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

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 aging in a healthy way. It's a coenzyme called nicotinamide adenine dinucleotide (NAD+), and it's starting to generate some buzz.

One way NAD+ seems to exert its health-promoting properties is by helping sirtuins do their job3. 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 one type of sirtuins, SIRT14, which has been found to induce the formation of new mitochondria and extend life span, as well as SIRT65, which helps maintain the length of telomeres (the end caps on DNA)—longer telomeres are associated with longevity.

Animal studies have shown that supporting healthy levels of NAD+6 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 can improve health:

NAD+ is vital to DNA repair and resistance to neuronal stress. Because of this, it help enhance memory and slow down age-related memory loss. According to a recent animal study7, researchers developed a strain of mice with features mimicking human age-related memory decline, 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 memory issues), NR seemed to clear existing DNA damage or prevent it from spreading farther. The NR-treated mice also performed better on memory tests.

Animal research suggests that increasing your levels of NAD+ may help support metabolism and weight maintenance, even if your diet is high in fat. One study8 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.

As we age, muscle function and strength tend to decline. But according to animal studies, 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.

Several studies9 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 SIRT110, 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 SIRT65, which helps maintain the length of telomeres—the end caps on DNA that are associated with longevity.

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 here's the catch, taking an NAD+ supplement might not actually be the best way increase NAD+ levels in the body. This is because NAD+ is a large molecule11, so in order for NAD+ to enter your cells and get to work, your body has to take it apart, transport it piece-by-piece into the cell, and then put it back together again. But if NAD+ is not a nutrient present in food or practical to take by supplement, 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:

Restricting calories12 (20 to 30 percent less than what you normally consume) and fasting13 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 diets14 might have a similar impact on NAD+ levels15—while being much more sustainable—but more research needs to be done to confirm this.

Nicotinamide riboside (NR) is a newly discovered form of vitamin B3, which is found in trace amounts in milk. No one really thought much about NR until scientists discovered that our bodies convert NR into NAD+. Two recent human trials on NR-containing supplements found that they both effectively increased levels of NAD+16 in the body, which is promising. More studies are needed, but it looks like NR could be the future of healthy aging research.

Additionally, there are some things you can do that can 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 help your body use NAD+ more efficiently or sparingly.

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, and seem to be the next promising thing in healthy aging supplementation.