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Benefit

Sleep & Circadian Rhythm

BMAL1/CLOCK-NAMPT loop and sirtuin-driven circadian control.

Preclinical only

NAD+ biosynthesis is itself a clock-controlled process: BMAL1/CLOCK drives NAMPT transcription, and the resulting NAD+ oscillation regulates SIRT1 and SIRT3 activity on circadian targets. Sleep loss depletes brain NAD+ and disrupts sirtuin-dependent metabolic rhythms, while circadian misalignment lowers NAD+ salvage capacity. Human data on NAD+ precursors and sleep outcomes remains sparse.

Key studies

  1. Science · 2009 · PMID 19286518

    Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis

    Ramsey KM, et al.

  2. Science · 2009 · PMID 19286519

    Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1

    Nakahata Y, et al.

  3. Cell Reports · 2013 · PMID 23375372

    SIRT3 reverses aging-associated degeneration

    Brown K, et al.

Editorial note

NADFaq grades evidence on a 4-tier scale based on human trial quality, sample size, reproducibility, and mechanistic plausibility. This is a conservative framework — many published benefits of NAD+ precursors rest on preclinical (rodent or cell) work that has not yet translated to humans.

How we grade evidence