Introduction
In 1982, the Nobel Prize in Medicine was granted jointly to Sune Bergstrom, Bengt Samuelsson, and Sir John Vane, which, in essence, explained the mechanism for the analgesic effect of aspirin.
The Nobel Summary pointed out that prostaglandins and related substances constitute part of a new biological system formed from unsaturated fatty acids, primarily arachidonic acid. It further noted that the Nobel Laureates had made fundamental contributions to the elucidation of the significance of this new biological system in which aspirin was shown to block the synthesis of the prostaglandins.
“Thanks to this important discovery [of] the mode of action of aspirin, the most frequently used drug all over the world, was clarified. It also provided the prostaglandin researchers with a useful tool in their analyses of the role of these compounds in various biological processes”(1). Thus began a new chapter in the century-old saga of aspirin.
The Era of NSAID Proliferation
The finding that analgesia produced by aspirin was due to its ability to block conversion of arachidonic acid (AA) to inflammatory eicosanoids opened a goldmine for the pharmaceutical industry. To a biochemist’s ear, the words “aspirin blocks conversion” suggest that aspirin inhibits the enzyme that catalyzes the procedure. To “inhibit” means to prevent the enzyme’s action by somehow inactivating it.
Consider the fortune that could be made by a drug that competed in the same manner as aspirin in relieving pain but was not tainted by the disdain of the medical profession. Importantly, at the time, aspirin was no longer under patent protection or patentable. It was inevitable that aspirin would become the model for the class of new patentable pharmaceuticals known as non-steroidal anti-inflammatory drugs (NSAIDs) and that a massive program by the pharmaceutical industry to develop competitors for aspirin would ensue.
But the going was not easy. The cyclooxygenase enzyme, now commonly known as COX by the consuming public, was the enzyme of concern in the search for aspirin substitutes. It was an unexplored enzyme and not completely understood by the research community. One of the first findings during NSAID development was that the COX enzyme had two forms: COX-1 and COX-2.
COX-1 is the constitutive form of the cyclooxygenase enzyme, which means that it is always present and available in the body. It can be thought of as a housekeeping form of COX that attends constantly to prostaglandin activity, which, among other things, involves protection of the stomach against bleeding.
The COX-2 form of the enzyme was found to be inducible, which means it is only produced when there is a demand for it, such as an illness or trauma that requires immediate first aid treatment. The COX-2 form is the form that causes the pain associated with illness or injury.
The existence of two forms of COX complicated the task of NSAID research teams. It changed the ultimate goal of the pharmaceutical effort to a search for drugs that would inhibit only COX-2 without interfering with the ability of COX-1 to protect against stomach bleeding. The extreme difficulty of the goal is confirmed by the fact that, to date, no NSAID has met its requirement.
In the decades since 1982, many different versions of COX-inhibitors have been synthesized to add to the aspirin-NSAID group. Currently about twenty generic varieties are available, the majority of which are sold only by prescription. Of the many generic varieties that have been prepared, only four generic forms have been proven to be of adequate safety to be sold over-the-counter. They are celecoxib, diclofenac, ibuprofen, and naproxen. Only two, ibuprofen and naproxen, are widely available under numerous brand names as over-the-counter painkillers.
Despite the tremendous investment in time and money in NSAID research through the decades, clinical experience has shown that no NSAID has been found that is more effective or safer to use than aspirin.(2) Further, a few NSAIDs have been recalled because of unacceptable adverse effects. Interestingly, the excellent safety record of aspirin has done nothing to improve the acceptance of aspirin by the medical community. The decades have rolled by quietly with family and emergency room physicians routinely rolling their eyes when the word “aspirin” is mentioned.
But then, on a quiet July morning in 2015, the US Food and Drug Administration (FDA) notified the medical community:
FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes.(3)
Aspirin was excluded from the warning with the exception of the statement that certain NSAIDs could undo aspirin’s cardioprotective effect:
“Some NSAIDs, including those in OTC products such as ibuprofen and naproxen, can interfere with the antiplatelet action of low dose aspirin used for cardio-protection by blocking aspirin’s irreversible COX-1 inhibition.(3)
WHAT HAPPENED? Nothing more happened than USFDA finally acknowledging that NSAIDs cannot serve as a replacement for aspirin; something scientists and students of lipidomics have known for more than ten years.
Aspirin Does Not “Inhibit” Cyclooxygenase
The fact that aspirin and the non-aspirin NSAIDS exerted their analgesic effects by different means was not recognized until about a decade ago when Serhan and co-investigators discovered the biochemical pathway by which aspirin worked.(4) By that time, the pharmaceutical industry had already spent a fortune producing a host of NSAIDs, all of which actually accomplished the original goal of producing analgesics by inhibiting the COX enzymes.
Unfortunately for the pharmaceutical industry, it was later discovered that aspirin did not inhibit COX enzymes in order to prevent them from metabolizing arachidonic acid to pain-producing inflammatory eicosanoids – as they had assumed. Serhan and colleagues discovered that aspirin did not inhibit the COX enzymes but rather modified their structures by acetylating them.(4) Aspirin thus prevents conversion of arachidonic acid to pain-producing inflammatory eicosanoids by changing the products made from arachidonic acid rather than by inhibiting the COX enzymes.
This elegant but complicated mechanism responsible for the remarkable phenomenon of changing inflammatory arachidonic acid into anti-inflammatory eicosanoid end products is described in the next section. It helps explain why “no NSAID has been found that is more effective or safer to use than aspirin.”(2)
The Biochemistry and Benefits of Aspirin
The cyclooxygenase enzymes occur in two isoforms, COX-1 and COX-2. They are similar in many, but not all respects. Each has two catalytic sites. The first active site converts arachidonic acid to a prostaglandin called PGG-2. The second active site changes PGG-2 to prostaglandin PGH-2. PGH-2, is further processed by specific isomerases that generate three eicosanoid groups; prostaglandins, thromboxanes, and prostacyclins.
COX-1 is the smaller of the two enzymes in both size and eicosanoid production capacity. COX-1 can process only arachidonic acid. It exists primarily in what is called the constitutive form. This means COX-1 is constantly present and active in most tissues. COX-1 has been called the housekeeping enzyme because it does its work by continually releasing small amounts of eicosanoids as required to regulate normal cell activity.(5)
The prostacyclins biosynthesized by COX-1 are generally protective. For example, they are antithrombotic (prevent clotting) when released in the endothelium, the layer of cells that line the inside of blood vessels, the heart, and some other closed cavities. They are cytoprotective when released by the gastric mucosa, the thin lining of the stomach that secretes a protective slimy substance called mucin.
COX-2 exists primarily in inducible form. This means that COX-2 is not detectable in most healthy, resting cells. COX-2 is induced and made active by increased levels of its substrate arachidonic acid and by inflammatory stimuli, such as cytokines and trauma. Cytokines are a group of biochemicals that trigger inflammation by recruiting other eicosanoids and immune cells to fight infectious organisms and foreign bodies including cancer cells. COX-2 can process a wider range of fatty acids than COX-1, including arachidonic acid, dihomo gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), and other lipids.(6)
When COX enzymes are acetylated by aspirin, they trigger the biosynthesis of lipid mediators inside the body that are biochemically similar and slightly more potent than the naturally-formed lipid mediators known as lipoxins, resolvins, protectins, and maresins. In brief, aspirin “jump-starts” the endogenous (within the body) pathways of resolution and healing by triggering the biosynthesis of pro-resolving lipid mediators.(7)
Biochemically, aspirin works by acetylating and blocking both of the two active catalytic sites in the COX-1 enzyme and blocking one of the two active catalytic sites in the COX-2 enzyme. COX-1, when disabled by aspirin, benefits individuals with cardiovascular diseases because the COX-1 enzyme can no longer produce anything, including thromboxane, and other inflammatory eicosanoids.
The single site that remains active on the acetylated COX-2 enzyme causes COX-2 to produce the prostaglandin 15R-HETE from arachidonic acid instead of the usual inflammatory PGE-2 series prostaglandins, thromboxanes, and prostacyclins. This 15R-HETE is immediately transformed by the enzyme 15-LOX-1 to 15-epi-lipoxin A4, also called ATLXA4 (aspirin-triggered lipoxin A4). Aspirin literally forces the COX-2 enzyme to produce anti-inflammatory eicosanoids from arachidonic acid, which normally is a major source of proinflammatory compounds.
The naturally-formed lipid mediators that aspirin copies in aspirin-triggered form (mentioned above) are chemically the same except that the former are synthesized from 15S-HETE rather than 15R-HETE, the stereochemistry of which is slightly different. The difference is that an alcohol moiety (OH) is connected to carbon number 15 at an unusual angle in the aspirin-triggered 15R-HETE. This dissimilarity does not materially change the effectiveness of the ATLXs except that the ATLXs remain biologically active in the human body for a longer time and are more potent than those naturally formed.(8)
A very important benefit of aspirin is the fact that arachidonic acid is disposed of when it is converted the prostaglandin 15R-HETE; arachidonic acid is no longer available as a substrate for inflammatory eicosanoids. This is an important difference between aspirin and NSAIDS in their interaction with the COX-2 enzyme. NSAIDS do not eliminate arachidonic acid but merely prevent it from being metabolized by the COX enzymes to inflammatory, pain producing eicosanoids. This has positive, immediate pain-relieving effects; however, the unused arachidonic acid is diverted to the 5-lipoxygenase enzyme where it is converted to inflammatory leukotrienes that do damage elsewhere in the body. Hence, NSAIDs have the potential for adverse effects not seen with aspirin.
Another benefit of aspirin relates to the fact that although COX-2 is not normally expressed (not active) in the body, it is constitutive (always expressed) in blood vessels due to the fluid motion of blood flow. During chronic inflammation, this active COX-2 within the vascular system is constantly converting arachidonic acid to inflammatory PGE-2 series prostaglandins and thromboxanes. This is an important cause of cardiovascular diseases.
On the contrary, when COX-2 is acetylated by aspirin, this damage cannot occur because acetylated COX-2 transforms arachidonic acid to 15R-HETE that is further converted within the vascular system to pro-resolving ATLXs. The statement in the FDA notice confirms that NSAIDs can interfere with aspirin used for cardio-protection by blocking aspirin’s irreversible COX-1 inhibition.(3)
Biochemical Lesson: Aspirin alone without the long chain essential fatty acids, will not produce maximum health benefits. Dietary arachidonic acid is usually ample in the modern American diet, but dietary supplementation with EPA and docosahexaenoic acid (DHA), the principal essential omega-3 fatty acids in fish, cod liver, krill oils, and animal fats, in a low-carbohydrate or ketogenic diet are required for aspirin to do its work.
Aspirin is Not Just an Analgesic Anymore
Aspirin is a unique medication. There is no other drug known that can do what aspirin does. As important as aspirin is in its fundamental role in modifying inflammatory eicosanoid pathways, perhaps of even greater consequence for the health and well being of present and future generations are the more recent discoveries of the hitherto unsuspected role of aspirin in resolution (the healing process) and the unanticipated existence of whole new classes of aspirin-triggered anti-inflammatory eicosanoids and docosanoids, also termed lipid mediators, that have been uncovered by the research into aspirin’s mechanism of action.(9)
“Inflammation is now widely appreciated in the pathogenesis of many human diseases. These extend from the well-known inflammatory diseases such as arthritis and periodontal disease to those not previously linked to aberrant inflammation that today include diseases affecting many individuals such as cancer, cardiovascular diseases, asthma, and Alzheimer’s disease”.(4)
References
- http://www.nobelprize.org/
nobel_prizes/medicine/ laureates/1982/press.html Accessed July 03, 2015. - Metcalf E. Aspirin: The Miracle Drug. New York, NY: Avery: a member of the Penguin Group, 2005.
- http://www.fda.gov/downloads/
Drugs/DrugSafety/UCM453941.pdf Accessed July 03, 2015. - Serhan CN. Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammatory and resolution. Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2005; 73 141-162.
- Vane JR, Botting RM. Mechanism of action of anti-inflammatory drugs. In: Szczeklik A, Gryglewski, RJ, Vane JR, eds. Eicosanoids, Aspirin, and Asthma. New York, NY: Marcel Dekker, Inc., 1998.
- Christie WW. Eicosanoids and Related Compounds, Lipid Library. http://lipidlibrary.aocs.org/
Lipids/eicintro/index.htm Accessed July 03, 2015. - Serhan CN. Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation. American Journal of Pathology, 2010; 177(4) : 1576-1591.
- Serhan CN, et al. Anti-inflammatory and pro-resolving lipid mediators. Annual Review of Pathology. 2008; 3: 279-312.
- Ottoboni A, Ottoboni F. The Modern Nutritional Diseases and How to Prevent Them,Second Ed. Fernley, NV: Vincente Books, 2013.
Thank you for the informative post. Aspirin has always concerned me for its potential to interfere with clotting. I do a lot of outdoor athletic activities, and I have (hereditary) high-blood pressure, so I’m more concerned about the possibility of uncontrolled bleeding after an injury, or a popped vessel in my brain that won’t clot, than I am about heart disease. I’ve also read that low dose aspirin and vitamin E taken together can doubly inhibit clotting and they should not be taken together. So I’ve decided for myself to take vitamin E (450 IU daily) rather than aspirin. Your blog post about the benefits of aspirin has me wondering if I should reconsider. Any thoughts about my particular concerns and situation?
Hi Allen,
Thank you for your kind words. We are not physicians, so we do not give advice on aspirin dosage, but we can answer questions about aspirin biochemistry and effects.
About aspirin versus vitamin E, if one must choose between them, it must be remembered that vitamin E cannot substitute for aspirin. It cannot do what aspirin does. Therefore, if one wants the benefits of aspirin, aspirin would be the choice.
Nice, interesting post…Al-Fred.
I (similar to ‘Ellen’) find these waters a bit murky. And in her case I would have imagined that she would be a contender for compulsory protection from TIA’s with daily 100mg asprin.
Which brings me to question.
(1) What ‘genius’ decided that 1/3rd of an aspirin is the ‘safe and effective dose’. I remember in the 1950’s/60’s, it was not uncommon for people to consume roughly 1,800mg daily for headaches/pain.
(2) On the ‘Poison is in the dose’. Is it time to re-visit the optimum dose. My understanding was that it was based on tolerance regarding stomach sensitivity/bleeding. It could be a case for ‘more is better’….depending on risk.
(3) Omega 3…the synergistic effect of EPA and DHA, combined with aspirin. Do they need to be taken together, or many hours apart?
(4) Antiflammatory action…winner, winner.
michael
Hi Michael, good to hear from you. Hope all is going well.
1. We never thought to wonder about whom the genius was who chose the dose for “baby aspirin.” You have to admit that 81.25 mg was a brilliant pick. It made it possible to easily divide an adult aspirin (325 mg) by four to yield four really unintimidating doses. Fortunately, clinical experience and statistics showed that 81.25 mg worked – but could a larger dose have worked better? Probably.
You are right. People once consumed aspirin as needed with no worry before NSAIDs became available. Which brings us to your question of optimum dose.
2. We also never considered what an “optimum” dose of aspirin might be. Toxicologists make lots of chart from the massive amounts of data they collect. Graphs of dose versus effect show a continuum of effect from zero dose to the maximum dose in the study. Optimum dose is taken from the range of doses that show no adverse effect.
Actually, aspirin-induced stomach bleeding is not a common event, so it would not be practical to use it to determine a safe dose. We do not know the criterion used for the label recommendation of maximum daily dose. It might be the highest analgesic dose below the amount that can cause ringing in the ears (the most subtle untoward effect of excess aspirin).
3.) There is no specific information on this question. It can be assumed that an aspirin or two every day would provide a constant low level of circulating aspirin ready to trigger lipid mediators. To be on the safe side, a baby aspirin taken with each dose of fish oil could assure a supply of aspirin at the right time.
Hope the above is helpful.
Your response is peculiar because the bleeding incidence HAS been studied, in depth, and it is QUITE common. It’s uncommon that it results in hospitalization, true, but a failure to discontinue aspirin therapy after a bleed begins will eventually get you in the hospital.
Aspirin-induced bleeding is quite common. Most people stop the aspirin when they have painful stomach symptoms first, but some are asymptomatic until they begin to bleed. A “baby aspirin” dosage is recommended based on typical tolerance. A 325-mg dose is fine and likely preferable if you tolerate the “baby aspirin” dose well, but if you get strong symptoms, you should return to the lighter dose.
However the 82.5mg (or more often 81mg) figure was arrived at, it’s close to the same figure used internationally in aspirin studies (80mg).
I cannot take aspirin therapy even at 82.5mg because I am too sensitive to it. My stomach begins to develop ulcers within two weeks, and my body starts bruising everywhere at the slightest touch–a worrying state with regards to the possibility of a bleeding stroke.
What’s up for debate, though, is whether aspirin is so protective that, for people with serious cardiovascualr disease, it’s better to treat the side-effects of aspirin than it is to discontinue the aspirin.
Hi Mimi,
We do not know your professional background, but it is a common belief among physicians we know that aspirin poses a serious risk for stomach bleeding. A search of the medial literature does not support such a conclusion; it is not “quite common.” so we can only repeat what we said below to Nancy, “although aspirin-induced bleeding may be a major event when it occurs, the population affected is very small.”
However, we are very sorry to hear of your personal difficulties with aspirin therapy. We cannot tell from you comment whether your major problem with aspirin is stomach ulcers and/or bleeding. Have you been tested for H. pylori? Coincidentally, a headline in todays’ Daily Mail (http://www.dailymail.co.uk/health/article-2097418/Aspirin-blame-stomach-bleeding–thats-bug-say-scientists.html/) says “Aspirin ‘not to blame’ for stomach bleeding – that’s due to a bug, say scientists.”
The article says “In a study by Nottingham University, 60 per cent of patients who suffered internal bleeding while taking low-dose aspirin tested positive for the bacterium (H.pylori is detected using a breath test). As the researchers explained: ‘Our hypothesis is that H.pylori causes the ulcer, and aspirin, by thinning the blood, makes it bleed.”
We send sincerest good wishes that you find a remedy for your stomach ulcer problems.
Is aspirin worse/better/same as far as gastric bleeding is concerned? I haven’t had any luck trying to figure that out.
Hi Nancy,
You are not alone in your concern about aspirin and stomach bleeding. It is a worry of just about every aspirin-user who has had to visit an emergency room or his family doctor. The warnings against aspirin use are difficult to ignore. As toxicologists/biochemists we have been very interested in the magnitude of this problem.
A search of the medical literature for cases of aspirin-induced medical problems related to aspirin’s anticoagulant effect is pretty nonproductive. Since the advent of NSAIDs, the few cases and reviews reported either do not include aspirin or do not separate aspirin data from NSAID data. We conclude that although aspirin-induced bleeding may be a major event when it occurs, the population affected is very small.
So our answer, Nancy, would be that aspirin-induced stomach bleeding is no different now that it was a hundred years ago.
On the subject of ‘Fish Oil’ , (not accounting for DHA and EPA amounts) I have seen extraordinary dosages ranging from 1 gram to 60 grams per day. This obviously needs to be managed/tailor made by a physician who knows what they are doing in regards to medication and situation, to guess at optimum and safe.
It becomes more confusing when highly respected Cardiologists like Eric Topol, “implores (yes! He actually said this) people not to consume fish oil”……..go figure.
Hello again, Michael,
Fish oil and its components EPA and DHA are foods and should be classified as such rather than as drugs. We would guess that most physicians would prefer not to venture into the realm of nutrition in dealing with patients.
It has been estimated that the omega-3 deficit in the current American diet is about 8 grams a day, which is the equivalent of about 7 teaspoons of liquid fish oil or about 28 capsules. If a dose of 60 grams of DHA/EPA were recommended, we are sure it would be given in divided doses. The volume of fish oil containing 60 grams DHA/EPA would be equivalent to about a cup; (8 oz) (2 tbsp/ounce) (3.6 grams/ tablespoon) = 57.6 grams of fish oil. What a stomach ache!
Do not worry, Michael. There are no known adverse effects from diets containing large amounts of fish oil. DHA is a requirement for the remarkable self-healing process that humans possess. The really wonderful thing is that we do not have to know how or why it is so for it to be so.
Enlightening post!
Hi Raphael,
Many thank you’s for your kind comment. We appreciate it very much.
Another terrific article!
My recent interest is Vitamin K2, specifically its potential role in avoiding vascular calcification and osteoporosis. Regular use of Vitamin K antagonists (like warfarin) have the potential to increase vascular calcification by interfering with proper K2 function, even though the target is really K1 coagulation.
I’m not clear how aspirin fits in here. Does its regular use affect Vitamin K function, for instance, inhibit carboxylation of Matrix Gla Protein? If so, its value in cardiac care appears conflicted.
You have me eating much better. My latest bloodwork was outstanding, thanks! I’d rather control inflammation as much as I can through diet and exercise, and so far I seem to have the flexibility to do that.
Hi Katherine,
Many thanks for sharing your good news with us. You are to be congratulated on having the wisdom and dedication to follow proper nutrition for your body, which we call the Temple of the Mind. It is the only way to prevent inflammation and assure self-healing. Your comment tells that the joys of feeling good are well worth the effort.
As you indicate, K1 is involved with the body’s blood coagulation system and K2 with prevention of tissue deposition of calcium. Normally, aspirin and vitamin K work well together (albeit in different steps of the process) to keep blood coagulation time in proper physiological range. However, we do not know of any biochemical reason to believe that aspirin would interfere with tissue deposition of calcium. But because the benefits of K2 are your concern, you might check with your physician on this latter point.
Although animals can make K2 from K1, it appears that K2 has to be furnished preformed for the human. The major sources of K2 are fermented food such as natto and sauerkraut. But K2 is not alone in preventing tissue deposition of calcium.
A great deal of attention is given theses days to encouraging adequate intake of calcium; however, the deposition of calcium in tissues, particularly vascular tissues, is a matter to which insufficient attention is given. In addition to K2, magnesium is another vital micronutrient that is also known as a “calcium tissue blocker.” Daily magnesium intake should equal from at least 50 percent to 100 percent of the daily calcium intake.
Keep up the good work.
Thank you for the response! I do take a magnesium supplement, at half the dosage of my calcium supplement. I’m chuckling at the thought that my physician might have a clue about something as important but undiscussed as K2.
Yo! Alice and Fred
Thank you for the reply regarding ‘Aspirin/Fish oil’.
Although I am 66, I have adopted you both as my grandparents/mentors…..I never new any of my blood relatives apart from mum/dad/brother.
As you know! I smoke and drink like a witch….post CABG. And have weaned myself of moronically watching the News and Health blogs (with very few exceptions) it’s all basically meaningless with no simple/basic directives.
You said “The really wonderful thing is that we do not have to know how or why it is so for it to be so.” ….I enquired from many, the mechanism of the deleterious effects from smoking. And actually nobody had an answer, although intuitively it appears that inhaling smoke is carcinogenic and (indisputably) is a cause of COPD. Although the correlation to the ‘heart muscle’ cannot be defined.
Michael, we are honored,
We have no grandchildren, but if we did, your age is a perfect fit. Welcome to the fold, and thank you.
Now, as part of the family, you must know we disapprove of smoking and of drinking to excess. But because you are now a grown man and responsible for your own life, we will refrain from lecturing you. But we will encourage you to do all you can to help your body counter the effects of your bad habits. We want you to follow the diet that has been shown to enable the body to heal itself. It requires low or no carbohydrates, a balanced omega-6: omega-3 ratio, and adequate vitamins and minerals. Now, behave yourself, or we may have to disown you.
Seriously, about smoking, we thank you for giving us the opportunity to talk about lung cancer (here comes the promised-not-to-be lecture). As you will see, lung cancer is not inevitable no matter how many years you have smoked. Just because you’ve tried and failed multiple times doesn’t mean you can’t do it. We both know from personal experience it is very difficult, but oh so worthwhile!
Here is a brief, simplified description of lung cancer: The airways inside the lungs are lined with columnar cells. These cells have cilia, which are like little tails that project into the airway. Columnar cells are piled up like bricks with the result that all the cilia inside of a healthy airway make it fuzzy looking. These cilia work together and constantly sweep the airways upward. They deposit any foreign junk up at the top of the airway and dump it into the throat where it is either swallowed or spit out. They constantly clean the lungs.
These columnar cells do not become cancerous. What happens is that smoke irritates the cilia of the cells to the point where columnar cells are slowly replaced by squamous cells. Squamous cells have no cilia; they are regular skin cells. So, smokers eventually develop airways that have no way of cleaning themselves, hence coughing is the symptom.
Squamous cells lining the airways are susceptible to damage by carcinogens in smoke, and with time squamous cells can become cancerous. The carcinogens are benzpyrenes, which are found in all kinds of smoke. For example if cigarettes were made out of lettuce instead of tobacco, the smoke could be cancer-causing.
The very important part of this story is that if a smoker stops smoking before the squamous cells have grown too far along the path to cancer, the squamous cells will die off and be replaced by columnar cells, perhaps in just a matter of weeks or months; the airways will recover normal columnar cell linings.
So, dear grandson, you are now in a long-lived family; prepare for the next 30 years.
Yo! Ma and Pa
Thank you for your acceptance with approving of one of the ‘great unwashed’. BTW: my birthday is 18th June …and I don’t need any presents. I am into minimalism now and all I require is
(1) peace of mind
(2) a partner who I love and share the ups and downs
(3) sufficient clean fresh food and water
(4) reasonable health with no debilitating pain…having my gallbladder extracted in 4 days time, and wishing it is the cause of my right sided back pain that has debilitated me for 15-20 years. What is of interest is that if the radiating pain is gallbladder related? Why has is taken so long to diagnose (7-8 GP’s and 4 specialists, not to mention chiropractors and physio’s). Cart before horse….but will let you know. Although my intuitive perceptions have a good strike rate. You can’t help but feel for the zillions who go undiagnosed with there problems for a big chunk of their lives. Which brings us to the bedside manners of most physicians (you would not feed half of them). I do understand the stress and acquired apathy that many patients create for this scenario upon the doctor.
(5) Faith/Religion…perhaps another time
(6) Random kindness
Your explanation on Big C of the lungs was excellent and written in a manner that anyone could understand, you would have been wonderful clinicians…..the world has lost.
My pathetic excuses for counteracting my vices: smoking/drinking
(1) For some unexplained reason I have taken 6 crystals of ‘Sodium theosulphate’ and 1 gram of VitC daily to create a counter-effect of smoking.
(2) With regards to alcohol/ethanol…..I consume ‘Milk thistle’ to support the Liver in it’s filtration.
Keep well
michael
I have read your posts with great interest and thank you for better publicizing this important research. I have looked a bit a “popular” wisdom on the use of aspirin and find they generally appear to be unaware of the work of Serhan. Given the positive results of aspirin on inflammation I am continually surprised that this has not received more attention (rather than being ignored). No comment is really necessary on this, I’m sure it’s largely a matter of “follow the money”.
But on a positive note, I found the following post from the medical biochemistry page very interesting and though you would like it: Aspirin and Anti-Inflammatory Lipids
Thanks for the good work, I look forward to your posts.
The website didn’t make it into my post so here it is again: http://themedicalbiochemistrypage.org/aspirin.php
Many thanks, Ward, for your kind words. Your message makes us very happy. However, the continued proscription against aspirin by the medical profession dismays us. News reports of Serhan’s discovery of the actual biochemistry of aspirin and its anti-inflammatory properties are at least 10 years old. Comments such as yours are what are needed to help spread the word so that people can learn and take matters in their own hands.
Thank you, too, for the reference to the discussion of aspirin on the medical biochemistry page. It is a great site that we often use, but we missed this one on aspirin, Thank you very much.
Any further updates in this arena? I’ve been looking into difusinal an asprin analog. Would this be that holy grail that mainly targets COX 2 and uses the acetylation mechanism that asprin does?
*Diflunisal
Hi Eric
Many thanks for your stimulating comment. We do not try anymore to keep up with big pharma’s attempts to find a substitute for aspirin. The literature on NSAID research is too voluminous, and none have been proven to be more safe or effective than aspirin.
Now that it is known that aspirin does NOT inhibit the COX-2 enzyme, but rather modifies the enzyme by acetylating it to convert inflammatory omega-6 arachidonic acid to anti-inflammatory eicosanoids, the research to find a substitute for aspirin seems rather fruitless. The aspirin mechanism is unique.
It is apparent, Eric, that you are familiar with the biochemical mechanism by which aspirin exerts its analgesic and anti-inflammatory effects (see: http://ketopia.com/aspirin-a-unique-remedy/#more-1425). In answer to your astute question about diflusinal mimicing aspirin, we Googled “diflunisal+structure.”
We received the following response “Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor.” Further, difusinal does not have an acetyl group in its structure. Thus, it cannot acetylate proteins (enzymes) as aspirin does.
We hope this helps. We thank you very much for getting us back to the books.