Paracetamol disrupts early embryogenesis by cell cycle inhibition

https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf116/8234396

by XzetaU8 • 11 months ago

191 157 11 months ago

academic.oup.com

nine_k• 11 months ago

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.

oh_my_goodness• 11 months ago

I think rapid cell division might occur during embryo development. Not a biologist. Just a guess.

10-1-100• 11 months ago

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.

bitwize3• 11 months ago

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.

epgui4• 11 months ago

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)

greesil• 11 months ago

Or maybe it's genetic. Or whatever. Cite yer sources matey, or it be all hot sargassum.

SoftTalker6• 11 months ago

The general advice is to not take any medication during pregnancy without a physician’s advice. This includes all over the counter medicines.

odyssey7• 11 months ago

Unsure if this is related, but I’ve heard that taking painkillers for delayed onset muscle soreness will reduce muscle gains.

cenamus• 11 months ago

Same goes for icebaths, they reduce inflammation, which is the whole point of working out.

rkomorn2• 11 months ago

So, literally "no pain, no gain" ?

ed• 11 months ago

Just NSAID’s - they’re anti-inflammatory and muscle synthesis happens in response to inflammation.

15155• 11 months ago

Anti-inflammatories - not all painkillers.

VirusNewbie• 11 months ago

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.

stanford_labrat• 11 months ago

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.

artvandelai2• 11 months ago

NSAIDs reduce inflammation. Since inflammation is part of healing, they can slow recovery, but they’re useful when inflammation itself is a problem.

e40• 11 months ago

paracetamol is not an NSAID.

latchkey2• 11 months ago

"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.

roughly• 11 months ago

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.

bena• 11 months ago

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.

SoftTalker6• 11 months ago

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.

docfort• 11 months ago

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.

AngryData2• 11 months ago

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.

latchkey2• 11 months ago

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".

GeekyBear• 11 months ago

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.

m463• 11 months ago

maybe should add (tylenol) to the article subject?

de6u99er• 11 months ago

Can the effects of a drug on the body be reversed after a person stops taking it?

epgui4• 11 months ago

Sometimes yes, sometimes no.

thisislife2• 11 months ago

Yes, in most cases. Or are you specifically asking about Paracetamol?

davikr2• 11 months ago

For paracetamol intoxication, there is n-acetylcysteine.

ck2• 11 months ago

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

Terr_2• 11 months ago

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

jonkoops• 11 months ago

As with all things, the poison is in the dose. A tonne of incredibly useful medicine can kill you if dosed incorrectly.

pjerem• 11 months ago

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,

skybrian• 11 months ago

It is scary, but I assume caution improves your chances of avoiding an overdose considerably.

lr4444lr• 11 months ago

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.

littlestymaar14• 11 months ago

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).

a3w• 11 months ago

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.

Terr_2• 11 months ago

"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.

kuschku• 11 months ago

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.

anjel• 11 months ago

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.

formerly_proven• 11 months ago

- 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?)

hdgvhicv• 11 months ago

You can overdose on water and oxygen too. What’s your point?

whazor4• 11 months ago

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.

XorNot• 11 months ago

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).

verbify2• 11 months ago

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).

littlestymaar14• 11 months ago

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).

Dave3of52• 11 months ago

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.

thayne3• 11 months ago

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.

tobias3• 11 months ago

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.

mullingitover• 11 months ago

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/

akk02• 11 months ago

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.

basisword3• 11 months ago

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?

amenhotep• 11 months ago

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

thayne3• 11 months ago

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.

laughing_man• 11 months ago

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.

moi2388• 11 months ago

“ 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?

oliveiracwb• 11 months ago

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.

moritzwarhier2• 11 months ago

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.

davikr2• 11 months ago

Metamizole is safe to take on the long-term, which is not the case for NSAIDs (nephrotoxic) and corticosteroids.

thrance• 11 months ago

I'm sure an untreated infection might be more upsetting.

hollerith• 11 months ago

Except that paracetamol does not treat infections.

mythrwy2• 11 months ago

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.

javcasas• 11 months ago

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.

mythrwy2• 11 months ago

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 :)

Noe20973• 11 months ago

Isn't paracetamol forbidden in the US for pregnant women already? It is in other countries

sarchertech2• 11 months ago

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?

Noe20973• 11 months ago

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".

jeroenhd2• 11 months ago

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.

mynegation• 11 months ago

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.

Noe20973• 11 months ago

Yes indeed, you are absolutely right. Sorry about that.

WorkerBee284742• 11 months ago

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...

zoeysmithe• 11 months ago

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.

sigpwned• 11 months ago

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.

WorkerBee284742• 11 months ago

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."

nikolay14• 11 months ago

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.

littlestymaar14• 11 months ago

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.

nikolay14• 11 months ago

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!

efnx• 11 months ago

I’m not a doctor but I’m pretty sure ibuprofen is _not_ acetaminophen.

nikolay14• 11 months ago

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!

tralarpa• 11 months ago

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.

nikolay14• 11 months ago

Studies showed negative efficacy. At best, no difference. [0]

[0] https://c19early.org/ib

locallost• 11 months ago

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.

nikolay14• 11 months ago

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!

notcodingtoday• 11 months ago

Expected in-depth discussions about the topic, but got pseudo-science medical advice instead. I guess HN _is_ a 'social media' after all.

Cornbilly• 11 months ago

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.

dbg31415• 11 months ago

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.

jongjong• 11 months ago

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.

wiredpancake• 11 months ago

Anyone know what the long term side effects are?

I've been taking multiple paracetamol tablets for years now, almost out of habit now.

vrighter• 11 months ago

An unhappy liver, mainly

tsoukase• 11 months ago

Embryonic development is so sensitive, especially that if nervous system. I suggest to my patients total drug avoidance. Even peeling off the tomatoes.

Paracetamol disrupts early embryogenesis by cell cycle inhibition

Related Stories