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Objective  Thousands of years after dietary therapy was proposed to treat seizures, how alterations in metabolism relates to epilepsy remains unclear, and metabolism‐based therapies are not always effective.    Methods  We consider the state of the science in metabolism‐based therapies for epilepsy across the research lifecycle from basic to translational to clinical studies.    Results  This analysis creates a conceptual framework for creative, rigorous, and transparent research to benefit people with epilepsy through the understanding and modification of metabolism.    Interpretation  Despite intensive past efforts to evaluate metabolism‐based therapies for epilepsy, distinct ways of framing a problem offer the chance to engage different mindsets and new (or newly applied) technologies. A comprehensive, creative, and inclusive problem‐directed research agenda is needed, with a renewed and stringent adherence to rigor and transparency across all levels of investigation.

Metabolism‐based therapies for epilepsy: new directions for future cures