NAD⁺ Precursors: A Questionable Redundancy

The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD⁺ bioavailability. Among them, the dietary supplementation with NAD⁺ precursors-classically known as vitamin B3-has received most of the attention. Multiple molecules can act as NAD⁺ precursors through independent biosynthetic routes. Interestingly, eukaryote organisms have conserved a remarkable ability to utilize all of these different molecules, even if some of them are scarcely found in nature. Here, we discuss the possibility that the conservation of all of these biosynthetic pathways through evolution occurred because the different NAD⁺ precursors might serve specialized purposes.