N-acetylcysteine and histamine/allergies

In my last post on vagus nerve and IBS, I noticed some of the discussion mention impacts on acetylcysteine. This caused me to wonder about NAC and histamines/allergies/Mast cell issues. I know someone with severe allergies that was advised to take NAC for liver support by her naturopath.

Since the late 1970s N-acetylcystein has been used as an antidote after paracetamol intoxication. The treatment is traditionally given as three consecutive infusions for 20 hours and 15 minutes. The total dose given is 300 mg/kg. Half of this amount is given as a bolus during the first 15 minutes of treatment. This regime has proven very efficient in avoiding liver injury. However, side effects, caused by histamine release, are common (10-15%). 

Simplified N-acetylcystein treatment after paracetamol overdose – new recommendations from Swedish Poisons Information Centre [2019]

Similar citations:

  • “exposure to antihistamines prior to NAC treatment may protect against these [anaphylactoid] reactions.” [2020]
  • ” Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients” [2019]
  • ” Previous studies suggest the incidence and severity of non-allergic anaphylactic reactions (NAARs) are influenced by the rate of acetylcysteine infusion.” [2015]
  • “N-acetylcysteine (NAC) enhances the release of histamine induced by the fluoride-calcium system” [1991]

Histamine now seems to be an important mediator of the response [to NAC], and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. … The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms.

Adverse reactions associated with acetylcysteine [2009]

Bottom Line

If you are female with histamine issues, asthma or allergies — taking NAC will make some of your worst or more sensitive. If your MD or ND have recommended NAC and you have told them about allergies, asthma etc. you should print this off to inform them. It has been known since at least 1991, just 30 years ago.