Nicotinamide riboside did not improve cognition in a 12-week trial
In a 12-week randomized trial, supplementation doubled blood nicotinamide adenine dinucleotide from baseline but did not improve cognition or total brain blood flow versus placebo.
12 weeks, double-blind, placebo-controlled, sample size calculated, registered NCT03482167
Limit: Only 42 participants completed the study: 22 on NR and 20 on placebo
Stake: Niagen Biosciences supplied the product tested.
Edited by Boris Djordjevic · AgingResearch.News
Of 52 adults aged 65 and older with amnestic mild cognitive impairment—memory difficulties without dementia—42 completed a 12-week randomized, double-blind, placebo-controlled trial, including 26 women and 16 men. Participants took 500 milligrams of nicotinamide riboside twice daily or placebo. The supplement doubled blood nicotinamide adenine dinucleotide, a molecule involved in cellular energy use. It did not improve cognitive function, the primary outcome, total brain blood flow or blood pressure versus placebo. Exploratory analyses suggested potential increases in regional brain blood flow, particularly in the hippocampus, a brain region involved in memory.
No serious adverse events were reported. Reported events included nausea, diarrhea and mild headaches, with similar types and frequencies in both groups. Four participants stopped because of adverse events: one taking the supplement because of low estimated kidney filtration, and three taking placebo because of flatulence, sleep disturbance, heart palpitations or chest pain.
Why it matters
Declining nicotinamide adenine dinucleotide may elevate the risk of Alzheimer's disease. The authors call for larger, longer trials to determine whether supplementation can slow cognitive decline.
Caveats
The statistical analysis evaluated only the 42 participants who completed the trial rather than the full randomized group. Findings from this small 12-week pilot study in older adults with memory impairment may not apply to cognitively healthy individuals or over longer treatment periods.
From the paper
- Participants
Among those consented, 52 participants (33F/19 M) were randomized to treatment, and 42 participants (26F/16 M) completed the intervention, achieving 72% of our completion target.
- Who took part
Community‐dwelling older adults (aged ≥ 65 years) with aMCI were recruited through the Delaware Center for Cognitive Aging Research (DECCAR), as previously described …
- Duration
The study design was a 12‐week double‐blind, randomized, placebo‐controlled parallel‐arm clinical trial of NR (500 mg b.i.d.) in older adults with aMCI.
- Harms
No serious adverse events were reported in either the NR or placebo groups.
- Limitation
Participants were recruited solely based on a research diagnosis of aMCI using behavioral assessments, as this study was initiated prior to the widespread availability of reliable blood biomarkers for AD pathology.
- Cognitive function
However, there were no group‐by‐time interactions indicating no significant improvement with NR over the 12‐week intervention period.
- NAD+
Consistent with prior studies of NR supplementation reporting an increase in NAD⁺ metabolites or catabolites,,,,, we observed a robust increase in blood NAD⁺ concentration in the NR group compared to placebo, with levels nearly doubling from baseline.
- Total CBF
Total CBF (secondary endpoint) was not significantly improved in the NR group relative to placebo.
- Blood pressure
NR supplementation was associated with modest reductions in blood pressure and arterial stiffness (secondary endpoints), although these changes were not statistically significant.
Quoted word for word from the full text on PubMed Central.
- Nicotinamide riboside
- NAD+ metabolism
- Amnestic mild cognitive impairment
- Mild cognitive impairment
- Blood pressure
- Humans
The paper
University of Delaware; Thomas Jefferson University
Alzheimer's & Dementia, Jul 2026, Open access
Presented at AAIC 2025 as an abstract
