Food-induced methemoglobinemia: A systematic review

Abstract

Methemoglobinemia is a sporadic, potentially fatal disease of poor tissue oxygenation in which ferrous hemoglobin (Fe²⁺ ) is oxidized to the ferric (Fe³⁺ ) state, rendering it incapable of binding oxygen (O₂ ). Fortunately, it is diagnosable and treatable. Here, we present a systematic review of food-induced methemoglobinemia. PubMed and Embase databases were searched using the term “methemoglobin*,” for articles up to December 31, 2020. Inclusion criteria were confirmed or probable cases of methemoglobinemia with an oxidant confirmed in food or body tissue samples, or the oxidant likely to have come from food. We found 97 articles describing 568 cases. Median age was 6 years (range: 2 weeks to 80 years). Median methemoglobin fraction was 30% (n = 142). Oxidizing agents were predominantly nitrites and nitrates. The commonest type of presentation was children eating vegetables (30%), followed by accidental ingestions (27%), and meat curing misadventures (22%). Favism was found to result in mild methemoglobinemia, highest fraction reported was 15.8%. Of the 35 deaths, 32 were from accidental ingestions (91%). In some fatal cases, diagnosis was likely delayed or missed, and antidote was not administered. The majority of cases survived, even with severe methemoglobin levels of up to 89%, provided that methylene blue was administered. Treatment with methylene blue alone resulted in an average methemoglobin drop of 39.1% (n = 22). Methemoglobinemia cases continue to occur due to accidental exposure, meat curing misadventures, and babies ingesting nitrate-rich vegetables which have been inappropriately stored. Early recognition of the toxidrome, instituting antidote treatment, and notifying public health authorities are key to improved outcomes.

Keywords: curing agent; food additive; methemoglobin; methylene blue; nitrites.