NMN vs. NR: Everything You Need to Know About NAD Supplements

If you're interested in health and wellness, and especially healthy aging, you've almost certainly heard about supporting NAD levels. But what is NAD? And why do you only see NAD supplements that speak to supporting NAD levels, instead of actually containing this substance? Is there a reason we can't just take NAD directly, and instead opt for precursor supplements that contain NR or NMN? And for that matter, what are NAD, NR and NMN?

If all the acronyms and conflicting information are making your head spin, you aren't alone! Read on for all the NAD knowledge you could ask for (and maybe more).

What is NAD?

Let's start with the most important question: why do we want to boost NAD in the first place? NAD, or nicotinamide adenine dinucleotide, is a coenzyme found in every single cell in your body. It plays a massive role in basically every aspect of health, from energy metabolism to DNA support and other cellular functions. In fact, NAD is required for over five hundred enzymatic reactions in your body and virtually every biological process.

Unfortunately, levels naturally decline with age, and boosting NAD levels has been an area of fascination to healthy aging enthusiasts everywhere.

And while you can consume CoQ10 to improve your CoQ10 levels, or take melatonin when you're yearning for more sleep, NAD is different. We can't just take NAD directly as a supplement since it is poorly absorbed by the digestive system and cannot pass through the cell membrane.

Scientists have therefore turned to NAD precursors to raise NAD levels. (A precursor is a molecule that is used to build other molecules.) That brings us to the NMN vs. NR supplement debate: NMN and NR are both NAD precursors that can help boost your body's NAD levels. So which is better?

NAD glossary of terms

Before we get too far into which is better for boosting NAD levels, NMN or NR, let's first do some defining of acronyms. Here are most of the terms and acronyms you'll see:

• NR = nicotinamide riboside
• NMN = nicotinamide mononucleotide
• NAD = nicotinamide adenine dinucleotide
• NAM = nicotinamide (also called niacinamide)
• Niacin = nicotinic acid

You may notice that these words all look awfully similar, which definitely lends to the confusion. The reason they all have similar names, though, is because they are all similar in their molecular structure.

Apologies in advance for the minor biochemistry lesson, but we did warn you this was going to be comprehensive!

Think of a molecule as a small Lego structure, made up of teeny individual Lego pieces (atoms) stuck together. Small Lego structures can be attached to each other to build larger structures, just as small molecules can be used to build larger, more complex molecules. The most basic "Lego structure" molecules we listed above are nicotinamide and niacin, which are both forms of vitamin B3.

When a ribose (a kind of simple sugar) is attached to the nicotinamide, you get nicotinamide riboside (NR). And when a phosphate group is attached to the ribose (which is attached to the nicotinamide), you get nicotinamide mononucleotide (NMN). And when that whole molecule is attached to adenosine monophosphate (AMP), you've finally arrived at nicotinamide adenine dinucleotide, or NAD. Phew!

In humans and other mammals, most of the NAD in the body is synthesized from these precursor molecules using various cellular pathways (i.e., your body uses the small "Lego structures" to build larger ones).

Here is how it works:

1. First, you consume one or more forms of vitamin B3 from your diet or supplements (usually niacin, NAM, and/or NR). They are then carried inside the cells by a cell membrane transporter.
2. Once they've passed inside the cells, they are converted to NMN—NAM is converted to NMN by enzymes called nicotinamide phosphoribosyltransferase (NAMPT), while NR is converted to NMN by enzymes called nicotinamide riboside kinases (NRKs).
3. Finally, NMN is converted to NAD by enzymes called nicotinamide mononucleotide adenylyl transferases (NMNAT).

And with that, you've passed an introductory biochemistry class!

Is NR better than NMN?

Yes, NR is generally better than NMN. Let's dive into why. Numerous NAD precursors have been studied for their ability to raise NAD blood levels. The most well-known include niacin, NAM, NMN, and NR. We can go one by one to illustrate why NR is the precursor generally considered to be the best:

1. Niacin

   – requires a three-step process (called the Preiss-Handler pathway) to become NAD. High doses cause flushing. So that makes it one of the less efficient options…with some aftereffects not everyone loves.

2. NAM

   – does not cause flushing, but research suggests it may not activate sirtuins as efficiently as other NAD precursors (important enzymes that are involved in cellular repair). Also, it does not raise NAD levels as effectively as NR.

3. NMN

   – is the closest structurally to NAD. However, it is too large to cross into cells and is actually converted back to NR before entering the cellular interior, introducing an additional metabolic step in the path to NAD. NMN supplements are also currently not permissible to be sold as a dietary supplement in the United States, as they are under investigation by the FDA as a potential drug.

4. NR

   – nicotinamide riboside does not cause flushing, activates sirtuins, and is the closest in structure to NAD while still being able to cross into cells and raise NAD levels significantly.

To recap: all these NAD precursors can raise NAD levels in humans. The question is, which one is the best to take as a supplement? Well, one precursor ticks all the boxes and does not come with any caveats: nicotinamide riboside.

NR supplements (like Niagen) are well-tolerated, effective at raising NAD levels, and are available as a dietary supplement in the United States.

Should I take NMN or NR?

Considering that NMN supplements must be converted back to NR before being able to cross into the interior of the cells (and the fact that they are not permissible in the US at this time), NR is our preferred NAD precursor. NR is easily shuttled into cells via a membrane transporter, where it is converted to NMN and then to NAD. Remember, you want to take an ingredient that is as close to the final product (NAD) as possible, while still being able to easily pass into your cells.

Sidenote: A preclinical study was published that suggested there is an NMN-specific transporter, called Slc12a8. However, these results have been hotly contested and there is currently no real consensus on the matter.

Are NR supplements safe?

Yes! NR supplements have been investigated in numerous clinical studies and have been shown to promote NAD levels, support mitochondrial function and number in skeletal muscle, and positively affect metabolism. Additionally, they don't cause the "niacin flush."

If you and your healthcare provider decide an NAD-boosting supplement is right for you, look for a reputable and well-studied ingredient like Niagen. Always follow label instructions and your healthcare provider's guidance to ensure you are getting a proper dose.

The bottom line: the best way to boost NAD

If you're looking for a way to promote healthy aging and energy production, an NAD-boosting supplement is something you'll want to have in your arsenal. Healthy NAD levels are key when it comes to many of your aging-related goals—aging gracefully, maintaining optimal health, and keeping your energy up! Nicotinamide riboside, or NR, is a great way for you to help your body increase NAD levels and ensure your cells have enough of this essential coenzyme.

References

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