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.
I randomly bought NAC just to try it. I dont know about the chemical interactions, but going out with collegues at that time taught me that it's basically impossible to get drunk. Usually a pint of beer is enough to make le feel at least a little dizzy, but when taking NAC, it was all like drinking water
If you all think NAC is great, wait till you try liposomal glutathione (glutathione is one of the things NAC is a precursor for, one of the general take-out-the-trash compounds for your cells). Of all the supplements I’ve tried, it has probably the most immediately noticeable positive effect (maybe because you take it by leaving it under your tongue to be absorbed sublingually for a bit before swallowing). Generally leaves me feeling great, even if I was kind of dragging and tired beforehand.
NAC taken before consuming alcohol has a positive effect apparently, but taken afterwards it's detrimental as mentioned here: https://en.wikipedia.org/wiki/Acetylcysteine
On mice.
Vaccine Ordering https://xkcd.com/2422/
Took me a while, because i pronounce "Pfizer" as "pfee-tseh-r" in my head
That's the original pronunciation
Same! I thought I was going crazy but the effect is clear and reproducible. My hangovers are also less bad.
Just a note: “research about the safety of taking NAC every day for the long term is limited.” cf. a concerning 2019 animal study regarding higher risks of cancer https://doi.org/10.1172/jci.insight.127647 also discussed at https://www.science.org/content/blog-post/n-acetyl-cysteine-...
When I go out drinking with my pharmacist buddy, we take NAC before going out. He swears it makes hangovers less likely. I can't say I've noticed that particular effect, but I do seem to sleep a bit better on those nights.
Here in Singapore NAC is sold to make muckus more liquid to alleviate coughs.
Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
> 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.
You'll find a detailed description oft potential effects and uses here: https://en.wikipedia.org/wiki/Acetylcysteine (aka NAC)
My anecdotal experience is that NAC makes me much more tolerant to alcohol. As in, I can drink a lot more without feeling the effects. Since I don't get the same buzz, I care less about reaching for a beer.
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…
Dissolvable tablets & powders are still useful for getting rid of mucus. Maybe inhaling is better, but anecdotally the tablets seem to work.
The dissolvable tablets completely fix a runny nose for me. Much better than any nose spray, which tend to irritate the nose and lead to chronic runny nose if taken for too long.
Have you tried a neti pot or similar?
Same where I'm from, it's in pill / capsule form
Could somebody package Tylenol with a sufficient amount of NAC to de-risk it? I suspect such a formulation would not require trials?
Certain esters have been found to be much safer (in mice, at least):
> The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg^-1 and the intraperitoneal LD50 was 1900 mg kg^-1 ...
That's for pyroglutamic and glutamic acid esters of paracetamol: https://pubmed.ncbi.nlm.nih.gov/8799871/
and more general analogs apparently can also be designed to not produce NAPQI:
> Thus, in 2020, N-sulpharyl-APAP prodrugs 39–40 (Fig. 11) were developed. [...] They are not hepatotoxic because they do not generate toxic metabolite NAPQI, even in concentrations equal to a toxic dose of APAP (600 mg kg^−1 in mice).
https://pubs.rsc.org/zh-tw/content/articlepdf/2024/ra/d4ra00... p. 9702.
These would probably require trials, though.
See superscript 6 on the article. Apparently NAC might has side effects of its own.
One of the side effects in a study in mice was inducing lung cancer: https://doi.org/10.1172/jci.insight.127647
NAC is so amazing for us in terribly polluted areas. Also great before drinking
I am blessed with living in one of the most polluted areas in the world (PM2.5 going into thousands of µg/m³ in winter; summers are not much better due to dense chemical smog). Can you say more about how you're using it to combat that? Thanks!
Glycine + NAC even better, both precursors for Glutathione, Glycine also great for sleeping.
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.
Extra strength tylenol is 500mg a tablet, so 20 pills. Think most of the accidental ODs are due to people not realizing its included in other cold meds, and also being loopy from whatever illness they're trying to manage, and so end up forgetting when they last took the meds.
Its also a pretty popular choice for people trying to kill themselves, though, so I suspect a non-trival chunk of ODs in the statistics given in the article were intentional.
I've been prescribed slightly more than 5g per day (2 x 650mg tablets every 6 hours) for pain after an operation jointly with ibuprofen, which is scarily close to the limits.
I managed to overdose by accident with severe dental pain. Wasn't thinking straight, took about 8g - which is even more scarily close to the limits.
I'm fairly sure that caused some liver damage. I wasn't aware of anything apart from feeling a bit weird.
At the time, I had no idea it was potentially deadly.
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.
It is mind boggling how statements like that are possible in the US.
I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
> I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
Having a condition that actually warrants strong opioids and not being able to get them at any price is definitely not an improvement.
The problem is fundamentally that we want to pretend doctors can always distinguish two people describing the same symptoms when one person actually has them and the other is trying to get drugs. The often can't, so you can either make it hard for people to get pain medications even if they need them, or you can make it easy for people to get them even if they don't. And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
> And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
Could not agree more. Depriving people with legitimate pain of opioids is IMHO legitimate torture. It's a bit of a variance on the trolley problem in that the doctor/government isn't causing the pain, but their inaction is prolonging it.
Whenever people here mention to my critique of US healthcare how its now mostly solved problem now, its 'good' to see the other side and reality. It certainly doesn't seem solved unless you have a million or two just laying around on the account, while mortgages and kids tuitions are paid. And I can easily imagine a long term condition or 10 which, if unlucky in terms of treatment cost coverage can wipe out that sum in a decade or two, for a single person.
Seriously, how can you guys consider this acceptable. I am not of faith but doesn't bible teach to be kind to your fellow men above all? One would expect more adherence to such basic moral rules in such conservative christian society.
> Whenever people here mention to my critique of US healthcare how its now mostly solved problem now
Who says that? I don't think anyone sane can believe that US healthcare is "solved".
I don’t know a single person in my life who thinks US healthcare is good, so that’s weird. And many my peers a have good jobs with good health insurance. Everyone I know has at least one bad story about insurance, if you’ve ever had more than really basic checkups.
The problem with the US system is that it doesn't know what it's trying to be.
If you did a socialist system then everything is "free" but possibly slow and expensive on the back end when the government isn't efficient.
If you did a libertarian system then everything is cheap but it's caveat emptor because nobody is stopping you from buying morphine for $10 from Amazon.
The US system isn't either one. It pretends to be a market sometimes but then has a bunch of rules to thwart competition. Doctors are required by law to do residency but the government limits the number of residency slots in response to lobbying from the AMA so there aren't enough doctors. "Certificate of need" laws explicitly prohibit new competitors for various services. Insurance is tied to employment to make it hard for individuals to shop around. Laws encourage, require or have the government provide "prescription drug coverage" to make patients price insensitive so drug companies can charge a huge premium for patenting a minor improvement or simple combination of existing drugs and have the patient will something which is marginally if at all better even if it's dramatically more expensive because they don't see the cost when the insurance/government is required to pay for it.
It's a big pile of corruption, because all that money is going to places. But then if you try to fix it, half the population insists on doing the first one and the other half is only willing to do the second one, and the industry capitalizes on this to prevent either one.
Maybe instead we should do both rather than neither. Have the government provide a threshold level of services, like emergency rooms and free clinics and anything more than that the local government wants to fund, and then have a minimally regulated private system that anyone can use if the government system doesn't satisfy them.
> What does ingesting 10g of acetaminophen even look like?
20 not-especially-large tablets
As an American this is such a weird question to me. I purchase my ibuprofen and benadryl in bottles of anywhere from 400 to 1000 pills every few years.
Is this not suicidal behavior?
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.
---
[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.
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.
Doin' the Lord's Work here, sir.
Also, loved your TV show back in the day. :-)
I took 2 full packs in a day once while trying to recover from severe pain. Didnt find out until later that it was supposedly a fatal dose.
Mm. Apparently i don't understand pain and the medication it drives people towards.
> Apparently i don't understand pain
I didn't until I had a bulging lower back disc pressing on my sciatic nerve. My leg felt like it was constantly on fire no matter what position I put myself in. In the past I've torn my ACL and had surgery to reconstruct and that pain was like stubbing my toe compared to the back pain. I understood how people become addicted to pain meds after my back situation.
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.
Pain management can be crazy but in your case it sounds like they simply didn't prescribe the appropriate medication presumably due to the anti opiate hysteria that has taken hold.
While that's quite possibly true, I forgot to mention that I'm not in the US but India. I was conscious the whole time, with only local anesthesia. Also the dentist in question is actually our "family" dentist, and he's a pretty knowledgeable/skillful guy (easily more knowledgeable than many GPs on health matters of the body).
Fun fact, you can totally get them to pause the procedure without saying a word. All you have to do is end up in a lot of pain, have your heart rate skyrocket like anything, and get everyone in the OT very concerned ;)
> Apparently i don't understand pain...
Speaking as someone who is not-infrequently in significant pain, I sincerely hope that you never have to.
Did you suffer any liver function damage as a result?
I presume your protein intake was adequate and diverse prior to this misadventure....
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.)
Only if you take them all at once.
Also dementia
Or 10 slightly larger ones
edit: https://www.24pharma.nl/paracetamol-eg-1000mg-120-tabletten
I’ve pretty much only ever seen them sold at 500mg; are you regularly seeing them where you are sold in 1g form?
The .nl indicates the netherlands. Many people in the netherlands vent/joke about how the doctors here only ever tell you to take paracetamol and come back in two weeks if it's still a problem (recursive solution).
However the last time I went to my GP she scoffed at me taking the maximum and suggested I take literally double the maximum recommended dose 4-5 times a day which totaled I think 2.5x the daily maximum on the package. I am very much a "believer" in science and reasonable medical authority but this experience sowed the seeds of doubt, because from what I have always heard, that can actually kill you or cause permanent liver issues. I was also taking diclofenac simultaenously, and when I told her how many mg, she asked "where can you even buy such small doses, that's what I would give a small child" =/
They are widely sold at 1000 mg (1g) tablets in Europe, but in many countries they require doctor's prescription. There are also purchase limits to the number of pills you can buy at once.
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).
The linked size is also quite common in Belgium.
In Europe for sure they're also sold in 1g dosing. I think the packages don't contain lots of pills, though. Definitely not US style buckets of pills.
Buy a pack of 20x500mg (just checked, common size in Germany), take 2-3 every half hour for a while.
Sure, that's extreme. But if you're unaware of the risks, you feel sick, and you believe it's helping you.
I mean, people aren't killing themselves in masses with it, but it happens every now and then. Easily imaginable that one in a few million people will have enough tendency to take more pills and is unaware of the overdose danger.
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.
Similar rules in Europe, or at least, Portugal.
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.
When was this changed?
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.
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.
Oh right - that's probably what we did, buy a big pack from behind the counter.
I don't think you can even do that in the UK.
Yeah we usually have a few packs hanging around, and I get the 'it seems stupid' thing, but sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life. I dunno, I hope that's shown in the evidence anyway. Otherwise it's just pointless like the whole pseudoephedrine song and dance, which has inconvenienced anyone looking for a decongestant while doing sweet FA to the availability of meth.
> Oh right - that's probably what we did, buy a big pack from behind the counter.
No, when you visited they were still on the shelf. They only put them behind the counter in 2025.
> sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life
I'm philosophically not for making suicide harder. If someone wants to die, that's their right. And practically, while you might be able to show a stat-sig decrease in paracetamol poisoning, I'd expect the suicides to largely just move to other methods.
> I hope that's shown in the evidence anyway
tl;dr: Yes
Paraphrasing from [0], after September 1998 when the restriction was introduced, "The annual number of deaths from paracetamol poisoning decreased by 21% [...] the number from salicylates decreased by 48% [...] Liver transplant rates after paracetamol poisoning decreased by 66% [...] The rate of non-fatal self poisoning with paracetamol in any form decreased by 11%"
See also [1]: "in the 11 years following the legislation there were an estimated 765 fewer suicide and open verdict deaths from paracetamol poisoning, which represented a reduction of 43% [...] This reduction was largely unaltered after controlling for a downward trend in deaths involving other methods of poisoning and also suicides by all methods."
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC31616/
[1] https://www.psych.ox.ac.uk/research/research-groups/csr/rese...
Jan 2025: https://www.psa.org.au/changes-to-paracetamol-scheduling-wil...
It's the usual public health balancing act of help vs harm.
You can still die if you take your idiot-proof Aussie blister packs with alcohol. So it's more an inefficient use of cabinet space.
You can overdose on water too, they haven't banned 5-gallon jugs (yet).
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]
[0]: https://pubmed.ncbi.nlm.nih.gov/440889/
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.
No.
Alcohol and Acetominophen/paracetamol should not be mixed.
https://www.medicalnewstoday.com/articles/322813Sorry, crappy link. If you don't like it, it is easy to search for a better one.
There is a danger in chronic abuse resulting in upregulation. Mixing the two at once is no problem for the liver, which is also why patient information leaflets for paracetamol do not contain a warning to avoid alcohol, only about chronic alcohol abuse.
Your crappy source is vague in what consumption pattern constitutes a risk and actually cites a better source that supports the idea that acute alcohol consumption reduces paracetamol toxicity. https://www.biorxiv.org/content/10.1101/2020.07.07.191916v1....
That's a mathematical model, but this relationship between the two is what I was taught in medical school and it is still supported by the science. There's plenty of other sources, I just picked that one because your article cites it. Just search for "paracetamol ethanol" on Google Scholar.
This is correct.
s/idiot-proof/idiot-resistant/g
Also applies to most similar phrases ending in -proof. Should be eye-opening.