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NAD+: What Is It, and How Does It Affect Aging?

What Is NAD+?

Wondering what NAD is? NAD+, short for nicotinamide adenine dinucleotide, is a coenzyme essential for the healthy functioning of all living cells. Acting alongside enzymes, coenzymes accelerate specific chemical reactions vital for cellular functions. With thousands of enzymes at work in the body, NAD+ stands out as indispensable. It's involved in over 500 enzymatic reactions, playing a pivotal role in regulating nearly all significant biological processes. 

A Brief History of NAD+

The history of NAD+ traces back to its discovery in 1906 during research on fermentation. Scientists William John Young and Arthur Harden identified a substance in brewing yeast that boosted sugar fermentation, naming it a "coferment," known today as NAD+. Their work laid the foundation for further exploration, leading to Hans von Euler-Chelpin and Arthur Harden's Nobel Prize-winning research in 1929, which deepened our understanding of NAD+ and fermentation processes. 

In 1930, Otto Warburg uncovered NAD+'s pivotal role in biochemical reactions, particularly in electron transfer—a process crucial for energy generation in the body. Despite these breakthroughs, NAD+ gained widespread attention only in the late 1930s, when niacin, a precursor to NAD+, proved effective in treating pellagra—a severe condition prevalent in the American South, characterized by skin inflammation, diarrhea, dementia, and mouth sores. Further studies revealed that niacin-rich sources like milk and yeast could alleviate pellagra symptoms due to their NAD+ precursor content. 

Over time, scientists identified various NAD+ precursors, such as nicotinic acid (NA), nicotinamide (NAM), and nicotinamide riboside (NR), each serving as pathways to NAD+ production. Understanding the historical context and significance of NAD+ and its precursors sheds light on their crucial roles in cellular processes and health maintenance. 

What Role Does NAD+ Play in Energy Production?

How is energy generated from NAD+ different from just drinking a cup of coffee? 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. Without it, the electron transport chain assembly line would halt.

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Does NAD+ Help Cellular Repair?

NAD+ isn't just crucial for energy production; it's a powerhouse coenzyme driving cell regulation and DNA repair alongside sirtuins and PARP (poly (ADP-ribose) polymerase) enzymes. Factors like overeating, excessive alcohol intake, sleep disturbances, or sedentary lifestyles can harm cells, but NAD+ is the key to cellular rejuvenation. 

Sirtuins, essential for metabolic balance, manage fat and glucose metabolism in response to energy fluctuations, ensuring energy homeostasis. Additionally, they safeguard chromosome stability, mend DNA, and alleviate cellular stress. 

PARPs also play pivotal roles in DNA repair and chromosome stability. When DNA damage occurs due to metabolic stressors or environmental factors like radiation, PARPs spring into action, initiating repair processes. NAD+ is crucial for PARPs to synthesize new DNA strands, aiding in the restoration of damaged cells. 

NAD+ depletion is associated with human skin aging, and in animal studies, 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 home to a staggering 86 billion neurons, the dynamic cells that orchestrate the exchange of neurotransmitters, vital chemical messengers facilitating communication between brain cells. These neurons, often dubbed “excitable cells,” possess an extraordinary ability to generate electrical impulses, essential for transmitting information. 

This electric activity comes at a cost, as neurons demand significant energy to function optimally, making them susceptible to “excitotoxicity,” defined as when nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high. NAD+ is a pivotal molecule revered for its function in neuronal resilience. NAD+ serves as a primary substrate for mitochondrial activity, facilitating the production of adenosine triphosphate (ATP), the fundamental energy currency driving neuronal functionality within the brain.  

Does NAD+ Help the Heart?

Research suggests that sustaining optimal NAD+ levels may play a pivotal role in safeguarding cardiovascular health. A pioneering pilot study, partially funded by the American Heart Association, delved into the impact of nicotinamide riboside (NR), a precursor to NAD+, on mitochondrial health within the heart. 

This study focused on analyzing peripheral blood mononuclear cells (PBMCs), commonly known as white blood cells. The findings revealed a significant improvement in the mitochondrial respiration rate of PBMCs following supplementation with NR over a span of five to nine days. 

Can I Get NAD+ from Food? 

Foods like broccoli, cabbage, poultry, beef, rice, and milk contain small amounts of the NAD+ precursors tryptophan and niacin (vitamin B3). B3 vitamins are precursors used as building blocks to create NAD+. There are three main forms of vitamin B3: niacin, nicotinamide, and the less common NR. 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.  

NAD Declines graph

Taking NR 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. Since vitamin B3 deficiency is rare, you may not know how vital this nutrient is for health, or what happens when you don’t have enough of it.  

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 apparent 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, 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 where it has been administered in servings of up to 2,000mg/day.    

What About NMN?

NR has been suggested to have better bioavailability compared to NMN. This means it may be more efficiently absorbed and utilized by cells. NR is 25% more efficient (per Conze et al., 2019 and Pencina et al., 2022) than NMN at converting to NAD+ based on a 2019 NIAGEN study. NR can directly enter a cell, raising NAD+ via a few enzymatic steps, whereas NMN cannot enter cells directly. Some studies suggest that NR may be more effective in raising NAD+ levels in certain tissues, such as the liver, compared to NMN. NR may be more readily available and cost-effective compared to NMN, which can influence individual preferences. Most importantly, NMN was banned for sale in dietary supplements by the FDA in November 2022; Another reason why health-conscious consumers choose NR.

Can I Take 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. NAD+ is made up of different parts including two phosphate groups which contribute to its large size. Unlike NAD+, when NR is ingested, it can enter cells directly because of its smaller size. The breakdown and reassembly of NAD+ requires extra time and energy, which is why vitamin NR 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.  

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 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.   

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