Nicotinamide Riboside Fails to Improve Measures of Cognitive Function in Mild Cognitive Impairment Patients
Using vitamin B3 derivatives as a means to modestly improve metabolism to treat various conditions has a several decade history. The results have been poor; largely this is a history of failed clinical trials. This mostly predates the recent focus on declining NAD+ levels in mitochondria in aging, and the use of vitamin B3 derivatives, such as nicotinamide riboside, to increase NAD+ levels. Exercise produces larger gains than these supplement approaches in NAD+ levels. The clinical trial noted here is fairly characteristic of the type; one sees modest gains in some of the parameters that one might expect to be linked to improved mitochondrial function, but no significant effect on the disease state.
Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 gram/day) on cognition and plasma Alzheimer's disease biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.
The primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (z-scores) for cognition and step counts from wearables.
Forty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau217 concentrations after taking NR, while an 18% increase with PBO. No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores, or step counts. For the within-individual comparison, pTau217 concentrations significantly decreased during the NR phase compared to the PBO, while step counts significantly increased during the NR phase than PBO.
Have always been curious, Reason often points out that lifestyle choices produce similar or greater effects than various supplements - fasting, exercise, etc. But is there data looking at the combination? Do supplements, let us say, supplement these lifestyle choices, to increase the total effect, or are they entirely wasted in these cases?