NAD+ Precursors NMN and NR Support Neuron Health and Mitochondrial Function
Axons—the projections of nerve cells—are very sensitive to all sorts of changes, including aging processes and disruptions to blood sugar regulation. Both aging and blood sugar dysregulation cause disturbances to the health of axons because of their effects on the function of the energy-producing structures in our cells called mitochondria. At the core of the cell fueling processes driven by mitochondria is a molecule called NAD+, which is present in each and every cell in our body. However, there is evidence that NAD+ levels drop with aging, which, ultimately, can lead to disrupted axonal health.
A study from the University of Maryland School of Medicine demonstrates that the NAD+ precursors NMN (nicotinamide mononucleotide) or NR (nicotinamide riboside) supported the health of axons in mice subject to certain age-related stressors and blood sugar imbalances. The administration of NMN or NR improved sensory function in mice modeling age-related perturbations to axonal health. These results indicated that the correction of NAD+ depletion in mouse nerve cells may be sufficient to support axonal health but does not significantly affect blood sugar regulation.
Axons, Mitochondria, and NAD+
Neurons are the wires of our body. In order to communicate with one another and drive the circuits that execute all of the functions necessary for us to live and experience life, neurons demand high energy. Signals typically come in through a web of antennae that funnel to the cell body. When the signals in the cell body accumulate and cross a threshold, the neuron sends off a signal down its axon, which projects onto antennae on other cells, sometimes near and sometimes quite a distance away—like the several feet it can take from the brain all the way down the spine.
The survival and functionality of these axonal cables depend on the shuttling of a cornucopia of compounds along a filament-based highway that connects the tip to the cell body. This molecular transportation is highly dependent on the energy produced by mitochondria. When mitochondria begin to fizzle, axons begin to frizzle due to the failure to fulfill the energy demand. This is why the loss of NAD+, whether due to aging or imbalances like blood sugar dysregulation, which is essential for mitochondria to create energy, is so detrimental to neuron health and can drive axonal degeneration. This is supported by research showing that the deletion of NAD+ degrading enzymes or boosting proteins that resynthesize NAD+ supports axonal health and prevents degeneration.
NAD+ Precursors Support Neuron Health In Poor Blood Sugar Conditions
But in humans, we can’t just go in and delete enzymes—at least not yet. But what we can do to alter NAD+ levels is to supplement with precursors like NMN and NR. That’s why Chandrasekaran and colleagues tested the effects of NAD+ precursors on axonal health and function in young mice fed high-fat diets, which disrupts blood sugar regulation. For some of the mice, the Maryland-based research team supplemented their diet with NR daily (150 mg or 300 mg). The high-fat diet without supplementation led to drops in NAD+ levels in the dorsal root ganglion—a collection of nerve cell bodies that sit off the spinal cord and collect sensory signals. However, the mice that ate food supplemented with NR demonstrated increases in NAD+ levels of 17%.
In a separate model, Chandrasekaran and colleagues injected a chemical called streptozotocin to cause blood sugar dysregulation (as opposed to using a high-fat diet). Some of these mice were also injected with NMN. In the mice that were injected with only streptozotocin, the number of neurons in the dorsal root ganglion decreased and the speed of signal transmission in dorsal root ganglion neurons dropped, indicating poor survival and health. Co-injection with NMN prevented the drop in neuron number in dorsal root ganglion and decreased signal transmission velocity, suggesting that NMN can support neuronal health and function in conditions of poor blood regulation.
Together, this data shows that NAD+ precursor supplementation can support neuronal health and survival in the face of blood sugar dysregulation. It does not say that NAD+ precursor supplementation can support the recovery of neuronal health and number after damage has occurred due to blood sugar regulation. While this data is encouraging, it’s a little strange that NR and NMN were used in different experiments instead of being consistently tested throughout both models of blood sugar regulation, and the NAD+ precursors were administered differently: NR via food and NMN via injection.
As of now, we can’t directly compare the effects of NMN and NR in these models and how to best administer them, but it is a step forward in understanding the potential of these NAD+ precursors in supporting neuron health.
References:
Chandrasekaran K, Najimi N, Sagi AR, et al. NAD+ Precursors Repair Mitochondrial Function. Int J Mol Sci. 2022;23(9):4887. Published 2022 Apr 28. doi:10.3390/ijms23094887