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Herb Drug Interaction: Glutathione, Acetaminophen and Your Liver

By Robert Rountree, M.D.
May/June 2002
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Milk thistle can raise glutathione levels and help protect the liver.
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Not long ago, I was called to the emergency-care unit of a local hospital to assist in the treatment of a young woman who had attempted suicide by taking an overdose of acetaminophen, a popular over-the-counter medication. Acetaminophen is found in Tylenol and many cold and flu remedies. Despite the general perception that acetaminophen is a gentle and safe treatment for pain and fever, the bad news is that high doses (7 to 10 g taken over an eight-hour period) are extremely toxic. Without proper treatment, such a dose can cause massive liver failure within a couple of days.

When a healthy person ingests a therapeutic dose of acetaminophen (approximately 500 to 1,000 mg for adults), a chemical disposal system is set into motion that involves modifying the drug into a series of byproducts. Some of these byproducts are very toxic. The final step in this disposal process involves neutralization of these byproducts in the liver. This is accomplished by combining them with a proteinlike substance called glutathione. When excessive doses of acetaminophen are ingested, the supply of glutathione is quickly used up, leaving the liver cells susceptible to rapid destruction.

Obviously, the key to reversing this process hinges around maintaining a steady supply of glutathione. In fact, the antidote for acetaminophen toxicity is a modified amino acid called N-acetyl-cysteine (NAC), which works by providing one of the main building blocks used to increase glutathione in the liver. When given in massive quantities (25 to 40 g daily), it can raise the level of glutathione high enough to neutralize the toxins produced from acetaminophen overdose.

Understanding glutathione

The story of how glutathione works has vast ramifications for doctors, herbalists and any person who must take medications that are potentially toxic to the liver. This remarkable compound is found inside the cells of all living things. It is made of three amino acids: cysteine, glutamic acid and glycine. An extremely potent antioxidant, glutathione is essential for the elimination of highly toxic free radicals. When cells become depleted of glutathione, they rapidly die. In humans, the highest concentration of glutathione is found in the liver, where it is used as an “anti-toxin” to inactivate drugs, hormones, and foreign chemicals.

Administration of NAC—the acetaminophen overdose antidote— remains the best-known conventional method for enhancing glutathione production. However, a number of medicinal herbs also have this ability. Traditional healers have known for hundreds of years that certain herbs are beneficial for treating a range of liver problems. While these herbs undoubtedly work through complex and diverse mechanisms, it may be that increasing glutathione in the liver is the common denominator for their medicinal effects. Interestingly, glutathione itself can be taken orally, but it must be taken in massive quantities to raise tissue levels, and this has made it impractical for routine use.

Herbs and foods

Laboratory studies have found that schisandra (Schisandra chinensis), garlic (Allium sativum), globe artichoke (Cynara scolymus), green tea (Camellia sinensis), milk thistle (Silybum marianum) and turmeric (Curcuma longa) all raise glutathione levels. Nutritional supplements including vitamin C, alpha lipoic acid, S-adenosylmethionine (SAMe) and whey protein all raise glutathione. Foods rich in limonene, including citrus fruits, dill weed and caraway seeds, have also been shown to increase glutathione production. Cruciferous vegetables such as broccoli, cabbage and Brussels sprouts are rich in glutathione and well-known for their ability to support liver function. Other herbs known for their hepatoprotectant properties, such as boldo (Peumus boldus), bupleurum (Bupleurum chinense), dandelion (Taraxacum officinale) and licorice (Glycyrrhiza glabra), may also turn out to raise glutathione.

So how does all this information relate to everyday life? Hundreds of scientific publications now indicate that one of the keys to optimal health depends on maintaining adequate stores of glutathione. Chronically low levels render a person more susceptible to recurrent infections, asthma, chronic fatigue syndrome, diabetes, cataracts, cancer, heart disease, premature aging and neurological disorders such as Parkinson’s and Alzheimer’s diseases. But glutathione reserves are highly dependent on adequate nutrition—fasting for longer than twenty-four hours is one of the quickest ways to drain your glutathione stores. Glutathione is also depleted through the process of detoxifying common environmental pollutants, such as pesticides, herbicides, solvents, heavy metals and cigarette smoke.

Recent evidence indicates that even normal therapeutic doses of acetaminophen may deplete glutathione levels, especially when the drug is taken regularly. Given that the liver uses large amounts of glutathione to detoxify alcohol, one of the most dangerous things you can do is take acetaminophen for a hangover. Numerous prescription medications such as anti-acne drugs, anticonvulsants, cholesterol-lowering drugs, tricyclic antidepressants and major tranquilizers are potentially toxic to the liver as well.

Preventive steps

If you must use acetaminophen or any medication that carries with it the warning that it could cause liver damage, why not offer yourself some protection by taking a regular, daily “cocktail” of milk thistle, turmeric, green tea and/or artichoke along with a large serving or two of cruciferous vegetables? I can’t offer you the results of any published studies that prove this will keep your liver healthy, nor can I tell you the optimal dose of these herbs with any degree of certainty. But I do know that these herbs have long histories of safe use as foods and folk medicines. And I also know that there is strong evidence that they can increase your glutathione levels.

One last comment about the young woman I treated for the acetaminophen overdose: In addition to her conventional treatment, I did my best to get the hospital pharmacy to give her a few capsules of milk thistle by writing an order for it in her chart. After running into an impasse where I was forced to admit to the pharmacist that I could not back up my recommendation with a double-blind placebo-controlled trial, I finally gave up and asked the patient’s mother to pick up a bottle of the herb at a local health-food store so that she could start taking it right away. The patient made a full recovery.


Robert Rountree, M.D., is a physician in private practice in Boulder, Colorado, where he practices integrative medicine. He is co-author of Smart Medicine for a Healthier Child (Avery, 1994) and Immunotics (Putnam, 2000) and is an Herb Research Foundation advisory board member.

References

Chiba, M., and K. S. Pang. “Glutathione depletion kinetics with acetaminophen. A simulation study.” Drug Metabolism and Disposition: The Biological Fate of Chemicals 1995, 23(6): 622–630.

Flora, K. “Milk thistle (Silybum marianum) for the therapy of liver disease.” American Journal of Gastroenterology 1998, 93(2): 139–143.

Micheli, L., et al. “Effect of acetaminophen on glutathione levels in rat testis and lung.” Environmental Health Perspectives 1994, 102 (Supplement 9): 63–64.


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