Key Takeaways

• NAD+ is essential for cellular health and energy: However, directly supplementing with or receiving NAD+ infusions (IV) has biological limitations, including poor cellular uptake.
• NAD+ IVs have several drawbacks: NAD+ IV therapy can cause discomfort and requires long infusion times, and product quality can vary widely by manufacturer and across clinics..
• Pharmaceutical-grade only: Only pharmaceutical-grade, sterile NAD+ products sourced from FDA-registered 503B facilities or validated 503A pharmacies are appropriate for IV use.
• NR IV (Niagen® IV) is an emerging, next-generation alternative: It offers shorter infusion times, fewer side effects, and more efficient support of NAD+ metabolism.
• Transparency and medical oversight are critical: Patients should verify sourcing, sterility, and qualifications before receiving any NAD+ or NR IV treatment.

Interest in intravenous (IV) NAD+ therapy has surged in recent years, expanding beyond biohackers and longevity enthusiasts to reach celebrities, elite athletes, wellness clinics, and curious consumers alike.

As nicotinamide adenine dinucleotide (NAD+) becomes more widely recognized for its role in metabolic function, cellular repair, mitochondrial energy production, and healthy aging,¹ more people are seeking strategies to sustain optimal levels—particularly to support both lifespan and healthspan.

Yet, despite its central role in biology, NAD+ naturally declines with age.² This decline can be accelerated by lifestyle stressors such as poor diet, excessive alcohol intake, and physical inactivity—factors associated with faster cellular aging and increased disease vulnerability. 

These trends have helped to position NAD+ IVs as a “fast track” to replenishing NAD+ and purportedly supporting energy, cognitive function, exercise recovery, and overall vitality—however, these benefits have not been researched in published clinical studies. Plus, because IV administration bypasses the body’s digestive checkpoints (the gut), ensuring proper formulation, sterility, and clinical oversight becomes even more critical.

In addition, there is a growing debate regarding the efficiency of delivering NAD+ itself into the bloodstream versus using NAD+ precursors—such as nicotinamide riboside (NR). 

In this article, learn more about how NAD+ IV therapy works, what to consider when evaluating its safety and quality, why directly infusing NAD+ presents biological limitations, and how emerging IV approaches using NR could offer a better solution.

What Are NAD+ IVs and How Do They Work? 

NAD+ is essential for mitochondrial energy production, DNA repair, and overall cellular resilience. However, supplementing with NAD+ itself is not typically effective.

Orally supplemented NAD+ is largely ineffective because the molecule is too large to cross the cell membrane intact. Before it can enter a cell, it first needs to be broken down into smaller recognizable precursor components, enter through the cell wall, and then be reconstructed—an inefficient process that limits its direct utility as an oral supplement.

IV administration is a way to address this limitation. NAD+ IV therapy involves administering high concentrations of NAD+ directly into the bloodstream, bypassing the gastrointestinal tract and first-pass metabolism. This can allow for greater systemic exposure to NAD-related metabolites and more rapid uptake into circulation compared to oral routes.

NAD+ infusion is not entirely new. While consumer-facing “NAD+ clinics” have expanded significantly over the past two decades, intravenous NAD+ has been used since the 1960s in addiction recovery programs, where early research suggested benefits in alcohol withdrawal support.³

More recently, NAD+ IV therapy has been promoted anecdotally for metabolic support, cognitive function, athletic recovery, and general wellness. However, high-quality clinical evidence in these broader applications remains limited.

As the use of NAD+ IVs continues to grow, product purity, delivery rate, and an understanding of underlying biology have become essential factors in evaluating their safety and effectiveness.

Ensuring Safe NAD+ IV Therapy: The Role of 503A and 503B Compounding Pharmacies

Unlike medications approved by the United States (U.S) Food and Drug Administration (FDA)—which undergo rigorous manufacturing and quality oversight—there are currently no FDA-approved NAD+ products indicated for infusion. As a result, most clinics offering NAD+ IVs depend on compounding pharmacies to supply sterile formulations suitable for IV administration.

Compounding pharmacies prepare medications that are not commercially available or require customization. In the case of NAD+ IVs, compounding pharmacies produce sterile solutions of NAD+ that can be administered via infusion in clinical or wellness settings. 

However, not all compounding pharmacies operate under the same regulatory structure. In the U.S, they fall into two categories defined under the Federal Food, Drug, and Cosmetic Act (FD&C): 503A compounding pharmacies and 503B outsourcing facilities. 

503A compounding pharmacies prepare medications for individual patients based on a prescription. They are primarily regulated by state pharmacy boards and must comply with safety and quality standards such as USP 797 for sterile compounding. However, 503A pharmacies are limited in their ability to produce bulk medications. They cannot compound large quantities of IV products for office administration and typically have shorter beyond-use dates due to differences in sterility testing and manufacturing controls.

In contrast, 503B outsourcing facilities are FDA-registered and permitted to manufacture sterile medications in bulk for distribution to clinics and hospitals without patient-specific prescriptions.

These facilities must meet Current Good Manufacturing Practices (cGMP)—the same standards required of pharmaceutical manufacturers. Production processes must be validated, sterility must be consistently demonstrated batch by batch, and environmental quality must be continuously monitored. 

This distinction has meaningful implications for NAD+ IV therapy. Because NAD+ is delivered directly into the bloodstream, any contamination, formulation inconsistency, or dosing variability can pose immediate and serious clinical risk. 

Therefore, sourcing infusion products from FDA-registered 503B outsourcing facilities—or, at a minimum, from 503A pharmacies with validated sterile production capabilities—is an essential step to ensuring safe and reliable IV administration.

For both clinics and consumers, understanding where and how NAD+ IV formulations are prepared is a critical component of evaluating treatment safety and quality. Choosing products manufactured under rigorous sterility controls and federal oversight is an important safeguard for patient health.

Food-Grade vs Pharmaceutical-Grade NAD+: What Clinics Must Use for IV Therapy

As NAD+ IV therapy continues to expand, it’s critical to understand that not all NAD+ compounded materials are manufactured to the same standards.

Clinics and IV providers should rely on pharmaceutical-grade NAD+ because sterile compounding—whether through a 503A pharmacy or a 503B outsourcing facility—requires ingredients that meet strict quality, sterility, and endotoxin specifications. Food-grade NAD+ does not meet these criteria.

While food-grade NAD+ is suitable for dietary supplements, it is only intended for oral consumption. These products are manufactured to meet purity standards appropriate for ingestion, not the sterility or endotoxin controls required for IV administration.

Pharmaceutical-grade NAD+ is required to meet higher standards, including demonstrated sterility and the absence of endotoxins—bacterial components that can trigger severe immune reactions if directly infused into the bloodstream. It undergoes stricter manufacturing, validated purification processes, and stringent microbial and endotoxin testing to ensure it is safe for IV use.

The U.S. Pharmacopeia (USP), which sets national quality standards for medicines, clearly defines that sterile production is mandatory for all injectable therapies, stating:

“Medications that are required to be sterile include those administered through injection, intravenous infusion (IV), intraocular (injection in the eye) or intrathecal (injection in the spine).”

Even trace levels of bacteria, endotoxins, particulates, or chemical residues that would be harmless if swallowed can cause systemic infection, fever, chills, severe inflammatory responses, or septic shock when infused. 

For NAD+ IV therapy, pharmaceutical-grade sourcing is non-negotiable. It ensures the formulation is sterile, safe, and suitable for direct entry into the bloodstream, safeguarding patients from preventable and potentially serious harms.

Why Sterility Matters: FDA Guidance, Safety Risks, and NAD+ Recalls

Because infusions deliver substances directly into the bloodstream, bypassing protective barriers in the digestive and immune systems, any contamination—microbial, endotoxin, or particulate—can trigger severe or life-threatening reactions (fever, chills, systemic inflammation, or sepsis).

Last year, the FDA issued a public reminder to compounding pharmacies that food-grade NAD+ is not suitable for injectable or IV products, citing contamination risks and reports of adverse events when non-sterile (food-grade) NAD+ was used instead of pharmaceutical-grade.

In the FDA’s findings, some NAD+ injectable preparations were associated with reactions such as “severe chills, shaking, vomiting and fatigue,” symptoms consistent with endotoxin exposure.

Because of these documented risks and the need for strict sterility, only pharmaceutical-grade NAD+, which is formulated and tested for sterile compounding, should be used in IV products. Food-grade NAD+, intended for oral consumption, lacks the manufacturing controls, sterility testing, and endotoxin screening required for safe infusion.

To better understand the difference between food-grade and pharmaceutical-grade NAD+, consider an analogy using contact lenses and tap water. If you’re one of the 34 million Americans who wear contact lenses, you know the importance of using a specialized contact lens solution in your lens case every night instead of tap water.

While tap water is (generally) safe to drink, it’s completely unsafe for cleaning or storing contact lenses because it can introduce harmful microorganisms that cause serious eye infections.

A similar principle applies to neti pots—small teapot-like devices used to irrigate nasal passages and remove mucus or allergens. Public health agencies strongly advise using only distilled, sterile, or previously boiled water for nasal rinses. Although tap water is safe for drinking, using it in a neti pot can lead to rare but severe infections, including bacterial meningitis and exposure to microorganisms such as Naegleria fowleri—because it bypasses the body’s normal protective barriers. 

Similarly, food-grade NAD+ might be acceptable for ingesting, but when introduced directly into the bloodstream, even small contaminants can have dangerous consequences.

Recent recalls have underscored the importance of this distinction. One such recent recall was classified as  Class II by the FDA due to a lack of assurance of sterility, meaning they could not confirm that the injectable solution was free from microbial contamination. 

Another such recall was classified as a Class I recall (the most serious level) for a batch of injectable NAD+ due to elevated endotoxin levels—a clear signal that sterility and purity standards were not met and a violation that poses serious risk to patient safety.

These recalls reinforce that in NAD+ IV therapy, sourcing, compounding, and sterility are not optional “nice-to-haves”—they are foundational requirements for patient safety.

Challenges with NAD+ IV Therapy and Why NR IV Offers a Better Solution

There are challenges with using oral NAD+ to boost NAD+ levels—and there are also challenges with using NAD+ IVs. While IV delivery can raise circulating NAD-related metabolites, fundamental biochemical and practical limitations remain.

As a result, there is growing interest in IV delivery of an NAD+ precursor called nicotinamide riboside (NR), which may offer a more efficient and better-tolerated approach.

Some key biological and practical barriers involved with NAD+ IV therapy include:

• Uncomfortable side effects: Side effects can be intense enough that patients may slow or stop infusions, including chest tightness, anxiety, headaches, nausea, hot flashes, stomach cramping, lightheadedness, and diarrhea.
• Long infusion times: Infusions typically take 2 to 3 hours, but sometimes 4 or more hours, which reduces practicality for many individuals.
• Inflammatory potential: Early pilot data suggest that NAD+ IV administration increases white blood cell counts, suggesting an inflammatory immune response.⁴

Therefore, using NR may be a better option. Once inside the body, cells convert NR into NAD+ through well-established metabolic pathways, meaning NR is in a more efficient form for cellular uptake.

Currently, the only commercially available, pharmaceutical-grade IV NR formulation is Niagen® IV, a proprietary nicotinamide riboside chloride (NRCl) product with:

• Sourcing exclusively from FDA-registered 503B outsourcing facilities
• Full sterility and endotoxin testing to support safe IV administration

This level of manufacturing control helps ensure reliable performance and patient safety, two factors that have challenged NAD+ IV therapy.

Although both therapies aim to support NAD+ levels, they can lead to very different infusion experiences. With NAD+ IVs, the bloodstream is exposed to unnaturally high levels of intact NAD+ that must be broken down before cells can use it, contributing to slower delivery rates and uncomfortable symptoms.

Niagen IV delivers NR directly, in a form the body can readily use. Early clinical evidence indicates shorter infusion times, fewer side effects, and a more rapid rise in blood NAD+ markers compared to NAD+ IV administration.⁴

NR IVs represent a next-generation approach that aims to overcome the key drawbacks of NAD+ IV therapy, including being better tolerated, more biologically efficient, supported by stronger quality-control standards, and offering more convenient delivery.

Table 1. NAD+ IV vs. Niagen IV (NR IV): A Side-by-Side Comparison

*Based on a randomized, placebo-controlled pilot study (Preprint: Hawkins et al., 2024). 

How to Ensure Your NAD+ IV Therapy Is Safe

Because IV therapy involves direct infusion into the bloodstream, rigorous safety standards are essential. Before receiving any NAD+ IV treatment, patients should feel confident asking questions and verifying that proper safeguards are in place.

Below is a practical checklist to help ensure you are receiving a high-quality, medically responsible infusion:

• Confirm pharmaceutical-grade NAD+: Is the NAD+ being infused pharmaceutical-grade and sterile? 
• Verify endotoxin testing results: What verification do you have that the product is free of contaminants and endotoxins? 
• Verify compounding pharmacy: What verification of compounding pharmacy credentials do you have? Specifically, is the NAD+ sourced from an FDA-registered 503B outsourcing facility or a 503A compounding pharmacy registered with the state?
• Who is administering the IV? NAD+ IVs should only be administered under licensed medical supervision. A clinician must be present who is trained in IV administration and able to manage infusion-related reactions. 

Some red flags to watch out for include:

• The clinic won’t confirm that the NAD+ is pharmaceutical-grade and sterile.
• They cannot or will not provide sterility testing or product sourcing details.
• IVs are administered outside a clinical environment or without medical personnel.
• No compounding-related credentials, such as USP compliance or Pharmacy Compounding Accreditation Board (PCAB) certification, are available.
• The provider cannot identify whether the product came from a 503A or 503B facility.
• Pricing is unusually low or “too good to be true,” often a sign of non-sterile or substandard sourcing.

A reputable provider should welcome these questions and be eager to demonstrate that they prioritize sterility, quality, and medical oversight. Any resistance to transparency is a serious warning sign.

As NAD+ IV and NR IV therapies continue to grow in popularity, the safest choice is always the one supported by proper sourcing, validated sterile manufacturing, and qualified clinical care. 

Conclusion: Making Informed Choices in NAD+ IV Therapies

As interest in NAD+ IV therapy continues to rise, it’s important to make informed and safe choices. While NAD+ plays a vital role in cellular energy production and healthy aging, directly infusing NAD+ comes with notable limitations—including the difficulty of NAD+ entering cells, inconveniently long infusion times with uncomfortable side effects, and significant variability in product quality and sterility.

These drawbacks have led researchers and clinicians to explore the use of nicotinamide riboside (NR) as a more advanced approach. Early findings suggest that NR IV therapy may offer a better overall experience, including shorter infusion times, fewer side effects, more efficient support of NAD+ metabolism, and reduced signs of inflammatory stress.

Even more important is ensuring that any NAD+ or NR infusion is sourced and administered safely. Recent recalls and regulatory warnings have made one thing clear: only pharmaceutical-grade, sterile ingredients belonging in IV medications should ever be infused into the bloodstream. Clinics should be fully transparent about their sourcing, sterility validation, and compounding partners. 

Ultimately, your health and safety are the top priority. By asking smart questions, verifying sterility and sourcing, and choosing providers who follow proper medical standards, you can feel confident that you’re making a responsible and informed decision about NAD+ IV therapies.

IV therapies can be powerful tools—and when used with the right science, standards, and oversight, they have the potential to support wellness in meaningful ways.

 

References

1. Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metabolism, 27(3), 529–547. https://doi.org/10.1016/j.cmet.2018.02.011
2. Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., & Guillemin, G. J. (2012). Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue. PLoS ONE, 7(7), e42357. https://doi.org/10.1371/journal.pone.0042357
3. O’HOLLAREN, P. (1961). Diphosphopyridine nucleotide in the prevention, diagnosis and treatment of drug addiction. A preliminary report. Western Journal of Surgery, Obstetrics, and Gynecology, 69, 213–215.
4. Hawkins, J., Idoine, R., Kwon, J., Shao, A., Dunne, E., Hawkins, E., Dawson, K., & Nkrumah-Elie, Y. (2024). Randomized, placebo-controlled, pilot clinical study evaluating acute Niagen®+ IV and NAD+ IV in healthy adults. medRxiv, 2024.06.06.24308565. https://doi.org/10.1101/2024.06.06.24308565