Life Extension Magazine December 2007
The Little-Known Dangers of Acetaminophen
By Jay S. Cohen, MD,
What if a dietary supplement was proven to cause liver damage, liver failure and death? What if each year, this same supplement caused 100,000 calls to poison control centers, 56,000 emergency room visits, 26,000 hospitalizations, and more than 450 deaths from liver failure alone?
You know the answer. The FDA would immediately shut down the supplement company and seek to incarcerate the principals for life.
What if, on the other hand, a highly profitable drug caused this much disease and death? To no one’s surprise, the FDA’s response is to do the equivalent of nothing.
As we learned long ago, the FDA too often functions to protect the financial interests of pharmaceutical companies. The FDA’s intentional inaction in this instance proves that this agency could care less about how many Americans suffer and die each year.
In his eye-opening article, Dr. Jay Cohen exposes a lethal hoax that has been perpetrated on infants, children, and adults by immoral drug companies and their conspirators within the FDA.
Many people assume that over-the-counter medications are safe when taken as directed. Yet even at recommended doses, aspirin can cause ulcers, antihistamines can cause sedation, and acetaminophen can cause serious liver damage.
You can read about some of these risks in the product information that accompanies over-the-counter medicines. For example, the acetaminophen package insert warns about taking the drug if you consume three or more alcoholic drinks a day. The link between acetaminophen, alcohol, and an increased risk of liver damage was identified in the 1980s. This research identified another factor that can increase the risks associated with acetaminophen: fasting. This can refer to fasting due to abdominal upset or pain, nausea, vomiting, loss of appetite, anorexia, or malnutrition. Consider this case published in 1992:
A 25-year-old, healthy Swedish man developed gastroenteritis while on holiday in Turkey. For a day and a half before flying home, the man experienced nausea and vomiting, and he was unable to keep food or liquid down. Noticeably ill during the flight, upon landing he was taken directly to a hospital. As his condition worsened, he was diagnosed with liver failure and transferred to await a liver transplant. Information from his brother, who had been with him in Turkey, indicated that the patient had taken 500 mg to 1,000 mg of acetaminophen two to three times each day, with a maximum total intake of 5,000-6,000 mg over two days. Unexpectedly, the patient’s condition began to improve, liver transplantation was canceled, and he was discharged ten days later.1
What had the Swedish man done wrong to develop liver failure? Nothing. His use of acetaminophen was within the recommended dosage range. The maximum recommended dosage of acetaminophen is 4,000 mg/day. The man took only 2,000 or 3,000 mg/day. He took acetaminophen merely to ease the pain of acute gastroenteritis, as do thousands of people each day. He followed the rules but nearly died.
The doctors presenting this case concluded that liver toxicity “can occur after low, repeated doses of acetaminophen.” They added, “the drug should not be used under conditions of starvation, including acute gastroenteritis with nausea and vomiting.”1 Yet today, despite this report and many others, acetaminophen products do not list a warning against using the drug when unable to eat.
A Powerful Liver Toxin
Many drugs can cause liver damage, liver failure, and death. Yet, acetaminophen prompts the most calls to poison control centers—more than 100,000 per year. Each year, acetaminophen accounts for about 56,000 emergency room visits, 26,000 hospitalizations, and more than 450 deaths from liver failure.2 Acetaminophen causes more cases of acute liver failure than all other medications combined.3
In comparison to the millions of people who take acetaminophen each day without harm, the occurrence of liver failure and death is relatively rare. Still, many experts believe the numbers are too high and must be reduced. Dr. William Lee, a highly respected expert on acetaminophen, wrote, “It still must be asked: Is this amount of injury and death really acceptable for an over-the-counter pain reliever?”4
Why does acetaminophen affect the liver? Acetaminophen is a dose-dependent liver toxin. Even at standard doses, the metabolism of acetaminophen in humans releases small amounts of a toxic substance, N-acetyl-benzoquinoneimine (or NAPQI).5 With excessive doses, a much larger amount of this toxin is formed. There is a fine line between a safe dose of acetaminophen and one that is dangerous, which means that doses even slightly above the maximum recommended dose of 4 g/day can cause liver damage. “Just doubling the maximum adult dosage for a few days can be toxic, even deadly,” warns Consumer Reports.6 Dr. T.M. MacDonald adds, “Used incorrectly and taken in excessive dose either accidentally or intentionally, acetaminophen is a very toxic drug.”7
Fasting reduces the body’s store of glutathione, which is needed to metabolize acetaminophen safely. Decreased levels of glutathione lead to an increased risk of acetaminophen toxicity. Liver damage may occur at recommended doses, as seen with the Swedish man, or in people who unintentionally overmedicate with acetaminophen.
Unintentional Overdoses Take a Heavy Toll
Another daunting statistic about acetaminophen is that nearly half of all overdoses are unintentional.8 These people do not intentionally take excessive amounts of acetaminophen; instead, they lose track of the amount they are taking and inadvertently take more than recommended.
Other individuals intentionally take 5,000-8,000 mg/day of acetaminophen because their pain is not relieved by the recommended doses. These people are not trying to harm themselves, but merely seeking relief from pain and are not aware that doses even slightly above the maximum therapeutic dose of 4,000 mg/day can be toxic.
Another type of accidental overdose occurs when people take multiple remedies, for example, for the flu, cough and cold, headache, and fever, without realizing that each contains acetaminophen. Accidental overdoses can also occur in those who take prescription medications containing acetaminophen, such as Vicodin® or Percocet®, since they may not be aware of the medications’ acetaminophen content. Unknowingly, they can overmedicate with acetaminophen when they reach for an over-the-counter product containing this drug at the onset of flu, a cold, or fever. It is all too easy to make this mistake. A 2003 study found that when doctors prescribed narcotic-acetaminophen combination pain medications to 108 patients, not one was warned that the medications contained acetaminophen and that they should reduce or discontinue the use of other acetaminophen-containing products, including over-the-counter remedies.9
Unintentional overdoses of acetaminophen are often more toxic and difficult to treat than intentional overdoses.10 Doctors often see people who take intentional overdoses within a few hours of ingestion. In these cases (usually attempted suicide), the amount taken is usually known and liver damage is not yet extensive. The acutely high blood levels of acetaminophen seen in these cases help doctors make a quick diagnosis and start treatment.
In contrast, unintentional overdose cases usually occur after people have been taking acetaminophen over several days and the exact amount ingested may not be known. Blood levels of acetaminophen are often deceptively low, yet liver damage may already be extensive and critical time may be lost while doctors struggle to make a diagnosis.
Requests for Better Warnings Ignored
In addition to its alcohol warning, over-the-counter acetaminophen packaging also warns against use “with any other product containing acetaminophen.”11 Unfortunately, this weak warning does not convey the serious risks of acetaminophen overmedication, even at slightly elevated doses. Overuse can cause liver injury, liver failure, and death, but you would never know it by reading the information provided with acetaminophen products.
You would also never know about the risks of taking acetaminophen while fasting. Current product information does not mention it at all. Meanwhile, cases continue to be reported as highlighted below:
A 45-year-old man developed severe liver toxicity while taking 4,000 mg/day of acetaminophen for four days. He had several risk factors, including malnutrition and illness-induced starvation.12
A 54-year-old woman developed liver failure after unintentionally overmedicating with 5,000-6,000 mg/day of acetaminophen for six to eight weeks. She had taken 3,000 to 4,000 mg/day of over-the-counter acetaminophen and was unaware that her prescription pain medication (Lortab®) also contained acetaminophen.13 Her history provided no risk factors except for a gastric bypass, which can lead to malabsorption of micronutrients needed to synthesize glutathione.14
A 16‑year‑old boy underwent surgery for severe scoliosis. Fever developed postoperatively, and a low dose of 1,200 mg/day of acetaminophen was given for three days. The boy was malnourished, and he was fasting during the postoperative period with only limited intravenous support. A few days later, the boy developed acute liver failure, and he died soon after. Autopsy revealed liver injury consistent with acetaminophen toxicity. The doctors commented, “This case may illustrate that acetaminophen may cause liver injury even in therapeutic doses, if certain risk factors are present. Such factors are malnutrition and starvation.”15
A 58-day-old infant girl was seen in an emergency room after two days of fever, decreased appetite, lethargy, and irritability. As instructed, the parents had given acetaminophen every four hours to the infant. Tests revealed highly elevated liver enzymes and an elevated acetaminophen level. Tests for other liver disorders were negative. The girl improved quickly with treatment. The authors noted that children who have fever, vomiting, or diarrhea often have inadequate oral intake, and that a fasting state could increase the toxicity of acetaminophen.16
Two children developed severe liver and kidney damage after receiving repeated doses of acetaminophen for illness and fever. The authors commented that when low doses of acetaminophen are used at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for liver and/or kidney toxicity.17
In this last case, the authors added that there was a need for increased caution and awareness among health care professionals about the toxic effects of acetaminophen. This increased awareness required “appropriate package‑label warnings,”17 and is one of many calls for more informative warnings on acetaminophen products.