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<p>Cellular NAD<sup>+</sup> depletion, altered tryptophan metabolism and gut microbiome dysbiosis are associated with disease progression and unfavourable clinical outcomes in COVID-19. Here, we show that supplementing tryptophan metabolism with nicotinamide alleviates COVID-19 symptoms. We evaluate a 4-week intervention with a novel nicotinamide formulation (1,000 mg) in a prospective, double-blind, randomized, placebo-controlled trial in 900 symptomatic outpatients with PCR-proven COVID-19. In the primary analysis population of participants at risk for severe COVID-19, 57.6% of those receiving nicotinamide and 42.6% receiving placebo recover from their performance drop at week 2 (<i>P</i> = 0.004). Nicotinamide is also beneficial for returning to normal activities (<i>P</i> = 0.009). Effects on gut metagenomic signatures parallel clinical efficacy, suggesting that nicotinamide influences COVID-19-associated faecal microbiome changes. After 6 months, responders to nicotinamide in acute COVID-19 show fewer post-COVID symptoms than placebo responders (<i>P</i> = 0.010). No relevant safety signals are observed. Overall, our results show that nicotinamide leads to faster recovery of physical performance and modulates COVID-19-associated faecal microbiome changes.</p>

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Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月12日

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  • Stefan Schreiber,
  • Georg H. Waetzig,
  • Víctor A. López-Agudelo,
  • Corinna Geisler,
  • Kristina Schlicht,
  • Sina Franzenburg,
  • Romina di Giuseppe,
  • Daniel Pape,
  • Thomas Bahmer,
  • Michael Krawczak,
  • Elisabeth Kokott,
  • Josef M. Penninger,
  • Oliver Harzer,
  • Jan Kramer,
  • Tammo von Schrenck,
  • Felix Sommer,
  • Helena U. Zacharias,
  • Bernd Bokemeyer,
  • Romina di Giuseppe,
  • Wolfram Gronwald,
  • Danielle M. M. Harris,
  • Katharina Hartmann,
  • Tim Hollstein,
  • Peter J. Oefner,
  • Sandra Plachta-Danielzik,
  • Florian Tran,
  • Tammo von Schrenck,
  • Belén Millet Pascual-Leone,
  • Sofia K. Forslund,
  • Jan Heyckendorf,
  • Konrad Aden,
  • Regina Hollweck,
  • Matthias Laudes,
  • Philip Rosenstiel

摘要

Cellular NAD+ depletion, altered tryptophan metabolism and gut microbiome dysbiosis are associated with disease progression and unfavourable clinical outcomes in COVID-19. Here, we show that supplementing tryptophan metabolism with nicotinamide alleviates COVID-19 symptoms. We evaluate a 4-week intervention with a novel nicotinamide formulation (1,000 mg) in a prospective, double-blind, randomized, placebo-controlled trial in 900 symptomatic outpatients with PCR-proven COVID-19. In the primary analysis population of participants at risk for severe COVID-19, 57.6% of those receiving nicotinamide and 42.6% receiving placebo recover from their performance drop at week 2 (P = 0.004). Nicotinamide is also beneficial for returning to normal activities (P = 0.009). Effects on gut metagenomic signatures parallel clinical efficacy, suggesting that nicotinamide influences COVID-19-associated faecal microbiome changes. After 6 months, responders to nicotinamide in acute COVID-19 show fewer post-COVID symptoms than placebo responders (P = 0.010). No relevant safety signals are observed. Overall, our results show that nicotinamide leads to faster recovery of physical performance and modulates COVID-19-associated faecal microbiome changes.