NAD+ is the awkward case in its own family. The precursors NMN and NR have oral human trials behind them; the intact dinucleotide has almost none, because it is large, charged and poorly taken up by cells as such. That is the reason the intranasal route was investigated for NAD+ at all. Not as a convenience format, but because the molecule's own chemistry closes off the easy routes.
Why the route question exists for NAD+ specifically
Most route comparisons ask which of two workable options delivers more. For NAD+ the question is sharper, because the intact molecule does not readily cross cell membranes and is not meaningfully absorbed orally in the way its precursors are. The published field went two directions: administer a precursor and let the salvage pathway rebuild NAD+ inside the cell, or find a route that puts intact NAD+ where it is wanted. Intranasal delivery belongs to the second strategy, and its target is the brain, where the barrier problem is hardest and the nose-to-brain pathway offers a way around it.
The delivery evidence
The clearest result comes from Tsuchiyama and colleagues in 2009. Working in mice, they administered NAD+ intranasally at 10 and 20 mg/kg and reported that intranasal delivery raised NAD+ content in the brain. That is direct evidence the route works as a delivery mechanism for the intact molecule: the compound was measured where it was aimed.
Won and colleagues followed in 2012 with a rat weight-drop traumatic brain injury model, administering NAD+ intranasally at 20 mg/kg immediately after injury. Neurons in hippocampal CA1, CA3 and dentate gyrus were protected. Delayed microglial activation, normally seen at seven days after the insult, was reduced. The proposed mechanism is specific: excessive PARP-1 activation after injury depletes NAD+ and causes energy failure, and the intranasal dose replaces what was lost. Superoxide production and PARP-1 accumulation were unchanged, placing those events upstream of the depletion the treatment addressed.
The result that matters most is the negative one
In the same 2009 mouse study that demonstrated raised brain NAD+, the treatment failed. Tsuchiyama and colleagues induced intracerebral haemorrhage by collagenase injection and measured neurological function, haemorrhage volume and brain oedema at 24 hours. Neither 10 nor 20 mg/kg reduced brain injury. Their conclusion was explicit: no neuroprotective effect at 24 hours after intracerebral haemorrhage.
Read the two studies together and the useful lesson is not about NAD+ at all. Intranasal administration demonstrably raised brain NAD+ content, and in one injury model that translated into protected neurons while in another it did not. Delivery and effect are separate claims. A route that reaches the tissue has established exactly that, and nothing further.
The two studies also differ in more than model. Different species, different injury mechanisms, different endpoints, different assessment windows. Won measured neuronal survival across days; Tsuchiyama measured function and oedema at 24 hours. Treating either as the general verdict on the route overreads both.
What this does not tell you about injection
There is no published head-to-head study administering NAD+ intranasally and parenterally in the same model and comparing exposure. The intranasal work above establishes what intranasal NAD+ did in specific rodent injury models. It does not produce a bioavailability ratio against injection, and no such ratio can be inferred from it.
Intravenous NAD+ has been used clinically, but published protocols are sparse and heterogeneous, which leaves the comparison underdetermined from both sides. The honest position is that the intranasal route has more published rodent brain-delivery data behind it than the injectable route has controlled human data, and that this says more about which experiments were run than about which route is superior.
Rodent nasal anatomy is also a real limit here. Mice and rats carry proportionally far more olfactory epithelium than humans, and that surface is exactly what the nose-to-brain pathway depends on. Quantitative extrapolation from these doses is not supported.
The takeaway
Intranasal NAD+ has something most research peptides in spray format do not: published animal evidence that the route delivers the intact molecule to the brain. It also has a published negative result showing that delivery did not help in one injury model. Both belong in the same sentence. We stock NAD+ as an intranasal format and as lyophilised vials in several strengths, and the precursors NMN and NR as separate research lines, because the literature treats the routes and the molecules as distinct questions.
All products are intended for research use only. Not for human consumption. Must be 21 years of age or older to purchase.
References
1. Tsuchiyama, R., Sozen, T., Manaenko, A., Zhang, J. H., & Tang, J. (2009). The effects of nicotinamide adenine dinucleotide on intracerebral hemorrhage-induced brain injury in mice. Neurological Research, 31(2), 179-182. https://doi.org/10.1179/174313209X393609
2. Won, S. J., Choi, B. Y., Yoo, B. H., et al. (2012). Prevention of traumatic brain injury-induced neuron death by intranasal delivery of nicotinamide adenine dinucleotide. Journal of Neurotrauma, 29(7), 1401-1409. https://doi.org/10.1089/neu.2011.2228
3. Agrawal, M., Saraf, S., Saraf, S., et al. (2018). Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. Journal of Controlled Release, 281, 139-177. https://doi.org/10.1016/j.jconrel.2018.05.011
