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Aspirin (ASA, acetylsalicylic acid)

Aspirin is natural in that salicylic acid is widely produced by plants mainly to protect plants from microbial and fungal infestations.  As such mammals have, like with vitamins, developed positive uses for salicylic acid.  Aspirin is a modified form of salicylic acid to improve its gastric tolerance.  It is rapidly hydrolyzed in the digestive system to salicylic acid.   Moreover, as an acetate its bioactivity is not diminished.  It is distinguished from all the other NSAIDs which the American Heart Association, among others, warns that all NSAIDs but aspirin very significantly increase the risk of heart attack.  Simply put, “Take the natural aspirin rather than a weird unnatural chemical with its various serious side effects , such as naproxen and ibuprofen.”  Below you will learn of its many benefits.  A sampling of journal articles on aspirin and the other NSAIDs are to be found at http://healthfully.org/aspirin and http://healthfully.org/nsaid   

JK takes a 325 mg aspirin a day--often 2--since 1992 because it reduces risk for cancer, for which we have a lifetime risk of 50%, and it reduces the risk for Alzheimer’s disease the 4th biggest killer after heart attacks, strokes, and cancer.  It reduces the risk of heart attack by reducing blood clotting.  A heart attack and stroke (ischemic events) is a two step process:  first leaking young, immature plaque from an artery wall that partially obstructs the flow of blood.  The turbulence at the point of partial blockage initiates a blood clotting response.  With aspirin and other NSAIDs they block a clotting factor thus reducing or preventing an acute ischemic event. 

For these reasons I am willing to doubling the risk of an ulcer from 2% to 4%.  Moreover, since persistent heart burn proceeds an ulcer, I would go to the doctor and have my H. pylori eradicated with antibiotics. 

Think like a CEO of a big pharma company, the mandate is to maximize profits.  This explains their position on aspirin, and the reluctance to treat h. pylori.



 

Aspirin (ASA, acetylsalicylic acid) (7/17/16) http://healthfully.org/rc/id3.html, on aspirin http://healthfully.org/aspirin/, /nsaids

Reduces risk for cancer of Breast 39%, Colorectal 63%, Esophageal 73%, Hodgkin’s Lymphoma 60%, Ovarian 47%, Melanoma 55%, Prostate 39%, Stomach 62%, and other cancers including Bladder, Skin, Gastric & Leukemia.  Aspirin increases survival of stages I, II, & III cancers:  Breast 66%, Colon by 74%, and by extension all adenocarcinomas.  Aspirin reduces the risk of Alzheimer’s Disease 60%, and Heart Attacks 51%, and its anti-inflammatory action inhibits atherogenesis thus CVD; 350 mg or more, not low dose, see below.  Summaries of ASA on cancer protection and on atherosclerosis protection

Why doesn’t everyone know of these benefits and doctors recommend a 325 mgs of aspirin daily?   The short answer is corporatization of medicine.  The perception in the press is the opposite of the truth, a truth which was succinctly stated by Harvard Prof. Marcia Angell, MD.:  “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.  The list of benefits from taking aspirin (acetic salicylic acid) long-term is in the next section.  These benefits explain pharma’s multifaceted attack, which includes use of too low a dose (85 mg), coated aspirin which takes hours to dissolve, scare about ulcers & Reyes syndrome (bottom for rebuttals).   We have tobacco science generated by pharma.  However aspirin in its bioactive form of salicylic acid is found in plants as part for its immune function.  Given its wide distribution in plants mammals have evolved similar and other healthful uses, and they/us even biosynthesize the molecule—click on link.  Find out below why aspirin clearly should be your first choice.        

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 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, 11th 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 too low a dose for prevent of cancer, 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 50 to 80% of aspirin is bound to albumin protein, while the rest remains in active, ionized state.   From 80 to 100% is excreted in the urine, sweat, saliva, and feces.   It has now slipped to 6th, 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.  However, as 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.  As for Reyes syndrome, diagnosis was based on symptoms.  “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.  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 (other cause high carb diet).  Nearly everyone dies earlier thanks to pharma’s corporate tobacco ethics.   

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%.

Age related diseases , main cause is glycation, “of exposure to sugars”, 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 tissue) from damage by reactive chemicals produced from the metabolism of carbohydrates in the destructive process of glycation (Maillard reaction), also. 

ALZHEIMER’S & ALS reduced 60% by COX-2 inhibition--Neurology, 997; 48: 626-632.  Swedish twin matching study shows low dose and other NSAIDs don’t, and Parkinson 56%.  Note:  testosterone and estradiol also greatly reduce risk.   Chronic use of aspirin inhibits beta amyloid-aggregation [the physical sign of Alzheimer’s], at 2001.

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.  ROS are the major cause of age related degenerative diseases.   For example SA 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)

Anti-inflammatory 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.  Note, Peter Gotzsche expresses doubt of NSAIDs ability to reduce inflammation, and this is supported by measure of finger diameter. 

Atherogenesis slowed:  “strong evidence that atherosclerosis is slowed down in a dose term” by 47%, and stopped. 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.

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 of63% 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.  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. 

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.

 Heart attack deaths lowered 51% for higher dose; it prevents aspirin resistance, and.  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. 

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.

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. 

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.

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 rarer risk of hemorrhage stroke 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 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 over an hour to dissolve, thus not for prompt relief, and variable absorption rate.  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.  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 many of the plants we eat as part of their immune system, mammals evolved similar functions for salicylic acid; it is thus quite safe. 

Recommendation:  For all NSAID uses.  For minor pain & anti-inflammatory 975 mg (the old standard) to start, than as needed to 4 gm daily.  Enteric coated has delayed action and should not be used for acute pain.  For arthritis, 2.5 to grams per day (see Merck Manual 1992 and before); for protection from cancer 325 mg; for cancer treatment 1,300 mg daily. For arrhythmia risk of blood clot, 650 mg daily.  For heart burn use Tums a source of calcium--protein pump (PPI) inhibitors the worst choice.   Avoid pharma’s anticoagulants, 975 mg aspirin daily, best choice.  Atherosclerosis is caused by infection in artery walls is reduced by aspirin, thus prevention MI, stroke, and hypertension.  Prevention is through anti-inflammatory effect of 325 mg with meals.  From 92 to 95 I was prescribed 2.5 grams for chronic back pain involving muscle spasms.  A daily 15 minute abdomen strengthening routine cured this disability.  Having read that aspirin prevents colon cancer in Science News, I decided to continue taking aspirin.  Subsequent research, starting in 2004 with posting the website healthfully.org, convinced me that I was doing the right taking 325-650 mg uncoated daily for risk reductions listed above, and I don’t get heart burn, ever.      



[1] Acetylsalicylic acid (aspirin) is readily converted (hydrolyzed) in the stomach to salicylic acid, and in this form is bio-active. 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^  Non-technical summation


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 8th 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 11th Ed, 2006.  Promotes healing of osteoarthritis and is drug of choice Merck 15th 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.  Finally on dosage:  to reduce its primary use as an NSAID for pain and inflammation, 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.  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.



[1]  NSAID are None Steroidal Anti-Inflammatory Drug, this includes naproxen in Aleve, ibuprofen, Celebrex, and over 30 others.  Naproxen, for example, has been shown when taken long-term to increase the risk of heart attacks at least 50% and Celebrex 200%, yet both are widely prescribed for arthritis.  Vioxx was voluntarily removed by Merck when it was shown to increase the death rate from heart attacks by 400% in a study on the prevention of Alzheimer’s disease.  



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

 

The pharmaceutical industry is the most lucrative, the most cynical and the least ethical of all the industries," Dr. Philippe Even tells The Guardian. "It is like an octopus with tentacles that has infiltrated all the decision-making bodies:  world health organizations, government agencies, parliaments, high administrations in health and hospitals and the medical profession." Author of "The Guide to the 4,000 Useful, Useless or Dangerous Medicines" http://www.fiercepharma.com/story/official-french-report-trashes-pharma-calls-many-drugs-useless/2012-09-14

 

 

Basic fact:  4 times as many duodenum ulcers as stomach ulcer.  Helicobacter pylori is the cause of 90% of duodenum and 60% of stomach ulcer.  10-20% of adults that have chronic pylori infection will develop an ulcer.

Edit Text

Peptic ulcers:  an ulcer of the duodenum, esophagus, or stomach.  Common errors are made by doctors and nurses, and repeated by the public based on marketing science and education by the pharmaceutical industry, hereafter referred to as PhARMA.  The typical response of a physician or nurse to a patient concern over heart-burn is for them to blame aspirin (or other NSAID) when possible.  PhARMA and its thought leaders have trained physicians and nurses to blame the non-prescription drugs for this side effect of medication (please read the above link on the state of corporate medicine).  PhARMA teach that the NSAIDs anti-platelet effect through COX-1 inhibition, which reducing blood clotting, that this is the causes the, stomach lesions, bleeding, and ulcers.  More frequently they hear the simple message that aspirin causes ulcer.  But this conflicts with the underlying mechanism, and lack convincing research.”[1]   

Over 80% of peptic ulcers are caused by chronic colonization in the stomach by the Helicobacter pylori bacteria that cause chronic inflammation by colonizing under the mucus membrane which protects the stomach.  Most of the peptic ulcer arises for pylori colonization in the pyloric antrum, which is the last portion of the stomach, just prior to the pyloric sphincter at the entrance to the duodenum.[2]  See illustration above.  This resulting inflammation is called “gastritis”, which causes a defect in the regulation of gastrin.  Gastrin regulates the production of hydrochloric acid (HCl), and this plyori-induced defect causes too much acid, thus making the stomach too acidic, even when empty.  Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer.[8]  The type of ulcer depends upon which portion of the stomach the chronic infection is found:  in the pyloric antrum is more likely to lead to duodenum, and the corpus (body) portion to a body portion of the stomach (gastric ulcer).  Four times as many peptic ulcers arise in the duodenum (the first part of the small intestine just after the stomach) as in the stomach itself.”   The stomach produces hydrochloric acid (HCl); the duodenum uses enzymes to breakdown food.  The pylori bacteria alone is sufficient to cause a peptic ulcer; some drugs simply increase the risk, similar in a way to that of hot peppers and alcohol.  These drugs are caustic will irritate the stomach lining once the mucus membrane has been compromised by the pylori bacteria.  Increased risk of ulcers from the use of NSAIDs is a result of surface irritation.

 PhARMA in changing the prescription practice of doctors’ first sold doctors on the grave risks associated with aspirin as to peptic ulcers and Reyes Syndrome in the 70s.  In the 50s through the 70s aspirin was the most popular of arthritic medications.  This attack on aspirin helped them sell their palliative, patented arthritic drugs.  In addition the shift promoted their meg-block buster Plavix,[3] Warfarin and other blood thinners for those with high risk for a heart attack or venous thrombosis.  They persuaded doctors to prescribe these then patented drugs as being safer and more effective.[4]  The shift also promoted sales of their patented NSAIDS.  They also pushed through the media the over-the-counter more expensive NSAIDs with direct to consumer advertising, which has always been legal.  When Vioxx (1999) and other COX-2 inhibitors were approved the FDA, doctors already were trained not to recommend aspirin except in the low dose 82 mgs for those who would take the patented Plavix or its competitors.  By then (permitted in 1997) direct to consumer advertise created a demand for these selective COX inhibitors (the common label for this family of COX-2 inhibitor drugs).  Now all PhARMA needed to do is persuade doctors that the selective COX inhibitors were both safer and more effective.  With their control of the production of information that was quickly accomplished.  They told doctors that the selective COX-2 inhibitors since they don’t affect palliate production, they don’t increase the risk of peptic ulcers like the other non-selective NSAIDs.  As argued above, platelet inhibition does not increase the risk for dyspepsia (impaired digestion) and ulcers, but rather the corrosiveness of the drug itself.[5]  The conscientious physician thus would warn their patients about the non-selective NSAIDS causing indigestion and peptic ulcers, and then sold them on the safer and more effective selective COX-2 inhibitors such as Vioxx and Celebrex.   This ploy worked and $10’s of billions were sold of these drugs.  However, the perceived benefits over aspirin were never convincingly demonstrated as Goodman and Gilman (supra) wrote.  Moreover, they weren’t safer for all COX-2 inhibitors, but aspirin promote atherogenesis and thus heart attacks, the selective ones by far the most.  Vioxx in its 5 years before Merck took it off the market, Vioxx caused an estimated 125,000 heart attacks and 55,000 deaths.  Celebrex, which has the same affect but to a lesser degree, is still widely advertised, though the FDA advisory panel unanimously recommended that its direct-to-consumer advertising be barred.  As noted in the footnote Celebrex increases the risk o f thrombosis, hypertension, and accelerated atherogenesis. 

   

    The bottom line is that one should NOT put a strange, unnatural chemical in your body unless it resembles one that the body normally encounters and has been shown through long usage to be safe; except of course if the condition it is to treat is severe enough to merit the risk.  Opiates are a family of drugs that are extremely safe.  And long-term usage is both safe and non-addicting, unless one takes it in sufficient amounts on a daily basis to become intoxicated.  If the pain isn’t severe, grin and bear it.  Reaching for an NSAID for minor pain is based on a false perception of safety, they all increase the rate of cardiovascular disease and it consequences.  The only exception is aspirin, which protects against cardiovascular disease, MI, and reduces the risk of cancer very significantly, and promotes survival of early stages of cancer, and reduces the risk of Alzheimer’s disease.  For dyspepsia there are over-the-counter antacids such as Tums.  Even the seeming inoxious acetaminophen (Tylenol) has dire consequences.  The use of proton pump inhibitors have made the do-not take list of Worst Pill for good reasons.  The long-term risk of ulcer for aspirin users is about 4%, about twice that of non-users.   JK finds it worth the risk, and has been taking 325 mgs since 1991, when a doctor recommended 2,500 mgs per day. 



1[6]  In the leading pharmacology textbook, Goodman and Gilman the Pharmacological Basis of Therapeutics, 11th Ed. 2006, p. 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.” 

2[7]  The sphincter contracts to close off the stomach so that it doesn’t drain into the duodenum while the food is digesting in the stomach.  It opens 2-3 hours later.   This delay provides a way for distinguishing the more common duodenum ulcer from that of the stomach based upon when pain occurs, with meal or hours later.  The HCL about 0.5% causes the protein to unravel so that digestive enzymes in the duodenum can break down the long chains into amino acids for absorption.  

3[8] Plavix is the 2nd most profitable drug, after Lipitor, with world-wide sales as of 2007 of $60 billion. 

4[9] This was accomplished head-to-head testing a low dose aspirin to their patented products.   Moreover , the very unscientific (without testing) habit of doctors automatically attribute a hospital emergency from GI (gastro-intestinal) distress as being caused by the NSAID (other than the selective COX inhibitors) entails that most of such events are reported as a result of the NSAID, rather than the other medication, or combinations of medications.  Many seniors are taking 6 or more drugs, plus an assortment of over-the counter vitamins and herbs.  Moreover studies funded by PhARMA attribute all stomach irritation to the NSAIDs.  For an example of how bad it gets, 

5[10]  This was born out in a review of the evidence by Goodman and Gilman authors on the section on Celebrex  which compared the family of tNSAID (traditional NSAIDS) to the selective COX-2 inhibitors:  “None of the coxibs [selective COX-2 inhibitors] has established clinical efficacy over tNSAIDS, while celecoxib [Celebrex] failed to establish superiority over tNSAIDS in reducing gatro0intestinal adverse events.  While selective COX-2 inhibitors do not interact to prevent the anti-platelet effect of aspirin…. Current evidence does not support use of coxib as a first choice among the tNSAIDS… {because of] the risk of thrombosis, hypertension, and accelerated atherogenesis are mechanically integrated” (supra. 704).    

 

 

From Wikipedia:    

The pathophysiology of the H. pylori centers on its thwarting the stomach’s protective acid environment. “To colonize the stomach, H. pylori must survive the acidic pH of the lumen and use its flagella to burrow into the mucus to reach its niche, close to the stomach's epithelial cell layer.[23] Many bacteria can be found deep in the mucus, which is continuously secreted by mucus-secreting cells and removed on the luminal side. To avoid being carried into the lumen, H. pylori senses the pH gradient within the mucus layer by chemotaxis and swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface.[24] H. pylori is also found on the inner surface of the stomach epithelial cells and occasionally inside epithelial cells.[25] It produces adhesins which bind to membrane-associated lipids and carbohydrates and help it adhere to epithelial cells. For example, the adhesin BabA binds to the Lewis b antigen displayed on the surface of stomach epithelial cells.[26] H. pylori produces large amounts of the enzyme urease, molecules of which are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia. The ammonia is converted to ammonium by accepting a proton (H+), which neutralizes gastric acid. The survival of H. pylori in the acidic stomach is dependent on urease. The ammonia produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including proteases, vacuolating cytotoxin A (VacA), and certain phospholipases—, damages those cells.[27]

Inflammatory processes of H. pylori infections are also mediated by highly disulfide-bridged proteins. Helicobacter cysteine-rich proteins (Hcp), particularly HcpA (hp0211), triggers an immune response through the differentiation of human myeloid Thp1 monocytes intomacrophages.  In analogy to eukaryotic cytokines, they interfere with host cell functions and change the morphology of monocytes, inducing the expression of the surface marker protein CD11b, phagocytic activity, as well as cell adherence, which are indicative of monocyte differentiation into macrophages.[28] Colonization of the stomach by H. pylori results in chronic gastritis, an inflammation of the stomach lining. The severity of the inflammation is likely to underlie H. pylori-related diseases.[29] Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances.  The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization.[30] The acidity within the stomach lumen affects the colonization pattern of H. pylori, and therefore ultimately determines whether a duodenal or gastric ulcer will form.  In people producing large amounts of acid, H. pylori colonizes theantrum of the stomach to avoid the acid-secreting parietal cells located in the corpus (main body) of the stomach.[8] The inflammatory response to the bacteria induces G cells in the antrum to secrete the hormone gastrin, which travels through the bloodstream to the corpus.[31] Gastrin stimulates the parietal cells in the corpus to secrete even more acid into the stomach lumen. Chronically increased gastrin levels eventually cause the number of parietal cells to also increase, further escalating the amount of acid secreted.[32] The increased acid load damages the duodenum, and ulceration may eventually result. In contrast, gastric ulcers are often associated with normal or reduced gastric acid production, suggesting the mechanisms that protect the gastric mucosa are defective.[32] In these patients, H. pylori can also colonize the corpus of the stomach, where the acid-secreting parietal cells are located. However chronic inflammation induced by the bacteria causes further reduction of acid production and, eventually, atrophy of the stomach lining, which may lead to gastric ulcer and increases the risk for stomach cancer.[33]

About 50–70% of H. pylori strains in Western countries carry the cag pathogenicity island (cag PAI).[34] Western patients infected with strains carrying the cag PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island.[8] Following attachment of H. pylori to stomach epithelial cells, the type IV secretion system expressed by the cag PAI "injects" the inflammation-inducing agent, peptidoglycan, from their own cell wall into the epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic pattern recognition receptor (immune sensor) Nod1, which then stimulates expression of cytokines that promote inflammation.[35]

The type IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelial cells, where it disrupts thecytoskeleton, adherence to adjacent cells, intracellular signaling, cell polarity, and other cellular activities.[36] Once inside the cell, the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then allosterically activates protein tyrosine phosphatase/protooncogene Shp2.[37] Pathogenic strains of H. pylori have been shown to activate theepidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. It has also been suggested that a C-terminal region of the CagA protein (amino acids 873–1002) can regulate host cell gene transcription, independent of protein tyrosine phosphorylation.[21][22] There is a great deal of diversity between strains of H. pylori, and the strain with which one is infected is predictive of the outcome.

Two related mechanisms by which H. pylori could promote cancer are under investigation. One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a "perigenetic pathway",[38] and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins, such as adhesion proteins. H. pylori has been proposed to induce inflammation and locally high levels of TNF-α and/or interleukin 6 (IL-6). According to the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF-α, can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations intumor suppressor genes, such as genes that code for cell adhesion proteins.[39] 

 

 

 



[1]  In the leading pharmacology textbook, Goodman and Gilman the Pharmacological Basis of Therapeutics, 11th Ed. 2006, p. 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.” 

[2]  The sphincter contracts to close off the stomach so that it doesn’t drain into the duodenum while the food is digesting in the stomach.  It opens 2-3 hours later.   This delay provides a way for distinguishing the more common duodenum ulcer from that of the stomach based upon when pain occurs, with meal or hours later.  The HCL about 0.5% causes the protein to unravel so that digestive enzymes in the duodenum can break down the long chains into amino acids for absorption.  

[3] Plavix is the 2nd most profitable drug, after Lipitor, with world-wide sales as of 2007 of $60 billion. 

[4] This was accomplished head-to-head testing a low dose aspirin to their patented products.   Moreover , the very unscientific (without testing) habit of doctors automatically attribute a hospital emergency from GI (gastro-intestinal) distress as being caused by the NSAID (other than the selective COX inhibitors) entails that most of such events are reported as a result of the NSAID, rather than the other medication, or combinations of medications.  Many seniors are taking 6 or more drugs, plus an assortment of over-the counter vitamins and herbs.  Moreover studies funded by PhARMA attribute all stomach irritation to the NSAIDs.  For an example of how bad it gets, 

[5]  This was born out in a review of the evidence by Goodman and Gilman authors on the section on Celebrex  which compared the family of tNSAID (traditional NSAIDS) to the selective COX-2 inhibitors:  “None of the coxibs [selective COX-2 inhibitors] has established clinical efficacy over tNSAIDS, while celecoxib [Celebrex] failed to establish superiority over tNSAIDS in reducing gatro0intestinal adverse events.  While selective COX-2 inhibitors do not interact to prevent the anti-platelet effect of aspirin…. Current evidence does not support use of coxib as a first choice among the tNSAIDS… {because of] the risk of thrombosis, hypertension, and accelerated atherogenesis are mechanically integrated” (supra. 704).   

 

 

 

 

 

 Mechanism by which Helicobacter pylori potentiates the effect of aspirin.  Namely aspirin and other drugs are irritants to the lining of the stomach.  Within a few days the adaptive healing process kicks in, however in the presence of H. pylori, it does do so adequately.  Pylori bacteria is the cause for GI problems with drugs.

Journal of Physiology and Pharmacolog: an Official Journal of the Polish Physiological Society [1997, 48(1):3-42] http://europepmc.org/abstract/MED/9098824

 

Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H. pylori-derived gastrotoxins

Konturek PC  Department of Medicine I, University of Erlangen-Nuremberg, Germany.

 

Abstract:

Gastric mucosa is continuously exposed to various aggressive factors such as stress, ulcerogenic drugs including aspirin-like agents, gastro-toxic bacteria, particularly Helicobacter pylori (Hp) and many other exogenous and endogenous irritants. The maintenance of mucosal barrier depends upon the activation of pre-epithelial (mucus-alkaline secretion), epithelial (surface active phospholipids, mucosal cell restitution and proliferation) and post-epithelial (mucosal microcirculation) lines of mucosal defense. The mucosa exposed to aggressive factors develops acute lesions, which usually heal completely within few days, but following repeated exposures to hostile environment it adapts to survive the challenge of noxious agents. This adaptation may be of short term (adaptive cyto-protection) and follows the exposure to "mild" irritants that activate local mucosal biosynthesis of protective prostaglandins (PG) and nitric oxide (NO) and stimulate sensory nerves and mucosal cell migration and proliferation through enhanced expression of growth factors such as EGF, TGF alpha and trefoil peptides. The fact that exogenous PG, NO-donor agents, growth factors and capsaicin, stimulating sensory nerves, protect the mucosa against strong necrotizing agents (direct cyto-protection), supports the notion that endogenous PG, NO, growth factors and sensory nerves are involved in the complex process of adaptive cyto-protection. With repeated insults of ulcerogens such as stress aspirin, Hp-derived gastro-toxins, especially ammonia, a long-term adaptation develops which is mediated mainly by over expression of EGF and TGF alpha and their common receptor (EGFR) with subsequent increase of mucosal cell proliferation and enhanced healing of mucosal lesions. The failure of mucosal adaptation seems to play a pivotal role in the pathogenesis of gastric lesions and peptic ulcerations.

 

 


regions_of_stomach.jpg

Picture in TEMP-JEPG

Peptic Ulcers and causes

http://upload.wikimedia.org/wikipedia/commons/thumb/2/29/Regions_of_stomach.svg/300px-Regions_of_stomach.svg.png

Basic fact:  4 times as many duodenum ulcers as stomach ulcer.  Helicobacter pylori is the cause of 90% of duodenum and 60% of stomach ulcer.  10-20% of adults that have chronic pylori infection will develop an ulcer.

A large body of journal articles are to be found at http://healthfully.org/aspirin/  and http://healthfully.org/nsaids/

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment.