What Is NAD+? And What Role Does It Play in Aging?

What Is NAD+?

NAD+ is an acronym for nicotinamide adenine dinucleotide, a coenzyme vital to the many biological processes carried out by every living cell. A coenzyme is a molecule that works with an enzyme to speed up a specific chemical reaction. You have thousands of enzymes in your body, each working as a catalyst for a different biological function. NAD+ is required for over 500 enzymatic reactions and plays key roles in the regulation of almost all major biological processes.  

A Brief History of NAD+

Scientists first discovered NAD+ in 1906 when studying fermentation. William John Young and Arthur Harden noticed there was something in liquid extracted from brewing yeast that could boost the fermentation of sugar into alcohol. They called it a “coferment.” Today, it’s called NAD+. Harden kept exploring the science of fermentation and partnered with Hans von Euler-Chelpin to investigate further. In 1929, they won the Nobel Prize for their research and increased understanding of the fermentation process, which included the chemical structure and properties of NAD+. In 1930, Otto Warburg discovered that NAD+ played a role in numerous biochemical reactions in the body. Warburg found that NAD+ was important in the transfer of electrons from one molecule to another. This transfer is the basis for the energy required for all biochemical reactions in the body.

Despite these advances, NAD+ did not receive much public fanfare until the late 1930s, when the NAD+ precursor niacin played a role in treating pellagra, a fatal disease in the American South. Pellagra caused inflamed skin, diarrhea, dementia, and sores in the mouth. Scientists discovered that milk and yeast alleviated pellagra symptoms because they each contain NAD+ precursors.  Over time, scientists identified several NAD+ precursors — including nicotinic acid (NA), nicotinamide (NAM), and nicotinamide riboside (NR), which are all essentially different roads that lead to NAD+ production.

How Is NAD+ Important to Energy Production?

Enzymes work in tandem with NAD+ to help produce the body’s energy within your cells’ mitochondria. Mitochondria are nicknamed “the powerhouses of the cell” because they produce energy for all your cellular functions. In fact, 90% of your body’s energy is made within your mitochondria. There are several ways your cells and mitochondria produce energy, and the most efficient way is the electron transport chain process. NAD+ temporarily binds with mitochondrial enzymes, and when the bond breaks,  NAD+ transfers electrons with the enzymes. These electrons help catalyze a chemical reaction, triggering the production of cellular energy. It’s called a “chain” because multiple enzymes work together like an assembly line, passing the electrons down to the following enzyme. NAD+ drives this process by acting as a delivery mechanism, providing and accepting negatively charged electrons to and from many enzymes that sit in the mitochondrial membrane. NAD+ ignites these mitochondrial power plants in your body, and without it, the electron transport chain would not start—the assembly line would halt.

Does NAD+ Help Cellular Repair?

In addition to energy production, NAD+ also powers cell regulation and DNA repair by playing the coenzyme role with sirtuins and poly (ADP-ribose) polymerase (PARPs) enzymes. Overeating, excess alcohol consumption, sleep disruption, or lack of exercise can all damage your cells. Sirtuins and PARPs are vital to repairing cellular damage, and NAD+ is the coenzyme that drives this cellular restoration. 

Sirtuins manage fat and glucose metabolism in response to physiological changes in energy levels, regulating the network that controls energy homeostasis. Sirtuins also keep chromosomes stable, repair damaged DNA, and reduce cellular stress. 

PARPs also play key roles in DNA repair and chromosomal stability. PARPs initiate responses to DNA breaks from harmful metabolic conditions, chemicals, or radiation. Once PARPs detect a DNA breakage, they bind to DNA and begin the synthesis of a new chain of DNA with the help of other DNA-repairing enzymes. PARPs require NAD+ to generate the new DNA strands. 

NAD+ depletion is associated with human skin aging, and in animal studies, a NAD+ deficiency increased the sensitivity to ultraviolet (UV) rays and impaired the ability to repair skin cells after sun damage. 

Does NAD+ Influence Brain Function? 

Your brain is packed with roughly 86 billion neurons, which are responsible for sending and receiving neurotransmitters—chemicals that carry information between brain cells. Neurons are called “excitable cells” because they can become electrically excited in order to produce an impulse—a tiny electrical current. Neurons require large amounts of energy to support their survival and various functions, and as a result, they are susceptible to energy depletion called “excitotoxicity.” Not only have NAD+ levels been identified as critical for neuronal survival, but as stated earlier, NAD+ powers the mitochondria that generate your body’s energy—the same energy that the neurons in your brain neurons need to operate effectively. 

Does NAD+ Help the Heart?

Research suggests that maintaining healthy NAD+ levels may help protect the health of the cardiovascular system. A pilot study funded in part by the American Heart Association looked at the health of mitochondria in the heart after supplementation with the NAD+ precursor nicotinamide riboside (NR). The study analyzed peripheral blood mononuclear cells, or PBMCs (white blood cells). The study showed the mitochondrial respiration rate of PBMCs improved following nicotinamide riboside supplementation for five to nine days.   

Does Food Contain NAD+?

Foods like broccoli, cabbage, poultry, beef, rice, and milk contain small amounts of the NAD+ precursors tryptophan and niacin (vitamin B3). The amino acid tryptophan yields NAD+, but requires excessively more biosynthetic steps for NAD+ production than the different forms of vitamin B3, thus rendering this amino acid an estimated 60 times less efficient for NAD+ production compared to niacin. Research also indicates that NAD+ levels decrease by up to 65% between age 30 and 70, so food alone won’t compensate for the NAD+ decline with age.

Taking Vitamin B3 Is the Best Way to Boost NAD+ Levels

NAD+ is naturally produced by cells in your body, and while fasting and exercise can increase NAD+ production, the most effective way to boost NAD+ levels is from consuming NAD-boosting supplements in the form of vitamin B3.

B3 vitamins are precursors used as building blocks to create NAD+. There are three main forms of vitamin B3: niacin, nicotinamide, and nicotinamide riboside (NR). 

Niacin is the most prevalent B3 vitamin and is commonly found in multivitamins and breakfast cereals. Unfortunately, niacin can cause the unwanted side effect of flushing (redness and heat in the face and upper body) at high doses. Furthermore, there are potential side effects when taking niacin while also taking certain cholesterol drugs called statins. As such, niacin is not the preferred B3 vitamin for NAD+ creation.   

Nicotinamide has no visible side effects, but a study published in the Journal of Biological Chemistry shows that nicotinamide inhibits sirtuins, which could result in diminished cellular repair. 

Although related to niacin and nicotinamide, nicotinamide riboside (NR) is structurally and biochemically different. NR’s discovery was a critical turning point in NAD+ research because of its unique property of elevating NAD+ levels far more efficiently than its vitamin B3 rivals; it requires fewer steps to convert to NAD+ in the body than niacin and promotes sirtuin activity, unlike nicotinamide. To date, NR has no attributable adverse effects in published clinical studies.  

Can You Consume NAD+ Directly?

Direct supplementation of NAD+ is inefficient due to its inability to enter cells directly. Your body must break down orally administered NAD+ into smaller molecules and then reassemble them again in order to be utilized. This breakdown and reassembly requires extra time and energy, which is why vitamin B3 supplementation is the superior method of increasing NAD+ levels.

What’s the Difference Between NAD, NAD+, and NADH?

You might see the terms NAD, NAD+, and NADH used interchangeably online and on store shelves. “NAD” is a collective term that defines the different forms NAD takes on its molecular journey. NAD+ and NADH are just two versions of the same compound, nicotinamide adenine dinucleotide. NAD+ represents the oxidized form of NAD, meaning it has lost an electron. Gaining and losing an electron like this is called a redox reaction. NADH represents the reduced form of NAD, meaning it has regained the lost electron and is ready to transport it to a different molecule. The letter H in the acronym stands for hydrogen. NAD molecules frequently switch back and forth between these two forms as they transport electrons elsewhere to power metabolic reactions.

Why Has NAD+ Become Popular?

Recent interest in the aging process and age-related health issues has brought NAD+ to the forefront of scientific research. In a review published in Cell, a team of researchers proposed nine hallmarks of aging, one of which is related to the health of mitochondria.  With further exploration of how to prevent mitochondrial dysfunction, NAD+ became the central focus due to its direct role in mitochondrial health and healthy aging. Furthermore, NAD+ is getting more attention in the press thanks to high-profile celebrities like Kendall Jenner and listicles like the Forbes Holiday Gift Guide 2022. As the population ages and the science improves, the development of and demand for efficient NAD-boosting supplements like Tru Niagen continues to grow. 

What Is NAD+? Summary:

• NAD+ is essential for cellular energy production.

• NAD+ supports a healthy-aging process.

• NAD+ promotes cellular repair.

• NAD+ declines as you age.

• NAD+ is best boosted via vitamin B3 (in the form of NR) supplementation.

The Future of NAD+.

This is an exciting time for NAD+. Research and clinical trials continue to investigate the potential benefits of supplemented NAD+ levels. Also, NAD+ has been receiving media coverage from news sources that investigate its healthy-aging and cellular-energy-boosting capabilities. 

Now that you have a better understanding of the history, the science, and the advantages of increasing NAD+ levels, stay on the lookout for news and developments by keeping an eye on the Tru Niagen news page and signing up for our regular emails.