NAD+ (nicotinamide adenine dinucleotide) is a vital molecule found in every living cell in the body. It plays a crucial role in cellular energy metabolism, helping to convert food into usable energy. It plays a key role in cellular energy metabolism by helping convert food into usable energy. Additionally, NAD+ supports vital cellular functions, including DNA repair and maintaining cellular health.

NAD+ levels naturally decline with age and can be depleted further by lifestyle stressors such as excess alcohol consumption, a sedentary lifestyle, a poor diet, immune stress, or excess sun exposure. Because of its central role in cell function and aging, NAD+ is a major focus of healthy aging research.

Learn more in our detailed article: “What is NAD+?”.

NAD is a general term for nicotinamide adenine dinucleotide. While NAD and NAD+ are often used interchangeably, the “+” in NAD+ indicates its oxidized form, which can accept electrons during biochemical reactions. When NAD+ accepts electrons, it becomes NADH, the reduced form. 

In certain contexts, the terms NAD+ and NADH may overlap when discussing the balance between oxidation and reduction within the cell, especially in metabolic pathways. The specific form used depends on whether the reaction is oxidative or reductive. For instance, in oxidation reactions, NAD+ functions as the electron acceptor, while in reduction reactions, NADH donates the electrons. This cycle of reduction and oxidation is crucial for maintaining the cell’s energy balance and sustaining metabolic processes.

NAD+ precursors are molecules that the body can convert into NAD+, a vital coenzyme found in all cells. These include nicotinamide riboside (NR), niacin, nicotinamide (niacinamide or NAM), and nicotinamide mononucleotide (NMN). Supplementing with these precursors can help replenish NAD+ levels, especially as they decline with age and metabolic stress. 

Learn more in our detailed article: “NAD+ Precursors.”

Increasing NAD+ levels is linked to numerous health benefits, including enhanced mitochondrial function, support for healthy aging, and brain, heart, and muscle health benefits. Because NAD+ naturally declines with age, restoring its levels may help maintain optimal cellular function and overall wellness. Emerging research also suggests potential benefits for cognitive and reproductive health, though more studies are needed to confirm these effects.

Discover the full range of benefits in our article: NAD+ Benefits”.

Lifestyle choices like regular exercise, intermittent fasting, calorie restriction, and eating a diet rich in tryptophan and vitamin B3 can all support your body’s natural production of NAD+. However, these lifestyle approaches tend to contribute modestly compared to supplementation with NAD+ precursors. 

Explore the science in our article: “How to Increase NAD+.”

Although NAD+ is essential for cellular health, taking it directly—whether orally or intravenously—is not the most efficient way to raise NAD+ levels in your cells. NAD+ is naturally produced and functions intracellularly, within the cells themselves. 

Given its large size and the presence of multiple phosphate groups, NAD+ is not well absorbed and cannot cross the cell membrane intact. Thus, NAD+ administered through oral supplementation or intravenously must be broken down first into smaller components, like NR, which can enter cells and then be converted back into NAD+. As a result, taking an NAD+ precursor like NR directly is far more efficient than taking NAD+ itself.

In the case of intravenous NAD+ administration, the process takes several hours, and many consumers report unpleasant side effects, including nausea, headaches, and gastrointestinal discomfort. These side effects are generally not experienced with oral NR supplements or NR administered intravenously.

A recent study demonstrated that intravenous NR begins increasing NAD+ levels immediately post-infusion, and peaks at 3 hours post-infusion with 20% higher NAD+ than intravenous NAD+.1 

In conclusion, taking NAD+ precursors like NR is a more effective and comfortable way to support your body’s NAD+ levels. 

Learn more in our blog post: “Why Can’t I Take NAD+ Directly?”

Currently, there is no clinical evidence demonstrating that liposomal delivery of NR is either safe or effective in humans.

Liposomal technology involves enclosing active ingredients in liquid vesicles—tiny, fat-like bubbles that can offer improved absorption. This method is typically used for ingredients with poor bioavailability in the body. However, because liposomes have an aqueous core, NAD+ and NAD+ precursors will not remain stable and will degrade rapidly (within weeks). 

Some products claim improved absorption by using dried liposomes instead. The caveat to this is that if the liposomes are dried, they collapse and shrink, no longer providing a protective barrier around the active ingredient. Analytical testing has shown that both soft gel and dried liposomal NR products contained no detectable NR—raising concerns about the reliability of this delivery method.

In short, liposomal delivery is not currently a validated or stable option for NAD+, NR, or other NAD+ precursors.

Learn more in our article on Liposomal Delivery.

While NR and NMN are both NAD+ precursors, the difference between the two comes down to biochemical efficiency. Due to a phosphate group attached to NMN, it must first be converted to NR before it can enter the cell, and preclinical data has demonstrated that NR has a greater NAD-boosting effect than NMN. Therefore, it is more efficient to consume an NAD+ precursor, like NR, rather than NMN. 

In addition to these biological differences, the regulatory status of NMN has changed. On November 4, 2022, the United States (US) Food and Drug Administration (FDA) stated that NMN is excluded from the definition of a dietary supplement. Despite its past popularity, NMN can no longer be legally marketed in dietary supplements. You can read more about the regulatory update in this article from Supply Side Supplement Journal, and review the FDA letter here.

NR is a unique, naturally occurring form of vitamin B3 and a precursor to NAD+. Once ingested, NR is converted into NAD+ through the nicotinamide riboside kinase (NRK) pathway. NR is one of the most well-researched NAD+ precursors, supported by extensive preclinical and clinical studies demonstrating its ability to safely and effectively increase NAD+ levels in the body. 

To dive deeper, explore our educational article: “What is NR”?

NR was first identified in the 1940s and has been the subject of decades of scientific research. Its role as a precursor to NAD+ and its vitamin activity were first discovered by Dr. Charles Brenner in 2004. Building on decades of preclinical research, the first human study on NR was published in 2016.2 Since then, more than 35 peer-reviewed human clinical studies on NR have been published, with over 40 additional clinical trials currently planned or in progress.

Explore the growing body of published research and ongoing clinical trials on NR.

Clinical studies have evaluated NR at doses ranging from 100 mg to 3,000 mg per day, all of which have shown an increase in NAD+. Among these, 1,000 mg per day is the most commonly studied dose.

Yes, NR is considered safe when used as directed. There are currently no known interactions or contraindications associated with NR supplementation. NR has been successfully notified as a New Dietary Ingredient (NDI) to the U.S. FDA and has achieved GRAS (Generally Recognized as Safe) status, which defines the levels at which it can be incorporated into various foods and beverages.

Clinical studies have evaluated NR at doses of up to 3,000 mg per day with no clinically meaningful adverse effects attributed to its use.3 While NR has been well tolerated in these trials, as with any supplement, you should discontinue use and consult your healthcare provider if you experience any persistent discomfort or side effects.

Niacin (nicotinic acid), nicotinamide (niacinamide or NAM), and NR are all forms of vitamin B3, but they are processed differently in the body and have distinct biological effects and safety profiles. While there’s no published evidence suggesting that combining NR with niacin or nicotinamide is harmful, taking them together does not appear to provide additional benefits.

NR stands out for its ability to efficiently increase NAD+ levels without the flushing associated with niacin or the potential sirtuin inhibition seen with nicotinamide. In comparative research, NR demonstrated superior effectiveness in both boosting NAD+ and activating sirtuin enzymes—key regulators of cellular health and repair.2

To learn more about each NAD+ precursor and how they work, visit our NAD+ Precursors page.

Yes, current evidence shows NR is safe for individuals with MTHFR variants. One clinical study found NR had no impact on DNA methylation in individuals with common mutations in the MTHFR gene.4 However, we recommend consulting with your healthcare provider prior to use. 

Read more in our educational article on methylation.

No, NAD+ or its precursors do not cause cancer. There is no scientific evidence showing that increasing NAD+ with precursors like nicotinamide riboside (NR) raises cancer risk in humans. While a few animal studies involving genetically modified models predisposed to cancer have explored potential links, these findings do not translate to human outcomes.

In contrast, hundreds of preclinical and clinical studies have examined the potential benefits of raising NAD+ levels with precursors like NR. The vast majority show no association with cancer, and some even suggest protective effects.

Most recently, in a clinical study involving adult survivors of childhood cancer, NR was well tolerated, with no serious adverse events attributed to its use.5 

As with any supplement, individuals with a history of cancer should consult their healthcare provider before beginning use. 

To learn more, visit our blog post on NAD+ and Cancer.