NAD Supplementation for Dementia: No Proven Benefits
Current evidence does not support the use of NAD (nicotinamide adenine dinucleotide) supplementation for preventing or treating cognitive decline in dementia, and it should not be recommended in clinical practice. 1
Guideline-Based Position
The European Society for Clinical Nutrition and Metabolism (ESPEN) provides clear guidance that nutrient supplements, including NAD precursors, are unlikely to be effective in treating dementia and should not be used systematically for preventing or correcting cognitive decline. 2, 1
The fundamental principle is that supplementation should only occur when documented deficiencies exist—not as a preventive or therapeutic strategy for cognitive symptoms. 2
Clinical Evidence for NAD Supplementation
Human Studies Show No Benefit
A 3-month open-label study of oral NADH (10 mg/day) in 25 patients with mild to moderate dementia found no evidence of cognitive improvement on established psychometric tests. 3
One small randomized controlled trial (26 patients, 6 months) suggested NADH-treated subjects showed no progressive cognitive deterioration compared to placebo, with some improvements on specific subscales of the Mattis Dementia Rating Scale. 4 However, this contradicts the larger body of evidence and represents a single small study with methodological limitations.
A comprehensive systematic review of over-the-counter supplements found insufficient or low-strength evidence that any supplement, including NAD-related compounds, reduces risk for cognitive decline. 5
The Evidence Quality Problem
The available studies on NAD supplementation suffer from critical limitations: 2, 5
- Small sample sizes (as few as 19-26 patients completing studies)
- Short follow-up periods (3-6 months)
- High attrition rates
- Highly variable cognitive outcome measures
- Lack of consideration for baseline nutrient status
What About Other Nutrients?
The ESPEN guidelines systematically evaluated multiple nutrients with theoretical neuroprotective properties, all showing no benefit when no deficiency exists: 2
- Omega-3 fatty acids: No effect on cognition in dementia patients (Grade of evidence: high) 2
- B vitamins (B1, B6, B12, folic acid): No benefit for cognitive decline without documented deficiency (Grade of evidence: low to very low) 2
- Vitamin E: No benefit for preventing or correcting cognitive decline (Grade of evidence: moderate) 2
- Selenium: Insufficient evidence (Grade of evidence: very low) 2
Clinical Approach to Supplementation
Screen each patient with dementia for specific nutrient deficiencies through appropriate laboratory testing, and supplement only when deficiencies are documented. 2, 1
When deficiencies are identified: 2
- Supplement the specific deficient nutrient
- Use normal doses, not mega-doses
- Consider potentially toxic effects of high doses
- Address underlying causes (malabsorption, metabolic disorders, unbalanced diets)
When no deficiency exists, provide adequate nutrition through a balanced dietary pattern rather than supplements. 2
Important Caveats
The theoretical rationale for NAD supplementation (role in cellular energy production, brain metabolism) does not translate to clinical benefit in human trials. 3, 4
Animal studies showing benefit with NAD precursors like nicotinamide riboside do not reliably predict human outcomes. 6 One preclinical study showed improvements in aged and AD model mice, but this has not been validated in human trials.
The lack of benefit extends across all stages of cognitive impairment—from normal cognition to mild cognitive impairment to established dementia. 5