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Glucosamine is better than Rapamycin for autophagy

glucosamine rapamycin autophagy

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#151 William Sterog

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Posted 27 September 2020 - 09:00 PM

I stumbled upon this article. Any opinions?
Glucosamine promotes hepatitis B virus replication through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling
https://pubmed.ncbi....h.gov/31204557/


It looks really bad.

In addition, GlcN promoted influenza A virus, enterovirus 71, and vesicular stomatitis virus replication in vitro. In conclusion, GlcN efficiently promotes virus replication by inducing autophagic stress through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling. Thus, there is a potential risk of enhanced viral replication by oral GlcN intake in chronically virally infected.

#152 Guest

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Posted 27 September 2020 - 09:08 PM

I don't think you noticed, that I was talking about that exact same study here:

 

https://www.longecit...ndpost&p=897782

 

 

 

The key take-away is not so much that autophagy is utilized by certain viruses to replicate. Some of those even induce elevated AP themselves, as they need it for replication. That has been long known and is bound to be an issue for all substances and interventions that promote AP (rapamycin, metformin, sulforapane, fasting, caloric restriction.... you name it).

 

 

More interesting is the time-course of the AP-activity for GS - namely doing both: enhancing vesicle-formation, but gradually de-acidifying the lysosomes. As a result it might be a good idea not to take a high dose every day.


Edited by Guest, 27 September 2020 - 09:16 PM.

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#153 Guest

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Posted 27 September 2020 - 09:26 PM

And just to be clear: most viruses are counter-acted by autophagy. But there are some hands full of human ones (including polio and hepatitis), that need AP to replicate. Maybe even coronavirus. Or maybe the opposite: "Digesting the crisis: autophagy and coronaviruses"

https://www.ncbi.nlm...les/PMC7199282/

 

 

Point being: that got nothing specifically to do concerning GS - but all AP-related substances and interventions.


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#154 Guest

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Posted 30 September 2020 - 06:47 PM

Just in case someone is still concerned about the headline of that GS study - let's have a look at Rapamycin and fasting (2 of the most famous/popular methods to raise AP):

 

 

Rapamycin promotes Hepa-B-virus replication:

 

https://sites.kowsar...cles/15431.html

 

 

 

Rapamycin and prolonged fasting heavily promote Influenza A replication and infection:

 

https://jvi.asm.org/.../93/4/e01984-18

https://www.research...and_replication

 

 

 

Rapamycin promotes replication and viral load for entero-viruses (among others polio):

 

https://www.spandido...2/mmr.2018.9037

 

 

 

Very simply: the same layers that are released by the endoplasmic reticulum to form autophagic vesicels are hijacked by certain viruses to instead form bubbles that serve as breeding grounds for more viruses. More up-regulation of AP means more available substrate for those class of viruses to form their replication bubbles (this is already too simplistic, as some appear to use it as building blocks as well)

 

But look at the bright side: the fact that GS also enhances the replication of the same viruses as rapamycin is proof, that GS indeed is up-regulating AP. In turn this means it's beneficial against most (but evidently not all) virus infections.


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#155 William Sterog

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Posted 01 October 2020 - 11:18 AM

Those are great points. Thanks for the clarification, it was, at least for me, needed. 


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#156 Guest

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Posted 01 October 2020 - 04:59 PM

Glucosamine is fighting Influcenza-A viruses:

 

https://www.cell.com...1247(19)31001-0

 

 

While in an in-vitro-study (isolated cells in a dish) GS was promoting Influenza-A replication because of upregulation of autophagy, the same is not true in living animals. There is a secondary effect of glucosamine, that is enabling the living tissues to better fight viruses (among others influenza). Quoting from above study in mice (GlcN = glucosamine):

 

 

GlcN Protects Mice against IAV Infection

 

Based on these observations, we examined the protective role of GlcN against IAV infection. Mice were fed a standard diet with or without 2.5% GlcN for 3 days, and then were intranasally infected with IAV-WSN. The total level of O-GlcNAcylation in peripheral blood mononuclear cells and peritoneal macrophages was upregulated by GlcN (Figure S6). Consistent with our in vitro data, the induction of both Ifnb1 and Ifit1 was significantly higher in GlcNfed mice than control littermates, after 24 h pi (Figures 7A and 7B). The virus load was much higher in lungs of control mice than that of GlcN-fed mice (Figure 7C). Lung injury caused by IAV infection was greatly reduced in GlcN-fed mice (Figure 7D). Moreover, GlcN-fed mice were significantly more resistant to IAV infection compared to wild type mice (Figure 7E). In contrast, GlcN did not show any protective effect on Ogt-deficient mice, MAVS-KO mice, or IFNR-KO mice (Figures 7F–7H), suggesting that GlcN promotes host antiviral immunity via O-GlcNAcylation and IFN signaling. Furthermore, GlcN-fed mice were more resistant to the challenge of other RNA virus including VSV and coxsackievirus A6 (Figures 7I and 7J). Taken together, these data demonstrated that GlcN can protect mice against infections of a broad range of RNA viruses via increasing MAVS O-GlcNAcylation.

 

 

Note: this study was done in living mice. It gives a better picture of the effects of glucosamine than in-vitro studies. On the other hand, there is one mice study of rapamycin, that demonstrated increased IVA replication due to AP. So what is the additional effect of GS that gives it anti-viral activity, despite increasing AP? The answer is in the study just quoted:

 

the so called hexosamine biosynthetic pathway is an intra-cellular process, that is able to alter a broad range of proteins in a cell - however, it's function is limited by the availability of a certrain enzyime, which is creating Glucosamine within a cell. Further downstream products of GS subsequently alter proteins. This enzyme is only snythezised in limited quantity. By feeding a cell GS, the limited pool of that enzyme can be by-passed. As a consequence the so-called mitochondrial antiviral-signaling protein (MAVS) is among the proteins that is activated leading to an elevated anti-viral immune-response - able to overcompensate the increased AP (and therefore IVA replication) caused by GS.

 

 

 

Leading to my initial statement:

 

 

Glucosamine is better than Rapamycin, if you want to increase your autophagy. No Mtorc2 supression. And even anti-viral effects for certrain virsues (in living animals, not cell cultures), where Rapamycin and other compounds that increase AP are causing more viral infections.


Edited by Guest, 01 October 2020 - 05:04 PM.

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#157 Guest

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Posted 01 October 2020 - 07:54 PM

1-s2.0-S2211124719310010-gr7.jpg

 

 

 

picture E portraits the survival for influenca A virus infection of wild-type mice being supplemented GS and controls

 

D depicts lung tissue changes upon infection by IAV (bottom row) of controls and GS

 

I and J are survival curves for different RNA-viruses

 

 

Activated mitochondrial antiviral-signaling proteins are alerting the immune system to an infection by RNA-viruses. They are not automatically activated by the downstream product of GS, but by a different class of proteins that is released upon infection of a cell by an RNA-virus. However, this activating class of proteins is not sufficient to fully activate the MAVS - in a second step a downstream product of GS is needed for the MAVS to be fully activated. But endogenous (intracellular) production of glucosamine is rate-limited by the availability of a certain enzyme. Exogenously supplying GS circumvents this rate-limiting process and fully activates all MAVS.

 

 

This study used the human equivalent of 10 g of GS per day for 3 days before infection.

 

 

 

These results are in line with the finding of a prospective cohort study, that found a markedly reduced mortality from respiratory diseases in participants taking GS - a reduction by 41%

 

https://www.ncbi.nlm...les/PMC3557824/


Edited by Guest, 01 October 2020 - 08:11 PM.

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#158 Engadin

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Posted 01 October 2020 - 09:37 PM

Correct me if I am wrong, but from E to J graphs, E, I and J don't look very favorable to GS supplementation to say the least, doesn't them?. In them, control mice seems to evolve much better than those on GS and all three are of the Wild Type mice.

 

Thanks for your comments.


Edited by Engadin, 01 October 2020 - 09:39 PM.

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#159 Guest

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Posted 01 October 2020 - 09:46 PM

Correct me if I am wrong, but from E to J graphs, E, I and J don't look very favorable to GS supplementation to say the least, doesn't them?. In them, control mice seems to evolve much better than those on GS and all three are of the Wild Type mice.

 

Thanks for your comments.

 

 

 

I'm not sure that you are reading this correctly.

 

 

You are looking at survival curves. ALL mice are wild type mice in E, I and J. Some are taking glucosamine (GlCN), some are controls (Con.).

 

 

In E about 60% of the mice taking GS survived - but only about 10% of those not taking GS.

 

In I and J 100% of mice taking GS survived.



#160 William Sterog

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Posted 02 October 2020 - 08:30 AM

suggesting that GlcN promotes host antiviral immunity via O-GlcNAcylation.

It is possible then that the effectivity of N-acetyl-glucosamine is higher as an antiviral?

#161 Engadin

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Posted 02 October 2020 - 05:46 PM

I'm not sure that you are reading this correctly.

 

 

You are looking at survival curves. ALL mice are wild type mice in E, I and J. Some are taking glucosamine (GlCN), some are controls (Con.).

 

 

In E about 60% of the mice taking GS survived - but only about 10% of those not taking GS.

 

In I and J 100% of mice taking GS survived.

 

 

My bad, I was looking at the graphs upside down. Thanks for your explanation. GS is back where is has always been.



#162 Skyguy2005

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Posted 03 October 2020 - 03:01 AM

I don't think you noticed, that I was talking about that exact same study here:

 

https://www.longecit...ndpost&p=897782

 

 

 

The key take-away is not so much that autophagy is utilized by certain viruses to replicate. Some of those even induce elevated AP themselves, as they need it for replication. That has been long known and is bound to be an issue for all substances and interventions that promote AP (rapamycin, metformin, sulforapane, fasting, caloric restriction.... you name it).

 

 

More interesting is the time-course of the AP-activity for GS - namely doing both: enhancing vesicle-formation, but gradually de-acidifying the lysosomes. As a result it might be a good idea not to take a high dose every day.

 

But is anybody taking Glucosamine for immune enhancement? One imagines people are taking Ginkgo, Reishi, Lions Mane etc



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#163 experimenting

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Posted 04 October 2020 - 09:43 PM

I should have posted here, from my other thread, what are the liver effects of glucosamine?

I started last few days and it seems to coincide with a “fat” feeling after eating, as if my body isn’t breaking fats down properly. The same feeling I got a few years ago when I had some liver difficulty. What’s going on here? Pancreas and liver toxicity?
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