NAD+ Supplementation for Alzheimer's Disease Treatment
NAD+ supplementation is not recommended for treating Alzheimer's disease in older adults, as current evidence does not support its use for cognitive improvement in established dementia.
Guideline-Based Recommendations
No Support for Nutrient Supplementation in Dementia
The European Society for Clinical Nutrition and Metabolism (ESPEN) provides clear guidance against systematic nutrient supplementation for dementia treatment:
Do not use nutrient supplements systematically to prevent or correct cognitive decline in persons with dementia, as present evidence suggests supplements are unlikely to be effective in dementia treatment 1.
This recommendation applies broadly to all nutrients examined for dementia treatment, including NAD+ precursors and related compounds 1.
Supplementation should only occur when specific nutrient deficiencies are documented, preferably using normal doses rather than mega-doses 1.
Established Treatment Options
The U.S. Preventive Services Task Force evidence review identifies only FDA-approved medications (acetylcholinesterase inhibitors and memantine) as having demonstrated effects on cognitive function in Alzheimer's disease, though these effects are modest (1-3 point improvements on ADAS-cog) 1.
- Dietary supplements were specifically evaluated and showed no evidence of benefit for global cognitive or physical function in persons with mild to moderate dementia 1.
Current Research Evidence on NAD+ Precursors
Preclinical vs. Clinical Data Gap
While recent research shows promise in animal models, human clinical evidence remains extremely limited:
A 2024 systematic review found only 2 human clinical trials using nicotinamide riboside (NR, an NAD+ precursor) for Alzheimer's disease, despite multiple positive preclinical studies 2.
The most recent 2025 trial (n=37 completers) showed NR supplementation (1g/day for 8 weeks) did not improve cognition as measured by RBANS or digital cognitive assessments, though it reduced plasma pTau217 biomarker levels 3.
An older 2000 study of oral NADH (10mg/day for 3 months) in 19 patients with dementia found no evidence for any cognitive effect on established psychometric tests 4.
Theoretical Mechanisms Without Clinical Translation
NAD+ precursors like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) show therapeutic effects in animal models through autophagy activation and antioxidant pathways 5.
However, these mechanistic findings have not translated to meaningful cognitive improvements in human trials 2, 6, 3.
Clinical Practice Approach
What to Do Instead
Focus on evidence-based interventions:
Use FDA-approved medications (donepezil, galantamine, rivastigmine, memantine) for appropriate patients with mild to moderate Alzheimer's disease 1.
Address nutritional status through adequate, balanced nutrition according to individual needs and preferences rather than specific supplements 1, 7.
Avoid unnecessary dietary restrictions that may worsen nutritional status in this high-risk population 1.
When Supplementation May Be Appropriate
Only supplement when documented deficiencies exist (e.g., vitamin D deficiency should be corrected for bone health and other systemic benefits, though not specifically for cognitive improvement) 1.
Screen for and address specific nutrient deficiencies that occur with malabsorption, metabolic disorders, or long-term unbalanced diets 1.
Critical Caveats
The increasing popularity of NAD+ precursors as over-the-counter supplements creates patient expectations that are not supported by clinical evidence 6, 4.
Further properly controlled clinical research is needed before NAD+ supplementation can be recommended for cognitive health 2, 6.
Safety data from the 2025 trial showed NR was well-tolerated with no difference in adverse events compared to placebo, but efficacy for cognition remains unproven 3.