NAD+ (Nicotinamide Adenine Dinucleotide)

NAD is an essential enzyme that has a role in many important cell functions, such as energy metabolism, DNA repair, and cellular health. NAD levels naturally decline with age and may relate to various signs of aging, such as lower energy, impaired cellular repair, and higher risk of age-related diseases.

Nicotinamide adenine dinucleotide, otherwise known as NAD+, is a substance found in all cells in the human body and helps them function well. It is important for the regulation of metabolism, repair of DNA and production of energy. But NAD+ levels decline as we get older, and many believe this is linked to the aging process.

In the past decade, a significant body of evidence has demonstrated that systemic decreases in NAD+ levels drive the age-associated physiological decline in tissue functions and the pathogenesis of age-associated diseases. A number of excellent review articles have already summarized these critical findings that support the notion that systemic NAD+ decline is a key driving force of aging7,8,9,10,11. This NAD+ decline appears to be caused by two underlying molecular events: decreased NAD+ biosynthesis23,24,26,27,28 and increased NAD+ consumption29,30,31,32,33.

NAD+ activates a group of enzymes called sirtuins, which help with cell repair, regulating inflammation and stress resistance. When these processes become less efficient—as in the aging process—there is a higher risk of certain chronic diseases, such as dementia, heart disease and diabetes.

As such, some health experts believe that increasing NAD may help promote longevity and slow the aging process. However, evidence from human studies is limited due to small sample sizes, researchers found in a 2023 literature review.

Preclinical studies in rodents have suggested that NAD-boosting supplements may help:

• Delay signs of aging

• Boost metabolism

• Improve insulin resistance

• Promote cognition

• Protect heart health

• Improve fertility

• Fight gut inflammation

However, there is currently no conclusive evidence that NAD supplementation can slow aging, and more research is necessary to understand its possible benefits.

In a 2018 study published in Nature, healthy adults were given NR supplements for six weeks as part of a randomized controlled trial. "It was really the first time NR had been given chronically over several weeks to humans," says Martens, who co-led the study.

The results showed that NR supplements effectively increased concentrations of NAD+ in the blood. “We know in both animals and humans, if we ingest these precursors, the amount of NAD in blood goes up dramatically,” says Martens. Recent research shows these precursors can also increase NAD+ levels in multiple tissues.

"What we don’t know is whether that increase in NAD is having a real, meaningful effect on the function of our cells, and from there, the function of our organ systems and health outcomes," he adds.

Early research suggests NAD-boosting compounds are promising, but more high-quality studies are needed among both healthy individuals and populations with risk factors associated with lower NAD levels, the experts say.

Low NAD+ levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD+ levels.

Dr. Shin-ichiro Imai, a professor at Washington University School of Medicine in St. Louis, has studied the effects of increasing NAD+ levels, which increases the production of sirtuins, on aging for more than 20 years. In 2016, Imai discovered that boosting molecules that increase NAD+ in the body led to effects similar to anti-aging in mice.

One of the few studies in humans showed that boosting NAD+ levels improved cardiovascular health, reduced skin ulcers, and helped protect kidney function in patients.

Because NAD+ is a form of vitamin B3-related compound, true allergic reactions are uncommon; however, any prior adverse reaction to niacinamide/NAD+ products would warrant against use of NAD+ Injection.providers may advise against NAD+ injections in patients with serious underlying medical conditions as a precaution. For example, those with severe liver or kidney impairment, unstable heart disease, or other significant systemic illnesses are typically approached carefully if considering NAD+ therapy. The metabolism and elimination of NAD+ (and its by-products) could be altered in advanced hepatic or renal dysfunction, and high-dose NAD+ might theoretically affect cardiovascular dynamics, so practitioners generally avoid or closely supervise NAD+ use in such settings. Similarly, individuals with active cancer are usually counseled not to use NAD+ Injection.

NAD shots are injected subcutaneously, or under the skin, and enter the bloodstream more quickly because they bypass the digestive system

For general wellness or anti-aging purposes, providers often start with relatively low doses and adjust based on patient response. A common protocol, for example, is to begin with about 20 mg of NAD+ administered subcutaneously and gradually increase the dose over subsequent injections up to around 100 mg per injection. These injections may be given a few times per week - a usual schedule is 1 to 3 times weekly - depending on how well the patient tolerates NAD+ and the goals of therapy¹⁰. By ramping up the dosage slowly, patients can often avoid side effects like headache or nausea while still obtaining the energizing or cognitive benefits of NAD+. A maintenance plan might involve ongoing injections of 50-100 mg weekly or as directed by the prescribing provider.