Key Points
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NAD+ decline is tied to key drivers of NDDs
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Animal studies show strong therapeutic potential
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Early human trials indicate promising clinical benefits
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Brain delivery and individual response differences remain challenges
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Larger, longer trials are needed to confirm effectiveness
Why NAD+ Restoration Is Gaining Attention in NDD Research
Early research suggests that boosting levels of NAD+ inside brain cells might protect them and even slow down NDDs like Alzheimer's and Parkinson's.
“This premise is supported by multiple NAD-regulated pathways and mechanisms that influence key pathophysiological processes implicated in NDDs.”
A major reason for this interest is that NAD+ levels naturally decrease as we age, which is the biggest known risk factor for many brain diseases.
“One of the most compelling arguments lies in the observation that NAD levels decline with age, which remains the strongest known risk factor for neurodegenerative diseases such as AD and PD.”
The graphic below illustrates the essential role of NAD+ in many vital functions in the brain that are often impaired in NDDs.
NAD+ impacts many processes that are impaired in NDDs like Alzheimer's and Parkinson's. Boosting NAD+ appears to strengthen multiple defense systems in brain cells - supporting energy production (mitochondrial health), antioxidant protection against oxidative stress, DNA repair, gene regulation (epigenetics), anti-inflammatory responses, and cellular cleanup (autophagy, lysosomes), and healthy protein management.
Because NAD+ plays so many important roles, boosting its levels could be a promising therapeutic strategy for NDDs by targeting multiple problems at once.
“NAD augmentation may act as a multitarget strategy that exerts synergistic effects across several crucial pathways for NDDs, thereby enhancing cellular resilience to disease.”
Research Points to Strong Potential of NAD+ for NDDs
Boosting NAD+ shows potential in supporting brain health across several NDDs.
“Early-phase clinical trials show encouraging results regarding target engagement and preliminary efficacy in several NDDs.”
Here’s a breakdown by condition:
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Parkinson’s Disease (PD)
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Animal models show NR improves mitochondrial function and reduces neurodegeneration
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Early human trials demonstrate NR safely increases brain NAD levels, reduces inflammation, and may improve symptoms
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Alzheimer’s Disease (AD)
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NMN and NR improve mitochondrial health and reduce amyloid and tau pathology in animal studies
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Early human trials show mixed results; some show biomarker improvements, while others show no significant cognitive benefits yet
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Additional trials are ongoing to determine effective doses and outcomes
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Amyotrophic Lateral Sclerosis (ALS) and Other Diseases
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NAD+ shows promise in ALS models and a small clinical trial indicated potential benefits
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Animal evidence supports benefits also in Huntington’s disease, ataxia telangiectasia, and multiple sclerosis, with clinical trials planned or ongoing
Current Challenges and Future Directions
Research on NAD+ therapy for NDDs is advancing rapidly, but the field is still in its early stages.
- To fully realize its potential, several key questions and challenges must be addressed:
- Getting Enough NAD+ to the Brain: Improving delivery methods beyond oral supplements, such as targeted systems, is crucial for effective NAD+ therapy in NDDs.
- Delivery Methods Need Improvement: Targeted delivery systems, such as specialized carriers or brain-specific vehicles, are being explored to enhance brain NAD+ levels
- Wide Variation in Individual Responses: Differences in response to NAD+ supplementation, likely influenced by genetics and the gut microbiome, highlight the need for personalized approaches.
- Limitations of Animal Models: Promising results in animal studies have not always translated to humans, emphasizing the importance of well-designed clinical trials
Conclusion
There is growing scientific interest in the role of age-related NAD+ decline in NDDs and the therapeutic potential of restoring NAD+ levels.
“This age-dependent decline of NAD is hypothesized to contribute to the onset and progression of age-related diseases including neurodegeneration.”
Boosting NAD+ offers promise as a multi-target strategy for treating NDDs, addressing mitochondrial dysfunction, oxidative stress, inflammation, and more.
“Augmenting NAD metabolism via supplementation of precursors has been shown to confer rejuvenating effects, including lifespan and healthspan extension in multiple animal models, neuroprotection in preclinical models of neurodegeneration, as well as promising early-phase clinical findings.”
Initial research has shown encouraging outcomes regarding the safety and efficacy of NAD+ boosting therapies.
“Building on these results, treatment with biosynthetic NAD precursors has moved into focus as a potential multi-target intervention for NDDs.”
However, important challenges remain—including improving delivery to the brain, understanding individual response variability, and confirming long-term effectiveness in large-scale trials.
Ongoing research continues to drive momentum in the field.
“Several early clinical trials of NAD augmentation have been completed, and many more are currently underway, reflecting the growing optimism and urgency within the field.”
For those interested in a more detailed scientific discussion and a comprehensive list of the scientific studies, please refer to the original review paper.
