By Dr. Mercola,
Millions of people take acetaminophen (also known as paracetamol outside the USA), commonly known as the brand name drug Tylenol, frequently. People use acetaminophen for treating everything from fevers and muscle aches to headaches, hangovers and other pain. Because acetaminophen is available over the counter and is an ingredient found in many other preparations such as those for cold and flu, few people think twice about taking it. They should.
Acetaminophen is the top cause of acute liver failure in the U.S.1 and overdoses are a leading cause of emergency department visits and hospitalizations.2 According to UT Southwestern Medical Center, more than 200 people a year die from acetaminophen poisoning in the U.S. and there are 15,000 hospital visits due to accidentally taking too much.3
Acetaminophen is also correlated with serious side effects4 such as certain skin conditions, abdominal and gastrointestinal problems and allergic reactions. As I mention later in this article, it also could be dangerous for pregnant women. And, if California state regulators are correct, the latest risk to be associated with acetaminophen may be cancer. The regulators are in the process of determining whether to classify acetaminophen as a carcinogen on the Proposition 65 list.
Public Hearing on Carcinogenicity May Be in Spring 2020
California's Proposition 65, enacted in 1986, requires the state to maintain a list of chemicals known to cause cancer or reproductive toxicity. Businesses are required to provide a warning if the products they sell or use expose the public to chemicals on the Proposition 65 list.5,6
California state regulators reviewed 133 acetaminophen studies in peer-reviewed journals and are considering whether to classify the drug as a carcinogen. They will hold a public hearing in spring 2020. According to The Associated Press, acetaminophen is:7
" … known outside the U.S. as paracetamol and used to treat pain and fevers. It is the basis for more than 600 prescription and over-the-counter medications for adults and children, found in well-known brands like Tylenol, Excedrin, Sudafed, Robitussin and Theraflu. Acetaminophen has been available in the U.S. without a prescription since 1955.
Concerns about its potential link to cancer come from its relationship to another drug: phenacetin. That drug, once a common treatment for headaches and other ailments, was banned by the FDA in 1983 because it caused cancer."
Since the drug is so popular, some fear that a warning will unnecessarily worry the public but Thomas Mack, chairman of the Carcinogen Identification Committee, the group appointed by the governor to identify chemicals linked to cancer,8 dismisses the fears. "That’s not what our mandate is," he says.9
In addition to the tremendous popularity of acetaminophen, inclusion of a chemical on the Proposition 65 list can pave the way for lawsuits, so industry is resisting the classification.10 For example, reports The Associated Press:
"After the state listed glyphosate — widely known as the weed killer Roundup — as a carcinogen in 2017, a jury ordered the company that makes Roundup to pay a California couple with cancer more than $2 billion. A judge later reduced that award to $87 million."
What Are the Possible Cancer Links to Acetaminophen (Paracetamol)?
Suspicion of acetaminophen’s carcinogenic potential stems from the fact that it is a major metabolite of phenacetin, a drug connected with cancer more than three decades ago. In 2001, researchers in the International Journal of Cancer wrote:11
"Concern has been raised about the carcinogenic potential of paracetamol (acetaminophen) because it is the major metabolite of phenacetin, which was classified as a human carcinogen by the International Agency for Research on Cancer (IARC) in 1987 and has been withdrawn from the market in most countries …
Because of the established link between phenacetin and malignant tumors of the urinary tract, most epidemiologic studies of paracetamol and cancer have focused on these tumors.
Some of these have reported slightly elevated risks of renal cell cancer or transitional cell cancers of the renal pelvis, ureter or urinary bladder with regular or long-term use of paracetamol, whereas other studies have failed to demonstrate such associations."
Still, the researchers added that they did not find what you would interpret as very strong cancer links with acetaminophen:12
"We found no evidence of an association between use of paracetamol and risk of urinary bladder cancer, but some evidence of an association with upper urinary tract cancers, including cancers of the renal parenchyma, renal pelvis and ureter."
Nearly 20 years later, in January 2020, the Los Angeles Times weighed in on the possible risks and downplayed them, saying the "standards for inclusion" for the Proposition 65 list are so low, even coffee was put on it.13
Acetaminophen (Paracetamol) Can Cause Liver Damage
As I wrote before, acetaminophen is the top cause of acute liver failure in the U.S. It can even be toxic to your liver at recommended doses when taken daily for just a couple of weeks.14 Part of the reason for the risk is that acetaminophen's recommended dose and the amount of the drug that causes an overdose are very close. There is not much margin of safety.
In fact, studies reveal that taking just a little more acetaminophen than the recommended dose over a few days or weeks (referred to as "staggered overdosing") can be deadlier than one large overdose.15 Research in the Journal of Clinical and Translational Hepatology found:16
"Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and … it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases.
… Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients."
Acetaminophen (Paracetamol) Is Linked to Fatal Skin Reactions
Few people have heard of three serious skin reactions linked to acetaminophen, but they are concerning enough that the FDA issued a warning in 2013:17
"Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur with the use of drug products that contain acetaminophen. These reactions can occur with first-time use of acetaminophen or at any time while it is being taken …
Anyone who develops a skin rash or reaction while using acetaminophen or any other pain reliever/fever reducer should stop the drug and seek medical attention right away.”
The three skin conditions that the FDA warns of are very rare but also life-threatening:
- Stevens Johnson Syndrome (SJS) — This reaction begins with flu-like symptoms that progress into a painful rash that blisters and causes the top layer of the skin to slough off. This can lead to serious infections, blindness, damage to internal organs, permanent skin damage and death.
- Toxic Epidermal Necrolysis (TEN) — TEN also typically begins with flu-like symptoms (cough, headache, aches and fever) and progresses into a blistering rash. Layers of the skin may peel away in sheets and hair and nails may fall out. TENS is often fatal.
- Acute Generalized Exanthematous Pustulosis (AGEP) — This skin eruption causes numerous pustules to appear on the skin, often accompanied by fever. This condition typically resolves within two weeks once the acetaminophen is stopped.
No one knows why acetaminophen can cause these extreme skin conditions and there is no way to predict who may be at risk before they take the drug. Even more concerning, as the FDA points out in its warning, the reactions can occur in someone who has safely taken acetaminophen before.
Acetaminophen (Paracetamol) Not Safe During Pregnancy
Acetaminophen is likely not safe to take for women who are pregnant. A study in JAMA Pediatrics found disturbing links between hyperkinetic disorders (HKD), a severe form of attention-deficit/hyperactivity disorder (ADHD), and ADHD itself.18 The study found a 29% increased risk for ADHD in the children whose mothers had used acetaminophen during pregnancy in the first seven years of their lives and a 37% increased risk of being diagnosed with HKD.19
In a 2015 communication, the FDA cited the JAMA Pediatrics ADHD study. It also cited research that found a possible connection between the use of acetaminophen and other drugs called nonsteroidal anti-inflammatories (NSAIDs) and miscarriage but found the evidence inconclusive.20
The fetal exposure of mothers taking acetaminophen during pregnancy may also increase a child's chances of developing asthma.21 Researchers analyzed data from the Norwegian Mother and Child Cohort Study, which includes many mother/child pairs, and found that prenatal acetaminophen exposure was associated with an increased risk of asthma in offspring.22
Finally, use of acetaminophen during pregnancy may cut levels of testosterone in the womb, negatively affecting males, according to research in mice.23 It's possible that this apparent testosterone reduction interferes with the development of the male reproductive system and explains genital birth defects, infertility and testicular cancer, according to other research.24
In addition to harm to male fetuses, a rat study found that the use of acetaminophen or NSAIDs in pregnancy could reduce the size of ovaries and follicles, and if applied to humans, might indicate that it could affect fertility of resulting daughters and granddaughters.25
Other Acetaminophen (Paracetamol) Risks
Acetaminophen may not be safe to take when you are drinking alcohol. Research suggests it can greatly increase your risk of kidney dysfunction — even if the amount of alcohol is small.26Combining alcohol with acetaminophen was found to raise the risk of kidney damage by 123% compared to taking either of them individually.
Besides alcoholics, young adults are particularly at risk of kidney harm as they're more likely to consume both alcohol and acetaminophen.27
Acetaminophen can also affect the immune system. According to a study in Human Vaccines & Immunotherapeutics,28 infants who received acetaminophen right after getting a vaccination experienced lowered immune response and developed significantly fewer antibodies against the disease they were vaccinated against.
Acetaminophen's anti-inflammatory activity might explain the apparent effects by interfering with the body's immune system antibody response, say the researchers.
Other risks that have been associated with the use of acetaminophen include chronic obstructive pulmonary disease (COPD) and reduced lung function, brain damage, increased blood pressure and hearing loss. Finally, acetaminophen may have psychiatric effects, according to research conducted by University of British Columbia researchers in 2016.29
The researchers found that use of acetaminophen may both lessen the ability of people to recognize errors that they make and their concern about whether or not they have made an error.30
Past research has also revealed subtle cognitive effects associated with acetaminophen use, like a 2010 study that indicated acetaminophen may reduce the pain of social rejection.31 Research also showed that acetaminophen had the ability to blunt both positive and negative emotions.32
Regardless of whether acetaminophen is added to California's Proposition 65 as a carcinogen, there are many reasons to avoid this drug when possible and use it cautiously. Further, there are many pain-relieving herbs and practices that you can use to replace acetaminophen for natural relief.