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I can't see inside your medicine cabinet, but if there's one thing I'd be willing to bet you have in there, it's acetaminophen. Depending on where you live, it may be labeled with a brand name like "Tylenol," "Calpol, or "Panadol." Acetaminophen may be the most widely used over-the-counter pain reliever in the world, and that's partly because for a long time common wisdom was held that other over-the-counter pain relievers have a slightly worse safety profile: being tough on your stomach, kidneys, and heart.

However, recently, experts have been taking a second look at whether acetaminophen is actually safer, and whether it works at all. So, is it time to toss out that bottle? Let's dig into this question.

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On paper, acetaminophen - or "paracetamol" in most places outside the US - looks like it should work as a pain reliever. It does a couple of different things: it stops the body from making prostaglandins, or fats that deal with inflammation; it slows down the body's reabsorption of certain pain-killing chemicals so they can hang around longer; and it can also dampen pain signals in the central nervous system. We don't 100% understand everything about it, but that all seems pretty solid.

What's more, acetaminophen has had a sterling safety reputation for a long time, at least compared to its main competitors - the non-steroidal anti-inflammatory Drugs (NSAIDs), like ibuprofen and naproxen. That reputation might come down to how rough NSAIDs can be on the stomach, plus their many known side effects, like increasing a person's risk of heart attacks, bleeding in the gut, and stroke. A 2004 study found that some 30% of hospital admissions for drug side effects at two large UK hospitals came from NSAIDs alone.

Now, acetaminophen comes with its own list of potential side effects, but generally that list is much more tame, and serious complication are rare when taking the right dose. Plus, we tend to think it works, right?

Well, if you're used to reaching for acetaminophen for your minor aches and pains, it might be distressing to hear that a large review of the literature published in 2021 found shockingly little evidence that the stuff actually works for that purpose. This review collected the findings from more than 35 studies that each analyzed how well acetaminophen worked for 44 painful conditions, ranging from sore throat all the way up to pain related to cancer. And out of all of that research, they only found two conditions where the drug was definitely better than placebo at treating pain. Those were knee or hip osteoarthritis, which is a reason many people might want a pain reliever, and craniotomy a.k.a. removing a bit of the skull, which is... less so.

The review also found moderately good evidence that acetaminophen helps with perineal pain after childbirth as well as tension headaches. But for the other 40 or so conditions, acetaminophen was no better than a sugar pill. What's more, the review noted one study that concluded it was no good at all for treating lower back pain, which might just be one of the most common reasons for wanting pain relief.

Now, I see you getting up to trash that bottle in your medicine cabinet, but hang on - the video's not over. The reason it was so hard to find cases where acetaminophen did its job well, according to the reviews' authors, is that most of the evidence was too poor quality to draw any real conclusions. It wasn't proof that the drug doesn't work; it was a stunning lack of proof that it does. For almost half of the conditions they studied, the evidence was inconclusive or totally absent.

See, the way participants in these studies were taking acetaminophen doesn't match up with how you'd use it in real life. Most of the time, people in the studies would take a single dose instead of several pills every few hours. That might've been because the study was trying to figure out how long a single dose of pain relief would last, or just because it makes it easier to compare between participants, since everyone gets the dose at the same time. So, it makes sense that those studies  underestimated how well it works, but also underestimated any negative side effects.

The authors also point out a couple of other issues, like the tendency for scientists to only publish something if they found an effect, or that there were inconsistent results for the same condition across studies. It adds up to our having very little understanding of how this incredibly common drug performs in real life, which is what a drug needs to do, after all.

So, it's hard to say whether acetaminophen works. But is it at least safe for regular people using it for stuff like headaches? An earlier review from 2015 found that actually, it was pretty hard to answer that question, too.

The authors of that review specifically wanted to find studies of typical people taking regular doses of acetaminophen and watching what happened, because that would actually inform physicians who ar trying to give people advice. And there are surprisingly few of those.

Out of almost 2,000 studies, the researchers only identified eight that met their criteria. Out of those they did choose, they could sum up acetaminophen safety as - the more acetaminophen adults take, the more likely they are to have issues with their kidneys, heart, or gut. We've also known for a while that it's touchy for the liver. These risks are why doctors don't recommend you take acetaminophen for days on end.

But this review, again, points out how hard it was to come to that conclusion because there are so few studies out there that reflect how the general adult population actually takes acetaminophen instead of, say, how it works for someone who's just had surgery or a long-term illness like osteoarthritis.

And out of those that do exist, there were other problems. Like how participants had to report how much and how often they took the pills. So, what we know about their dosage comes down to the accuracy of the participants' memories. Plus, some participants may have been prescribed acetaminophen specifically because they couldn't take something else because of a heath issue. So, you're starting out with a study population that's already more at risk of something going wrong.

What both of these reviews tell us is that the problem is not that acetaminophen flat out doesn't work or isn't safe; it's that the quality of evidence that it does work or is safer than other options isn't great, which is not the same thing. It tells us as much about how we study drugs in the real world as it does about acetaminophen per se. But it does also tell us that a worldwide staple of our medicine cabinets might not be as reliable as many patients and doctors have assumed for a long time.

So although you might have heard the old mantra that acetaminophen is better than something like NSAIDs, we don't entirely know that. But, that being said, some people do need to avoid certain drugs, like NSAIDs, for other reasons. So, as always, follow your doctor's advice.

Right now, some doctors are rethinking their recommendations around over-the-counter pain relief. But mostly, they're asking for better trials so they can be more informed. Because, of course, patients want to understand the risks and benefits of the medicine we take, and doctors want to be able to provide that information. Just goes to show there's always more science to be done.

And you can do more science right now by logging on to Brilliant, the online learning platform with thousands of interactive lessons  in science, computer science, and math. They even have a course on "Knowledge and Uncertainty," so you can explore how having more information can make you more confident in things like your medicine. The course is all about how learning something new can change the way you understand how the world works, and that's a big thing we care about here at SciShow. It's the perfect mix of mathematics that you can use in your real life, but applied enough that you don't need a calculator or graphing tools.

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