This is interesting..
**Disclaimer - I've been an investor in Chromadex* for over 5 years. Chromadex is the manufacturer and patent-holder of a novel form of B3 vitamin called nicotinimide riboside chloride (abbreviated as NR) - brand-name TruNiagen. TruNiagen is a NAD+ precursor, with some advantages over other NAD+ precursors such as niacin.
NR and NAD+ augmentation is currently fashionable among 'biohackers'. (No, I don't consider myself a biohacker!). I've taken NR daily since 2014, originally in the hope it might help during the healing of a damaged sciatic nerve, then as evidence started emerging for its general health benefits.**
A fellow Chromadex investor named Shelly Albuam has blogged about some emerging research on the mechanism of covid-19 virus within human cells, and the role played by depletion of NAD+ in development of severe symptoms. Researchers suggest a hypothesis that covid19 patients augment their NAD+ levles, by taking NAD precursors such as NR or Niacin, and this may reduce severity of symptoms.
I've copy/pasted the text below from
Shelly's blog, there are a lot of links to old research papers as well as the two new pieces - visit his blog for the links to read the papers:
Don't shoot the messenger here btw, I'm posting this for interest of others and for people to do their own research on the studies, and note my disclaimer. (first port of call for those DYOR should be Charles Brenner's twitter).
...............
..............
New research suggests that the process by which COVID-19 damages lung tissues includes NAD depletion. And so people ask whether Vitamin B3-based NAD precursors, which replenish NAD, might protect against tissue harm caused by COVID-19?
First, an important disclaimer: There is no scientific study that says that NAD replenishment by any method treats, cures, or prevents any disease, including COVID-19. The human evidence only shows that B3 vitamins like Niagen are safe and effective at replenishing NAD. The effect of that replenishment in humans remains unproven. It is only in animal studies that we see NAD replenishment having a positive effect on physical conditions involving NAD depletion.
One more thought before we get to the research. Niacin is the most famous of the B3 vitamins. It was identified early on as a cure for the wasting disease Pellagra, which was very common in the first half of the 20th century. Today Pellagra is rare because flour and cereals are enriched with Niacin. But the US government's RDA for Niacin is only what's necessary to prevent pellagra (15mg).
Now we know that Vitamin B3 can do much more than just prevent pellagra, so supplementing at a higher level could be smart, regardless of what the science may show about COVID-19. However, Niacin itself is not the B3 vitamin of choice. This article compares the different NAD precursors. And this article compares to the two NAD precursor finalists, NR and NMN.
BACK TO THE SCIENCE
Here is the emerging science on COVID-19, and why it points toward the potential of NAD precursors. It turns on "Cytokine Storms."
Cytokines are small proteins released by the immune system. When the COVID-19 coronavirus enter the lungs, cytokines are released, causing inflammation. But in some patients too many cytokines are released -- an uncontrolled storm. This severe overreaction can cause deadly levels of inflammation. Cytokine storms are more likely to occur in older patients, who have both well-developed immune systems and diminished levels of NAD.
This Editorial published in Nature on March 23, 2020, says,
"We propose some simple, but largely ignored, approaches to the treatment of COVID-19 patients...Since Vitamin B3 is highly lung protective, it should be used as soon as coughing begins..."
That may be enough by itself for some people to act. As usual, the best NAD precursor is the most expensive, but Nicotinamide and Niacin probably would do the job, and the article does not suggest otherwise.
But let's go deeper and try to understand WHY Vitamin B3s are recommended.
This preprint manuscript (not yet peer-reviewed) says that in the "pathology pathway of COVID-19, almost all procedures lead to or originate from NAD+ depletion." Specifically, SIRT1 regulates cytokines to modulate inflammation, and the depletion of NAD prevents the operation of SIRT1, and thus cytokine storms can develop.
What I just described is an oversimplification of the "pathology pathway," which is more completely expressed in the paper thus: "NAD is consumed in large scale by PARP and its depletion inhibits the activity of other protective protein like SIRT1 and CD38. Expression of NFkB and cytokines and blood and immune cell defects are the consequences of SIRT1 and CD38 inhibition respectively."
But the bottom line is to suggest therapeutic approaches that prevent or respond to NAD depletion. Or, as the authors say,
"In conclusion, it seems interruption of the explained lethal circles may convert COVID-19 to a simple common cold."
That again may be enough to suggest for some people Niacin, Nicotinamide, or Nicotinamide Riboside as a prophylactic. [I do not think NMN makes any sense at this time, despite Dr. Sinclair's enthusiasm, for reasons explained here. If nothing else, the commercially available versions of NMN are expensive and unstable.]
If you want to go even deeper into the mechanisms involved, the science gets complex. For example, the study says that normally PARP-1 functions as an antiviral agent by removing a ribose from the cell's NAD and then attaching it to the virus, which inhibits the virus's function. But coronaviruses like COVID-19 code for PARG, which removes ribosides. As a result, “Excessive activation of PARP occurs to compensate ADP-ribose hydrolyzation of PARG which is associated with catalytic consumption of NAD+ followed by ATP reduction leading to depletion of energy and cell death."
Or, as one online commenter helpfully explained, "PARP1 tries to inhibit viral replication by breaking ribose off NAD and attaching it to the viral RNA. But the virus encodes PARG which whips that ribose right off. So PARP1 and PARG are fighting over ribosylation of the viral genome, all the while burning through the cell’s supply of NAD. Fiendish."
BUT Dr. Charles Brenner has said that the mechanism involving PARP1 is not correctly described in this paper:
"Note that a recent publication saying PARP1 is activated by coronavirus is completely wrong. It’s clearly coming from a group that doesn’t know the literature and hasn’t done an experiment." (emphasis added)
In the end, it nonetheless appears that COVID-19 causes NAD depletion, which in turn triggers a cascade of troubles which can, among other things, result in lung damage. We await further details on the mechanisms.
Even before COVID-19, researchers were focusing on NAD repletion as a method of preventing lung damage from inflammation. For example, in this ongoing study that began before the COVID-19 outbreak, the researchers noted that "supplementing mice with the unique NAD+ precursor nicotinamide riboside (NR)" reduced both age-related and induced fibrosis, and therefore the researchers hypothesized that attempts to "boost NAD+ bioavailability will restore SIRT activity and limit fibrosis" including in inflammation-dependent models of systemic sclerosis. That study is a mouse study, it isn't complete, and their method of NAD repletion is to inhibit CD38 (because CD38 also depletes NAD). But the general idea that excess inflammation can result in NAD depletion, which in turn can cause lung damage, which in turn can be prevented by replenishing NAD, predates COVID-19. COVID-19 is just be the most recent example of an NAD-depleting illness that could potentially be addressed with NAD-replenishing strategies.
CONCLUSION
In summary, there is zero evidence that a vitamin can prevent COVID-19 infection. But there is emerging science that suggests that preventing NAD depletion might be an important strategy in mitigating the effects of COVID-19 infection.
Numerous ways of preventing NAD depletion exist, including replenishment of NAD using one or more of the Vitamin B3 NAD precursors, such as Niacin (NA), Nicotinamide (NAM), Nicotinamide Mononucleotide (NMN), or Nicotinamide Riboside (NR).
There are no human studies that show whether NAD replenishment will in fact have any effect on COVID-19 symptoms. The animal studies suggest that it might. The human studies only show that Vitamin B3s are safe and effective at replenishing NAD.
I will update this article as new COVID-19 studies emerge that support or contradict the NAD replenishment hypothesis.
........................
........................
* For anyone interested in researching an epic tale of bloody warfare between scientists, research institutions and commercial interests over a novel molecule thought to be beneficial for health in the ageing process, you might find the back-story behind NR very interesting! Various characters, companies and research institutes involved: Chromadex/Elysium, Dartmouth/MIT, Dr's Brenner, Guarente and Sinclair. I've been following the story since 2014 as a side-line to being an investor in Chromadex. It looked like the various legal trials would reach a conclusion in 2020 until coronavirus delayed everything some more..
edit: also interesting is the suggestion of an association between certain HPA (immune response) genes and likelihood of developing severe covid-19 symptoms.
