New insights into why aspirin works so well | Hacker News Reader

New insights into why aspirin works so well

eurekalert.org

272 pointsgumby272 comments

Aspirin has been a life changer for long Covid. The other painkillers make symptoms 10x worse. Many people wonder if aspirin anti platelet/blood thinning capabilities is helping breakup microclots which brings relief.

There’s also a thing called nattokinase that apparently has similar properties to aspirin and is being studied for heart disease. It has been shown to break down blood clots and even degrade the spike protein.

NK might be a viable alternative. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043915/

Along these lines, you might have even better luck with serrapeptase, which breaks down fibrin protein.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265778/

These are known tissue plasminogen activators.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553328/table/t...

Thank you. I do take this “silkworm supplement” in addition to NK. Thanks for sharing some research behind it. I hadn’t come across it yet.

Aspirin+Claritin was what I used when I had a few weeks of extended COVID effects past the actual infection. It really does seem to work!

Or at least I think I had it... I never actually tested, I just assumed I should probably isolate regardless of whether it was COVID or the flu.

Tests are plentiful and easy. If you think you have it, get a test and find out. You still did the right thing by isolating, but advocating for aspirin and Claritin as relief for covid while not actually knowing for sure you had it is not as good. In fact, it can be dangerous, given those two drugs may interact with things others take but then read this and assume it's an effective treatment. You could have just been having an allergic reaction to early spring.

What kind of extended COVID effects did you have? I have a nagging cough about six weeks after my infection.

Do you have any good literature on Aspirin and LC? Not a doubter, actually I have LC myself.

I do not. I have my personal anecdote and experiences with common painkillers and LC. I've had it since January 2021 so there wasn't really anything known when I started taking aspirin outside of the many years of research as mentioned in OP's article. Here's my experience so far.

https://jondouglas.dev/long-covid/

I've swapped aspirin about a year in for nattokinase and have noticed much better management. I still take aspirin here and there, but NK is doing its job.

https://pubmed.ncbi.nlm.nih.gov/36080170/

https://www.webmd.com/covid/news/20221207/microclots-may-exp...

https://pharmd.substack.com/p/frequency-asked-questions-natt...

Hope that helps you.

EDIT: I heard about triple anticoagulant therapy but never realized aspirin is included in it. Check out this study here: https://www.researchsquare.com/article/rs-2697680/v1

Just adding a +1 for long covid and aspirin, aspirin + CBD cream (Momma Canna Cream, I think only available in Canada) was a game changer for me! I rubbed the CBD cream into my head and neck and took bayer "daily" low dose aspirin till I started to feel normal again (brain fog cleared).

How long did it take?

Seemed like it was never going away, 9 months in to "long covid" I kept saying "this needs to clear soon, it should clear soon" - I was going nuts because of the brain fog (end of 2021 into 2022). Did a lot of research, saw the clotting and inflammation research so I put myself on aspirin and CBD, after about a week and a half/2 weeks I noticed a slight improvement, about 3 months thereafter things were getting back to normal. To be perfectly honest, I'm not sure I've really ever fully recovered from covid, but hard to say if it's covid, getting older, stress. Never the less, I feel personally confident that aspirin + cbd helped.

The degradation effect paper is authored by among others James Yu, Kate Hsu, Shinder Chen (employees of NK producer) and Ayako Ishii (company involved in NK supply chain). Take it with a grain of salt.

While not Aspirin alone Etheresia Pretorius has been pioneering research on microclots in LC. In a recent preprint they used Aspirin and a bunch of other stuff:

>The anticoagulant regime included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once a day, and a direct oral anticoagulant (DOAC- Apixaban) 5mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection.

Results:

>..Following completion of treatment, each of the different symptoms resolved in the majority of patients.

https://www.researchsquare.com/article/rs-2697680/v1

I was surprised to read recently that Metformin has been a helpful therapy for LC. It's also an old drug (not as old as Aspirin of course!) with a surprising number of therapeutic use cases.

The micro-clots in covid and long-covid are fibrin clots, not platelet clots.

There is endless documentation and photos of this, it looks like tangled spaghetti.

Every report of aspirin vs covid is wishful thinking, it does nothing.

The amount of misinformation with covid and long-covid is astounding.

This article talks about how aspirin works and what was learned. Inhibiting the COX enzyme and reducing the activation of platelets can indirectly help prevent the formation of fibrin clots.

When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma.

Seems like we're still grinding up rhino horns and tiger penis and hoping for the best outcome, just that we do it with extensive testing now so we get a statistically acceptable outcome viable for marketing.

No. Science has all along been testing if something works and then finding out why. Often the „why“ is orders of magnitudes harder to find out than the „if“.

For example, we can observe how the brain functions in some instances, but why it works like does will elude us perhaps forever. Highly complex systems like the inner biomechanical workings of our brains are essentially a black box.

"Why" questions in general are pretty difficult question to answer in a satisfactory way.

[1] https://www.youtube.com/watch?v=36GT2zI8lVA

Feynman doesn't disappoint. Although, I would have liked for him to make clear how quickly we (including physicists like him) get to "we have no idea". Sort of the overall arc of his answer made it seem that, well we know why but it would be impossible to explain it to you because it is incomparable to anything else you might know. But the reality is, we quickly arrive at the four fundamental forces (the we know of) for which we have no explanation, no further reducibility (that we know of). We know they exist because we can observe them or work them out mathematically. But we have to just accept them on their face as they are in order for the rest of the universe to make sense.

I think “how” is more appropriate in the GP’s comment.

We can understand a thousand instances "how", but it will always be "why" that ties them together.

Like software incompatibility: every program is the story of "how", written explicitly, and translated into instructions. The only way to fit them together is to implement "why". If we could write both stories together, we could factor out incompatibility.

I knew it was the Feynman video!

I'm not sure that invalidates GP's point. Your comment is basically just repeating his premise. If we don't understand the why, we don't understand the how. We can spend years testing that "it works," but we're only testing for a specific outcome and checking for specific risks. Without understanding the how or why, we have little way of knowing what we don't know.

Ground rhino horn and tiger penis don't have measurable results, sure it's not ideal we might not understand how aspirin does what it does, but at least we know that it does something. That's not even in the same ballpark as Chinese medicine so comparing them just for that reason is disingenuous.

We don't test medicine for marketing, we test them for results. If homeopathy and Chinese medicine would teach us one thing it's that testing only for marketing would be the greatest waste of time and money ever.

Not only that, but it's based on a very certain, but false, idea of why it "works".

Indeed, chinese medicine and homeopathy show us that spending a dime on testing that you could be spending on marketing instead is always a waste

We start with what then much later to how which finally leads us to why.

For an example in CS, we currently use machine-learning algorithms that work very well in practice. However, why they work so well is still unclear in many cases (although we are making progress).

I find it fascinating that describing an automated learning process is so much easier than manually teaching. Once trained, looking inside a model to gather information about how it comes up with an answer to a question is somewhat similar to doing exactly that with a real brain.

Not always in pharmacology. There are many cases in drug development where people decide to target a particular biological process and tailor a molecule to do that.

This might surprise you, but we don't actually fully understand how most drugs work. Not just common OTC drugs, either, but also complex synthetic drugs used for things like autoimmune disorders, preventing organ rejection, and so on. Not just drugs that have been in use since the inception of modern medicine, but also about brand new drugs.

Often we have some idea how they work and what the internal end result appears to be, but the pathways that the drug seems to work on aren't fully understood. So we know the drug does something to that pathway, but it is to some extent a black box for us. But the fact that the drug operates on the pathway also opens new avenues for the scientists to gain a better understand of that pathway.

Modern medicine is optimized for end results. If a drug appears to work, the "how" is of secondary importance. We can always figure that out later. Sometimes we find stuff in nature, for example, like chemicals produced by fungi or bacteria, and we discover that they have medicinal properties. They nevertheless get productized as drugs, even when we don't fully understand them or the pathways they target.

> Modern medicine is optimized for end results

except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY

> except thousands of common herbal remedies are replaced by patent medicine with legal controls, because $MONEY

Except they are not being replaced? Just like in the good old days™ you can still get out and collect the herbs you're looking for. It's just that nowadays we know that component X of a herbal remedy actually does the job so you just buy that in tablet form (or whatever) instead eating of the whole thing.

> get out and collect the herbs you're looking for.

on the small chance that you are not being sarcastic.. Our city here has >300,000 residents.. and most cities nearby are paved. Where do the herbs come from ?

The same place herbs have always come from. If you don't want to step outside of your city or visit the local farms/greenhouses, then import. You can also import seeds, but it's up to you to ensure the seeds are the right ones and they have the proper environment they need to grow, and then the right tools to actually process those herbs in the "traditional" ways (or in your own experimental ways I suppose).

Herbs aren't magic you know, you've come across many if you've walked through any trail. Although I wouldn't blindly go picking anything and everything you see, some are toxic!

They're still not being replaced... Not sure what you're getting at.

If there is a flower in the Amazon with "heal all" properties, but it's only found in the Amazon, do you fault the company that creates a pill form and sells it in France?

Big Pharma has it's problems, but it's done wonders for the availability of medicines for the vast majority of people on Earth.

People will collect them for you and sell them in bottles in the shops, you know.

If anything the pseudo-scientific, barely regulated industry of "herbal" and "natural" remedies and supplements is booming right now and has been for two decades at least. Nobody is replacing anything, you can buy whatever you want.

I dont think you know the history of the regulated drug industry, or computational pharmacology in California.

Do you?

two years writing code computational pharma here

Hardly a long career, no? :p

Which ones?

"When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharm"

This isn't a problem with big pharma, but rather, an issue with your understanding of how little we know about medicine. We occasionally still find new body parts, and we've been dissecting bodies for centuries.

We don't cure some diseases because we don't know the reasons they happen, but find out some medicines that seem to help. Others, we don't cure simply because we don't know how to prevent them.

And this sort of thing isn't limited to medicine: We weren't sure the astronauts would survive. We did what we could to me reasonably sure, but... we weren't. This isn't new, nor is it contained to medicine. We've done a lot of things without understanding the underlying mechanisms.

As a doctor, i can confidently tell you as much as we know, we know so damn little. I get headaches everytime a patent asks me to explain why. The truth is for most diseases at best we have some plausible mechanism that's sorta supported up with some biology, and some treatment that works and we think we have some idea why. The real answer is we don't know, we have some reasonable theories that may or may not be true

>I get headaches everytime a patent asks me to explain why.

Maybe pop an aspirin!

I'm sure a doctor can make up jargon to assure the patient that its understood

>a patent asks me to explain why

Freudian slip of the week !!

ex-computational pharmacology here .. EX- !

Yes it's somewhat disheartening for those raised on illusions of our scientific supremacy to discover that we understand very little about the human body or how to correct its defects or failures. The illusion is quickly punctured once you start having any medical problems. The vast majority of the time the answer is "we don't know what it is, but it will probably get better on its own" or "we know what it is, but it's not going to get better and there's nothing we can do about it."

We don’t even fully understand how cuts heal...

The idea that doctors (or even the medical community) are standing on the top of a Mountain of Truth is a harmful fantasy.

Honestly, aspirin is really closer to "grinding up rhino horns" than to complex pharmaceuticals you have to make in a lab. It's literally "drink this tea made from willow bark" except we got better at isolating the active components and finding other ways to produce them and more reliably measuring the dosage.

The difference is that empirical studies have demonstrated the effect of "willow bark tea" and the lack of an effect of "ground up rhino horn".

That's not technically true, willow has salicin in it. Aspirin is intentionally a slight modification.

Yes, penicilin is probably a better example.

> When you say in 2023 that they have "new insights" as to why a common over the counter drug works it really doesn't instill great confidence in pharma.

When you read of new work on friction in 2023 does it reduce your confidence in the field of physics?

It is true that we are still just scratching at the surface of biology, but incrementally we (humanity) are making progress every day. It's not engineering.

If we could reliably show that ground rhino horns and tiger penises work, we'd be using them, or finding an easily mass produced derivatives.

Same as we did with willow bark and ended up with aspirin we have today.

History of aspirin: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14520

If they'd work we we would quickly start trying to find the one chemical in them that is responsible for that, and once successful find a way to synthesize it from cheaper to source ingredients. In the end you'd just have an ointment that says "active ingredient: acetylsalicylic acid" and it's up to the marketing department whether they want to mention rhinos or not.

That's skipping a few steps.

When insulin was discovered in 1921-2, it was only known that a pancreatic extract that has gone through some specific chemical processes could lower blood sugar.

International units of insulin were initially defined not by the quantity of material, but rather by their effect.

An international unit was defined to be the amount of extract that once given to a 24-hour fasted 1 kg rabbit, would lower its blood glucose level to 45 mg/L.

Only in the 1950s, it was discovered that insulin was a specific protein, and the definition was updated accordingly.

We could use rhino horns well before the chemical is isolated and a synthesized.

Gives new meaning to Tiger balm

efficacy and safety are the benchmark targets for regulatory approval.

mechanism of action isn’t even on the list.

“it works, it won’t kill you faster than the thing it treats, we have no idea why” is totally legit. welcome to biology, the dance of control with non-engineered systems.

The dance of control with non-engineered systems. Nice summary. And the systems reuse hits for distinct purposes like mad. For a little while in lockdown I tried to understand the biology of ACE receptors and my god, I couldn’t even memorize all the different types and subtypes nor the tissues they were found in, much less what functions that might imply.

“Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.” – Voltaire

This is not about "pharma" though, where "pharma" means pharmaceutical companies.

There is nothing of any interest in aspirin for commercial pharmaceutical organizations - any money spent in research is not recoverable. They will of course focus their efforts on researching new drugs, as their shareholders would expect.

Sorry gotta share but when we had my first daughter 13 years ago we got to take a tour of the doctors office . He walked us over to an antique cabinet that was full old dusty worn looking bottles… the doctor as I recall said: “these are all medicines from around 100 years ago they are all pretty much alcohol based and would reduce your pain - medicine really hasn’t improved much since… we can help you with pain but otherwise it’s pretty much up to you”. He went on to point out this is why he avoids keeping patients in the waiting room as he pointed to kids finger prints on the glass wall. So take this as you will his name was Dr. Jones so that was even cooler IMO but he did pass away sadly shortly after we started there… maybe his insight still applies today…

If I had to guess that’s probably a result of the incentives at play here: extending life and lowering suffering.

Like everyone else has said, it’s normally easier to find out « if » something works before the « why » and only one of those questions needs a « yes » to stop someone suffering.

Recently started working in pharma and this was somewhat of a surprise for me as well having never taken any biology in school - drug approval for bio equivalence has tolerance intervals of like 5-10% - on my first day I worked on some data for an aspirin generic that showed crazy high variance across subjects I think biochemistry might be one of those final frontier sciences we are such a long way from what physics has in the standard model (if the standard model is correct)

Would you say if we had new insights into how electrons behaved that it doesn't instill great confidence in our understanding of physics?

You joke but most drugs are made from interesting things. NAC's components for example are human hair and chicken feet.

If aspirin were introduced today it would be prescription-only drug, and might not even be approved for that.

Ironically, new discoveries and ongoing research is exactly what instills confidence for me.

Must read BBC article : The medications that change who we are - https://www.bbc.com/future/article/20200108-the-medications-...

Discussed here at the time: https://news.ycombinator.com/item?id=22019202

I imagine different people tolerate different anti-inflammatory over-the-counter drugs differently. Side effects of overuse are significant however and include liver, kidney, and gastrointestinal damage (acetaminophen, ibuprofen and aspirin respectively I think with some crossover effects).

Use judiciously, and only take regularly under a doctor's supervision as side effects can be minimized with additional drugs while retaining the benefits, e.g.

https://www.telegraph.co.uk/news/2017/06/13/daily-aspirin-be...

Ibuprofen and aspirin can both reliably produce internal gastrointestinal bleeds after a single dose in people with underlying digestive diseases. Over enough time with constant usage, they'll cause that in anybody.

I avoid both aspirin and (especially!) ibuprofen because of this. Admittedly my fault because 10+ years ago there was a period where I had a persistant nasty toothache and took too much ibuprofen over several months when I should have been trying harder to get the tooth treated (I did go to the dentist, but several expensive attempts at regular fillings didn't solve the problem and in the end I had to get a root filling). Ended up with stomach pain which lasted for months/years afterwards and even now its sometimes not 100%. Now days I feel like even taking just a few aspirins or ibuprofens can trigger it again. I reckon there should be stronger warnings about this.

Can confirm (anecdotally)

Ibuprofen gives me either gas or the runs.

Paracetamol works just fine - but it does have a liver effect, so it's a big no-no for hangovers.

>Paracetamol works just fine - but it does have a liver effect, so it's a big no-no for hangovers.

The worse part here for you is if you have hangovers too often. After dry January this year I noticed how much even non-hangover inducing alcohol usage decreases my QoL.

I lost weight without trying, I was more awake, I felt fogged up in the brain less often.

I reduced my alcohol consumption a lot now. And I wasn't even getting wasted often. I think it's worth trying if you don't want to destroy your body.

"it can cause detrimental side effects such as internal bleeding and organ damage"

NSAIDs are also ototoxic, meaning that they cause hearing damage.

Yeah, I once managed to foolishly induce this while taking too much aspirin over a too long period to deal with tooth pain. I'll never forget the sensation: out of nowhere it sounded like someone was crinkling paper inside my head for about a second, and then quite loud and constant tinnitus with regular sounds becoming muffled. Was quite frightening.

It thankfully went away after a day or so after I (immediately) stopped and I don't seem to have suffered any permanent damage that I know of, but it taught me to not fuck around with NSAIDs.

You just sent me on a research adventure. I have struggled with chronic neck tension and pain for the last 15 years with no obvious origin event, and sometimes take 2-3 ibuprofen every day to take the edge off, when it's at its worst.

Thank you for bringing this up!

Background for me for those interested:

Within a few years of struggling with chronic pain and tension headache episodes (vomiting, catch-my-breath level of pain for hours), I had my first "vertigo event". I was sitting in a chair in an office in front of a whiteboard, writing and thinking and chatting with a team, nothing special or different. Never had an inner ear issue before this moment.

Since then, I have struggled (seemingly randomly) where I have ear fullness (almost entirely without hearing on left ear for a month about 6 months ago, then everything slowly came back, for example), varied tinnitus levels, light-headedness, unable to turn around too fast without losing balance... and it waxes and wanes.

Now I am wondering if any of the waxing or waning of these symptoms have anything to do with my usage of ibuprofen. I found a study suggesting this back from 2010 just now, and wonder how I've never connected these two dots.

Of course, I have to mention neck tension and inner ear related issue, aren't the only health issue I've had in the last 15 years. I've gained GERD (probably not surprising), hashimoto's and vitiligo, as well as sudden onset of mild astigmatisms after the first few years.

I have tried my best to avoid using ibuprofen at all, but it is the only thing that can take the edge off of the neck trouble before it turns into that awful, torturous headache/barf session.

PS) I know most folks will see "neck tension" + "inner ear problems" and jump to pinched nerve, spinal damage, ergonomics, posture, etc, but even after a great deal of lifestyle changes, reduced time at an office desk, yoga, Feldenkrais method, numerous physical therapy stints, I am confident that it is not the cause and "how good I am doing posture/movement" has no strong correlation to pain levels or inner ear trouble on any given day - it is seemingly random.

PPS) Definitely open to suggestions or ideas, but I will be surprised if something is mentioned that I have not tried or looked into.

What you describe sounds complex, but for the vertigo part, check out BPPV (benign paroxysmal positional vertigo). If you have seen an ENT, they've probably covered this base, but even though it's the most common cause of vertigo-induced trips to the ER, my ER doc didn't cover it. It was two weeks before I saw an ENT who basically fixed it with the Epley maneuver. "Basically fixed" because I still have some lingering (and annoying) effects that echo some of the other symptoms you describe. BPPV is unique in my experience of medicine in that it has a simple test (Dixie-Hallpike maneuver), and an easy fix.

The other thing that comes to mind is Ménière’s disease, a disease affecting the pressures of the inner ear. It's probably also considered if you've seen an ENT. A friend worked on his Ménière’s with diet (low salt, low glycemic index foods), and diuretics, but what is helping now is allergy shots. His ENT noticed that there was a seasonal component to his symptoms and sent him to an allergist. (The first allergist he went to did testing but found nothing; the next allergist found plenty of reactions and hit on an effective treatment.) Actually, his symptoms sound quite similar to yours. The Mayo clinic page on Ménière’s mentions various treatment modalities, though not allergy treatment.

Thanks for the response!

Yeah, Ménière’s and BPPV has been ruled out, thankfully.

The oddity is that the sets of symptoms waxes and wanes on the order of months. I had sudden hypertension (170/100, not overweight, ~155lbs and 5'9, decently healthy diet for sodium, etc) from 2016-2019, then within a couple months it completely disappeared and went back to normal (120/65). No known or significant changes in diet or lifestyle when it dropped or leading up to it.

I've kind of just "accepted" that I will have these various, "random" health issues, and am just doing my best to figure things out / mitigate them as they come along. The neck-tension-turning-into these "cervicogenic headaches" are the largest common hurdle to my life on a frequent basis. I can deal with the other noise of issues.

Anyway. Thanks again for responding!

I've had similar issues a while ago and I was able to resolve them. Of course everyone is different but in case you want to check: for me the cause was that my bite was off, not balanced across all teeth and my jaw was being pushed back. I Resolved it by re-aligning the teeth, moving jaw forward and having special retainer that I can clench on at night without issues.

I used to wear a special bite splint / alignment device thing after I had the misfortune of an accident that messed up my jaw in my teens. To this day, one side of teeth make contact before the other side by just a mm or 2.

My teeth don't grind at night, but the next time I head to the dentist I'll look into seeing if I can have the issue corrected... worth a shot!

Thanks for the suggestion!

Edit for more info:

My wife helps out with back and neck massages, and my traps (neck and between the shoulder blades) usually have knots on the days I have trouble. I plan on ruling out weak traps and other muscular imbalances for good this spring, but as I mentioned in my initial comment, I have had three different rounds of PT sessions with different workout strategies over the last decade, and still no resolution (nor improvement during/after).

This tension thing waxes and wanes just like the other symptoms, but far more frequently.

You're welcome! And thank you for expounding.

I am very protective of my hearing, so I don't take NSAIDS and I carry earplugs to every restaurant, pub, and other noisy venue. Yet I recently suffered depressing and life-degrading damage to my hearing, which is being blamed on COVID vaccine. After it happened, people came out of the woodwork saying, "Oh yeah, I've heard of that." And now, too late for many of us, the information is trickling out. National Geographic featured an article about it last month.

I've seen two of the top hearing specialists on the west coast (if not the USA), and both vehemently stated that this is a true phenomenon; one of them stated with equal assurance that information about it is being suppressed. Even vaccine experts are afraid of being "canceled."

And indeed, my experience here reflects why. I have been buried and shadow-banned at least three times for posting references to reports of COVID-vaccine-induced hearing damage. It's disgusting and dangerous behavior that will cause more people's lives to be ruined. Obviously I'm not an anti-vaxxer; if I were, I wouldn't have had all my shots and a second (ultimately disastrous and nearly useless) booster.

I hope you find relief. Here are some links to what I'm talking about yet again. There are probably more since I collected these. Unfortunately the Nat Geo one is paywalled and it seems my subscription has run out:

https://www.nationalgeographic.com/magazine/article/covid-va...

https://www.abc15.com/news/local-news/investigations/can-the...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443418/

https://www.news-medical.net/news/20220523/Pfizer-COVID-19-v...

https://www.nbcnews.com/health/health-news/tinnitus-rare-sid...

Facebook group for victims, with several thousand members: https://www.facebook.com/groups/265035901879921/

... and it has not become common knowledge yet that ibuprofen is not recommended for males due to its reductive effect on testosterone production

Not recommended by whom? I’ve never had a medical professional tell me that.

Yeah, for all the hype about opioids being bad, these 'safe' drugs are way more dangerous than commonly purported. Acetaminophen is especially bad because the toxicity threshold is only slightly above the therapeutic dose. That is why they have to put so many warnings on this 'safe' drug. Yet let's blame opioids. https://en.wikipedia.org/wiki/Therapeutic_index

Acetaminophen has become a target lately, but the numbers don't really support that level of worry. Relatively few people are injured by acetaminophen overdose, and a large fraction of those are intentional suicide attempts. It's not even close to being the most dangerous OTC drug, ibuprofen kills way more people.

10:1 is still a pretty big ratio. You could take 20 Panadol every few hours before getting sick. That’s a LOT.

not really. you will be quite sick before you hit 10. also, double dosing is a major problem and makes it easier to hit the threshold .

Is the definition of “toxicity ratio” not “ratio of therapeutic dose to the amount required for toxic effects”?

Acetaminophen is simply an analgesic. It isn't considered to be an nsaid.

This paper from 2005 suggests the same: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809338/

"It’s important that we understand how it works so we can develop safer drugs with fewer side effects."

Allow me to translate: it's important to understand how it works so we can develop a patented drug that costs 100x more per dose, then we will work on getting aspirin banned due to its "side effects"

Tangentially, does anyone know how aspirin promotes bleeding?

I've searched (and also searched nutrient depletions for aspirin) and I'm not really getting an answer.

Prevents arachidonic acid from being converted to thromboxane needed for platelet aggregation. Here's a diagram I find helpful of the arachidonic pathway and which drugs inhibit which parts of the pathway: https://files.mari.casa/aapathway.jpg

Thanks - this type of reply is what separates Reddit from HN

You can find this kind of reply on Reddit if you’re in the right subreddit. /r/science and /r/drugnerds come to mind as potential candidates.

Thanks - just scrolled through drugnerds, but it’s still an example of Reddit’ preoccupation and persistent desire to prove cannabis as a wonder drug.

Thanks, I'm kind of stuck on the arachidonic acid bit. When I was very ill, I read a comment by a guy with a PhD in chemistry who probably typoed arachidic acid and ..ugh. I need to at some point sort a few things out.

Linoleic acid can be converted by the body into arachidonic acid, so that part I got right all those years ago.

Blood clotting in mammals is done by platelets, which float around in the blood. Platelets are kind of like (simple) cells in a way. Platelets have a membrane. Inside the membrane are the molecular tools—that’s what I usually call enzymes despite being an enzymologist—they use to clot blood.

Inside platelets, chemical reactions are sped along by the enzymes. One of the important chemical reactions for clotting is the conversion of arachidonic acid (through a couple of intermediates) to thromboxane. Now, arachidonic acid is so simple: a linear, 20-carbon chain with a carboxylic acid group at one end, and four double bonds in the chain. Converting it to thromboxane takes a couple of steps: the enzymes need to kink the chain and oxidize specific carbons to make them polar.

The trouble is, aspirin inhibits the enzymes! So the enzymes inside the platelets can’t make their thromboxane. And, as such, clotting is inhibited, which results in bleeding. So this is why aspirin can cause bleeding

COX enzymes produce a promotor of platelet activity and aspirin knocks it out. That's why they thought COX-2 selective inhibitors would be better.

Fwiw, chatgpt gave an impressive sounding result that is very inline with sibling comments and would at least give more terms to search for.

It’s an antiplatelet medication.

How it’s that, I haven’t the faintest.

Aspirin inhibits COX-1 and COX-2 irreversibly, which decreases synthesis of thromboxane which is key to platelet aggregation and vasoconstriction

Thank you. That gives me a place to start:

https://www.ncbi.nlm.nih.gov/books/NBK537062/

I heard that if Aspirin would be discovered today it would not be sold as over-the-counter by big pharma because too dangerous.

I've always though Aspirin was a deprecated drug but lately I've heard reports from people who claim it's the only thing that helps their arthritis or other issues. Maybe there is something behind it.

Aspirin deprecated? It's one of the most useful and most widespread in use drug on the planet - for far more than "arthritis". It's the WD-40 of drugs. Ah, it's even in TFA:

"Aspirin, which is a nonsteroidal anti-inflammatory drug, is one of the most widely used medications in the world. It is used to treat pain, fever and inflammation, and an estimated 29 million people in the U.S. take it daily to reduce the risk of cardiovascular diseases."

Its been years since I've seen any bottles or packs of full dose Aspirin in a pharmacy here (Singapore). Seems like nowadays you can only get those low-dose tablets for blood thinning and they cost a fortune (compared to generic Panadol or what normal Aspirin used to cost)

I moved to Asia and suddenly found it nearly impossible to get full strength Aspirin. Kind of frustrating as it seems to be the somewhat less harmful NSAID.

Some research later, I found that it possibly interacts with certain bacteria that cause stomach ulcers and that these bacteria are more likely to be in poorly stored food. So, street food basically. This is a risk factor that would be much lower back home in Europe.

I wasn't able to get a definitive answer on this, but it's the best one I found so far as to why Aspirin is common in Europe and almost totally absent in Asia.

Here in Romania I always have aspirin at hand.

I take a pill of ibuprofen every once in a while when I have a bad headache, and paracetamol-based drugs only as a last resort when I have a bad cold or similar.

Same here, aspirin is as accessible as ibuprofen and paracetamol. I’ve switched away from it for the odd pain management, but mostly because I get nosebleeds easily, and aspirin is not helpful then.

Note that Aspirin is just a brand's name, and you could find the same thing under different names in different markets.

E.g. Panadol Extra is the same thing.

Panadol Extra is paracetamol with caffeine, not acetylsalicylic acid, which is Aspirin.

Ah, my bad. So, could look for "acetylsalicylic acid + caffeine" combos from brands other than Bayer. Except if there's some special legal restriction for acetylsalicylic acid in Singapore.

Hm, now that you mention it, it's not common to see Aspirin here in the drug stores. Apparently you can buy low dosage Aspirin online but the regular dosage seems elusive. I'll ask in the pharmacy next time...

NSAIDs : https://news.ycombinator.com/item?id=35311721

Non-Steroidal Anti-Inflammatory Drugs (NSAID) : https://en.wikipedia.org/wiki/NSAIDs

  'NSAIDs and Gastrointestinal (GI) Injury'

<https://scholar.google.com/scholar?&q='NSAIDs and Gastrointe...>

Proton Pump Inhibitors (PPIs) : https://en.wikipedia.org/wiki/Proton-pump_inhibitor

List of Proton Pump Inhibitors - Uses, Side Effects : https://www.drugs.com/drug-class/proton-pump-inhibitors.html

----

Acetaminophen : https://news.ycombinator.com/item?id=35310951

N-acetyl-para-aminophenol (APAP), Acetaminophen, Tylenol, Paracetamol, Panadol, others : https://en.wikipedia.org/wiki/Acetaminophen

  'Acetaminophen and Alcohol Hepatotoxicity, Liver damage'

<https://scholar.google.com/scholar?&q='Acetaminophen and Alc...>

----

  'P450 Drug Interactions'

Cytochrome P450 : https://en.wikipedia.org/wiki/P450

List of Cytochrome P450 Modulators : https://en.wikipedia.org/wiki/List_of_cytochrome_P450_modula...

I think it's a lot more common in the US than elsewhere. Certainly in Europe and Asia paracetamol (acetominaphen) looks to be more common.

I love to see some info like this and want to share my experiences.

I'm a fan of small-molecule, well-tolerated, out-of-patent (cheap), widely available pharms like this in the class of "maintenance" and "enhancement" rather than "acute therapy" (although there is cross-over: i.e, have an acute headache? aspirin helps).

Some things in my list right now: acetylcysteine, aspirin, metformin

Besides aspirin, I don't take these regularly. And these days I take aspirin less and less, because I found I don't need it any more and I built up a healthy routine anyway.

In general I think eating right (lots of vegetables), good microbiome, plant medicine (for example turmeric (with milk and black pepper) black seed / nigella sativa as seeds or oil), and exercise are better than pharmaceuticals for general enhancement and maintenance of health--but there are some really good pharmaceuticals.

Everyone's body is different to some extent tho, and bodies change over time (for eg, gene expression changes over time), so what works for you might change over time.

This isn't medical advice, consult your doc, but here's other things I think a worth a shot (worked for me in the past) in limited doses:

piracetam - for building new brain cells, and increasing oxygen and decreasing blood viscosity

pentoxifylline - for de-aging your vascular system

fexofenadine - great for me for pollen allergies, and generalized severe inflammation (ie, say you had a really stressful thing)

doxycycline - good antibiotic in small dose but can have some weird side effects in some people, or if taken for long time, but strangely it also help with tissue repair.

fluorometholone - great in eye drop for itchy eyes, also instantly reduces brain inflammation / headache, and chills you out--for me at least--after dropping a couple drops in each eye--but use sparingly as it's a strong corticosteroid so you don't want to dampen the immune system in your sinuses etc as that will lead to infection!

In general I have the view that all pharams and most plant medicines are "toxins" (on some level, at some dose obviously, but in general too) in the sense that there's very few things which are just uniformly healthy in the class of drugs--yet nevertheless there are some wonder drugs like these that I think can be really enhancing to health if used right.

After a couple years taking aspirin at low dose regularly, I started noticing I no longer needed it. That coincided with me adopting a regular meditation/energy work/ some yoga practice.

Currently on my to-try list is: ashwagandha

Please exercise caution in your exploring -- some of what works for me might even be dangerous for you--everyone is different!! :) ;p xx ;p

If you're interested in ashwaganda for its effects on GABA in the brain, you may be interested in these other molecules as well.

So to compare Ashwagnda to Benzos/L-Theanine/Apigenin, here's how they work.

Ashwaganda - has compounds called withanolides that bind to GABA receptors & increase GABA release. Very similar to how benzos bind to GABA receptors.

L-Theanine - increases GABA release Apigenin - increases GABA activity, but more so supercharges the existing GABA activity by binding to other non-GABA receptors. Careful with this one as it can really lower blood pressure though.

But before messing with GABA directly, I'd also highly recommend trying out Magnesium Threonate, as this particular Mg can cross the blood brain barrier and has fantastic effects. It's a bit of a do-all as it's a cofactor for about 80% of the chemical reactions in the body, but being able to cross the BBB is a huge benefit to mental health.

Regarding plants that are toxins on some level, I believe you're referring to some plants that do have a hormetic effect on the body. In small amounts, they are actually beneficial since they activate a variety of counter mechanisms, so the net effect is more positive than had they not been consumed at all.

Thank you, I wasn't caring about GABA specifically, but interesting! I know Pu-Er tea also affects GABA. I appreciate your info on these! :)

What's hormetic? I'll look it up. Actually I think I just meant things like: if you eat too much of any plant medicine, or take something too regularly, it's not going to be good, normally--especially for maintenance and enhancement... I mean, too much of something! :P ;xx ;p :)

PS - I meant ashwaganda in its adaptogen / stress lowering / cortisol response / cortisol lowering effect. Thank you! :) ;p xx ;p

Thank you again!! :P :) xx;p

For a while it was recommended that older folks take a daily baby aspirin to lower their risk of ischemic heart attacks and strokes due to aspirin's function as a mild blood thinner. Large studies have shown the increased risk of hemorrhagic stroke offsets the benefits to ischemia and now taking a daily baby aspirin is not recommended except in certain cases.

Aspirin still has many uses and long term use is associated with other positive outcomes, like lower cancer risk.

Aspirin and other NSAID were supposed to go the way of the dinosaurs. COX2 inhibitors we’re supposed to be the golden child. Too bad it caused kidney and liver damage

As far as I know, aspirin is the one NSAID that doesn't potentially raise risks of heart attacks or strokes. Other drugs also can be hard on the liver and kidneys.

TBF it literally does the opposite, even in countries which have (culturally?) switched away from aspirin as an analgesic, it’s still in use as a blood thinner for stroke prevention and management.

I know a lot of doctors recommend ibuprofen over aspirin because ibuprofen is perceived to be a safer NSAID. I'm not sure if it's actually safer in adults or only in children though.

GI side effects in general and bleeding in particular are higher in analgesic dose level of aspirin. Aspirin is a very blunt instrument - it is both anti-inflammatory and anti-thrombotic - it destroys your platelet function even in low doses - this can be a feature/benefit (ie stroke and coronary artery disease or MI) - but for pure analgesia it usually just means increasing bleeding risk for no benefit.

I don't believe this is a meaningful risk for a healthy person just taking a few aspirin. Certainly you don't want to consume too much (like all medicines) nor use it chronically (unless the alternative risks are worse).

deprecated for children.

works well for people with atherosclerosis.

ibuprofen and acetominophen are hardly safe...

They are very safe when taken as prescribed but quite dangerous when you don't read the directions.

Although IIRC taking fever reducers when sick significantly increases how long it takes to recover. Those fevers are there for a reason.

The problem with acetaminophen is that the dangerous dose is not much higher than the recommended dose for a subset of the population. There are people who can die if they only take a few extra... and since it has a reputation as a safe drug, people don't think twice about taking extra.

This is so strange to me. I would never in a million years go beyond the recommended dosage without consulting a doctor. But I now realize that's just me, and if we can offer safer drugs that won't be as harmful if people exceed the dosage, so much the better.

> taking fever reducers when sick significantly increases how long it takes to recover

I’ve also heard this, and always wondered whether it was true or a myth. I really have no idea. Any chance you have a reputable source?

Searching for "antipyretic prolong pubmed" turns up some good trailheads. Seems like consensus is that fever is likely beneficial and routine suppression is probably not supported by evidence. There's conflicting data on whether suppressing fever delays recovery.

A few jumping off points:

https://pubmed.ncbi.nlm.nih.gov/23664629/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703655/

https://pubmed.ncbi.nlm.nih.gov/20920066/

https://pubmed.ncbi.nlm.nih.gov/11130213/

Would you turn off your CPU fan when it spins to 100% from opening ${electron app} just because the sound was annoying?

Suppressing the fever is more like significantly undervolting your CPU because the heat output of your gaming computer makes your room uncomfortably warm. Sure your room isn't too hot anymore, but the CPU needed that power to do useful work, and it's possible it won't be able to keep up with what you need anymore.

I guess theres always a caveat, but fevers can get too high and go for too long, in which case reducing the fever might be a good idea. But if it gets to that point, you should be working with a doctor to make those decisions.

This is a misnomer though. Your body will not make the fever too high in the case of fighting a virus, so danger is low. From an evolutionary standpoint this would make no sense. For a bacterial infection I think the chance of going to the danger zone is higher though.

Typically it's better to just let the fever ride when you have a virus, unless it's making you you so uncomfortable you can't rest/sleep.

Well, brain damage may not be a detriment to some.

Btw, "misnomer" doesn't mean what you think it means.

Are you perhaps thinking Tylenol?

It only seems that way because it's dirt cheap and pharma can't profit off of it very much.

An old mentor of mine used to say: "If they ever invent a miracle drug, it will be aspirin"

annecdata:

aspirin is pretty good as an anti-inflamitory and hence pain-killer. the reason i don't take it is that it irritates the stomach, and i have enough issues with my insides as it is (irritable-bowel syndrome - not fun)

i currently use cocodamol (codeine and paracetomol) to control my arthritic pain, but it isn't doing so great. at the end of the day, if you really need pain control, you probably want a pure opioid of some kind. and yes, i do know that codeine is an opioid.

I have a friend who has suffered from something known as juvenile idiopathic arthritis since he was still a teenager, and he doesn't function very well without pretty decent doses of CBD for the past long while I've known him. I recognize legality issues are prohibitive in many parts of the world but if this is an option to you I would suggest trying this or anything else that takes the actual inflammation down instead of dulling the pain. The other thing a friend of mine practicing general medicine who was working in a country where CBD wasn't legal yet used very large doses of carefully sourced curcumin - it's not something you want to eat tons of from the grocery store in many places as apparently there's a ton of contamination in the supply [1] but it's actually really easy to just grow tumeric and make sure you're getting it from a decent source in much of the world

One thing may be about it, much like oregano, is that it might just naturally be a nice absorbent of heavy metals in the soil but the fact that people add stuff like lead or cadmium in there to improve color or weight is just terrifying. We need raman spectroscopes in every phone already.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415259/

According to Wikipedia [1] there is no proven medical effect to curcumin (the yellow substance from turmeric):

Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly bioavailable. It is unlikely to produce useful leads for drug development.

[1]: https://en.wikipedia.org/wiki/Curcumin#Stability

There are no proven medical effects to many medicines that work wonderfully.

That's oxymoronic - if there are no proven medical effects, definitionally they do not work wonderfully.

It's not, proving a medical effect and having a medical effect are orthogonal concepts. The world doesn't wait on medical science to keep turning.

A lot of medical recommendations are based on expert opinion, which means there is no proof of their effectiveness but there is a logical basis based on our current understanding of the human body.

New studies come out every day proving the effect of certain herbs, extracts or therapies for certain pathologies, yet these therapies were known to work long before the studies came out.

Even some synthetic drugs are approved without having been demonstrated to be effective at what they claim, for example osteoporosis drugs still haven't been proven to reduce fractures yet get prescribed every day for that very use.

Except proven has a strict definition here that leaves out other possibilities.

You could find some compound that reliably induces an effect in your own body, but has never been studied by anyone else. By the definition we're using here, that could be something thats working wonderfully but has no "proven" medical effects.

Not saying this is advisable, only that pharma companies and their trials don't dictate reality.

Thanks for posting about the lead in tumeric issue. Never knew this was a thing, but it seems pretty widespread based on that study.

thanks, but no thanks

There's something like a downward spiral into hell that is opiates which starts with low doses like what you're on and escalates into worse and worse bullshit because you're not even trying to treat the underlying inflammation before masking the pain with opiates, and then the movement the pain is trying to prevent you from doing happens anyways and you just end up with more damage.

I'm telling you these alternatives because I know many more people than the ones I just told you about who are just fucking dead now. Opiates are fucked.

Opiod abuse is no joke and they are about as addictive as prescription drugs get, and yet the abuse rate is something like 50% in developed Western countries (Abuse ranging from taking them slightly longer than you're supposed to, to taking more than your prescribed dose all the way to crushing and injecting). There are many millions of people who take opiods and don't get addicted or abuse them in any negatively impactful way.

Your comment is based on a personal bias and in no way based on medical fact. There are many types of pain that only opiods can treat. We absolutely need more options that are as powerful and less addictive.

The mechanism for addiction is well understood, but what we don't understand is why some people can take opiods, even extremely powerful ones and don't become drug fiends.

I am sitting here with two 250ml bottles of Morphine next to my bed, there is nothing stopping me from drinking it all. I know how it makes me feel, I know it eases my depression, removes my pain, clears my mind and calms my anxiety, I have restful sleep when I take it right before bed and yet I have never taken it when I didn't need to, never increased the dose, in fact I often take a lower dose than prescribed and sometimes don't take it as scheduled and subject myself to some of the pain until it reaches a point where I require relief, my goal is not to completely escape all pain, all the time, I like to remind myself that i am in control and that I'm not afraid of the pain and that experiencing 'some' pain is not a bad thing. However, I have seen all the documentaries and dramatisations and accounts of people who do the complete opposite. Perhaps it's because I have taken Ritalin for most of my life and am used to the sensations of cravings, perhaps it's because I don't drink alcohol and don't smoke, I do not have any addictive tendencies whatsoever (unless we're talking about chocolate!), maybe it's genetics, maybe it's socioeconomic, but for sure, for me in any case opioids have vastly and dramatically improved my quality of life and I'm grateful that we have such drugs available. Obviously there is work to be done on education, monitoring and support. I wonder if the opioid crisis is so bad in the US because of the private system and lack of coordinated care between specialists and clinics as well as lax pharmacy monitoring.

"just try weed bro" is the absolute worst most condescending advice you can give to someone suffering from chronic pain who didn't ask for advice.

Do you really, really think someone just "went to opiates" before trying absolutely everything to identify and treat the underlying cause?

CBD is not equal to THC, its not psychoactive at all. So no it is not “just try weed bro” and the fact you are so confident about something you know nothing about is quite shocking to be honest. Also opiates are over prescribed for many things they shouldn’t be, so yes a lot of doctor “just went to opiates” and it is literally ruining lives.

P.S. the only condescending person in this thread is you.

> Do you really, really think someone just "went to opiates" before trying absolutely everything to identify and treat the underlying cause?

Given that doctors regularly prescribe opiates and pretty much never prescribe cannabis that would seem highly plausible.

Depends on the medical system in whoever's country

It's really different depending on where you are

Also I think "weed" and "large doses of CBD" are really different things

believe me, i know all about pain, from experience. cannabis derived products are not going to do anything, and i have no idea what you were going on about with tumeric. the only real actual pain-killers are opioids.

Arthritic pain can be treated by things other than pain killers, such as compounds with anti-inflammatory properties. That'd be the logic for turmeric I assume, in that same vein you have everything containing rosemarinic acid (Spearmint, oregano, rosemary).

You say only but I would say alcohol is decent at pain reduction in a lot of cases.

Ethanol seems to be an anti-inflammatory drug:

https://heart.bmj.com/content/90/4/355

Is that so? You haven't tried cannibis derived products or you would have said "did not do anything.". But ok sell the opioids.

believe me, i have used lots of cannabis products, and i am not selling anything

>>I'm telling you these alternatives because I know many more people than the ones I just told you about who are just fucking dead now. Opiates are fucked.

Please don’t project the irresponsibility of others onto those with self control, especially those with chronic conditions that induce extreme, long lasting, & completely debilitating pain.

They did not ask for health advice from random internet strangers. Trying to bully someone into following medical advice they didn't ask for is not cool.

I revel in how mad my mere suggestions made people here

Making a suggestion is “bullying” now?

Get a grip

No, doubling down and trying to insist they take your advice after they said "No thank you" is bullying.

  'list of Types of Arthritis'

Arthritis Types : https://www.cdc.gov/arthritis/basics/types.html

>Arthritis means inflammation or swelling of one or more joints.

It describes more than * 100 conditions *,

that affect the joints, tissues around the joint, and other connective tissues.

Specific symptoms vary depending on the type of arthritis, but usually include joint pain and stiffness.

Kratom might be of use, a friend used it as an alternative to morphine at the last stage of her live. She was much less drowsy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309661/

I've had multiple friends developing light opioid addictions from kratom. It's no heroin, but it didn't look easy to get away from it

I feel like this sort of anecdotal advice should be avoided on HN

You might be a poor codeine metaboliser. My mom and I both have this and need about twice the normally prescribed amount to have any workable effect. Always check with a medical professional before assuming you are since if it's the reverse you could easily od yourself due to rapid metabolisation of codeine to morphine.

Doubling your dose of cocodamol is a bad idea for the paracetamol too.

1 in 6 caucasians don't metabolise codeine to any useful form and therefore derive zero benefit from it. Opiates are never a good lifestyle option for chronic pain.

If you haven't seen it:

>consumer451 3 months ago | next [–]

>I was diagnosed with arthritis at a very young age. [...]

>One day I learned about modifying my diet to avoid inflammation. I greatly limited, but did not entirely eliminate, tomatoes and potatoes in my diet.

>[...]

https://news.ycombinator.com/item?id=34163231

unhappily, i was diagnosed with arthritis at quite an old age (60+) after happily eating tomatoes and tatties for all my life. i won't say what i think about advice like this.

There are two kinds of arthritis and the age-related one shouldn't be linked with food.

> tatties for all my life.

Hey, a fellow Scot? ;)

Assuming so, something that might be worth considering is medical cannabis, which has been legal in the UK since 2018 - I mention it, as very few people are aware of this. Both THC oil and dried cannabis flower for vaping are available. I use it for chronic neuropathic and muscular pain, and it works amazingly well.

Alternatively, as some others have mentioned, your body may not process codeine correctly (quite a few people can't), so you may wish to try co-dydramol, a mixture of paracetamol and dihydrocodeine. I personally found dihydrocodeine to work much better than codeine.

not a scot (actually i'm english - shock, horror) but i was married to a scottish girl and lived in edinburgh off and on for about 10 years, and some things have stuck.

i think that i am processing codeine ok, as when i took some of my late mum's pure codeine tablets (she got them for awful menstrual/menopause problems) it sent me off into a warm nice place. but try getting them from your gp these days, if you are a man.

Arthritis and inflammation in general can be caused by many things. For some, it can be the good one eats. Nightshades are a real problem for some people.

Have you found anything that works for you?

There are other, even OTC, painkiller medications that might be worth trying. Diclofenac (Voltaren/Flector etc) or Metamizole (variously banned, prescription-only or OTC seemingly random around the world) for example, and then there some newer non-opioid painkillers maybe worth trying but those are mostly prescription only.

Also meloxicam, a higher potency anti-inflammatory tolerated by the stomach better than other options

thank you, didn't know about that one.

Fun fact:

They would give Aspirin to Tzar Nikolas II's (or III?) son who suffered from hemophilia.

Came Rasputin the mystic around the corner and advised the Tzar's wife to keep the doctors off her son. As she did, her son miraculously recovered to a great degree.

Turns out little did they know Aspirin actually worsenes hemophilia due to thinning the blood.

Today an allergist told me the random lip swelling I experience (angioterma) has been caused in many other patients by NSAIDs like Aspirin, Tylenol (acetaminophen), and a Alleve (naproxen sodium). I hate to think that's true, but apparently it is a studied phenomena: https://aacijournal.biomedcentral.com/articles/10.1186/1710-...

> Tylenol (acetaminophen)

Is not an NSAID. One of its primary uses is as a medication for people who can’t use NSAIDs.

NSAID: Non Steroidal Anti Inflammatory Drug

Tylenol:

* Non steroidal? Check.

* Anti inflammatory? Hrmmm... not so much.

So what are you taking it for again?

https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory...

It's still a COX-2 inhibitor.

I also get reactions. My eyes get swollen. It works very well as painkiller though but I feel I must avoid it.

I had to stop taking aspirin in all forms about ten years ago because it produces tinnitus-like symptoms, even in small dosages. No idea why.

It’s ototoxic and damages your hearing, causing tinnitus, that’s why.

Aspirine considered harmful. By me. Even single dosages reliably induce tinnitus for me.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025186/

> With short-term administration, the effects appear to be completely reversible whereas long-term administration appears to induce a unique form of damage to SGN (spiral ganglion neurons)

PSA: Are you using minoxidil for treating hair loss? In that case you must not take Aspirine, as it significantly reduces the effectivity of minoxidil.

https://pubmed.ncbi.nlm.nih.gov/30226287/

For me Aspirin takes about three times longer to reach effect compared to Ibuprofen or Paracetamol which "kicks in" after just 15 to 20 minutes. As for getting rid of a headache they're all equally efficient on me.

I remember an old interview with Milton Friedman where he stated using aspirin every other day to reduce the dangers of heart attacks. My grandfather did the same. So I guess this wasn’t such a good idea after all?

no it is still a mainstay of treatment for those at high risk

my father in law (76 years old) does the same, but it's not the same kind of aspirin i'd take.

Iirc there's a special version for that use. I think it's called cardio-aspirin or something?

The downside is that it's an anti-coagulant, so if you bleed for any reason it will not stop bleeding as easily as without the cardio-aspirin.

It’s just a baby dosage of it 81mg.

The article says

> Peer-Reviewed Publication

But the article seems to describe an upcoming poster?

Some fields' conferences have refereed talks and posters, so it's not automatically suspicious. A prominent field where this is standard is computer science! Not sure about this particular instance, however.

I rarely take any sort of medication other than my daily allergy tablet and usually a Mucinex during the allergy seasons. My exception is either BC Powder or Goody's for tension headaches and migraines. I'll have em once or twice a month, almost always after sleeping at a crooked angle due to my adjustable bed, and my solution is two packets of powder that usually eradicate the pain within 20 minutes.

Thousands of people are hospitalized yearly due to bleeds from 'allegedly' safe drug. The overdose occurs due to double-dosing or people taking too much owing to the drugs not working. Same for drugs containing acetaminophen. Overall, overpriced , infective drugs that cause more harm than good except for the most minor of pain. The notion that these drugs are supposed to be safer seems clearly false.

"The dose makes the poison", as Paracelsus said. Everything (including water and oxygen) is toxic at the wrong levels.

You can overdose with everything. I use half an aspirin once in every 12 months. This is the only drug I ever use 'regularly' and I feel an immense impact: I sleep 12 hours from this half-portion because I my body is not used to any drugs.

The OG COX blocker.

Edit: we're all adults here, and a little humor on a wednesday morning never hurt.

> we're all adults here

well there's no ID check to access HN :)

When I was a kid aspirin was used for everything, from a headache to fever, etc, now no one uses it anymore, and everyone uses paracetamol and ibuprofen instead...

It's shocking to me how we still refer to paracetamol and ibuprofen in the same breath when their relative risks are so different.

Are they? Maybe acetaminophen (i.e. paracetamol) is many times more dangerous than ibuprofen, but still, in absolute terms it must be low if used according to guidelines.

I mean, most people don’t know anyone who has died or been injured from acetaminophen, so from most normal people’s everyday perspective it simply does the same thing as ibuprofen, regardless of whether that’s scientifically correct. Thus it’s easy to understand why people talk about them in the same breath.

The issue (in my view) is that the dose of efficacy to the dose of issue (when it starts causing problems) is MUCH closer for acetaminophen.

Acetaminophen 'usage' dose is usually 500-1000mg (1-2 pills). The dosage where it becomes significantly toxic is ~7500-10000mg (7.5-10g), which is somewhere in the range of 10x the dose.

Ibuprofen on the other hand, 'usage' dose is 200-400mg (1-2 pills, again). Toxic dosage is closer to ~16000-25000mg (16-25g), which is more like 50x the usable dose.

Since people invariably take more than the recommended dose when they're really in pain, I'd prefer the NSAID that is less toxic at higher doses... since it's not like they post toxic doses on the side of bottles.

Having a bad liver at old age. Is these issues contribute to earlier death? Can it be proven to linked to paracetamol? No. So we know nothing basically

Having a bad liver will mean its not capable of generating enough glutathione. Paracetamol is a state licenced poison which depletes the body of glutathione. In order to replenish glutathione or help the liver recover from state licenced poisons like alcohol and paracetamol, take/increase cysteine. Some other experts will step in and say its hard to absorb from the gut so take N-Acetyl Cysteine aka NAC, but what they dont tell you about the acetyl part is it stimulates immune cells which then cause their own problems namely inflammation. Acetic Acid which is the Acetyl part of NAC lowers the GI of food, which is why adding vinegar to food is useful at reducing the blood sugar spike and used to be used in some diabetic conditions. The immune cells attack the sugars except starch. Ironically the liver also needs glucose to make glutathione, so what I havent established is this. Do we feed off our own immune cells or do we simply excrete them through the usual methods or a bit of both? If we are not catabolising and feeding off the immune cells which have attacked the food we have eaten, is our immune system helping us to stay slim and healthy?

On the subject of aspirin being a COX inhibitor, so are Omega 3's. Omega 3's interact with the COX enzyme's so their Nett Effect is tantamount to being a COX inhibitor! Omega-3's also reduce inflammation but they take several weeks to months to have a noticable effect, in which time, weather can improve which is cited as the cause of the improvements.

Short term once or twice use cases, Aspirin can be useful, but if anyone is needing to consume anti inflammatories like Aspirin, consider looking into dietary changes which can also reduce inflammation, like increasing Omega-3 intake.

On the point of the indoleamine dioxygenase, there are many enzymes which can target cancer, copper will increase some of the InterLeukins which modulate the immune response.

It is handy to know that aspirin slows the breakdown of the amino acid tryptophan into its metabolite kynurenine by inhibiting associated enzymes called indoleamine dioxygenases, or IDOs.

I'll have to try taking some aspirin with some tryptophan on an empty stomach or protein free meal so that the tryptophan is not crowded out by the handful of amino acids typically found in meat and other protein sources at the blood brain barrier, in order to see if it will improve my mood. Blue light exposure via the eyes is needed to increase the serotonin in the brain according to some studies.

Yeah, take too much paracetamol and you die, literally, of liver failure, which is not that hard to do. Take too much ibuprofen is survivable. Taking 20+ ibuprofen at once will give you nasty stomach ache but you will probably not die. The fact people do not know this difference is why overdosing is such a big problem with paracetamol-based pills. They look identical yet one is pretty much a toxin...it very easy to confuse them.

What risks are you referring to?

I think the fact that for most people there is almost no risk is why they are mentioned in the same Breathe

For most people oxycodone presents very little risk, and it is an extremely effective painkiller. But for some people it will ruin their lives, so (at least in Australia) it is tightly regulated.

It's the risk of seriously damaging a small subset of people even if they stick strictly to the recommended dosage that I find strange. Maybe that's the case for a lot of medicines and I'm just less aware of those. But I see people popping ibuprofen like candy and I don't think many of them have even considered whether they might be in that small group of people that definitely shouldn't touch it.

Which is riskier? One comment says it's paracetamol, another says it's ibuprofen..

He's probably referring to paracetamol's narrow therapeutic index[1]. 1 paracetamol may relieve your headache, 10 will do lasting damage to your liver, or even be fatal[2]. It's kind of nuts. Of course, Ibuprofen is not without (GI) issues, but I don't think it kills as many people as paracetamol does.

[1] The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. https://en.wikipedia.org/wiki/Therapeutic_index

[2] Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance https://en.wikipedia.org/wiki/Paracetamol

Paracetamol toxicity is the foremost cause of acute liver failure in the Western world,

yup people are shocked when they learn it is good ol' Tylenol that is killing people or making them deathly ill, not those evil steroids or opioids hyped by the media. That is not to say those are not dangerous, but paracetamol is way easier to accidentally overdose. Taking to much of an oral steroid at once will not cause liver failure. Neither will too much codeine.

Okay, I need to revisit my position. Now I'm shocked that _both_ paracetamol and ibuprofen are available "off the shelf" (without talking to anyone).

I wonder if people in general are or were always as blasé about the risks of easily obtainable medicines as the people around me seem to be today. Could trust in government regulations to protect us from harm have the side effect of eroding personal responsibility? Or could the era of click-through EULAs and warnings on everything etc. be training people to not bother reading any instructions/warnings? ("This product contains water, which is known to the state of California to cause cancer and birth defects.")

I'm rambling. Maybe I don't have a coherent point. But something bugs me about it.

I'm based in Ireland, and while you can buy paracetamol on the supermarket, you're only allowed by law tú purchase one product of paracetamol at a time. Of course you can enter the shop again and buy another one immediately after or go to another shop, but you can't buy 2 paracetamol products on the same purchase.

>It's shocking to me how we still refer to paracetamol and ibuprofen in the same breath when their relative risks are so different.

And it's shocking to me how we still refer to paracetamol (Acetominophen for us USAians) and ibuprofen in the same breath, when paracetamol might as well be a sugar pill, for all the good it does and ibuprofen is the liniment of the gods!

Ibuprofen being an NSAID is high risk for anyone who’s had stomach ulcers due to its risks involved in causing GI bleeding.

For people like me it’s simply not even an option.

>For people like me it’s simply not even an option.

Good. More for me. ;)

More seriously, you're absolutely right. Which is why even folks who can take ibuprofen should only do so within appropriate limits (IIUC, 2400mg/day maximum).

I have spinal issues (disc degeneration, stenosis) which have, in the past, caused serious amounts of pain. If that pain is acute and not too serious, ibuprofen has been a life saver for me. Naproxen sodium, acetaminophen and other NSAIDs have absolutely no effect on me.

Without ibuprofen, my life would be a nightmarishly painful endeavor. And so, while I do understand your circumstance (which sucks because NSAIDs are wonderful as analgesics, it's a shame you can't use them), those who ibuprofen can help is a much larger pool than those it harms.

Hopefully, one day we'll discover/invent analgesics which don't cause GI issues.

If that pain (usually sciatica) becomes chronic, ibuprofen isn't enough. When that's happened, I've ended up having epidural steroid injections[0] which knocks out that inflammation post-haste.

[0] https://paindoctor.com/faq-epidural-steroid-injections/

Edit: Fixed typo, removed extraneous text.

I totally concur. Got a condition comparable to yours and ibuprofen makes a real difference whereas paracetamol just doesn't do anything. Dunno why.

Does it have an inflammatory component?

Paracetamol is an analgesic and antipyretic, but it is not anti-inflammatory. And there are other divergences e.g. ibuprofen has been linked to protecting against Parkinson’s, where neither paracetamol nor aspirin (which is an anti-inflammatory) have shown such property.

The TLDR is that they’re different molecules, and while they have overlap in their antipyretic and analgesic properties, that does not make them substitutable in all cases.

Dam, forgot that. Ibuprofen definitely is NSAID and I do have inflammatory condition. So yeah, that's why it works. Thanks for reminding me :-)

While it's rare, ibuprofen is associated with an alarming (but transient) condition called DIAM, Drug-Induced Aseptic Meningitis, and autoimmune reaction that mimics ordinary meningitis. It resolves after the drug leaves the system, but does require the patient to avoid that drug henceforth.

https://en.wikipedia.org/wiki/Drug-induced_aseptic_meningiti...

This is the kind of thing I'm thinking of, not people taking higher doses than recommended on the pack. For some people, no amount of ibuprofen is a good risk, and I don't think people in general understand this. Nobody reads the label and wonders "could this apply to me?"

I guess what I'm suggesting is it should be available over the counter, but not off the shelf.

I think this must depend on the person. Acetaminophen helps me a lot more than ibuprofen, consistently.

>I think this must depend on the person. Acetaminophen helps me a lot more than ibuprofen, consistently.

I think you're probably right.

Acetaminophen does absolutely nothing for me. Nor does Naproxen Sodium. But ibuprofen does. And consistently over decades.

I wonder if there's been any research into what makes different analgesics more or less effective for various cohorts. Unsurprisingly, there has been[0][1].

[0] https://www.npr.org/sections/health-shots/2011/09/26/1407055...

[1] The meta-study referenced in the link is from 2011.

Right, I'm European.

I figured.

I added "acetaminophen" because most USAians wouldn't know what "paracetamol" was if it came up and smacked them upside the head.

I used to have the impression that the advance of LLM is peak human ignorance - we know how things work in a recipe like fashion, but not why. I even compared this with tribal rituals - follow a recipe with a probably misguided why. News like this gradually make me realize that this is how human wisdom have long been working, discovery and invention first, understanding later.

Airplanes and lift are an example of this that I always come back to.

Hopefully we realize and reach the off-switch before too late

Are you suicidal, or is there a deeper meaning to your comment that I missed?

It's the doomer narrative around GPT, nothing to see here.

Poe's law apply here again.

I use nothing for reducing inflammation, nor any drugs since decades, when I'm ill from time to time (once or twice a year), I let the fever go, the body is just working actively, it's not especially uncomfortable

I'm sure you didn't mean it this way, but this does read as if you're shaming people for using painkillers.

No-one should have to endure pain and there's nothing wrong with the responsible use of drugs to reduce it.

Avoiding pain is an anti-goal. There is starting to be good evidence that aggressive pain management with a goal of having patients feel no pain is linked heavily to opiod overprescriptions (which become fent users).

That doesn't mean the answer is no pain medicine. You should try to keep pain in a bearable, functioning range.

I don't see it in his (downvoted) comment. It's getting unhealthy. Nowadays you need to be super careful when you write to not possibly offend anyone the tiniest bit. It's fuc*ed up.

no, just going in the direction of the article about the fact that drugs for things like inflammation are more counter-productive than useful

I wouldn't know how old you are, some people just have such wildly good genetics they can smoke and drink till they get hit by a bus jogging at night at 98 years old.

Other people don't, you wave a celery stick near them and they put on eight pounds, a pollen particle passes within thirty kilometres of them and they're hayfever nearly kills them.

yes but I really believe it doesn't have much to do with genetics, like for intelligence. It's more the lifestyle, eating as much vegetable as possible, raw, fermented, I eat rice as well, working remotely definitely helped too, outdoor exercise (bike as a vehicle) or just walking, sun exposure, cold showers (because it's broken and it's not unpleasant as well), no heating as well all year long (south of France) so my body is trained to heat and probably have good immunity

The body handles inflammations just fine, but you can actively help it to get it done more quickly. Doesn't have to be Aspirin though, chamomile tea and lots of other things work wonders, too.

> The body handles inflammations just fine, but you can actively help it to get it done more quickly.

The body doesn't "handle" inflammations, inflammation is something the body _does itself_ in response to issues.

In the vast majority of cases you don't have to help it do anything, it's intentionally doing that. The only reason to interfere at all is if it's making you uncomfortable or actively causing you problems (the body isn't perfect, it fucks up too).

The same thing applies to fevers. The body doesn't (in the vast majority of cases) need your help getting rid of a fever, it _caused_ a fever because that's part of its immune response. If the fever is becoming dangerous, sure go nuts, but usually you're just reducing its ability to fight off an infection.

Although HN is not a medical site, comments like yours need a disclaimer. Cause even the phrase “the body handles inflammations just fine” needs a it depends clarifier.

“the body handles inflammations just fine, in normal conditions (for a healthy person)” and for why it does, it's because of million years of evolution and the incredible complexity of our bodies I guess

Actually there are a lot of things which do not do anything.

Its probably one of the most fake markets out there.

Tumeric. People who say that doesn't actively work against inflammation simply haven't tried it enough.

I don't know if there is a upper limit but 5-10g in Form of moon milk or tea definitely go down just fine.

Yes, and everybody here thinks you're a brave little boy. Have a lollipop.

Perhaps the parent’s anecdote s not particularly instructive, but your comment is not what this site is about and goes against the posting guidelines.

yea and if you think a bit more, you could see it's applicable to almost everyone. This article explains how it's counter-productive to do anything else, there are working on new molecules that will be found later than similarly they inhibit something else..

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