167 replies to this topic

[William Sterog]

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.

[Guest]

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.

[Guest]

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.

[Guest]

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.

[William Sterog]

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

[Guest]

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.

[Guest]

 

 

 

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.

[Engadin]

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.

[Guest]

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.

[William Sterog]

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?

[Engadin]

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.

[Skyguy2005]

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

[experimenting]

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?

[Guest]

Last year an analysis of UK Biobank data showed an association between low dose Glucosamine intake and protection against diabetes:

 

https://care.diabete...01/23/dc19-1836

 

 

Now, epidemological data can not directly establish causality. But 2 recent studies in mice and rats demonstrated independently, that in  pro-diabetogenic high-fat diets (an animal model of diabetes) glucosamine supplementation improved blood sugar control and decreased insulin resistance. So it seems that the effect observed in humans is causal and Glucosamine indeed got a protective effect against diabetes:

 

Ameliorative Effects of Oral Glucosamine on Insulin Resistance and Pancreatic Tissue Damage in Experimental Wistar rats on a High-fat Diet

https://www.ingentac...et.x-ic-live-01

 

Glucosamine Ameliorates Symptoms of High-Fat Diet-Fed Mice by Reversing Imbalanced Gut Microbiota

https://www.frontier...021.694107/full

 

 

[Guest]

There is plenty of data from living rodents and rabbits, that glucosamine is anti-inflammatory and ant-oxidative - however, there are to my knowledge only 2 or 3 studies collecting inflammation data in-vivo in humans and none for anti-oxidative effects. So the study below is interesting, as it collects data for both:

 

Combined effect of celecoxib and glucosamine sulfate on inflammatory factors and oxidative stress indicators in patients with knee osteoarthritis

https://www.ajol.inf...cle/view/184537

 

 

Compared to blood drawn before the study, taking glucosamine changes both markers of oxidation under investigation positively:

 

 

superoxy dismutase (SOD) from 87 to 103 U/L

https://en.wikipedia...oxide_dismutase

 

SOD is a key endogenous anti-oxidant produced by the human body. Glucosamine in itself is not an anti-oxidant, but it promotes the production of native human anti-oxidants. Now, you could argue that's because GS is doing oxidative damage. There is actually evidence for a hormetic effect - i.e. GS is causing just a little damage, but the reaction of the body is overcompensating by increasing damage-avoidance and repair-mechanisms to a much larger degree. This can be seen in the second marker investigated:

 

 

malondialdehyde (MDA) changed from 13 to 8 nmol/ml

https://en.wikipedia...Malondialdehyde

 

MDA is an important end product of intra-cellular oxidative damage - ROS damaging lipids. It's also able to damage DNA. As the amount of MDA registered decreased, the total reaction to GS clearly overall is highly anti-oxidative.

 

 

There are some caveats in the study. It's from a no-name Chinese hospital, so the quality of data collection might be off. Secondly the dose is denoted as 500 mg per kg 3 times per day. That's implausibly high - 105 gram for a 70 kg human per day (so 70 of the typical 1,5 gram pills - that should by impossible to do for 2 months in elderly volunteers). It is more likely that they mean 500 mg 3 times per day - which is supported by the anti-inflammation data. TNF-a and IL-1 didn't decrease greatly - but did so much more remarkably in animal data and 1 human study using a higher dose than 1500 mg (but much lower than the equivalent of 105 gram or 500mg/kg/3 times per day).

Edited by Guest, 23 August 2021 - 09:39 PM.

[Guest]

There is a somewhat strange study, finding negative effects of Glucosamine in mice - in complete contradiction of previous studies:

 

https://www.science..../sciadv.aaz7086

 

 

The focus of the study was not GS, but broadly metabolic responses to influenza viral infections. The relevant illustrations can be found in the images below:

 

 

 

 

The relevant images are G and I - IAV means mice infected with influenza A virus, GlcN means glucosamine

 

In those images, glucosamine is increasing markers of inflammation. If given to mice who are no infected, GS increases inflammation moderately. If given to infected mice, it increases it by a lot. More importantly in image I, GS seems to make an IAV infection just a little more deadly.

 

 

These findings are troublesome - but are also the complete opposite of the established literate so far. For example in the study discussed here:

https://www.longecit...ndpost&p=898823

Mice given GS massively improved survival. In addition in every study investigating inflammation markers so far (we are talking about dozens if studies, including in humans) GS decreased inflammation markers compared to controls - not increased as in this study.

 

 

Some issues which are strange or could be an explanation (if we exclude sloppy work or fraud from the Wuhan Lab the scientists are based in):

 

 

1. The mice were given a really low dose; for a 70 kg human about 433 mg by injection..... by oral intake that would be about 1,5 g. At that dose you would not expect much of an effect on anything.

 

 

2. The mice were given injections of GS. If done improperly, this procedure could explain the worse health effects compared to controls. The mice in the previous study received GS added into their water. Also previously so called "wild type" mice got used - this time it's an inbred strain of C57BL/6 mice.

 

 

3. The authors of the study do not discuss the difference of their findings to the established literature. The previous study in IAV infected mice got published 18 month before this one in an equally well ranked journal. It is common practice to at least address similar experiments - particularly with different outcomes.

 

 

 

I would not yet be too concerned. The study in humans in my last post for example found a decrease of TNF-a from 16,59 ng/l to 12,56 ng/l - not an increase as in these mice. This really is the first study finding an increase.... The more likely explanation is some error by the authors - so unless there is a string of those studies, I find it hard to make the results the basis of any decision.

[William Sterog]

Background: Coronavirus disease 2019 (COVID-19) has affected millions globally, with a continued need for effective treatments. N-acetylglucosamine has anti-inflammatory activities and modulates immune response. This study evaluated whether N-acetylglucosamine administered orally improves clinical outcomes for patients admitted to the hospital due to COVID-19.

Materials and methods: This single-center, prospective, observational cohort study used a retrospective control group for comparison. Multivariate analyses evaluated whether N-acetylglucosamine was an independent predictor of primary outcomes (rate of intubation, hospital length-of-stay, and mortality) and select secondary outcomes (intensive care unit [ICU] admission, ICU length-of-stay, supplemental oxygen use duration, hospice initiation, and poor clinical outcome [defined as combined hospice initiation/death]).

Results: Of the 50 patients enrolled in the N-acetylglucosamine treatment group, 48 patients had follow-up data (50.0% [24/48] male; median age 63 years, range: 29-88). Multivariate analysis showed the treatment group had improved hospital length-of-stay (β: 4.27 [95% confidence interval (CI) -5.67; -2.85], p < 0.001), ICU admission (odds ratio [OR] 0.32 [95% CI 0.10; 0.96], p = 0.049), and poor clinical outcome (OR 0.30 [95% CI 0.09; 0.86], p = 0.034). Mortality was significantly lower for treatment versus control on univariate analysis (12.5% vs. 28.0%, respectively; p = 0.039) and approached significance on multivariate analysis (p = 0.081).

Conclusions: N-acetylglucosamine administration was associated with reduced hospital length-of-stay, ICU admission rates, and death/hospice rates in adults with COVID-19 compared to those who received standard care alone. An upcoming trial will further investigate N-acetylglucosamine's

https://pubmed.ncbi....h.gov/34306677/

[illerrre]

Is shellfish derived glucosamine likely to be high in heavy metals and other harmful substances?