NAD + precursor supplementation in human ageing: clinical evidence and challenges.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing existing preclinical and clinical literature without systematic review methodology.
PubMed 41083806 · doi:10.1038/s42255-025-01387-7
What was done
The authors reviewed published human clinical evidence evaluating whether NAD+ concentrations decline with chronological age and assessed the tissue-specific metabolic outcomes of NAD+ precursor supplementation in human trials.
What was found
The abstract reports no quantitative metrics or effect sizes. The review found that evidence for age-related NAD+ decline in humans is confirmed in only a limited number of studies, clinical trials evaluating NAD+ precursor supplementation have demonstrated limited therapeutic efficacy, and direct extrapolation from preclinical rodent models to human tissue metabolism remains unsupported by robust data.
Why it matters
This review highlights a substantial translational gap between robust preclinical rodent studies and human clinical trials, cautioning against assuming that NAD+ precursor supplementation reliably combats human aging phenotypes.
Limits
As a narrative review, it lacks a documented systematic search protocol or quantitative meta-analytic pooling. Available human data across different target tissues are sparse, sample sizes in underlying primary trials are historically small, and the abstract provides no specific patient characteristics, dosages, or trial counts.
Cited by
- contradicts By age 50, humans have approximately half the levels of NAD compared to when they were young.