The Risks and Benefits of N-acetylcysteine (NAC) and Selenium Supplements

Tylenol toxicity is the leading cause of liver transplantation in the United States, responsible for more acute liver failure than all prescription drugs combined. Tylenol is a widely recognized brand name of acetaminophen, also known as paracetamol. Acetaminophen breaks down into small quantities of a toxic metabolite that is almost immediately detoxified by glutathione, but at excessive doses, glutathione levels become depleted. Though liver damage can result from doses as low as 4 grams a day in adults (8 “extra strength” tablets), 12 to 15 grams carries a whopping 50 percent mortality rate if untreated. The antidote is N-acetylcysteine, which the body can use to rapidly restore glutathione levels. Is there any benefit to taking N-acetylcysteine routinely?

N-acetylcysteine does reduce markers of oxidative stress and can improve symptoms of schizophrenia and chronic bronchitis, but its preclinical longevity effects are mixed. N-acetylcysteine increases the lifespan of male (but not female) mice but only, apparently, because it led to reduced food and water consumption. In C. elegans and fruit flies, lifespan was extended at one dose but dramatically cut short (by up to 70 percent) at a higher dose. Researchers concluded that the “high-dose associated increase in mortality…consistently observed in all experiments studying NAc’s effects on longevity…raises a serious concern on consumer behavior of taking NAc as a diet supplement….”

Concern has also been raised about selenium, a critical component of key antioxidant enzymes and, therefore, considered an essential trace mineral. Brazil nuts are one of the most concentrated sources, averaging about 100 micrograms per nut, nearly twice the recommended dietary allowance, but ranging up to more than 1000 µg per nut. That’s not good, since the tolerable upper limit for adults is only 400 µg. The narrow safety margin is why selenium has long been termed an “essential poison.”

Indeed, the consumption of just a single high-selenium brazil nut a day was found to have pro-inflammatory effects. That’s why I got so concerned about people misinterpreting my suggestion in How Not to Die to try eating four Brazil nuts once a month, based on a too-good-to-be-true study showing a 20-point drop in LDL cholesterol within nine hours of such a snack which seemed to stay down a month later. But eating so much selenium every day could get you into trouble.

There are observational data that look promising. For example, selenium lower levels were found in Alzheimer’s brains on autopsy, and lower selenium levels o in the blood correlate with increased risk of cataract and premature death. But you don’t know if it’s cause and effect until you put it to the test in interventional trials, especially since high blood selenium levels are also associated with dying prematurely.

A dozen randomized, controlled trials found selenium supplements failed to affect mortality, and at 300 µg, may even shorten lifespan. Even just 200 µg a day, despite possibly reducing markers of oxidative stress, was found to worsen blood sugar control in diabetics and actually increase the risk of developing diabetes in the first place, compared to placebo.