> But if acetaminophen is safer, then why don’t official sources tell you that?
Guess it depends on country. Here in Norway official sources[1][2] do say acetaminophen (paracetamol here) should be the default for treating fever and pain in kids, adults, pregnant women and elderly, and have for some time. Ibuprofen they say should be used with caution.
Yup - in the UK, paracetamol is usually recommended for general pain relief before Ibuprofen. Additionally, Ibuprofen and NSAIDs have a lot of interactions which can make them unsafe - SSRIs or blood thinners for example.
"since 2019, on the advice of the National Agency for the Safety of Medicines and Health Products, French health workers have been told not to treat fever or infections with ibuprofen." [1]
But yet in some countries pediatricians will libreally prescribe it to toddlers
Also
from [2] "In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution."
Really lovely article. In paramedicine we usually treat 10g of acetaminophen in a 24-hour window as a potentially fatal overdose. That's also why the law in Australia was changed to require acetaminophen to come in blister packs (harder to get each pill out) of no more than 16. At 500 mg, that only gets you up to 8 g if you eat the whole thing, which is still hopefully non-fatal.
I always thought a simple over-the-counter supplement (NAC) being the cure for an overdose was so cool. It's a pretty cool substance in a lot of ways, and this is a great spur to myself to research it more thoroughly.
> Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
I'd believe it. I first heard of NAC on the nootropic subreddit in a past lifetime. The benefits vary, but generally it's a safe thing with a low chance of making anything worse, but a possibility to improve things. Many neurodivergent folk have written about how they benefit.
I'd give more info on the exact benefits they found (iirc OCD and rumination loops could be broken more easily), but unfortunately my memory is failing me.
How is nac (acetylcysteine) delivered there? I can buy dissolvable tablets here in Europe but from what I see that’s less helpful for mucous, things like mucomyst require inhalation, which isn’t in otc products I know of.
In the Philippines it's available as an effervescent tablet to be dissolved in water. They still tend to work better than the western remedies (guaifenesin etc) even in this form IME.
Usually here in Canada it's available in capsule form which I find less effective.
Same here actually, I find it slightly helpful but the effect’s useful time is limited. I’ve wondered if I could capture the gas released while bubbling and inhale that…
What does ingesting 10g of acetaminophen even look like? I've got to imagine the fatal dose is far, far, far lower with chronic usage. Finding out that people are ingesting grams is profoundly disturbing.
I have taken 4-5g in a day while suffering from intense pain before.
There is a limit to the amount of opioids they will prescribe you, even if you are in mind shattering pain. For instance while attempting to get your dental insurance to actually cover a treatment you may find yourself between risking organ damage or risking $5000+ in ER visit bills only to have them refuse to give you anything but Tramadol.
Apparently a common source of problems is taking two different medications without realizing they both contain acetaminophen.
Suppose your arthritis is acting up, so you start taking Tylenol 8hr Arthritis Pain[1]. That's 2 tablets every 8 hours. They're extended-release with 650mg per tablet. A total of 3900 mg in 24 hours.
A few days later you get the flu, so you decide to add what seems like a completely different medication: Theraflu Flu Relief Max Strength[2]. It has a cough suppressant and an antihistamine. But each caplet also contains 500 mg of acetaminophen. It says to take 2 caplets every 6 hours, so you take 8 of them in 24 hours[3]. That's another 4000 mg.
Between the two, you're at 7900 mg.
Then you wake up in the morning and take both medications, but 30 minutes later you've forgotten you took them. You're not thinking straight because you're sick. So you accidentally take a second dose. That additional 2300 mg brings your total to 10200 mg.
[3] You weren't supposed to take 8 of them, though. If you'd read the label very carefully, you'd have seen it also says not to exceed 6 in a 24-hour period.
My personal rule is to only purchase over-the-counter meds with a single active ingredient. I'd rather separately take an antihistamine, expectorant and painkiller than a concoction where I have to read the whole label and do math while sick to separate the doses and timings.
There are some that are very hard to find as a single ingredient. Recently I was purchasing a medication for back pain, I had a choice as to which other ingredient I wanted, but I didn't have the choice of none. I picked the combined ingredient I don't like to take, because I wouldn't be adding it on top.
I did toss on the other option, stand alone, at one point so I could get some sleep.
It left the medication I was more comfortable taking as an add-on option if things got bad enough. (This particular medication has much lower risk of overdose, so if I got stupid and took it again there would be no significant additional risk.)
It's ironic, but taking the combined medication with a known higher risk of its own was better than taking the lower risk medication.
One was controlled, higher risk, taken at specific times, while the other was taken in addition, on demand, as required.
Specifically this is one reason they’ll sell you cocodemol or Vicodin but not codeine or hydrocodone directly — if you take enough to get a codeine high, you’ll have taken a toxic amount of paracetamol/acetaminophen, so they assume you won’t.
Totally get it, I too only understood it "theoretically" till I had a (fairly minor!) dental operation.
... Suddenly I'm maintaining a continuous note of when I'm taking which medicine to avoid crossing safe limits (which I anyway was crossing most days).
I was only told to take 2 paracetamols a day (bullshit dose, I'd be waking up from the pain even with more pain meds).
"Diclofenac for rare use" - well, if nothing else is touching the pain, is it an emergency?
Eventually after forever I was able to transition to Ibuprofen + paracetamol. And I already have a health condition which is heavy on my kidneys... pain management can be absolutely crazy.
This can easily happen over the course of 24 hours if you're in "fuck me I'll do anything to make it stop" levels of pain. I've taken more than 20 ibuprofens in a day a few times in my life, which, while not medically advised, did not kill me. I actually had no idea acetaminophen was so dangerous.
Just in case, ibuprophen does not work well for pain relief [at lest for some kind of pain]. Paracetamol [acetaminophen] usually is much better against pain.
And paracetamol + ibuprophen can help with strong pain for which neither paracetamol or ibuprophen work at normal doses.
Not really. Both address different sources of pain, and do so using different processes.
Ibuprofen is a Nonsteroidal Anti-inflammatory Drug (NSAID) that reduces pain and inflammation, while acetaminophen does not. (Acetaminophen is believed to act mainly in the brain rather than at the site of injury).
Ibuprofen- Fundamentally, if the pain is caused by inflammation, reducing the immune systems response to it can reduce pain, but if the pain is more acute it won't make a dent.
With acetaminophen, taking more isn't a solution in most cases, you need another method to reduce the pain further if it doesn't achieve its goal.
(That's why it's combined with things like codeine, which affects the brain in a different way for an additive effect)
> you need another method to reduce the pain further
I don’t know about “most cases” but often you don’t want to reduce the pain _further_, you want to reduce the pain _again_. (Having an alternative definitely helps in the meantime.)
They are common in France, but not in such packages: There are restrictions that prevent you from buying more than than 8g/day (theoretically at least, I don't believe they are strictly applied in practice).
Taking too much acetaminophen is bad for you but 10g is 20 extra strength pills and that much isn't likely at all to kill you but damage your organs is quite possible. Reading this might make someone in a bad place think that much will do the job and it won't. Tylenol poisoning's most likely outcome is permanent organ damage and pain, don't try it.
I've heard it suggested that acetaminophen just come with a small dose of NAC alongside it to make it safer. I guess this would require a lot of regulatory work to approve, but given that 500 people a year OD, it seems like a thing we should at least consider.
Meanwhile, it's funny that it seems like acetaminophen should safer in more scenarios, but the other has a lot of overdoses with typical use, I guess that's why there's a gap between the two, because ODs are apparently a lot more common or at least more legible than problems caused by the other drug.
You can still buy 100 packs, they are just behind the counter at chemists. TBH it's a rather stupid restriction - do they think people only ever own 1 packet of paracetamol at a time? In my household we have at least half a dozen, including a 100-pack from Oz and a 500-pack from America.
Yes, and you can still die in a car crash if you're wearing your seatbelt, and wearing a helmet on your motorcycle won't save you from a head-on with a truck, and you can still drown in a pool with a lifeguard, and you can still die in a burning building with smoke detectors.
Harm reduction is about shifting probability distributions, not guaranteeing outcomes. Kids can still get into pill bottles with childproof medication caps, but accidental ingestion of aspirin by children reduced by 40-55% after they were mandated. [0]
No. Ethanol and tylenol compete for CYP2E1 that produces toxic NAPQI, so no, acute alcohol intoxication has a protective effect at least where it comes to tylenol toxicity.
The right tool for the right job. When it comes to medication, in the right dosage.
I'm aware of acetaminophen's down sides, and yet recently I was taking it combined with 2 other medications at the time.
Why? Because all three medications are recommended for dealing with the issue I had. (Alone and in combination)
The moment it wasn't helping further? Done.
There is this broken idea, particularly apparent in North America, but in western society that more is better for many things. It's not.
More pain killers don't do anything if they max out the relief they can give you, overloading their mechanism doesn't reduce anything, but taxing your liver or your kidneys.
All medications are potentially toxic, your body wants to dispose of them. In appropriate dosages they will benefit you, but more isn't inherently better.
Even water can kill you in sufficient quantity.
We do the same with diet; where someone declares one ingredient in a meal healthier than another; it isn't. A single ingredient isn't better or worse for you in a meal. Your diet however can be good or bad; over time that matters.
It's a very strange cultural thing too, Australians (and I presume other Commonwealth countries) default to paracetamol (acetaminophen) before ibuprofen
Paracetemol has always been seen as first thing you'd take for pain relief, and you'd "step up" ibuprofen as an escalation, but that might more to do with marketing of Panadol (paracetemol) vs Nurofen (ibuprofen).
We'd look on at the US where you were taking Advil like candy in confusion.
One great thing you learn as a parent, you can alternate acetaminophen and ibuprofen. Both of them are recommended every four hours, but you can stagger one by two hours to maintain consistency of pain-relief taking ibuprofen then paracetemol two hours later
I lived with an ICU nurse for years and one of the things he emphasized was the risk of acetaminophen overdose. He's more than once treated the liver failure (and death) from it and by his words, it's one of the worse ways to go.
The positive of it is it got me in the habit of logging whenever I take it, either in a note on my phone or just a sheet of paper I place on my dresser under the bottle. This helps make sure I stay under the 3-4g/d limit.
Last year I was diagnosed with a rare headache disease (NDPH). We thought it completely came out of nowhere, but I had logs in my phone recording headaches and acetaminophen use intermittently from a few weeks prior. This proved useful in the diagnosis.
Moral of the story: log when you take it to avoid overdosing. Combine that with some basic symptom logging (like 1 line, 10 words or less). You never know when that might be useful for your doctors later on.
P.S. like someone mentioned in a comment below happened to them, be careful with NSAIDs over the long term. Until recently I took them daily for better part of 3 years. I was recently diagnosed with chronic kidney disease. Can't definitively say causation, but they definitely contributed. They're fine for short term use but can really f$%# you up with long term, daily use.
It is absolutely valid to warn about long term use, and NSAIDs in particular (I was lucky and had a gastroscopy before they'd done any serious damage, but they found significant erosion of my stomach lining due to NSAIDs), but acetaminophen/paracetamol isn't an NSAID (ibuprofen and aspirin, for example, are)
People who are in a lot of pain and don’t know the risks.
Rationalizations like “they probably put the limit way lower than the real limit so idiots don’t OD themselves, so I can safely take a bit more” become very attractive when you’re in a lot of pain.
Okay that's right, if you just keep upping the dose because you're still in pain it might be easy to just slam a few every 4 hours
From personal experience if i have a headache I'll take 1000 mg all at once; it either works right away or it doesnt and I stop bothering until I've had a good nights rest...
It often happens when people take the max dose of straight paracetamol, and then also take another drug that has paracetamol in it without knowing that (e.g. a codeine/paracetamol or ibuprofen/paracetamol combination).
If you take 2 on average every 4 hours, you're at 12. If you're feverish or otherwise feeling ill enough and sleep deprived enough, forgetting when you took them last is easy. Personally I write down the time I took the last one.
I grew up with the understanding that acetaminophen was the safe choice for fever or aches, and ibuprofen what the more potent compound for inflammation and severe pain. I recall casual anecdotes that "my doctor said 1.5x or 2x ibuprofen dose is ok when warranted" to address major incursions.
I've never once thought about taking more than the recommended dosage of acetaminophen, largely because I had no expectation that it would provide additional benefit..
In reality, I try to consume 1/2 doses of anything or nothing at all, unless it's a serious medical treatment being administered by a professional.
> largely because I had no expectation that it would provide additional benefit..
An interesting thing with ibuprofen is that at the regular dose of 400mg it inhibits pain but if you take 1600mg it doesn't inhibit much more pain than the 400mg dose, but the inflammatory effect does increase significantly. A lot of people don't know that and take too much thinking it scales linearly.
I think most overdoses happen as a result of someone trying to hurt themselves, but I’ve also previously been in sufficient pain (always dental) that I’m counting the minutes down to when I can take more painkillers, so it’s easy to see how you could take double the expected dosage.
If your doctor recommends to take a specific dose, take the specific dose. Don't half it. Taking half of stuff can also cause further damage. Like with antibiotics, where it can lead to bacteria becoming resistant.
So don't be the "smarter" person. Do as your doctor says and if you have doubts, consult another doctor before just doing what you think is safe, but actually isn't.
Acetaminophen (paracetamol) is the drug of first choice for addressing pain and fever, in India at least. To the extent that it's regularly abused, and I know people who have been hospitalized because of abuse.
Even then, doctors are usually disapproving of ibuprofen (or some combination of it with paracetamol) unless paracetamol is contraindicated for some reason, and I had always wondered why.
I did listen to this 99% Invisible story about the use of NSAIDs in India once[1]
What you describe in an interesting contrast to the situation in The Netherlands.
Here, virtually no one is prescribing ibuprofen _without_ also prescribing a baseline of paracetamol.
I went from introvert only-child to married with kids. As they hit daycare, I was perpetually riddled with disease for about 15 months. I still had to take care of the kids though, so I was liberally taking Ibuprofen. At some point, I started to get horrible heartburn. I tried all kinds of dietary restrictions until I realized it was probably the Ibuprofen. Now, if I take even one pill, the heartburn comes back. I switched to Acetaminophen and found it was much more effective at reducing fever with no apparent side effects.
The article doesn't touch on it, but from what I've read NSAIDs like ibuprofen also slow healing. I have also read, but am unsure how reliable this is, that they can harm the remodeling process during healing and lead to chronic pain.
That said, I've found great relief at times taking a moderately large dose of ibuprofen for several days to break what seems to be a cycle of persistent inflammation. YMMV I guess.
This is some of the most useful information I've received in a while. Like the author, the low overdose threshold of acetaminophen made me avoid it, even though I always take low doses anyway and ibuprofen gives me acid reflux almost every time.
Both ibuprofen and naproxen sodium are NSAIDs and are bad for your kidneys especially in long term. I had kidney failure due to what was eventually diagnosed as an autoimmune disease but they first thing the ER doctor will ask is if you have been taking NSAIDs. My nephrologists told be its still safe to take acetaminophen at the proper dose.
None of us are your doctors but Naproxen has well-known gastric issues up to ulcers and stomach bleeding which is why it's advised to be taken with food and why it's also often prescribed with a PPI or H2 Antagonist. Cox-2 selectives such as Celecoxib greatly reduce this risk but seem to be associated with some small cardiovascular risk (admittedly this is a feature of all NSAIDs though less so in Naproxen apparently).
I had to use naproxen for some time as most effective way to control inflammation. Actually the only way, ibuprofen had some effect only in horse dozes. After visiting doctor, analyses, checking available sources was able to eliminate the reason of inflammation. Apparently it was a well known problem/solution. So far so good. Not sure about the long lasting effects of naproxen use.
Some believe naproxen sodium is worse for you because it lasts longer. Longer duration for reduced mucous membrane coverage in your stomach and intestine. Longer duration for reduced blood flow to your kidneys.
I would definitely have a chat with a doctor about it.
I’ve alternated these for fever, especially for kids, especially when it’s high and hard to control. That way you keep below the daily limit of each and don’t overdose on either.
Have gotten into a habit of keeping a note of which med when on the fridge.
I had intestinal bleeding after double ibuprofen dosage over several weeks for back pain. Definitely watch out for any prolonged and heavy use of NSAIDs.
My father, who is otherwise in very good health for a ~60 year old, has severely reduced kidney function from taking an ibuprofen+antihistamine most days of his early life to deal with allergies.
I'll second the claim that no doctor at any point in his life had told him the risks of doing that, and many encouraged the use of ibuprofen over any other alternative (including the alternative of not using OTC painkillers every single day).
I've known people who've overdosed on Tylenol and died. I'm not saying that ibuprofen won't give you acid reflux and won't damage your kidneys, but due to <reason> I tend to take a lot of ibuprofen and also for <reason> take another medication that constricts my arteries and for <reason> get a lot of blood/urine work done... and my kidney function is good and despite everything I'm generally healthy. So I would say, like many things, what medicines you take probably depend on your specific body and situation. Regardless, you won't die accidentally from an acute ibuprofen overdose. You just might die from taking tylenol if you don't realize your liver is already damaged for other reasons. So there you go!
My mom fell (88 yo) X-rayed, nothing broken but ignored her history of ulcerative colitis (tough to do, given the colostomy bag she’s worn for 50 years). Sent her home with Motrin. Ended up in the hospital for two weeks with bleeding ulcers.
Unless you’re in Rhabdo. If you’re in so much muscle pain and your kidneys are working overtime to clear broken down tissue and you then hit them with too much ibuprofen, then you can go into kidney failure and die accidentally.
I created this open-source application (https://alexcpn-faers-signal-detection.hf.space/) to analyse the FDA FAERS data set a few weeks back, just to do some good work and use Claude Code completely. I got roasted on Reddit for attempting this. But this is meant for specialists to use, as most platforms that analyse this data charge a lot from what I read.
FDA FAERS is the official dataset for reporting Adverse events from taking a drug. FDA adverse event reports about 2 million cases and 4,067 unique drugs
I agree the results are not easy for non medical professionals to interpret correctly. For example DEATH is very strong with Parecetemol and so is DEPENDECE. The latter because from AI it is a confounding factor. Acetaminophen/parecetemol is frequently co-formulated with opioids (like Hydrocodone or Codeine). The "Dependence" signal is likely attributed to the opioid, not the Acetaminophen itself...
I keep reading about this lately but what doesn't make sense then is how few deaths/injuries there are relative to how much acetaminophen is consumed. If tens of millions take it every day, that's billions of doses a year of acetaminophen. Why don't we see MORE injuries/deaths?
"Acetaminophen toxicity is the second most common reason for liver transplantation worldwide and the most common cause of acute liver failure in the United States. Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States."
56,000 emergency room visits is the key here, because "the mortality associated with acetaminophen overdose is low if recognized and treated within the first 8 hours after an acute ingestion."
So I guess it depends on if you think 56,000 is low or not.
For migraines, I take two CVS Migraine about every week to ten days. It's a cocktail of acetaminophen, aspirin and caffeine which tallies to 500 mg of acetaminophen, well under then 4g limit. It's good for four hours but you can only take two per day.
I didn't know about this acetaminophen risk. So I'll be looking for alternatives. Ibuprofen is for inflammation and not headaches. Naproxen is a candidate.
High dose aspirin (1000mg) + caffeine worked much better for me for migraines than paracetamol/ibuprofen/naproxen which did nothing. There're some studies supporting this too...
Ibuprofen is very well supported as a treatment for migraines. Not necessarily headaches generally, but definitely migraines.
But there are multiple classes of abort drugs now that a doctor might be able to prescribe you, like triptans and CGRP inhibitors, that work much better than either NSAIDs or acetaminophen.
I once read that if acetaminophen were introduced today it 100% would require a prescription because of how dangerous an overdose is.
Unrelated, but it feels like an oversight that this article said nothing about how both acetaminophen and ibuprofen reduce fevers. They aren't used solely for reducing pain.
After severe cramps once when I had to use a lot of ibuprofen (dental surgery / wisdom tooth) I now only use ibuprofen with a stomach protector to avoid stomach cramps, H. Pylori, and reflux.
Acetaminophen is part of ECA stack weight loss formula, while article says not OK with fasting. Either way, more safe solutions are known these days.
Plus caffeine, for those who don't drink coffee. Quite standard combo for people suffering from migraine. I stick to 500mg+200mg and I find it suspicious adverts for painkillers somehow always show 2 pills while dosage recommend in leaflet is just one.
Well, I mean, drats. I too always assumed Ibuprofen was safer than Acetaminophen; not the least because of massively oversimplificatic "reduced inflammation - GOOD!" 'Logic'. I'm 47 now and have probably preferred ibuprofen for last 27 or so.
Max dose combination (IBU/APAP FDC) can be useful as a substitute in emergency therapeutic situations compared to opiates. Not recommended ordinarily because of liver, kidney, and stomach impairment.[0]
Taking ibuprofen with questionable stomach condition may want to consider taking a famotidine adjuvant or duexis [1] or acetaminophen instead.
Overdose treatment of acetaminophen poisoning is the stinky N-acetylcysteine (NAC), so that maybe worth stocking whenever Tylenol is kept in a house with kids. Overdose of ibuprofen is palliative, requiring IV fluids and dialysis.
"Good for fever"? Only ignorant consumers would attempt to counteract the body's very own defenses against infection and disease.
A fever is not dangerous within normal parameters, except for being dangerous to the virus and bacteria that threaten the body. Your body runs a fever because it engages in a battle to the death with these microbes.
If you defeat the body's own defenses by lowering the fever, for example if you are a nervous mother who hates her baby's fussing, or if you're hospitalized and the nurses are laser-focused on "number go down" treatments, then you can expect to be ravaged by the contagion for much longer than expected.
The priorities have drifted. In the middle of night I don't care about getting healthy, I need to get rid of fever, so I can fall asleep and able to got to work/school in the morning. And somehow there is never right time to be sick and everyone just want to supress syndromes here and now.
For non-habitual pain relief, combinations outperform either in isolation. Studies show a significant effect, and anecdotally for me it's often the difference between dampening and outright curing a headache. Combo pills are widely available in most countries (branded as Advil Dual Action and Motrin Dual Action in the US), but they're pretty new so consumer awareness isn't yet super high.
Depends what you’re taking it for. Generally people take NSAIDs for muscle and dental pain, or anything that’s obviously inflammation, and paracetamol for anything else, particularly headaches, and is a common adjunct treatment if you have a cold or flu.
The article is not signed, we don't even know if the person writing it has any sort of medical background, take it with a grain of salt, the about page lists people and none of them has a medical background
Both of these pills are really dangerous for dogs.
Ibuprofen damages the kidneys -- and that damage is often permanent. The little filtering devices inside the kidneys don't grow back once they're destroyed. A dog who survives the poisoning can end up with lifelong kidney disease, which means special diets, more frequent vet visits, and a shorter life than she should have had.
(I watched this happen to my own dog after a house sitter stepped on her paw and gave her ibuprofen to "help." My dog lived, but she needed a special diet for the rest of her life.)
Acetaminophen wrecks the liver, and it also can damage red blood cells so they can't carry oxygen properly. A poisoned dog may get lethargic, vomit, start to breathe heavily... This is especially dangerous for older dogs, or any dog whose red blood cells are already compromised, by conditions like IMHA.
Honestly this article is mixing a lot of different factors
> Acetaminophen has a scarily narrow therapeutic window. The instructions on the package say it's okay to take up to four grams per day. If you take eight grams, your liver could fail and you could die.
Gee I don't know, I think this is a wide enough window to not miss it. That difference is 8 500mg pills
> that for most people in most circumstances, acetaminophen is safer than ibuprofen, provided you use it as directed. I think most doctors agree with this.
Could be but I think a lot of doctors underestimate the dangers of paracetamol as well
All of the factors the author mentions about IBP are true. But it's all about the details. Safer? Safer in which condition?
"Dehydrated" ok take a glass of water. Active bleeding? Most NSAIDs interfere with that, and no you won't become a hemophiliac by taking one Ibuprofen
An as a conclusion, I find it "funny" that nobody considers how healty/safe it is to take paracetamol and have mild analgesia (translation - you're still in pain) and taking ibp and having better analgesia
Mischkowski’s own research has uncovered a sinister side-effect of paracetamol. For a long time, scientists have known that the drug blunts physical pain by reducing activity in certain brain areas, such as the insular cortex, which plays an important role in our emotions. These areas are involved in our experience of social pain, too – and intriguingly, paracetamol can make us feel better after a rejection.
Mischkowski wondered whether painkillers might be making it harder to experience empathy
And recent research has revealed that this patch of cerebral real-estate is more crowded than anyone previously thought, because it turns out the brain’s pain centres also share their home with empathy.
For example, fMRI (functional magnetic resonance imaging) scans have shown that the same areas of our brain become active when we’re experiencing “positive empathy” –pleasure on other people’s behalf – as when we’re experiencing pain.
Given these facts, Mischkowski wondered whether painkillers might be making it harder to experience empathy. Earlier this year, together with colleagues from Ohio University and Ohio State University, he recruited some students and spilt them into two groups. One received a standard 1,000mg dose of paracetamol, while the other was given a placebo. Then he asked them to read scenarios about uplifting experiences that had happened to other people, such as the good fortune of “Alex”, who finally plucked up the courage to ask a girl on a date (she said yes).
The results revealed that paracetamol significantly reduces our ability to feel positive empathy – a result with implications for how the drug is shaping the social relationships of millions of people every day. Though the experiment didn’t look at negative empathy – where we experience and relate to other people’s pain – Mischkowski suspects that this would also be more difficult to summon after taking the drug.
What? Read the article fully; it has to do with "negative empathy" different from "positive empathy".
Dominik Mischkowski is a Pain Researcher at Ohio University who has been studying this for a while. The word "suspects" here is statistical research-speak meaning there is a correlation (w.r.t. positive empathy) but more studies are warranted (w.r.t. negative empathy). That is all.
This is pretty misguided.A casual mistake like forgetting your cough syrup has acetaminophen can easily cause an overdose and then you fucking die. That’s not the risk profile you want for “most people in most circumstances”.
500mg from a capsule and 500 from cough syrup 4 times a day is still fine. With a 100% safety margin still.
If you’re taking more meds than that without clinical supervision Id say something is wrong in the system or your medicine practices.
Where I’m from it’s common to walk to the nearest pharmacy and get meds when needed. Even over the counter stuff like paracetamols. And talking to the pharmacist. They’ll ask what you’re already taking and tell you what else to get.
You don't want either of these; what you want is naproxen.
It works similarly, but stays a lot longer (half life is cited as being anywhere from 12 to 17 hours).
Acetaminophen and ibuprofen are just for temporary problems, like a headache that would go away on its own in a couple of hours.
They are uneconomic and inconvenient if you have something more persistent to keep at bay. Four ibuprofens or one naproxen? No brainer.
The main disadvantage of naproxen is that it's not approved for kids. So there is no naproxen syrup for infants or anything of the sort. Thus, you still need acetaminophen for that.
As pointed out in the article, naproxen is an NSAID like Ibuprofen, though slightly more COX1 selective. It likely has a somewhat lower risk of serious renal and cardiovascular events, but higher risk of GI bleeds. There are some studies that show little to no increase cardiovascular risk, but most do show some or even comparable to ibuprofen.
Convenience vs ibuprofen is a thing given the longer half life, but it still generally comes with similar risks. If you are taking anything for more than just an occasional headache, definitely discuss with a doctor, COX2 selectives like celecoxib may be a better risk profile and even more convenient.
(COX1 and COX2 selectivity loosely separate which systems get the brunt of the side effects)
Guess it depends on country. Here in Norway official sources[1][2] do say acetaminophen (paracetamol here) should be the default for treating fever and pain in kids, adults, pregnant women and elderly, and have for some time. Ibuprofen they say should be used with caution.
[1]: https://www.dmp.no/nyheter/behov-for-smertestillende-slik-ve...
[2]: https://nhi.no/for-helsepersonell/nytt-om-legemidler/arkiv-2...
> but it does absolutely nothing with actual pain. It is placebo at best.
This is simply false.
It works against fewer or maybe mild inflammation and what not ... but it does absolutely nothing with actual pain. It is placebo at best.
But yet in some countries pediatricians will libreally prescribe it to toddlers
[1] https://www.bmj.com/content/368/bmj.m1086
Also from [2] "In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution."
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.1451...
I always thought a simple over-the-counter supplement (NAC) being the cure for an overdose was so cool. It's a pretty cool substance in a lot of ways, and this is a great spur to myself to research it more thoroughly.
Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
I'd believe it. I first heard of NAC on the nootropic subreddit in a past lifetime. The benefits vary, but generally it's a safe thing with a low chance of making anything worse, but a possibility to improve things. Many neurodivergent folk have written about how they benefit.
I'd give more info on the exact benefits they found (iirc OCD and rumination loops could be broken more easily), but unfortunately my memory is failing me.
Usually here in Canada it's available in capsule form which I find less effective.
There is a limit to the amount of opioids they will prescribe you, even if you are in mind shattering pain. For instance while attempting to get your dental insurance to actually cover a treatment you may find yourself between risking organ damage or risking $5000+ in ER visit bills only to have them refuse to give you anything but Tramadol.
I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
20 not-especially-large tablets
Suppose your arthritis is acting up, so you start taking Tylenol 8hr Arthritis Pain[1]. That's 2 tablets every 8 hours. They're extended-release with 650mg per tablet. A total of 3900 mg in 24 hours.
A few days later you get the flu, so you decide to add what seems like a completely different medication: Theraflu Flu Relief Max Strength[2]. It has a cough suppressant and an antihistamine. But each caplet also contains 500 mg of acetaminophen. It says to take 2 caplets every 6 hours, so you take 8 of them in 24 hours[3]. That's another 4000 mg.
Between the two, you're at 7900 mg.
Then you wake up in the morning and take both medications, but 30 minutes later you've forgotten you took them. You're not thinking straight because you're sick. So you accidentally take a second dose. That additional 2300 mg brings your total to 10200 mg.
---
[1] https://www.tylenol.com/products/arthritis/tylenol-8hr-arthr...
[2] https://www.theraflu.com/products/day-night-flu-relief-max-s...
[3] You weren't supposed to take 8 of them, though. If you'd read the label very carefully, you'd have seen it also says not to exceed 6 in a 24-hour period.
I did toss on the other option, stand alone, at one point so I could get some sleep.
It left the medication I was more comfortable taking as an add-on option if things got bad enough. (This particular medication has much lower risk of overdose, so if I got stupid and took it again there would be no significant additional risk.)
It's ironic, but taking the combined medication with a known higher risk of its own was better than taking the lower risk medication.
One was controlled, higher risk, taken at specific times, while the other was taken in addition, on demand, as required.
Also, loved your TV show back in the day. :-)
I presume your protein intake was adequate and diverse prior to this misadventure....
... Suddenly I'm maintaining a continuous note of when I'm taking which medicine to avoid crossing safe limits (which I anyway was crossing most days).
I was only told to take 2 paracetamols a day (bullshit dose, I'd be waking up from the pain even with more pain meds).
"Diclofenac for rare use" - well, if nothing else is touching the pain, is it an emergency?
Eventually after forever I was able to transition to Ibuprofen + paracetamol. And I already have a health condition which is heavy on my kidneys... pain management can be absolutely crazy.
Have you considered clean cannabis products?
Speaking as someone who is not-infrequently in significant pain, I sincerely hope that you never have to.
Ibuprofen is a Nonsteroidal Anti-inflammatory Drug (NSAID) that reduces pain and inflammation, while acetaminophen does not. (Acetaminophen is believed to act mainly in the brain rather than at the site of injury).
Ibuprofen- Fundamentally, if the pain is caused by inflammation, reducing the immune systems response to it can reduce pain, but if the pain is more acute it won't make a dent.
With acetaminophen, taking more isn't a solution in most cases, you need another method to reduce the pain further if it doesn't achieve its goal.
(That's why it's combined with things like codeine, which affects the brain in a different way for an additive effect)
I don’t know about “most cases” but often you don’t want to reduce the pain _further_, you want to reduce the pain _again_. (Having an alternative definitely helps in the meantime.)
edit: https://www.24pharma.nl/paracetamol-eg-1000mg-120-tabletten
Meanwhile, it's funny that it seems like acetaminophen should safer in more scenarios, but the other has a lot of overdoses with typical use, I guess that's why there's a gap between the two, because ODs are apparently a lot more common or at least more legible than problems caused by the other drug.
I arrived in Aus in 2021 and was amazed to be able to buy a pack of 40+, coming from the UK where the limit had been in place for some years.
It's the usual public health balancing act of help vs harm.
You can overdose on water too, they haven't banned 5-gallon jugs (yet).
Harm reduction is about shifting probability distributions, not guaranteeing outcomes. Kids can still get into pill bottles with childproof medication caps, but accidental ingestion of aspirin by children reduced by 40-55% after they were mandated. [0]
[0]: https://pubmed.ncbi.nlm.nih.gov/440889/
I'm aware of acetaminophen's down sides, and yet recently I was taking it combined with 2 other medications at the time.
Why? Because all three medications are recommended for dealing with the issue I had. (Alone and in combination)
The moment it wasn't helping further? Done.
There is this broken idea, particularly apparent in North America, but in western society that more is better for many things. It's not.
More pain killers don't do anything if they max out the relief they can give you, overloading their mechanism doesn't reduce anything, but taxing your liver or your kidneys.
All medications are potentially toxic, your body wants to dispose of them. In appropriate dosages they will benefit you, but more isn't inherently better.
Even water can kill you in sufficient quantity.
We do the same with diet; where someone declares one ingredient in a meal healthier than another; it isn't. A single ingredient isn't better or worse for you in a meal. Your diet however can be good or bad; over time that matters.
Paracetemol has always been seen as first thing you'd take for pain relief, and you'd "step up" ibuprofen as an escalation, but that might more to do with marketing of Panadol (paracetemol) vs Nurofen (ibuprofen).
We'd look on at the US where you were taking Advil like candy in confusion.
One great thing you learn as a parent, you can alternate acetaminophen and ibuprofen. Both of them are recommended every four hours, but you can stagger one by two hours to maintain consistency of pain-relief taking ibuprofen then paracetemol two hours later
The positive of it is it got me in the habit of logging whenever I take it, either in a note on my phone or just a sheet of paper I place on my dresser under the bottle. This helps make sure I stay under the 3-4g/d limit.
Last year I was diagnosed with a rare headache disease (NDPH). We thought it completely came out of nowhere, but I had logs in my phone recording headaches and acetaminophen use intermittently from a few weeks prior. This proved useful in the diagnosis.
Moral of the story: log when you take it to avoid overdosing. Combine that with some basic symptom logging (like 1 line, 10 words or less). You never know when that might be useful for your doctors later on.
Rationalizations like “they probably put the limit way lower than the real limit so idiots don’t OD themselves, so I can safely take a bit more” become very attractive when you’re in a lot of pain.
From personal experience if i have a headache I'll take 1000 mg all at once; it either works right away or it doesnt and I stop bothering until I've had a good nights rest...
I've never once thought about taking more than the recommended dosage of acetaminophen, largely because I had no expectation that it would provide additional benefit..
In reality, I try to consume 1/2 doses of anything or nothing at all, unless it's a serious medical treatment being administered by a professional.
An interesting thing with ibuprofen is that at the regular dose of 400mg it inhibits pain but if you take 1600mg it doesn't inhibit much more pain than the 400mg dose, but the inflammatory effect does increase significantly. A lot of people don't know that and take too much thinking it scales linearly.
So don't be the "smarter" person. Do as your doctor says and if you have doubts, consult another doctor before just doing what you think is safe, but actually isn't.
Even then, doctors are usually disapproving of ibuprofen (or some combination of it with paracetamol) unless paracetamol is contraindicated for some reason, and I had always wondered why.
What you describe in an interesting contrast to the situation in The Netherlands. Here, virtually no one is prescribing ibuprofen _without_ also prescribing a baseline of paracetamol.
[1]: https://99percentinvisible.org/episode/579-towers-of-silence...
That said, I've found great relief at times taking a moderately large dose of ibuprofen for several days to break what seems to be a cycle of persistent inflammation. YMMV I guess.
I avoid both and stick with naproxen sodium. Any issues with that one? Lasts the longest too.
I would definitely have a chat with a doctor about it.
Have gotten into a habit of keeping a note of which med when on the fridge.
I'll second the claim that no doctor at any point in his life had told him the risks of doing that, and many encouraged the use of ibuprofen over any other alternative (including the alternative of not using OTC painkillers every single day).
IBU: -stomach -kidneys -bp+ -clotting --NERD --NECD --NEUD --SNIUAA --SNIDR --DRESS
APAP: -liver --DRESS
-- extreme, rare side-effects
If you don’t realize your kidneys are already damaged you might die from kidney failure because of ibuprofen.
FDA FAERS is the official dataset for reporting Adverse events from taking a drug. FDA adverse event reports about 2 million cases and 4,067 unique drugs
I agree the results are not easy for non medical professionals to interpret correctly. For example DEATH is very strong with Parecetemol and so is DEPENDECE. The latter because from AI it is a confounding factor. Acetaminophen/parecetemol is frequently co-formulated with opioids (like Hydrocodone or Codeine). The "Dependence" signal is likely attributed to the opioid, not the Acetaminophen itself...
Adverse Event Acetaminophen PRR (95% CI) Acetaminophen n ibuprofen PRR (95% CI) ibuprofen n ACUTE KIDNEY INJURY 0.87 (0.80-0.96) 498 4.27 (3.91-4.67) * 483 ANAPHYLACTIC REACTION 0.61 (0.51-0.72) 122 9.85 (8.90-10.90) * 382 ANGIOEDEMA 1.31 (1.13-1.53) 170 15.26 (13.77-16.92) * 378 DEATH 1.44 (1.40-1.49) 3958 0.07 (0.06-0.10) 42 DEPENDENCE 237.12 (231.51-242.88) * 39679 0.02 (0.01-0.05) 4 DEPRESSION 2.18 (2.05-2.31) * 1157 0.39 (0.29-0.52) 43 DRUG EFFECTIVE FOR UNAPPROVED INDICATION 16.77 (16.11-17.46) * 3180 44.17 (42.18-46.25) * 1921 DRUG HYPERSENSITIVITY 0.57 (0.51-0.64) 327 3.30 (2.98-3.65) * 372
56,000 emergency room visits is the key here, because "the mortality associated with acetaminophen overdose is low if recognized and treated within the first 8 hours after an acute ingestion."
So I guess it depends on if you think 56,000 is low or not.
Source: "Acetaminophen Toxicity", David H. Schaffer; Brian P. Murray; Babak Khazaeni. 2026/02/19. https://www.ncbi.nlm.nih.gov/books/NBK441917/
I didn't know about this acetaminophen risk. So I'll be looking for alternatives. Ibuprofen is for inflammation and not headaches. Naproxen is a candidate.
Ibuprofen is very well supported as a treatment for migraines. Not necessarily headaches generally, but definitely migraines.
But there are multiple classes of abort drugs now that a doctor might be able to prescribe you, like triptans and CGRP inhibitors, that work much better than either NSAIDs or acetaminophen.
Unrelated, but it feels like an oversight that this article said nothing about how both acetaminophen and ibuprofen reduce fevers. They aren't used solely for reducing pain.
Acetaminophen is part of ECA stack weight loss formula, while article says not OK with fasting. Either way, more safe solutions are known these days.
1g of Paracetamol with 400mg of Ibuprofen gives similar pain relief as 2mg of IV morphine.[1]
[1] https://pubmed.ncbi.nlm.nih.gov/29017585/
This is semi recent research on how it might be blocking pain
Max dose combination (IBU/APAP FDC) can be useful as a substitute in emergency therapeutic situations compared to opiates. Not recommended ordinarily because of liver, kidney, and stomach impairment.[0]
Taking ibuprofen with questionable stomach condition may want to consider taking a famotidine adjuvant or duexis [1] or acetaminophen instead.
Overdose treatment of acetaminophen poisoning is the stinky N-acetylcysteine (NAC), so that maybe worth stocking whenever Tylenol is kept in a house with kids. Overdose of ibuprofen is palliative, requiring IV fluids and dialysis.
0. https://www.researchgate.net/publication/382639515_Ibuprofen...
1. https://pubmed.ncbi.nlm.nih.gov/25516006/
I Am Not A Doctor And This Is Not Medical Advice.
(I think?).
Tylenol/acetaminophen is good for fever which NSAIDs won't help. Otherwise, take both and alternate their dosing times for better pain coverage.
A fever is not dangerous within normal parameters, except for being dangerous to the virus and bacteria that threaten the body. Your body runs a fever because it engages in a battle to the death with these microbes.
If you defeat the body's own defenses by lowering the fever, for example if you are a nervous mother who hates her baby's fussing, or if you're hospitalized and the nurses are laser-focused on "number go down" treatments, then you can expect to be ravaged by the contagion for much longer than expected.
Yes, ignorant consumers and physicians across the world.
You can't just 'vibe medicine' or 'vibe biology' - please don't comment if you don't know what you're talking about.
Ibuprofen damages the kidneys -- and that damage is often permanent. The little filtering devices inside the kidneys don't grow back once they're destroyed. A dog who survives the poisoning can end up with lifelong kidney disease, which means special diets, more frequent vet visits, and a shorter life than she should have had.
(I watched this happen to my own dog after a house sitter stepped on her paw and gave her ibuprofen to "help." My dog lived, but she needed a special diet for the rest of her life.)
Acetaminophen wrecks the liver, and it also can damage red blood cells so they can't carry oxygen properly. A poisoned dog may get lethargic, vomit, start to breathe heavily... This is especially dangerous for older dogs, or any dog whose red blood cells are already compromised, by conditions like IMHA.
> Acetaminophen has a scarily narrow therapeutic window. The instructions on the package say it's okay to take up to four grams per day. If you take eight grams, your liver could fail and you could die.
Gee I don't know, I think this is a wide enough window to not miss it. That difference is 8 500mg pills
> that for most people in most circumstances, acetaminophen is safer than ibuprofen, provided you use it as directed. I think most doctors agree with this.
Could be but I think a lot of doctors underestimate the dangers of paracetamol as well
All of the factors the author mentions about IBP are true. But it's all about the details. Safer? Safer in which condition?
"Dehydrated" ok take a glass of water. Active bleeding? Most NSAIDs interfere with that, and no you won't become a hemophiliac by taking one Ibuprofen
Also, some countries do add a notice for kidney problems for Paracetamol as well (e.g.) https://www.medicines.org.uk/emc/product/5164/pil
An as a conclusion, I find it "funny" that nobody considers how healty/safe it is to take paracetamol and have mild analgesia (translation - you're still in pain) and taking ibp and having better analgesia
The medications that change who we are - https://www.bbc.com/future/article/20200108-the-medications-...
Excerpt:
Mischkowski’s own research has uncovered a sinister side-effect of paracetamol. For a long time, scientists have known that the drug blunts physical pain by reducing activity in certain brain areas, such as the insular cortex, which plays an important role in our emotions. These areas are involved in our experience of social pain, too – and intriguingly, paracetamol can make us feel better after a rejection.
Mischkowski wondered whether painkillers might be making it harder to experience empathy
And recent research has revealed that this patch of cerebral real-estate is more crowded than anyone previously thought, because it turns out the brain’s pain centres also share their home with empathy.
For example, fMRI (functional magnetic resonance imaging) scans have shown that the same areas of our brain become active when we’re experiencing “positive empathy” –pleasure on other people’s behalf – as when we’re experiencing pain.
Given these facts, Mischkowski wondered whether painkillers might be making it harder to experience empathy. Earlier this year, together with colleagues from Ohio University and Ohio State University, he recruited some students and spilt them into two groups. One received a standard 1,000mg dose of paracetamol, while the other was given a placebo. Then he asked them to read scenarios about uplifting experiences that had happened to other people, such as the good fortune of “Alex”, who finally plucked up the courage to ask a girl on a date (she said yes).
The results revealed that paracetamol significantly reduces our ability to feel positive empathy – a result with implications for how the drug is shaping the social relationships of millions of people every day. Though the experiment didn’t look at negative empathy – where we experience and relate to other people’s pain – Mischkowski suspects that this would also be more difficult to summon after taking the drug.
Also see the previous thread; A social analgesic? Acetaminophen (paracetamol) reduces positive empathy - https://news.ycombinator.com/item?id=31263305
Why should I trust someone who doesn’t test properly but just suspects?
Dominik Mischkowski is a Pain Researcher at Ohio University who has been studying this for a while. The word "suspects" here is statistical research-speak meaning there is a correlation (w.r.t. positive empathy) but more studies are warranted (w.r.t. negative empathy). That is all.
If you’re taking more meds than that without clinical supervision Id say something is wrong in the system or your medicine practices.
Where I’m from it’s common to walk to the nearest pharmacy and get meds when needed. Even over the counter stuff like paracetamols. And talking to the pharmacist. They’ll ask what you’re already taking and tell you what else to get.
Of course, we could press the fix this immediately button by requiring acetaminophen to be sold mixed with NAC but that would be too easy.
It works similarly, but stays a lot longer (half life is cited as being anywhere from 12 to 17 hours).
Acetaminophen and ibuprofen are just for temporary problems, like a headache that would go away on its own in a couple of hours.
They are uneconomic and inconvenient if you have something more persistent to keep at bay. Four ibuprofens or one naproxen? No brainer.
The main disadvantage of naproxen is that it's not approved for kids. So there is no naproxen syrup for infants or anything of the sort. Thus, you still need acetaminophen for that.
Convenience vs ibuprofen is a thing given the longer half life, but it still generally comes with similar risks. If you are taking anything for more than just an occasional headache, definitely discuss with a doctor, COX2 selectives like celecoxib may be a better risk profile and even more convenient.
(COX1 and COX2 selectivity loosely separate which systems get the brunt of the side effects)