by pharma and the pharma friendly FDA, they continue to warn about Reye’s syndrome.  Finally on dosage:  pharma reduce the pill from 500 mgs to 325, and initial dose from 1 gram to 325 mg, which is too low to be effective for pain.  And to insure it being ineffective they coated the aspirin (enteric) so that it doesn’t peak level isn’t 5 hours and 8.9 hours with food. The delay entails a much lower level of absorption, at 1987.  The older journal literature shows that aspirin benefits more than justify its risks.  Effective doses are daily 325 to 650 mg for protection; 2.5 grams daily for pain reduction and arthritis and treatment of thrombosis (see anticoagulant).  Finally aspirin is natural:  it is produced both by plants and mammals as salicylic acid to fight infections.   Thus for mammals with their complex bio-systems, salicylic acids has evolved multiple functions with minimal side effects.  

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Eleven Reasons why I take aspirin, why pharma should be limited.  1) Aspirin lowers risk of Alzheimer’s disease.   2) Aspirin increases survival of stage I, II, AND III adenocarcinoma by over 60%.  3) Lowers risk of most cancers over 30% through destruction of abnormal cells, thus lowers the risk for precancerous polyps and other tumors.  4) Alternatives NSAIDs have far worse side effects than aspirin AHA warns.  Except for aspirin, all prescription and over-the-counter NSAIDs with long term usage greatly increase the risk of myocardial infarction (MI) and cardiovascular disease repeatedly warns the American Heart Association because they prolong the formation of plaque once the process starts.  In the APPROVe Study Naproxen increased 50% and Vioxx 300% heart attacks.[2] Celebrex is still on the market.  5) the second step in a myocardial infarction is the formation of a blood clot cutting of oxygen to the heart muscle, and aspirin blocks that formation by its affect upon platelets.  6) Prevents atherogenesis thus cardiovascular disease the basis for most heart attacks by reducing the inflammation response. 7) Powerful antioxidant.  8) Lowers the risk for Alzheimer’s disease, other types of dementia, and Parkinson’s disease.  9) Prevents type-2 diabetes by lowering the level of glucose in the blood, and has been used to treat t2d.  10) by lowering blood levels to glucose it reduces the risk of development of fatty liver, metabolic syndrome, and the age related conditions associated with the western diet. 11) Use of anticoagulants Warfarin, Plavix, et al to prevent venous embolism and MI are inferior to full dose aspirin and they caused thousands of major bleeding episodes.

For more on aspirin and NSAIDs go to NSAIDS and ASPIRIN:  THE BEST NSAID