What is Nrf2? Here’s Everything You Need to Know About the Secret to Aging Well

What is Nrf2? Healthy man photo | Gapin Institute


Feel like you’re just not operating at the level you used to?

People tell us that that happens with age—that our bodies start to break down.

But the most recent science is actually calling into question the inevitability of the symptoms of aging. New research in microbiology, chemistry, and genomics is showing us that those uncomfortable symptoms of aging might not be locked in.

This is where “biohacking” comes from: it’s the idea that you can give your body exactly what it needs to properly repair and rejuvenate itself. The result? Optimized health and performance.

Nrf2 is one of the most exciting discoveries in this area and holds some real promise as an anti-aging agent and as a support for your long-term health. In this article, I’ll explain what it is, what it does, and why it matters for your aging. 

What is Nrf2?

Nrf2, short for “nuclear factor erythroid 2-related factor 2”, is a protein that is found in your cells. It is a type of protein called a “transcription factor”, which means that it is involved in gene expression—activating and deactivating parts of a genetic sequence. 

Which genes does Nrf2 affect? It regulates the expression of antioxidant proteins and enzymes, increasing their production to help your body fight off molecules that attack your cells. 

Nrf2 has been found to be an important part of your body’s system of regulating metabolism, inflammation, and immune responses

What’s special about Nrf2?

 Nrf2 is a big deal because it could be the key to aging gracefully and healthily.

When you’re young, your body is good at balancing all the needs of your body at the cellular level. But as you age, these important chemical signallers decline. You begin to produce less of the substances that you need to properly regulate your body.

That means that there are fewer of the peptides, proteins, hormones, and enzymes that help your body repair and rejuvenate. Things start to break down.

The result is that your body gets slower at repairing itself. That’s why you feel tired more often, your body takes longer to recover from exercise, and your skin begins to see signs of aging. You might also notice issues with your sleep or even erectile dysfunction

Oxidative stress contributes to symptoms of aging

At the cellular level, what’s happening is that free radicals are constantly bombarding your cells. The damage caused by these attacks causes your cells to go into a state called oxidative stress, and stop functioning properly. 

When you’re young, your body can easily fight free radicals back. But as you get older, your body can’t do this as effectively. That’s when symptoms of aging start getting worse.

Antioxidants fight free radicals and reduce oxidative stress

You’ve probably heard of the health benefits of antioxidants. Some foods are high in antioxidants and that’s why health professionals sometimes encourage you to include them in your diet. 

Antioxidants  help neutralize free radicals and minimize the damage that they cause. That helps reduce the symptoms of aging. 

But antioxidants aren’t very efficient. One antioxidant molecule neutralizes only one free radical. With more and more free radicals, we need more and more antioxidants. At some point, the antioxidants can’t keep up. 

What does Nrf2 do?

Nrf2 provides a powerful solution to overcome free radicals. It’s known as the “master regulator” of our body’s antioxidant response.

When Nrf2 is activated, it enters the nucleus and turns on several hundred genes, known collectively as “survival genes.” This, in turn, initiates the production of several of your body’s own powerful enzymes that fight free radicals. These enzymes include catalase, glutathione, and superoxide dismutase (SOD)

These enzymes are much more effective than antioxidants at getting rid of free radicals—they can neutralize over 1 million free radicals a second. What that means is that your body can clean itself out quickly and fewer of your cells get into a state of oxidative stress. 

Ultimately, that means you feel fewer symptoms of aging: better energy, better sleep, and even a better sex life

How do I get Nrf2?

Great, Nrf2 can support my health. How do I get it?

You actually don’t need to get Nrf2—it’s already right there in your cells. It comes pre-installed.

The problem is that it’s not activated. It’s a bit like an engine: it just sits in your cells not doing anything until it’s turned on. That’s what Nrf2 activation therapies do: they get into your cells to turn on Nrf2 so that it can enter the nucleus and work its magic. 

Some foods have been shown to activate Nrf2 and the Nrf2 pathway. These have been supported by studies in nutrigenomics—the study of how food influences gene expression and cellular function. 

Some Nrf2-activating foods include:

  • Dark chocolate 

  • Legumes, like lentils, beans, and peas

  • Vegetables, especially dark leafy greens like spinach and cruciferous vegetables like broccoli, cauliflower, and bok choy

  • Spices, especially ginger, turmeric, cinnamon, cloves, and yellow mustard

  • Herbs, like oregano

  • Red wine

  • Tea, especially green and white teas

What about Nrf2 supplements? Do they work?

In addition to activating Nrf2 through the diet, there are now supplements that activate Nrf2 and significantly reduce oxidative stress. 

These have been extremely well-researched by the scientific community and some of the supplements have very strong evidence supporting their use. 

Protandim®, for example, is a supplement designed to activate Nrf2. There have been numerous studies that demonstrate that it improves your body’s antioxidant response capacity. Peer-reviewed, human clinical studies show that it reduces cellular stress in humans by an average of 40 percent in 30 days. Research even suggests that it could be effective in preventing age-related diseases like:

The takeaway for your health: Nrf2 activators could help you feel younger. A men’s health secret.

We often think that there isn’t much we can do about the declines in our bodies that come with age. But science is showing us that that’s not necessarily the case. 

There actually may be ways that we can give our body what it needs to better regulate, repair, and rejuvenate itself.

Nrf2 appears to be one of those ways. Activating the Nrf2 pathway could be a relatively simple—but powerful—way to help you feel younger again. 

It might be as easy as making good diet choices or taking a supplement. 

Schedule a consultation to learn how to personalized health advice so you can live your life to the fullest. 

Ready to take the next steps?

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In Male 2.0™, Dr. Tracy Gapin has turned everything we once thought we knew about men’s health and performance upside down. The old model of how to be “a man” is broken. A man who works himself to death.  Unfortunately, a man who tries to NOT get sick but isn’t really healthy either.  And a man who takes a pill for every ill but is never really cured. That was Male 1.0. Now, imagine being THE MAN ─ owning your performance in the bedroom, the weight room, and the boardroom. Living a fully optimized life. Becoming limitless. This is Male 2.0!

Tracy Gapin, MD, FACS  is a board-certified Urologist,  world renowned Men’s Health & Performance Expert, Author, and Professional Speaker. Using state-of-the-art biometric monitoring, nutrition and lifestyle intervention, Dr. Gapin coaches Fortune 500 executives and evolutionary leaders of business, sports medicine, and high performance. He specializes in cutting-edge precision medicine with an emphasis on epigenetics, providing men with a personalized path to optimizing health & performance. www.GapinInstitute.com

Want more tips to optimize your health?  Listen to the latest podcasts. Click HERE


Houghton, C. A., Fassett, R. G., & Coombes, J. S. (2016). Sulforaphane and other nutrigenomic Nrf2 activators: can the clinician’s expectation be matched by the reality?. Oxidative Medicine and Cellular Longevity, 2016. https://doi.org/10.1155/2016/7857186

Hybertson, B. M., Gao, B., Bose, S. K., & McCord, J. M. (2011). Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Molecular Aspects of Medicine, 32(4-6), 234-246.

Lim, J. L., der Pol, V., Susanne, M. A., Baron, W., McCord, J. M., De Vries, H. E., & Van Horssen, J. (2016). Protandim protects oligodendrocytes against an oxidative insult. Antioxidants, 5(3), 30. https://doi.org/10.3390/antiox5030030

Anti-Aging Tips For Men


anti aging tips for menClose-up shot of a handsome young man with towel in his neck admiring looking at his face in the bathroom mirror.

Traditional doctors approach aging as something that is imminent, unavoidable, and uncontrollable. Their goal is to merely treat your age-related symptoms as they pop up, like a medical version of whack-a-mole. 

But I view aging VERY differently. 

Science has shown us that there’s a lot we can do to slow, and actually reverse, the course of your aging process. That’s because healthy aging is NOT about hitting the genetic jackpot. Instead, it’s about adopting preventative strategies that slow the cellular processes associated with aging, improve your immune system, prevent disease, and ultimately boost your sense of youth and vitality.

How Inflammation Impacts Aging

There’s one factor that dramatically speeds up the process of aging – inflammation. In fact, chronic inflammation underlies nearly every disease associated with aging, including hypertension, cardiovascular disease, dementia, arthritis, cancer and diabetes, just to name a few.[1]

Chronic inflammation may not directly cause aging per se. Rather, it acts like gasoline, turning the normally smoldering embers of cellular degeneration into a raging fire that causes destruction throughout the body and brain. Inflammation wreaks havoc on your immune system, your gut health, your brain health and your mental wellbeing.

Unfortunately, our modern routines are riddled with factors that increase inflammation—from highly processed diets to a sedentary lifestyle to environmental toxins. But it doesn’t have to be that way. With a few tweaks to your daily regimen, you can smother the flames of inflammation and be on your way to living a long, energetic, disease-free life.

How to Reduce Inflammation and Promote Healthy Aging

1. Eat for Life

If you are like most people, your major source of inflammation comes served on your dinner plate. Eating a typical American diet high in omega-6 poly-unsaturated fats (think canola oil, safflower oil, etc.) , highly-processed oils (think ‘partially hydrogenated’ anything), and refined sugars all directly promote inflammation and increases your risk of disease. Conversely, eating a healthy diet reduces inflammation, boosts your immune system, and protects you against both infectious and chronic diseases.

Let’s break down the three key pillars that form the basis of a healthy, anti-aging diet.

The first pillar involves choosing complex carbohydrates over simple ones.

Simple carbs are found in anything made with sugar, but they are also found in things we don’t consider sweet, like white bread, potatoes, pasta, white rice, pizza dough and pasta.

What makes simple (or refined) carbohydrates unique is that they’ve been stripped of all their fiber, bran, and nutrients. As a result, your body is able to quickly break them down into sugars, which sounds like a good thing but it isn’t. Eating simple carbs floods your system with sugar, resulting in body-wide inflammation

This sugar spike also triggers your pancreas to create a surge in insulin in order to clear the sugar from your bloodstream. But all that insulin makes you feel hungry again, which is why we tend to crave simple carbs rather than vegetables. 

Over time, this dramatic rise and fall in blood sugar causes you to overeat, gain weight (especially dangerous belly fat), and develop insulin resistance (i.e., type-2 diabetes). It also causes unhealthy fluctuations in your mood and energy levels. And if that isn’t bad enough, a diet high in simple carbs puts you at greater risk for high blood pressure, heart disease, cancer, depression and bipolar disorder.[2, 3]

Simple carbs are also dangerous because they produce a particularly nasty substance called Advanced Glycation End Products (AGEs). AGEs are toxic molecules that form when protein or fat combines with the sugar in our bloodstream.[4

When AGEs accumulate, they form a sticky, inflexible substance that clogs our blood vessels and coats our major organs, sometimes resulting in organ failure. AGEs promote oxidative stress, which is a fancy way of saying they make our cells old before their time. Scientists are just starting to discover the ways in which AGEs drive age-related illnesses, but what is clear is that consuming a healthy diet is the main way to keep these toxic molecule levels low.[5]

Now trying to quit anything cold turkey is hard, so instead of just cutting out sugars and simple carbs, think about replacing them with complex carbs. 

  • Swap out sugary desserts with fresh fruit like strawberries or apples. 
  • Switch white bread with wheat or even better, a lettuce leaf. 
  • Opt for brown rice, lentils, or an ancient grain like amaranth or quinoa versus white rice.
  • Switch from regular pizza dough to a cauliflower crust. With a few creative tweaks to your diet, you are less likely to feel deprived and more likely to stick with your new eating habits.

The second pillar in an anti-aging diet is eliminating bad fats and incorporating good fats. In the 1980s, fat got a bad rap. Doctors argued that eating a diet high in fat skyrocketed cholesterol and caused heart disease. 

But experts now recognize this assumption was wrong. In truth, there are good fats and bad fats and a key to anti-aging is knowing the difference.

Generally, fats fall into these broad categories:

  • Trans fats: Trans fats are the worst kind of fats because they raise your LDL (bad cholesterol) and triglycerides and lower your HDL (good cholesterol). For this reason, the FDA started banning trans fats in 2018, but they can still be found in some food sources, including vegetable shortening, fried fast foods, and some brands of microwave popcorn.
  • Omega-6 polyunsaturated fats: These are the fats found in oils such as safflower oil, sunflower oil, canola oil, soybean oil, corn oil, and most other oils that are used for cooking. Unfortunately, when you eat out at a restaurant, almost ALL of the foods are cooked using these oils. These fats stimulate your fat cells to produce cytokines, which are proteins that cause low-level, chronic inflammation. They have been linked to a number of age-related, inflammatory-based illnesses, including diabetes, heart disease, cancer, and arthritis.
  • Omega-3 polyunsaturated fats: These are considered to be “heart-healthy” fats because they raise your HDL and lower your LDL, thereby protecting you against vascular diseases. These fats are found in fish, vegetables such as avocados, and healthy nuts.
  • Monounsaturated fats: These are also considered to be the most “heart-healthy” fats. They reduce inflammation, promote cellular efficiency, and protect you from vascular disease. These fats are found mostly in olive oil, and healthy nuts such as almonds and macadamia nuts.
  • Saturated fats: A diet high in saturated fats can increase your risk for developing heart disease and vascular disease, which is why most nutritionists recommend limiting saturated fats to no more than 10% of your daily fat intake.[6] Saturated fats are found in animal-based foods such as red meat, cheese, and dairy, as well as plant-based oils like coconut and palm oil. These oils are also commonly used in commercially produced baked goods like boxed cookies and crackers.

Both are types of the polyunsaturated fats (omega-3 and omega-6) are considered “essential fats” which means the body requires them for normal functioning. Our body doesn’t naturally produce these fats, which means the only way to get them is through our diet. But an important distinction is that omega-6s are pro-inflammatory and omega-3s are anti-inflammatory.

Omega-6 fats, like soybean oil, are far cheaper which means they are more likely to appear in processed foods. And since processed foods make up a significant proportion of the American diet, we as a nation are consuming too many omega-6s and not enough omega-3s. 

The recommended ratio of omega-6 to omega-3 fatty acids in 4:1, but the Western diet ratio is more like 10:1 or even 50:1![8] This imbalance increases body-wide inflammation and negatively alters cell-membrane health.

To correct this imbalance, try to reduce the amount of omega-6s in your diet and boost the omega-3s. An excellent way to do this is to follow the World Health Organization’s recommendation to consume two servings of oily fish per week. 

In fact, research shows people who eat seafood 1-4 times per week are less likely to die of heart disease or strokes.[9] You can also stock up on flaxseeds, chia seeds, walnuts, avocados, and grass-fed beef, which are all high in omega-3s.

Excessive saturated fats also promote inflammation, weight gain, and ultimately aging. Depending on your genetics (remember how important ‘epigenetics’ is?), some people can tolerate more saturated fats than others. But for some, consuming more than 10% of your fat intake as saturated fat can dramatically increase your risk for early ALzheimer’s Disease and cardiovascular disease.

But here is the good news—the negative impact of these fats can easily and quickly be reversed. One study found that after just two weeks of swapping out saturated fats with monounsaturated fats, cytokines were reduced and as a result, brain functioning was significantly improved.[7] So by making just a few simple swaps to your diet, you can quickly reduce inflammation, prevent disease, and enable your body and brain to age healthier.

The third pillar of an anti-aging diet is to “eat the rainbow,” which means eating a wide range of vegetables and fruits to ensure a wide range of vitamins and minerals.

Focus on incorporating dark greens (broccoli, watercress, kale) and brightly colored vegetables and fruits (red bell peppers, carrots, blueberries).

Supplements can also help you incorporate important nutrients into your diet. Research supports the use of several anti-aging supplements, including CoQ10 and Vitamin C (to learn more, check out my article on the 7 supplements every man should be taking).

2.Keep Moving

What you put into your body is only half of the anti-aging equation; just as important is what you do with your body. Exercise isn’t just a solution for weight loss. It actually equips your body with the tools it needs to successfully navigate the aging process.

With the rise of wearable tech, there has been an emphasis on counting the number of daily steps to improve health, but there is no scientific evidence to support the well-known “10,000 steps a day” rule. Instead, what you should be focusing on are the minutes you spend each day in your target heart rate. 

Heart Rate Matters

Your target heart rate varies depending on your age. First, you need to calculate your maximum heart rate (MHR), which is 220 minus your age. So a 40-year old man would have a MHR of 180.

The key to heart-benefiting exercise is to work out at the proper intensity and duration. In terms of intensity, you want to exercise hard enough to raise your heart rate, but not so much that it reaches all the way up to your MHR. 

Moderate aerobic activity is generally defined as 50-70 percent of your MHR. So in the case of our 40-year old man, that would be a heart rate range of 90-126. 

Vigorous aerobic activity is defined as 70-85 percent of your MHR, which for a 40-year old man would be 126-153. Either way, you should always avoid going over the 85 percent upper limit since it offers no health benefits and can actually strain your heart.

In terms of duration, the Mayo clinic recommends you strive for at least 150 minutes of moderate aerobic activity—brisk walking, swimming, yard work and household chores—per week, but you could go all the way up to 300 minutes for maximum benefit.[10] If instead you prefer vigorous aerobic activity—running, aerobic dancing—strive for at least 75 minutes per week.

Keep in mind that exercise doesn’t just keep your heart young, it keeps your brain young too. Once study published in the Journal of Alzheimer’s Disease found that a lack of exercise in older adults raised their risk of developing dementia to a level that was equivalent to people who were genetically predisposed to the disease.[11]  

Studies like this prove that despite what your genes say, you have a great amount of control over your aging process. This is just one reason why I’m so passionate about epigenetics—the idea that your external environment affects the way our genes behave. And to clarify, your environment is not just chemicals or toxins in your environment, but also what you eat, how you move, how you breathe, how you sleep, etc.. 

In addition to aerobic exercise, the other essential component to an anti-aging workout is strength training. As we age, muscles lose their flexibility and shrink. 

In fact, after the age of 30, you lose 3-5 percent of your muscle mass every decade, and men on average lose 30 percent of their muscle mass over their lifetime.[12] On top of that, ligaments, tendons and connective tissues dehydrate and degrade as we age, further reducing our mobility and increasing risk of injury. 

But as exercise physiologist Dr. Thomas Storer makes clear, “Older men can indeed increase muscle mass lost as a consequence of aging. It takes work, dedication, and a plan, but it is never too late to rebuild muscle and maintain it.”[12]

To kick start muscle gain, focus on high rep workouts rather than heavy weights. A typical program might include 8-10 different exercises that target all major muscle groups, with 2-3 sets of 12-15 reps, performed 2-3 times per week. Once this program is established, you can increase the weights, drop the number of reps down to 10, then eventually work your way up to 15 and repeat the process. 

And don’t forget that muscle building requires protein. According to the American College of Sports Medicine, men engaging in strength training should consume 0.5-0.8 grams of protein per pound of body weight.[13] That means a 165-pound man generally needs around 80-135 grams per day, although remember that your genetics direct specifically how much protein your body needs (epigenetics!!).

Lastly, consider supplementing with things known to prevent muscle loss, including fish oil, vitamin D, and hormone replacement therapy. And don’t forget to fortify your bones too, with calcium and vitamin D (take these together for maximum absorption), as well as vitamin C, B12, and magnesium.[14]

3. Build a Better Brain

Our body isn’t the only thing that degrades as we age. The older we get, the longer our brains have been exposed to inflammatory triggers like toxins, chronic stress, and unhealthy foods. Only now are scientists discovering that conditions we assumed were inevitable as we age, like dementia and Alzheimer’s disease, are actually caused by brain-wide inflammation.[15]

The good news is that most of the things we’ve discussed that prevent the body from age-based decline benefit the brain as well. Exercising, avoiding sugar, keeping your cholesterol in check and maintaining a healthy diet are all excellent ways to protect your brain against aging. Additional strategies include getting 7-8 hours of sleep every night, limiting alcohol, quitting smoking, and reducing stress.

Certain supplements have also been shown to preserve cognitive functioning and prevent neurodegenerative conditions like Alzheimer’s and Parkison’s disease.[16] For example, vitamin D and B12 play vital roles in memory formation and cognitive functioning, which is why a deficiency in these vitamin has been linked to cognitive impairments, depression, and Alzheimer’s disease in older adults.

Fat is another important factor when it comes to brain health. Omega-3s account for 40 percent of the fatty acids found in our brains cells and they are especially concentrated at the synaptic connections where all communication between brains cells occurs.[17] Research shows higher intake of omega-3s is associated with larger brain volume and a decreased risk of developing Alzheimer’s disease, so consider adding a fish oil supplement to your daily routine.

Putting it All Together

Aging isn’t something you have to take lying down. With just a few tweaks to your routine and the addition of a few foods and supplements, you can actively slow down or even reverse the effects of aging. 

To see the power of lifestyle changes in action, look no further than a study published in The Lancet Oncology.[18] In this study, researchers had a group of men start a plant-focused diet, exercise for 30 minutes six days a week, and practice yoga or meditation for three months. After the three months, the researchers examined the men’s telomeres. 

Telomeres are a lot like those plastic endcaps on shoelaces that stop the laces from fraying and falling apart. In each of our cells, we have telomeres that cap off the ends of our chromosomes and keep the DNA strands intact. 

Cells replenish by copying themselves and each time they do, these telomeres get shorter and shorter. Eventually, they become too short to do their job, the DNA becomes damaged and the cell stops working. 

For this reason, the length of our telomeres is considered an indicator of our biological (rather than chronically) age. The shorter our telomeres, the “older” our cells are and the more likely we are to succumb to age-related illnesses.

So what did the study find? After just twelve weeks of adopting these simple lifestyle changes, the men’s telomeres grew by a whopping 10 percent. As lead researcher Dr. Dean Ornish stated, “This study is the first of its kind that scientifically proves you can reverse aging at a cellular level through lifestyle changes.”[19

With some adjustments in your lifestyle, you can turn the clock back on your cells too. If you want to take control of the aging process and feel better, schedule a consultation.  You’ll learn how a personalized health strategy can let you live your life to the fullest.

Men’s Health: Reverse Aging with NAD+

Aging is inevitable – but there’s a whole new frontier for optimizing our health through the latest genetic science and biohacking that can help you to slow down the aging process and maybe even reverse aging with NAD+.  NAD (short for nicotinamide adenine dinucleotide and also known as NAD+) has recently been getting a lot of attention as a cutting-edge tool to promote longevity.  

We’re taking it all the way down the cellular level here.

Properly functioning cellular metabolism is essential to health. The sum of every chemical reaction that happens inside the body, along with its molecular interactions, keeps the body in a state of balance. This is all made possible by coenzymes (“helper molecules”) and specific proteins acting as metabolic sensors that respond to conditions in the cells and body. NAD is a tiny coenzyme that plays an important role in this delicate dance. As you age, NAD+ decreases and with it goes cellular function that prevents disease and maintains vitality.

What is NAD+ and why is it important?

NAD+ is vital to cellular metabolism because it turns nutrients into cellular energy. It also activates a set of proteins called sirtuins that regulate cellular health. NAD+ creates the cellular energy that helps us to retain our youthful function, muscle strength, and physical stamina. When sirtuins were discovered they were quickly nicknamed “the longevity genes.” 

A fascinating aspect of NAD+ is its dual role in protecting against the factors that age us. This includes inflammation, DNA damage, and failing mitochondria (cell respiration). NAD+ promotes longevity by facilitating DNA repair and protecting mitochondria from early death. As a result, NAD lowers the risks for age-related brain diseases like Alzheimers or Parkinson’s and cardiovascular diseases (a leading cause of death for men). 

NAD is the building block for ALL of our systems such as the lymphatic, cardiovascular and nervous systems. It is responsible for our immune function, insulin regulation, and fatty acid oxidation. Without it, we would literally die!

Improving Health Through NAD+ Boosting Photo Credit: The Sinclair Lab

NAD+ and Aging

A NAD+ molecule isn’t consumed alone to create energy like fuel in a car. Instead, it works with proteins to carry out essential biological processes like cellular energy creation and maintaining healthy DNA. Sirtuins are some of the proteins that play a key role in these processes. They only function in the presence of NAD+ and this means that the body needs to constantly synthesize it to maintain cellular function. However, NAD levels markedly decline with age, creating an energy deficit that decreases the body’s ability to retain optimal health.

Sirtuins and NAD+ work together to help promote overall health.

For example, at age 50 a typical person may have only half the NAD+ they did in their younger years but by age 80, NAD+ levels drop to only 1-10 percent of the levels measured in youth. But recent studies have now shown that increasing NAD+ in the body can restore the body’s cellular function as though turning back time – actually slowing down the aging process. Essentially, men can reverse aging by restoring healthy levels of NAD+.

One study done on mice, showed an average 5 percent increase in their lifespan —even though supplementation did not begin until the mice were nearing the end of their natural lifespan of 24 months. That would be the equivalent of gaining nearly an additional four years of life to today’s average human expectancy of 79 years!

Another side effect of decreased NAD+ is that muscles begin to shrivel and grow weaker due to vascular aging (thinning and aging of blood vessels, reducing cellular health). Vascular aging is responsible for many disorders for men.  These may include cardiac and neurologic conditions, muscle loss, and impaired wound healing. The process can be slowed down with regular exercise, but gradually even exercise becomes less effective at holding off this weakening.  In further research findings, mice with NAD+ supplementation showed between 56 and 80 percent greater exercise capacity. This points to a reversal in vascular aging and an ability to maintain a youthful physical stamina. 

Furthermore, in two different animal models of neurodegenerative disease, increasing cellular NAD+ reduced the severity of the disorder, normalized neuromuscular function, and delayed memory loss.  Most studies started on mice, but more recently clinical studies have shown positive effects on humans. You can begin to see how crucial NAD+ is to a vital life – and how its depletion can rob you of this vitality as you age.

Reversing Aging with NAD+ Precursors

Most of the ways of increasing NAD+ do not include supplementing with NAD+ itself, but rather precursors to NAD+. There are 5 precursors to NAD+:

  • tryptophan
  • nicotinic acid (pyridine-3-carboxylic acid)
  • nicotinamide (nicotinic acid amide)
  • nicotinamide mononucleotide (NMN)
  • and nicotinamide riboside (NR).

We can get NAD+ in our bodies through diet.  This is done by consuming foods with NAD+ precursors in them – like fish, crimini mushrooms, and raw green vegetables. However, you can’t really eat enough of anything to significantly boost NAD+ levels. Taking a NAD+ precursor supplement can help mitigate the decline, improve cellular health, and even mitigate loss of telomeres.

NMN and NR are the most popular precursors found in the latest anti-aging supplements. However, NR (a unique member of the vitamin B3 family) has been found to be the most efficient. If you’re a wine fan, you may be familiar with another famous anti-aging compound: resveratrol. NR is 4x more bioavailable than resveratrol, quickly kicking the red-wine derivative to the curb.

It has a positive impact on Metabolism

NR doesn’t just have anti-aging effects, it has a positive impact on metabolism. Mice on high-fat diets with NR supplementation gained 60 percent less weight than they did on the same diet without NR. In addition, none of the mice on NR showed signs of diabetes. Instead, their energy levels improved. 

Nicotinamide adenine dinucleotide (NAD+) is an important target to extend lifespan and health span.

NAD+ Supplements

Renowned Harvard University geneticist David Sinclair is the pioneer in the supplementation business of NAD+ with Elysium Health. Although his anti-aging claims were first met with controversy because most studies had been done on mice (https://khn.org/news/a-fountain-of-youth-pill-sure-if-youre-a-mouse/), the study arena has since been expanded to human trials done at the Mayo Clinic and the University of Washington.  Gaining support of researchers at the top of their field, these human studies point to the same benefits found in our small furry friends.

Dr. Sinclair has conducted a study to show the effectiveness of his supported supplement, Basis.  Previous studies had shown an increase in NAD+ over a 24 hour period. His study sought to determine whether cellular NAD+ levels could be sustained over the entire study period of eight weeks, and it did.

In a placebo-controlled trial of 120 healthy adults between the ages of 60-80, participants taking the recommended dose of Basis saw cellular NAD+ levels increase by an average of 40 percent over baseline after 30 days, sustained at this number to 60 days. Participants taking twice the recommended dose saw those levels increase by 90 percent after 30 days and 55 percent at 60 days. 

ChromaDex, another leading anti-aging company has taken the running lead in scientific support for their supplement TruNiagen. With over 100 preclinical trials, 5 published studies and 3 FDA safety reviews, the evidence surrounding NAD+ supplementation is overwhelming.

It was previously thought that NAD+ could not be given in oral form and only intravenously due to poor bioavailability and low intestinal absorption.  Newer research shows that oral forms of NAD+ supplementation do have positive effects.  NADOVIM is one of the first and earliest supplements on the market to contain actual NAD+ instead of NAD+ precursors in its formulation. https://nadovim.com/top-5-reasons-to-take-nadovim-a-doctors-perspective/

Researchers are still willing to explore the value of IV infusions of NAD+. This is a new area for further, detailed study and could potentially be an effective delivery method in some ways. Preliminary animal study evidence suggests that intravenously administered NAD+ may hold some interesting promise. Currently, there are no pre-clinical or clinical human studies, but this is a fast-moving advancement in what we are learning about the way NAD+ and NAD+ precursors are processed in tissues and across the blood-brain barrier. Stay tuned.

How to Increase NAD+ Levels Naturally

Before you go out and buy a Vitamin B3 or NR supplement, remember that reversing aging requires a systems-based, holistic approach. There is no such thing as a magic anti-aging pill. NAD+ treatment in addition to other lifestyle changes and structures is what ultimately adds more years to your life. It is important to take a high quality NAD+ supplement.  Also, here are additional recommendations to ensure you increase NAD+ and its anti-aging effects.


Fasting, or reducing your calorie intake for extended periods, is an excellent method for indirectly boosting the body’s NAD+ levels. It has been shown that, fasting is effective in increasing NAD+ levels.  However, a drastic reduction in calorie intake or fasting long term can have a counterproductive effect. Consider intermittent fasting or adopting a low carb-ketogenic diet to provide similar positive results.


Exercise is one of the easiest and most cost-effective methods for boosting NAD+ levels. In a nutshell, exercise forces our body muscles to produce more mitochondria. The increased production of mitochondria results in a natural boost in NAD+ levels in the body.


Research has shown that too much direct sunlight exposure can deplete the body of NAD+ because our body uses NAD+ to repair sun damaged cells from over exposure to UV rays. Reduce exposure to strong sunlight and wear sunscreen.

Healthy Diet

Eating a well balanced whole foods diet full of NAD+ precursor rich foods is a one-way ticket to reversing aging. Be sure to add more of the following into your diet: 

  • Fish – Varieties of fish like tuna, salmon and sardines are rich sources of NAD+ for the body. Be sure to source your fish from sustainable, wild-caught sources.
  • Green Vegetables – green vegetables contain all sorts of nutrients in them which are beneficial in a variety of ways including NAD+ precursors. Of these vegetables peas and asparagus have the highest amount.
  • Whole Grains – high in Vitamin B3 which also contains RN. Remember that vegetables and grains that are cooked or processed lose their nutrition as well as the vitamin source. Therefore, it is recommended that you should also eat raw vegetables and choose whole grains (rice, quinoa, etc) over processed foods such as chips and cereals.
Reduce Alcohol Intake

Alcohol interferes with healthy cellular processes and reduces the efficacy of NAD+. In fact, alcohol consumption has been shown to directly reduce levels of NAD+ (and testosterone) in the body. 

NAD+ precursors, exercise and caloric restriction can increase NAD+ levels.
NAD+ helps you get energy out of the food you eat, it protects cells from stress, it maintains healthy sleep cycles and it helps your cells repair damaged DNA.


If you are looking for supplements that reverse aging, the NAD+ research is very promising.  It should be considered as a part of a holistic health plan for every aging male.  Without exercise and a whole foods diet, NAD+ supplementation will have minimal effects. For men who are looking to take their performance and health to the next level, NAD+ can give you that extra edge.

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In Male 2.0, Dr. Tracy Gapin has turned everything we once thought we knew about men’s health and performance upside down. The old model of how to be “a man” is broken. A man who works himself to death. A man who tries to NOT get sick but isn’t really healthy either. A man who takes a pill for every ill but is never really cured. That was Male 1.0. Now, imagine being THE MAN ─ owning your performance in the bedroom, the weight room, and the boardroom. Living a fully optimized life. Becoming limitless. This is Male 2.0!

Tracy Gapin, MD, FACS  is a board-certified Urologist, Men’s Health Expert, Author, and Professional Speaker. Using state-of-the-art biometric monitoring, nutrition and lifestyle intervention, Dr. Gapin coaches Fortune 500 executives and evolutionary leaders of business, sports medicine, and high performance. He specializes in cutting-edge precision medicine with an emphasis on epigenetics, providing men with a personalized path to optimizing health & performance. www.SmartMensHealth.com