NAD Supplement: Importance & Function

NAD Supplement: Importance & Function

What is NAD?

Nicotinamide adenine dinucleotide (NAD) is a coenzyme form of vitamin B3 (niacin) found in every cell in the body. As a coenzyme, NAD supports the activity of several enzymes with essential roles in cellular function, particularly in cellular energy metabolism and ATP production and in cell signaling pathways essential for cellular health. NAD also plays a central part in maintaining redox homeostasis and balanced levels of cellular oxidants [1,2].

The Difference Between NAD, NAD+, and NADH

It’s not unusual to see NAD used as a synonym for NAD+, but they are different things biochemically. NAD refers to both NAD+ and NADH, which are two forms of the same molecule. These two forms are converted into each other in redox reactions, which are reactions where electrons are transferred between molecules. Electrons are particles with a negative electric charge (e–) that orbit the nuclei of atoms. The word redox is a blend of the words reduction, which means gain of electrons, and oxidation, which means loss of electrons. In redox reactions, the molecule that donates electrons is said to be oxidized and acquires positive charge, while the molecule that receives electrons is said to be reduced and acquires negative charge; the negatively charged molecule may bind to protons, i.e., positively charged hydrogen atoms (H+).

As you may have guessed, NAD+ is the oxidized version of NAD (NAD minus one electron), while NADH is the reduced form of NAD (NAD plus one electron and one proton). NAD+ and NADH are the main forms in which NAD exists in cells and they are constantly converted back and forth between these two forms in redox reactions; NAD+ is converted into NADH by receiving two electrons and binding one proton.

Figure 1. NAD+ ←→ NADH Redox Reaction

A very important detail about NAD+ and NADH is that they must be maintained at a high NAD+/NADH ratio (i.e., higher levels of NAD+ than NADH) to sustain healthy cellular function [3–5]. This high ratio is essential for maintaining efficient cellular energy metabolism and healthy mitochondrial function. To maintain a high NAD+/NADH ratio, NAD+ must be continuously synthesized, metabolized, and recycled and cells have multiple strategies to do so. You can learn more about them in our article “What is NAD+? Everything You Need to Know.”

The Benefits of NAD+

One of the most crucial functions of NAD+ is to carry electrons extracted from nutrients in cell energy pathways (glycolysis, fatty acid oxidation, and the citric acid cycle) and deliver them to the electron transport chain where they are used to power the production of ATP through oxidative phosphorylation in mitochondria [3]. NAD+ is therefore essential for mitochondrial function and ATP production; consequently, it is essential to every process that requires ATP, such as macromolecule synthesis, cellular growth, muscle contraction, heartbeat, and neuronal signaling, just to name a few.

NAD+ also participates in signaling pathways and processes essential for cell health [6]. NAD+ is a co-substrate of NAD-dependent enzymes such as PARPs and sirtuins that mediate important processes such as supporting mitochondrial function, DNA repair, genomic stability, cellular senescence, cell differentiation and survival, and metabolic adjustments, among others [5–9]. These actions are essential for cell and tissue health and general healthspan and underlie many of the benefits of NAD+. 

Some of the main NAD benefits include:

• Supporting mitochondrial function*
• Supporting muscle function* 
• Supporting cardiovascular function*
• Supporting metabolic health* 
• Supporting cognitive function*
• Supporting healthy aging*

How is NAD+ Related to Aging?

As we age, NAD+ levels in cells and tissues decline because NAD+ consumption by NAD-dependent enzymes can exceed cells’ capacity to synthesize or recycle NAD+. The decline in NAD+ levels can impact mitochondrial function and ATP production, impair cellular growth and regeneration, compromise DNA repair, destabilize cellular redox balance, and allow for oxidative stress to develop [1,10]. These cellular changes can drive and accelerate the aging process and age-related physiological decline [1,11–13]. Accordingly, low NAD+ levels have been linked to several age-related features, including poorer brain and muscle performance, and poorer cardiac, metabolic, liver, and kidney health [1,10].

Is The Recommended Daily Value of Niacin/ Vitamin B3 Enough?

Vitamins are essential nutrients needed for proper cellular function and metabolism that cannot be synthesized in the body in sufficient amounts for survival. Therefore, vitamins must be obtained through the diet, either from foods or from dietary supplements. Because NAD+ is a coenzyme form of vitamin B3, its levels are dependent on the vitamin B3 status of the body. Dietary compounds that contribute to the vitamin B3 status of the body, and consequently to NAD production, are known as niacin equivalents or vitamin B3 equivalents. 

The daily value (DV) for vitamin B3 equivalents is 14 mg/day for women and 16 mg/day for men. As mentioned above, as we age, NAD+ levels gradually decline in tissues, which contributes to the aging process and poorer health outcomes[14–17]. Preclinical research has shown that restoration of NAD+ levels in aged animals promotes health, supports mitochondrial and cellular function, and supports healthspan [4,18–24]. These studies indicate that the daily value might not be sufficient to maintain NAD+ levels as we age but that boosting NAD+ levels with an NAD supplement may help to counter age-related decline.

How To Promote NAD+ Levels

NAD+ levels can be promoted by supporting its biosynthesis. This can be done by providing substrates and intermediates for NAD+ production. NAD+ is continuously synthesized, metabolized, and recycled in cells through three different pathways: NAD+ can be produced from the amino acid L-tryptophan through the de novo synthesis pathway and from the vitamin B3 forms nicotinic acid and nicotinamide through the Preiss-Handler pathway and the salvage pathway, respectively. L-tryptophan, nicotinic acid, and nicotinamide can therefore support NAD+ synthesis in the body. 

In addition, NAD+ levels can be supported by intermediaries of these biosynthetic pathways such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). NMN and NR are both part of the salvage pathway of NAD+ synthesis; NMN is an intermediate of the pathway, while NR can be converted into NMN to enter the pathway. Both NMN and NR can therefore also support NAD+ synthesis [24]. Other molecules that can contribute to the vitamin B3 status of the body include NAD—which as you’ll recall means both NAD+ and NADH—itself and the other coenzyme form of vitamin B3, NADP [25]. 

Foods with NAD+-Boosting Compounds

Niacin equivalents are found in all animal, plant, and fungal foods because these organisms also require NAD for life. Meat, fish, dairy, eggs, some vegetables, and whole grains are good sources of vitamin B3, but the form of niacin equivalents can differ between them [25]. 

Animal-based foods are the best sources of nicotinamide. NAD and NADP are actually the main forms of niacin equivalents in animal foods [26], but these molecules are broken down during digestion into nicotinamide, which is the form that is absorbed [27,28]. Red meat, chicken, and fish are among the richest sources of nicotinamide [25,29].

Nicotinic acid is the main form of vitamin B3 in plant foods. In some cereal grains, nicotinic acid is part of a complex called niacytin, which is concentrated in the outer layers of whole grains; because these are removed by milling, whole grains are a better source of vitamin B3 [25,29]. 

NMN is found in small amounts in fruits and vegetables such as edamame, avocado, broccoli, cucumber, cabbage, and tomato, and in smaller amounts in meat and shrimp [30]. NR has been found in small amounts in cow milk [31] and Brewer's yeast [32].

Overall, nicotinamide is the main form of vitamin B3 absorbed from food sources [33–37] (and the preferred precursor for NAD+ synthesis in most peripheral tissues [14,38,39]). 

Food sources of NAD-boosting compounds:

• Red meat
• Chicken
• Fish
• Shrimp
• Dairy
• Eggs
• Whole grains

NAD Supplements

NAD+boosting supplements are an additional strategy to promote NAD+ levels. These supplements can support NAD+ synthesis in two ways: by providing the dietary precursors and/or intermediates for NAD+ biosynthesis that are found in smaller amounts in food sources, such as nicotinic acid, nicotinamide, and NR, and/or by supporting the activity of crucial enzymes in these biosynthetic pathways.

An example of the latter is resveratrol, a polyphenol found in grapes and berries. Resveratrol supports the activity of the rate-limiting enzyme in the salvage pathway (NAMPT). This pathway is essential for restoring the NAD+ that is consumed by NAD-dependent enzymes by recycling nicotinamide produced as a byproduct of those reactions back to NAD+ [40]. It's the activity of NAMPT that determines the rate at which nicotinamide is recycled to NAD+. By promoting its activity, resveratrol may consequently support NAD+ synthesis.

Several enzymes in the different pathways of NAD+ synthesis need ATP for their activity. However, ATP must be bound to a magnesium ion to be biologically active [41,42]. Therefore, magnesium can also support NAD+ synthesis by allowing the activity of enzymes that require ATP. 

How Qualia NAD+ Supports NAD+ Levels

The NAD+ molecule is so crucial for cell function that cells have multiple ways to produce it. With Qualia formulations we believe a better approach for long-term health is to support the functional redundancy inherent in the human body for NAD+ maintenance. So rather than supporting only one pathway of NAD+ production, we developed Qualia NAD+ to support different ways to make it. This entails providing several substrates for NAD+ biosynthesis (NIAGEN® Nicotinamide Riboside, nicotinamide, and nicotinic acid), as well as supporting rate-limiting steps in the different pathways. This has been our approach in designing Qualia NAD+. You can learn more about it in our article Qualia NAD+ Ingredients.*

Frequently Asked NAD Supplement Questions

What is NAD supplement used for?

NAD supplement is used to boost NAD+ levels in the body. 

Is NAD the same as vitamin B3?

Vitamin B3 is any of a group of molecules that share an ability to be used to make the “N” part of an NAD molecule. NAD stands for nicotinamide adenine dinucleotide. All forms of vitamin B3 can be used to supply the nicotinamide part of NAD. So think of vitamin B3, as it’s most commonly used, as being part of NAD.

Which form of niacin/vitamin B3 is the best?

The different forms of vitamin B3—nicotinic acid and nicotinamide—as well as their related derivatives, such as nicotinamide riboside (NR), can all contribute to the vitamin B3 status of the body and consequently, NAD+ levels. Rather than thinking whether one is better than the other, we see them as complementary molecules that support NAD+ through different pathways. We believe that the best form to support NAD+ is by combining them.

*These statements have not been evaluated by the Food and Drug Administration.  This product is not intended to diagnose, treat, cure, or prevent any disease.

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