A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment.
Level 2 - randomized trial
Individual randomized placebo-controlled trial
PubMed 37994989 · doi:10.1007/s11357-023-00999-9
What was done
Twenty older adults with mild cognitive impairment were randomized to receive placebo or nicotinamide riboside titrated to 1 g/day over a 10-week duration. The primary outcome was change from baseline in Montreal Cognitive Assessment scores. Secondary outcomes included cerebral blood flow, blood NAD+ levels, additional neurocognitive, psychometric, and physical performance tests, and exploratory peripheral blood mononuclear cell DNA methylation.
What was found
Target dosing led to a 2.6-fold increase in blood NAD+ in the nicotinamide riboside group (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse event reporting. Montreal Cognitive Assessment and other neurocognitive and psychometric metrics remained stable throughout the study. Nicotinamide riboside reduced cerebral blood flow in the default mode network (p = 0.013, μ = 0.92, 95% CI [0.23, 1.62]) and left inferior parietal lobe (p = 0.009, μ = 1.66, 95% CI [0.5, 2.82]), though statistical significance would not withstand multiple comparisons correction. Walking speed improved across the study in the placebo group (p = 0.0402) but not the nicotinamide riboside group (p = 0.4698). Global methylation analyses showed modest increases in DNA methylation and concomitant reductions in epigenetic age via PhenoAge and GrimAge.
Why it matters
This pilot study demonstrates that oral nicotinamide riboside safely elevates circulating NAD+ in older adults with mild cognitive impairment. It provides dosing and feasibility data for future, larger clinical trials evaluating cognitive outcomes.
Limits
The trial had a very small sample size of 20 participants and a short 10-week duration. Observed cerebral blood flow differences did not survive correction for multiple comparisons, and DNA methylation findings were exploratory.
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