NAD+ (nicotinamide adenine dinucleotide) and NADH (reduced nicotinamide adenine dinucleotide) are two forms of the same coenzyme, NAD (no plus).

We're not trying to be nit-picky here, but the plus sign is a key distinction because NAD refers collectively to its two molecule forms, NAD+ and NADH.

Together, these two forms of NAD play a critical role in many of the biological processes within a cell, from energy production to DNA repair, gene expression, and much more.

Grasping the differences between the two halves (NAD+ and NADH) of the whole (NAD) is important for understanding many of the metabolic processes essential for life.

This article will explain the differences between NAD+ and NADH, how they work together, and the potential benefits of taking supplements that increase NAD levels.

Key Takeaways: Differences Between NAD and NADH

• NAD+ and NADH are two different forms of the same molecule that play major roles in cellular metabolism and energy production.

• NAD+ is the oxidized form of the molecule, while NADH is the reduced form.

• The ratio of NAD+ to NADH is important for maintaining proper cellular function, and disruptions to this ratio can contribute to age-related decline and disease.

• Supplementation with compounds like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) has been shown to increase NAD+ levels and potentially offer health benefits like supporting a healthy aging process, more energy, and cognitive performance.

• However, more research is needed to fully understand the effects of NAD+ and NADH supplementation on human health.

What Is NAD?

Let's start with the larger picture and work our way to the smaller details.

NAD (no plus) stands for nicotinamide adenine dinucleotide, and it's a coenzyme that exists in all our cells.

NAD exists in two forms: NAD+ and NADH, which is the main topic of this article. And together, NAD+ and NADH are called a "redox couple." Its two molecule forms NAD+ and NADH acts as a helper in many important enzymatic reactions in the body, which can include:

• Energy production: converting food into ATP

• Control gene expression: how genes are turned on or off in response to different signals in the body

• DNA repair: remove damaged DNA and replace it with new DNA

• Immune function: regulates the activity of immune cells

You can think of a redox couple like players in a game of catch. And the game itself is called "redox reactions."

In this game, the ball represents elections, and the two players are NAD+ and NADH—the redox couple.

One person throws the ball (electrons) to the other person. This player becomes "oxidized" because they no longer have the ball, but are now primed to catch a ball.

The second player catches the ball (electrons) and becomes "reduced" because they now have the ball (gains electrons). But their hands are full and can't catch any more balls. They'll need to throw what's in their hands to keep the game going.

• Oxidized = lose elections

• Reduced = gains electrons

The two molecules then switch roles and the process repeats.

The balls (electrons) is what fuels the chemical reactions in the mitochondria, and without a steady supply of NAD, the mitochondria can't properly convert the nutrients from foods into usable energy or participate in cellular signalling.

What Is NAD+?

NAD+ is the oxidized form of NADH. It's also considered to be the biologically functional form of NAD because it has catalytic properties (facilitates chemical reactions).

The plus sign indicates that it has a positive charge, meaning it lost electrons.

But it doesn't stay in this oxidized form.

During cellular respiration, NAD+ accepts electrons and a hydrogen ion to turn into NADH.

This back and forth between the same molecule, which is refed to as the electron transport chain, contributes to adenosine triphosphate (ATP) production.

NAD+ is also involved in DNA repair, gene expression, and other important cellular processes.

In these functions, NAD+ serves as a cofactor for enzymes that modify DNA, regulate gene expression, and repair damaged DNA.

One interesting feature of NAD+ is that it is believed to be unable to cross the mitochondrial membrane, which may have important implications for its role in cellular metabolism and whether or not NAD+ IV infusion is a valuable way support NAD levels long term [1].

What Is NADH?

NADH is the reduced form of the coenzyme NAD+, meaning that it can transfer electrons to other molecules.

Specifically, NADH is involved in the electron transport chain, which is a series of redox reactions that occur in the inner mitochondrial membrane that ultimately generate ATP (cell's fuel), a process known as oxidative phosphorylation.

What's The Difference Between NAD+ And NADH?

NAD+ and NADH are virtually the same molecule (with some small differences).

NAD+ is the oxidized form of NAD, which means it loses two electrons (in the form of hydrogen atoms) and a proton (hydroden ion) during a redox reactions.

NADH is the reduced form of the NAD molecule, which means it gains two electrons and hydrogen proton.

NAD+ and NADH are essentially two halves of a whole. However, there isn't an always a equal NAD+ and NADH ratio.

The ratio can vary on the metabolic state of the cell. For instance, there is a higher concentration of NADH during cellular respiration than NAD+ [2].

The NAD+ and NADH ratio is important because it can affect the balance of many metabolic processes in the body. The mitochondrial NAD+/NADH ratio can influence the activity of enzymes, and as a result, the many biological processes that occur within the cell.

An large imbalance in the ratio can lead to disruptions in these processes, which can contribute to a variety of health conditions [3].

Therefore maintaining a healthy NAD+ to NADH ratio is key for one's overall health and wellness.

Supplements That Increase NAD

NAD levels are important because it's involved in many various metabolic processes that are essential for cellular function and health.

As we age, and experience stress, or illness, NAD levels decrease, leading to as slowdown of these metabolic processes, which could be a factor for various health conditions.

By increasing NAD levels, it's believed that we can potentially enhance these metabolic processes and promote overall health.

The problem is that it's not possible to simply take oral NAD supplements, as the molecule size is too large to enter the cells, which is why precursors to NAD like nicotinamide riboside and nicotine mononuleotide supplements are popular as they eventually convert into NAD in the body.

Let's take a look at popular supplements used for NAD therapy.

1. Nicotinamide riboside (NR)

This form of vitamin B3 has been shown to increase NAD+ levels in animals and humans, especially when taking through Nicotinamide Riboside Capsules. NR is found naturally occurring, but it's not found in enough concentrations in foods to substantially raise NAD+ levels, which is why it's taken as a dietary supplement.

2. Nicotinamide mononucleotide (NMN)

Nictoinamide mononucleotide (NMN) is another precursor to NAD. It's actually the next step in NR synthesis into becoming NAD+.

Some studies have also suggested that NMN supplementation may improve exercise performance, insulin sensitivity, and cognitive function, though further research is needed to confirm these potential benefits [4].

Nicotinamide Mononucleotide supplements come in various forms such as NMN capsules, gummies, and powders, making them easy to add to your daily routine.

3. Resveratrol

Resveratrol is a natural compound found in various plant species, including grapes, berries, and peanuts. It is a type of polyphenol, which is a group of plant compounds known for their antioxidant properties.

It's believed to activate a protein called SIRT1, which in turn increases NAD+ levels.

4. Quercetin

Quercetin is a flavonoid, which is a type of plant pigment found in many fruits, vegetables, and grains. Quercetin capsules are suggested to have antioxidant and anti-inflammatory properties, and is believed to have potential health benefits such as reducing the risk of heart disease and cancer, improving immune function, and supporting brain health [5].

It is believed to increase NAD+ levels by inhibiting an enzyme called CD38.

5. Melatonin

Melatonin is a hormone naturally produced by the pineal gland in the brain that helps regulate sleep and wake cycles. It's believed to increase NAD+ levels by activating an enzyme called SIRT1.

Factors To Consider When Choosing A Supplement

It can be a rewarding experience finding the right wellness supplement that helps you feel your best.

Here's some advice on what to look for when shopping for a supplement that supports cellular health through increasing NAD levels.

• Safety: Always choose safe supplements that have been tested for purity and safety with a third-party lab.

• Format: You can find supplements in the form of pills, soft chews, and even NAD+ IV infusions. Not all formats will give you the same results. and you should carefully consider what will fit into your budget and lifestyle best.

• Quality: Look for supplements that are manufactured by reputable companies and come from high-quality ingredients that you can trust.

• Dosage: Make sure the supplement dosage is appropriate for your needs and matches the recommended dosage based on scientific research.

• Ingredients: It's good practice to check the ingredients list to ensure there are no potential allergens or fillers you may be sensitive to.

• Effectiveness: Look for supplements that have been shown to be effective through clinical studies or research.

• Cost: Consider the cost of the supplement and compare it to other options to ensure that you are getting good value for your money.

Frequently Asked Questions: Differences Between NAD+ And NADH

1. What are NAD+ and NADH?

NAD+ and NADH forms of NAD. These two forms of the same molecule are what fuel many of the chemical reactions within the cell that play important roles in cellular metabolism, including energy production and DNA repair.

2. What is the difference between NAD+ and NADH?

NAD+ is an oxidized form of the coenzyme NAD molecule, while NADH molecules are the reduced form. NAD+ can accept electrons, while NADH can donate electrons. The cell requires both in order to complete a range of biological processes.

3. How does NAD+ become NADH?

NAD+ becomes reduced to NADH when it accepts two electrons and a hydrogen ion (proton) from another molecule.

During a redox reaction, NAD+ accepts two electrons and a hydrogen ion from a substrate molecule, which becomes oxidized in the process. This reaction converts NAD+ to its reduced form, NADH, which gains two electrons and a hydrogen ion.

4. How can I increase my NAD+ levels?

Some supplements and compounds, such as nicotinamide riboside, NMN, and resveratrol can help increase NAD+ levels. Exercise and calorie restriction may also help have also been observed to increase energy demands on the body, requiring higher levels of NAD.

5. What are the benefits of increasing NAD+ levels?

Increasing NAD+ levels may have potential benefits for age-related diseases, such as neurodegenerative diseases and metabolic disorders. It may also improve cellular function and metabolism.

6. What Does NADH do?

NADH is the reduced form of NAD+ and is produced by the transfer of electrons and a hydrogen ion (proton) from substrates to NAD+ during cellular respiration and other metabolic pathways.

NADH is also involved in many other metabolic pathways, including the metabolism of amino acids, fatty acids, and nucleic acids. NADH serves as a cofactor for enzymes that catalyze reactions in these pathways, and its ability to donate electrons is critical for the conversion of substrates into products.

The Takeaway: What's The Difference Between NAD+ And NADH?

NAD+ and NADH are two crucial molecules involved in various metabolic processes, with NAD+ acting as an electron acceptor and NADH as an electron donor. The balance between the two molecules is vital for maintaining cellular functions and energy production.

Supplements like nicotinamide riboside, resveratrol, and quercetin are believed to increase NAD+ levels and potentially provide health benefits, although more research is needed to fully understand their effectiveness.

For those considering NAD+ or NADH supplementation, it's essential to consult with a healthcare professional to determine if it's appropriate and safe for their individual needs. Overall, understanding the difference between NAD+ and NADH is crucial for comprehending how the body generates energy and maintaining overall health and wellness.

References:

1. Engelking, L. R. (2015). Oxidative Phosphorylation in. Textbook of Veterinary Physiological Chemistry, 219-224.

2. Yang, Y., & Sauve, A. A. (2016). NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1864(12), 1787-1800.

3. Liao, B., Zhao, Y., Wang, D., Zhang, X., Hao, X., & Hu, M. (2021). Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition, 18(1), 54.

4. Broman-Fulks, J. J., Canu, W. H., Trout, K. L., & Nieman, D. C. (2012). The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial. Therapeutic Advances in Psychopharmacology, 2(4), 131-138.