TweetA major stunning review article was released by the prestigious British Medical Journal on March 31, 2015. The study evaluated the efficacy and safety of acetaminophen treatment for treatment of low back pain and osteoarthritis. The results provided a revealing wake-up call. After combing through mountains of data, the authors determined that acetaminophen, the active ingredient in Tylenol, was ineffective in the treatment of low back and neck pain. Those who used acetaminophen as directed had higher prevalence of liver injury. In addition, they concluded that acetaminophen provided minimal short-term benefit for people with osteoarthritis or degenerative joint disease.
The study was a systematic review with meta-analysis evaluating studies through several different medical data sources. Only randomized, controlled trials were used that compared placebo effects versus acetaminophen pain and inflammation reduction in those who had neck or low back pain or osteoarthritis/degenerative joint disease of the hip or knee. The authors used two independent reviewers to extract the data. A total of 13 randomized control trials were thoroughly scrutinized in order to reach their conclusion.
Does Tylenol Help Neck Pain, Low Back Pain, and Arthritis?

There were two main reasons why the authors did this study. The first was to evaluate the efficacy of the use of acetaminophen for pain management and arthritis. That is, do acetaminophen medications like Tylenol really help osteoarthritis pain? Millions of Americans suffer from low back and neck (spinal) pain. These concerns are leading causes of disability worldwide. Over nine percent of the world’s population or nearly one out of ten people are affected by significant spinal pain. Degenerative joint disease affects nearly four percent of the global population. The management of these concerns greatly contributes to the rising costs of health care. In the desire to provide cost-effective health care management, it is vital to know what works and what truly is marginal or ineffective. The researchers concluded that acetaminophen is ineffective for these concerns.
Acetaminophen Safety

The second concern of the study relates to acetaminophen use and safety. The full recommended dose of acetaminophen is 4,000 mg per day for regular use. In this review article, the statistics revealed solid, high quality evidence that regular therapeutic use increases the risk of having an abnormal liver function test by four-fold. A number of the studies included in this review found patients with osteoarthritis taking acetaminophen regularly as directed had elevated liver enzymes ALT and AST of 1.5 times the upper limit of the lab reference range or higher. Liver cells release certain types of enzymes upon cell death. This reflects pathological liver cell damage.
Liver Failure

Acetaminophen use is certainly not without risk. Acetaminophen overdose or chronic use is a known major cause of acute liver failure. There are over 600 drugs that contain acetaminophen, with Tylenol being the most widely recognized name brand. Tylenol/acetaminophen use is the leading worldwide cause of drug overdose and acute liver failure. It can happen as a result of a single overdose and even with recommended ongoing therapeutic doses below the 4,000 mg/day dose. One study called it a “therapeutic misadventure” when Tylenol use led to acute liver failure. Another study found that in the majority of acute liver failure cases was due to chronic use of Tylenol causing chronic poisoning. The number of cases of acute liver failure is certainly on the rise with the pervasive use of the drug. It has been known for nearly three decades that Tylenol is a toxic drug that depletes the liver’s antioxidants system.
Acute liver failure occurs when 80-90 percent of the liver has sustained severe damage usually with no known liver disease. It occurs rapidly in days or weeks, with life threatening consequences. Not a good “therapeutic misadventure” to embark on. Several factors can increase the risk of acetaminophen induced liver failure. These include minor alcohol use or alcohol abuse, use of certain medications including antibiotics, NSAIDs (ibuprofen, Motrin, etc), and anti-seizure medications, viral infections like hepatitis A, B, and E, Epstein Barr virus, herpes simplex virus, and cytomegalovirus, and other problems.
When acetaminophen is ingested, it must be detoxified through the major cytochrome P450 enzyme system in the liver. It uses the master antioxidant glutathione to do so. If glutathione levels are deficient, then processing the drug causes toxic mitochondrial damage and high levels of oxidative stress or inflammation. It eventually leads to liver cell death which then causes liver enzymes (ALT and AST) to elevate. The destructive cycle stops when the insults are removed or glutathione stores are replenished.. How well the body responds depends on how replenished and equipped your body is. You can get your glutathione status measured through blood tests from your health care provider.
Alcohol Use and Tylenol

Alcohol use is an obvious insult to the liver as a consequence of depleting mitochondria glutathione. However, the damage is easily ramped up when combined with medications like acetaminophen. The liver mitochondria experience a significant damaging blow to function when acetaminophen is combined with alcohol. In an animal study, liver damage was found within 6 weeks of acetaminophen and alcohol use. Think about this information in a more personal context – a glass of wine at dinner, a dose or two of Tylenol during the day because of an old nagging injury or some arthritis. How does this impact the repetitive strain that the medication and alcohol place on the mitochondria and liver of repeating this week after week or even longer?
Fatty Liver Disease, Diabetes, Obesity and Tylenol Poses Risk to Mitochondria

Tylenol/ acetaminophen affect the mitochondria within liver cells leading to higher levels of oxidative stress and free radicals. The mitochondria’s ability to aerobically do their job producing energy is compromised. This phenomenon can reverse itself when the toxin is removed. Now add in common epidemic level disorders that put a substantial strain on the mitochondria and liver function even without the strain of acetaminophen intake. Brand new research has identified that fatty liver disease, diabetes, and metabolic syndrome occurs with impairment in mitochondria function and in-turn creates a vicious cycle perpetuating itself. This leads to a marked increased risk for liver injury in those who have these underlying concerns and then take acetaminophen for ongoing aches and pains.

The fact is Tylenol drug-induced liver injury affects mitochondria function on a large scale level with overdose, but it should make one wonder about the “subclinical” level insults. With the millions of Americans popping acetaminophen drugs for joint pain problems who have blood sugar, obesity, and fatty liver problems and the underlying mitochondria dysfunction in all of these arenas, it would appear like a train-wreck happening to the liver and body on an imperceptible level. And at what cost to the individual and the health care system?
The underlying constant here is that obesity, diabetes, fatty liver disease and degenerative joint disease have mitochondria impairments present. At the same time, Tylenol intake impairs mitochondria function as does alcohol use. To tease apart all this information and put it into the confines of research studies is tricky, but certainly these various studies open the door to understanding dangerous unhealthy trends and consequences. This information should make one think twice about taking acetaminophen or Tylenol especially in context of higher risk situations that have been mentioned. We need to recognize that Tylenol is not a benign substance albeit immensely popular. It is a drug; a powerful drug often used without second thought.
Other Factors Affecting Tylenol Toxicity

Those who have gone through weight loss surgery are at higher risk of liver failure and toxicity from Tylenol or acetaminophen. Drugs are metabolized and absorbed differently as a consequence of the surgery. The same changes apply to nutritional status that affects liver function.
Add another variable to mix of acetaminophen toxicity risks. A new study released last month uncovered an interesting finding that may impact millions. The animal study focused on liver toxicity induced by acetaminophen and how serotonin impacted liver health. Serotonin not only functions as a neurotransmitter in the brain, but is also involved with liver function and the development of disease. Serotonin can be helpful or harmful. It helps the liver repair and regenerate, but serotonin can be detrimental in certain cancers and some other liver disorders. In this study, the scientists caused acetaminophen toxicity in mice that had no other liver disorders. The mice that experienced acute liver failure were serotonin deficient. The mice with adequate serotonin levels did not experience liver failure with the same drug exposure. The serotonin helped to protect the liver from oxidative stress and inflammation. How this applies to humans has yet to be determined, but this information may potentially affect the millions who suffer from serotonin deficits (depression, anxiety, panic attacks, irritable bowel syndrome, sleep disorders, etc). The study did not look at serotonin prescription medications. Certainly, several concerns are raised with this information.
Acetaminophen Toxicity Effects More Than Liver Function

New research agrees with the questionable safety of acetaminophen use, but for different reasons. Research published in Expert Opinion Drug Safety in August 2015 provides the expert opinion that not only is acetaminophen toxic to the liver; it causes toxic damage to the gastrointestinal tract and heart. They also reported on the fact that acetaminophen is a poor pain reliever for osteoarthritis. Their expert opinion was that acetaminophen should be used at the lowest effective minimal dosage and for the shortest amount of time.. Their recommendations are far more conservative than the full dosage recommendation of 4,000 mg per day on a regular basis for osteoarthritis pain. The Journal of Pain Research also questions the toxicity effects on the gut and heart with acetaminophen. The authors recommended practitioners significantly evaluate risk versus benefits in all patients.
The take away message from the British Medical Journal study and these other studies is that acetaminophen is not the best resource for chronic degenerative joint disease and neck and low back pain and has safety concerns. Acetaminophen/Tylenol poses increased threats to health especially with these other concerns. If you suffer from chronic spinal pain or arthritis and need to use medical support, talk with your health care provider and consider using the least amount of medication needed for the shortest period of time.
Protecting the Liver with NAC and Adiponectin

The standard medical treatment for Tylenol or acetaminophen injury is the use of N-acetyl cysteine (NAC). NAC is available as a nutritional supplement and is also naturally found in whey protein. NAC is fundamental for glutathione production and supports liver detoxification. In fact, new research shows that taking NAC with acetaminophen blocks toxic injury to the liver. Researchers proved that using the both medical treatment and nutritional support work well together. In fact, the authors recommended that industry standards change with acetaminophen administration. They recommended that all acetaminophen meds contain NAC to prevent any liver injury in any and all settings.
New research shows that supporting the hormone adiponectin protects the liver from drug-induced acetaminophen liver failure and mitochondrial injury. Adiponectin works in harmony with leptin to regulate metabolism. When adiponectin is depleted, obesity, blood sugar problems, metabolic syndrome, inflammation, and oxidative stress are problematic. It is essential to support adiponectin, thereby providing significant protection to the liver and reducing risk.
We need to take charge of our health before the economic burden of poor health runs this country into the ground. Taking medications that fail to help but rather cause acute or insidious chronic harm has been identified on the most popular pain ingredient on the market. If you rely on these types of medications to get you through the day, reconsider your approach. At least combine protective nutrients and a healthy adiponectin-leptin balance into your daily life. There are wonderful natural resources to help manage mild-moderate musculoskeletal pain and breakdown.
Supportive nutrients include DHA, curcumin, boswellia, hyaluronic acid, vitamin D, and more. There are several nutrients that protect and support healthy mitochondria such as PQQ, acetyl-l-carnitine, lipoic acid, B vitamins, magnesium, resveratrol, coenzyme Q10 and many others. If your health status poses higher risk for drug injury, it is absolutely essential to work on weight management, blood sugar, and fatty liver problems. Wellness Resources provides many tools to help with weight management, blood sugar, and obesity that increase the risk of liver injury with Tylenol use. Don’t run the risk of liver failure and “therapeutic misadventure” from single isolated use or chronic use of the most common drug ingredient in America. There are many choices. Several have been identified. You choose the direction and consequences you face.


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