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 catalyse 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.
