A landmark human clinical trial published in Nature Metabolism demonstrates that commonly supplemented NAD⁺ precursors follow fundamentally different metabolic routes after ingestion, challenging one-size-fits-all approaches to supplementation. Researchers compared nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide in healthy volunteers, revealing distinct absorption patterns and systemic effects. Nicotinamide produces rapid but transient NAD⁺ elevation through upper-gut salvage metabolism, while nicotinamide riboside and nicotinamide mononucleotide take a slower route through the colon, where gut microbiota convert them to nicotinic acid. Notably, the latter two precursors trigger sustained NAD⁺ increases and stimulate short-chain fatty acid production, suggesting dual benefits for cellular energy and intestinal health. These findings underscore the critical role of individual metabolism and microbiome composition in determining supplement efficacy.
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