Study analysis · Alzheimer's & Dementia · 2026
NAD+ booster fails to boost memory in MCI trial, but a surprising brain blood flow clue emerges
A vitamin-like pill (NR) safely doubled a key energy molecule in the blood of older adults with mild memory loss, but it didn't clearly improve memory or brain blood flow after 12 weeks.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
In simple terms
This study gave one group of people a vitamin-like supplement and another group a fake pill. They wanted to see if the supplement could help with memory and blood flow in the brain. After 12 weeks, memory and overall brain blood flow were not better in the supplement group. But there were small hints that blood flow increased in one tiny part of the brain, but we need bigger studies to be sure.
What’s the bottom line?
Researchers gave a supplement called nicotinamide riboside (NR) or a placebo to older adults with mild memory problems for 12 weeks. NR is a form of vitamin B3 that helps cells make energy. They wanted to see if it improved memory and brain blood flow.
How strong is this study?
This study was designed like a fair test: neither the participants nor the doctors knew who got the real pill or the fake pill. That helps make sure the results are trustworthy. But only 42 people finished the study, which is a small number, so the findings might not apply to everyone. Also, because the researchers looked at many things without special corrections, some of the small hints they found might just be by chance.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
80 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=42)+3.8/20
- Follow-up+10/10
100 / 100
77 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervalsno confidence intervals
- Pre-registration+15/15
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 575 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. Although this is an RCT, it is a phase II pilot study with a small sample size (n=42) and was not powered to detect definitive effects on clinical outcomes. The primary and secondary endpoints were not statistically significant, and exploratory findings are hypothesis-generating. Therefore, causal claims are theoretically supported by the design but are limited by the study's pilot nature and lack of significant primary results.
Moderate COI
Moderate conflicts that may influence study outcomes
Study testing NR supplied by Niagen Bioscience (ChromaDex); no other conflicts declared.
Funders
Conflict Details
Niagen Bioscience (ChromaDex): Provided study intervention under Material Transfer Agreement
Independent Analysis Safeguards
- Double-blind, randomized, placebo-controlled design
- Data and Safety Monitoring Board (DSMB) oversight
- Blinded biostatistician
Text appears to be incomplete; conflict of interest and funding sections may be present in the full paper.
Key takeaways
- 01
NR doubled a key energy molecule (NAD+) in the blood, but memory and overall brain blood flow did not improve significantly.
- 02
However, some exploratory measures showed possible increases in blood flow in the hippocampus, a memory-related brain region.
- 03
The improvements in memory and brain blood flow were not strong enough to be considered real effects in this small study.
- 04
The results are not clinically meaningful yet, but they suggest that longer or larger studies might find benefits.
Surprising findings
- NR did not improve total cerebral blood flow or blood pressure, despite previous studies suggesting vascular benefits.Earlier work by the same group found NR lowered blood pressure and arterial stiffness in older adults. This study's null results may be due to lower baseline blood pressure or shorter duration.
- Exploratory hippocampal CBF increase contrasts with another trial that found reduced CBF in the default mode network.Two similar trials found opposite effects on brain blood flow. Differences in dosing schedule and participant demographics (Hispanic vs. predominantly White) might explain the discrepancy.
Practical takeaways
If you're considering NR for cognitive health, wait for larger confirmatory trials. The current evidence does not support its use for memory improvement.
NR may still have vascular benefits in people with higher baseline blood pressure, but this study didn't test that subgroup.
low confidenceWhy this study matters
NR is safe and doubles NAD+
Over 12 weeks, 1000 mg/day NR doubled blood NAD+ levels in older adults with aMCI. Adherence was 85%, and adverse events were similar to placebo. No serious side effects occurred.
This confirms that oral NR can effectively raise NAD+ in a vulnerable population, which is a prerequisite for any future brain benefits.
No cognitive boost – but a trend
Primary cognitive outcomes (CVLT-III, WMS-IV, NIH Toolbox) showed no significant improvement. However, delayed recall on the Logical Memory subtest had a moderate effect size (d=0.607, p=0.062) – not significant but hinting at possible benefit.
The trend suggests that longer or larger trials might detect real cognitive effects, keeping hope alive.
Hippocampal blood flow may increase
Exploratory analyses showed a significant increase in left hippocampal CBF in the NR group. This was not corrected for multiple comparisons, so it's hypothesis-generating. Total CBF did not change significantly.
The hippocampus is critical for memory, so improved blood flow there could be a mechanism for future cognitive benefits.
Want the whole report?
Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.
Overview
What the study found
The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Researchers gave a supplement called nicotinamide riboside (NR) or a placebo to older adults with mild memory problems for 12 weeks. NR is a form of vitamin B3 that helps cells make energy. They wanted to see if it improved memory and brain blood flow.
Research results
NR doubled a key energy molecule (NAD+) in the blood, but memory and overall brain blood flow did not improve significantly. However, some exploratory measures showed possible increases in blood flow in the hippocampus, a memory-related brain region.
What this means - more context
The improvements in memory and brain blood flow were not strong enough to be considered real effects in this small study. The results are not clinically meaningful yet, but they suggest that longer or larger studies might find benefits.
To evaluate safety, tolerability, and preliminary efficacy of nicotinamide riboside (NR) supplementation (1000 mg/day for 12 weeks) on cognitive function and cerebral blood flow (CBF) in older adults with amnestic mild cognitive impairment (aMCI).
In this phase-II pilot RCT, 42 older adults with aMCI completed the study. NR doubled blood NAD+ levels but did not significantly improve cognitive function (primary outcome), total CBF, or blood pressure. Exploratory analyses suggested potential increases in regional CBF, particularly in the hippocampus, and non-significant trends in delayed recall and aortic augmentation index. NR was safe and well-tolerated.
Methods Used
Double-blind, randomized, placebo-controlled pilot trial over 12 weeks. 52 participants randomized, 42 completed (NR=22, placebo=20). NR dose 1000 mg/day (500 mg b.i.d.). Primary outcome: cognitive function (CVLT-III, WMS-IV, NIH Toolbox). Secondary: total CBF via pCASL MRI, blood pressure, arterial stiffness. Exploratory: regional CBF and pulse wave analysis.
Main Finding
NR did not significantly improve cognitive function, total CBF, or cardiovascular measures compared to placebo. Exploratory analysis showed a significant increase in left hippocampal CBF (not corrected for multiple comparisons) and non-significant trends in delayed recall (d=0.607, p=0.062) and aortic augmentation index (d=0.628, p=0.054).
Confidence Level
Moderate to low. Small sample size, pilot design, exploratory findings uncorrected for multiple comparisons, and only ~30% of participants had biomarker-confirmed Alzheimer's pathology limit reliability. Results are hypothesis-generating.
Study Flags
Red Flags
- •Small sample size (42 completers) limits statistical power and generalizability.
- •Only ~30% of participants had biomarker-confirmed Alzheimer's pathology, introducing heterogeneity.
- •Exploratory findings (e.g., hippocampal CBF) were not corrected for multiple comparisons, increasing risk of false positives.
Surprising Findings
NR did not improve total cerebral blood flow or blood pressure, despite previous studies suggesting vascular benefits.
Earlier work by the same group found NR lowered blood pressure and arterial stiffness in older adults. This study's null results may be due to lower baseline blood pressure or shorter duration.
Practical Takeaways
If you're considering NR for cognitive health, wait for larger confirmatory trials. The current evidence does not support its use for memory improvement.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 575 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
High probability
on the GRADE evidence scale
This study gave one group of people a vitamin-like supplement and another group a fake pill. They wanted to see if the supplement could help with memory and blood flow in the brain. After 12 weeks, memory and overall brain blood flow were not better in the supplement group. But there were small hints that blood flow increased in one tiny part of the brain, but we need bigger studies to be sure.
Moderate conflicts detected — such as industry funding with partial involvement. A meaningful penalty has been applied.
Strengths
- Randomized, double-blind, placebo-controlled design.
- Good adherence and tolerability.
- Objective biomarker confirmation of NAD+ elevation.
Weaknesses
- Small sample size (n=42 completers) limits statistical power.
- Pilot study not powered for definitive efficacy.
- No correction for multiple comparisons in exploratory analyses.
Methodology
Evidence Keywords
Statistical Reporting
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Researchers gave a supplement called nicotinamide riboside (NR) or a placebo to older adults with mild memory problems for 12 weeks. NR is a form of vitamin B3 that helps cells make energy. They wanted to see if it improved memory and brain blood flow.
Research results
NR doubled a key energy molecule (NAD+) in the blood, but memory and overall brain blood flow did not improve significantly. However, some exploratory measures showed possible increases in blood flow in the hippocampus, a memory-related brain region.
What this means - more context
The improvements in memory and brain blood flow were not strong enough to be considered real effects in this small study. The results are not clinically meaningful yet, but they suggest that longer or larger studies might find benefits.
To evaluate safety, tolerability, and preliminary efficacy of nicotinamide riboside (NR) supplementation (1000 mg/day for 12 weeks) on cognitive function and cerebral blood flow (CBF) in older adults with amnestic mild cognitive impairment (aMCI).
In this phase-II pilot RCT, 42 older adults with aMCI completed the study. NR doubled blood NAD+ levels but did not significantly improve cognitive function (primary outcome), total CBF, or blood pressure. Exploratory analyses suggested potential increases in regional CBF, particularly in the hippocampus, and non-significant trends in delayed recall and aortic augmentation index. NR was safe and well-tolerated.
Methods Used
Double-blind, randomized, placebo-controlled pilot trial over 12 weeks. 52 participants randomized, 42 completed (NR=22, placebo=20). NR dose 1000 mg/day (500 mg b.i.d.). Primary outcome: cognitive function (CVLT-III, WMS-IV, NIH Toolbox). Secondary: total CBF via pCASL MRI, blood pressure, arterial stiffness. Exploratory: regional CBF and pulse wave analysis.
Main Finding
NR did not significantly improve cognitive function, total CBF, or cardiovascular measures compared to placebo. Exploratory analysis showed a significant increase in left hippocampal CBF (not corrected for multiple comparisons) and non-significant trends in delayed recall (d=0.607, p=0.062) and aortic augmentation index (d=0.628, p=0.054).
Confidence Level
Moderate to low. Small sample size, pilot design, exploratory findings uncorrected for multiple comparisons, and only ~30% of participants had biomarker-confirmed Alzheimer's pathology limit reliability. Results are hypothesis-generating.
Study Flags
Red Flags
- •Small sample size (42 completers) limits statistical power and generalizability.
- •Only ~30% of participants had biomarker-confirmed Alzheimer's pathology, introducing heterogeneity.
- •Exploratory findings (e.g., hippocampal CBF) were not corrected for multiple comparisons, increasing risk of false positives.
Surprising Findings
NR did not improve total cerebral blood flow or blood pressure, despite previous studies suggesting vascular benefits.
Earlier work by the same group found NR lowered blood pressure and arterial stiffness in older adults. This study's null results may be due to lower baseline blood pressure or shorter duration.
Practical Takeaways
If you're considering NR for cognitive health, wait for larger confirmatory trials. The current evidence does not support its use for memory improvement.
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 575 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Human RCT
Subject
High probability
on the GRADE evidence scale
This study gave one group of people a vitamin-like supplement and another group a fake pill. They wanted to see if the supplement could help with memory and blood flow in the brain. After 12 weeks, memory and overall brain blood flow were not better in the supplement group. But there were small hints that blood flow increased in one tiny part of the brain, but we need bigger studies to be sure.
Moderate conflicts detected — such as industry funding with partial involvement. A meaningful penalty has been applied.
Strengths
- Randomized, double-blind, placebo-controlled design.
- Good adherence and tolerability.
- Objective biomarker confirmation of NAD+ elevation.
Weaknesses
- Small sample size (n=42 completers) limits statistical power.
- Pilot study not powered for definitive efficacy.
- No correction for multiple comparisons in exploratory analyses.
Methodology
Evidence Keywords
Statistical Reporting
Scoring
How strong is this study?
This study was designed like a fair test: neither the participants nor the doctors knew who got the real pill or the fake pill. That helps make sure the results are trustworthy. But only 42 people finished the study, which is a small number, so the findings might not apply to everyone. Also, because the researchers looked at many things without special corrections, some of the small hints they found might just be by chance.
40 / 100
- COI disclosure+40/40
- Data availabilitydata not shared
- Code availabilitycode not shared
80 / 100
- Randomization+20/20
- Blinding+15/15
- Control group+15/15
- Sample size (n=42)+3.8/20
- Follow-up+10/10
100 / 100
77 / 100
- P-values+15/15
- Effect size+20/20
- Confidence intervalsno confidence intervals
- Pre-registration+15/15
Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.
Where it sits
RCT reviewsReviews of RCTs (Meta-analyses)
Max 100Randomized TrialsRandomized Trials
Max 90Reviews of Cohort StudiesReviews of Cohort Studies
Max 85Cohort StudiesCohort Studies
Max 72Reviews of Case-Control StudiesReviews of Case-Control Studies
Max 63Case-Control StudiesCase-Control Studies
Max 58Cross-Sectional & Case SeriesCross-Sectional & Case Series
Max 50Expert OpinionExpert Opinion
Max 575 / 100
Probability of being correct
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
This design can establish causation. Although this is an RCT, it is a phase II pilot study with a small sample size (n=42) and was not powered to detect definitive effects on clinical outcomes. The primary and secondary endpoints were not statistically significant, and exploratory findings are hypothesis-generating. Therefore, causal claims are theoretically supported by the design but are limited by the study's pilot nature and lack of significant primary results.
Moderate COI
Moderate conflicts that may influence study outcomes
Study testing NR supplied by Niagen Bioscience (ChromaDex); no other conflicts declared.
Funders
Conflict Details
Niagen Bioscience (ChromaDex): Provided study intervention under Material Transfer Agreement
Independent Analysis Safeguards
- Double-blind, randomized, placebo-controlled design
- Data and Safety Monitoring Board (DSMB) oversight
- Blinded biostatistician
Text appears to be incomplete; conflict of interest and funding sections may be present in the full paper.