N-acetylcysteine (NAC) is a popular supplement invented in the 1960s used primarily to optimize glutathione levels. It is normally used in hospitals in emergency situations to treat overdoses of acetaminophen (e.g. Tylenol), which results in an acute and deadly shortage of glutathione in the liver. When acetaminophen is taken as directed, it is safely metabolized by the liver enzymatically. A small amount is oxidized to form N-acetyl-p-benzoquinone imine (NAPQI), which is highly toxic. NAPQI is detoxified in the liver by conjugation with glutathione. However, in overdoses of acetaminophen, NAPQI levels rise dramatically as the regular detoxification processes are overwhelmed. The liver literally cannot regenerate glutathione fast enough to quench the toxic NAPQI. Extensive liver damage and death often ensues. NAC helps by being quickly converted into cysteine, which enables the production of fresh glutathione.
NAC is also sold as a dietary supplement as a means of optimizing glutathione levels on an everyday basis. Glutathione is the master antioxidant in the human body, responsible for detoxifying compounds in the liver as well as reacting with reactive oxygen species that are harmful in large amounts. Glutathione differs significantly to other antioxidants (such as Vitamin C) in that it is made by humans. Our body makes glutathione from three amino acids - glutamate, cysteine and glycine. Levels can get low when our diet is short of these amino acids. The rate-limiting amino acid is usually cysteine, which the body can obtain from the diet following the digestion of protein, and also enzymatically from methionine. When cysteine levels in the diet are inadequate, glutathione levels in the body become inadequate, resulting in general inflammation. Most chronic illnesses are characterized as having low glutathione levels and restoring glutathione levels may help reduce inflammation, if not actually reverse the underlying problem. Moreover, for acute conditions such as viral infections that reduce glutathione levels (e.g. covid), supplementation with NAC has been found to be useful in glutathione regeneration.
Vitamin U (S-methylmethionine) is a naturally abundant nutrient found in vegetables and fruits, especially cruciferous (e.g. cabbage, kale) and stalky vegetables (e.g. celery, asparagus). Like NAC, one of the functions of Vitamin U is to facilitate glutathione biosynthesis via its conversion to cysteine. Its use as an alternative to NAC in the treatment of acetaminophen overdose has been proposed and remains under investigation. One of the advantages of Vitamin U is that unlike NAC, Vitamin U is already found in many of the foods available in the fresh market, and is therefore unlikely to cause side effects.
While Vitamin U should not be used in an emergency situation as its efficacy has not been tested, Vitamin U may serve as an alternative to NAC by those looking for a natural choice to boost their glutathione levels and restore their redox balance on an everyday basis.
It should be emphasized that any possible overdose of paracetamol/acetaminophen should be treated at a hospital by a doctor and not self-treated with NAC or Vitamin U.
People who should not replace NAC with Vitamin U are those with hyperhomocysteinemia due to cystathionine beta synthase (CBS) deficiency that doesn't respond to B6 supplementation. As Vitamin U enters the cysteine biosynthesis pathway upstream of CBS, homocysteine levels will increase when Vitamin U is ingested, making the condition worse. In contrast, NAC enters the cysteine biosynthetic pathway downstream of CBS, and consequently doesn't raise homocysteine levels. This is one of the reasons why avoiding cruciferous vegetables rich in Vitamin U is part of a the low methionine diet prescribed to people with a B6-insensitive CBS block. A combination of methyl donors that don't generate more homocysteine like betaine (TMG) with NAC might be useful, betaine to support methylation and NAC to generate cysteine.
Edited - 23Nov2025
