Many people are looking for ways to help them feel as young and as vibrant as they once did in their glory days.

NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are two of the most promising supplements that are giving Father Time a run for his money.

How do these supplements work? And which compound NMN vs. NR offers the best health benefits?

NMN and NR are biosynthetic precursors to an essential molecule called NAD+ (nicotinamide adenine dinucleotide), which is required in all cellular metabolism functions.

NAD+ levels naturally decline with age, which is linked to various health-related issues [1]. Numerous animal studies have observed that increasing NAD in aging animals helped increase the subjects' lifespan and overall vitality, which has led to increased interest in the potential benefits of NR and NMN supplementation to raise NAD+ levels in humans.

In this article, we'll take a closer look at the research surrounding NMN and NR.

At present, comparing the effectiveness of NR supplementation versus NMN won't be entirely meaningful to most people's lifestyles as the two compounds have never been examined side-by-side in human clinical studies, but we think it's worth having a look at the differences and similarities of both compounds for better understanding of the supplements in this wellness niche, so you can decide for yourself what makes sense for your wellness goals.

The Key Takeaways: NMN Vs. NR Overview

• NMN and NR are two supplements that have been shown to increase NAD+ levels in the body.

• Both NMN and NR have been studied in animal and human trials, with promising results.

• NMN may increase NAD levels in some tissues, such as the liver, while NR may be more effective in other tissues, such as muscle.

• NMN and NR are generally considered safe, but more research is needed on long-term safety and efficacy.

• The cost and availability of NR and NMN supplements vary, with NR generally being more widely available and less expensive.

• NAD+ is a crucial molecule that exists in all cells and is required for a number of physiological processes, from cellular energy production to DNA repair, gene expression, and more.

NMN Vs. NR: What Are The Main Differences?

1. Chemical Structure

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have slightly different chemical structures, which affects how the body processes and uses each compound.

They're nearly identical with riboside sugar and a nucleotide base, but NMN is a larger molecule because of an added phosphate group.

Some scientists speculate that the NMN molecule is too large to cross cellular membranes to exert its effects. However, on the other side of the argument, NMN is closer to NAD+ than NR, making it easier for the body to convert it to NAD+.

2. Safety Profiles & Scope Of Research

Safety is a top priority when an individual is considering a new supplement.

Nicotinamide riboside has been studied more extensively than NMN, but both compounds have been found to be generally considered safe for use in healthy humans [2,3].

NR has been the focus of several human clinical trials, and it has been shown to increase NAD+ levels in various tissues and organs, potentially improving age-related health issues. However, research on NMN is still relatively new, and more studies are needed to determine its efficacy and safety.

However, it's important to speak with your healthcare provider for personalized guidance with any supplement, especially if you have any underlying health conditions or are on other supplements or medications.

3. Cost And Availability

When it comes to cost and availability, NR has been on the market longer than NMN and is, therefore, more widely available and often less expensive.

However, as NMN supplements gain popularity, it becomes more readily available, and costs decrease.

The price of both supplements can vary depending on the brand and the form of the supplement (e.g., powder, capsules, IV drips). Most supplements you'll find are powders and convenient NMN pills, but we do have NMN in gummies and tincture form. 

It's important to note that while cost is a factor to consider, it shouldn't be the only factor.

The quality and purity of the supplement should also be considered when making a purchasing decision, which is why we always recommend looking at third-party testing to validate the product's safety.

4. Bioavailability

We understand that both NMN and NR do similar things in terms of existing as precursor compounds to NAD+, but which one gets the gold medal for absorption?

Bioavailability refers to the concentration of the substance that enters the bloodstream and has an active effect.

Indicators of bioavailability include measurement of NMN and NR levels in the blood following orally administered NMN and NR.

While it is true that NMN has a larger molecular size than NR, making it more challenging to cross the cell membrane to exert its effects, recent studies have suggested that NMN may have another advantage over NR.

The biggest advantage NMN has over NR is that it is one step closer than NR to becoming NAD+, as NR needs to be converted to NMN before it becomes NAD+.

There are studies that point to the rapid absorption of NMN oral supplementation, which showed a direct increase in NAD+ synthesis [4].

Studies indicate that NMN can assist in the production of NAD+ in various tissues throughout the body, including the pancreas, adipose tissues, skeletal muscle, blood vessels, kidneys, and the heart [4].

It's worth noting that only NR has human studies on bioavailability, while NMN bioavailability has only been observed in animal subjects, and further research is needed to draw a clearer conclusion on which has the higher level of bioavailability in humans.

How Do NMN And NR Become NAD+?

Once NMN or NR are ingested, they undergo several steps to become NAD+.

A specialized enzyme called nicotinamide riboside kinase (NRK) converts NR into NMN.

From this step, NMN turns into NAD+ with the enzyme called mononucleotide adenylyltransferase (NMNAT).

Think of the enzymes that transform NMN or NR into NAD+ as little bakers in a kitchen, working together to bake a cake.

Just as bakers mix together different ingredients like flour, sugar, and eggs to create a cake, the enzymes in our body mix NMN or NR to create NAD+.

The enzymes act like little machines, precisely measuring and transforming the NMN or NR into NAD+, just as bakers precisely measure and mix ingredients to create a delicious cake. The end result is a fully-baked cake, or in the case of our bodies, NAD+ to support various physiological processes by increasing cellular energy production.

NMN vs. NR: Efficacy

There are studies that prove oral NMN administration and NR supplementation are effective in increasing NAD+ levels in the body [4]. However, no clinical research specifically on humans investigates which compound comes out on top.

Animal studies have suggested that NMN may increase NAD+ levels in some tissues, such as the liver, while NR may be more effective in other tissues, such as muscle [5].

Personal accounts of older people using NMN and NR supplements have reported positive effects such as increased energy levels, improved cognitive function, and even notice changes in fine lines and wrinkles, which is why these supplements have become so popular.

However, increasing NAD+ levels isn't the same as taking an energy drink for a quick boost or enhancing physical attributes overnight, like muscle strength or endurance.

When we're talking about cellular energy, it's about giving the cells enough NAD+ so that they can perform their basic (yet very important) functions.

But if your body already has sufficient NAD+ levels, taking more NAD+ isn't going to make you superhuman. It's like adding grease to a wheel that's already well-lubricated. NR and NMN supplements are best suited for middle-aged to older adults.

Even though you may hear lots of the positive effects of these anti-aging supplements, it's important to conduct your research and speak to a healthcare professional before integrating a new supplement into your long-term routine.

These supplements also shouldn't be considered a band-aid fix to a healthy lifestyle that considers a balanced diet, regular exercise, and stress management.

Frequently Asked Questions About NMN Vs. NR

1. What is NAD+, and why is it important for our health?

NAD+, or nicotinamide adenine dinucleotide, is a coenzyme found in every living cell and is required for many biological processes, including cellular energy production, mitochondrial function, DNA repair, and gene expression.

NAD+ also regulates the circadian rhythm, the immune system, glucose metabolism, and aging processes.

Research on the function of NAD+ has been gaining serious momentum, giving us insights into the cause of many age-associated diseases. As we age, the body naturally starts producing less and less NAD+, and early research in this space is looking at ways to increase NAD+ to support metabolic disease, slow cognitive decline, and improve insulin sensitivity to help people liver longer, healthier lives.

2. Why can't you supplement NAD+?

Supplementing NAD+ isn't an effective way to increase NAD+ levels in the body as the molecule structure is too large to pass through the cell membrane.

Instead, the body needs to synthesize NAD+ from smaller molecules such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR).

3. Which anti-aging supplement is best, NMN vs. NR?

With limited research on NMN supplements in humans, it's difficult to say which compound comes out on top, but both NR and NMN have promising results in animal models for anti-aging.

Many scientists in the anti-aging space, like Dr. David Sinclar, choose an NMN supplement over NR. There are many personal accounts of people using NMN supplements with more results in energy levels over NR supplementation.

3. Are NMN and NR safe to use as supplements?

Studies conducted so far suggest that both NMN and NR supplements are safe for most healthy adults

However, it's always recommended to consult with a healthcare professional before starting any new supplement regimen, especially if you have any pre-existing medical conditions or are taking other medications.

On top of this, it's important to purchase supplements from reputable brands to ensure the purity and quality of your NMN or NAD supplement.

4. What are the side effects of NR and NMN supplementation?

Based on the available research, oral NMN and NR supplements are generally well-tolerated by healthy adults. But there's not enough research looking at the long-term safety of these compounds.

And while both NR and NMN and safe to use, there are some side effects associated with them which may include: adverse effects on the liver (in high doses), gastrointestinal upset (nausea, diarrhea, abdominal discomfort), and in some rare cases, people may have an allergic reaction to the ingredients in the supplements.

This is why carefully choosing your NMN and NR supplements is important, and only purchasing them from trusted brands that can provide third-party lab testing.

5. How much NMN or NR should I take, and how often?

The optimal dosage and frequency of NMN and NR supplementation are not yet fully established, and more research is needed to determine the most effective and safe doses for humans. However, most studies on NMN and NR supplementation in humans have used doses ranging from 250-1000 mg per day, with some studies using up to 2000 mg per day.

Like with any wellness supplement, it's best to start on the lower end and work your way up slowly.

The Takeaway: NMN Vs. NR Supplementation

Research shows that both NMN and NR effectively increase NAD+ levels as precursor compounds while maintaining a favorable safety profile.

Because NAD+ is a coenzyme needed for nearly all cellular functions, it's believed that increasing NAD+ levels can help slow down age-associated physiological decline.

There isn't any scientific literature comparing NMN and NR side-by-side in humans, so it seems that the choice comes down to personal preference, as they both accomplish very similar things.

Ultimately, the choice between NMN and NR may come down to individual preference and personal goals. Remember that while these supplements may promise to improve health and longevity, they are not a magic bullet and should be used with a healthy lifestyle, including a balanced diet and regular exercise.

If you want to try NMN or NR supplementation, research and consult a healthcare professional before using NAD+ precursors.

Resources:

1. Cantó, C., Menzies, K. J., & Auwerx, J. (2015). NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell metabolism, 22(1), 31-53.

2. 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), 1-13.

3. Irie, J., Inagaki, E., Fujita, M., Nakaya, H., Mitsuishi, M., Yamaguchi, S., ... & Itoh, H. (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.

4. Yoshino, J., Baur, J. A., & Imai, S. I. (2018). NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell metabolism, 27(3), 513-528.

5. Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., ... & Auwerx, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838-847.