Longevity Briefs: Can Vitamin B3 Reduce Cognitive Decline?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Nicotinamide riboside (NR) is a member of the vitamin B3 family, and is an interesting compound when it comes to slowing the progression of age-related disease and decline. This is because NR can be converted into another molecule called nicotinamide adenine dinucleotide (NAD+). This molecule plays an essential role within the mitochondria, the structures within each cell that extract energy from food nutrients. NAD+ is also involved in other vital processes like the repair of damaged DNA.

As we age, levels of NAD+ decline, with grave consequences for the mitochondria and for the functioning of our cells in general. Some scientists think that declining levels of NAD+ could be a significant driver of ageing, and are hopeful that restoring NAD+ levels (such as via NR supplementation) might slow the ageing process down. Despite some promising animal studies, however, the benefits of this strategy have yet to be well demonstrated in humans. In this study, researchers test the effects of NR supplementation in people with age-related cognitive decline.

The discovery:

The researchers recruited 41 people, aged 55 and above, who had either subjective cognitive decline (SCD, a self-reported decline in cognitive function but that was within the normal range for their age) or mild cognitive impairment (MCI, cognitive performance below the normal range for their age). They randomised participants to receive either 1g/day of NR or a placebo for 8 weeks. After that, the placebo group and the treatment group swapped over, with those who had previously received the placebo now receiving NR for 8 weeks and vice versa.

Researchers found that after the first 8 weeks of treatment, there was a significant difference in blood levels of pTau217 (a marker of neurodegeneration) between the two groups. People taking NR had a 7% reduction in pTau217, while those taking placebo saw an 18% increase. After 8 weeks of crossover, those now taking placebo saw their pTau217 levels increase by a statistically significant 17%, while those taking NR experienced a (non-significant) 3% reduction. There was also a significant change in step count (as measured by wearable step-counting devices) after the crossover. Participants crossing from the placebo group to the NR group increased their step count by 11% during the subsequent 8 weeks, while those crossing from the NR group to the placebo group decreased their step count by 4%.

Despite these seemingly beneficial changes, no significant differences in any test of cognitive function were found after controlling for confounding factors.

The implications:

Studies continue to provide us with hints that restoring NAD+ levels might delay ageing in humans, but ultimately remain inconclusive. In this study, NR treatment led to changes that might be expected to lead to improved cognitive function, but did not actually do so. This could be because the study didn’t last long enough – 8 weeks may not be enough time for NR supplementation to produce measurable cognitive improvements. Other factors like dosage, age and cognitive health of the participants when treatment begins are all factors that need further investigation.

Irrespective of the benefits they provide, NR supplements do appear to be safe even in doses as high as 2-3 grams per day, though recommended doses are typically much lower. NR is present in many foods, but not at sufficient concentrations to make achieving the same dose as a supplement realistic.