Vitamin A5: Evidence, Definitions, Gaps, and Future Directions

With the emergence of a new vitamin concept-vitamin A5-it is essential to first clarify the basic definition of vitamins, particularly vitamin A. This article summarizes the foundational concepts and definitions of vitamins with particular relevance to the discovery, establishment, and categorization of new vitamin concepts. Vitamin A5 was discovered 80 years after the last vitamin was identified. It serves as an umbrella term for the dietary precursors 9-cis-β,β-carotene and 9-cis-13,14-dihydroretinol for the endogenous activator of the nuclear hormone receptor RXR, 9-cis-13,14-dihydroretinoic acid. However, several questions arise: Which criteria are typically used to identify a substance as a vitamin? How does vitamin A5 fit into the sometimes misleading definition of vitamin A? This review summarizes key findings and provides a comprehensive assessment of the current understanding, concluding that (a) vitamin A5 is a newly identified micronutrient that plays an important role in the prevention of diet-related diseases and (b) vitamin A5 is an important micronutrient that provides a plausible, mechanistic explanation for why a Western lifestyle diet low in vegetables and especially leafy vegetables can lead to a high prevalence of Western-lifestyle diseases, particularly neurological diseases and poor mental health.