NAD+ Nasal Spray | A Comprehensive Overview

NAD+ is an actively studied molecule whose potential benefits range from enhanced muscle function to a general anti-aging effect.

Short for nicotinamide adenine dinucleotide, NAD+ is the oxidized form of NADH and is key to both cellular metabolism and extracellular communication. In its pure form, NAD+ is typically administered via subcutaneous injection or as a nasal spray.

Given the unique benefits of administering this support molecule intranasally, our research team has published this informative NAD+ nasal spray review.

Read on as we discuss the potential benefits and side effects of NAD+ and reveal our pick of the best NAD+ nasal spray online.

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What is NAD+?

NAD+ (nicotinamide adenine dinucleotide) is a universal coenzyme, electron transporter, and signaling molecule that is found in every cell of the body. Cellular concentrations of NAD+ change during the natural aging process and in cases of infection. Modulation of NAD+ levels may thus yield favorable effects like prolonging lifespan and supporting neurocognitive function [1].

NAD+ is found in great abundance in the mitochondria. It is required for the addition of poly-ADP ribose to proteins and the deacetylating activity of sirtuin enzymes, which are critical to cell growth, energy metabolism, stress resistance, managing inflammation, and neuronal function [2].

NAD+ in supplemental (oral) form has poor bioavailability, so researchers have turned to injectable NAD+ or nasal spray formulations to test the range of applications of this support molecule. NAD+ sold as a research chemical is intended for use by qualified researchers for in vitro testing and laboratory experimentation only.

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NAD+ Benefits

Research has established the therapeutic potential of NAD+ in a range of contexts. It has specifically been targeted as a potential treatment of neurodegenerative conditions [3].

There is currently a phase II study underway at the Keio University School of Medicine, where researchers are looking at the long-term effects of NMN (a NAD+ precursor) on glucose metabolism in healthy adults. Another, at Hiroshima University, is studying the impact of long-term NMN supplementation on hormone levels in healthy populations [4]. These studies will be useful to researchers interested in NAD+ as a therapeutic agent.

In the interim, there is a wealth of documentation and clinical studies to support the use of NAD+.

Neurocognitive Health

Changes in NAD+ have documented far-reaching effects on the brain, and NAD+ appears as neuroprotective in both human and animal studies. NAD+ helps to protect against cognitive impairment and neuroinflammation, preserves the mitochondria, inhibits reactive oxygen species (ROS) via SIRT1 activation, and improves cognitive function in patients with neurocognitive disorders or traumatic brain injury [5, 6, 7, 8].

In a case of Parkinson’s Disease, researchers intravenously administered NAD+ at 1,500mg on day one of treatment, followed by gradual lower doses. Over the course of treatment, symptoms including hand tremors and visual hallucinations decreased substantially. Aftercare for this patient included a daily regimen of 300mg/ml NAD+ nasal spray, which helped to keep tremors at tolerable levels [9].

Drug Rehabilitation and Addiction Treatment

NAD+ has recently been found to influence signaling processes and pathways involved with the neurobiology of addiction. Raising intracellular NAD+ levels could thus be a therapeutic option for managing or treating drug addiction and substance abuse [10].

Many of the factors implicated in difficulty with rehabilitation are related to withdrawal symptoms or cravings. The underlying causes are associated with circadian rhythm disruption, endocrine dysregulation, and alternations in the dopamine pathway. NAD+ increases adenosine levels, which can counteract the degenerative impact of dopamine on neuronal cells. This is more evidence of NAD+ as essential for promoting cellular regeneration and repair in neuropsychiatric conditions, including addiction [11].

Anti-Aging

Research in mice has revealed that increasing NAD+ metabolism can extend lifespan and mitigate premature aging diseases [12].

In a 12-month rodent study, oral administration of the NAD+ precursor NMN suppressed weight gain, enhanced energy metabolism, and improved insulin sensitivity in the test subjects. The authors deemed NMN as having preventative effects on age-associated physiological changes, with the hope that these results could be replicated in humans [13].

The concern with supplementing oral NMN is that its effects in neurons are unclear. Increased intracellular NMN activates SARM1, which is an executor of axon degeneration [14]. NAD+ nasal spray may help to “by-pass” this activation of SARM1 from oral supplementation of the NAD+ precursor NMN.

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NAD+ Side Effects

While we cannot determine all possible side effects of NAD+ intranasal administration at this time, current research indicates its favorable safety profile. NAD+ and its precursors have been administered to human and animal populations in randomized and controlled studies, with no deleterious effects reported.

Intramuscular injections of NAD+, IV NAD+ administration, and intranasal NAD+ all seem to be well-tolerated and safe [15, 16, 17, 18, 19]. Minor, transient side effects have been noted in the research. These include:

• Headaches
• Hot flashes
• Constipation
• Nausea
• Stomach irritation; cramps, abdominal discomfort
• Discomfort at the injection site for IM administered NAD+ (burning)
• Shortness of breath

A study conducted by Klein and colleagues evaluated the metabolic effects and potential side effects of NMN in women over 55. This was a small clinical trial, consisting of 12 postmenopausal women who were also prediabetic. The volunteers took 250mg of NMN orally for 10 weeks. The study did not document any adverse effects. However, NMN at this dose also failed to lower blood glucose or blood pressure [20].

Published in Endocrine Journal (The Japan Endocrine Society), a clinical trial looked at the impact of supplemental doses of NMN on healthy Japanese men. This single-arm non-randomized intervention was conducted with an oral administration of 100, 250, and 500 mg NMN. The oral administration of NMN was deemed safe, and effectively metabolized in healthy men without causing any deleterious effects [21].

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NAD+ Dosage Guide

As NAD+ nasal spray is not currently approved for human use, there are no official dosing guidelines in place for this compound.

However, based on current research, researchers are encouraged to consider the following points when administering NAD+ intranasally:

• Intranasal administration of NAD+ is considered to be effective for treatment of neurocognitive disorders. In a rodent model, intranasal administration of NAD+ significantly increased NAD+ content in the brain [22].
• In another rat model, intranasal doses of NAD+ 10mg/kg proved effective in reducing ischemia-induced neurological deficits in cases of ischemic brain injury [23]. It is important to note that dosages in rodents do not scale to humans.
• Research indicates that oral NAD+ precursors are safe when taken long-term (4+ months) and short-term (2 weeks) across various clinical trials at doses ranging from 250mg to 2000mg [24, 25, 26].
• NAD+ and NAD+ precursors have a high safety profile, even when used at higher single doses, and long-term. The optimal dosing schedule will depend upon the desired clinical outcome and the body mass of the subject(s).

Sample NAD+ Nasal Spray Dosing Protocol

For reference, we are including a sample dosing protocol for researchers studying NAD+ and using a nasal spray that contains 100mg of NAD+ per dose (spray). This is comparable to the NAD+ nasal spray offered by our preferred vendor.

Assuming the above, the researcher may administer as follows:

• NAD+ Dosage: 100mg administered daily. Administer one spray in one nostril daily. Alternate nostrils with each administration.
• Course Duration: One month.
• Notes: This protocol requires 3x 1000mg nasal spray bottles for a one-month supply per subject. Researchers can adjust dosing and duration depending on the severity of condition, clinical outcomes, and research methodology.

As research on NAD+ is continually expanding, researchers are advised to stay informed on the latest developments regarding NAD+ and intranasal delivery.

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NAD+ Nasal Spray | A Comprehensive Review

NAD+ is typically administered via injection for maximum bioavailability, yet in some cases researchers may opt to use a nasal spray depending on the research objective and study design.

Intranasal NAD+ Delivery

Researchers have long held that nasal formulations may be suitable for delivering medication, specifically in cases of neurological disease [27].

A number of clinical studies in the 1980s demonstrated that intranasal administration may help enable substances to enter the brain through pathways involving the olfactory bulb and olfactory epithelium [28]. In 1995, Thorne et al. showed that intranasal administration could deliver large-sized molecules to the brain, bypassing the blood–brain barrier (BBB) [29].

A 2008 review of animal and human studies found that intranasal delivery of medication has proven beneficial in the treatment of neurological diseases and brain injury [30].

Researchers have looked at the effects of NAD+ on brain protection in a mouse model of intracerebral hemorrhage (ICH). The subjects were intranasally administered NAD+ at doses of 10 and 20 mg/kg NAD+, with the authors observing that intranasal delivery resulted in an increase in NAD+ content in the brain [31].

We can extrapolate these findings to the potential of NAD+ in benefitting cognition and overall brain function when administered intranasally, which allows the molecule to enter the CNS through olfactory pathways or the trigeminal nerve.

Benefits of Intranasally Administered NAD+

There are a number of potential advantages of NAD+ intranasal delivery:

• Intranasally administered NAD+ can be delivered directly to the brain, bypassing the BBB.
• Potential unwanted side effects, related to high doses of NR or NMN on the gastrointestinal and peripheral system, could be drastically minimized.
• Smaller amounts of NAD+ would be required to produce the same desired concentration of NAD+ in the CNS when compared to oral administration.
• Intranasal delivery is non-invasive. Researchers can minimize subject pain or discomfort, compared to injection.
• Intranasal delivery of NAD+ is simple. If ultimately approved for clinical use, it may be conducted by patients themselves or any other non-professional, which would minimize delay of treatment and reduce barriers to treatment.

Precautions with NAD+ Nasal Spray

Researchers who wish to administer NAD+ as a nasal spray should take note of certain precautionary measures to ensure optimal bioavailability.

• For maximum absorption, wait one to two minutes between repeating sprays in the same nostril to prevent oversaturation.
• The subject’s head must be tilted upward to ensure proper administration.
• The nozzle of the spray bottle needs to be kept clean and sanitary at all times to prevent any contamination or degradation of the product. NAD+ solution, including nasal spray, should be kept refrigerated.

Aside from the aforementioned guidelines, researchers should ensure they purchase NAD+ from a reputable supplier. Factors to consider when purchasing NAD+ nasal spray include evaluating any third-party or in-house laboratory tests done on the product, customer feedback on the vendor, and satisfaction guarantees.

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Where to Buy NAD+ Nasal Spray Online? | 2024 Edition

Researchers looking to source a high-quality NAD+ nasal spray online have a number of options. However, for the aforementioned reasons, it is important to carefully vet all potential vendors for certifications, reputation, and quality control measures.

Limitless Life

In our experience, Limitless Life stands out for their NAD+ nasal spray.

They currently offer a high-quality product at 5mg of NAD+/spray in a convenient nasal spray bottle containing 500mg of NAD+.

Here are some reasons as to why we endorse Limitless Life:

• High-Quality Products: Limitless Life submits their products for third-party purity testing by a reputable laboratory. Online reports and our own experience confirm the high standard of purity of this vendor’s products.
• Affordable Pricing: Limitless Life products are very well-priced and their 500mg NAD+ nasal spray currently retails for $55. They regularly offer promotional discounts for email newsletter signups.
• Reliable Customer Service: The company is easily accessible via phone and email, and is quick to resolve any shipping concerns. They have a strong online presence and a wealth of possible reviews reinforcing the quality of their products.
• Fast Shipping: Limitless Life is based out of the U.S., so ordering from them means quick shipping compared to international suppliers. The vendor typically uses USPS Priority, with a standard timeframe of 1-3 business days.

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NAD+ Nasal Spray vs. Injectable NAD+

Researchers interested in testing NAD+ may wonder why they would need to opt for an injectable version or nasal spray, rather than oral tablets or capsules.

Research continually reaffirms that oral NR and NAD+ supplements do not reach the bloodstream as NR, only as NAM. Subjects therefore do not derive comparable benefits from oral supplementation compared to injection or nasal spray. This is due to degradation of NAD+ and NAD+ precursors in the intestine, as well as first-pass metabolism by the liver [32].

NAD+, NMN, NADH, and NR all have limited oral bioavailability, despite positive clinical results with higher long-term doses. A research study published in 2018 shows that NMN and NR cannot utilize the CD43 gap to effectively cross the BBB. Precursors will thus not be the most effective means to replenish or modulate NAD+ levels [33].

Nicotinamide riboside (NR) has potent biosynthetic NAD+ effects, for example. However, NR is not stable in circulation, utilization is rate-limited by the expression of nicotinamide riboside kinsases, and it is degraded easily in plasma [34]. NAD+ nasal spray and injection can bypass these pitfalls of oral supplementation.

While injections are commonly preferred for most peptides and small molecules for maximum bioavailability, it appears as though, at least in certain contexts, nasal spray is a comparably efficacious method of delivering NAD+.

In clinical studies, both intraperitoneal injections and intranasal administration of NAD+ inhibited neuroinflammation and prevented cognitive deficits by protecting the mitochondria and decreasing ROS production. By comparison, NAD+ precursors like NR when injected or administered intravenously are not as effective at increasing NAD+ levels in the liver or brain [35].

Researchers looking to administer injectable NAD+ should opt for the formulation from our preferred vendor.

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NAD+ Nasal Spray | Verdict

NAD+ is a naturally occurring molecule that is studied for benefits like improved neurological function, reduced inflammation, and anti-aging.

While the supplement market is rife with “NAD+ boosters,” these products almost always contain NAD+ precursors and not NAD+ itself, due to the latter’s poor oral bioavailability. By consequence, researchers have turned to injectable NAD+ and NAD+ nasal sprays as routes by which to deliver the support molecule to test subjects.

NAD+ nasal spray has several key advantages, namely that it bypasses the digestive system to deliver the molecule directly into the bloodstream in a non-invasive and painless manner.

Based on our testing criteria and experience, we recommend selecting the best vendor of NAD+ nasal spray online.

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