- NAD+ is deficiency and reduction of circulating levels of NAD+ in the body.
- NAD+ is involved in a metabolic pathway, deficiency may impair metabolism.
- NAD+ deficiency is largely dependent on the transmembrane molecule CD38.
NAD+ is a coenzyme acting as a transport for energy for different metabolic cellular pathways. The transportation of electrons for the formation of adenosine triphosphate can be disrupted with decreasing levels of NAD+. It happens commonly in aging or we are born with a NAD+ deficiency due to environmental and genetic factors.
The CD38 molecule which is found in chromosome 4 acts as a receptor in signaling pathways and adhesions. However, with insulin resistance, its expression gets higher which leads to an age-dependent reduction of NAD+ levels. An increase in CD38 expression is also linked with being a factor involved in increasing the mortality rate among patients suffering from COVID-19.
There are various factors involved in the deficiency and impairment of NAD synthesis.
Insufficient dietary intake in vitamin B3 and NAD synthesis is affected by many pathophysiological diseases such as type II diabetes mellitus, obesity, and inflammatory diseases.
On the contrary, the genetic variant factor such as gene-related heterozygous variation of NAD synthesis could also lead to NAD deficiency. This is due to the involvement of various genes involved in the synthesis of NAD including amino acid encoding transporters, salvage, and de novo pathways enzymes. The NAD+ deficiency is due to mutation in these genes.
According to a scientific study on pregnant women, it was observed that the NAD deficiency could also be caused by pregnancy. The reduction in levels of NAD co-enzymes during all three trimesters of pregnancy was observed in the blood even with sufficient diet and intake of multivitamin supplements during pregnancy. This finding indicates that during pregnancy, there are chances of developing a deficiency in NAD levels which are required to aid the body for normal embryonic development.
Recent studies have shown that NAD+ decline has been associated with diseases such as myocardial ischemia, cerebral ischemia, and diabetes. NAD deficiency is considered a central common pathological factor in such diseases and aging. This is not only due to an increase in CD38 level, but also due to nicotinamide phosphoribosyltransferase (NAMPT) decreased activity with the biological pathways. However, further investigations and clinical studies are still required to measure the exact therapeutic potential of NAD+ in aging and various diseases, but the findings so far are nothing short of exciting.
It is important to understand that the consumption of NAD through various co-enzymes such as polymerases, sirtuins, and NAD can significantly decrease in case of physiological and oxidative stress. According to a study, NAD levels can fall due to improper lifestyles such as irregular sleeping habits and improper eating habits such as consumption of alcohol, overeating, and viral infections. Due to the involvement of NAD in various metabolic pathways, the deficiency of NAD+ means encountering various symptoms such as depression, anxiety, nausea, drowsiness, and fatigue. If the levels are not restored, the individual may develop chronic fatigue syndrome and many other conditions hindering a healthy quality of life.
To conclude, NAD+ deficiency has a detrimental impact on our health and quality of life. A decline in NAD+ is imminent, especially with increasing age, poor lifestyle choices, stress and illness. The mechanism is somewhat unclear, but various causes of NAD+ deficiency have been identified by research. It includes gene mutations, increases of CD38, followed by a decrease in NAMPT functions along with some other factors, such as infections and a sedentary lifestyle. NAD+ intervention is fast being recognised as an absolute necessity in the prevention of age related disease and essential to ensuring our genetic health from the embryonic stage of life.