Herb Drug Interaction: Glutathione, Acetaminophen and Your Liver

| May/June 2002

  • Milk thistle can raise glutathione levels and help protect the liver.
    Steven Foster
  • Milk thistle can raise glutathione levels and help protect the liver.

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.

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