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<p>This study examines the biological and clinical relevance of NAD⁺ supplementation using a combined review and mathematical modelling approach. NAD⁺ plays a central role in cellular energy metabolism, redox balance, and signaling pathways linked to aging, neurodegeneration, and metabolic health. Current evidence shows that oral NAD⁺ precursors such as nicotinamide riboside and nicotinamide mononucleotide can increase circulating NAD⁺ levels, although their clinical benefits remain variable and context-dependent. Intravenous NAD⁺ administration is less well characterized and lacks robust clinical validation. The modelling framework presented here highlights that NAD⁺ responses are nonlinear and influenced by factors such as dose, age, metabolic state, and route of administration. Rather than following a simple dose–response relationship, NAD⁺ supplementation appears to operate within a complex regulatory system involving feedback mechanisms and biological saturation. Overall, these findings emphasize the need for cautious interpretation of current data and for well-designed clinical studies to define effective and safe therapeutic strategies.</p>

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NAD⁺ biology and supplementation: From mechanisms to clinical perspectives

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月23日

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  • Sergio Pandolfi,
  • Charlye Ghezzi,
  • Geir Björklund,
  • Marco Metalla,
  • Francesco Maria Paone,
  • Salvatore Chirumbolo

摘要

This study examines the biological and clinical relevance of NAD⁺ supplementation using a combined review and mathematical modelling approach. NAD⁺ plays a central role in cellular energy metabolism, redox balance, and signaling pathways linked to aging, neurodegeneration, and metabolic health. Current evidence shows that oral NAD⁺ precursors such as nicotinamide riboside and nicotinamide mononucleotide can increase circulating NAD⁺ levels, although their clinical benefits remain variable and context-dependent. Intravenous NAD⁺ administration is less well characterized and lacks robust clinical validation. The modelling framework presented here highlights that NAD⁺ responses are nonlinear and influenced by factors such as dose, age, metabolic state, and route of administration. Rather than following a simple dose–response relationship, NAD⁺ supplementation appears to operate within a complex regulatory system involving feedback mechanisms and biological saturation. Overall, these findings emphasize the need for cautious interpretation of current data and for well-designed clinical studies to define effective and safe therapeutic strategies.