the "daily" recommended doses are for a single day. If you are taking it daily you need to at least halve the recommended dose. I wouldn't have said a week was a problem but... yeah. Tylenol is dangerous.
> One study reported that ingestion of the recommended maximum amount of 4000 mg of APAP for 2 weeks resulted in the asymptomatic elevation of alanine transaminase, up to three times normal, in 40% of patients.19 These transaminase elevations did not amount to any clinical significance, and after the APAP was discontinued the transaminase levels returned to normal.19 Yet, while asymptomatic, chronically elevated aminotransferases may be of concern to healthcare providers, leading to further costly diagnostic studies or changes/restrictions in necessary medications
If anything the summary in that review is underselling it. Average was 2.78x baseline (3x is considered clinically significant) and 20% of the population was over 5x the peak (so, 20% had clinically significant elevations from the study). By peak levels, around 27% of the population saw peak levels of 8x baseline. So basically, even the "average" participant was almost to the threshold of clinical significance just from this study (at the recommended daily dose) and a cohort of around 20-25% will see clinically-significant warning signs at the recommended dosage, even among healthy patients. And risk factors significantly increase that.
That's basically a "liver stressor" enzyme, even if it's not killing the patients over the course of the study, it's not a good thing. That's your body's warning signal that it's stressed. And generally that's an uncontroversial finding I think, everyone agrees tylenol is a liver stressor, but they just have various thresholds of the acceptable risk. Would I do it daily? No.
And in med-speak, that's what they're saying here too. Use with caution, don't go above the recommended dosage in acute situations and use caution with chronic dosing. https://pubmed.ncbi.nlm.nih.gov/11847957/
Anyway, the rule of thumb I always heard is that half of the "daily" dose appears to be more appropriate for chronic daily usage. I am not a doctor and you can do whatever you want, but that is personally what I would hold to. Going less, or picking a different FDA-approved alternative like ibuprofen or aspirin, is always a perfectly acceptable choice.
That number appears to be reasonably supportable too. Instead of "half of our patients were over triple their baseline ALT level" this study found that 50% of the daily doage, chronically over 12 weeks, gets you to a 20% average increase in ALT levels. It's never not going to be a liver stressor and if you have other risk factors then you should probably stay away entirely (I think that's just good advice in general) but 20% increase in ALT after 12 weeks is a hell of a lot better than tripling your ALT in 2 weeks. But even then, during a 12-week study of 94 healthy adult patients, at half the recommended dose, they still had to withdraw one participant due to hepatotoxicity. https://pubmed.ncbi.nlm.nih.gov/25899926/
(as far as risk factors, see the first link above for a good review, aggravating factors for hepatoxicity can include things like non-alcoholic fatty liver or nutritional deficiency. Which basically describes an overweight computer-toucher with a poor diet to a tee.)
> the "daily" recommended doses are for a single day.
No. We've got thousands of people living more or less permanently on the maximum daily dose, including some children and vulnerable populations. Yes, some of those people have elevated liver enzymes. Yes, Tylenol is dangerous, but certainly not more than the alternatives. NSAIDs are certainly not any less dangerous, especially in populations with high prevalence of diabetes and kidney failure.
Tylenol overdose is one of the most frequent suicide plans in teens, with lethal doses usually starting from 8g. This is one of the reasons Tylenol has such a bad reputation.
The intervention-based study (giving patients a controlled dose and measuring the enzyme response) found that over half of study participants will have clinically-significant elevation of ALT at the recommended dose, and 20-30% will have numbers as bad as 5x sustained. Short study aside, that's not what I would personally choose.
Remember, there were never Phase trials showing 4g is the right maximum either. It’s just grandfathered in Uber the “well I guess if it were dangerous we’d have noticed by now” standard. But did a statistically large enough segment take exactly 4g over a course of years such that we can definitively say that’s safe? Most people are taking lower doses and shorter doses. At least on paper.
It's "there's no double-blind study that shows masks can prevent the spread of covid!" redux. And actually it's worse because there already is a standard for what clinically-significant elevated levels of that enzyme are, and healthy study participants are blasting right by it. That's not relevant .... because?
It's not just a random number going up from some un-related mechanism, it's liver stress, they even think they know what the mechanism is. It’s a reaction that is well-known for this drug, as a warning sign for this problem. Claiming that it suddenly doesn’t mean the same thing it’d mean if you took 0.001mg more is just pedantic. It was never formally studied and approved, it would be completely unsurprising if they got the number a little wrong.
And again - that's study participants who are chosen to be healthy. If you're fat, or aren't getting your macronutrients, your risk is much higher.
Using a lower dose or using something else is always a valid option. "The dose makes the poison" and using the lowest effective dose is absolutely standard practice and any doctor is going to tell you that's a baseline they always operate under.
Anyway, do whatever you want personally, but I would personally think strongly about staying at half the recommended dose or less for chronic usage, or looking for an alternative option. 20% of the healthy population, plus the unhealthy population, is a decent chunk of people.
I personally prescribe loads of painkillers, including the whole range of the WHO ladder, and many of those patients have liver tests. It rarely happens that we have to discontinue Tylenol due to hepatitis. I see people on NSAIDs with kidney failure every week. So again yes, Tylenol is toxic. But from personal experience, it's rarely a clinically relevant problem.
Frankly, I'm not sure why NSAIDs are considered the safer option. There was a period of time when I was young, where I had tried various painkillers for treatment of headaches. Every time I had tried an NSAID, my chest felt like it was going to explode, and it became difficult to breathe. Later learned that they may increase the risk of heart attacks and strokes (of which I have a family history). For these reasons, I've sworn to never take them, and only take acetaminophen on rare occasions when pain is bad enough.
the "daily" recommended doses are for a single day. If you are taking it daily you need to at least halve the recommended dose. I wouldn't have said a week was a problem but... yeah. Tylenol is dangerous.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/
Specifically this study referenced: https://jamanetwork.com/journals/jama/fullarticle/211014
> One study reported that ingestion of the recommended maximum amount of 4000 mg of APAP for 2 weeks resulted in the asymptomatic elevation of alanine transaminase, up to three times normal, in 40% of patients.19 These transaminase elevations did not amount to any clinical significance, and after the APAP was discontinued the transaminase levels returned to normal.19 Yet, while asymptomatic, chronically elevated aminotransferases may be of concern to healthcare providers, leading to further costly diagnostic studies or changes/restrictions in necessary medications
If anything the summary in that review is underselling it. Average was 2.78x baseline (3x is considered clinically significant) and 20% of the population was over 5x the peak (so, 20% had clinically significant elevations from the study). By peak levels, around 27% of the population saw peak levels of 8x baseline. So basically, even the "average" participant was almost to the threshold of clinical significance just from this study (at the recommended daily dose) and a cohort of around 20-25% will see clinically-significant warning signs at the recommended dosage, even among healthy patients. And risk factors significantly increase that.
That's basically a "liver stressor" enzyme, even if it's not killing the patients over the course of the study, it's not a good thing. That's your body's warning signal that it's stressed. And generally that's an uncontroversial finding I think, everyone agrees tylenol is a liver stressor, but they just have various thresholds of the acceptable risk. Would I do it daily? No.
And in med-speak, that's what they're saying here too. Use with caution, don't go above the recommended dosage in acute situations and use caution with chronic dosing. https://pubmed.ncbi.nlm.nih.gov/11847957/
Anyway, the rule of thumb I always heard is that half of the "daily" dose appears to be more appropriate for chronic daily usage. I am not a doctor and you can do whatever you want, but that is personally what I would hold to. Going less, or picking a different FDA-approved alternative like ibuprofen or aspirin, is always a perfectly acceptable choice.
That number appears to be reasonably supportable too. Instead of "half of our patients were over triple their baseline ALT level" this study found that 50% of the daily doage, chronically over 12 weeks, gets you to a 20% average increase in ALT levels. It's never not going to be a liver stressor and if you have other risk factors then you should probably stay away entirely (I think that's just good advice in general) but 20% increase in ALT after 12 weeks is a hell of a lot better than tripling your ALT in 2 weeks. But even then, during a 12-week study of 94 healthy adult patients, at half the recommended dose, they still had to withdraw one participant due to hepatotoxicity. https://pubmed.ncbi.nlm.nih.gov/25899926/
(as far as risk factors, see the first link above for a good review, aggravating factors for hepatoxicity can include things like non-alcoholic fatty liver or nutritional deficiency. Which basically describes an overweight computer-toucher with a poor diet to a tee.)