Is NAD Plus Legitimate? Exploring the Science, Benefits, and Controversies

December 17, 2025 •

5 min read

By the age of 40, a person's levels of the vital coenzyme NAD+ (nicotinamide adenine dinucleotide) have dropped by nearly 50%. This age-related decline has fueled immense interest in whether supplementing to boost NAD+ is legitimate for improving healthspan and reversing aspects of aging.

Quick Summary

The legitimacy of NAD+ supplements is a complex topic, backed by promising preclinical animal research but limited and mixed human trials. While NAD+ precursors like NMN and NR can boost levels, their definitive impact on human health and longevity is still being studied, alongside ongoing safety and regulatory questions.

Key Points

Limited Human Evidence: While animal studies show promise for NAD+, human clinical trial results are mixed and lack definitive proof for anti-aging effects.
Precursors Boost Levels: Oral supplements like NMN and NR can effectively increase NAD+ levels in the body, but consistent health benefits are not yet confirmed.
Considerable Cost & Side Effects: Treatments like IV therapy are expensive and carry potential side effects like nausea and anxiety, with no guaranteed benefits.
Regulatory Uncertainty: The regulatory landscape for NAD+ precursors is in flux, with the FDA raising concerns about certain supplements like NMN.
Long-Term Safety Unknown: Long-term safety and potential risks, particularly regarding cancer, have not been fully studied in humans.
Prioritize Proven Strategies: For healthy aging, evidence-backed strategies like diet and exercise remain more proven and reliable than NAD+ supplements.

What is NAD+ and Why Does it Decline?

Nicotinamide adenine dinucleotide (NAD+) is a fundamental molecule present in every living cell, playing a crucial role in metabolic processes that convert food into energy. It is also essential for critical cellular functions, including DNA repair, stress response, and the activation of sirtuins, a family of proteins that regulate cellular health and longevity.

As we age, our natural NAD+ levels decline due to various factors, including increased consumption by enzymes and reduced production efficiency. This depletion is linked to many hallmarks of aging and age-related diseases, leading researchers to explore whether replenishing NAD+ can counteract these effects.

The Scientific Evidence: What Does Research Say?

Initial interest in NAD+ supplementation was driven by compelling preclinical studies in mice. Restoring NAD+ in animal models has shown promising results, including improved insulin sensitivity, enhanced cardiovascular function, and potential cognitive benefits in models of Alzheimer's. However, translating these findings to humans is challenging, and the evidence is still accumulating.

Clinical Findings in Humans

Several human clinical trials, primarily using NAD+ precursors like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), have yielded variable results.

Increased NAD+ Levels: Many studies confirm that oral NR and NMN supplementation can effectively raise NAD+ levels in blood and other tissues.
Inconsistent Clinical Benefits: Despite increased NAD+ levels, improvements in clinical outcomes such as insulin sensitivity, energy expenditure, and exercise performance have been inconsistent across different trials. Some studies have noted a reduction in inflammatory markers and minor improvements in physical function in certain cohorts, but these findings are not universal.
Anti-Aging Claims Unproven: As of now, there is no conclusive human evidence that NAD+ supplementation slows, stops, or reverses aging. Claims of being a "miracle drug" or "fountain of youth" are not supported by robust, large-scale clinical trials.

Types of NAD+ Supplementation

NAD+ can be delivered to the body through several methods, each with different bioavailability and cost considerations.

Oral Precursors: Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are the most common over-the-counter supplements. They are derivatives of Vitamin B3 and act as precursors, meaning the body converts them into NAD+. Bioavailability and efficacy can vary, as some amount is degraded by the digestive system.
Intravenous (IV) Therapy: Delivering NAD+ directly into the bloodstream through an IV bypasses the digestive system, potentially offering higher and more immediate bioavailability. However, IV therapy is significantly more expensive, requires medical supervision, and is not FDA-approved for general anti-aging purposes. Users have reported side effects like nausea and anxiety during infusions.
Transdermal Patches: These patches use technology to deliver NAD+ through the skin. Proponents suggest this offers a steady release and better absorption than oral supplements, bypassing digestion. While transdermal delivery is a promising technology, research specifically on NAD+ patches is limited.

Potential Risks and Regulatory Issues

While short-term use of NAD+ precursors appears generally safe, questions remain about long-term safety, particularly concerning cancer risk.

Cancer Concerns: The relationship between NAD+ and cancer is complex. Cancer cells have high energy demands and consume significant amounts of NAD+ to fuel their rapid growth. Some animal studies have raised concerns that boosting NAD+ could potentially feed tumors in cancer-prone situations. Experts advise caution for those with active cancer or a high risk.
Side Effects: Commonly reported side effects from supplementation include nausea, fatigue, headaches, and flushing. Side effects like rapid heartbeat or anxiety have been noted with IV therapy.
Regulatory Uncertainty: In the U.S., the regulatory status of some NAD+ precursors, like NMN, is uncertain. The FDA ruled in 2022 that NMN could not be marketed as a dietary supplement, leading to its removal from major retail platforms. This flux creates ambiguity for consumers.

How to Evaluate NAD+ Supplementation

Given the mixed evidence, a critical and cautious approach is warranted for anyone considering NAD+ supplementation. It is crucial to distinguish between promising animal research and the more limited human data.

Here are some factors to consider:

Bioavailability: The body’s ability to absorb and use a substance. Oral supplements can have lower bioavailability than IV therapy, which has its own risks.
Delivery Method: Different methods (oral, IV, patches) have varying efficacy, cost, and potential side effects.
Dosage: The optimal dosage for humans is still under investigation, and different clinical trials have used a wide range of doses.
Individual Health Status: A person's current health, underlying conditions, and age can all influence how they respond to NAD+ supplementation.
Reputable Sources: The quality and purity of supplements vary widely. Finding products from reputable brands that use third-party testing is essential.

Comparison of NAD+ Delivery Methods


Feature	Oral Precursors (NMN/NR)	IV Therapy	Transdermal Patches
Effectiveness	Can boost NAD+ levels, but clinical benefits are inconsistent in humans.	High bioavailability, direct delivery to bloodstream.	Promising for steady release, but limited research.
Cost	Widely accessible and more affordable.	Expensive, ranging from hundreds to thousands of dollars per session.	More affordable than IV, but more than oral supplements.
Convenience	Easy to take daily as a capsule or powder.	Requires in-clinic sessions, which can take several hours.	Convenient, non-invasive, applied to the skin.
Safety & Side Effects	Generally considered safe in the short term. Side effects can include nausea, fatigue, and headaches. Long-term safety unknown.	Potential side effects include nausea, anxiety, dizziness, and rapid heartbeat.	Minor skin irritation possible. Specific safety data limited due to lack of research.
Regulation	Varies; regulatory status is in flux, particularly for NMN.	Largely unregulated by the FDA for anti-aging use.	Varies by product, but generally lacks specific regulation.

Conclusion

In summary, the question of whether NAD plus is legitimate does not have a simple yes or no answer. The science is compelling at a cellular and preclinical level, and it is clear that NAD+ is a critically important coenzyme for health. Oral supplements have been shown to increase NAD+ levels in human trials, but this has not consistently translated to the significant, life-altering benefits sometimes claimed by supplement marketers. The long-term effects and safety profile, especially regarding cancer risk, are still not fully understood. While promising, NAD+ supplementation should not be viewed as a proven "fountain of youth." For now, focusing on proven longevity strategies like a healthy diet, exercise, and avoiding excessive sun exposure remains the most reliable path to cellular health. Anyone considering NAD+ supplementation should have an open conversation with a healthcare professional, especially given the varying regulations and lack of definitive clinical outcomes. The field is rapidly evolving, and staying informed about new, larger-scale human trials is key to understanding the true potential and limitations of NAD+ supplementation.

For more detailed research on NAD+-boosting compounds, review studies from the National Institutes of Health.

Frequently Asked Questions

There is currently no conclusive scientific evidence from human clinical trials showing that NAD+ supplementation can reverse aging. While animal studies have shown promising results, large-scale, long-term human data is still needed.

The most common forms are oral precursors like Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR). Other delivery methods include intravenous (IV) therapy and transdermal patches, but these have different levels of evidence and regulation.

Short-term use of NAD+ precursors appears generally safe, with side effects like nausea and headaches possible. Long-term safety is unknown, and potential risks, including for individuals with cancer, have been raised. IV therapy has also been associated with side effects like anxiety.

The availability of NMN is in flux due to regulatory changes. In 2022, the U.S. FDA ruled it could not be sold as a dietary supplement, leading major platforms to restrict sales.

Yes, proven lifestyle interventions can help support healthy NAD+ levels. These include regular exercise, a balanced diet, and adopting strategies that promote cellular health and stress response.

NAD+ levels decline with age due to several factors. As we get older, NAD+ consumption by certain enzymes increases, while the efficiency of recycling pathways decreases, creating an imbalance that depletes the coenzyme over time.

The choice depends on your needs, but oral supplements are less expensive and more convenient, while IV therapy has higher bioavailability but is costly, inconvenient, and not FDA-approved for anti-aging. Given the mixed evidence, a discussion with a healthcare provider is recommended before starting any form of supplementation.

While certain foods contain forms of Vitamin B3 that act as NAD+ precursors (like NR in milk), the amounts are generally too low to significantly boost NAD+ levels in the body to the extent seen in supplementation studies.