ScopeThe reported ability to modulate the production of the wild‐type transcript in cells bearing the splice‐altering familial dysautonomia (FD)‐causing mutation in the IKBKAP gene prompted an evaluation of the impact of commonly consumed nutraceuticals on the splicing of this transcript.Methods and resultsScreening efforts revealed the ability of the isoflavones, genistein, and daidzein, to impact splicing and increase the production of the wild‐type, exon‐20‐containing, transcript, and the full‐length IKBKAP‐encoded IΚB kinase complex associated protein(IKAP) in FD‐derived cells. Genistein was also found to impact splicing in neuronal cells, a cell type profoundly impacted by FD. The simultaneous exposure of FD‐derived cells to genistein and epigallocatechin gallate (EGCG) resulted in the almost exclusive production of the exon‐20‐containing transcript and the production of wild‐type amounts of IKAP protein.ConclusionThis study represents the first demonstration that the isoflavones, genistein and daidzein, possess splice‐altering capabilities and that simultaneous treatment with genistein and EGCG reverses the splice‐altering impact of the FD‐causing mutation. These findings support the clinical evaluation of the therapeutic impact of the combined administration of these two commonly consumed nutraceuticals on this patient population and suggest a broader evaluation of the impact of these nutraceuticals on the in vivo RNA splicing process.