What Is NAD+ And Why Is It Important?

ScienceApril 21, 202213min read

mitochondrial energy generation through NAD+

Introduction 

Imagine looking and feeling young as you age. Is it possible?

Yes, it is!

When it comes to our health, there are some things we just cannot take for granted. Our bodies are constantly working hard to keep us going, and sometimes they need a little help.

That is where supplements come in. One molecule that has been gaining a lot of attention lately is NAD+. Here is a closer look at what it is and why it’s so important for keeping your body functioning at its best.

What Is NAD+? 

NAD+ stands for Nicotinamide Adenine Dinucleotide. It is a coenzyme that is necessary for life and cellular activities needed for the body’s normal functions and survival. Enzymes operate as catalysts that allow biological processes to happen at a faster rate, while coenzymes are molecules that act as ‘assistants’ to enzymes, allowing them to work properly. 

In the early 1900s, scientists first discovered NAD+ and began researching its advantages. But in recent years, we have started to realize the full extent of its potential. 

Because of the vital function of NAD+ in so many different biological processes, scientists and clinicians are currently investigating the many ways it may be utilized to preserve the health of organs in humans who are suffering from age-related diseases. 

What Does NAD+ Do? 

As an “assistant molecule”, NAD+ interacts with the enzymes in the body, causing them to become activated and drive critical functions of cells. In the human body, NAD+ has two tasks: aids in converting nutrients to energy during metabolism. And acts as a helper molecule for proteins that govern other cellular activities. 

Further, NAD+ is an important regulator in important processes, for example, DNA Damage Control and Mitochondrial Energy Generation.

DNA Damage Control 

The anti-aging proteins called Sirtuins are essential for various biological functions in the human body. Sirtuins depend on NAD+ as a coenzyme to function effectively.

When NAD+ levels are elevated, Sirtuins become highly activated and help to slow down the aging process by controlling inflammation and DNA damage. And since NAD+ promotes Sirtuin activities, then Sirtuins stabilize the telomeres to maintain healthy telomere length.  

Additionally, NAD+ also facilitates the activities of the proteins called Poly ADP-ribose polymerases (PARPs). PARPs are involved in DNA repair and use NAD+ in the process. When NDA+ levels are high, PARPs are actively performing their job and influence the maintenance of healthy cells.

Mitochondrial Energy Generation

Mitochondria are tiny organelles inside the cells and are deemed as the “powerhouse of the cells” because it is where the energy production process (known as “cellular respiration”) happens.

Cellular respiration is dependent on the movement of electrons to generate energy. During this process, the mitochondria break down the glucose (the basic unit of sugar and carbohydrates from the food that we eat) to produce energy.

Originally, glucose converts into the energy molecules of the cells called adenosine triphosphate (ATP). Then, NAD+ functions as an electron carrier – it picks up the electrons from the metabolized glucose, transforming it into NADH (nicotinamide adenine dinucleotide hydride).

During cellular respiration, NADH is converted back to NAD+ to generate more ATP molecules along the process.

mitochondrial Energy generation by NAD+

Physiological benefits of high NAD+ levels. Image source

Why Is NAD+ Important?  

NAD+ has been gaining a lot of attention because of its abundance in the body and its critical involvement in biochemical pathways that keep our bodies working.

With the role of NAD+ in supporting efficient DNA repair, NAD+ is imperative for the survival and the prevention of disorders that are triggered or influenced by DNA abnormalities. Some of these disorders are cancer, diabetes, cardiovascular disease, dementia, and immune function decline.

And since NAD+ is pivotal to energy production, the lack of NAD+ results in lower energy levels. As we age, our bodies produce less and less of this coenzyme. And this explains why elderly people are weak or have low energy to fuel their physical and physiological processes.

For adults who have low NAD+ levels, it hastens the aging process and we become more susceptible to age-related disorders. Raising the NAD+ levels in the body has shown promise in study areas such as metabolism, organ function, and longevity.

Without NAD+, our bodies will not be able to perform as efficiently as they should, will be less effective at self-repair, and will be susceptible to degenerative disorders.

graph showing NAD+ levels decline with ageNAD+ levels decline as we age. Image source

What Causes A Decrease In NAD+? 

Unhealthy habits and aging are the primary culprits of decreased NAD+ levels. 

Here are the factors that cause a decrease in NAD+ 

  • Smoking
  • Heavy alcohol intake
  • Poor diet
  • Lack of exercise
  • UV exposure
  • Aging
  • CD38 molecule

Prolonged UV radiation from sun exposure, cigarette smoking, and alcohol intake, as well as poor diet, induce tissue damage and oxidative stress. This requires a lot of NAD+ to provide the energy needed for the cellular repair processes, leading to NAD+ depletion.

Aging also influences cellular production and a study has previously shown the significant decline of NAD+ levels from birth until 80 y/o.

Alarmingly, one major reason why NAD+ decreases as we age is that it is being destroyed. A recently-discovered enzyme called CD38 NADase directly degrades NAD+ causing the NAD+ levels to drop significantly. What’s worse is that CD38 levels rise as we age, hence causing the NAD+ levels to plummet through time.

lifestyle and diet to maintain NAD+ levels high

Image source

What Happens When The NAD+ Levels Are Reduced? 

The levels of available NAD+ fluctuate based on which systems are prioritized at any particular time. Our bodies divert NAD+ away from non-essential functions, freeing up biochemical resources that would otherwise be dedicated to these processes. As a result, we may suffer from a variety of health issues if we don’t have enough NAD+.  

Here are the disorders that are triggered when the NAD+ levels are depleted: 

Cardiovascular Diseases 

According to the Centers for Disease Control, one person in the United States dies from heart disease every 37 seconds. In total, the mortality from heart disease is around 659,000 individuals every year, which is one out of every four deaths in the country. 

Atherosclerosis may be avoided by keeping the arteries in excellent shape. Arteries are flexible enough to buffer against the pressure every time the heart beats. However, as we get older, they get stiffer.

NAD+ helps preserve the flexibility in cells by preserving their capacity to create energy and repair themselves, which helps keep them clear and reduces the risk of cardiovascular issues. NAD+ may also help control the heart’s inflammatory response. While inflammation is a mechanism for the immune system to restore the body, abnormal inflammation can hasten the heart failure process. Immune cells can regulate this process, but they rely on mitochondria to generate energy that is dependent on NAD+ levels.

According to a study published by a research team from the University of Washington, inflammation in patients’ hearts was connected to impaired mitochondrial activity. The patients were orally administered 1,000 mg (twice daily) of nicotinamide riboside (NR), a precursor to NAD+.

According to their findings, these patients’ mitochondrial activity improved, and their inflammatory responses decreased. In another research, increased NMN, another NAD+ precursor, was also shown to lower inflammation and enhance heart function in mice.

Immune System

The immune cells manage our body’s response to disease and infection. Since NAD+ is a key player in cellular and metabolic processes, it is an important determinant of immune cell function and response to infection.

The research team of Dr. David Sinclair, a Harvard scientist, an expert, and pioneer in the aging and longevity field, explained that NAD+ could be a game-changer in influencing immune response, antiviral mechanisms, and curbing hyper inflammation, particularly in COVID-19.

Viruses like SARS-CoV-2 can trigger an abnormally overactivated immune system that contributes to a deadly immune state called cytokine release syndrome (CRS).

Originally, the immune cells trigger inflammation and release antiviral molecules to get rid of the infection, but if the person has an overactive response, CRS happens. Previous research demonstrated reduced NAD+ levels in severe COVID-19 infections and that viral infections deplete NAD+ cellular stores.

Therefore, correcting the NAD+ levels is a potential therapeutic strategy to regulate the immune response during viral infection.

Cancer 

Lower levels of NAD+ may lead to more significant cancer risks and dysfunctional mechanisms to fight cancer. With NAD+ depletion, it can substantially limit the amount of produced energy required for immune attack and impair the DNA repair mechanisms.

NAD+ is also an essential protective factor in the pre-cancer or early stages of carcinogenesis. Meaning it can prevent or may slow cancer growth, respectively.

As a result, researchers believe that restoring NAD+ might prevent or reverse the morphology of malignant cells at an early stage. This is believed to be done by activating cellular repair and stress adaptive responses. And by controlling the proliferation of cancer cells and promoting the elimination of damaged cancer cells via a cell death process called apoptosis.

Ironically, however, NAD+ can also be cancer’s lifeline. Like normal cells, cancer cells may also depend on NAD+ to sustain their high energy demand during rapid growth. Therefore, scientists think that cutting off the NAD+ supply can kill cancer cells.

Neurodegenerative Diseases 

Increased lifespans are correlated with a rise in dementia cases, including Alzheimer’s disease.  

According to recent research, unless risk factors are addressed, the worldwide dementia rates might quadruple by 2050 – the number of people living with dementia may rise from 57 million to 153 million.  

Finding solutions to reduce the effect of neurodegeneration will be a fundamental pillar of the push for longevity, ensuring that individuals live longer and have a better quality of life.

NAD+ may blunt the process of neurodegeneration and prevent the emergence of diseases by boosting the capacity of cells to repair themselves. It may also help prevent the buildup of proteins that impair cell communication and it can improve cognitive function.

Higher NAD+ levels can also help protect the brain cells from dying, especially when there’s a risk of decreased blood flow to the brain like during stroke or when the blood vessels have plaques (cholesterol-containing deposits in blood vessels that cause them to become narrow and stiff).

Ways To Boost NAD+ Levels

The body’s function is dependent on NAD+. It keeps us youthful and healthy. However, since now we know that NAD+ levels drop as we become older, we need to get more of it to keep our cells repairing and working correctly. So, how to boost your NAD+ levels? 

  • Calorie restriction. Often known as fasting, calorie restriction has been demonstrated to boost NAD+ levels and Sirtuin activity. Through the same mechanism, it has also been found that it slows down the aging process in mice.  
  • Exercise. Physical activity causes energy stress. At the cellular level, this causes the utilization of NADH molecules to ramp up the energy. After the electrons from NADH are used, NAD+ is produced. Interval training is optimal, but aerobic exercise may also induce and maintain the energy stress needed to increase NAD+ production. 
  • Heat therapy. Sauna sessions can raise your cellular NAD+ levels. Heat sources like in a sauna or hot tubs can naturally make your heart pump faster, requiring more energy to regulate your body’s temperature, and hence trigger NADH to NAD+ conversion.   
  • IV Nutrition therapy. Intravenous NAD+ therapy is also available to deliver NAD+ through injection. It’s a terrific approach to enhancing NAD+ levels rapidly and efficiently because it provides 100% absorption if infused through the bloodstream. 
  • Supplementation. Various supplements have been associated with boosting NAD+ levels in human studies, in addition to the above-mentioned strategies. 

NAD+ is present in several foods, but the levels are inadequate to affect intracellular concentrations. NAD+-boosting supplements include nicotinamide riboside (NR), nicotinamide (NAM), nicotinic acid (NA), malic acid, resveratrol, and apigenin.

Benefits Of NAD+ Supplementation

NAD+ is so important for longevity that it is recommended for everyone. 

However, oral NAD+ supplementation does not result in the enhancement of NAD+ levels in the body. But, it is feasible to provide the fuel it needs to begin this process by giving the body its precursors. One of the most effective NAD+ precursors is nicotinamide mononucleotide (NMN).  

Unfortunately, ordinary oral NMN pills are not too useful since it is not very stable and bioavailable when it reaches our gut. On the other hand, liposomal NMN formulations are the best to be optimally absorbed by our system.

Boosting the NAD+ levels provides the body with the fuel it needs to support numerous bodily functions. Sirtuins are supplied with the energy they need to keep up with the rising demands of cell repair and function regulation. Inflammation, decreased metabolism, lowered immunity, brain degeneration, and many other issues may be prevented, and individuals may successfully keep themselves younger, extending their lives and improving their quality of life.

In a randomized, double-blind, placebo-controlled study, a daily dosage of a combination pill with NAD+ precursors raised the NAD+ levels by roughly 40%, according to a 2017 research. This, in principle, should increase the body’s function, which should boost one’s chances of living a longer life.

How to boost NAD+ levels

Prospects for therapeutic NAD+ modulation. Image source

The Future Of NAD+

NAD+ became a very significant molecule in human medicine since its discovery a century ago. But scientific studies and technological advancements are recently just beginning to explain how it may be currently used, which may open more applications in the future.

NAD+ has incredible potential for aging and longevity, and the most fascinating component of modern research is determining how it will be realized.

Due to its promising therapeutic capabilities demonstrated in animal experiments, researchers are advancing the understanding of how NAD+ precursors act in the human body. Animal studies important methods to validate the effects at the organism level, but more human data are also needed.

In a recent clinical study in Japan, the molecule was shown to be safe and well-tolerated at the dose utilized. There will be further research and human trials in the near future. It’s a fascinating and adaptable chemical from which we can still learn a lot.

From all the research data, many scientists believe that we can largely reverse the aging process by restoring healthy NAD+ levels to reinvigorate the body’s cellular functions. This highlights NAD+ as one of the strongest candidates for making the future anti-aging pill.

Closing remarks

A deficiency in NAD+ is a deficiency in the fuel that the body needs to live healthily.

NAD+ boosting treatments are a near-future promise that can solve many issues in aging. They are now in small-scale human trials and soon, they can progress to more extensive human studies. This medication may be regarded as a natural regeneration therapy since it is a natural necessity that powers up the cells during a healthy state.

Now that you know all about NAD+, it’s time to take action and increase your levels. We’ve shared a few ways to do this, so start incorporating them into your life today. Not only will you be doing something good for your health, but you may also see a decrease in the signs of aging.

Imagine looking and feeling younger – it’s possible with NAD+ on your side!