Nicotinamide adenine dinucleotide (NAD+) is a universal cellular electron transporter that transfers energy from the macronutrients in foods to cells in your body where it can be used for energy. There is a lot of supporting evidence that NAD+ plays a key role in longevity and long-term cellular health. A quick search on ClinicalTrials.gov yields over 1,000 clinical trials investigating the role of NAD+ in preventing and treating disease. NAD+ is a cofactor for many chemical reactions, including those involving sirtuin deacetylase enzymes and poly (ADP-ribose) polymerases (PARPs). Sirtuins play an important role in the aging process. They may protect the end of chromosomes from breaking down and mitochondria from oxidative stress. PARPs use NAD to transfer energy to proteins and for DNA repair.
NAD is also involved in defending cells against toxins and stress, optimizing mitochondrial function, reducing inflammation, and maintaining healthy circadian rhythms. Unfortunately, cellular NAD+ decreases with age. By the age of 50, NAD+ levels are approximately one-half those of an adult.
NAD+ therapy helps replenish NAD levels in the body. When you consume carbohydrates and fats, your body breaks them down to release the energy stored in their chemical bonds. This energy is stored as adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide + hydrogen (NADH). ATP and NADH can power chemical reactions that build and repair cellular structures and DNA. As NADH is converted to NAD+, it donates electrons to chemical reactions, helping them along.
Many different pathways produce and break down NAD+. It can be made from nicotinamide riboside or L- tryptophan or produced in your body via the salvage pathway. The salvage pathway is the most effective way to increase NAD+. The pathways used to produce NAD+ vary by cell type. For example, brain cells and liver cells may use different pathways.
Supplementing with NAD+ precursors (nicotinamide riboside or niagen) can help increase NAD+ levels in various cell types. These precursors are believed to be orally bioavailable and feed directly or indirectly into the salvage pathway, bypassing the rate-limiting enzyme NAMPT. Supplementing with NAD+ does not work well because NAD+ is not very bioavailable to cells, and it is rapidly broken down to nicotinamide. For this reason, NAD+ is given either by intravenous or subcutaneous injections.
Lifestyle factors can also affect NAD+. A key enzyme in the NAD+ pathway, NAMPT’s activity can be increased with exercise and decreased by abnormalities in the circadian rhythm. When carbohydrates and fats are available in excess, NADH levels increase at the expense of NAD+.
Learn more about NAD+ by reading What is NAD+ (Nicotinamide Adenine Dinucleotide)?
NAD+ therapy will most likely benefit people living with age-related diseases or people concerned about the effects of the aging process on their body. Some of the age-related conditions that NAD+ may improve include the following:
Human clinical trials testing NAD+ benefits are rare. Therefore, there is potential for NAD+ to have unforeseen negative consequences, including tumor development, increased inflammation, and suppressing feedback loops. On the other hand, other researchers have found that increased NAD+ levels may reduce cancer risk by protecting against DNA damage and oxidative stress.
NAD+ may protect brain cells from oxidative stress and impaired mitochondrial function by controlling the production of PGC-1-alpha. Reducing oxidative stress on brain cells may delay or prevent the development of changes seen in the nervous system due to aging. More research is needed to determine whether NAD+ supplementation can improve symptoms of age-related brain disorders. However, based on animal studies, researchers believe that impaired mitochondrial function and oxidative stress are linked to neurologic conditions such as Parkinson’s and Alzheimer’s disease.
NAD+ is a proven antioxidant that reduces skin inflammation and increases ceramides. For this reason, many people use NAD+ face cream to reduce skin damage, inflammation, and disease. NAD+ prevents actinic keratosis (a precursor to skin cancer) and mitigates the effects of UV radiation on the skin. Reducing the negative effects of UV radiation on the skin may be by improving PARP function. NAD+ is also used to treat psoriasis, a skin condition that results from abnormal skin cell division.
Researchers are exploring the potential benefits of NAD+ on body composition. The research is inconclusive. Some studies show an improvement in cholesterol and lipid profile, exercise capacity, and muscle fiber composition after supplementing with NAD+, while others show no benefit in terms of improving insulin sensitivity and decreasing the risk of Type 2 diabetes.
Several clinical trials (36 completed) have assessed the effectiveness and safety of NAD+ use for treating symptoms associated with aging and aging-related disease. No study reported severe side effects which support the safety of NAD+. Therefore, NAD+ is considered “likely to be safe.” However, there are some concerns that NAD+ supplementation may contribute to cancer growth, and these need to be further explored using well-controlled clinical trials.
Potential side effects of NAD+ include:
Animal studies suggest that NAD+ may have potential mental benefits, and clinical trials are currently underway, but there is not much published research yet. NAD+ is used to treat substance use disorders, and there is some evidence that it may be beneficial. It is not, however, FDA- approved for any medical indication. NAD+ performs numerous functions in all body cells. However, there are still questions about how bioavailable it may be in different body tissues and how increasing NAD+ levels may affect other chemical pathways in cells.
In animal studies, normal aging processes result in lower NAD+ levels in brain cells. Animal models also show that NAD+ supplementation restores mitochondrial function in brain cells, which increases nerve cell survival and improves cognitive function. The results of animal studies are promising, and clinical trials are underway. Once these are finished, more information on NAD+ supplementation safety, therapeutic effects, and side effects will be available.
To boost NAD+ levels naturally:
Contact your doctor if you are experiencing signs of aging, whether physical or mental, that concern you. Supplements can be very helpful in optimizing cellular functions that lose efficiency with aging, but if you have concerns about your physical or mental health, it is important to discuss your concerns with your doctor.
Start a NAD+ face cream or NAD+ injections treatment plan today!
While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.