It's probably worth mentioning that this drug is called Acetaminophen in the US, and is the active ingredient in Tylenol and other over the counter medicines.
It's a cheap and effective drug that has minimal side effects as long as you follow the instructions on the packaging. Pretty much all of the alternatives are worse.
Ibuprofen is usually rated to be on the same level (damaging your kidneys rather than your liver during long term use) but from what I've read I believe the potential side effects are more extreme (i.e. the elevated stroke/heart attack risk).
Using any pain medication for prolonged periods of time without consulting a doctor is dangerous. Many people do it, and most are absolutely fine, but when things go wrong, things go terribly wrong.
I had kidney stone surgery (laser lithotripsy) in Manhattan last Friday morning and literally the first thing I was given after changing into the paper gown was 2 500mg Tylenol pills and a cup of water. I don’t know if you’re a physician but the medical staff in manhattan tend to be at the top of their game, and they are cool with Tylenol.
If I ever had to say anything about Paracetamol, it would be:
Remember: Paracetamol is hepatotoxic, very strong for your liver. Never take it if you have been drinking alcohol or have a weak/damaged liver. Paracetamol is the worst thing you can have for hungover: it might reduce your headache but will hurt a liver that it's already under pressure by the alcohol you drank last night.
In moderation, as prescribed, shouldn't be bad. I'm more of an ibuprofen guy though (although I rarely take it).
While true, this is slightly overblown. I work at a liver transplant center where we treat patients with end stage liver disease and Tylenol is often the safest choice given these patients comorbidities. Granted, they’re getting their liver labs checked 1-2 times a day and are under close supervision but < 2g acetaminophen a day is considered fine. [I am not your doctor this is not medical advice]
The episode shows how even small overdoses of acetaminophen can cause fatal liver damage, while decades of FDA delays and confusing drug labeling left millions of Americans at risk.
Ibuprofen also increases risk of strokes and NSAIDs have been linked to increased risk of intracerebral hemorrhage. It’s a question of whether benefits outweigh cons on population level and I am not an expert, but recommending ibuprofen over acetaminophen might be over-simplifying things. It depends on the person (their meds, their pre-existing conditions, their genetics etc)
"Tylenol is very safe if taken as prescribed. The overdose amount is relatively low, but not uniquely low."
The issue is that the overdose of Paracetamol is relatively similar to the effective, or safe, dose:
"(overdose) of paracetamol is caused by taking more than the recommended maximum daily dose of paracetamol for healthy adults (three or four grams),[38] and can cause potentially fatal liver damage. A single dose should not exceed 1000 mg ..." [1]
See the problem ? A mere 3x the single dose puts one in "potentially fatal liver damage" territory.
This problem is compounded dramatically in small children where errors in the estimation of the child's weight can put you half way to overdose before you even start. Now add a meniscus error as you fill a clear plastic cup in the middle of the night ... or Mom gives a dose at 5am without knowing that Dad already gave a dose at 2am ... ugh.
Compare this to Aspirin where the overdose is as high as 15-30x the effective dose.
I’ll note that if you aren’t used to taking Tylenol, be mindful of the difference between extra and regular strength. My dentist just wrote down a number of Tylenols to take every X hours, and I took them, but because they were extra strength I started hallucinating and chugging water during, I think, Detective Pikachu or some nonsense like it. My liver came out of it fine. But if I’d taken another handful poison control said they would have directed me to the ER. One more after that and it would have been permanent liver damage.
ibuprofen and similar are also much more likely to destroy your kidneys as well and exacerbate heart disease. Intermittent regular dose use is unlikely to cause kidney harm but people get in trouble in two ways: chronic extended use of higher “therapeutic” doses (800mg for ibuprofen) or they have other medical problems weakening kidney function.
I always reach for aspirin for mild pain and people have this weird idea that its way more dangerous than paracetamol because its a blood thinner and "what if you bleed for some reason and it doesnt stop" - How is that worse than guaranteed liver damage if you take paracetamol? It almost seems like there was this big push to get people away from Aspirin to tylenol and thats why people have that idea stuck in their heads
NSAIDs (which includes more than aspirin, to be fair) cause like three orders of magnitude more injuries every year than paracetamol. The majority of incidents of liver damage from paracetamol are intentional.
Because it is way more dangerous. Guaranteed liver damage is nonsense. Aspirin and other non selective NSAIDs are much more likely to cause GI bleeding, kidney and heart problems.
An aspirin here or there is probably fine but multiple day dosing of full dose aspirin for chronic pain has gotten a lot of middle age people to bleed out their GI tract and end up dead.
Do you happen to be a heavy coffee drinker? Caffeine withdrawal can cause immense pain, as I can confirm from first hand experience. For me, it starts ~24 hrs after the last coffee and it usually takes a very strong double espresso and a nap to get back to normal. Maybe Exedrin's Caffeine + Aspirin + Paracetamol has the same effect for you?
Those have caffeine in them right? I'm sure you know your body well, but that could be part of what's helping you as well; could be constricting blood vessels or something like that
Agreed. The one thing that invariably works for me is Excedrin. Not too surprising given it has all three of the most likely solutions in a single pill.
The authors touch on potential wider implications in the abstract:
> These results suggest that APAP should be used with caution by women attempting to conceive. Given that cell division is fundamental to all development, further investigation is now warranted to substantiate these findings and to elucidate possible implications for other developmental processes, such as gonadal and brain differentiation.
Painkillers like ibuprofen are NSAIDs which inhibit the enzyme COX1/2, reducing prostaglandin production.
Prostaglandins are an inflammatory hormone that do a variety of things, but specifically PGE2 plays a role in muscle stem cell activation to divide and produce more muscle fibers. The effect is probably realistically small, but you will leave gains on the table by taking ibuprofen after hard workouts.
Are you saying that lifting weights makes more muscle fibers? I was under the impression it does not, that it simply makes your existing muscle fibers bigger and stronger.
The whole point of working out is to stress the organism in order to induce a physiological adaptation. Inflammation is NOT the point, but rather an unfortunate side effect.
Interesting, I didn't know. My original question was more about whether that affects muscle gains differently though, do you happen to have any insights into that?
The vaccine-autism smoking gun that Andrew Wakefield and RFK Jr. heroically tried to find has, so far, failed to turn up. But there was a study recently that showed that autism is correlated with the mother taking acetaminophen during pregnancy.
> Andrew Wakefield and RFK Jr. heroically tried to find
I'm not sure if that was supposed to be sarcastic, but these two people have done more harm to public health, and are responsible for more health dis/mis-information, than pretty much anyone I can think of. (I am a biochemist, no conflict of interest)
In gp’s defense—I interpreted their formulation to suggest vaccine skeptics applied effort to an heroic degree/amount, not that the effort was of heroic virtue. That is, that those people applied ridiculously high levels of effort to searching for an effect, and still did not find an effect.
As distinct from the retort that “absence of evidence is not evidence of absence”: It can be, if you’ve tried hard enough to gather the evidence and come up short—which is what these guys have done.
Yeah that was my charitable reading as well, but with the incredible prevalence of anti-vax/vaccine skepticism, you can never be sure. I thought clarifying could be helpful!
I live in Brazil. We have broad access to non-steroidal anti-inflammatory drugs. Even the best-known medicines have unexpected and unknown adverse effects: in general and specifically in people with unexpected genetic, enzymatic, and protein variations. This has no solution. The medicine acts differently in each body, which is subtly diverse from the others. I see a lot of research criticizing any "old" general medicine and introducing the "new" one. I don't know if this is the case. Every medicine has its rush, half-life, and side effects, and its actions are not fully mapped. My preference for long-term treatments is: dipyrone. Short term: ibuprofen. Lymphatic pain: paracetamol. It may not make sense, but that's how I use it.
Interesting how you put metamizole at #1 for long-term treatment. As far as my experience goes, many doctors do the same in Germany. On the other hand, I've heard that the medication is banned in many other countries.
I guess the safest way is to take up the treatment in a hospital, to check for immediate bad reactions.
On the other hand, like with many medications, severe allergies and individual sensibilities causing side effects often don't show up often in the short term, but rather suddenly after many dose intakes.
So I'm back where I started. Not disagreeing with what you say. It seems like these non-steroidal pain relief medications are poorly understood regarding their interaction with the whole body though.
Many OTC medications and even some prescribed ones (especially psychiatric medications) suffer from a very poor understanding and apparent lack of effort in improving the understanding of their mechanisms of action.
I guess that's why metamizole is often a part of the standard treatment for mid-term exogenic pain here, for example after injuries or during some treatments involving pain.
Not addictive, not hepatotoxic, not nephrotoxic.
Seems the reason for the ban / harder regulation in some countries is about the disturbance of blood-forming in some individuals (which can also be deadly, but I have no idea of the quantified risk here).
Ibuprofen and acetaminophen are more common for short-term treatment, at least that's what I've been taught.
Avoid taking them on a schedule, take them as needed and at the lowest effective dosage.
A.s.s. (lol) too, apart from the low-dose usage that some claim to be helpful with heart/artery diseases.
I've always had an (unreasonable?) dislike of Paracetamol/Tylenol ever since I found out it was the #1 cause of acute liver failure in the US. Liver failure is scary.
The UK started requiring that Tylenol always be sold in blister packs instead of convenient-to-kill-yourself-with whole bottles of pills.
Results: "Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths."[1]
I am familiar enough with the numbers that I am not necessarily surprised, but I still find it emotionally hard to grok that more than one in five would-be paracetamol suicide victims would be dissuaded by having to pop the pills out of a blister pack first.
Actually nowadays it's less that it's a problem to pop the pills out the booster pack and more that you are limited to the number you can buy.
So if you're going to off yourself you'd have to stock pile or roam around shops picking up.
There is a not insignificant number of suicides where people just say fck it I'll just kill myself but they don't want to go out to any real bother to do it i.e. they don't pre-plan it it's just spur of the moment. A bottle of kill yo self pills is pretty easy. Cupboard, swallow, drink down some water, die. But having to go out and buy a bunch over a few days or like drive around in your car just buying as many as you can. Like you'd have to look it up to check you're going to buy enough.
Back when that law came in when they didn't reduce the total amount you could buy at one time so if you went in and bought like 10 packs at the supermarket then the person at the till would be like ok this person's going to kill themselves so again that would require a bit of balls from the would be kill yo selfer.
I think you can buy a bottle of like 100 x 500mg for like $20 in the USA. That's like over 2 weeks swigging at the max amount. Like you don't need that many, 3-4 days is enough shouldn't be taking that much of the stuff.
That's a different matter that wasn't mentioned though. Where I live (continental Europe) I've never seen any kind of medication as a bottle, but I'm also not aware of there being an amount restriction on paracetamol, which where I grew up in in the Netherlands can be bought in any supermarket. Interestingly I was surprised to find that in France paracetamol can only be sold in pharmacies but hard liquor is available in supermarkets.
- Metamizole has a tendency to kill some percentage of native Brits and their descendants. Yet globally it's one of the most popular painkillers, it's even OTC in countries with sufficiently low numbers of British and related people. (Has anyone ever done research to try and figure out why Brits are on the order of 1000x-10000x more sensitive to that side effect?)
That's why it's recommended to combine a half dose of ibuprofen and a half dose of paracetamol at the same time. (Plus some vitamin C)
Together they have higher pain killung effects than each alone, and the side effects are reduced as they affect different body parts. And the vitamin C reduces the damage to the stomach lining.
Or if you need stronger painkilling you can take a full dose of paracetomol and either ibuprofen or aspirin. OTOH aspirin and ibuprofen use the same pathways so combining a full dose of ibuprofen and aspirin is not recommended.
Aspirin and ibuprofen are both NSAIDs with not too dissimilar pathways, so combining them won't be as effective as combining either with paracetamol. They'll both do their jobs, but if the ibuprofen is already doing its job, aspirin won't have much work left to do.
Meanwhile, taking ibuprofen can negate the effect aspirin has when taken against cardiovascular diseases. Not a huge problem if you're just taking it as a painkiller, but not everyone can combine the two. That's another potential reason to take paracetamol over some NSAIDs, though you should obviously consult a doctor if you're taking prescription medicine of any kind.
That's very interesting about vitamin C, I never heard that it can reduce stomach lining damage. It's surprising because things with vitamin C tend to give me heartburn, I assumed because they were acidic. Do you have any references?
Adding to this, its the margin between a therapeutic dose and a harmful dose is most relevant. That margin for aspirin is wide, the same effective vs toxic margin for paracematol is shockingly narrow.
Furthermore, the "aspirin is rough on your stomach whereas Tylenol is gentle" turns out to be McNeil Marketing puffery.
"Any medicine can be poison" is kinda missing the point.
There is a rich and varied multidimensional field of danger, from aspects like the safety-margin between regular/dangerous dose levels, the chronology of how it can spike or accumulate, whether there's feedback in advance of damage, etc.
Yeah, I can poison myself drinking clean water, but it's hard.
It's pretty hard to overdose on water unless you're in some state like extreme dehydration where water consumption needs to be overseen by a doctor. Unless you're talking about drowning, then you're just being silly. As a healthy adult, drinking too much water until the point that you're injured is hard to do. You likely need a mental disorder to ignore simple signals like "my stomach is very full right now". Whereas OTC medications can be very easy to overdose. If you don't read the instructions and regularly take more than recommended, you can injure your liver or other organs. Pills are not very big so a handful of them can easily be in the LD50 area.
Oxygen toxicity is not a risk for most people. You either are a scuba diver regularly working at depths beyond what most do or are taking supplemental oxygen while under the care of a doctor. You are not at risk of oxygen toxicity reaching into your bathroom medicine cabinet.
It's not just that it causes liver failure: it's that the difference between the therapeutic dosing range for pain relief it's prescribed for is dangerously close to the toxicity level.
Other drugs like theophylline have ceased to be prescribed for a similar reason alternatives were available, but due to drug marketing, acetaminophen is touted as the "safe" pain reliever.
> but due to drug marketing, acetaminophen is touted as the "safe" pain reliever.
Paracetamol's patents have expired long ago and there's not much profit to be made out of it (nowadays it's mostly not being made in the West, but imported from China, unlike profitable medicine).
The reason why it's still used it's that it's much better than the alternatives, despite the risks (it's only risky if you don't respect the doses by the way).
> Public awareness that Tylenol causes liver failure which will last weeks before death might dissuade some.
I suspect it will: There's statistical evidence from how Britain migrated its cooking gas systems away from carbon-monoxide-heavy mixes [0] indicating overall suicide-rates are sensitive to convenience and involve short-term periods of vulnerability. As contrasted to "if they really want to they'll find a way no matter what." [1]
[1] That said, I wouldn't be surprised if there's a bimodal distribution lurking in there, between "depressed but otherwise healthy" versus "terminal diagnosis and chronic pain." The latter-group might not be deterred by inconvenience.
Sure but it’s pretty easy overdose on paracetamol.
Since it’s a mild and really common painkiller, sometimes seen as not dangerous, someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.
Unlike a lot of drugs, you are not going to have a lot of immediate side effects if you overdose on paracetamol. You’ll just horribly die some days after,
How can you reach adulthood and think it's ok to take 3 or 4x the specific dose of any medication? If you're in that much pain you go to a doctor. Which makes me think maybe the issue is the private health system and not the drug.
Conversely, my grandmother's Alzheimer's became apparent when she was overdosing on either ibuprofen or aspirin, I forget which.
She would take a dose for a headache, ten minutes later she'd forgotten so she'd take another dose, ten minutes later, she had forgotten, take another dose, rinse and repeat until it's time for a trip to the hospital.
Maybe it wasn't ten minutes between, probably fewer given how much she'd ended up taking. This happened thirty or so years ago.
> someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.
And the solution is simple: educate people about that.
And it's not something hard to do, just have pharmacists say “respect the dose as it will kill you if you don't” every time they sell things and it'll work.
But Tylenol/acetaminophen/paracetamol is an over the counter drug, so there is no pharmacist involved in most sales. And I certainly wouldn't count on everyone reading the tiny text on the bottle.
Tylenol is unusual among OTC medications in that you can get liver damage from as little as double the recommended dosage. It doesn't play well with alcohol, either. I wonder how many of those liver failures are the result of people drinking and taking too much of the drug either because the alcohol causes them to lose track, or from the alcohol interaction itself.
I'm finding all the 'liver failure' comments on this post fascinating. The dose is on the back on the packet, as is the time interval between doses and the maximum number of pills per day. To overdose you need to ignore that. Given all the mention of 'Tylenol' I'm assuming most of the commenters are American - is this a thing in the US where you just take a random number of pills and ignore the labelling or treat it as a guide? Is it a consequence of the fact you can buy these in bottles by the hundred?
- different packages of the same medication have different doses per pill. So you might read one package that says to take two pills, then later you buy a different package of the same painkiller that says one pill, but you're lazy, and don't read the label for this, and assume it is the same as last time, so you end up doubling the dose.
- For ibuprofen, the label often says if one dose isn't sufficient, then you can take another pill (with a maximum number in 24 hours). People may assume this is the case for Tylenol as well, but I don't think it is.
- people may read the size of the dose, but skip over the warning about the maximum you can take in a 24 hour period.
- The directions are in small hard to read text, which makes all of the above points worse.
Not that any of those are a good excuse not to read the label, but, well, people make bad decisions all the time.
I choose to believe that all of the movies and TV shows showing Americans pouring a handful of pills out of a bottle into their hands and throwing them in their mouths (then chewing them!!!) are 100% accurate to life rather than cinematic shorthand
This send me into a whole rabbit hole. Mostly children get paracetamol overdose. Then I learned that in US/UK kids get paracetamol in liquid form with all kinds of flavours. Which is much harder to dose correctly when the kid spits or drools it out.
Total culture shock for me, as in Europe the default for children is rectal ingestion (which is probably a culture shock as well for Americans). Any how, with pills it is much easier to avoid overdose.
Recently had a prescription error with my two month old baby. The doctor prescribed 7 times as much iron supplement as they intended (confusing labelling - so while I'm annoyed, I can see how it happened). This went on for a month until we uncovered the error.
We had blood test done (on the doctor's recommendation), and luckily there is no sign of any damage, but prescription errors do happen (even if they are rare) and it's much easier with liquids (you probably wouldn't give 8 pills to a baby, but 8ml doesn't seem so bad).
There's no “as in Europe”, every European country is different. In France the default is also liquid form, but the pipette is graduated is kilograms of baby weight, which limit the errors you can make (you know your kid doesn't weight 15kg when his weight is around 8).
> Which is much harder to dose correctly when the kid spits or drools it out.
Never met a non autistic child who would spit or drool out calpol. I'd take the stuff myself as an adult it tastes brilliant.
> Total culture shock for me, as in Europe the default for children is rectal ingestion (which is probably a culture shock as well for Americans)
Huh are you talking about new born babies or something? I've been to a few different EU countries and you can buy liquid stuff for kids in the chemists. (Spain, france, germany, italy) source me as a child getting the stuff when I was sick abroad and the local doc sold my parents basically some off brand calpol.
> "Smoking and alcohol are established risk factors for spontaneous abortion, underscoring the importance of the chemical environment during embryonic development."
Both of my parents are/were heavy smokers drinkers from their teenage years. Mom died of lung cancer from smoking. Kind of wild to think that the odds were really stacked against my birth.
Nature really, really, really wants you to have kids. It took us collectively as a species most of our existence to find genuinely effective methods to alter our biology sufficient to block this process, and we still have a hard time doing it without dramatically impacting the host organism.
This is probably one of those things where the risk is normally small, so small increases cause large changes in percentage.
For instance, if spontaneous abortion is normally 1% and smoking increases it to 2%, then that’s a 100% increase. Now, I don’t know the actual numbers, and smoking is just generally not good for one’s health, but I wouldn’t go as far to say things were stacked against you.
Millions of kids have been born to parents who smoked and drank all the way through their pregnancies, especially before the 1970s or so. It raises risks, but doesn’t guarantee bad outcomes.
Many, many more but here's a few you might want to start with:
"The meta-analysis showed a significant association between maternal tobacco smoking during pregnancy and increased risk of ADHD in offspring."
Mohammadian M, Khachatryan LG, Vadiyan FV, Maleki M, Fatahian F, et al. (2025) The association between maternal tobacco smoking during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring: A systematic review and meta-analysis. PLOS ONE 20(2): e0317112. https://doi.org/10.1371/journal.pone.0317112
"Compared with unexposed controls, individuals with PAE reported significantly higher frequencies of problems with hearing, dentition, heart, cancer, gastritis, kidney stones, bladder, diabetes, thyroid, skin, and seizures."
Coles, C.D., Shapiro, Z.R., Kable, J.A., Stoner, S.A., Ritfeld, G.J. & Grant, T.M. (2024) Prenatal alcohol exposure and health at midlife: Self-reported health outcomes in two cohorts. Alcohol: Clinical and Experimental Research, 48, 2045–2059. https://doi.org/10.1111/acer.15441
"Our results indicate that perinatal exposure to maternal smoking is associated with increased risks of CVD events, and such relations are modified by adulthood smoking behaviors."
H., Liang, Z., Wang, H., Cardoso, M. A., Heianza, Y., & Qi, L. (2021). Perinatal exposure to maternal smoking and adulthood smoking behaviors in predicting cardiovascular diseases: A prospective cohort study. Atherosclerosis, 328, 52–59. https://doi.org/10.1016/j.atherosclerosis.2021.05.009
"Our findings support previous findings suggesting the detrimental effects of prenatal binge drinking on child cognition. Prenatal alcohol exposure at levels less than daily drinking might be detrimentally associated with child behavior. The results of this review highlight the importance of abstaining from binge drinking during pregnancy and provide evidence that there is no known safe amount of alcohol to consume while pregnant."
Flak, A. L., Su, S., Bertrand, J., Denny, C. H., Kesmodel, U. S., & Cogswell, M. E. (2014). The association of mild, moderate, and binge prenatal alcohol exposure and child neuropsychological outcomes: a meta-analysis. Alcoholism, clinical and experimental research, 38(1), 214–226. https://doi.org/10.1111/acer.12214
You may not not want to hear this, but let's put it plainly: Prenatal smoking and alcohol is clear and obvious child maltreatment.
It is wrong to claim that ADHD is exclusively hereditary. Also, epigenetics show that behavior changes what is inherited. This is a chance and a responsibility. [1]
More broadly speaking, anything that is claimed to be "hereditary" (which for ADHD the scientific consensus is that it is not exclusively but estimated at around 70%) could also be early nuture and prenatal environment. The way genetic inheritance is researched (identical twins vs. fraternal twins) cannot account for this. [2]
[1] e.g.
"ADHD has been clearly linked with numerous environmental risk factors, particularly around the prenatal and perinatal period. Some of the most robust risk factors identified are maternal prenatal health conditions and psychological distress (e.g. hypertension, obesity, pre-eclampsia, immune activation), in utero exposure to poor diet (with critical factors still being determined), teratogenic effects of certain medications (e.g. acetaminophen) and environmental exposures (e.g. lead), as well as neonatal factors such as prematurity and low birth weight [27]. Other extreme exposures in the postnatal environment (such as extreme infant emotional neglect) have also been associated with an ADHD syndrome [28, 29]."
Cecil, C. A. M., & Nigg, J. T. (2022). Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential. Molecular diagnosis & therapy, 26(6), 581–606. https://doi.org/10.1007/s40291-022-00609-y
"The convincing evidence for genes as risk factors for ADHD does not exclude the environment as a source of etiology. The fact that twin estimates of heritability are less than 100% asserts quite strongly that environmental factors must be involved. ADHD’s heritability is high, and that estimate encompasses gene by environment interaction. Thus, it is possible that such interactions will account for much of ADHD’s etiology. Environmental risk factors likely work through epigenetic mechanisms, which have barely been studied in ADHD [148]. The importance of the environment can also be seen in the fact that, as for other complex genetic disorders, much of ADHD’s heritability is explained by SNPs in regulatory regions rather than coding regions [149]."
Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular psychiatry, 24(4), 562–575. https://doi.org/10.1038/s41380-018-0070-0
"Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes."
Robinson, L. R., Bitsko, R. H., O'Masta, B., Holbrook, J. R., Ko, J., Barry, C. M., Maher, B., Cerles, A., Saadeh, K., MacMillan, L., Mahmooth, Z., Bloomfield, J., Rush, M., & Kaminski, J. W. (2024). A Systematic Review and Meta-analysis of Parental Depression, Antidepressant Usage, Antisocial Personality Disorder, and Stress and Anxiety as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children. Prevention science : the official journal of the Society for Prevention Research, 25(Suppl 2), 272–290. https://doi.org/10.1007/s11121-022-01383-3
[2]
"twin studies fail to separate the effects of genes and the prenatal environment. This failure casts doubt on claims of the relative effects of genes and environment on intelligence, psychiatric disorders, personality and other psychological variables, and other conditions."
"Although many twin studies have been conducted (which is quite an understatement; there are almost
9,000 hits for “twin study” on PubMed!), there have long been critics who argue that they are scientifically
worthless."
"Because heritability is defined by both genetic and environmental influences, it is not a fixed characteristic of a disease or trait, but a population-specific estimate, analogous to, for example, the mean height, cholesterol level or life expectancy in a population. It also cannot be interpretated at the family or individual level."
Kaprio J. (2012). Twins and the mystery of missing heritability: the contribution of gene-environment interactions. Journal of internal medicine, 272(5), 440–448. https://doi.org/10.1111/j.1365-2796.2012.02587.x
Smoking certainly isn't good, but it also isn't some super-poison like some people like to pretend. Nearly half of US smoked in the 40s and 50s and they had no problem having tons of kids.
It's interesting because my wife has been using Ibuprofen for headache relief, whereas I use Paracetamol. I usually got Paracetamol growing up but recent studies showing adverse effects of Ibuprofen on male fertility solidified my resolve and consistency in choosing Paracetamol. My wife's reason for using Ibuprofen was simply because it worked better for her. Now it's kind of surprising to learn that Paracetamol has negative effect on women's fertility... I guess this means that both drugs are harmful to a different gender? What a coincidence? We were both using the optimal one for ourselves for reasons beyond our understanding... Until more data comes out.
Anyway, I understand arguments for avoiding drugs, medicines and chemicals altogether. Clearly, everything is more complex than it seems and side effects can never be fully known or understood; especially on a case-by-base basis given that everyone's DNA is different and responds differently to chemicals. I only take Paracetamol if I have a migraine with visual aura which is quite rare. I don't take it for standard headaches.
Embryonic development is so sensitive, especially that if nervous system. I suggest to my patients total drug avoidance. Even peeling off the tomatoes.
“ APAP could contribute to early embryonic loss by impairing initial cell divisions. These results suggest that APAP should be used with caution by women attempting to conceive. Given that cell division is fundamental to all development, further investigation is now warranted”
By the same logic it would now be effective against cancer, no?
As far as I can tell from my local health organisations, paracetamol is one of the safest painkillers for pregnant women.
That doesn't make it very safe, but NSAIDs carry well known risks during later stages of pregnancy, and opiods aren't exactly harmless either. Even aspirin carries risk (and aspirin doesn't even work as well compared to other drugs).
As far as I can tell paracetamol is still the first choice for painkillers while pregnant, but only because none of them are completely safe to use. It's probably fine for short term usage, but that also goes for non-pregnant people to be honest.
No it’s the only allowed pain reliever for pregnant women in the US. It’s also allowed in the UK and the EU from what I can tell. What countries are you talking abou?
Sincere apologies, I mixed ibuprofen and paracetamol.
Ibuprofen is forbidden for pregnant women in the last 4 months in France at least - and by "forbidden", I mean "strongly advised against in a case of self medication".
You are probably thinking of ibuprofen which is considered non safe during pregnancy. Paracetamol is pretty much the only OTC pain relief medication that is recommended for pregnant women.
I won't take acetaminophen (usually) learning of the liver toxicity and low overdose potential. And I have a friend that destroyed his kidneys with ibuprofen and is on a transplant list.
But from what I understand acetaminophen also dulls emotional pain like from being fired or breaking up with a girlfriend which is interesting.
I still prefer to take neither if I can avoid it and I'll hurt a little bit instead. Hurt a lot and I'd probably change my mind though.
This site is populated by mid-level code monkeys and “founders” of junk B2B startups. So, two groups that have an inflated sense of their own intelligence and believe everything that leaves their lips (or tips of their fingers) is on level of God’s word.
What scares me about this is that Tylenol is a drug that's been handed out to everyone, for everything, for decades. And if we could miss how dangerous this one is, what are the odds other drugs aren't just as risky?
Side note, here's a Scrubs clip from 2001 that shows just how ubiquitous Tylenol was.
I know the anti-vax crowd is full of homeopaths, chiropractors, and tarot readers. But they're not wrong about one thing: drug companies make money by selling drugs. If we can't guarantee real oversight before those drugs hit the market, we're in deep trouble.
Not denying that acetaminophen/paracetamol has a horrible therapeutic index, but there are reasons why it is still so widely used. Despite potential hepatoxicity, it is considered the safest pain relief drug (this emerging research notwithstanding)
Ibuprofen is not better in every way. For instance ibuprofen, as well as other NSAIDs, is much less gentle on gastrointestinal tract and puts much more strain on kidneys.
Some people (e.g. with inflammatory bowel diseases or renal diseases) do not tolerate NSAIDs well, which is why acetaminophen is on the same step of analgesic ladder - it is still considered better in some cases.
Both are also used complementary to each other in pediatrics.
Your comment is fair; obviously I wrote a pretty flippant comment, but the message is largely useful for most people.
The fact is that (largely due to the incredible marketing of Johnson & Johnson's Tylenol brand in the US) way too many people think acetaminophen is "safe and effective" when it's actually both pretty unsafe and pretty ineffective. Most people just "pop a Tylenol" by default without realizing it's not much better than placebo.
Sure there are cases where people have unique risks and should avoid NSAIDs. But for the vast majority of the public, if they or their kid are dealing with a headache, fever, menstrual cramp, or other transient pain or fever, they should reach for ibuprofen (with a snack) over acetaminophen. It's not remotely a close call.
I'm frankly pleased that people are becoming more aware of this and I don't mind taking a couple correction comments for presenting the info in a superficial way.
Taking ibuprofen (or other NSAIDs) long-term can wear away the stomach lining, causing ulcers. Acetaminophen is generally better tolerated to manage mild long-term pain than NSAIDs, as long as you don't overdose / take with alcohol.
This is a dangerous advice. Please folks. disregard this OPs comment. I doubt he is a doctor.
Ibuprofen is not better in every way. Ibuprofen is active in so many different parts of the body at the same time that inevitably it has unintended effects which is more pronounced especially in the elderly. It's bad for stomach, bad for kidneys, bad for mental status. and very bad with long-term use.
TLDR. Both aren't great for different reasons. Tylenol can be acutely OD'd and evidence is starting to show it isn't great embryos. Outside of those 2 situations that can be easily avoided, it is overall less bad than ibuprofen.
Give me paracetamol over ibuprofen in most cases. Ibuprofen is much more likely to cause stomach issues than I am to miscalculate "take 2 paracetamol every 4-6 hours".
Naproxen sodium is also a lot better, and is slightly safer than ibuprofen to take for extended periods. I had severe sciatica for the better part of a year, and the only thing that kept me somewhat functional was ~1000mg/day of naproxen, which isn’t great for you but would’ve been a lot worse if it had been ibuprofen (never mind opiates or something).
Did your sciatica go away on its own or did you introduce some new exercises to your routine? I've had some pain in my left leg for a few months now that is likely sciatica. I did go to the doctor, but it wasn't a particularly helpful visit.
I did physical therapy which mostly involved strengthening core muscles - if the cause is a herniated disc, which it usually is, this can slightly speed up the recovery process because a stronger core can push the disc back into place. But this is a speedup in the sense of "8-10 months instead of 10-12". Welcome, certainly, but not a silver bullet.
The other thing the PT taught me was nerve glides (also called nerve flosses). These don't seem to make recovery any faster, but help a decent amount with pain and tightness .
Sadly, that plus loading up on NSAIDs appears to be about all you can do for most cases of sciatica. I got a consult with a back surgeon who basically said, "I can operate if you want, but it probably won't help much, you just have to wait".
Good luck: it can be a pretty miserable time, but the good news is that most cases of sciatica do in fact clear up on their own even without PT. It can just take a while and you'll be hurting in the meantime.
At a standard dose, paracetamol slightly reduces fever,[13][17][18] though it is inferior to ibuprofen in that respect[19]
[13] Warwick C (November 2008). "Paracetamol and fever management". J R Soc Promot Health. 128 (6): 320–323. doi:10.1177/1466424008092794. PMID 19058473. S2CID 25702228.
[17] Chiumello D, Gotti M, Vergani G (April 2017). "Paracetamol in fever in critically ill patients-an update". J Crit Care. 38: 245–252. doi:10.1016/j.jcrc.2016.10.021. PMID 27992852. S2CID 5815020.
[18] de Martino M, Chiarugi A (December 2015). "Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management". Pain Ther. 4 (2): 149–68. doi:10.1007/s40122-015-0040-z. PMC 4676765. PMID 26518691.
[19] Pierce CA, Voss B (March 2010). "Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review". Ann Pharmacother. 44 (3): 489–506. doi:10.1345/aph.1M332. PMID 20150507. S2CID 44669940.
Question: Does acetaminophen use during pregnancy increase children’s risk of neurodevelopmental disorders?
Findings: In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use.
Meaning: Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding.
The 1 study you linked does not disprove the newer 46-study analysis that I linked. Quoting from it:
"We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations."
Autistic moms are more likely to have chronic illness, sensory issues, auto immune issues, etc thus are more likely to be taking medications. In the end, the autistic mom just passes her autistic genes to the baby.
I never took Tylenol/Paracetamol/acetaminophen, or anything containing it or given it to my children. We never reduce fever below 39.5/103.1 either - risks of febrile seizures are overstated and if you're a responsible parent, not a lazy one, you can see if things are going South, but there are other traditional means to lower fever. People are just too spoiled nowadays!
I tested positive with COVID-19 on Tuesday and had a pretty high fever (103) with a terrible headache, but I didn't take ibuprofen. First, because it could lower my fever, second, because its anti-inflammatory effect would compromise my immune system response to the pathogen. Most people I know immediately try to lower their fever to reduce their discomfort and would immediately take it for headaches, too.
Of course it's not - I clearly said I never take acetaminophen, if for headache/fever I would rather take ibuprofen instead... but I don't take even that w/o a solid reason!
People do that because they haven't been "educated" (even superficially) about what fever really is, which is your body working hard to fight of the infection. And messing with it is counterproductive.
They also do it with their kids because they want to help them. Also, some people have a lot on their plate, calling them lazy is not right thing to do. I have health insurance that covers me when my kids are sick (not in the US), so I can take care of them "properly ". This doesn't make me more responsible and someone else that works two jobs and can't afford to have sick kids lazy.
Also, I don't lower fever, even with my kids unless it prevents them from sleeping. But overstated is relative, it's happened to the kid next door from me. You don't want to be careless with infants.
They are lazy if they don’t educate themselves about what they are doing and what they are giving their children. Don’t get offended. I’ve never done anything health-related to my kids without doing thorough research. I’ve witnessed four major medical mistakes made right in front of me in Orange County, California, in some of the best medical facilities and by the best pediatricians in the area! That’s why I don’t blindly trust anyone, whether it’s a doctor or not. I use critical thinking and always look for alternative advice. Doctors often find me a nuisance, but that’s okay with me. Just try asking a doctor when they prescribe Tylenol for a fever: “Why should I try lowering their fever?” or “Why should I give them Tylenol exactly?” The hepatotoxicity of acetaminophen occurs when the production of the toxic metabolite NAPQI exceeds the liver’s glutathione detoxification capacity, which can happen quite frequently during infections! So, then ask your doctor: “Doesn’t it make sense to give them NAC with Tylenol as well, just in case?” They won’t know what to say, trust me!
I have not found any study published after 2020 (the year when the French minister made the statement) that advises against ibuprofen for COVID-19. But I'm not a doctor, so I'd be interested to know your source.
But it's the truth. Something that has just a 2% incidence should not dictate 98% of the treatments. Compromising the innate immunity of the 98% is more disgusting!
No it's not, in many case there's just no way the parent can tell something is about to go wrong.
> Something that has just a 2% incidence should not dictate 98% of the treatments.
This isn't the same argument, and I would agree if it was true, but you're distorting numbers as the actual prevalence estimations lie between 2 and 14%[1].
Now you could make the argument that 10% is low enough of incidence it shouldn't dictate the treatment of the other 90%, but that's not what you're doing, instead you are blaming helpless parents and cherry picking numbers, making nothing but noise.
Oh, and by the way, most parents aren't in fact giving their kids paracetamol for that particular reason (as most parents are simply unaware of the existence of febrile seizures), but to help their children sleep and rest (and so themselves can sleep). And in fact, resting being key in innate immunity efficiency, I'm not particularly convinced about the effectiveness of letting your kids cry all night because of the pain and fever. You do what you want with your own kids, but there's no justification for insulting other parents.
The vast majority of these seizures are benign. If your child had a febrile seizure, then there's a 30% chance of having it again, so, then you have some excuse to keep their fever under control (hopefully not with Tylenol as there are other antipyretics, too). Here's a nice summary by Gemini:
Key Takeaways
- No Lasting Damage: Simple febrile seizures do not cause long-term brain damage, intellectual impairment, or learning disabilities.
- Benign Nature: Despite how terrifying they are to witness, febrile seizures are considered benign events in the vast majority of cases.
- Focus on Reassurance: The primary goal for healthcare providers is to reassure parents and caregivers, providing them with the knowledge and tools to manage a fever and understand the low risk of lasting effects.
I have 3 kids, all grown up and healthy. They all slept perfectly well with fever, so, there's no such thing as a febrile insomniac kid. High fever has a potent detox element as you sweat out the toxic metabolites. I'm tired of parents who overprotect their children while harming them this way - there are so many studies - from overdrugging kids (thank God that most anti-cough drugs are now off the shelves), to forcing them to wear helmets, no go alone, etc.
> They all slept perfectly well with fever, so, there's no such thing as a febrile insomniac kid.
Please stop believing your sample of 3 kids is representative of the entire population. You were lucky to have kids who sleep well and that's good for you, but that doesn't make other parents lazy or irresponsible.
> I'm tired of parents who overprotect their children
You know what's even more tiring? Parents who judge other parents while not knowing anything about kids in general just because they happened to be lucky on one particular topic. You won't be lucky all the time though.
> to forcing them to wear helmets
I hope you won't regret saying that ever in your life, but being anti-helmet really is as idiotic as being an antivaxxer.
It's probably worth mentioning that this drug is called Acetaminophen in the US, and is the active ingredient in Tylenol and other over the counter medicines.
maybe should add (tylenol) to the article subject?
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It's a cheap and effective drug that has minimal side effects as long as you follow the instructions on the packaging. Pretty much all of the alternatives are worse.
Ibuprofen is usually rated to be on the same level (damaging your kidneys rather than your liver during long term use) but from what I've read I believe the potential side effects are more extreme (i.e. the elevated stroke/heart attack risk).
Using any pain medication for prolonged periods of time without consulting a doctor is dangerous. Many people do it, and most are absolutely fine, but when things go wrong, things go terribly wrong.
I had kidney stone surgery (laser lithotripsy) in Manhattan last Friday morning and literally the first thing I was given after changing into the paper gown was 2 500mg Tylenol pills and a cup of water. I don’t know if you’re a physician but the medical staff in manhattan tend to be at the top of their game, and they are cool with Tylenol.
Are you saying one of the most used drugs on the planet is safe just because someone gave it to you in manhattan?
Being safe acutely after surgery does not necessarily translate into being healthy over decades when habitually used as a hangover cure.
Being habitually hungover is a bigger problem than taking paracetamol after being habitually hungover.
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If I ever had to say anything about Paracetamol, it would be:
Remember: Paracetamol is hepatotoxic, very strong for your liver. Never take it if you have been drinking alcohol or have a weak/damaged liver. Paracetamol is the worst thing you can have for hungover: it might reduce your headache but will hurt a liver that it's already under pressure by the alcohol you drank last night.
In moderation, as prescribed, shouldn't be bad. I'm more of an ibuprofen guy though (although I rarely take it).
While true, this is slightly overblown. I work at a liver transplant center where we treat patients with end stage liver disease and Tylenol is often the safest choice given these patients comorbidities. Granted, they’re getting their liver labs checked 1-2 times a day and are under close supervision but < 2g acetaminophen a day is considered fine. [I am not your doctor this is not medical advice]
My cousin worked in a toxicology lab in a hospital.
Way back in the 80s he was commenting on how understudied and under published Acetaminophen toxicity was.
In particular, taking Tylenol for hangovers was (and still is) a common but very dangerous practice.
As others have said, it is crazy easy to overdose on the stuff and suffer liver damage.
Yes, https://www.thisamericanlife.org/505/use-only-as-directed
The episode shows how even small overdoses of acetaminophen can cause fatal liver damage, while decades of FDA delays and confusing drug labeling left millions of Americans at risk.
Tylenol is very safe if taken as prescribed. The overdose amount is relatively low, but not uniquely low.
The alternatives are worse - ibuprofen destroys your stomach lining if taken at the regular dose for too long.
Ibuprofen also increases risk of strokes and NSAIDs have been linked to increased risk of intracerebral hemorrhage. It’s a question of whether benefits outweigh cons on population level and I am not an expert, but recommending ibuprofen over acetaminophen might be over-simplifying things. It depends on the person (their meds, their pre-existing conditions, their genetics etc)
"Tylenol is very safe if taken as prescribed. The overdose amount is relatively low, but not uniquely low."
The issue is that the overdose of Paracetamol is relatively similar to the effective, or safe, dose:
"(overdose) of paracetamol is caused by taking more than the recommended maximum daily dose of paracetamol for healthy adults (three or four grams),[38] and can cause potentially fatal liver damage. A single dose should not exceed 1000 mg ..." [1]
See the problem ? A mere 3x the single dose puts one in "potentially fatal liver damage" territory.
This problem is compounded dramatically in small children where errors in the estimation of the child's weight can put you half way to overdose before you even start. Now add a meniscus error as you fill a clear plastic cup in the middle of the night ... or Mom gives a dose at 5am without knowing that Dad already gave a dose at 2am ... ugh.
Compare this to Aspirin where the overdose is as high as 15-30x the effective dose.
[1] https://en.wikipedia.org/wiki/Paracetamol#Overdose
> Tylenol is very safe if taken as prescribed
I’ll note that if you aren’t used to taking Tylenol, be mindful of the difference between extra and regular strength. My dentist just wrote down a number of Tylenols to take every X hours, and I took them, but because they were extra strength I started hallucinating and chugging water during, I think, Detective Pikachu or some nonsense like it. My liver came out of it fine. But if I’d taken another handful poison control said they would have directed me to the ER. One more after that and it would have been permanent liver damage.
> ibuprofen destroys your stomach lining if taken at the regular dose for too long.
This is how the VA killed my dad :/
ibuprofen and similar are also much more likely to destroy your kidneys as well and exacerbate heart disease. Intermittent regular dose use is unlikely to cause kidney harm but people get in trouble in two ways: chronic extended use of higher “therapeutic” doses (800mg for ibuprofen) or they have other medical problems weakening kidney function.
I always reach for aspirin for mild pain and people have this weird idea that its way more dangerous than paracetamol because its a blood thinner and "what if you bleed for some reason and it doesnt stop" - How is that worse than guaranteed liver damage if you take paracetamol? It almost seems like there was this big push to get people away from Aspirin to tylenol and thats why people have that idea stuck in their heads
NSAIDs (which includes more than aspirin, to be fair) cause like three orders of magnitude more injuries every year than paracetamol. The majority of incidents of liver damage from paracetamol are intentional.
Because it is way more dangerous. Guaranteed liver damage is nonsense. Aspirin and other non selective NSAIDs are much more likely to cause GI bleeding, kidney and heart problems.
An aspirin here or there is probably fine but multiple day dosing of full dose aspirin for chronic pain has gotten a lot of middle age people to bleed out their GI tract and end up dead.
Excedrin is the only thing besides morphine that cures my occasional but brutal headaches.
Do you happen to be a heavy coffee drinker? Caffeine withdrawal can cause immense pain, as I can confirm from first hand experience. For me, it starts ~24 hrs after the last coffee and it usually takes a very strong double espresso and a nap to get back to normal. Maybe Exedrin's Caffeine + Aspirin + Paracetamol has the same effect for you?
Those have caffeine in them right? I'm sure you know your body well, but that could be part of what's helping you as well; could be constricting blood vessels or something like that
Agreed. The one thing that invariably works for me is Excedrin. Not too surprising given it has all three of the most likely solutions in a single pill.
Basically, paracetamol turns out to be mildly contraceptive, by meddling with cell division cycle.
I wonder if it might also slow healing of wounds, or wherever else intense cell division happens.
The authors touch on potential wider implications in the abstract:
> These results suggest that APAP should be used with caution by women attempting to conceive. Given that cell division is fundamental to all development, further investigation is now warranted to substantiate these findings and to elucidate possible implications for other developmental processes, such as gonadal and brain differentiation.
NSAIDs reduce inflammation. Since inflammation is part of healing, they can slow recovery, but they’re useful when inflammation itself is a problem.
paracetamol is not an NSAID.
Yes, but since the parent was talking about drugs with similar effects slowing healing, I thought it was appropriate to mention.
True but one of the proposed mechanisms of action is on the same pathway as NSAIDs
You are right COX-1/2 difference
Unsure if this is related, but I’ve heard that taking painkillers for delayed onset muscle soreness will reduce muscle gains.
Painkillers like ibuprofen are NSAIDs which inhibit the enzyme COX1/2, reducing prostaglandin production.
Prostaglandins are an inflammatory hormone that do a variety of things, but specifically PGE2 plays a role in muscle stem cell activation to divide and produce more muscle fibers. The effect is probably realistically small, but you will leave gains on the table by taking ibuprofen after hard workouts.
Are you saying that lifting weights makes more muscle fibers? I was under the impression it does not, that it simply makes your existing muscle fibers bigger and stronger.
The main muscle fiber cells don't divide (usually), but satellite cells reproduce. Those fuse with the fibers though.
Though the science is not completely established here and there are some exceptions (obvious ones like cancer, etc...)
So, literally "no pain, no gain" ?
Anti-inflammatories - not all painkillers.
Just NSAID’s - they’re anti-inflammatory and muscle synthesis happens in response to inflammation.
Same goes for icebaths, they reduce inflammation, which is the whole point of working out.
The whole point of working out is to stress the organism in order to induce a physiological adaptation. Inflammation is NOT the point, but rather an unfortunate side effect.
Does the opposite hold true as well? If I taunt a wasp nest after hitting the gym will I discover the fast route to mad gains?
You'll certainly get swole.
What about ginger? Because that apparently only downregulates COX-2 without affection COX-1 (most inflammation-reducing drugs affect both)
Etoricoxib does just that and is widely available at least in the EU
Interesting, I didn't know. My original question was more about whether that affects muscle gains differently though, do you happen to have any insights into that?
The studies I saw had people taking a lot, it wasn’t looking at people taking 400mg once a week of their knee or shoulder got sore during the workout.
I think rapid cell division might occur during embryo development. Not a biologist. Just a guess.
The vaccine-autism smoking gun that Andrew Wakefield and RFK Jr. heroically tried to find has, so far, failed to turn up. But there was a study recently that showed that autism is correlated with the mother taking acetaminophen during pregnancy.
> Andrew Wakefield and RFK Jr. heroically tried to find
I'm not sure if that was supposed to be sarcastic, but these two people have done more harm to public health, and are responsible for more health dis/mis-information, than pretty much anyone I can think of. (I am a biochemist, no conflict of interest)
In gp’s defense—I interpreted their formulation to suggest vaccine skeptics applied effort to an heroic degree/amount, not that the effort was of heroic virtue. That is, that those people applied ridiculously high levels of effort to searching for an effect, and still did not find an effect.
As distinct from the retort that “absence of evidence is not evidence of absence”: It can be, if you’ve tried hard enough to gather the evidence and come up short—which is what these guys have done.
I was being highly, highly sarcastic. People still banging the vaccine-autism drum are heroes only in their own mind.
Thanks for clarifying, it was really not obvious given the incredible prevalence of vaccine skepticism!
Yeah that was my charitable reading as well, but with the incredible prevalence of anti-vax/vaccine skepticism, you can never be sure. I thought clarifying could be helpful!
The general advice is to not take any medication during pregnancy without a physician’s advice. This includes all over the counter medicines.
Physicians find it hard, perhaps impossible, to say "do nothing and go home". They always prescribe something or other.
Okay some don't, particularly North American and Northern/Western European ones.
But mostly, on average, physicians always try to prescribe you something.
Provide a reference please. Which country is that from?
Read a paper long time ago, something to do with increase of sulfur in the brain
USA, what my wife’s OB told her. 20 years ago.
Oh I was hoping for a written down reference from an organisation responsible for giving medical advice rather than an single doctor.
Well here’s one:
https://health.clevelandclinic.org/pregnancy-safe-medication...
While they do list some medicines, note that they also say check with your doctor first.
The OB will give you a list of what you can and can’t take. Tylenol is the only pain reliever you can take.
I’d say that qualifies as physician advice.
Or maybe it's genetic. Or whatever. Cite yer sources matey, or it be all hot sargassum.
Arrh, be this good enough for ye?
https://hsph.harvard.edu/news/using-acetaminophen-during-pre...
https://ehjournal.biomedcentral.com/articles/10.1186/s12940-...
I live in Brazil. We have broad access to non-steroidal anti-inflammatory drugs. Even the best-known medicines have unexpected and unknown adverse effects: in general and specifically in people with unexpected genetic, enzymatic, and protein variations. This has no solution. The medicine acts differently in each body, which is subtly diverse from the others. I see a lot of research criticizing any "old" general medicine and introducing the "new" one. I don't know if this is the case. Every medicine has its rush, half-life, and side effects, and its actions are not fully mapped. My preference for long-term treatments is: dipyrone. Short term: ibuprofen. Lymphatic pain: paracetamol. It may not make sense, but that's how I use it.
Interesting how you put metamizole at #1 for long-term treatment. As far as my experience goes, many doctors do the same in Germany. On the other hand, I've heard that the medication is banned in many other countries.
I guess the safest way is to take up the treatment in a hospital, to check for immediate bad reactions.
On the other hand, like with many medications, severe allergies and individual sensibilities causing side effects often don't show up often in the short term, but rather suddenly after many dose intakes.
So I'm back where I started. Not disagreeing with what you say. It seems like these non-steroidal pain relief medications are poorly understood regarding their interaction with the whole body though.
Many OTC medications and even some prescribed ones (especially psychiatric medications) suffer from a very poor understanding and apparent lack of effort in improving the understanding of their mechanisms of action.
Metamizole is safe to take on the long-term, which is not the case for NSAIDs (nephrotoxic) and corticosteroids.
I guess that's why metamizole is often a part of the standard treatment for mid-term exogenic pain here, for example after injuries or during some treatments involving pain.
Not addictive, not hepatotoxic, not nephrotoxic.
Seems the reason for the ban / harder regulation in some countries is about the disturbance of blood-forming in some individuals (which can also be deadly, but I have no idea of the quantified risk here).
Ibuprofen and acetaminophen are more common for short-term treatment, at least that's what I've been taught.
Avoid taking them on a schedule, take them as needed and at the lowest effective dosage.
A.s.s. (lol) too, apart from the low-dose usage that some claim to be helpful with heart/artery diseases.
I've always had an (unreasonable?) dislike of Paracetamol/Tylenol ever since I found out it was the #1 cause of acute liver failure in the US. Liver failure is scary.
https://en.wikipedia.org/wiki/Paracetamol_poisoning
The UK started requiring that Tylenol always be sold in blister packs instead of convenient-to-kill-yourself-with whole bottles of pills.
Results: "Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths."[1]
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC526120/
I am familiar enough with the numbers that I am not necessarily surprised, but I still find it emotionally hard to grok that more than one in five would-be paracetamol suicide victims would be dissuaded by having to pop the pills out of a blister pack first.
Actually nowadays it's less that it's a problem to pop the pills out the booster pack and more that you are limited to the number you can buy.
So if you're going to off yourself you'd have to stock pile or roam around shops picking up.
There is a not insignificant number of suicides where people just say fck it I'll just kill myself but they don't want to go out to any real bother to do it i.e. they don't pre-plan it it's just spur of the moment. A bottle of kill yo self pills is pretty easy. Cupboard, swallow, drink down some water, die. But having to go out and buy a bunch over a few days or like drive around in your car just buying as many as you can. Like you'd have to look it up to check you're going to buy enough.
Back when that law came in when they didn't reduce the total amount you could buy at one time so if you went in and bought like 10 packs at the supermarket then the person at the till would be like ok this person's going to kill themselves so again that would require a bit of balls from the would be kill yo selfer.
I think you can buy a bottle of like 100 x 500mg for like $20 in the USA. That's like over 2 weeks swigging at the max amount. Like you don't need that many, 3-4 days is enough shouldn't be taking that much of the stuff.
That's a different matter that wasn't mentioned though. Where I live (continental Europe) I've never seen any kind of medication as a bottle, but I'm also not aware of there being an amount restriction on paracetamol, which where I grew up in in the Netherlands can be bought in any supermarket. Interestingly I was surprised to find that in France paracetamol can only be sold in pharmacies but hard liquor is available in supermarkets.
Most, if not all, medication would carry a poisonous symbol, if it were not taken out of regulation for that. Mostly, you kill organs by any overdose.
Roughly:
- Paracetamol overdose can cause severe liver damage and may be fatal.
- Ibuprofen in high doses can lead to kidney injury and stomach bleeding.
- Aspirin overdose may result in salicylate poisoning, causing ringing in the ears, confusion, and metabolic acidosis.
- Metamizole has a tendency to kill some percentage of native Brits and their descendants. Yet globally it's one of the most popular painkillers, it's even OTC in countries with sufficiently low numbers of British and related people. (Has anyone ever done research to try and figure out why Brits are on the order of 1000x-10000x more sensitive to that side effect?)
> Brits are on the order of 1000x-10000x more sensitive to that side effect?
That is wild.
If true, it would have to be genetic? I mean, unless it is chronic dehydration from their sense of humor?
That's why it's recommended to combine a half dose of ibuprofen and a half dose of paracetamol at the same time. (Plus some vitamin C)
Together they have higher pain killung effects than each alone, and the side effects are reduced as they affect different body parts. And the vitamin C reduces the damage to the stomach lining.
Or if you need stronger painkilling you can take a full dose of paracetomol and either ibuprofen or aspirin. OTOH aspirin and ibuprofen use the same pathways so combining a full dose of ibuprofen and aspirin is not recommended.
Aspirin and ibuprofen are both NSAIDs with not too dissimilar pathways, so combining them won't be as effective as combining either with paracetamol. They'll both do their jobs, but if the ibuprofen is already doing its job, aspirin won't have much work left to do.
Meanwhile, taking ibuprofen can negate the effect aspirin has when taken against cardiovascular diseases. Not a huge problem if you're just taking it as a painkiller, but not everyone can combine the two. That's another potential reason to take paracetamol over some NSAIDs, though you should obviously consult a doctor if you're taking prescription medicine of any kind.
Interesting, then why does Aspirin do almost nothing when I have a headache, while Ibuprofen works very well and very quickly?
Headaches have different causes.
That's very interesting about vitamin C, I never heard that it can reduce stomach lining damage. It's surprising because things with vitamin C tend to give me heartburn, I assumed because they were acidic. Do you have any references?
Adding to this, its the margin between a therapeutic dose and a harmful dose is most relevant. That margin for aspirin is wide, the same effective vs toxic margin for paracematol is shockingly narrow. Furthermore, the "aspirin is rough on your stomach whereas Tylenol is gentle" turns out to be McNeil Marketing puffery.
"Any medicine can be poison" is kinda missing the point.
There is a rich and varied multidimensional field of danger, from aspects like the safety-margin between regular/dangerous dose levels, the chronology of how it can spike or accumulate, whether there's feedback in advance of damage, etc.
Yeah, I can poison myself drinking clean water, but it's hard.
Thank you for this comment
You can overdose on water and oxygen too. What’s your point?
It's pretty hard to overdose on water unless you're in some state like extreme dehydration where water consumption needs to be overseen by a doctor. Unless you're talking about drowning, then you're just being silly. As a healthy adult, drinking too much water until the point that you're injured is hard to do. You likely need a mental disorder to ignore simple signals like "my stomach is very full right now". Whereas OTC medications can be very easy to overdose. If you don't read the instructions and regularly take more than recommended, you can injure your liver or other organs. Pills are not very big so a handful of them can easily be in the LD50 area.
Oxygen toxicity is not a risk for most people. You either are a scuba diver regularly working at depths beyond what most do or are taking supplemental oxygen while under the care of a doctor. You are not at risk of oxygen toxicity reaching into your bathroom medicine cabinet.
It's not just that it causes liver failure: it's that the difference between the therapeutic dosing range for pain relief it's prescribed for is dangerously close to the toxicity level.
Other drugs like theophylline have ceased to be prescribed for a similar reason alternatives were available, but due to drug marketing, acetaminophen is touted as the "safe" pain reliever.
> but due to drug marketing, acetaminophen is touted as the "safe" pain reliever.
Paracetamol's patents have expired long ago and there's not much profit to be made out of it (nowadays it's mostly not being made in the West, but imported from China, unlike profitable medicine).
The reason why it's still used it's that it's much better than the alternatives, despite the risks (it's only risky if you don't respect the doses by the way).
As with all things, the poison is in the dose. A tonne of incredibly useful medicine can kill you if dosed incorrectly.
> Public awareness that Tylenol causes liver failure which will last weeks before death might dissuade some.
I suspect it will: There's statistical evidence from how Britain migrated its cooking gas systems away from carbon-monoxide-heavy mixes [0] indicating overall suicide-rates are sensitive to convenience and involve short-term periods of vulnerability. As contrasted to "if they really want to they'll find a way no matter what." [1]
__________
[0] https://www.npr.org/2008/07/08/92319314/in-suicide-preventio...
[1] That said, I wouldn't be surprised if there's a bimodal distribution lurking in there, between "depressed but otherwise healthy" versus "terminal diagnosis and chronic pain." The latter-group might not be deterred by inconvenience.
Sure but it’s pretty easy overdose on paracetamol.
Since it’s a mild and really common painkiller, sometimes seen as not dangerous, someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.
Unlike a lot of drugs, you are not going to have a lot of immediate side effects if you overdose on paracetamol. You’ll just horribly die some days after,
How can you reach adulthood and think it's ok to take 3 or 4x the specific dose of any medication? If you're in that much pain you go to a doctor. Which makes me think maybe the issue is the private health system and not the drug.
Conversely, my grandmother's Alzheimer's became apparent when she was overdosing on either ibuprofen or aspirin, I forget which.
She would take a dose for a headache, ten minutes later she'd forgotten so she'd take another dose, ten minutes later, she had forgotten, take another dose, rinse and repeat until it's time for a trip to the hospital.
Maybe it wasn't ten minutes between, probably fewer given how much she'd ended up taking. This happened thirty or so years ago.
> someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.
And the solution is simple: educate people about that.
And it's not something hard to do, just have pharmacists say “respect the dose as it will kill you if you don't” every time they sell things and it'll work.
But Tylenol/acetaminophen/paracetamol is an over the counter drug, so there is no pharmacist involved in most sales. And I certainly wouldn't count on everyone reading the tiny text on the bottle.
That's entirely a sales (de)regulation problem though.
It's funny that in a country where you can win massive sums of money on stupid trials a drug like paracetamol is sold without supervision.
Tylenol is unusual among OTC medications in that you can get liver damage from as little as double the recommended dosage. It doesn't play well with alcohol, either. I wonder how many of those liver failures are the result of people drinking and taking too much of the drug either because the alcohol causes them to lose track, or from the alcohol interaction itself.
Also extra damage if the liver is already busy with alcohol. So not good to take for a hangover.
This is why Ibuprofen is perhaps the better default painkiller.
I'm finding all the 'liver failure' comments on this post fascinating. The dose is on the back on the packet, as is the time interval between doses and the maximum number of pills per day. To overdose you need to ignore that. Given all the mention of 'Tylenol' I'm assuming most of the commenters are American - is this a thing in the US where you just take a random number of pills and ignore the labelling or treat it as a guide? Is it a consequence of the fact you can buy these in bottles by the hundred?
I think there are a few possible factors:
- different packages of the same medication have different doses per pill. So you might read one package that says to take two pills, then later you buy a different package of the same painkiller that says one pill, but you're lazy, and don't read the label for this, and assume it is the same as last time, so you end up doubling the dose.
- For ibuprofen, the label often says if one dose isn't sufficient, then you can take another pill (with a maximum number in 24 hours). People may assume this is the case for Tylenol as well, but I don't think it is.
- people may read the size of the dose, but skip over the warning about the maximum you can take in a 24 hour period.
- The directions are in small hard to read text, which makes all of the above points worse.
Not that any of those are a good excuse not to read the label, but, well, people make bad decisions all the time.
I choose to believe that all of the movies and TV shows showing Americans pouring a handful of pills out of a bottle into their hands and throwing them in their mouths (then chewing them!!!) are 100% accurate to life rather than cinematic shorthand
It is scary, but I assume caution improves your chances of avoiding an overdose considerably.
This send me into a whole rabbit hole. Mostly children get paracetamol overdose. Then I learned that in US/UK kids get paracetamol in liquid form with all kinds of flavours. Which is much harder to dose correctly when the kid spits or drools it out.
Total culture shock for me, as in Europe the default for children is rectal ingestion (which is probably a culture shock as well for Americans). Any how, with pills it is much easier to avoid overdose.
Recently had a prescription error with my two month old baby. The doctor prescribed 7 times as much iron supplement as they intended (confusing labelling - so while I'm annoyed, I can see how it happened). This went on for a month until we uncovered the error.
We had blood test done (on the doctor's recommendation), and luckily there is no sign of any damage, but prescription errors do happen (even if they are rare) and it's much easier with liquids (you probably wouldn't give 8 pills to a baby, but 8ml doesn't seem so bad).
Paracetamol pills are labelled by age (and weight), available over the counter. So quite often we tend to under dose our child as children grow fast.
Calpol is paracetamol as a liquid - that's what we were prescribed after the vaccinations.
Liquid Panadol flavors were totally useless with my son. He would spit it out or upset himself so much he'd throw it up.
We ended up crushing and diluting tablets in milk, which he would drink (you waste a lot of milk to hit the right factor).
As someone in the US, I've only used liquid tylenol for my kids when they were infants and pills were a choking hazard.
Otherwise, it's much easier to get them to take a pill than drink a liquid.
Rectal pills use a different route than oral ones and are very safe.
> as in Europe the default
There's no “as in Europe”, every European country is different. In France the default is also liquid form, but the pipette is graduated is kilograms of baby weight, which limit the errors you can make (you know your kid doesn't weight 15kg when his weight is around 8).
Yeah, this is another rabbit hole. It seems to be Northern Europe and Japan that do rectal pills. Some countries only recommend them as backup.
I think the mistakes also come when the child spits out part of the liquid, and parents give another dose.
> Which is much harder to dose correctly when the kid spits or drools it out.
Never met a non autistic child who would spit or drool out calpol. I'd take the stuff myself as an adult it tastes brilliant.
> Total culture shock for me, as in Europe the default for children is rectal ingestion (which is probably a culture shock as well for Americans)
Huh are you talking about new born babies or something? I've been to a few different EU countries and you can buy liquid stuff for kids in the chemists. (Spain, france, germany, italy) source me as a child getting the stuff when I was sick abroad and the local doc sold my parents basically some off brand calpol.
> "Smoking and alcohol are established risk factors for spontaneous abortion, underscoring the importance of the chemical environment during embryonic development."
Both of my parents are/were heavy smokers drinkers from their teenage years. Mom died of lung cancer from smoking. Kind of wild to think that the odds were really stacked against my birth.
Nature really, really, really wants you to have kids. It took us collectively as a species most of our existence to find genuinely effective methods to alter our biology sufficient to block this process, and we still have a hard time doing it without dramatically impacting the host organism.
This is probably one of those things where the risk is normally small, so small increases cause large changes in percentage.
For instance, if spontaneous abortion is normally 1% and smoking increases it to 2%, then that’s a 100% increase. Now, I don’t know the actual numbers, and smoking is just generally not good for one’s health, but I wouldn’t go as far to say things were stacked against you.
The article says that implantation fails in humans 10-40% of the time. Your point is still valid, but the scale in reality is very significant.
Millions of kids have been born to parents who smoked and drank all the way through their pregnancies, especially before the 1970s or so. It raises risks, but doesn’t guarantee bad outcomes.
Many, many more but here's a few you might want to start with:
"The meta-analysis showed a significant association between maternal tobacco smoking during pregnancy and increased risk of ADHD in offspring."
Mohammadian M, Khachatryan LG, Vadiyan FV, Maleki M, Fatahian F, et al. (2025) The association between maternal tobacco smoking during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring: A systematic review and meta-analysis. PLOS ONE 20(2): e0317112. https://doi.org/10.1371/journal.pone.0317112
"Compared with unexposed controls, individuals with PAE reported significantly higher frequencies of problems with hearing, dentition, heart, cancer, gastritis, kidney stones, bladder, diabetes, thyroid, skin, and seizures."
Coles, C.D., Shapiro, Z.R., Kable, J.A., Stoner, S.A., Ritfeld, G.J. & Grant, T.M. (2024) Prenatal alcohol exposure and health at midlife: Self-reported health outcomes in two cohorts. Alcohol: Clinical and Experimental Research, 48, 2045–2059. https://doi.org/10.1111/acer.15441
"Our results indicate that perinatal exposure to maternal smoking is associated with increased risks of CVD events, and such relations are modified by adulthood smoking behaviors."
H., Liang, Z., Wang, H., Cardoso, M. A., Heianza, Y., & Qi, L. (2021). Perinatal exposure to maternal smoking and adulthood smoking behaviors in predicting cardiovascular diseases: A prospective cohort study. Atherosclerosis, 328, 52–59. https://doi.org/10.1016/j.atherosclerosis.2021.05.009
"Our findings support previous findings suggesting the detrimental effects of prenatal binge drinking on child cognition. Prenatal alcohol exposure at levels less than daily drinking might be detrimentally associated with child behavior. The results of this review highlight the importance of abstaining from binge drinking during pregnancy and provide evidence that there is no known safe amount of alcohol to consume while pregnant."
Flak, A. L., Su, S., Bertrand, J., Denny, C. H., Kesmodel, U. S., & Cogswell, M. E. (2014). The association of mild, moderate, and binge prenatal alcohol exposure and child neuropsychological outcomes: a meta-analysis. Alcoholism, clinical and experimental research, 38(1), 214–226. https://doi.org/10.1111/acer.12214
You may not not want to hear this, but let's put it plainly: Prenatal smoking and alcohol is clear and obvious child maltreatment.
> "The meta-analysis showed a significant association between maternal tobacco smoking during pregnancy and increased risk of ADHD in offspring."
The implied causation annoys me. ADHD is hereditary, even if if the mother does not smoke. People with ADHD smoke ten times more often.
It is wrong to claim that ADHD is exclusively hereditary. Also, epigenetics show that behavior changes what is inherited. This is a chance and a responsibility. [1]
More broadly speaking, anything that is claimed to be "hereditary" (which for ADHD the scientific consensus is that it is not exclusively but estimated at around 70%) could also be early nuture and prenatal environment. The way genetic inheritance is researched (identical twins vs. fraternal twins) cannot account for this. [2]
[1] e.g.
"ADHD has been clearly linked with numerous environmental risk factors, particularly around the prenatal and perinatal period. Some of the most robust risk factors identified are maternal prenatal health conditions and psychological distress (e.g. hypertension, obesity, pre-eclampsia, immune activation), in utero exposure to poor diet (with critical factors still being determined), teratogenic effects of certain medications (e.g. acetaminophen) and environmental exposures (e.g. lead), as well as neonatal factors such as prematurity and low birth weight [27]. Other extreme exposures in the postnatal environment (such as extreme infant emotional neglect) have also been associated with an ADHD syndrome [28, 29]."
Cecil, C. A. M., & Nigg, J. T. (2022). Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential. Molecular diagnosis & therapy, 26(6), 581–606. https://doi.org/10.1007/s40291-022-00609-y
"The convincing evidence for genes as risk factors for ADHD does not exclude the environment as a source of etiology. The fact that twin estimates of heritability are less than 100% asserts quite strongly that environmental factors must be involved. ADHD’s heritability is high, and that estimate encompasses gene by environment interaction. Thus, it is possible that such interactions will account for much of ADHD’s etiology. Environmental risk factors likely work through epigenetic mechanisms, which have barely been studied in ADHD [148]. The importance of the environment can also be seen in the fact that, as for other complex genetic disorders, much of ADHD’s heritability is explained by SNPs in regulatory regions rather than coding regions [149]."
Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular psychiatry, 24(4), 562–575. https://doi.org/10.1038/s41380-018-0070-0
"Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes."
Robinson, L. R., Bitsko, R. H., O'Masta, B., Holbrook, J. R., Ko, J., Barry, C. M., Maher, B., Cerles, A., Saadeh, K., MacMillan, L., Mahmooth, Z., Bloomfield, J., Rush, M., & Kaminski, J. W. (2024). A Systematic Review and Meta-analysis of Parental Depression, Antidepressant Usage, Antisocial Personality Disorder, and Stress and Anxiety as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children. Prevention science : the official journal of the Society for Prevention Research, 25(Suppl 2), 272–290. https://doi.org/10.1007/s11121-022-01383-3
[2]
"twin studies fail to separate the effects of genes and the prenatal environment. This failure casts doubt on claims of the relative effects of genes and environment on intelligence, psychiatric disorders, personality and other psychological variables, and other conditions."
https://www.psychologytoday.com/gb/blog/looking-in-the-cultu...
"Although many twin studies have been conducted (which is quite an understatement; there are almost 9,000 hits for “twin study” on PubMed!), there have long been critics who argue that they are scientifically worthless."
Smith, Jinkinson. (2020). The debate over twin studies: an overview. http://dx.doi.org/10.22541/au.159674847.78026661
"Because heritability is defined by both genetic and environmental influences, it is not a fixed characteristic of a disease or trait, but a population-specific estimate, analogous to, for example, the mean height, cholesterol level or life expectancy in a population. It also cannot be interpretated at the family or individual level."
Kaprio J. (2012). Twins and the mystery of missing heritability: the contribution of gene-environment interactions. Journal of internal medicine, 272(5), 440–448. https://doi.org/10.1111/j.1365-2796.2012.02587.x
More: https://en.wikipedia.org/wiki/Twin_study#Criticism
Don’t misunderstand that I’m advocating it.
Smoking certainly isn't good, but it also isn't some super-poison like some people like to pretend. Nearly half of US smoked in the 40s and 50s and they had no problem having tons of kids.
> but it also isn't some super-poison like some people like to pretend
My mom's dead from lung cancer, and my dad is basically on palliative care. He's a barely walking billboard for "smoking is bad for you".
Yeah that sucks, but now compare its mortality rate to other substances people get addicted to.
It's interesting because my wife has been using Ibuprofen for headache relief, whereas I use Paracetamol. I usually got Paracetamol growing up but recent studies showing adverse effects of Ibuprofen on male fertility solidified my resolve and consistency in choosing Paracetamol. My wife's reason for using Ibuprofen was simply because it worked better for her. Now it's kind of surprising to learn that Paracetamol has negative effect on women's fertility... I guess this means that both drugs are harmful to a different gender? What a coincidence? We were both using the optimal one for ourselves for reasons beyond our understanding... Until more data comes out.
Anyway, I understand arguments for avoiding drugs, medicines and chemicals altogether. Clearly, everything is more complex than it seems and side effects can never be fully known or understood; especially on a case-by-base basis given that everyone's DNA is different and responds differently to chemicals. I only take Paracetamol if I have a migraine with visual aura which is quite rare. I don't take it for standard headaches.
Embryonic development is so sensitive, especially that if nervous system. I suggest to my patients total drug avoidance. Even peeling off the tomatoes.
Acetaminophen/Paracetamol is a cox3 inhibitor
it also messes with bone formation so be careful using it for any length of time
especially after athletic activity
“ APAP could contribute to early embryonic loss by impairing initial cell divisions. These results suggest that APAP should be used with caution by women attempting to conceive. Given that cell division is fundamental to all development, further investigation is now warranted”
By the same logic it would now be effective against cancer, no?
Isn't paracetamol forbidden in the US for pregnant women already? It is in other countries
As far as I can tell from my local health organisations, paracetamol is one of the safest painkillers for pregnant women.
That doesn't make it very safe, but NSAIDs carry well known risks during later stages of pregnancy, and opiods aren't exactly harmless either. Even aspirin carries risk (and aspirin doesn't even work as well compared to other drugs).
As far as I can tell paracetamol is still the first choice for painkillers while pregnant, but only because none of them are completely safe to use. It's probably fine for short term usage, but that also goes for non-pregnant people to be honest.
No it’s the only allowed pain reliever for pregnant women in the US. It’s also allowed in the UK and the EU from what I can tell. What countries are you talking abou?
Sincere apologies, I mixed ibuprofen and paracetamol.
Ibuprofen is forbidden for pregnant women in the last 4 months in France at least - and by "forbidden", I mean "strongly advised against in a case of self medication".
You are probably thinking of ibuprofen which is considered non safe during pregnancy. Paracetamol is pretty much the only OTC pain relief medication that is recommended for pregnant women.
Yes indeed, you are absolutely right. Sorry about that.
Can the effects of a drug on the body be reversed after a person stops taking it?
Sometimes yes, sometimes no.
Yes, in most cases. Or are you specifically asking about Paracetamol?
For paracetamol intoxication, there is n-acetylcysteine.
Anyone know what the long term side effects are?
I've been taking multiple paracetamol tablets for years now, almost out of habit now.
An unhappy liver, mainly
I won't take acetaminophen (usually) learning of the liver toxicity and low overdose potential. And I have a friend that destroyed his kidneys with ibuprofen and is on a transplant list.
But from what I understand acetaminophen also dulls emotional pain like from being fired or breaking up with a girlfriend which is interesting.
I still prefer to take neither if I can avoid it and I'll hurt a little bit instead. Hurt a lot and I'd probably change my mind though.
> And I have a friend that destroyed his kidneys with ibuprofen
Acetaminophen is not ibuprofen. But I also don't like planes because a friend of mine died in a car crash.
I know and don't believe I implied they were.
There is also the final sentence about preferring to take "neither". Which of course indicates _two_ substances.
But just to be safe, I don't think the liver and the kidneys are the same organ either :)
Expected in-depth discussions about the topic, but got pseudo-science medical advice instead. I guess HN _is_ a 'social media' after all.
This site is populated by mid-level code monkeys and “founders” of junk B2B startups. So, two groups that have an inflated sense of their own intelligence and believe everything that leaves their lips (or tips of their fingers) is on level of God’s word.
I'm sure an untreated infection might be more upsetting.
Except that paracetamol does not treat infections.
What scares me about this is that Tylenol is a drug that's been handed out to everyone, for everything, for decades. And if we could miss how dangerous this one is, what are the odds other drugs aren't just as risky?
Side note, here's a Scrubs clip from 2001 that shows just how ubiquitous Tylenol was.
https://www.youtube.com/watch?v=EcDWj7kZcRc
I know the anti-vax crowd is full of homeopaths, chiropractors, and tarot readers. But they're not wrong about one thing: drug companies make money by selling drugs. If we can't guarantee real oversight before those drugs hit the market, we're in deep trouble.
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> Nobody should ever take it, ibuprofen is better in every way.
Please don't give health advice on the internet. I'm not a doctor but I'm a biochemist, and there are MANY situations where ibuprofen is less safe.
Not denying that acetaminophen/paracetamol has a horrible therapeutic index, but there are reasons why it is still so widely used. Despite potential hepatoxicity, it is considered the safest pain relief drug (this emerging research notwithstanding)
Ibuprofen is not better in every way. For instance ibuprofen, as well as other NSAIDs, is much less gentle on gastrointestinal tract and puts much more strain on kidneys.
Some people (e.g. with inflammatory bowel diseases or renal diseases) do not tolerate NSAIDs well, which is why acetaminophen is on the same step of analgesic ladder - it is still considered better in some cases. Both are also used complementary to each other in pediatrics.
Your comment is fair; obviously I wrote a pretty flippant comment, but the message is largely useful for most people.
The fact is that (largely due to the incredible marketing of Johnson & Johnson's Tylenol brand in the US) way too many people think acetaminophen is "safe and effective" when it's actually both pretty unsafe and pretty ineffective. Most people just "pop a Tylenol" by default without realizing it's not much better than placebo.
Sure there are cases where people have unique risks and should avoid NSAIDs. But for the vast majority of the public, if they or their kid are dealing with a headache, fever, menstrual cramp, or other transient pain or fever, they should reach for ibuprofen (with a snack) over acetaminophen. It's not remotely a close call.
I'm frankly pleased that people are becoming more aware of this and I don't mind taking a couple correction comments for presenting the info in a superficial way.
NSAIDs can cause GI issues if taken with or without a snack.
They reduce production of the stomach’s protective mucous lining. Snacks don’t help with that.
They can also cause kidney damage.
Occasional use for an otherwise healthy person is fine. But Tylenol as long as you are careful not to take too much is generally safer.
> ibuprofen is better in every way.
Taking ibuprofen (or other NSAIDs) long-term can wear away the stomach lining, causing ulcers. Acetaminophen is generally better tolerated to manage mild long-term pain than NSAIDs, as long as you don't overdose / take with alcohol.
Yes, you need to take it with food, but it won't cause liver failure.
> take it with food
That's not helpful for the various categories of people who are more prone to gastrointestinal bleeding.
Yeah, but on the long-term it will cause kidney injury.
This is a dangerous advice. Please folks. disregard this OPs comment. I doubt he is a doctor.
Ibuprofen is not better in every way. Ibuprofen is active in so many different parts of the body at the same time that inevitably it has unintended effects which is more pronounced especially in the elderly. It's bad for stomach, bad for kidneys, bad for mental status. and very bad with long-term use.
TLDR. Both aren't great for different reasons. Tylenol can be acutely OD'd and evidence is starting to show it isn't great embryos. Outside of those 2 situations that can be easily avoided, it is overall less bad than ibuprofen.
Barely effective? The difference 20 minutes after my toddler takes a dose is astonishing.
It's also a very effective drug for reducing high fevers in infants and children.
There are legitimate reasons to complain about APAP but calling it a placebo is nonsense.
> I won't get into the history of why people take so much acetaminophen despite how crappy a drug it is.
I'd love if you did. What's the story there?
Basically, the pharma industry's most successful marketing campaign ever. Here's an article from 1982:
https://www.washingtonpost.com/archive/politics/1982/10/02/h...
https://archive.md/rssPI
Barely effective? Seems to work well for me
>> ibuprofen is better in every way
Give me paracetamol over ibuprofen in most cases. Ibuprofen is much more likely to cause stomach issues than I am to miscalculate "take 2 paracetamol every 4-6 hours".
Naproxen sodium is also a lot better, and is slightly safer than ibuprofen to take for extended periods. I had severe sciatica for the better part of a year, and the only thing that kept me somewhat functional was ~1000mg/day of naproxen, which isn’t great for you but would’ve been a lot worse if it had been ibuprofen (never mind opiates or something).
Did your sciatica go away on its own or did you introduce some new exercises to your routine? I've had some pain in my left leg for a few months now that is likely sciatica. I did go to the doctor, but it wasn't a particularly helpful visit.
I did physical therapy which mostly involved strengthening core muscles - if the cause is a herniated disc, which it usually is, this can slightly speed up the recovery process because a stronger core can push the disc back into place. But this is a speedup in the sense of "8-10 months instead of 10-12". Welcome, certainly, but not a silver bullet.
The other thing the PT taught me was nerve glides (also called nerve flosses). These don't seem to make recovery any faster, but help a decent amount with pain and tightness .
Sadly, that plus loading up on NSAIDs appears to be about all you can do for most cases of sciatica. I got a consult with a back surgeon who basically said, "I can operate if you want, but it probably won't help much, you just have to wait".
Good luck: it can be a pretty miserable time, but the good news is that most cases of sciatica do in fact clear up on their own even without PT. It can just take a while and you'll be hurting in the meantime.
I have an emergency Naproxen stash for the occasional gout flare-up and it's so much more effective than Ibuprofen it's amazing.
It's also even worse at gastrointestinal problems, for those affected. That's why it's less commonly used.
That's fair, but naproxen is OTC or prescription-only in many jurisdictions.
I think Paracetamol is better for fever, but for other pain I always prefer Ibuprofen.
From wikipedia:
At a standard dose, paracetamol slightly reduces fever,[13][17][18] though it is inferior to ibuprofen in that respect[19]
[13] Warwick C (November 2008). "Paracetamol and fever management". J R Soc Promot Health. 128 (6): 320–323. doi:10.1177/1466424008092794. PMID 19058473. S2CID 25702228.
[17] Chiumello D, Gotti M, Vergani G (April 2017). "Paracetamol in fever in critically ill patients-an update". J Crit Care. 38: 245–252. doi:10.1016/j.jcrc.2016.10.021. PMID 27992852. S2CID 5815020.
[18] de Martino M, Chiarugi A (December 2015). "Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management". Pain Ther. 4 (2): 149–68. doi:10.1007/s40122-015-0040-z. PMC 4676765. PMID 26518691.
[19] Pierce CA, Voss B (March 2010). "Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review". Ann Pharmacother. 44 (3): 489–506. doi:10.1345/aph.1M332. PMID 20150507. S2CID 44669940.
> At a standard dose, paracetamol slightly reduces fever,[13][17][18] though it is inferior to ibuprofen in that respect[19]
It's good you can take both at the same time then! (For adults.)
There is mounting talk of a link between Paracetamol/Acetaminophen/Tylenol and autism.
Some links:
https://hsph.harvard.edu/news/using-acetaminophen-during-pre...
https://jennifermargulis.substack.com/p/why-this-doctor-is-c...
A study published in JAMA in 2024 concluded that there is no evidence for that claim (https://jamanetwork.com/journals/jama/fullarticle/2817406):
Question: Does acetaminophen use during pregnancy increase children’s risk of neurodevelopmental disorders?
Findings: In this population-based study, models without sibling controls identified marginally increased risks of autism and attention-deficit/hyperactivity disorder (ADHD) associated with acetaminophen use during pregnancy. However, analyses of matched full sibling pairs found no evidence of increased risk of autism (hazard ratio, 0.98), ADHD (hazard ratio, 0.98), or intellectual disability (hazard ratio, 1.01) associated with acetaminophen use.
Meaning: Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in other models may have been attributable to confounding.
The 1 study you linked does not disprove the newer 46-study analysis that I linked. Quoting from it:
"We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations."
It tends to be poor scholarship imho.
Autistic moms are more likely to have chronic illness, sensory issues, auto immune issues, etc thus are more likely to be taking medications. In the end, the autistic mom just passes her autistic genes to the baby.
I never took Tylenol/Paracetamol/acetaminophen, or anything containing it or given it to my children. We never reduce fever below 39.5/103.1 either - risks of febrile seizures are overstated and if you're a responsible parent, not a lazy one, you can see if things are going South, but there are other traditional means to lower fever. People are just too spoiled nowadays!
I tested positive with COVID-19 on Tuesday and had a pretty high fever (103) with a terrible headache, but I didn't take ibuprofen. First, because it could lower my fever, second, because its anti-inflammatory effect would compromise my immune system response to the pathogen. Most people I know immediately try to lower their fever to reduce their discomfort and would immediately take it for headaches, too.
I’m not a doctor but I’m pretty sure ibuprofen is _not_ acetaminophen.
Of course it's not - I clearly said I never take acetaminophen, if for headache/fever I would rather take ibuprofen instead... but I don't take even that w/o a solid reason!
People do that because they haven't been "educated" (even superficially) about what fever really is, which is your body working hard to fight of the infection. And messing with it is counterproductive.
They also do it with their kids because they want to help them. Also, some people have a lot on their plate, calling them lazy is not right thing to do. I have health insurance that covers me when my kids are sick (not in the US), so I can take care of them "properly ". This doesn't make me more responsible and someone else that works two jobs and can't afford to have sick kids lazy.
Also, I don't lower fever, even with my kids unless it prevents them from sleeping. But overstated is relative, it's happened to the kid next door from me. You don't want to be careless with infants.
They are lazy if they don’t educate themselves about what they are doing and what they are giving their children. Don’t get offended. I’ve never done anything health-related to my kids without doing thorough research. I’ve witnessed four major medical mistakes made right in front of me in Orange County, California, in some of the best medical facilities and by the best pediatricians in the area! That’s why I don’t blindly trust anyone, whether it’s a doctor or not. I use critical thinking and always look for alternative advice. Doctors often find me a nuisance, but that’s okay with me. Just try asking a doctor when they prescribe Tylenol for a fever: “Why should I try lowering their fever?” or “Why should I give them Tylenol exactly?” The hepatotoxicity of acetaminophen occurs when the production of the toxic metabolite NAPQI exceeds the liver’s glutathione detoxification capacity, which can happen quite frequently during infections! So, then ask your doctor: “Doesn’t it make sense to give them NAC with Tylenol as well, just in case?” They won’t know what to say, trust me!
I have not found any study published after 2020 (the year when the French minister made the statement) that advises against ibuprofen for COVID-19. But I'm not a doctor, so I'd be interested to know your source.
Studies showed negative efficacy. At best, no difference. [0]
[0]: https://c19early.org/ib
> risks of febrile seizures are overstated and if you're a responsible parent, not a lazy one, you can see if things are going South
Not always. Blaming “lazy” and irresponsible parents is disgusting.
But it's the truth. Something that has just a 2% incidence should not dictate 98% of the treatments. Compromising the innate immunity of the 98% is more disgusting!
> But it's the truth.
No it's not, in many case there's just no way the parent can tell something is about to go wrong.
> Something that has just a 2% incidence should not dictate 98% of the treatments.
This isn't the same argument, and I would agree if it was true, but you're distorting numbers as the actual prevalence estimations lie between 2 and 14%[1].
Now you could make the argument that 10% is low enough of incidence it shouldn't dictate the treatment of the other 90%, but that's not what you're doing, instead you are blaming helpless parents and cherry picking numbers, making nothing but noise.
Oh, and by the way, most parents aren't in fact giving their kids paracetamol for that particular reason (as most parents are simply unaware of the existence of febrile seizures), but to help their children sleep and rest (and so themselves can sleep). And in fact, resting being key in innate immunity efficiency, I'm not particularly convinced about the effectiveness of letting your kids cry all night because of the pain and fever. You do what you want with your own kids, but there's no justification for insulting other parents.
Good day.
[1]: https://www.bmj.com/content/351/bmj.h4240
The vast majority of these seizures are benign. If your child had a febrile seizure, then there's a 30% chance of having it again, so, then you have some excuse to keep their fever under control (hopefully not with Tylenol as there are other antipyretics, too). Here's a nice summary by Gemini:
Key Takeaways
- No Lasting Damage: Simple febrile seizures do not cause long-term brain damage, intellectual impairment, or learning disabilities.
- Benign Nature: Despite how terrifying they are to witness, febrile seizures are considered benign events in the vast majority of cases.
- Focus on Reassurance: The primary goal for healthcare providers is to reassure parents and caregivers, providing them with the knowledge and tools to manage a fever and understand the low risk of lasting effects.
Ah, a genius that need an artificial brain to overcome its lack of literacy and is somehow proud of that.
How surprising given the rest of the conversation …
I have 3 kids, all grown up and healthy. They all slept perfectly well with fever, so, there's no such thing as a febrile insomniac kid. High fever has a potent detox element as you sweat out the toxic metabolites. I'm tired of parents who overprotect their children while harming them this way - there are so many studies - from overdrugging kids (thank God that most anti-cough drugs are now off the shelves), to forcing them to wear helmets, no go alone, etc.
> They all slept perfectly well with fever, so, there's no such thing as a febrile insomniac kid.
Please stop believing your sample of 3 kids is representative of the entire population. You were lucky to have kids who sleep well and that's good for you, but that doesn't make other parents lazy or irresponsible.
> I'm tired of parents who overprotect their children
You know what's even more tiring? Parents who judge other parents while not knowing anything about kids in general just because they happened to be lucky on one particular topic. You won't be lucky all the time though.
> to forcing them to wear helmets
I hope you won't regret saying that ever in your life, but being anti-helmet really is as idiotic as being an antivaxxer.