George Sutphin returns to the podcast after a popular March 2024 interview on 3HAA and NAD+. In this episode, Matt and George explore recent findings that NAD+ supplements, often marketed for boosting levels of this key coenzyme involved in DNA repair and stress responses, may also increase molecular markers linked to kidney damage. They discuss the NAD+ signalling pathway, potential mechanisms behind the damage, and future research directions. George, now an Assistant Professor at the University of Arizona, leads a lab investigating longevity, kynurenine-based interventions, and environmental factors in ageing.

Key Points:

George Sutphin discuss the potential risks of oral NMN supplementation for boosting NAD+ levels, including its link to kidney damage. He and Matt also delve into the NAD+ signalling pathway, investigate potential mechanisms underlying the damage, and discuss future research directions.

• Exploring NMN and Kidney Health: The episode discusses a study on nicotinamide mononucleotide (NMN), an NAD+ precursor, showing potential kidney inflammation in aged mice, prompting a cautionary outlook on NMN supplementation.
• NAD+ Precursors and Ageing: NAD+ levels, vital for cellular metabolism and energy, naturally decline with age. NMN, NR (nicotinamide riboside), and other NAD+ precursors are popular supplements, but their long-term effects, especially in older individuals, remain uncertain.
• Study Design: The focus was on aged mice treated with NMN, an antioxidant peptide (Elam/SS31), or a combination of both. While previous studies showed benefits for heart and liver health, the same dose of NMN raised concerns about kidney inflammation.
• Signs of Kidney Inflammation: Elevated markers of kidney inflammation, particularly the cytokine IL-1β, were found in NMN-treated aged mice. These signs were mitigated when combined with the Elam treatment.
• Potential Metabolic Overload: Researchers observed elevated levels of methylated by-products of NMN metabolism (methyl nicotinamide), which may contribute to kidney damage, especially in aged animals.
• Caution in Human Use: The findings urge caution for NAD+ precursor supplements, especially for older individuals or those with compromised kidney function, and highlight the need for more comprehensive human clinical trials.