NAD+ is an acronym for nicotinamide adenine dinucleotide. NAD+ is a coenzyme found in every living cell in your body. A coenzyme is a small molecule that works together with an enzyme to speed up a specific chemical reaction. Coenzymes and enzymes are like two peas in a pod. In order to understand coenzymes like NAD+, we must first understand their best friend: the enzyme. 

What’s an enzyme?

Enzymes are made of proteins and we have thousands of them in our bodies, each working as a catalyst for a different biological function. The most commonly known enzyme is in saliva, known as amylase. These scientific names are difficult to remember but a good rule to note is that most enzymes end in -ase. 

For example, amylase breaks down carbohydrates we get from food into smaller molecules in order to be easily digested by our stomachs and small intestine. However, enzymes don’t just break down molecules. They also build molecules as well. We see one of the best examples of this in adenosine triphosphate (or ATP) synthase, an important enzyme that NAD+ works alongside to produce our energy.

What’s a coenzyme?

Coenzymes are structurally non-protein molecules. They work by loosely binding with the enzymes through covalent bonds. This bond is temporary. Coenzymes transfer electrons with the enzymes and break their bond. These electrons help catalyze a chemical reaction. In the case of NAD+ and the enzyme, ATP synthase, the transferred electrons trigger the production of cellular energy. Coenzymes are essentially microscopic transporters, dropping off their electrons to enzymes over and over again. 

Where do we get our coenzymes?

Coenzymes are either naturally created in the body or provided in the form vitamins, taken from either the foods we eat or the supplements we take. However, not all vitamins are treated the same. Some vitamins, like folic acid and other B vitamins, help the body produce coenzymes by providing the building blocks to construct them. Other vitamins like Vitamins C and E require no assembly; they act on their own, in this case as antioxidants.

How do we get NAD+?

NAD+ is naturally produced by every cell in your body. Methods such as fasting and exercise can increase the production of NAD+. Supplementation is also a proven way to boost your NAD+ levels. Foods with vitamin B3 or NAD supplements can help maintain your NAD+.

If you are looking for foods only, foods such as cow’s milk, mushroom, fish, green vegetables, and yeast, are all sources of vitamin B3 and can maintain your NAD+ levels. 

Direct supplementation of the molecule NAD+ is only modestly effective due to its inability to enter cells directly. A paper in the Journal of Nutritional Science and Vitaminology shows that your body breaks down orally-administered NAD+ down to smaller molecules in order to be used. Once in the cell, they will need to be reassembled again to form NAD+. This breakdown and reassembly requires extra energy and time, making direct supplementation of NAD+ an inefficient way to boost your body’s NAD+ levels.

The best way to supplement your NAD+ is through vitamin B3 supplements. Vitamin B3s are NAD+ precursors , meaning they are smaller molecules used as building blocks to create NAD+. Once they pass through the cell, they are assembled together by enzymes in order to form NAD+. 

There are 3 main forms of vitamin B3: niacin, nicotinamide, and nicotinamide riboside. Some may be better than others so it’s important to know the differences to ensure you are choosing the best micronutrient for your needs. Niacin, a form of B3 commonly found in multivitamins and breakfast cereals, can cause the unwanted side effect of flushing (redness of the face) at high doses. Nicotinamide does not cause this effect, but is an inefficient NAD+ precursor. It also inhibits sirtuins, an important class of enzymes that promote cellular repair. Nicotinamide riboside is both safe and effective at boosting NAD+ levels.

What does NAD+ do?

NAD+’s main function is in our cells’ mitochondria. Our mitochondria are often called ”the powerhouse of the cell”. They earn this nickname because of their ability to produce energy for all of our cellular functions. In order to create energy, they work to produce a molecule called adenosine triphosphate or ATP. ATP is essentially an energy-storage molecule, or tiny battery, that provides energy wherever and whenever the cell needs it. 

There are several ways our cells and mitochondria produce ATP. However, the most efficient way is a process called the electron transport chain which produces the majority of our cells’ ATP needs. The electron transport chain is a chemical process that occurs within our mitochondria, specifically in the mitochondrial membrane.

NAD+ participates in this process by acting as a delivery mechanism, donating and accepting negatively-charged electrons to and from several enzymes that sit patiently in the mitochondrial membrane.

When it accepts these electrons, NAD+’s molecular structure changes to NADH. NADH has an H at the end because it has a positively charged hydrogen molecule added to its structure. Once they drop off these electrons and expel the hydrogen proton, NADH turns into NAD+, indicating that the hydrogen molecule has now been wedged off its structure.

After the dropoff, NAD+ has completed its purpose. The electrons power the enzymes in the mitochondrial membrane, like electricity powers a factory. The enzymes work together like an assembly line, passing the electrons down to the next enzyme until they reach the last mechanism, ATP Synthase. ATP synthase completes the process by building out the final package, ATP. Afterwards, ATP is sent throughout the cell, providing energy where needed.

NAD+ is a vital electron carrier that essentially powers our mitochondria. Without it, the electron transport chain would not start. Like an abandoned factory, the enzymes in the mitochondrial membrane would remain unused and barren. 

NAD+, PARPs, and sirtuins.

NAD+ has other roles with other enzymes in the cell as well. For example, sirtuins and poly (ADP-ribose) polymerases (PARPs) are other classes of enzymes that require NAD+ in order to function properly. Sirtuins are the regulators of the cell, while PARPs play an active role in DNA repair. 

Things like overeating, drinking, lack of sleep, lack of exercise, and viral infections all lead to a depletion of NAD+, requiring an overproduction of energy from our mitochondria. This overproduction causes damage to our cells. Our sirtuins and PARPs are vital to repair the damage.

Rather than stripping NAD+ of its electrons, sirtuins use NAD+ as a coenzyme to perform a task called deacetylation, while PARPs use NAD+ to help perform a task called ribosylation. These are a first step in the important process of cellular response to stress and DNA repair. 

Why is NAD+ important?

NAD+ is a vital coenzyme that helps our bodies to generate energy and perform many other cellular processes. It keeps us breathing air into our lungs and pumping blood into our hearts. 

However, the focus on NAD+’s role in energy creation took some time to gain traction in the wider public eye. Scientists Arthur Harden and William John Young first discovered NAD+ in 1906 when studying fermentation. Continuing off of Louis Pasteur’s work with yeast cells, Arthur Harden sought to learn more about how yeast’s metabolic processes work. Unfortunately, the public did not express the same interest in the research as Harden or Young. Although heralded as a profound discovery among scientific circles, NAD+ never got the exposure necessary to truly highlight its importance until later.

The research accelerated In the 1930s when pellagra, also known as “black tongue” disease, started running rampant in the American South. Pellagra was a fatal disease that caused inflamed skin, diarrhea, dementia, and sores in the mouth. At the time, Joseph Goldberger identified the disease as a vitamin B3 nutritional deficiency. His experiments revealed that milk and yeast alleviated the symptoms. Eventually, Goldberger’s research led to the formulation of niacin, the earliest form of vitamin B3. Niacin became an effective micronutrient to treat the disease, demonstrating improvement in patients within a matter of days and putting NAD+ research back on the map.

Fortunately, pellagra is no longer a common affliction. However, efforts to study the hallmarks of aging reveal mitochondrial health to be at the forefront of the conversation about NAD+. Hassina Massudi and her team from the Department of Pharmacology at the University of New South Wales uncovered age-associated changes in NAD metabolism in humans. Massudi’s research shows us that NAD+ levels decline by over 50% after the age of 40 and that low levels of NAD+ are linked to mitochondrial inefficiency. 

As a result of this new wave of public interest, NAD+ research pioneered the discovery of nicotinamide riboside, a more effective way to increase NAD+ levels. We now better understand the science behind NAD+ and how it works in our bodies—and further research continues to provide promising news, challenging the natural degradation of our cells.

What are mitochondria? 

You may have heard mitochondria associated with the moniker, “the powerhouse of the cell”. How did they earn that nickname? 

Mitochondria are the miniature power stations or factories in each and every cell in your body. A typical living human cell contains anywhere from hundreds to thousands of mitochondria. 

Much in the same way as your digestive system, mitochondria are like small digestive systems in your cell, turning food into energy. Sugars, fats, and amino acids from proteins that we eat are converted into energy through the mitochondria. They are so effective at this that they generate an estimated 90% of the energy that our cells need.

What do mitochondria look like?

Mitochondria look like little beans in your cell. They are made of two membranes: the outer membrane and the inner membrane. 

The outer membrane acts as a wall, covering the entirety of the organelle. 

The inner membrane looks like a series of folds, consisting of several compartments. This layered shape is intended to maximize the mitochondria’s surface area, supporting a higher efficiency in its function. 

Within the inner membrane is a fluid called the matrix; this is where the magic happens.

Where did mitochondria come from?

Before the mitochondria became invaluable to human cells, they existed completely outside of them as single-celled, independent organisms. They looked a lot like bacteria. However, some time in ancient biological history, over two billion years ago, they merged with a simple cell to form a symbiotic relationship. 

At first, the plan wasn’t just to merge. The mitochondria, as bacteria, only wanted to rob the host cells of their energy and then leave them to die. But the bacteria soon realized the benefit of working together with simple cells.

The simple cells provide them with antioxidants to protect them from free radicals and toxic reactive oxygen species that the mitochondria generate as a byproduct of energy production. In return, the mitochondria produced the energy the simple cells needed. It’s a pretty sweet deal. It’s like the mitochondria are paying rent in return for housing and utilities.

Mitochondria are essentially aliens in your body. Our mitochondria even possess their own DNA, called mtDNA, giving them an independent genome. Furthermore, mitochondrial DNA is only passed down from mother to child, making you more genetically similar to your mother than your father. In fact, modern ancestry testing companies lean on your maternal ancestry line by using mitochondrial DNA.

The mitochondria’s purpose.

The mitochondria have one primary purpose: to produce energy. In order to create energy, they create a much-needed molecule known as adenosine triphosphate or ATP. 

What is ATP?

Our bodies don’t just create and harness energy straight away. It actually stores the energy we produce from our food in a molecule. ATP, or adenosine triphosphate, is the primary energy storage solution for our cells. They are like tiny batteries floating around, waiting to be used. “Tri”, meaning three, denotes that there are three phosphates in the molecular structure. 

When cells need energy, ATP is broken down through a process called hydrolysis. This is actually pretty easy to do because ATP is such an unstable molecule. The three phosphates in ATP are like three roommates sharing a room. They don’t like each other and are just waiting to be split up.

When the split happens, the molecular bond between the phosphates in ATP’s tri-phosphate group is snapped off, removing one of the phosphates in the ATP molecule. The trio becomes a duo, thus turning ATP into ADP or adenosine di-phosphate.

This breakage releases immense energy and our cells use the energy to power important cellular activity. 

Our mitochondria work hard to make sure our cells have enough of these ready-to-use “batteries”, or ATP, floating around.

How do mitochondria create ATP?

In order to create more ATP, our mitochondria go through a series of chemical reactions to break down our food, particularly glucose, amino acids, and fatty acids. Glucose is really the primary molecule that our food is broken down into so let’s focus on glucose to understand how our mitochondria convert food into energy.

Our mitochondria take our glucose molecules through a process called cellular respiration which is essentially just a process of breaking down and converting glucose by combining oxygen with a glucose molecule. The oxygen is derived from the air we breathe. 

This process of adding oxygen to glucose produces a string of molecules. At its most rudimentary form, the process looks like the following formula:

Glucose + Oxygen = Carbon Dioxide, Water, and ATP. 

Carbon Dioxide and water are byproducts of the process. This is cellular respiration, simplified.

However, our mitochondria do not take glucose in its raw form. It’s not usable in its regular state so our cells break glucose down even more before passing it to our mitochondria. This process is called glycolysis.

The broken-down form of glucose is what is really combined with oxygen to produce a net of carbon dioxide, NADH, FADH2, and ATP. This process is what’s called the Krebs Cycle. Let’s break the products of this process down:

Carbon dioxide: One of our byproducts. You breathe this out. 

NADH and FADH2: Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) are coenzymes that help generate more ATP. NADH and FADH2 are their electron charged forms. Ignore this for now. We’ll talk about these important players later.

ATP: Energy!

So the Krebs Cycle creates energy but the Krebs Cycle alone does not produce enough of the ATP our cells require. The real prizes are the NADH and FADH2 that are produced in the process. They are what really produce us the majority of our ATP through what’s called the electron transport chain. 

The electron transport chain is essentially a process where our mitochondria constantly “steal” from its guests. NADH and FADH2 are electron-charged molecules and our mitochondria “steal” these electrons from NADH and FADH2, turning them into NAD+ and FAD as a result. 

In turn, our mitochondria take these charged electrons and produce a ton of ATP, turning lemons into lemonade. This process is so efficient in producing ATP, the electron transport chain produces the majority of our ATP energy. Fortunately, the mitochondria’s willing friends, NAD+ and FAD, continue to come back bearing gifts of charged electrons to sustain the process. It's a perfect supply chain and the only byproduct in this process is water, thus completing our formula:

Glucose + Oxygen = Carbon Dioxide, Water, and ATP.

Mitochondria and aging.

Research from the School of Kinesiology and Health Science from York University shows we make fewer mitochondria as we age. Your mitochondria also gradually deteriorate as you grow older, making the few mitochondria you do have left work that much harder. In fact, mitochondrial dysfunction is considered a hallmark of aging.

The same researchers from York University believe this is a result of an imbalance between our number of free radicals and our cell’s ability to remove them. But most of the scientific community agrees that the mitochondria grow less effective over time because of their decreased ability to make ATP.

Mitochondria respond to your energy needs.

In most cases, the number of mitochondria we create correlates to the amount of energy we need. This means, in large part, our daily activity dictates the number of mitochondria we create and sustain. Whenever there is a significant change in our lifestyle or habits, our mitochondria adjust their numbers. 

David A. Hood, from York University, believes there is a connection between exercise routines and mitochondrial biogenesis. Mitochondrial biogenesis is a series of complex chemical reactions within the body that signal the need for more ATP and therefore more mitochondria. Our mitochondria essentially clone themselves through a self-replication process in order to meet the new energy demand.

However, the opposite is also true. A sedentary lifestyle can signal the body that we don’t need as much ATP and inhibit the mitochondria from replicating. As a result, your mitochondria produce less cellular energy overall, leading to more general metabolic dysfunction.

Mitochondria and NAD+.

As crucial as mitochondria are for creating energy, it’s not as simple as one organelle. A bunch of different chemical reactions and coenzymes are at play, namely one critical molecule known as nicotinamide adenine dinucleotide or NAD+.

As mentioned before, two coenzymes are created in cellular respiration, FAD and NAD+. However, between the two, we produce far more NAD+ than we do FAD. If the mitochondria were factories, the NAD+ molecules are the fleet of delivery trucks and the FAD molecules are the temp drivers that only work part-time.

NAD+ is like the mitochondrion’s most reliable friend, constantly delivering charged electrons to produce bountiful ATP in the electron transport chain. 

Unfortunately, the amount of NAD+ we produce naturally declines with age. Like the mitochondria, the number of NAD+ we have in our cells is also largely affected by our lifestyle and habits. A study published in Physiological Reports shows that exercise training can naturally increase NAD+ levels. Conversely, things like age, metabolic stress, immune stress, drinking, overeating can all contribute to NAD+ depletion. 

In pursuit of understanding the science of aging and how to best manage it, the scientific community has put a large focus on NAD+ research and its relationship to mitochondrial dysfunction. It’s widely accepted that mitochondrial health plays a huge part in our overall human health and NAD+ is part of that story. Luckily, maintaining healthy mitochondrial function is possible with a few lifestyle changes. Here are some tips on how to support mitochondrial health.

Every day, our bodies carry out all manner of tasks for us. From the moment we wake through the deepest phase of our sleep cycle, our cells continually manage the internal wear and tear of life. Cellular repair plays a fundamental role in maintaining our health. Regardless of environmental circumstances, life on earth unfolds the same way for us all: we start anew each day, expend energy, then rest in order to recoup for the day to come. Without cellular repair, this universal process would be impossible.

What is cell damage?

At some point in time, we’ve all seen images of cells: ethereal, rounded orbs that come in a variety of colors, shapes, textures, and sizes. Some cells are squishy and fragile. Every day, our cells are exposed to environmental toxins, hazardous compounds, and pathogens that are attempting to damage them.

These environmental factors and pathogens attempt to attack our DNA. Every time DNA is assaulted, our cells must figure out how to repair the damage.

Cell damage causes cell cycle arrest, where duplication and division are placed on hold and cells must find a way to repair any damage before the cell cycle can resume.

What sparks cellular repair within the body?

A vital coenzyme called NAD+ plays an important role in getting cellular repair processes started.

NAD+ is a “helper molecule” that assists in generating cellular energy and activating sirtuins, which regulate our cellular health across the board.

Unfortunately, many factors contribute to lower NAD+ levels over time. Examples of NAD+ damaging stressors and metabolic insults include:

• Sedentary lifestyle

• Alcohol consumption

• Overeating and poor nutrition

• Sleep deprivation

• Sun exposure

With enough cellular energy, your cells regenerate by re-creating any structures that were damaged or lost. Most cellular repair works this way, with various components working together to carry out different stages of the process until the cell is restored to its original structure.

Not all cells or cellular units operate in the same way when it comes to regeneration, either. In a study published in the Science journal, scientists demonstrated that in multi-cellular cases, some cells can generate entirely new cells to replace any lost ones. But at the single-cell level, regeneration becomes a more involved process.

In such cases, the cell usually rebuilds and replaces missing components after the damage has been stabilized. Restoring structure and functionality at the single-cell level requires more time, energy, and steps—and in some cases, the cellular structure becomes altered permanently.

Maintain NAD+ levels to support cellular repair.

Maintaining healthy NAD+ levels will help keep your cells ready to assist with all kinds of restorative action. From assisting with basic autophagy to helping rectify various forms of cell damage that come with aging, high levels of NAD+ can support cellular resilience across the board.

All in all, unparalleled repair capabilities make our cells biological superstars— and NAD+ boosting supplements can help support their function. Whatever your wellness regimen, take care of your cells. They constantly work to keep us healthy, energized, and resilient.