Friday Hope: Nicotinamide Riboside: A Compound Which Facilitates DNA Damage (Mistranslation) Repair
A Potential Powerful Therapeutic for COVID, Long COVID and Spike Protein Progeria Disease
While studying the pathology of the Spike Protein, I am equally committed to studying ways to combat the damage it is almost certainly causing. As readers of my Substack know, I now believe that COVID, Long COVID and what I call Spike Protein Progeria Disease (SPPD) is caused be the Spike Protein’s ability to induce mistranslations of proteins. Please see my previous posts for an explanation of the mechanism and supporting papers.
I believe a very powerful therapeutic against this mistranslation damage is Nicotinamide Riboside. So, first, what is Nicotinamide Riboside?
Nicotinamide riboside (NR) is an additional salvageable NAD+ precursor with a two-step or three-step pathway to form NAD+. Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs’ health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders.
Nicotinamide Riboside—The Current State of Research and Therapeutic Uses
Why I believe this compound is important in the treatment of COVID, Long COVID and SPPD, is because it addresses the very kind of damage I believe the evidence shows the Spike Protein is causing.
Instead, compounds and interventions that have the capacity to reduce DNA damage accumulation at its core are the ones that will be identified using DNA repair-deficient models. This is likely reflected in the positive effects noted by two different NAD+ precursors, NA and NR. NAD+ has shown to decline with age and its supplementation has shown promising results both in normal and accelerated aging and in (segmental) aging disorders of post-mitotic tissues (Xie et al., 2020; Imai and Guarente, 2014; Scheibye-Knudsen et al., 2014; Abdellatif et al., 2021a; Maynard et al., 2015). NAD+ is central for cellular processes such as metabolism and mitochondrial function, but also acts as a substrate for cAPD-ribose synthases (CD38), sirtuin deacetylases and poly-ADP-ribose polymerases (PARPs), a DNA damage sensors which is critical to various DNA repair processes and a trigger for apoptosis (Xie et al., 2020). Thus, it remains a possibility, that even though the mice are genetically deficient in TCR that NAD+ supplementation boosts complimentary alternative PARP-mediated DNA repair processes or influences signals triggered by DNA damage.
NA and NR follow different pathways of being synthesized into NAD, and their oral bioavailability is likely to differ (Trammell et al., 2016; Mehmel et al., 2020). Furthermore, the subcellular uptake of the distinct NAD+ precursors across tissues might differ with flux analysis showing, e.g., that NA is unlikely to be used in the brain but rather in spleen, intestine, pancreas and liver (Liu et al., 2018; Xie et al., 2020; Hikosaka et al., 2021). This could explain the difference we noted in our results; whereas NA specifically delayed the onset of imbalance, NR significantly extended lifespan, beyond the maximum age reached by any of the other drugs tested (Figure 4).
Together, our results show that progeroid mouse models can be used as efficient, economical, and relatively rapid screening platforms for validation of drugs or interventions that target DNA damage accumulation and/or benefit insufficient DNA repair.
The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside
So, I believe trials should be initiated immediately to determine the efficacy of Nicotinamide Riboside to treat the apparent translational errors which the Spike Protein of SARS-CoV-2 is inducing.
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