NAD+: A Complete Guide To This Longevity-Boosting Coenzyme

Photo by BONNINSTUDIO

After a certain age, not many of us look forward to our next birthday with the same level of enthusiasm we once did. Of course, there are many aspects of getting older that are beautiful—the memories we accumulate and even those smile lines that prove we've really lived and laughed—but if there were a switch we could flip to slow down the aging process (to counter the waning energy, to keep those memories sharp, to stay healthy enough to continue having amazing experiences), then we'd probably all flip it in a heartbeat.

The good news: There is something scientists have identified that may be the key—or at least part of it—to keeping your mind and body more youthful and potentially boosting longevity. It's a coenzyme called nicotinamide adenine dinucleotide (NAD+), and it's starting to generate some buzz.

What is nicotinamide adenine dinucleotide (NAD+)?

NAD+ is a coenzyme found in all living cells, and it plays a vital role in energy metabolism and maintaining proper cell functioning—particularly the functioning of our mitochondria, the power plants in our cells that turn our food and oxygen into energy. The problem is that our levels of NAD+ decline significantly as we get older (impairing mitochondrial functioning, among other things), and these declining levels drive the aging process. Which makes sense when you consider that underperforming or damaged mitochondria are thought to contribute to age-related diseases such as heart disease, diabetes, and Alzheimer's.

One way NAD+ seems to exert its health-promoting properties is by helping sirtuins do their job. Sirtuins are a class of proteins that regulate biological pathways, turn certain genes on and off, and help protect cells from age-related decline. For example, NAD+ increases the activity of SIRT1, which has been found to induce the formation of new mitochondria and extend life span, as well as SIRT6, which helps maintain the length of telomeres (the end caps on DNA)—longer telomeres are associated with longevity.

How to increase NAD+ levels in the body.

According to Ilene Ruhoy, M.D., Ph.D., an integrative neurologist and mindbodygreen health expert, "Appropriate levels of NAD+ are critical to support the body's response to stress, as NAD+ is used by these enzymes to modulate cellular activity in response to extrinsic and intrinsic assaults, including those triggered by environmental toxins, pro-inflammatory foods, microbes such as viruses and bacterium, trauma, disease, and even chronic use of medication. NAD+ is essential for continued health, wellness, and strength."

Knowing this, we want to try to keep NAD+ levels in a healthy place, especially since we know that they decline naturally as we age. But if it's not a nutrient present in either food or supplements, then why are we even talking about it? Turns out, there are a couple of indirect ways to increase your NAD+ levels, which may have positive results for your health:

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1. Calorie restriction

Restricting calories (20 to 30 percent less than what you normally consume) and fasting have been shown to increase NAD+ levels and increase activation of SIRT1. This SIRT1 activation, scientists say, is why calorie restriction has been associated with increased life span in animal studies. However, drastically cutting your calories or fasting for prolonged periods of time isn't realistic or advisable for most people. There is some speculation that intermittent fasting diets and low-carb ketogenic diets may have a similar impact on NAD+ levels—while being much more sustainable—but more research needs to be done to confirm this.

2. Supplements containing nicotinamide riboside (NR)

Nicotinamide riboside is a newly discovered form of vitamin B3, which is found in trace amounts in milk. No one really thought much about it until scientists discovered that our bodies convert it into NAD+. Two recent human trials on NR-containing supplements found that they both effectively increased levels of NAD+ in the body, which is promising. One study was performed with NIAGEN, the ingredient found in supplements like Tru Niagen; while the other study used the supplement Basis. However, we still don't know if these supplements can increase levels enough to actually slow down the aging process or result in any other meaningful health benefits. More studies are needed to determine that. That said, there don't appear to be any major health risks associated with NR supplements, so if you want to give one a try, it's likely safe to do so.

Additionally, there are some things you can do that may help maintain NAD+ levels—even if they don't necessarily increase them. For example, UV rays damage skin cells and your body uses NAD to repair that damage. Therefore, wearing sunscreen or protective clothing can help minimize that damage and preserve NAD+. A healthy, whole-food-based diet and a regular exercise routine (especially HIIT-type workouts) can't hurt, either—as they both boost the health of your mitochondria and may help your body use NAD+ more efficiently or sparingly.

Photo: Marc Tran

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Potential benefits of maintaining (or increasing) your NAD+ levels.

Animal studies have shown that boosting levels of NAD+ can lead to improved memory, resistance to weight gain, a longer life span, and other benefits. As mentioned above, NAD+ is able to do this by activating proteins called sirtuins and optimizing cell metabolism in other ways. Here are some of the most promising ways that maintaining or increasing healthy NAD+ levels may improve health:

1. Prevent age-related memory loss.

NAD+ is vital to DNA repair and resistance to neuronal stress. Because of this, it may help improve memory and prevent Alzheimer's disease. According to a recent animal study, researchers developed a strain of mice with features mimicking human Alzheimer's disease, then added an NR supplement to their drinking water for three months to increase NAD+ levels. Over this period, researchers found that the NR-treated mice had less DNA damage, higher neuroplasticity, increased production of new neurons, and lower levels of neuronal damage. In the hippocampus area of the brain (where damage and loss of volume is found in people with dementia), NR seemed to clear existing DNA damage or prevent it from spreading farther. The NR-treated mice also performed better on memory tests.

2. Counter high-fat diets and prevent weight gain.

Animal research suggests that increasing your levels of NAD+ may help boost metabolism and prevent weight gain, even if your diet is high in fat. One study found that mice on high-fat diets that received an NR supplement gained 60 percent less weight than they did on the same diets without NR. They also had more energy. These positive results, researchers say, were due to increased activation of the sirtuins SIRT1 and SIRT3, which led to improved oxidative metabolism. None of the mice receiving NR showed signs of diabetes, either.

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3. Boost strength and endurance.

As we age, muscle function and strength tend to decline. Increasing NAD+ levels by supplementing with NR seems to help. In one study, researchers used mice whose genes were altered so their muscle tissue contained just 15 percent of the normal amount of NAD+. They then measured muscle strength and endurance, which was quite low. But after giving the mice NR-enriched water to replenish NAD+ levels, their exercise capacity was restored to that of a normal, healthy mouse in just one week. In another study, supplementation with NAD+ precursors led to DNA repair and an improvement in the health of muscle tissue within the first week—to the point where researchers couldn't tell the difference between the tissue of a mouse that was two years old and a mouse that was four months old.

4. Increase longevity.

Several studies have found that replenishing levels of NAD+ with supplements containing NR lengthen the life span of mice by improving mitochondrial function and increasing activation of SIRT1, a specific sirtuin protein. This is the same mechanism by which restricting calories seems to lengthen life span. (Additional compounds that may mimic the life-extending effects of calorie restriction include pterostilbene and resveratrol.) Other studies suggest that NAD+ increases the activation of SIRT6, which helps maintain the length of telomeres—the end caps on DNA that are associated with longevity.

The bottom line on NAD+ and your health.

NAD+ is clearly an important molecule for optimizing a variety of cellular functions that promote overall health and longevity. While restricting calories is a natural way to increase NAD+ levels, it's likely not realistic for most people. Supplementing with an NAD+ precursor supplement such as NR, on the other hand, may be easier, but more research is needed to see if it can elevate NAD+ levels enough to actually counter the effects of aging and yield real health benefits.

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