What does NAD+ do for your brain?
NAD+ plays a biologically important role in brain cells and declines with age, but whether supplementation via NMN or other agents also protects humans has not yet been convincingly demonstrated. Anyone wanting to know more about NMN supplementation would be wise to await the outcomes of ongoing clinical studies before drawing firm conclusions.
NAD+ is a substance that occurs naturally in all cells of the body, including brain cells. It is indispensable for energy production, keeping DNA intact, the health of mitochondria (the powerhouses of cells) and the resilience of neurons under stress. In addition, several NAD+-dependent enzymes are involved in synaptic plasticity: the brain's ability to strengthen or weaken connections, which forms the basis of learning and memory1.
As we age, NAD+ levels decline in the brain, blood, skin, liver and muscles. This is seen as a possible explanation for why older brains become more vulnerable to disease and cognitive decline. It is a widely cited hypothesis, but the precise cause-and-effect relationship in humans has not yet been fully established2.
In Alzheimer's disease, the link with NAD+ has been studied most intensively, though so far this has been almost exclusively in animal and laboratory research. In mice with advanced Alzheimer's disease, restoring NAD+ balance (via the experimental compound P7C3-A20) led to less tau accumulation, less inflammation and oxidative damage, restoration of the protective blood-brain barrier and complete cognitive recovery. A blood-based Alzheimer's biomarker also declined. Separate mouse studies show that NAD+ supplementation reduces neuroinflammation and so-called senescence (damaged cells that continue to release harmful substances) via an immune signalling pathway3,4. These outcomes are impressive in mouse models, but translation to humans has not yet been demonstrated.
NMN (nicotinamide mononucleotide) is a precursor of NAD+ that is available as a supplement. In cell and animal research, NMN raises NAD+ levels and reduces age-related processes such as DNA damage and neurodegeneration. A specific mouse study shows that NMN counteracts leakage of the blood-brain barrier in ageing animals by restoring NAD+ levels in the brain's blood vessels5. Human clinical studies with NMN are currently small in scale or still ongoing; whether the same effects occur in healthy people has not yet been sufficiently demonstrated2.
There is also a broader context: the body produces NAD+ via a pathway that begins with tryptophan, an amino acid from food. Intermediate substances in this pathway are neuroactive. Some are protective for brain cells, others are neurotoxic and influence an important receptor for learning and memory. Dysregulation of this pathway is associated in animal models with depression-like behaviour and cognitive problems; in humans there is an association with psychiatric disorders in the context of inflammation6. This means that NAD+ production in the brain is not merely a question of quantity but also one of quality: which intermediate substances are produced matters for brain health.
All claims are based on the supplied abstracts (PMID 31577933, 37619764, 41435831, 31893583, 37683629, 30980044). The human evidence is limited to association studies and small trials; most mechanistic and intervention data come from animal and cell models.