Vitamin A5/X as a critical food factor for good mental health and prevention of neurological diseases

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A healthy and balanced diet is an important factor to assure a good functioning of the central and peripheral nervous system. Recently, vitamin A5/X, as a new concept of a vitamin, was identified that functions as the nutritional precursor for enabling retinoid X receptor (RXR)-mediated signaling. The active form of vitamin A5/X, 9- cis -13,14-dehydroretinoic acid (9CDHRA), induces RXR-activation, acting as the central switch for enabling various heterodimer-RXR-signaling cascades. This includes various partner heterodimers such as the fatty acid and eicosanoid receptors/peroxisome proliferator–activated receptors (PPARs)-, the cholesterol receptors/liver X receptors (LXRs)-, as well as the vitamin D receptor (VDR)-, and also the vitamin A(1) receptors/retinoic acid receptors (RARs). Thus, nutritional supply of vitamin A5/X might be a general nutritional-dependent switch for enabling this very large cascade of hormonal signaling pathways and could be highly important to guarantee an overall organism homeostasis. A new vitamin A5/X/provitamin A5/X concept is conceptualized in parallel to the vitamin A(1)/provitamin A(1) concept for daily dietary intake and towards dietary guidelines, with a focus on the existing national and international regulations for the physiological and nutritional relevance of vitamin A5/X. RXR-mediated signaling was shown to be dependent on vitamin A5/X with direct effects for beneficial physiological and neuro-protective functions mediated systemically or directly in the brain. Through control of dopamine signaling, amyloid β-clearance, neuro-protection and neuro-inflammation, the vitamin A5/X – RXR – RAR – vitamin A(1)-signaling might be “one of” or even “the” critical factor(s) necessary for good mental health, healthy brain aging as well as preventing drug addiction and prevention of a large array of nervous system diseases. Likewise, vitamin A5/X – RXR – non-RAR-dependent signaling relevant for myelination/re-myelination and phagocytosis/brain cleanup will contribute to such regulations, too. In summary, the basic science, plausible connections, nutritional/pharmacological expert recommendations and nutritional guidelines especially targeting the nervous system are discussed. Publication History Article published online: 22 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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