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A note on post 320, my previous commentary about this subject
I wrote about Tylenol (acetaminophen) and aspirin in post 320 on August 7, 2024, with much of the material supplied by my friend Jerome Kahn. The story it told was right. Four of its numbers were not, and I would rather correct them myself than have a critic find them.
● The cancer figures were too strong. I wrote that daily aspirin lowers cancer risk by over 50 percent. The best randomized evidence shows about a fifth lower risk of dying from cancer after five or more years of daily use, with follow-up up to twenty years. The above-50-percent numbers appear only in narrow slices of one investigator group’s reanalysis of heart trials. A long-term follow-up of the ASPREE trial, published in JAMA Oncology this February, found cancer mortality 15 percent higher on aspirin in adults over 70. The United States Preventive Services Task Force dropped colorectal cancer from its aspirin rationale in 2022. I will not defend the cancer claim, and this essay does not rest on it.
● I wrote that aspirin reduced unstable angina by 236 percent. A percentage reduction cannot exceed 100 percent. The Physicians’ Health Study found a reduction of about half.
● I called acetaminophen the leading NSAID. It is not an NSAID at all, and that turns out to be one of the strongest arguments against it.
● I reported 2,600 hospitalizations per year from acetaminophen overdose. The figure is 26,000. My number was ten times too low, and it came from a secondary source.
Summary
● American pediatrics swapped its standard fever drug between 1980 and 1986. Aspirin, which it gave up, had been evaluated in randomized trials with more than 100,000 participants and hundreds of thousands of person-years, with death, stroke, and bleeding as endpoints. Tylenol, which it adopted, had 52 safety experiments behind it, a median follow-up of 48 hours, and no measurement of neurodevelopment.
● The National Institutes of Health LiverTox database reports that no convincing case of aspirin-induced acute liver failure has ever been published. Acetaminophen accounts for 42 percent of acute liver failure cases in the United States.
● At the labeled maximum of 4 grams of Tylenol per day, 31 to 44 percent of healthy volunteers had liver enzymes more than three times normal within two weeks. None of the placebo subjects did.
● In a randomized crossover trial of hypertensive patients, the same 4 grams raised systolic blood pressure by 4.7 mmHg.
● Acetaminophen lacks peripheral anti-inflammatory action. That is why it does nothing measurable for arthritis, and the trials show exactly that: a 3-point improvement on a 100-point pain scale.
● It does nothing for acute back pain either. A trial of 1,652 patients found that the median time to recovery was 17 days on the drug and 16 days on placebo.
● A Cochrane review of 728 newborns found that it does not relieve procedural pain and, in one trial, worsened the response to a later heel stick.
● More than 600 products contain it. In 2011, the FDA capped prescription combinations at 325 mg, writing that anything above that lacked a sufficient margin of safety, then left the 500 mg and 650 mg bottles on the open shelf, where they sit today.
● Aspirin has fallen from co-leader of the analgesic market to third place, and low-dose aspirin for heart protection has more than halved since 2018.
● Pharma attacks cheaper competitors. I can prove it with guilty pleas rather than inference, and the relevant section is below.
The trade
Somebody made a decision about American children between 1980 and 1986, and almost nobody now remembers it.
Before that, a feverish child in this country received aspirin. Afterward, the same child received Tylenol. The switch was nearly total and permanent. Reported cases of Reye syndrome peaked at 555 in 1980. The Centers for Disease Control published its case-control findings that year. The Secretary of Health and Human Services announced in June 1982 that warnings were warranted, and the final labeling rule appeared in March 1986. By 1988, reported Reye cases had fallen to 20.
Pediatric ibuprofen could not have filled the gap. It was not approved as a prescription drug for American children until September 1989 and was not sold over the counter until June 1995. For most of a decade, there was exactly one substitute available, acetaminophen.
Set aside for a moment whether the Reye warnings were correct. Instead, look at what medicine gave up and what it took on, and how well it knew each.
By 1980, aspirin had been in use for eighty years, and by now it has been tested in randomized trials enrolling well over 100,000 participants and followed for several hundred thousand person-years, with hard adjudicated endpoints, including death. We know what it does and what it costs. In people with established cardiovascular disease, it prevents serious vascular events at a rate of 6.69 percent a year, compared with 8.19 percent on control, an absolute reduction of 1.49 percent a year. The bleeding price is quantified: about 1.2 excess major gastrointestinal bleeds per 1,000 patient-years in a meta-analysis of 22 randomized trials covering 75,005 people on low-dose aspirin. Those are unpleasant numbers. They are not mysterious numbers. Somebody counted them.
Acetaminophen came in on a different footing entirely, and Parker’s group put a number on it.
Fifty-two experiments, forty-eight hours
William Parker is a chemist who spent more than 27 years in Duke’s Department of Surgery and has authored more than 140 peer-reviewed papers. In 2022, his group published a citation-tracking study in the European Journal of Pediatrics that should be famous but isn’t.
They screened 3,096 PubMed papers. They identified 218 that asserted acetaminophen is safe in children. They traced 103 of those back to the sources of authority behind the claim. Fifty-two of those sources contained a safety experiment.
The median follow-up in those experiments was 48 hours. No one monitored neurodevelopment. None considered total exposure since birth.
Nobody has refuted this, and nobody has tried. The most-used pediatric drug on earth entered universal use with two days of observation per study, and the question of what repeated exposure does to a growing brain over years was never raised.
To Parker’s credit, the same paper says the evidence is sufficient to conclude that Tylenol does not cause acute liver damage in children when used as directed. His title is that the drug was never shown to be safe for neurodevelopment. It is not that it was shown to be unsafe. Hold onto that distinction. That is the true shape of this whole subject.
The liver
Here is the comparison that nothing else can match.
The National Institutes of Health maintains LiverTox, the reference database on drug-induced liver injury. Its aspirin entry states that no convincing cases of aspirin-induced acute liver failure have been published. High-dose salicylates produce a mild, usually asymptomatic, rise in liver enzymes. They do not destroy livers.
Now acetaminophen. Larson and the Acute Liver Failure Study Group enrolled 662 consecutive acute liver failure patients at 22 American centers over six years. Acetaminophen caused 275 of them, 42 percent, and the proportion rose from 28 percent in 1998 to 51 percent in 2003. Of those 275 patients, 131 had taken the drug without intent to harm themselves. Twenty-seven percent died without a transplant.
FDA’s own accounting estimates 1,600 cases of acute liver failure per year in the United States. For the 1990s, it cites 56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year from acetaminophen overdose.
Most of those deaths involve overdose rather than label dosing, and a large share of the overdoses are deliberate. That defense has a hole in it, and the hole is that 48 percent of the liver failure cases were unintentional. The reason unintentional overdose is so easy with this drug is that the gap between the dose that works and the dose that kills your liver is narrow, and more than 600 products contain it.
How narrow? Watkins and colleagues randomized 145 healthy adults in a controlled inpatient setting to placebo or 4 grams per day, the labeled maximum, for up to 14 days. Not one of the 39 placebo subjects developed an ALT above three times the upper limit of normal. Between 31 and 44 percent of the acetaminophen subjects did. Peak values reached 575 to 636 U/L. Nobody turned yellow or felt sick.
Defenders call that hepatic adaptation and point out that the enzymes settle with continued dosing. Perhaps. What nobody disputes is that the dose printed on the bottle injures the liver of a third to a half of healthy people within two weeks. That is not a margin of safety. That is standing on the edge.
Blood pressure, kidneys, and the rest of the bill
MacIntyre and colleagues conducted a double-blind, placebo-controlled crossover trial in hypertensive patients. Two weeks of 4 grams per day increased daytime ambulatory systolic pressure by 4.7 mmHg versus placebo and diastolic pressure by 1.6 mmHg. The authors wrote that this increases cardiovascular risk and calls into question the safety of regular use.
A randomized trial. The labeled dose. The population most likely to take it for years. An effect comparable to the NSAIDs for which acetaminophen is recommended as an alternative.
A systematic review of eight observational cohorts, covering nearly 600,000 people, found dose-response relationships across the board. All-cause mortality rose from a relative rate of 0.95 at low use to 1.63 at the highest. Cardiovascular events, hypertension, upper gastrointestinal bleeding, and kidney function decline all tracked with dose.
The kidney story begins with phenacetin, acetaminophen’s parent compound. Bayer introduced it in 1887. Brodie and Axelrod showed in 1948 that acetanilide converts in the body to acetaminophen, and extended the finding to phenacetin the following year. Chronic heavy phenacetin use produces renal papillary necrosis, with frank kidney disease after cumulative use of 2 to 3 kilograms. In 2012, the International Agency for Research on Cancer classified phenacetin as carcinogenic to humans, causing cancer of the renal pelvis and ureter. Canada withdrew it in June 1973. The United States waited until November 1983.
That ten-year gap spans the decade of acetaminophen’s commercial takeoff. America spent the 1970s permitting the sale of the parent compound while promoting the metabolite as the gentler choice.
For acetaminophen itself, a pooled analysis of five studies involving 13,114 participants found an adjusted odds ratio of 1.31 for newly developing kidney impairment. Perneger found that lifetime consumption above 1,000 pills doubled the odds of end-stage renal disease.
What it does to the mind of a grown adult
Six independent laboratories have now shown that acetaminophen blunts sensation in adults at ordinary doses.
DeWall and colleagues administered the drug to subjects for three weeks and observed fewer reports of social pain. Functional imaging showed a suppressed response to social rejection in the dorsal anterior cingulate and the anterior insula, regions that process physical pain.
Durso and colleagues found blunted evaluation of both pleasant and unpleasant images. Mischkowski and colleagues conducted two experiments with 80 and 114 subjects and found that a single gram reduced empathy for another person’s pain, in written scenarios and when the subject watched someone receive a noise blast. Randles and colleagues found the cortical error-evaluation signal attenuated in 62 subjects. Keaveney and colleagues, across three studies and 545 subjects, found increased risk taking and reduced risk perception.
These are modest effects, ranging from one-fifth to two-fifths of a standard deviation, and one risk study was null. Taken together, the direction holds across laboratories, methods, and outcomes. A drug that tens of millions of Americans swallow every day flattens emotional response and reduces empathy. Nobody planned for that, nobody measured it before approval, and nobody has asked what it means at the population scale.
What it does not do
Here, the record shifts from harm to futility, and this is where the drug’s missing anti-inflammatory action begins to matter.
The pharmacology reference is blunt about it. Acetaminophen has analgesic and antipyretic properties similar to the NSAIDs but lacks peripheral anti-inflammatory effects. It appears to inhibit the cyclooxygenase pathway in the central nervous system rather than in peripheral tissue. Aspirin, by contrast, acetylates cyclooxygenase irreversibly and does so in the tissues where inflammation occurs.
For an inflammatory condition, acetaminophen is pharmacologically the wrong choice. The trials say so.
Osteoarthritis is among the most common reasons a person takes this drug for years. A Cochrane review of ten randomized trials involving 3,541 patients found that placebo improved pain by 23 points on a 100-point scale, and paracetamol improved it by an additional 3.23 points. Function improved by 2.9 points beyond placebo. Both findings are supported by high-certainty evidence. A network analysis of 76 trials and 58,451 patients concluded that there is no role for single-agent paracetamol in osteoarthritis at any dose. Britain’s National Institute for Health and Care Excellence now advises clinicians against routinely offering it and tells them to inform patients accordingly.
Acute low back pain is another major indication. The PACE trial randomized 1,652 patients across 235 Australian practices to receive regular paracetamol, as-needed paracetamol, or placebo. The median time to recovery was 17 days, 17 days, and 16 days, respectively. A Cochrane review found high-quality evidence of no difference at 1, 2, 4, and 12 weeks, and no trials at all for chronic back pain.
Newborns next. A Cochrane review of nine trials involving 728 neonates found no pain reduction with heel lance compared with placebo, water, or topical anesthetic. Glucose worked better. Sucrose worked better during eye examination. After assisted vaginal delivery, paracetamol did not reduce pain scores and worsened the response to a subsequent heel stick. A randomized trial of 44 newborns undergoing circumcision found no difference in any intraoperative pain measure.
Fever last. The American Academy of Pediatrics stated in its 2011 clinical report that fever is a physiologic mechanism with beneficial effects in fighting infection. No evidence shows that fever itself worsens illness or causes neurologic damage. The Academy wrote that the goal of treating a febrile child should be comfort rather than a normal thermometer reading.
Antipyretics do not prevent recurrence of febrile seizures during subsequent fever episodes, with a pooled odds ratio of 0.92 across two randomized trials. In volunteers infected with rhinovirus, aspirin and acetaminophen both suppressed the neutralizing antibody response and increased nasal symptoms, with a trend toward longer viral shedding. A randomized trial of 700 critically ill patients with fever from suspected infection found no effect on ICU-free days or mortality.
Against all that, one open-label Japanese trial of 423 children found that rectal acetaminophen reduced febrile seizure recurrence within the same fever episode from 23.5 percent to 9.1 percent. One trial, no placebo arm, one center, and it is the strongest positive pediatric finding in the entire literature. Set it beside the 48-hour safety record and consider what medicine accepted as sufficient.
For ordinary pain at ordinary doses, the two drugs are about equal. A Cochrane review of 68 studies and 3,111 participants on aspirin found that its pain relief was closely similar to that of paracetamol, milligram for milligram. Aspirin’s advantages are its antiplatelet action in established heart disease and its anti-inflammatory action at gram-level doses. Better analgesia is not among them.
Six hundred products and a regulator that blinked
More than 600 medicines contain acetaminophen. That is the structural hazard because a parent who gives a child a cough syrup, a fever reducer, and a cold preparation has no way to count what has been given.
FDA convened a joint advisory committee of 37 members on June 29 and 30, 2009. The committee voted 24 to 13 to reduce the maximum single adult dose from 1,000 mg to 650 mg. It voted 26 to 11 to make the 1,000 mg dose prescription-only. It voted 20 to 17 to eliminate prescription combination products. It voted 36 to 1 for a boxed warning.
In January 2011, the FDA capped prescription combination products at 325 mg per unit and added the boxed warning. Products above that strength, the agency wrote in the Federal Register, do not provide a sufficient margin of safety against serious liver injury.
Over-the-counter products were left untouched. Extra Strength at 500 mg and Extended Release at 650 mg are sold without restriction on the same shelves today. The regulator that set 325 mg as the safety ceiling left them there and has taken no action in the fifteen years since.
Court documents released later revealed what the company was doing as this played out. In August 2009, McNeil’s president wrote to his executives that they were being too nice and too worried about stepping on the FDA’s toes. It might be time, he wrote, to have members of Congress put pressure on the agency. A senior executive presented Johnson & Johnson’s board with a plan to influence the FDA through the White House, the Office of Management and Budget, and lawmakers. Extra Strength Tylenol was worth about 400 million dollars a year, compared with 14 million for regular strength.
What to do with a feverish baby
Everything above is useless to a parent at two in the morning. Here is what the evidence supports, and it stays on this side of the paywall because how not to hurt your child should never cost money.
Know which fevers are an emergency. In an infant younger than 28 days, a rectal temperature of 100.4 degrees or higher is an emergency. Go to an emergency department. These babies need blood, urine, and spinal fluid cultures and admission because the danger is the infection, not the temperature. Between 29 and 60 days, the child needs same-day evaluation. Over three months, the number on the thermometer matters far less than how he looks, drinks, and responds to you. Occult bacteremia in children between 3 and 36 months is now about 0.25 percent, and blood cultures in that group return seven contaminants for every true pathogen.
Understand what fever does. Fever retards bacterial and viral replication, enhances neutrophil production, and drives T-lymphocyte proliferation. It has been conserved in vertebrates for 600 million years. It evolved for a purpose, and the Academy says so in print.
Treat the child, not the thermometer. A child at 102 degrees who is playing, drinking, and talking to you needs no medication. A child at 101 who is miserable and refusing fluids might. In one study, 25 percent of caregivers gave antipyretics for temperatures below 100 degrees, which is to say, for no fever at all. Eighty-five percent woke a sleeping child to medicate him. Most pediatricians think that is wrong.
For children under six months, ibuprofen is the better drug. A meta-analysis of 19 studies and 241,138 participants under two years found ibuprofen superior to acetaminophen for temperature reduction at both under four hours and four to twenty-four hours, and for pain at four to twenty-four hours. It was equivalent for serious adverse events, kidney impairment, and wheezing. Ibuprofen is an anti-inflammatory and has no toxic metabolite pathway. Do not use it under six months without your physician’s direction, and do not use it in a dehydrated child.
For children under six months, acetaminophen is often claimed to be the only option, so if you use it, dose it properly. Ten to fifteen milligrams per kilogram, no more often than every four to six hours, and no more than five doses in 24 hours. Use the oral syringe that came with the bottle. In a randomized study of 2,110 parents, 84.4 percent made at least one dosing error, and 21 percent made an error of more than double the intended dose. Dosing cups produced 4.6 times the error rate of syringes. Never use a kitchen spoon. My personal recommendation is to never use Tylenol under any circumstances for an adult or child, but what do I know?
Read every label in the house. Accidental overdoses come from cold preparations, cough syrups, and combination products. If you give a fever reducer and a cold medicine together, check both boxes before you open either.
Do not alternate the two drugs. A network analysis of 31 trials and 5,009 children found that combining or alternating clears fever faster than either alone, and that across six studies measuring discomfort, the scores did not differ. Alternating yields a lower number on the thermometer and no improvement in how the child feels, while doubling the chance of a dosing error.
Skip sponging. Tepid sponging lowers temperature without improving comfort and causes shivering and gooseflesh at five times the placebo rate. Alcohol baths are contraindicated because the alcohol is absorbed. Cold baths trigger shivering, which raises core temperature. Offer fluids, dress the child normally, and leave him alone.
During pregnancy, the calculus differs. Untreated maternal fever is associated with neural tube defects, with a pooled odds ratio of 1.9, and with congenital heart defects, with an odds ratio of 1.53. A study of 375 neural tube defect cases found that the association with fever held whether or not the mother took an antipyretic, meaning that treating the fever has not been shown to remove the risk. Discuss this with your obstetrician rather than settling it from an essay.
A note before the paywall
The rest covers where the aspirin went, what the retail numbers show, Pharma’s criminal record of attacking cheaper competitors, and what it all adds up to.
If your money is tight, Substack gives you a free trial. Take it. I would rather you read the whole thing than send me seven dollars you need for something else. Nobody gets left behind on my account.
As I went through all this data, I had to go to the bathroom several times to projectile vomit. I don’t know how anyone can see this evil and think there’s no conspiracy behind it. We have so much evidence of globalist control in other fields that this one can’t be different. I have written about much of this on my Substack, and you can find it by entering “psychopath” in the search bar in the upper-right corner.
The medical field is just a mess, and pediatrics is probably the worst because they have been paid huge sums of money to vaccinate every one of their precious babies and destroy their future health. If you don’t believe this, search for “vaccination” in my Substack. My evidence is clearly documented and accepted by the people in the know. I don’t know how anyone could give pediatricians credibility on any academic issue.
Don’t expect your doctor to tell you the truth about anything. They are fooled just like the rest of us are. It’s hard for anyone to see the truth if it interferes with their wallet.