NAD+: Is It Really a Key to Longevity?

Short for nicotinamide adenine dinucleotide, NAD+ supplements are being studied for their effects on cellular energy production, mitochondria function, and DNA repair. Before reaching for a supplement, though, it’s important to explore the role of NAD+ in the body and the existing evidence on its ties to longevity, as well as ways to boost NAD+ levels naturally.

As researchers work to uncover the mechanisms behind aging, NAD+ has emerged as a promising therapeutic.

What Is NAD+?

NAD+ is a coenzyme, a small molecule that acts as a catalyst for enzymes to perform their functions. NAD+ is found in all cells in the body and has a critical role in transferring energy within our cells.

NAD+ is involved in various metabolic processes, including converting the food we eat into the energy our cells need to stay alive. It helps generate adenosine triphosphate (ATP), a final product our bodies can use. ATP is the end fuel source all our cells use. Without NAD, you cannot make ATP—an essential part of life.

NAD vs. NAD+

NAD+ is the functional form of NAD in the body. Although these terms are sometimes used interchangeably, they are not the same molecule.

“NAD+ is the one we are primarily focused on when it comes to longevity, cellular health, and energy,” Dr. Orel Swenson, founder of Aeonic Health, a regenerative and longevity medicine practice based in Boston, told The Epoch Times in an email.

As observed in mouse models, NAD+ levels naturally drop as we age. By the time we reach middle age, our NAD+ levels are at half of what they were in our youth.

“NAD+ levels decline naturally with age partly because the accumulation of DNA damage and loss of mitochondrial efficiency demand more and more NAD+,” said Swenson.

NAD Supplementation

A few existing methods to restore NAD+ levels include oral supplements, nasal sprays, transdermal patches, self-injections, and fusion therapy. The main differences lie in the delivery. Some methods are considered faster and more effective than others.

“NAD+ itself isn’t really a supplement that can be effectively taken by mouth. The bioavailability is quite limited this way,” said Swenson.

For this reason, other methods of administering NAD+, such as via IV infusion or subcutaneous injections, are growing in popularity.

“Unsurprisingly, when taking an oral supplement, the increase in your NAD+ levels is more gradual. Infusions and injections are much quicker but are more expensive and require clinician oversight for safety,” he said.

“When given this way, it’s imperative to work with a healthcare professional familiar with NAD+ administration, as it can cause nausea, headaches, fatigue, and even low blood pressure if given incorrectly,” he continued.

NAD+ Precursors

Precursors are molecules that are converted into another substance or compound by a chemical reaction. NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are substances the body can use to produce NAD+. While NAD+ is more challenging for the body to absorb, these precursors are more easily converted into NAD+.

“NMN needs fewer steps (i.e., it is closer to becoming NAD+) than NR, but both are available as oral supplements with good bioavailability,” explained Swenson.

A study published in GeroScience in 2023 determined that NMN supplementation increases blood concentrations of NAD+ and is safe and well tolerated in oral doses of up to 900 mg per day.

NR, a new form of vitamin B3, is also recognized as safe and effective in raising NAD+ levels at a cellular level. NR oral supplements are often found at a lower price point than NMN varieties.

Swenson explained the role of NAD+ in terms of longevity in four points. As a coenzyme, it interacts with other enzymes in the body to facilitate:

1. ATP production: NAD+ acts as a coenzyme, interacting with other enzymes in the body to produce ATP, the final energy source for cells.
2. Mitochondrial health: Mitochondria can be likened to a refinery or power station where ATP production takes place. NAD+ is essential for maintaining optimal mitochondrial function and for mitochondrial biogenesis, which involves the creation of new mitochondria.
3. DNA repair: Sirtuins are signaling proteins that have a critical role in the aging process, including energy metabolism, inflammation, and extending lifespan. By interacting with sirtuins, NAD+ mediates the repair of damaged DNA, which accumulates as people age.
4. Reduction of inflammation: NAD+ plays a role in reducing inflammation. As we age and levels decline, we may experience an accumulation of inflammation, known as “inflammaging.”

A review published in The International Journal of Molecular Science concluded that the existing research on the benefits of NAD+ on aging and healthspan is currently based on cell cultures and model organisms, and research on humans is warranted. Further research is also needed on long-term effects and dosage.Swenson concluded, “It [NAD+] does not represent a magic bullet, but rather should be viewed as part of an overall strategy for maximizing healthy aging.”

Gauging NAD+ Levels

There may be too much of a good thing, as high NAD+ levels have been linked to cancer and impact immunity. Existing evidence on the exact mechanisms of the connection is limited. However, NAD+ levels seem to have both pro- and anti-cancer effects. It may serve as a protective factor early on in cancer development but as a promoting factor later in the progression of the disease.

A study published in Nutrients found that “Replenishing NAD pools by NR could inhibit tumor growth and cancer metastasis as well as promote the overall health status of tumor-bearing mice.”

Specifically, the authors suggested that boosting NAD by NR supplementation could be a novel strategy to prevent the progression of hepatocellular carcinoma.

Dr. Terry Simpson, a board-certified general surgeon and the first surgeon certified in culinary medicine from Tulane University told The Epoch Times in an email, “NAD metabolism is crucial for cancer cell survival and targeting NAD biosynthesis pathways such as the NAMPT-mediated salvage pathway has been explored as a therapeutic strategy.”

NAMPT is a gene that plays a role in the production of NAD+. The NAMPT-mediated salvage pathway is critical for DNA repair. A study published in Frontiers in Oncology found that an overexpression of NAMPT is observed in several types of cancerous tumors. Increased levels of NAD+ coupled with overexpression of the gene have been shown to facilitate the division of cancer cells and promote cancer cell survival.

“Inhibiting NAMPT can deplete NAD levels, leading to reduced cell viability and increased sensitivity to oxidative stress and DNA damage to breast cancer cells,” Simpson said.

“On the other hand, NAD supplementation has shown promise in limiting metastasis in triple-negative breast cancer,” noted Simpson, “NAD boosters have potential benefits for their use in cancer patients, especially those with breast cancer, [but] must be approached with caution due to the risks of promoting tumorigenesis enhancing metastatic potential and interacting with cancer therapies.”

“We clearly need further research to understand these risks and develop safe and effective strategies for NAD modulation in cancer patients.”

Raising NAD+ Levels Naturally

When it comes to NAD+ supplementation, more research on how much to take and for how long is needed. Additionally, the U.S. Food and Drug Administration does not regulate supplements, so labels may not always match contents.

There are several ways to potentially restore your NAD+ levels naturally:

Keto Diet

The keto diet can naturally replenish NAD+ levels. Following a high-fat and low-carb diet produces ketone bodies, which are a more efficient means of fuel for the body than glucose and enhance mitochondrial function within the cell.

A report published in Frontiers in Cellular Neuroscience found that in rats, ketone metabolism in the brain results in fewer NAD+ molecules being used than glucose metabolism does. Thus, the body has higher levels of usable NAD+ when on a keto diet.

Intermittent Fasting

Intermittent fasting is linked to a potential increase in NAD+ levels in the body. Research suggests that intermittent fasting may help stimulate the production of NAD+ and activate sirtuins, which are associated with various health benefits, including longevity.

“Caloric restriction and fasting upregulate NAD biosynthesis and reduce its consumption by sirtuins and PARPs [poly (ADP-ribose) polymerases], increasing NAD levels,” Simpson explained.

Nutrition

Simpson explained that tryptophan, an essential amino acid found in turkey, chicken, and dairy products, is the precursor to the de novo synthesis (a chemical process that creates complex molecules from simpler ones) of NAD+. Additionally, niacin, also known as vitamin B3, present in meat, fish, and whole grains, can be converted to NAD+ via a specific pathway.

Simpson also explained that resveratrol, an antioxidant in grapes and red wine, helps promote NAD+ levels. Quercetin, a flavonoid in apples and onions, has been shown to preserve NAD+ by inhibiting a particular enzyme, CD38, that degrades it.

NAD+ precursors may also be obtainable from food. A report published in Current Nutrition Reports found that both NR and NMN are found in vegetables, milk, and meat and can be produced by microorganisms in fermented beverages.

Exercise

In a study published in Physiological Reports, researchers found that older adults saw positive effects on NAD+ levels after 12 weeks of resistance and aerobic exercise.

“Exercise, regular physical activity has been shown to increase NAD levels by enhancing the activity of the enzymes involved in the NAD biosynthesis such as NAMPT,” said Simpson.

Temperature Exposure

Exposure to temperature extremes is linked to a rise in NAD+ levels. High heat sources for short periods of time, such as a sauna, may increase levels, as does cold shock therapy.

A review published in Oxidative Medicine and Cellular Longevity found that cold exposure activates NAD+ biosynthesis, and heat shock elevates an enzyme that triggers NAD+ synthesis and facilitates the function of sirtuin.

Factors That Deplete NAD+

Conversely, certain lifestyle factors may deplete NAD+ levels and are best avoided if you seek to increase yours.

“Maintaining a regular sleep schedule can support NAD levels, and NAD metabolism is closely related to the circadian clock,” said Simpson, “Avoiding excess alcohol, which [also] depletes NAD,” he continued.

Eating habits can play a role in influencing the decline of NAD+ levels. High-fat, high-sugar diets, such as those with excess ultra-processed foods, can stress the liver and lead to fatty liver, which is associated with lower levels of NAD+. Overeating and a high caloric intake, in general, also decrease NAD+ levels.

While more research is needed before NAD+ can be crowned the fountain of youth as it is often touted, evidence supports the benefits of maximizing your levels by adopting healthy lifestyle behaviors and avoiding those that deplete them. Supplementing with high-quality NAD+ precursors or speaking with a physician, nutritionist, or other health care professional about other possible delivery methods may be worth exploring and adding to your personal longevity toolbox.

Source: theepochtimes.com/health/exploring-nad-is-it-really-a-key-to-longevity-5735371