NAD+ Explained: What It Is, Who Actually Needs ...

NAD+ supplements are everywhere right now — IV clinics, social media, longevity podcasts. Many cost hundreds of dollars. The problem is that most people using them don’t understand how NAD+ actually works in the body and may be spending a lot of money for very little benefit.

I want to spend some time talking about NAD+ metabolism, what it is used for in the body, who is at greatest risk from perturbations in NAD+ status, and how to best use NAD+ boosting molecules for improving health.  If you are at all interested in NAD+, you have to read this first.

NAD stands for Nicotinamide Adenine Dinucleotide, which is a coenzyme used by nearly all cells of the body for things like energy production and cellular repair processes. Without adequate NAD+ availability, our bodies would be unable to efficiently produce energy or perform necessary repair functions vital for life. We know that NAD+ levels are very high when we are younger but homeostasis becomes disturbed with chronic diseases like diabetes, autoimmune diseases, chronic infections, sedentary lifestyles, and even natural aging. 

When it comes to metabolism, NAD+ and NADH (NAD+’s reduced, alternate form) serve to help power the mitochondria by facilitating the flow of electrons that eventually get converted into energy. In order for the mitochondria to function properly, we need to maintain higher levels of NAD+ compared to NADH.  If NADH becomes more abundant than NAD+, our cells are less able to make energy and health begins to decline.

For DNA repair, certain enzymes use NAD+ to power their function. Having enough NAD+ within the cell is critical because our DNA is constantly being damaged from inflammation, sun damage, and simple errors that happen with DNA replication.  Without proper DNA repair, we can see increased rates of mutations that may lead to cancer development. NAD+’s powerful ability to aid in DNA repair was highlighted in the ONTRAC trial, an Australian study that showed taking nicotinamide (a form of vitamin B3) reduce the rates of non-melanoma skin cancer by 23%. The idea was that B3 (see below) replenished the NAD+ pools necessary for proper DNA repair.

How is NAD+ Made?

What most don’t realize is that NAD+ is primarily recycled in the body rather than newly created. When NAD+ is used during DNA repair or inflammatory processes, it gets broken down into nicotinamide. Using the enzyme NAMPT, nicotinamide is converted into NMN, which is then converted back into NAD+ (this will be important when we talk about supplements!). Another form of vitamin B3, nicotinic acid (niacin), can also be converted into NAD+ through a different pathway.

It is also important to realize that NAD+ is compartmentalized inside cells. The NAD+ used in the nucleus, mitochondria, and cytosol is regulated separately. This means that nuclear NAD+ homeostasis may be preserved while mitochondrial NAD+ status is struggling. This is important to remember when are thinking of “boosting” NAD+ — we have to be sure that whatever supplement we are using is able to get inside and actually affect these individual compartments.

Conditions that Alter NAD+ Homeostasis

The most important question when considering supplementation is this: “Do I need this?”  Not everyone has problems with NAD+ that require supplementation; and, unfortunately, it is very hard to measure in blood work.  Therefore, we have to look to certain conditions that may point to problems with NAD+ availability:

• Aging
• Insulin resistance
• Obesity
• Fatty liver disease
• Autoimmune diseases
• Chronic infections
• Chronic alcohol use

Symptoms that may suggest poor NAD+ status:

• Fatigue
• Brain fog
• Poor exercise tolerance
• Frequent illnesses
• Poor recovery

These symptoms are not specific to problems with NAD+ but are common when NAD+ homeostasis is impaired. 

NAD+ Boosting Supplements

We have many NAD+ boosting options to choose from, often referred to as NAD+ precursors.  These are:

• Nicotinamide Riboside (NR) — oral
• Nicotinamide Mononucleotide (NMN) – oral
• NAD+ — IV infusion, injection, or oral

A simplified understanding of how these molecules play into the NAD+ system:  NR —> NMN —> NAD+

Which one to choose? This is the main reason I wanted to write this article! I have seen a big uptick in patients requesting (or purchasing from outside sources) NAD+ infusions or injections. These are often very expensive but have garnered a lot of hype recently. And it makes sense — if you want to increase NAD+ availability, why not give the body NAD+ directly? 

The problem lies in the idea of NAD+ compartmentalization, mentioned above.  NAD+ exists in pools in the body: nucleus, mitochondria, and cytosol of the cell. And since most of NAD+ is recycled, these pools tend to self-manage their own NAD+ supply. When we inject or use IV NAD+, the levels of NAD+ in the bloodstream go up, but intracellular NAD+ levels are only minimally affected. This is because the NAD+ molecule is too large to reliably enter cells or the mitochondria, therefore, needing to be degraded into NR or nicotinamide before it can reliably cross cellular membranes. If this conversion does not happen, it’ll just be excreted by the body. The sum is spending a lot of money for a fairly inefficient route of boosting NAD+ levels where it matters. And oral NAD+ performs even worse, as most of it is broken down in the stomach.

Oral NR+ (and to some extent NMN) is much better absorbed through the GI tract and can cross cell membranes better than NAD+ directly. Once inside the cell, it can then be converted to NAD+ and shuttled to areas of need. Ironically, oral NR and NMN are also far cheaper and have far more data behind their utility than direct NAD+ supplementation. So why spend more money on something with less data?

NAD Precursors and Contamination

As with any supplement, we want to make sure the quality is top-notch. What is on the label should be equal to what is in the capsule. Unfortunately, supplement quality is highly variable — especially with products sold on large online marketplaces like Amazon. 

Here are a few examples:  

* October 2021*: Out of 22 of the most popular NMN products on Amazon, only 14% met or exceeded their label claims. 64% of the products had NMN levels below detectable limits (under 1%), and 14% contained no NMN at all.

* February 2025*: Out of 39 Nicotinamide Riboside (NR)-containing products on Amazon, 36% of them had NR content below the method reporting limit or detection limit (less than 1%).

* May 2025*: Out of 22 of the most popular Nicotinamide Adenine Dinucleotide (NAD+) products on Amazon, 54% had NAD+ content below the method reporting limit or detection limit (less than 1%)

*IMPORTANT NOTE: The company that sponsored these studies is part of the research arm for a popular NAD+ precursor supplement, so there is risk of bias.

But I think the summary message is still true: don’t purchase on Amazon.

My Recommendations on NAD+ Precursors

The best way to improve NAD+ status is to identify and remedy the reason for its decline. The two main conditions I think are most critical would be insulin resistance and chronic inflammation.  Insulin resistance creates a metabolic bottleneck in the mitochondria. When excess nutrients enter the system but cannot be efficiently processed into energy, the balance between NAD⁺ and its reduced form (NADH) becomes disrupted. When NADH accumulates relative to NAD⁺, mitochondrial energy production becomes less efficient and metabolic health begins to decline. 

Chronic inflammation, which often increases with aging, also plays an important role. Inflammatory signaling increases the activity of enzymes such as CD38 and PARPs that consume NAD⁺ during immune activation and cellular stress. Over time, this increased NAD⁺ consumption can deplete cellular NAD pools.

Exercise is the best way to resolve inflammation in the aging body and has also been shown to directly upregulate the NAD recycling pathway.  Time-restricted eating and high-dose Omega 3 intake can also help reduce inflammation and allow better NAD+ homeostasis.

Once you are on the path to addressing these concerns and are interested in further boosting NAD+ status in the body, my recommendation is to use oral NR+ which has the most data, especially with resolving inflammation.  

1. Look for NR formulations that use the Niagen® branded ingredient 

2. Only source from reputable companies that undergo rigorous third party testing for verification of ingredients

3. Skip NAD+ infusions, injections, or oral formulations, which appear to be far less efficient ways of raising intracellular NAD⁺ levels

NAD+ biology is fascinating, and I think we should better prioritize “why” we choose to take something. With NAD+ homeostasis, the fundamentals matter most: increasing exercise, optimizing metabolic health, and reducing chronic inflammation. Supplements can help, but only when they’re used intelligently.