New Research on NAD+ and Its Role in Combating COVID-19

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In a healthy, young individual with adequate levels of NAD+, CoV may pose a less severe threat.

Note: Although the following study has yielded some encouraging developments, the information is published by bioRxiv as a preprint and has been publicly shared before peer review.  

In an effort to unravel the inner workings of the novel coronavirus sweeping the globe, a recent preclinical study published at the end of April 2020 shines a light on how the critical coenzyme called nicotinamide adenine dinucleotide (NAD+)  may assist the immune system in combating the virus. 

NAD+ is a coenzyme found in every cell in the body. The study’s findings may glean hope for understanding its critical role in more effective preventative and therapeutic interventions against COVID-19, particularly for the most vulnerable communities such as the elderly and immunocompromised. 

An Overview of NAD+

NAD+ is found in all living cells and is responsible for the most basic human tasks such as metabolizing food and regulating sleep, which results in the production of energy. There are four NAD coenzymes (NAD+, NADH, NADP+, and NADPH), all staples for maintaining homeostasis, the body’s innate balanced state. NAD+, in particular, plays a central role in the production of sirtuins, better known as the “longevity genes,” which slow down cellular aging and reduce the risk of developing chronic disease.

The ways in which NAD+ levels contribute to longevity and feelings of youthfulness abound, but how might it offer protection amidst the coronavirus pandemic? 

NAD+ levels are most often depleted due to inflammatory damage that typically accompanies illness, whether acute infections like COVID-19 or chronic illness like autoimmune diseases. The same inflammatory damage is seen as part of the aging process as well. Therefore, maintaining adequate levels of NAD+, especially as we grow older, could be a piece of the puzzle to help our bodies ward off a variety of diseases.  

NAD+ and COVID-19

Preliminary data suggests CoV impairs a portion of the NAD gene set by influencing poly (ADP-ribose) polymerase (PARP).

The April 2020 study, sponsored by ChromoDex and published in bioRxiv, examined tissue cultures of ferrets, as well as a lung biopsy of a deceased human victim of COVID-19. 

Preliminary data suggests COVID-19 impairs a portion of the NAD gene set by influencing poly (ADP-ribose) polymerase (PARP). PARP is an essential enzyme paramount to the repair of DNA damage in the body, as well as regulation of many other cellular processes. These enzymes are required for a natural and healthy response to the virus itself. 

“We showed that within 12 hours of initial infection, the virus greatly depresses levels of NAD, the central catalyst of metabolism,” states ChromaDex chief scientist and co-author of the study, Charles Brenner, PhD, in an article by Nutritional Outlook.

Furthermore, NAD+ is essential for healthy functioning of PARPs, which contains a family of 17 enzymes in humans. Of those 17, 16 are responsible for transferring ADP-ribose from NAD+ to proteins, DNA and RNA.

An immune response against COVID-19 is initiated by recognizing double-stranded RNA, at which point a PARP gene expression program is turned on, stopping or slowing the virus from replicating. But when the virus infects the cells, NAD+ is impaired, thereby rendering the PARP family ineffective in promoting an appropriate immune response.

In a healthy, young individual with adequate levels of NAD+, COVID-19 may pose a less severe threat. However, as we have seen in the elderly and immunocompromised with already depleted levels of NAD+, more severe symptoms and a potentially life-threatening emergency is possible. 

To further illustrate what happens in the body in response to COVID-19 infection, envision a computer encountering a virus. Computers typically have additional or built-in viral protection software running unnoticed in the background, scanning for potential harm. Our bodies, too, have antiviral “software” that turns on when alerted to the entrance of pathogens like coronavirus. Consider NAD+ as an antiviral software program. When the software functions optimally, invaders are effectively managed by a healthy immune response. When damaged or depleted, though, the grounds are fertile for viruses to replicate faster than they can be mitigated.

The study data specifically singled out the PARP14 gene, suggesting that it may be responsible for establishing an immune response in cells infected with COVID-19 as it is required to fully induce an interferon release. This interferon response is what alerts nearby cells to heighten their antiviral defense. Without adequate amounts of NAD+, healthy expression of the PARP genes is diminished, which may hinder an effective immune response.

Ultimately, NAD+ may play a pivotal role in supporting our immune system against COVID-19, but further research is still needed. “We need a bit more proof of concept, and then we’ll be able to do human clinical studies,” Brenner tells Nutritional Outlook. 

Show references

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