ArticleProceedings of the National Academy of Sciences of the United States of America2025
Flavin-deficient erythrocytes offer protection against malaria parasites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Studies from the 1980s and 1990s conducted in Italy, where malaria was once endemic, hypothesized that individuals with erythrocytes deficient in flavin mononucleotide and flavin adenine dinucleotide (FAD)-collectively known as flavins-are partially protected against malaria. The condition was reported to be familial, consistent with a genetic element. This hypothesis, however, has never been tested. Using an erythrocyte FAD-dependent glutathione reductase activity assay, we identified individuals with flavin-deficient erythrocytes (FDE) in Ferrara, Italy (23% of 150 individuals screened), and in Huye, Rwanda (13% of 169 individuals). None of the individuals with FDE had a dietary riboflavin deficiency. Importantly, FDE from individuals in Ferrara, as well as erythrocytes depleted of flavins in vitro by riboflavin starvation, inhibited the intraerythrocytic proliferation of
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