You may have seen headlines or social media posts claiming that restoring NAD⁺ levels can reverse Alzheimer’s disease, restore cognition, or replace medication.
These claims are largely based on a recent, high-quality preclinical study published in Cell Reports Medicine. The biology is interesting — but much of the public conversation is moving well ahead of the human evidence.
Before unpacking the research, it helps to clarify what NAD⁺ actually is.
What is NAD⁺?
NAD⁺ stands for nicotinamide adenine dinucleotide. It is a coenzyme found in all living cells and is essential for basic cellular function.
NAD⁺ plays a central role in:
Cellular energy production (helping convert food into usable energy, ATP)
Mitochondrial function
DNA repair processes
Cellular stress and repair pathways
Because NAD⁺ is involved in energy metabolism and cellular repair, and because levels appear to decline with age, it has become a target of interest in ageing and brain health research.
This biological importance, however, does not automatically translate into clinical benefit from supplementation.
The study behind the headlines
The paper driving much of the recent discussion is:
Chaubey et al., Cell Reports Medicine (2025/2026)
Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain
This was a rigorous preclinical study using advanced mouse models of Alzheimer’s disease.
What the researchers did
The investigators:
Used two established Alzheimer’s disease mouse models (5xFAD and PS19)
Initiated treatment after cognitive impairment and pathology were already present
Administered P7C3-A20, a compound designed to restore physiological NAD⁺ homeostasis
Measured cognition, synaptic plasticity, neuroinflammation, oxidative stress, BBB integrity, and molecular overlap with human post-mortem Alzheimer’s tissue
What the study showed
In mice:
Alzheimer’s disease was associated with marked disruption of brain NAD⁺ homeostasis
Greater NAD⁺ disruption correlated with worse cognitive and neurological outcomes
Restoring NAD⁺ homeostasis improved memory, learning, synaptic plasticity, and markers of brain resilience — even in advanced disease
This is strong animal data and a valuable contribution to understanding Alzheimer’s disease biology.
What the human data tells us
Human post-mortem brain analyses showed:
Reduced expression of NAD⁺-synthesising enzymes in Alzheimer’s disease
Increased expression of NAD⁺-consuming enzymes
Preservation of NAD⁺ homeostasis in individuals with Alzheimer’s pathology but no dementia
This suggests NAD⁺ dysregulation is associated with Alzheimer’s pathology in humans.
It does not demonstrate that increasing NAD⁺ improves symptoms, slows progression, or changes outcomes in living people.
Introducing an important concept: MCID
This is where minimal clinically important difference (MCID) becomes critical.
MCID refers to:
The smallest change in a biological marker or outcome that a patient would actually notice or benefit from.
In other words:
A change can be statistically significant
A biomarker can move in the “right direction”
And yet have no meaningful impact on symptoms, function, or quality of life
Why MCID matters for NAD⁺
In human studies, NAD⁺ supplementation has shown that:
Blood NAD⁺ levels can increase
What has not been established:
The MCID for NAD⁺ in humans
The level of increase required to improve cognition, function, or disease trajectory
Whether changes in blood NAD⁺ reflect changes in brain NAD⁺
Whether any observed changes translate into outcomes patients care about
In simple terms:
Raising NAD⁺ levels may look impressive on a graph, but without an established MCID, we don’t know if it actually does anything clinically meaningful.
Biomarkers are not outcomes
This is a crucial distinction.
NAD⁺ is a biochemical marker, not a clinical endpoint.
A biomarker can change without:
Improving memory
Preserving independence
Reducing disease progression
Enhancing quality of life
Until we can show that increasing NAD⁺ leads to improvements in outcomes that matter to people, the clinical relevance remains unknown.
Side effects and cost still matter
Even if a supplement reliably increases NAD⁺ levels, that does not automatically justify its use.
NAD⁺-related interventions are associated with:
Gastrointestinal symptoms
Headaches, flushing, palpitations
Sleep disturbance and fatigue
Poor tolerability with IV infusions
Unknown long-term safety in older adults
They also come with:
Significant ongoing financial cost
No proven human efficacy
No established MCID to guide dosing or benefit
This makes risk–benefit assessment particularly important.
Supplements vs the research compound
The compound used in the featured study:
Is not commercially available
Was not a supplement
Was carefully dosed to avoid supraphysiological NAD⁺ levels
Has not been tested in humans
Equating this experimental intervention with over-the-counter NAD⁺ products is scientifically inaccurate.
The HAP bottom line
This research is:
Mechanistically compelling
Scientifically rigorous
Worth further investigation
But at present:
There is no established MCID for NAD⁺ in humans
There is no evidence that increasing NAD⁺ improves clinical outcomes
There is no justification for presenting NAD⁺ supplementation as treatment
Raising a number is not the same as improving a life.
At The Healthy Ageing Project, we prioritise interventions that demonstrate meaningful, measurable benefits in humans, not just biochemical plausibility.
