Comment by pugio
9 hours ago
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.
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.
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.
> 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)
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.
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Dissolvable tablets & powders are still useful for getting rid of mucus. Maybe inhaling is better, but anecdotally the tablets seem to work.
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Same where I'm from, it's in pill / capsule form
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.
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-...
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/
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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.
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.
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.
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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.
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> 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?
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Or 10 slightly larger ones
edit: https://www.24pharma.nl/paracetamol-eg-1000mg-120-tabletten
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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.
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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/322813
Sorry, crappy link. If you don't like it, it is easy to search for a better one.
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This is correct.
s/idiot-proof/idiot-resistant/g
Also applies to most similar phrases ending in -proof. Should be eye-opening.