NAD+ Supplements: Do IVs, NMN, and NR Really Work?

Why Do We Need To Boost NAD+?

We have already discussed that if NAD+ were a city’s power grid, every light, factory, and repair crew would depend on it. Without NAD+, your cells can’t efficiently turn food into energy, repair DNA, or coordinate the thousands of molecular conversations that keep you alive.

That’s why researchers call NAD+ a “linchpin” molecule - and why there’s growing interest in ways to restore its levels as we age. But not all NAD+ boosting methods work the same way. I’ve spent some time looking at what science says about main strategies - and why the popular debate between NMN and NR matters more than marketing would have you believe.

How Your Body Makes NAD+ and Where Precursors Fit In

NAD+ isn’t something you only get from food or supplements - your body can make it through three main pathways:

• De novo pathway (from tryptophan) – This is a complex, multi-step process that builds NAD+ from scratch using the amino acid tryptophan, which is found in protein-rich foods like meat, eggs, and seeds. While it's an essential backup pathway, it's slow and requires a lot of energy. For this reason, it's not the body’s main source of NAD+ in adulthood; the body prefers the more efficient salvage pathway.

• Preiss–Handler pathway (from nicotinic acid) – This pathway uses nicotinic acid (also known as niacin or vitamin B3), which is a compound found in many foods. It was historically important in preventing diseases like pellagra. However, this pathway is used less often in modern diets, and a key drawback of supplementing with high doses of nicotinic acid is that it can cause "flushing," a temporary skin redness and tingling sensation.

• Salvage pathway (from nicotinamide and precursors) – This is the dominant route, recycling over 85% of NAD+ from nicotinamide (a byproduct of NAD+ use).

The salvage pathway is where the famous precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) come in. Both can be converted into NAD+ - but the conversion steps, bioavailability, and transport into cells differ (and this is where the “NR vs. NMN” debate starts).

Boosting NAD+ isn’t just about adding raw materials - it’s also about keeping the recycling machinery (enzymes like NAMPT) efficient and reducing unnecessary NAD+ drain.

IV NAD+ Therapy - Direct Delivery to the Bloodstream

The pitch: Clinics offer intravenous NAD+ infusions as the “fastest” way to raise NAD+ levels, bypassing digestion entirely.

What the science says:

• A small pilot study showed that a single IV dose rapidly increases NAD+ in the blood (Grant et al., 2019).

• A review of IV NAD+ pharmacokinetics confirms 100% bioavailability and notes potential for targeted, high-dose delivery (Braidy & Grant, 2020).

• However - there’s no large-scale human trial showing anti-aging or performance benefits in healthy people. Current research is mostly on safety, metabolism, and some addiction therapy protocols.

Pros: Immediate NAD+ elevation; bypasses absorption issues (which is common for oral supplements).
Cons: Expensive, time-intensive, and lacks long-term evidence for general wellness.

IV NAD+ reaches peak plasma levels far faster than any oral form - but how that translates into long-term benefit is still unproven.

Nicotinamide Riboside (NR) - The Direct Route

What it is: A naturally occurring form of vitamin B3, and a direct precursor to NAD+ via the salvage pathway.

Human evidence:

• Increases NAD+: In healthy middle-aged adults, 1000 mg/day NR raised NAD+ by ~60% over 6 weeks (Martens et al., 2018).

• Safety: Well tolerated up to 1000 mg/day long term, with no major adverse effects (Conze et al., 2019).

• Form: Typically sold as NR chloride in capsules; powders exist but are less common.

Why it’s compelling:

• Strongest human safety database of all NAD+ precursors.

• Avoids an extra conversion step that NMN usually needs to enter most cells (Ratajczak et al., 2016; Vreones et al., 2023).

• Stable in capsules and resistant to degradation in storage.

NR is FDA-recognized as “Generally Recognized As Safe” (GRAS) and has official New Dietary Ingredient (NDI) notifications - something NMN currently lacks in the US.

Nicotinamide Mononucleotide (NMN) - Popular, but with Caveats

What it is: Another NAD+ precursor one step “further” along the salvage pathway than NR.

Human evidence:

• First human trial in healthy men confirmed safety and NAD+ boosting (Irie et al., 2020).

• In prediabetic women, 250 mg/day NMN improved muscle insulin sensitivity (Yoshino et al., 2021).

• Sublingual NMN appears more bioavailable than capsules (Pencina et al., 2023).

Why it’s popular:

• Early marketing and animal data suggested a direct shortcut to NAD+.

• Often available in powders and sublingual forms, appealing to those seeking faster absorption.

The catch:

• Most oral NMN is converted to NR before entering cells (Ratajczak et al., 2016; Vreones et al., 2023). That's so interesting and complex to understand - but see below to see why.

• Regulatory uncertainty: In the US, NMN is under FDA investigation as a possible drug, limiting supplement sales.

NMN works - but in most tissues, it’s likely acting as an NR “pro-drug.”

NR vs. NMN - The Core Differences

Why NMN Seems Better - and Why That’s Not the Whole Story

On paper, it looks straightforward:
NR → NMN → NAD+.
So you might think: “If NMN is already one step closer to NAD+, why not skip NR and take NMN directly?” Here’s the catch:
Most cells can’t take NMN in directly.

Research shows that NMN usually has to be converted into NR first outside the cell (in the gut or bloodstream) before it can cross the cell membrane. Once NR is inside, it’s converted back to NMN and then into NAD+ (Ratajczak et al., 2016).

So the real-life pathway for NMN supplements often looks more like this:

NMN (outside cell) → NR (crosses membrane) → NMN (inside cell) → NAD+

Meanwhile, NR supplements skip that extra outside-the-cell conversion step:

NR (outside cell) → NR (crosses membrane) → NMN (inside cell) → NAD+

This is why some scientists describe NMN as acting like a “pro-drug” for NR — it often has to become NR to do its job (Vreones et al., 2023). That doesn’t mean NMN is useless - far from it. It raises NAD+, and some studies even show specific benefits in certain populations (Yoshino et al., 2021). But if your goal is the most direct route into the cell, NR is the molecule with its own built-in door.

Which to Choose?

If your priority is:

• Strongest human safety evidence & regulatory clarity → NR

• Specific metabolic benefits (per limited trials) → NMN

• Fastest measurable NAD+ spike → IV NAD+ (short-term)

For most people, starting with NR in capsules offers the best balance of science, stability, and legality. NMN can be considered for targeted purposes, ideally in sublingual form for better absorption.

If you hoped I will recommend exact supplements in this article - you will have to stay tuned. I am currently researching the best supplements for NR and NMN in the market (both for your health and pocket). I cannot wait to share it with you.

Bottom Line

Boosting NAD+ is possible - but context matters. Lifestyle strategies like exercise, good sleep, and time-restricted eating remain the foundation. From there:

• NR offers robust safety and direct conversion.

• NMN works, but may be less efficient and faces regulatory challenges.

• IV NAD+ is rapid but costly and under-researched for general use.

Future research will tell whether boosting NAD+ translates into longer, healthier lives - but for now, the smartest strategy is to choose the most efficient precursor for your needs, backed by real human data.

The Road Ahead

Next up, we’ll dive into NR and NMN separately - how they work, what human studies show, how to think about dosing and quality, and who might benefit. We’ll also explore other strategies (like targeting CD38) and how to track whether your NAD+ support is doing anything meaningful for you.

The science of NAD+ is still unfolding, but one truth remains: investing in your health today is the surest path to a stronger future.

Important Terms

Bioavailability - simply how much of a supplement you swallow actually gets into your body to do its job.

Tryptophan - amino acid - a building block for proteins - that your body can't make on its own, so you have to get it from food (meat and poultry, fish, dairy, eggs, nuts & seeds). Think of it as a special ingredient you can only buy at the store. Your body uses this ingredient to make several important things, including proteins, and also to start the long, slow process of making NAD+.

Sublingual form - means "under the tongue." A sublingual supplement is one that you place under your tongue, where it dissolves and the active ingredients are absorbed directly into your bloodstream through the surrounding tissues. This method can sometimes be faster and more effective than swallowing a pill because it bypasses the digestive system, which can break down some of the supplement before it gets to where it needs to go.

References

• Braidy, N., & Grant, R. (2020). Pharmacokinetics and metabolism of intravenous NAD+ in humans. Current Opinion in Clinical Nutrition & Metabolic Care, 23(6), 405–409.

• 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.

• Dollerup, O. L., Christensen, B., Svart, M., et al. (2018). A randomized placebo-controlled clinical trial of nicotinamide riboside supplementation in healthy men and women. The American Journal of Clinical Nutrition, 108(2), 343–353.

• Grant, R., Berg, J., Mestayer, R., Braidy, N., Guevara, J., & Cincotta, M. (2019). A pilot study of the safety and pharmacokinetics of a single dose of intravenous nicotinamide adenine dinucleotide (NAD+). Journal of Drug and Alcohol Research, 8, 1–8.

• Helman, T., & Braidy, N. (2023). Importance of NAD+ anabolism in metabolic, cardiovascular and neurodegenerative disorders. Drugs & Aging, 40, 33–48. https://doi.org/10.1007/s40266-022-00989-0

• Irie, J., Inagaki, E., Fujita, M., et al. (2020). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal, 67(2), 153–160.

• Martens, C. R., Denman, B. A., Mazzo, M. R., et al. (2018). Chronic nicotinamide riboside supplementation is well‐tolerated and elevates NAD+ in healthy middle‐aged and older adults. Nature Communications, 9(1), 1286.

• Pencina, K., et al. (2023). Sublingual NMN administration elevates blood NAD+ levels and alters the gut microbiome in a double‐blind, placebo‐controlled, crossover trial. GeroScience, 45(5), 3021–3034.

• Ratajczak, J., Joffraud, M., Trammell, S. A. J., et al. (2016). NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nature Communications, 7, 13103.

• Vreones, M., Røsland, G. V., & Brenner, C. (2023). The metabolic fate of NMN in mice and humans. Metabolism, 148, 155694.

• Yoshino, M., Yoshino, J., Kayser, B. D., et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224–1229.