Has Big Pharma been engaging in low-level individual decision-making?
“One study reported that subjects who took 1,000 mg of Tylenol (only one third of the “safe” daily dose) exhibited decreased empathy and other positive emotions, and “blunted evaluation sensitivity to both negative and positive stimuli.”[5] (footnote worth reading)
This worrying side effect is motivating researchers to look deeper into how acetaminophen depletes glutathione, a key compound for regulating detoxification throughout the body and brain. Some experts believe that glutathione depletion could be the key to understanding a wide range of acetaminophen’s dangerous side effects, from mood alteration and depression to organ toxicity.”
“”Acetaminophen seems to make people feel less negative emotion when they consider risky activities – they just don’t feel as scared,” explained neuroscientist Baldwin Way from The Ohio State University when the findings were published.
“With nearly 25 percent of the population in the US taking acetaminophen each week, reduced risk perceptions and increased risk-taking could have important effects on society.”
The findings add to a growing body of research suggesting that acetaminophen’s effects on pain reduction also extend to various psychological processes, lowering people’s receptivity to hurt feelings, experiencing reduced empathy, and even blunting cognitive functions.
In a similar way, the research suggests people’s affective ability to perceive and evaluate risks can be impaired when they take acetaminophen. While the effects might be slight, they’re definitely worth noting, given acetaminophen is the most common drug ingredient in America, found in over 600 different kinds of over-the-counter and prescription medicines.
Exploring such psychological alternative explanations for this phenomenon – as well as investigating the biological mechanisms responsible for acetaminophen’s effects on people’s choices in situations like this – should be addressed in future research, the team said.
… acetaminophen nonetheless remains one of the most used medications in the world, considered an essential medicine by the World Health Organization, and recommended by the CDC as the primary drug you should probably take to ease symptoms if you think you might have COVID.
In light of the findings about acetaminophen, we might want to rethink some of that advice, Way said.
“Perhaps someone with mild COVID-19 symptoms may not think it is as risky to leave their house and meet with people if they’re taking acetaminophen,” Way said.
“We really need more research on the effects of acetaminophen and other over-the-counter drugs on the choices and risks we take.””
“Other Adverse Reactions Observed During Clinical Studies of Acetaminophen in Adults
The following additional treatment-emergent adverse reactions were reported by adult subjects treated with acetaminophen in all clinical trials (n=1,020) that occurred with an incidence of at least 1% and at a frequency greater than placebo (n=525).
- Blood and lymphatic system disorders: anemia
- General disorders and administration site conditions: fatigue, infusion site pain, edema peripheral
- Investigations: aspartate aminotransferase increased, breath sounds abnormal
- Metabolism and nutrition disorders: hypokalemia
- Musculoskeletal and connective tissue disorders: muscle spasms, trismus
- Psychiatric disorders: anxiety
- Respiratory, thoracic and mediastinal disorders: dyspnea
- Vascular disorders: hypertension, hypotension”
Note the anxiety note there. Apparently a known side-effect can be increased anxiety.
So of course my next question is, how long has this drug been in active use? When did usage of this drug take off in modern society?
Acetaminophen would initially be “discovered” in 1852 due to a “mistake” by a pharmacist in filling an order using acetanilide by a couple doctors in France. In 1899, a German researcher would discover the body takes acetanilide and turns it into acetaminophen. 10 years later, another doctor would synthesize acetaminophen.
According to McNeil’s own history document:
“Although his research confirmed that the drug was effective against pain and fever, von Mering recommended extensive investigation into all analgesics and antipyretics.
Acetaminophen was not prescribed nor studied any further until 1949 when research on chemically related drugs revived interest in the compound.”
McNeil’s company would be bought by Johnson & Johnson in 1959.
The above PDF also shows us an example of pharmaceutical marketing directly to medical professionals. We read:
“In the spring of 1955, McNeil introduced TYLENOL Elixir for Children, the company’s first single ingredient acetaminophen product. The outstanding success of TYLENOL was attributed to a unique marketing strategy: to inform health care professionals of the undesirable effects of aspirin and ask them to recommend TYLENOL to patients susceptible to these effects.
Marketed directly to physicians and pharmacists as a prescription product by McNeil’s
pharmaceutical sales force, TYLENOL Elixir received widespread acceptance as a safe and effective alternative to aspirin for the temporary relief of pain and fever. Its success encouraged McNeil to develop other TYLENOL products.”
According to their own timeline, Tylenol became the 5th best selling analgesic in the US by 1975. So in the span of 20 years, and due to marketing directly to the medical establishment, the first successful acetaminophen product would become a best seller, and considered the #1 over-the-counter analgesic by 1976. By 1978, McNeil would be divided into a consumer division, and a pharmaceutical division for prescription drugs. The timeline in this document of the Tylenol brand, is fascinating.
However, although Tylenol was the first over-the-counter product containing acetaminophen, as noted by others now, the drug shows up in well over 600 other medical products, such as allergy, cold, sleep as well as other pain killers.
This fact is further brought home in an attempt by the Austin American Statesman Newspaper, to support fact-checking hyperbolic claims around the health issues related to Tylenol. But while they are trying to assist in refuting a Facebook post in April 2022, they include this quote:
“Annette Reichel, a spokesperson for Tylenol, said the drug has over 60 years of use to show that it is safe.
“When used as directed at recommended doses, Tylenol does not cause acute liver failure,” Reichel said. “However, per the Tylenol (over-the-counter) Drug Facts label, severe liver damage may occur if an individual takes more than 4000 mg of acetaminophen in 24 hours.”
For Extra Strength Tylenol, that means liver damage may occur if someone took two 500-milligram caplets over the recommended dose within a single day. That’s not a lot of pills, a fact that has raised concerns that the dosage guidelines should be tighter.”
They then go on to discuss another doctor’s findings:
“In fact, research referenced by the U.S. Food & Drug Administration shows that acetaminophen is the No. 1 cause of acute liver failure in the U.S.
Many medications contain acetaminophen, however, meaning that Tylenol, by itself might not be the leading cause of acute liver failure.
Dr. William Lee, a professor of internal medicine at the University of Texas Southwestern Medical School, has researched the connection between acetaminophen and acute liver failure for more than 20 years.
His research into acetaminophen and acute liver failure has continued to show that acetaminophen overdose, both accidental and intentional, is the “leading cause of acute liver injury and acute liver failure in the developed world.”
“I think that’s a little specious to blame it on Tylenol, specifically, because (acetaminophen) is such a ubiquitous product,” Lee said. “
Of course we now know that Politifact, one of FB’s paid-off opinion-pushers, can no longer be trusted with actual, honest fact-checking. However, even the attempt at refuting still reveals problems with this medication, just ‘nowhere near as bad as what was claimed’. As if that makes it any better.
What may have been quoted on FB, as I haven’t been there since February ’21, was this information:
“Every year, poison control centers receive more than 100,000 calls related to acetaminophen overdose. It causes more than 56,000 annual visits to the emergency room and an average of 458 yearly deaths. Liver failure causes most of those deaths. In fact, acetaminophen poisoning causes almost half of the overall cases of liver failure in the United States.
When humans metabolize acetaminophen at standard doses, they release the toxic byproduct N-acetyl-p-benzoquinone imine (NAPBQI). The more they take, the more toxin the body creates during digestion. Every person processes medication differently, and there is a thin line between a safe dose and one that causes liver damage.
People with a lower-than-average body weight or who are fasting may not have the glutathione needed to safely break down acetaminophen. Patients taking low doses repeatedly have experienced liver toxicity, especially when they haven’t ingested adequate nutrition.
The danger is especially acute in children. Doctors often recommend parents administer Tylenol when children and infants have fever. If a child has a stomach condition that causes vomiting or diarrhea, they may not have enough nutrients in their system to process acetaminophen. Their risk of kidney and liver damage increases.”
This article goes on to give examples of other medications that contain acetaminophen, both over the counter, and prescription.
EDIT Feb 16, 2024
“The link between acetaminophen and liver toxicity was established some time ago. But the drug’s effect on the developing nervous system in children — though suspected — was never formally investigated through a clinical study, according to William Parker, Ph.D., CEO of the nonprofit research firm WPLab.
Now, Parker’s new deep literature review has uncovered troubling associations between acetaminophen at typical pediatric doses and serious, likely permanent impairments in cognition and socialization in susceptible children.”
“The study, published last month in Clinical and Experimental Pediatrics, focused specifically on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).”
“He added: “A report that children with severe ASD could not safely process acetaminophen had already been published in 1999, but its significance was missed entirely, even by the study’s authors.””
“Acetaminophen use is associated with mild to moderate side effects that are common with OTC medicines, including agitation, constipation, headaches, insomnia, itchy skin and stomach irritation.
But many of those same symptoms are signs of serious liver injury, which for decades has been the most noted and studied side effect of the drug, particularly in individuals who consume alcoholic beverages or who take more than the recommended dose.”
In among these quotes from the article, are lists of findings from both animal and human studies, showing brain injury, brain cell death, and animal death in doses given to children or infants.
End edit
Knowing that acetaminophen shows up in well over 600 different kinds of medications, and knowing the dosage limits before inviting liver damage, it is highly possible that this attempt to save face by the Tylenol brand might be moot. Sure, one brand may not be 100% responsible, but as the brand that brought acetaminophen to the masses, they certainly are not immune from responsibility. This is yet another case where companies conveniently ignore accumulation of compounds in the body, and what that accumulation can do. Bio-accumulation IS a thing and MUST be more frequently considered. How many people are on multiple medications, all with different dosages, many containing acetaminophen, and unknowingly taking far more than the 4000mg required to cause internal damage? Here are some discussions about bio-accumulation.
In 2011, the FDA apparently announced that as of January 2014, the amount of acetaminophen in various products was not to exceed 325mg per tablet or capsule.
A study released in March 2020 had this to say regarding acetaminophen’s toxicity:
“Voluntary or accidental acetaminophen (N-acetyl-p-aminophenol, APAP) overdose remains the first cause of acute liver failure in western countries, accounting for up to 60–70% of patients in some observations1,2. Mechanisms of hepatotoxicity are incompletely understood. The mechanism of acetaminophen toxicity has been well studied.
A small fraction (<10%), undergoing oxidation and acetaminophen is metabolized by CYP450 isoforms, mainly CYP2E1, to N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite. Under normal conditions NAPQI, binding covalently to cysteine groups on proteins (APAP adducts), is rapidly detoxified by glutathione. With acetaminophen toxicity, cellular glutathione is depleted resulting of the accumulation of APAP adducts, mainly with mitochondrial protein, inducing oxidative stress and mitochondrial injuries that lead to centrilobular hepatocyte necrosis and liver failure3–6.”
“When glutathione is approximately 70% depleted, NAPQI begins to accumulate in the hepatocytes, resulting in hepatic damage.15,16,18 Therefore, the replacement of glutathione with glutathione-mimicking compounds such as N-acetylcysteine serves as a useful antidote to acetaminophen toxicity.”
This same article advises pharmacists on using activated charcoal to help cleanse the digestive tract of those who have knowingly ingested too much acetaminophen and are lucid enough to breathe normally.
In addition, they mention:
“The mainstay of treatment for acetaminophen toxicity is acetylcysteine. This agent replenishes hepatic glutathione stores and increases sulfate conjugation, preventing accumulation of NAPQI.31 Acetylcysteine may be beneficial in patients presenting with acetaminophen-induced hepatic failure, as it improves hemodynamics and oxygen use, decreases cerebral edema, and improves mitochondrial energy production.14,22
However, it is rendered ineffective when evaluating possible toxicity due to multiple ingestions over time, when time of ingestion is unknown, or when altered metabolism occurs.11 Taking this into consideration, acetylcysteine should be administered in any case of acute liver failure or when there is any evidence of liver toxicity in which acetaminophen overdose is suspected.11”
The article goes on to teach the pharmacist how to give this supplement under various circumstances to the suffering patient.
A PubChem article says this about acetaminophen:
“Although the exact mechanism through which acetaminophen exert its effects has yet to be fully determined, acetaminophen may inhibit the nitric oxide (NO) pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate (NMDA) and substance P, resulting in elevation of the pain threshold. The antipyretic activity may result from inhibition of prostaglandin synthesis and release in the central nervous system (CNS) and prostaglandin-mediated effects on the heat-regulating center in the anterior hypothalamus.
Acetaminophen (paracetamol), also commonly known as Tylenol, is the most commonly taken analgesic worldwide and is recommended as first-line therapy in pain conditions by the World Health Organization (WHO). It is also used for its antipyretic effects, helping to reduce fever. This drug was initially approved by the U.S. FDA in 1951 and is available in a variety of forms including syrup form, regular tablets, effervescent tablets, injection, suppository, and other forms. Acetaminophen is often found combined with other drugs in more than 600 over the counter (OTC) allergy medications, cold medications, sleep medications, pain relievers, and other products. Confusion about dosing of this drug may be caused by the availability of different formulas, strengths, and dosage instructions for children of different ages. Due to the possibility of fatal overdose and liver failure associated with the incorrect use of acetaminophen, it is important to follow current and available national and manufacturer dosing guidelines while this drug is taken or prescribed.”
Another source claims that a side effect can be increased anxiety as opposed to reduced anxiety found in the 2017 and 2022 studies.
A 2014 study also began sounding the alarm around acetaminophen as follows:
“The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect ‘epidemy’ (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound.”
You’ll notice the reference to the same benzoquinone as the 2020 study mentioned earlier.
Selenium however, is mentioned as a potential repair mechanism for oxidative stress-caused brain damage and mitochondrial dysfunction that are both caused by toxic doses of acetaminophen. The study, as usual, was done on mice. In scientific circles, acetaminophen is generally known by it’s acronym, APAP, created from it’s scientific, much longer name. Selenium however, did not reverse APAP decreasing effect on glutathione levels. It is known that selenium has antioxidant capabilities, and researchers feel this is what provided neuroprotective action against the damage caused by toxic levels of acetaminophen in mice.
The article specifically mentions:
“APAP treatment also caused a decrease in Na+ , K+ – ATPase activity and in mitochondrial membrane potential. These alterations observed in the brain of APAP-treated mice were restored by diphenyl diselenide (PhSe)2.”
EDIT Jan 26, 2024:
Further to the discussion around Selenium and mention of oxidative stress and the danger it poses to the neurological system, an article on mental health by Dr Mercola featured an interview with a Dr. Walsh, who had this to say:
“”By the way, oxidative stress runs through every single mental disorder we see, without exception,” Walsh says. “Every one of them seems to have extraordinary oxidative stress — schizophrenia, bipolar disorder, a violent child or an autistic child.”
Unfortunately, our modern lifestyle strongly promotes oxidative stress, with processed foods, processed vegetable oils, excessive net carbs and excessive protein being some of the most potent factors. This kind of diet causes a reduction in ketones and a radical increase in reactive oxygen species and secondary free radicals.
Exposure to nonnative electromagnetic fields, glyphosate and other pesticides, fluoride contaminated water and other toxic exposures only add to the problem.”
Walsh mentions later on in the same article:
“The fact that autistic children tend to have extraordinary copper and zinc imbalances means their metallothionein protein is not functioning. Metallothionein is required for homeostatic control of copper and zinc.”
“The most important antioxidants in the brain are somewhat different than the rest of the body. I call them the three musketeers. It’s glutathione, metallothionein and selenium. It’s specific to the brain,” he explains.”
Mercola adds:
Technically, selenium is not an antioxidant per se, but it does increase glutathione levels and enhances the function of metallothionein and, in the brain, glutathione and metallothionein work together. Glutathione is your first line of defense. The problem is, autistic children typically have a poor diet (it’s hard to get them to eat anything) and with the oxidative overload, they quickly run out of glutathione. When you run low on glutathione in your brain, your metallothionein level increases.”
“As noted by Walsh, of all the trace metals, selenium has the narrowest division between deficiency and overload, so you need to be careful when supplementing.
Zinc also needs to be normalized, as it is the No. 1 factor for enabling metallothionein to function and support glutathione. “
end edit
Now before we get any further into repairing, reversing or undoing damage caused by acetaminophen, because we don’t want to knowingly or unknowingly make ourselves susceptible to risk-based guidance that could lethally harm us (see 2020-2023 at time of writing for details). The question must be asked, can the effects of acetaminophen on the body be enhanced, amplified or somehow magnified by other compounds?
While we know that acetaminophen does not fall into the category of NSAIDS, its specific function is that of pain killer and fever manager, or to say it differently, analgesic and antipyretic. Now there are rules around taking analgesics and what you can and can’t eat or do while on them. One example of a general rule, is not to drink alcohol while taking analgesics. But how many know this applies to a simple dose of Tylenol to treat a headache?
Drug interactions according to MedicineNet include: carbamazepine, isoniazid, rifampin, alcohol, cholestyramine, and warfarin. Other sites mention St. John’s Wort as something to avoid when taking acetaminophen-containing medications. Two sites mentioned concerns over the combination of acetaminophen and anti-coagulants, specifically due to acetaminophen’s depression of other factors that interfere with and can cause lower platelet counts than intended.
So:
- We have two studies, 5 years apart, worried about cognitive suppression as it relates to risk assessment when taking acetaminophen.
- We have known side effects of acetaminophen that relate to kidney, liver, and central nervous system damage that has been known to affect the brain either with cerebral edema, mitochondrial function, or the potassium/sodium gates in the nerves themselves, depressing glutathione function, etc.
- We know that acetaminophen can negatively impact other drugs and that excessive alcohol can worsen acetaminophen’s own list of side effects, particularly in the liver damage area.
What does this mean in light of the apparent problem stocking store shelves with children’s Tylenol, supposed overflowing of children’s hospitals right now, and the level of risk the public was supposed to be willing to accept over the past three years dealing with the COVID-19 pandemic?
For starters, acetaminophen-containing medications may not be the wisest choice for yourself or your children going forward! You want full control of your faculties, including your ability to think, reason, and adequately respond to risk assessments in a manner that doesn’t unduly put you or your family in danger. The two studies quoted at the very top of this article, both mention how the changes to risk assessment seem “slight”, but had surprising results in their tests. As the saying goes, “a little goes a long way”.
Secondly, you want to be mitigating the liver, kidney, and brain/CNS damage that may have been done by accidentally and repeatedly going slightly over recommended dosages on perhaps a more frequent level than you may have been aware of in the past. This involves taking activated charcoal, and ensuring adequate intake of foods containing Selenium, and cysteine, L-Cysteine, or taking a NAC supplement. Helpful information on foods containing these compounds are:
https://www.livestrong.com/article/531520-food-sources-of-n-acetyl-cysteine/
https://www.blissplan.com/at-home/recipes/10-foods-that-contain-cysteine/
https://nutritionofpower.com/nutrition/food-causes-of-n-acetyl-cysteine
and https://draxe.com/nutrition/l-cysteine/
Third, you want to be using other means to deal with inflammation and pain that don’t require potential stomach ulcers or nerve and liver damage in the long run. To begin with, you want a diet high in anti-inflammatories for awhile if your body is riddled with it. Be aware however, that staying on a high anti-inflammatory diet can also cause the same stomach ulcer side effects as ibuprofen, so don’t make this an exclusive dietary change, and certainly don’t do it via supplements! Food is your medicine here, as the anti-inflammatory compounds are then offset by other nutrients that your body also needs. Bring down your body’s inflammation in a controlled, long-term manner.
For short-term issues, pain relief can be obtained via prickly lettuce tinctures, arnica topical applications, willow bark tea (the precursor to modern-day aspirin), muscle soaks, etc. For fever relief, a cool cloth to the forehead often helps, a warm cup of soup or tea to pull the blood away from the skin to help cool down the body as it processes the tea or soup, etc.
Go to your medicine cabinet and research each of the medicines you have there, looking for any that have acetaminophen in their ingredient or filler lists. Go to your pantry and see if you have foods containing selenium, cysteine, anti-inflammatory and anti-oxidant properties. Remember that salicate-containing foods are useful for pain as well as spices such as turmeric and pepper.
But whatever you do, do not render yourself open to suggestion by way of the medications you use.
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