Md. Asaduzzaman Khan, PhD

NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme found in every living cell in our body, involved in hundreds of metabolic processes that are incredibly important.

If you haven’t heard about NAD+, certainly you know about vitamins, right? Nicotinamide is a form of vitamin B3 (niacin) and a major constituent of NAD+. So, vitamin B3 deficiency is actually the lack of functioning of NAD+.

The ratio of NAD+/NADH should be balanced, and an imbalance in NAD+/NADH can destabilize cellular homeostasis, causing pellagra disease and also induces aging, inflammatory alterations, neurodegeneration, cancer etc.[1]

Functions of NAD+

To maintain life, the biochemical processes that occur within a living organism are called metabolism. NAD+ plays an important role in metabolism. NAD+ is the functional part of enzymes which are involved in energy producing metabolic reactions inside living organisms involved in producing energy (as ATP) to maintain the living system.

It is also related to aging or longevity process, and cancer. Interesting fact is, NAD+ depletion leads to aging and degenerative diseases, while the increase of NAD+ pool is related to carcinogenesis.[2] So, keeping a balance of NAD+/NADH ratio is very important for healthy lives. Do you know NAD+ also regulates your immune system?

The role of NAD+ in immunity

NAD+/NADH is essential for creation of energy and to regulate pivotal processes. Free radical damage causes cell injury and inflammation, which reduces immunity. NAD+ reduces free radical damage, and activates the innate immune system. [3,4] The innate immune system acts as the first line of defense (immune response) against invading pathogens or foreign particles (infectious agents).

Inflammation is one of the first responses of the innate immune system to infection. NAD+ regulates the inflammatory response in immune cells through sirtuins, a protein family, essential for the development and differentiation of the immune system.[2] Thus, NAD+ plays a big role in inflammation and generates immune response in aging, infection, cancer and other disease conditions.

• NAD+ and infection: Altered NAD+/NADH level is associated with infectious diseases, for example, infection by Mycobacterium tuberculosis causing tuberculosis. Recent findings indicate that SARS-CoV-2 infection and the disease state of COVID-19 is linked with the reduction of NAD+.[5]
• NAD+ and cancer: NAD+ is a key factor in anticancer response. NAD+ administration may boost the anticancer activity of T cells (one of the important blood cells that play a central role in immune response in preclinical models of human cancers, but NAD+/NADH balance must be taken into account in treating cancer patients. [6] Enzymes involved in NAD+ metabolism might be novel targets for adjuvant therapies in cancer treatment, especially in adoptive T cell therapies.
• NAD+ and aging related diseases: The most explored context of NAD+ depletion is aging, in which there is a significant reduction in sirtuin activity reported.[2] NAD+ is a substrate for sirtuin, and a combination of sirtuin activation and NAD+ intermediate supplementation might have anti-aging properties.[7] As well as, this might be also helpful in fighting against aging related diseases, such as neurodegeneration, especially in Alzheimer's and Parkinson's disease.[1]

Sources of NAD+

NAD+ supplementation is thus helpful in boosting immunity, slowing down aging process and fighting against cancer and neurodegenerative diseases. But NAD+ cannot be taken directly from a food source, rather its precursors should be supplemented for its synthesis and maintaining NAD+ balance. Dietary supplementation of NAD+ precursors can also increase the functional activity of mitochondria.[2]

1. NMN: Nicotinamide Mononucleotide (NMN) is an intermediary precursor of NAD+, and its supplementation can increase NAD+. NMN supplementation also restores certain gene expression involved in inflammatory response and improves cell survival.
2. Niacin: As niacin is the major constituent of NAD+, to keep physiological balance of NAD+/NADH and to ensure healthy metabolic process, we should intake enough niacin regularly. What are the sources of niacin? Many, actually, around us. Niacin is available in a variety of whole and processed foods, including meats from different animal sources, sea-foods and spices. Some rich sources of niacin are nutritional yeast, peanuts, sunflower seeds, green peas, mushrooms, whole wheat, brown rice, potato, almonds, beef, turkey, chicken, tuna fish, salmon fish, cod fish etc.

So, intake niacin rich foods regularly, take NMN supplementation (if necessary) and keep a balanced NAD+/NADH ratio that will boost your immunity and keep you healthy in following ways:

• Protect from oxidative stress
• Fight against infection
• Fight against cancer
• Fight against neurodegenerative diseases
• Slow down aging process

Md. Asaduzzaman Khan, PhD

Dr. Md Asaduzzaman Khan is a researcher and currently works as a Scientist at Southwest Medical University of China. Academically he holds a doctorate in Biochemistry and Molecular Biology. His research interests include several fields in biomedical science , such as biochemistry, molecular biology, cancer biology, human genetics, and natural products.

References

1. Belenky et al (2008). NAD+ metabolism in health and disease Trends Biochem Sci. 32(1):12-19.
2. Navas & Carnero (2021). NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. 6(1):2.
3. Massudi et al (2012). NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns. Redox Rep. 17(1):28-46.
4. Zhu et al (2016). Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy. Sci Rep. 31;6:26322.
5. Groth et al (2021). NAD+ Metabolism, Metabolic Stress, and Infection. Front Mol Biosci.8:686412.
6. Morandi et al (2021). The Key Role of NAD+ in Anti-Tumor Immune Response: An Update. Front Immunol. 2021;12:658263.
7. Imai & Guarente (2014). NAD+ and sirtuins in aging and disease. Trends Cell Biol. 24(8):464-471.