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Human randomized trial

The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans

Stefan Christen, Karine Redeuil, Laurence Goulet, Maria-Pilar Giner, Isabelle Breton, Riccardo Rota, Adrien Frézal, Atiye Nazari, Pieter Van den Abbeele, Jean-Philippe Godin, Sophie Nutten, Bernard Cuenoud

Nature Metabolism · 2026 · 8(1):62–73

Study at a glance

Design
Randomized, open-label, placebo-controlled four-arm trial lasting 14 days, supplemented by ex vivo gut-fermentation and whole-blood experiments.
Population or model
Healthy adults aged 18–50 years with BMI 18.5–27 kg/m²; the modified intention-to-treat population had a mean age of 34.7 years and included 32 men and 33 women.
Sample size
67 randomized; 65 analyzed (NR n=16, NMN n=15, nicotinamide n=17, placebo n=17)
Intervention
Daily oral NR 1 g, NMN 1 g, nicotinamide 0.5 g, or placebo for 14 days.
Publication type
Randomized controlled trial
Evidence class
human-study
Research area
NAD+ precursor metabolism and microbiome
Trial registration
NCT05517122

Study endpoints

  • Primary: change from baseline in whole-blood NAD+ after 14 days
  • Acute four-hour and chronic NAD+ metabolome responses
  • Exploratory plasma and urine metabolomics
  • Adverse events and ex vivo microbiome and whole-blood metabolism

Plain-language summary

Healthy adults were randomly assigned to NMN, nicotinamide riboside, nicotinamide, or placebo for 14 days. NMN and nicotinamide riboside approximately doubled whole-blood NAD+, while nicotinamide did not. The trial measured biomarkers rather than health outcomes. Laboratory experiments suggested that gut microbes may convert NMN and nicotinamide riboside into other forms, but that mechanism was not directly proven inside participants.

Key findings

After 14 days, NMN and nicotinamide riboside approximately doubled whole-blood NAD+ compared with placebo; nicotinamide did not. NMN and NR did not produce an acute four-hour circulating NAD-metabolome response, whereas nicotinamide caused a transient acute response. NADH, NADP+, and NADPH did not change significantly. Reported probable product-related events were abdominal pain in placebo, hypotension with NR, and headache with NMN. Ex vivo experiments showed microbial conversion of NMN and NR toward nicotinic acid and supported a possible gut-dependent pathway.

Limitations

The intervention lasted only 14 days and each arm was small. Treatment was open-label, and the primary outcome was a biomarker rather than a clinical endpoint. Two randomized participants were excluded after receiving the wrong product. The microbiome mechanism relied heavily on ex vivo fermentation and whole-blood assays, which do not prove the same pathway operates in vivo. Long-term efficacy and safety were not tested.

Funding and transparency

Funding

Not stated in the publication.

Competing interests

Stefan Christen, Karine Redeuil, Laurence Goulet, Maria-Pilar Giner, Isabelle Breton, Riccardo Rota, Adrien Frézal, Atiye Nazari, Jean-Philippe Godin, and Sophie Nutten were employees of Nestlé Research. Bernard Cuenoud was an employee of Nestlé Health Science. Pieter Van den Abbeele was an employee of Cryptobiotix SA.

HealthspanX observation

The authors were employees of Nestlé Research, Nestlé Health Science, or Cryptobiotix SA; the proposed gut-microbiome mechanism was supported mainly by ex vivo experiments.

Interpretive weight

Moderate

Randomization, a placebo arm, and a prespecified NAD+ biomarker strengthen the result, but the trial was open-label, short, and not designed to show clinical outcomes.

This record summarizes a publication; it is not medical advice or a claim that a HealthspanX product reproduces the study's results. Report a correction.

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