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Most people are aware of metabolism in the sense that they have probably once said they have a “fast” or “slow” metabolism. But metabolic function is about so much more than how quickly or slowly we gain weight; it’s a vital component of how we feel, how we age, and what diseases we develop—or don’t.
Metabolic health is involved with everything from blood sugar regulation and body fat distribution to cardiovascular health and cognitive function—and NAD+ is a vital component of metabolism, facilitating hundreds of enzymatic reactions involved with cellular energy and metabolic processes.
But what exactly is metabolic health, and how is NAD+ involved? Keep reading to find out the answers to these questions and more, including why NAD+ declines and the best ways to increase NAD+ for optimal metabolic functioning.
Why Is Metabolic Health Important?
To understand metabolic health, let’s first take a trip back to 8th-grade Biology class where you probably learned about energy metabolism and our mitochondria.
While metabolism refers to the entirety of chemical processes in the body that convert the food we eat into energy, “metabolic health” describes how well your body regulates these processes, including blood sugar, cholesterol, insulin, body fat, muscle mass, and blood pressure regulation.
All of these factors can play a role in how you feel day-to-day—like your energy, focus, and mood—as well as affect long-term health, including increasing the risk of conditions related to the heart, brain, liver, and glucose metabolism.
As one study found that only 12% of Americans are metabolically healthy, it’s become even more crucial to focus on how to improve it.
While there are many potential ways to support your metabolic health, such as building muscle and eating protein, there is one key but often overlooked molecule that powers metabolic processes: NAD+.
To understand how NAD+ influences metabolic health, let’s start with what it is and how it works in the body.
The Basics of NAD+
NAD+, or nicotinamide adenine dinucleotide, is a coenzyme that helps other enzymes to function correctly, supporting approximately 500 enzymatic reactions throughout our cells, organs, and tissues.
We need NAD+ for everything from repairing damaged DNA and pumping blood to contracting muscles and powering neuron activity. Simply put, life as we know it would cease to exist without adequate NAD+ stores.
One critical role of NAD+ is supporting metabolic function. It is absolutely central to energy metabolism, including facilitating processes that turn the carbohydrates, fats, and proteins we eat into energy that our cells can use to power our lives.
The Link Between NAD+ and Metabolic Function
One of the key ways that NAD+ is involved with metabolic health has to do with our mitochondria. You may recall mitochondria as the “powerhouse of the cell”—and the nickname holds true, as these little organelles inside our cells produce energy in the form of ATP that drives everything we do.
Mitochondrial function and NAD+ go hand in hand, as our mitochondria require NAD+ to transform food into cellular energy efficiently. A decline in NAD+ stores can lead to a drop in mitochondrial quality and, therefore, less efficient energy metabolism. This slows down all metabolic processes, leading to issues like fatigue, weight gain, insulin resistance, and other metabolic disorders.
Sirtuins, a family of enzymes that also rely on NAD+ to function properly, are another important component of metabolic health. Many of the sirtuins, especially SIRT1 and SIRT3, help control processes like glucose balance, lipid and cholesterol metabolism, and mitochondrial function.
Essentially, with NAD+ depletion, all of our enzymes, cells, and organelles involved with energy metabolism can begin to run at suboptimal levels, leading to metabolic disorders that can affect our heart, brain, vascular system, liver, and more.
The heart is particularly vulnerable to poor metabolic health due to its high energy demands. Without enough NAD+, the energy-demanding cardiomyocytes (heart muscle cells) cannot function properly, leading to a variety of heart conditions. According to a review paper published in Circulation, disrupted NAD+ metabolism can be considered a modifiable cardiovascular risk factor.
Another increasingly prevalent metabolic condition affected by low NAD+ is excess body fat. Obese people have been shown to have reductions in NAD+ biosynthesis pathways, which may be due to chronic low-grade inflammation and elevated metabolic stress that deplete NAD+.
In a preclinical study published in Cell Metabolism, the NAD+ precursor nicotinamide riboside (NR) was found to prevent metabolic abnormalities and obesity in mice on a high-fat diet. The mechanisms behind these results included that NR activated SIRT1 and SIRT3, enhanced oxidative metabolism, and increased NAD+ levels.
Lastly, a lesser-known effect of poor metabolic health is disrupted liver function. Metabolic-associated liver dysfunction is becoming more and more common, and low NAD+ stores may be a contributor.
In preclinical models of metabolic-associated liver dysfunction, NAD+ precursors like NR have been found to improve mitochondrial function in the liver and prevent a progression to worsening stages of the disorder. This is because key enzymes in NAD+ signaling pathways (like SIRT1) protect the liver from fat accumulation and scarring that disrupts function.
But why does NAD+ decline and cause these dysfunctions? Let’s take a closer look.
Why Does NAD+ Decline?
The most common reason for NAD+ decline is age, dropping 65% between age 30 and 70. This is primarily due to cellular damage that accumulates with age and increased cellular or metabolic requirements.
With low NAD+, signs of age-related physiological decline can accelerate, which begin to manifest internally as cellular dysfunction and age-related health conditions and can ultimately lead to the external signs of aging. Therefore, maintaining your NAD+ levels is a core component of healthy aging.
In addition to age, other reasons why NAD+ can decline include:
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Overexpression of CD38: CD38 is a molecule involved with immune functioning, cellular signaling, and energy metabolism, and it can deplete NAD+ levels when overactive. Elevated CD38 occurs with age, poor health, impaired mitochondrial health, metabolic dysfunction, and pro-inflammatory states.
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DNA damage: High amounts of DNA damage require enzymes called PARPs to repair it. PARPs are also NAD+-consuming enzymes, further depleting NAD+ stores.
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Chronic inflammatory states: Chronic illnesses and excess body fat can trigger low-grade chronic inflammation, which upregulates CD38 and can deplete NAD+.
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Impaired mitochondrial function: Mitochondrial health and NAD+ stores are like a vicious circle—reduced NAD+ causes impaired mitochondrial function, which further lowers NAD+ levels, and so on.
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Diet and lifestyle: High-fat diets, high-sugar foods, excessive alcohol, and a sedentary lifestyle can all play a role in reduced NAD+ production and poor mitochondrial health.
But it’s not a lost cause—no matter your age, there still is an opportunity to boost your NAD+ levels and support your metabolic health.
How Do You Elevate NAD+?
Although you may think you can simply pop a pill of NAD+ and call it a day, it’s not quite so easy. Oral supplemental NAD+ is ineffective, as it cannot easily cross over cell membranes in its original form—it first has to be converted into a smaller molecule before it can be taken up by the cell and turned back into NAD+.
Instead, NAD+ precursors like NR can be used to boost NAD+ stores. NR has been shown to safely and effectively elevate cellular levels of NAD+, as it is one of the most well-known compounds that act as an NAD+ precursor.
Other NAD+ precursors include nicotinamide or niacinamide (NAM), niacin or nicotinic acid (NA), and nicotinamide mononucleotide (NMN).
You can also find some of these precursors in foods like broccoli, edamame, shrimp, and cow’s milk. However, getting your NAD+ precursors from food is ineffective, as you would need to consume very large amounts of each of these foods to get clinically relevant amounts of NR or NMN.
Some other compounds—including CD38 inhibitors—can support NAD+ levels indirectly, typically by acting on enzymes that inhibit its degradation. As mentioned, excessive CD38 activity depletes NAD+, so CD38 inhibitors like quercetin, apigenin, and luteolin can help to preserve our NAD+ stores—in addition to fighting oxidative stress and inflammation that also contribute to aging.
Lastly, lifestyle habits like exercise, intermittent fasting or caloric restriction, and limiting alcohol can help increase or preserve NAD+ levels.
NAD+ Precursors: What to Look For
Like with all supplements, it’s crucial to look for NAD+ precursors that have been third-party tested for purity, potency, and efficacy. Tru Niagen® is a patented form of NR with the strongest clinical backing for its safety and effectiveness in raising NAD+ levels.
Over 35 human clinical studies, alongside collaborations with over 275 renowned research institutions—such as the Mayo Clinic, National Institute on Aging, and Harvard—underscore the credibility of Niagen®. Plus, over 65% of registered ongoing or completed nicotinamide riboside trials use Niagen®, underlying its safety and efficacy.
Unfortunately, fake NR supplements are being sold in increasingly high amounts by unauthorized resellers on sites like Amazon. Not only are these counterfeit supplements ineffective, but they can also be dangerous, potentially containing undisclosed ingredients that have not undergone safety testing and could cause toxicity or allergic reactions.
Conversely, every batch of Tru Niagen® is always rigorously tested for safety, quality, and efficacy, ensuring that you know what is in each bottle and what it can do for your health. If purchasing on Amazon, ensure that the seller is sold directly by Tru Niagen (listed as “Sold by: Tru Niagen”) or buy directly from the Tru Niagen website.
To verify that your product is authentic, enter your supplement’s lot number on the bottle on Tru Niagen’s Transparency page to immediately access your bottle’s Certificate of Analysis, which demonstrates the testing results for safety, quality, label claims verification, and purity of every batch of Tru Niagen.
Counterfeit supplements affect much more than just NR. These regulatory gaps and an overall lack of enforcement in the supplement industry as a whole are increasingly problematic issues. Purchasing only from authorized sellers and inspecting the products you receive are simple ways you can help to make the industry a safer place for everybody.