Why You Can't Take NAD+ Directly—and the Best Precursor to Boost NAD+ Effectively

Key Takeaways: 

• The NAD+ molecule as a supplement is largely ineffective because NAD+ cannot enter cells intact and is unstable in supplement form.

• No published human studies show that oral NAD+ supplementation increases NAD+ levels, a conclusion recently acknowledged by the National Advertising Division (NAD) of the Better Business Bureau (BBB).
  

• Liposomal NAD+ products don’t live up to the hype: manufacturing processes break down liposomes, reducing their ability to improve absorption.

• Nicotinamide riboside (NR), a small NAD+ precursor, efficiently enters cells and is reliably converted into NAD+, making it a smarter way to boost NAD+ levels.

• NR is backed by extensive clinical research demonstrating safety, bioavailability, and benefits for healthy aging, unlike direct NAD+ supplements, which lack solid human data.

 *Based on an established role of extracellular NAD+ as a danger signal (Linden et al., 2019); also observed with IV administration in humans as shown by an increase in inflammatory markers. Based on a randomized, placebo-controlled pilot study (Preprint: Hawkins et al., 2024). 

If you’re interested in healthy aging—or have noticed "longevity" and "anti-aging" topics trending more and more on popular podcasts like Andrew Huberman's Huberman Lab—NAD+ is likely already on your radar. 

But what exactly is NAD+, and why aren’t NAD+ supplements the best option? NAD+ (nicotinamide adenine dinucleotide) is a coenzyme, meaning it helps other enzymes carry out essential functions, supporting over 500 enzymatic reactions throughout the body.¹ We need NAD+ for everything from repairing DNA and pumping blood to contracting muscles and helping our mitochondria turn food into fuel, keeping our cellular engines running smoothly.

However, NAD+ levels naturally decline with age, dropping by as much as 65% between age 30 and 70.^2,3 This decline may be linked to increased metabolic stress, including greater activity of NAD-consuming enzymes, higher cellular demands, and accumulated DNA damage. As NAD+ levels fall, signs of aging—both internal and external—tend to accelerate. That’s why maintaining healthy NAD+ levels with NAD+ precursors is considered a key strategy for supporting healthy aging and long-term vitality.

The Truth About Oral NAD+ Supplements: They Don’t Actually Boost NAD+ Levels

You might think that taking an NAD+ supplement would be the easiest way to boost your levels—but it’s not that simple. NAD+ is a large molecule that cannot cross cell membranes in its whole form. Before your body can use it, NAD+ has to be broken down into smaller building blocks outside the cell. Only then can those components be transported across the cell membrane and converted back into NAD+ inside the cell, where it actually does its job.

As a recent scientific review explains,⁴ 

“Owing to its size and charged nature, NAD+ cannot passively pass through cellular membranes, including the plasma membrane.” 

“...this probably occurs indirectly through the generation of NAD+ degradation products, such as NMN, NR or NAM, which act as precursors.”

In other words, NAD+ taken orally must first be broken down into these smaller molecules before it can re-enter cells and contribute to NAD+ synthesis.

In fact, no published human studies have shown that oral NAD+ supplementation increases NAD+ levels. This finding is consistent with multiple published studies and review articles,^4,5 and was recently corroborated by the National Advertising Division (NAD), an independent self-regulatory body overseeing the truth in advertising. The NAD pointed out the lack of published human studies demonstrating that oral NAD+ supplementation elevates NAD+ levels, stating:

So, what’s the solution? In this article, we’ll dive into why taking NAD+ directly isn’t the best way to boost NAD+ levels—and why NAD+ precursors like nicotinamide riboside (NR) offer a smarter, more effective approach.

The Problem: NAD+ Cannot Directly Enter Cells

NAD+ is a relatively large molecule—more than twice the molecular weight of NR—and carries two negatively charged phosphate groups. Because of this large size, negative charge, and polarity, NAD+ cannot readily cross cell membranes.

Therefore, NAD+ taken orally or intravenously must first be broken down into smaller precursor molecules like NR or NAM (nicotinamide) before it can be taken up by cells. Once inside the cell, these precursors are used to reassemble NAD+ where it’s needed for cellular function.

Another reason why NAD+ supplements are not recommended is because the molecule is unstable, degrading rapidly when exposed to light, moisture, or heat. This instability can make it difficult to maintain the efficacy of oral NAD+ supplements. In fact, an FDA briefing document states that NAD+ is unlikely to remain stable in capsule form under normal storage conditions.

And it’s not just capsules—even intravenous (IV) infusions of NAD+ face significant challenges with efficacy. In a recent pilot study, researchers found that NAD+ IVs did not elevate blood NAD+ until 24 hours after infusion—and then only by about 2% compared to baseline.⁶ This suggests that much of the infused NAD+ is broken down outside cells into smaller components like nicotinamide (NAM) or ADP-ribose.

In that same pilot study, those receiving NAD+ IV also experienced an elevated white blood cell count, which may indicate an inflammatory immune response. When extracellular NAD+ levels in the bloodstream rise above normal, as can happen with high-dose IV infusions, the body may interpret this as trauma within the body, leading to an immune response, and potentially causing inflammation. Some researchers propose that extracellular NAD+ acts as a danger signal,⁷ prompting enzymes to rapidly break it down into NAM, ADP-ribose, and potentially NR.

Overall, supplementing with NAD+ directly—whether through capsules or IVs—is inefficient because the body must first break it down into smaller components before it can be used by cells, requiring extra energy and resources in the process. But before we dive into some better options (hint: we’ve already mentioned one a few times in this article!), let’s take a closer look at another popular delivery method that doesn’t live up to the hype: liposomal NAD+.

Does Liposomal NAD+ Improve Bioavailability? The Truth Explained

Liposomes are tiny, fat-based particles designed to encapsulate and protect molecules—often used to enhance absorption or bioavailability. But when it comes to boosting NAD+ levels, they may not be the best choice.

This is because liquid-form liposomes contain a water-based core, but NAD+ and NAD+ precursors are highly unstable in water and begin to degrade within weeks. Dried or powder-based liposomes are also ineffective, as they are easily damaged during the manufacturing process, causing them to break apart. This breakdown reduces the structural integrity of the liposomes and undermines their intended purpose of improving bioavailability.

Although many liposomal NAD+ and NAD+ precursor products on the market claim to enhance stability and absorption by encapsulating the molecules in these protective bubbles, the reality is that liposomes often break down during standard supplement manufacturing processes, ultimately diminishing their effectiveness.

In fact, one comprehensive industry analysis of liposomal NR products found that five out of eleven contained less than 1% of the labeled NR amount, while the remaining six also fell short, containing only 1-89% of what was claimed on the label.

On top of that, there is no substantial evidence showing that liposomal NAD+ increases cellular NAD+ levels more effectively than other forms.

The Best Approach: Supplement with NAD+ Precursors

So, if supplementing with NAD+ isn’t a good option, and liposomal NAD+ products also aren’t living up to the hype, what’s the solution? 

A more efficient method to increase NAD+ levels is by using smaller building blocks called precursors—and one of the most well-studied and bioavailable NAD+ precursors is NR, or nicotinamide riboside. NR has been extensively researched for its ability to efficiently and safely boost NAD+ levels.

Due to its small size and stable structure, NR can easily enter cells through known transporters called equilibrative nucleoside transporters (ENTs). Once NR is inside a cell, it is rapidly converted into NAD+, restoring NAD+ levels at the cellular level. 

In a randomized, placebo-controlled clinical study, NR supplementation was shown to increase NAD+ levels in a dose-dependent manner—meaning the more NR participants took, the more their NAD+ levels rose.⁸ Those who took 100 mg of NR daily experienced a 22% increase in whole blood NAD+ after two weeks, while those taking 1000 mg saw levels rise by 142%.

Another recent peer-reviewed study found that oral NR supplementation increased NAD+ levels in the human brain.⁹ This is the first human study to demonstrate that a single dose of NR can cross into the brain and directly raise cerebral NAD+ levels, providing evidence that NR boosts NAD+ where it matters most—at the cellular level in the brain.

The Evidence: NR Is Backed by Significantly More Research Than Oral NAD+

While NAD+ itself is well-understood biologically, there is surprisingly little data on the effects of oral NAD+ supplementation in humans. Some research exists on NADH (the reduced form of NAD+), but clinical studies using oral NAD+ are notably scarce.

In contrast, the NAD+ precursor NR has been extensively researched and featured in over 35 peer-reviewed clinical studies across various populations and conditions. These studies consistently demonstrate that oral NR supplementation significantly raises NAD+ levels in the blood and tissues.⁸

Clinical trials have suggested that NR supports heart health, brain health, healthy body composition, and muscle health.^10–13

Alongside this, NR has shown a strong safety and tolerability profile with minimal side effects, making it a reliable and well-established option for boosting NAD+.

Conclusion: Focus on What Your Cells Can Actually Use

While NAD+ is absolutely vital for cellular function, it’s essentially useless as a direct supplement because it can’t enter cells to be utilized. Only NAD+ precursors like nicotinamide riboside (NR) can efficiently cross into cells and be converted into NAD+, making NR a far more bioavailable and effective option.

Despite the hype, liposomal and intravenous NAD+ products also fall short, as they do not reliably replenish cellular NAD+ levels.

Boosting or maintaining your NAD+ with age is a smart strategy for health and longevity, but choosing the right products is crucial—you get much better value from efficient, bioavailable precursors like NR. 

Just because a product is labeled an “NAD+ booster” doesn’t mean it’s worthwhile. Trust scientific evidence over Instagram influencers and wellness buzzwords. For more on choosing safe, high-quality, and transparent NAD+ supplements, check out this article.

Overall, NR is a safe, smart choice—when sourced from reputable brands—that gives your body the tools it needs to build NAD+ and support your long-term health and vitality.

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8. Conze, D., Brenner, C., & Kruger, C. L. (2019). Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports, 9(1), 9772. https://doi.org/10.1038/s41598-019-46120-z

9. Nanga, R. P. R., Wiers, C. E., Elliott, M. A., Wilson, N. E., Liu, F., Cao, Q., Swago, S., Jacobs, P. S., Armbruster, R., Reddy, D., Baur, J. A., Witschey, W. R., Detre, J. A., & Reddy, R. (2024). Acute nicotinamide riboside supplementation increases human cerebral NAD+ levels in vivo. Magnetic Resonance in Medicine, 92(6), 2284–2293. https://doi.org/10.1002/mrm.30227

10. Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1), 1286. https://doi.org/10.1038/s41467-018-03421-7

11. Brakedal, B., Dölle, C., Riemer, F., Ma, Y., Nido, G. S., Skeie, G. O., Craven, A. R., Schwarzlmüller, T., Brekke, N., Diab, J., Sverkeli, L., Skjeie, V., Varhaug, K., Tysnes, O.-B., Peng, S., Haugarvoll, K., Ziegler, M., Grüner, R., Eidelberg, D., & Tzoulis, C. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism, 34(3), 396-407.e6. https://doi.org/10.1016/j.cmet.2022.02.001

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13. Lapatto, H. A. K., Kuusela, M., Heikkinen, A., Muniandy, M., Kolk, B. W. van der, Gopalakrishnan, S., Pöllänen, N., Sandvik, M., Schmidt, M. S., Heinonen, S., Saari, S., Kuula, J., Hakkarainen, A., Tampio, J., Saarinen, T., Taskinen, M.-R., Lundbom, N., Groop, P.-H., Tiirola, M., … Pirinen, E. (2023). Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Science Advances, 9(2), eadd5163. https://doi.org/10.1126/sciadv.add5163