Bioenergetic Homeostasis

submitted by EddieC from (self.Coronavirus)

Note 1: Work In Progress

Note 2: These are based on the Twitter tweets by:

Dr Dmitry Kats (DK) @Niatonin (formerly @NiacinIsHealth @Nia3in & @MELaNAphorsis)

Walter M Chestnut (WC) @Parsifaler

John Paul (JP) @WorldEdgeDG
 

DK: "At its heart, from as early as initial propensity to infection onset & over the entire pathology—just like any other disease or condition of the human—#COVID19 can be most fundamentally characterized as: (flush) niacin and melatonin deficiency (and the sequela ensuing from that)."

 

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[–]EddieC[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

Significantly elevated levels of blood plasma galectin-9 protein linked to cytokine storm in COVID-19 patients:

  • "COVID-19 patients have significantly elevated levels of the galectin-9 protein in their blood plasma.
  • "(There is) a positive correlation between the levels of galectin-9 and pro-inflammatory cytokines released in the blood, which can lead to a cytokine storm."
  • "Galectin-9 is responsible for instructing immune cells to release the pro-inflammatory cytokines quickly in response to COVID-19 infection by binding to immune cells and forcing them to produce the cytokines. Further, as tissues are damaged as a result of inflammation, more galectin-9 is released from the cells—which activates more immune cells and releases more cytokines in a vicious cycle. The resulting cytokine storm damages tissue and organs, causes severe inflammation and can lead to death."
  • "Even if patients survive the storm, the dysregulation of the immune system can have ongoing consequences and could be associated with the condition known as post-COVID-19 syndrome or long COVID."
     

JP:
"Niacin & Melatonin will directly affect galectin-9
NAC would marginally affect it, but there might be underlying mechanisms with NAC."

[–]EddieC[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

DK:
"The true power of flush niacin isn’t fully harnessed without sufficient melatonin"
 

"Repleting melatonin will make the GPR109A aka ACE2 receptors fully expressed across the body for the flush to bind to and induce autophagy / clear inflammasome / reset health"
 

"High dose melatonin (like 10 to even up to 50 mg for some)
+ flush niacin (500 mg up to even 2 g)
a few times a day within a week should do it for everyone"

[–]EddieC[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

Niacin fine-tunes energy homeostasis through canonical GPR109A signaling  
Niacin, "acting on GPR109A, shows the potential to maintain energy homeostasis through multi pathways, representing a potential approach to the treatment of obesity, diabetes and cardiovascular disease."
 

“Niacin exhibited inhibitory effects on:

  • PDH - the gatekeeping enzyme of pyruvate flux into acetyl-CoA, and
  • ACC1 - the key regulatory step of fatty acid synthesis

These findings were verified by real-time qRT-PCR.”

[–]EddieC[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

DK:

Melatonin is highly efficient at reducing oxidative stress and seems to prevent the conversion of mitochondrial OXPHOS of normal cells to aerobic glycolysis (the Warburg effect) of cancer cells.
 

Melatonin synthesis does not occur in cancer cell mitochondria because of acetyl-CoA deficiency.
 

When cells assume a Warburg-type metabolism, the cells
upregulate PDK the gatekeeper enzyme
downregulate/inhibit PDC, the enzyme that metabolizes pyruvate to acetyl-CoA,
causing a depletion of acetyl-CoA and, in turn, the deprivation of melatonin
 

If, however, nocturnal circulating melatonin levels are sufficiently elevated, it does enter mitochondria to inhibit PDK, allowing for nocturnal switch away from Warburg effect  

[–]EddieC[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

Niacin @ Nicotonic Acid (NA)

Anti-inflammatory effects of nicotinic acid in adipocytes (aka fat cells) demonstrated by

  • suppression of fractalkine, RANTES, and MCP-1 and
  • upregulation of adiponectin (a protein hormone and adipokine involved in regulating glucose levels & fatty acid breakdown)

Link: https://www.atherosclerosis-journal.com/article/S0021-9150(09)00707-2/fulltext
 

"NA suppresses pro-atherogenic chemokines and upregulates the atheroprotective adiponectin through a G-protein-coupled pathway. Since adipose tissue has the potential to contribute to both systemic and local (perivascular) inflammation associated with atherosclerosis our results suggest a new “pleiotropic” role for NA."