Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19
- Stefan Schreiber
- G. H. Waetzig
- V. López-Agudelo
- Corinna Geisler
- Kristina Schlicht
- S. Franzenburg
- R. di Giuseppe
- D. Pape
- T. Bahmer
- M. Krawczak
- E. Kokott
- J. Penninger
- O. Harzer
- J. Kramer
- T. von Schrenck
- Felix Sommer
- Helena U. Zacharias
- Bernd Romina Wolfram Danielle M. M. Katharina Tim Peter Bokemeyer di Giuseppe Gronwald Harris Hartmann Hol
- Bernd Bokemeyer
- W. Gronwald
- D. Harris
- K. Hartmann
- Tim Hollstein
- Peter J. Oefner
- S. Plachta-Danielzik
- Florian Tran
- Belén Millet Pascual-Leone
- S. Forslund
- Jan Heyckendorf
- K. Aden
- R. Hollweck
- Matthias Laudes
- P. Rosenstiel
What this study found
Nicotinamide improved acute COVID-19 recovery, with the main benefit seen in resolution of reduced physical performance at week 2. In the RFITT population, 57.6% of nicotinamide-treated participants versus 42.6% of placebo-treated participants achieved resolution of performance drop (OR 1.33, 95% CI 1.03 to 1.70; P = 0.004; NNT = 7). It also improved ability to perform normal activities at week 2 and reduced shortness of breath in baseline-affected participants (P = 0.012), while fatigue was similar between groups. Six-month post-COVID symptom burden was not improved overall, but responders…
- Study & population
- Randomized, placebo-controlled trial in nonhospitalized adults with PCR-confirmed symptomatic mild-to-moderate COVID-19 in Germany.
- Intervention
- Nicotinamide was given orally as 1,000 mg/day for 4 weeks, split as 500 mg immediate-release nicotinamide plus 500 mg controlled-ileocolonic-release nicotinamide (Setamer®).
- Key limitation
- The trial was relatively short and enrolled outpatients with mild-to-moderate disease, so generalizability to hospitalized patients or more severe COVID-19 is limited.
View source
Open PDFOriginal abstract
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. In a prospective, double-blind, randomized, placebo-controlled trial, supplementation with a combination of conventional and gut-targeted nicotinamide was safe and effective in ameliorating COVID-19 symptoms.