Numerous Medications Cause Drug-Induced Liver Injury – Protect and Restore Function

December 19, 2016 | Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

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Numerous Medications Cause Drug-Induced Liver Injury – Protect and Restore Function
Drug-induced liver injury is an all too common medical issue today. It is estimated that over 600 drugs and chemicals are associated with significant liver injury. Fifty percent of acute liver failure cases are caused by drug damage. Mitochondrial injury is a major factor underlying drug-induced liver disease. The good news is that this liver injury can be remedied and even prevented with a diet rich in polyphenols and other specific nutrients.

[Jump to: Nutritional Options]

Drugs that are toxic to the liver create a cascade of events with mitochondria, liver cells, oxidative stress, increased cellular debris, and inefficient clean-up responses. Damaging medications trigger mitochondrial membrane rupture, deplete cellular energy production and cause cell death within the liver. The process may occur acutely and result in full-blown liver failure. More commonly, it occurs with milder chronic forms, like fatty liver disease that develops into cirrhosis or liver scarring.

The susceptibility to liver injury occurs for several reasons. It may occur due to genetics or an acquired inability to metabolize and detoxify the drug. Other reasons include age, smoking, alcohol, diabetes, viral infections, pregnancy or obesity-associated metabolic syndrome.

Liver Stress


The first symptoms that the liver is struggling can be vague. These include fatigue, weakness, abdominal pain, and loss of appetite. As liver function worsens, there may be itching, easy bruising, fluid build-up in the legs, confusion, yellowing of the skin, dark, colored urine, increased number of bacterial infections, and elevated levels of liver enzymes, ALT and AST. Depending on the level of injury, the liver may recover once the drug is discontinued, or complications may set in and infection, kidney and liver failure may occur. The critical difference depends on the vitality of the liver before the insult.

Drugs that Cause Liver Stress


Drug-induced liver injury has led to drug recalls, severe black box warnings by drug agencies, and stopping of clinical research trials. There are many more drugs that do not have these strong warnings that can still cause drug-induced liver injury. Amoxicillin, clavulanate, isoniazid, and nonsteroidal anti-inflammatory/NSAIDs drugs are among the most common. Others include methotrexate, aspirin, acetaminophen, tetracyclines, minocycline, valproic acid, allopurinol, estrogen, oral contraceptives, tamoxifen, anabolic steroids, atorvastatin, verapamil, trazodone, TNF-a antagonists, phenytoin, doxorubicin, penicillamine, proton pump inhibitors, and several others. Children are especially at high risk for liver failure from toxic drugs like Tylenol and antibiotics.

AMPK – Master Enzyme Activation Required for Liver Protection


Reversal and prevention of drug-induced liver injury is of utmost concern. Key new research has focused on promising ways to intervene against this problem and allow for management of drug-induced liver injury. Scientists found key information pertaining to AMPK critical to drug-liver metabolism and detoxification. AMPK is an enzyme switch found in cells throughout the body, especially in the hypothalamus, liver, muscle, adipose tissue and pancreas. Activation of AMPK prevents and reverses drug-induced mitochondrial and liver cell damage.

AMPK (5’-adenosine monophosphate-activated protein kinase) is a master regulator of energy levels within the cells. It helps mitochondria function, supports clean-up of cellular debris and is a key molecule regulating mitochondria health and viability. When AMPK is present, mitochondria flourish and run efficiently, produce more energy and fewer free radicals. AMPK also triggers autophagy, a cellular clean-up mechanism.

In testing this application, scientists took animal liver cells and exposed them to either Tylenol/acetaminophen or another liver damaging pain-relieving medication, diclofenac. The substance that they used to activate AMPK was the amino acid acetyl-l-carnitine (ALC). Without AMPK activation, the liver cells stopped functioning and mitochondria fell apart. When AMPK was activated, it stopped the cellular damage and the liver could manage the toxic effects of the drug. ALC activated AMPK, which stopped breakdown of the mitochondria, helped these essential organelles regain health and regenerate, and engaged the cleanup process and restored cellular function. The cells damaged by acetaminophen responded the best. This is great news as acetaminophen/Tylenol use is a known major cause of acute liver failure, even when used as prescribed.

AMPK activation has been making headline news for other disorders as it is critical for healthy metabolism and energy production. We know that AMPK is defunct in other areas of the body and with other disorders like obesity, diabetes, chronic fatigue syndrome, and fibromyalgia.

Activating AMPK


AMPK is turned by exercise, diet, and nutrients. It can be turned on by two minutes of vigorous exercise. It is turned on between meals, i.e., three to four hours after a meal and no snacks. AMPK supporting nutrients include not only acetyl-l-carnitine used in the study, but also curcumin, N-acetyl-cysteine, silymarin, resveratrol, quercetin, olive leaf extract, bitter melon, and plant phenols. Not all these nutrients have been specifically investigated in drug-induced liver injury, but many of them help with fatty liver, which is a consequence of drug-induced liver injury. Additional support for liver detoxification and the Phase I and Phase II pathways requires several other nutrients. More information may be found in the article Endocrine Disruptor Compounds and Natural Solutions.

Chronic Fatigue Syndrome and Fibromyalgia


Individuals with chronic fatigue syndrome (CFS) and fibromyalgia (FM) are known to struggle with acetyl-l-carnitine deficiency and poor energy production related to acquired mitochondrial injury. They often have trouble with chemical sensitivity and poor tolerance of medications. AMPK activation is defunct in these disorders. Thus, individuals with CFS and FM need to pay special attention to supporting liver function, activating AMPK, and mitochondrial function.

No matter how enticing drug commercials and sale pitches are for promising results for medications, there are consequences to the body. There is no doubt that drugs are necessary for severe illness and dysfunction. However, drugs can cause injury to the liver. This can occur in a very subtle manner or acutely and result in liver failure and loss of life. What we want to make sure of is to “first do no harm” and ensure that our body, especially the liver, AMPK, and mitochondria have the proper fortification for today’s living and needs. Thomas Edison said it over a century ago - "The doctor of the future will no longer treat the human frame with drugs, but will rather cure and prevent disease with nutrition". Treat your diet and the obtainment of nutrients as a top priority in your life.

Nutritional Options



Acetyl-l-carnitine – This amino acid supports many activities in the body including the activation of AMPK. Mitochondria function depends on this nutrient. It is vital for energy production, memory, and burning fat for fuel. Vegetarian diets often lack adequate amounts of this amino acid.

Resveratrol – This powerful polyphenol plant based antioxidant activates AMPK. It has been widely used as an antioxidant and nutrient for blood sugar, cholesterol, heart, brain, and immune support. It protects mitochondria and is a natural anti-inflammatory agent.

Silymarin – Also known as milk thistle extract, this antioxidant has been used for liver support for ages. This compound helps the liver clear toxins, protects the liver from wear and tear, and helps activate AMPK.

Quercetin – Quercetin is a natural bioflavonoid found in produce like onions and apples. It is known for its role as a natural anti-histamine, anti-inflammatory, and anti-viral nutrient. Add quercetin to your list for natural support and AMPK activation.

Olive Leaf Extract – This plant based nutrient supports many different actions in the body as an immune compound, an antimicrobial agent, and gout fighting compound. It helps protect the brain, supports healthy blood pressure and blood sugar, and offsets the effects of high calorie intake. Add AMPK activation to the list of benefits found with olive leaf extract.

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