Review: vitamin B3 metabolites, gut microbiota and exercise in brain aging and neurodegeneration
This review links declining NAD metabolism, mitochondrial function, inflammation and gut-brain interactions to brain aging and neurodegeneration, and asks whether vitamin B3 NAD precursors, exercise and gut microbiota could together support cognitive health; long-term efficacy and clinical relevance remain unestablished. [1]
Automatic summary · not editorially reviewed
The key findings
Aging and neurodegenerative disorders are described as closely linked to a gradual decline in NAD metabolism, reduced mitochondrial function, persistent inflammation and altered gut-brain interactions. [1]
Preclinical and emerging clinical evidence suggests NAD-enhancing interventions may improve mitochondrial function and modulate neuroinflammatory pathways, but long-term efficacy and clinical relevance in neurodegenerative disorders remain to be fully established. [1]
The review proposes that combining vitamin B3 supplementation, physical activity and gut microbiota may be a promising framework for research, while definitive therapeutic applications require further validation. [1]
The source at a glance
- Study type / format
- Review (abstract only)
- Population / context
- People aging and people with neurodegenerative disorders, discussed through molecular, preclinical and clinical evidence
- Summary based on
- Study abstract
- Original publication
- September 23, 2026
NAD decline, mitochondria and inflammation in brain aging
The review states that aging and neurodegenerative disorders are closely linked to a gradual decline in nicotinamide adenine dinucleotide (NAD) metabolism, reduced mitochondrial function, persistent inflammation and altered gut-brain interactions. Vitamin B3 derivatives such as niacin, nicotinamide, nicotinamide riboside and nicotinamide mononucleotide are described as key NAD precursors that may support cellular energy processes and influence pathways of brain aging. The authors report that preclinical and emerging clinical evidence suggests NAD-enhancing interventions may improve mitochondrial function and modulate neuroinflammatory pathways, supporting processes involved in synaptic plasticity and cognitive function. They add that long-term efficacy and clinical relevance in neurodegenerative disorders remain to be fully established.
Supporting source [1]
Exercise and gut microbiota as proposed NAD-related influences
According to the review, physical exercise is a strong physiological stimulus that increases NAD biosynthesis, modulates adaptive responses dependent on hypoxia-inducible factor-1α, promotes neurotrophic signaling and improves vascular and metabolic brain health. Emerging evidence is said to suggest that the gut microbiota contributes directly to NAD homeostasis by regulating the availability of vitamin B3 precursors, tryptophan metabolism and host metabolic signaling. The microbiota is also described as influencing the efficacy of NAD-enhancing interventions and thereby systemic inflammation, metabolic balance and the production of neuroactive metabolites.
Supporting source [1]
Combined framework proposed, not yet a validated therapy
The review proposes that the interaction of vitamin B3 supplementation, physical activity and gut microbiota may be a promising framework for investigating strategies to support cognitive health and brain resilience during aging. The authors state that definitive therapeutic applications require further validation. They describe the work as integrating current molecular, preclinical and clinical evidence to establish mechanistic links between NAD metabolism, brain aging, cognitive dysfunction and neurodegeneration, while emphasizing current limitations and future translational challenges of combining vitamin B3 metabolites, exercise and microbiome-targeted approaches.
Supporting source [1]
How to interpret this
This is an abstract of a review; the full text was not reviewed. The abstract reports no specific study design, sample size, follow-up or outcome data, and it describes the evidence as preclinical and emerging clinical, with long-term efficacy and clinical relevance in neurodegenerative disorders not fully established. The combined framework is proposed for investigation, not a validated therapy.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Zhang W. · europepmc.org · September 23, 2026