167 replies to this topic

[GABAergic]

Studies use either Glucosamine sulfate or Glucosamine hydrochloride. NAG behaves biochemically very different than Glucosamine and is not used in any of those studies. The HCl-version of GS is more commonly used in animal studies on cancer and AP, the sulfate version commonly used in human studies and is the most prevalent as a supplement (and consequently in the cancer studies in humans). Both should be fine.

 

 

Another data point for GS:

 

"Glucosamine improves survival in a mouse model of sepsis and attenuates sepsis-induced lung injury and inflammation. (2019)"

http://www.jbc.org/c.../294/2/608.long

 

"To examine the effects of GlcN on septic mortality, we monitored mouse survival after cecal ligation and puncture (CLP) with or without GlcN (200 mg/kg) for 12 days (Fig. 1A). Based on Kaplan-Meier survival curves, mice with CLP-induced sepsis presented a 12-day survival rate of 11%. GlcN pretreatment increased the 12-day survival rate to 55% relative to that in mice with untreated sepsis (Fig. 1B). All sham-operated control mice treated with or without GlcN survived."

 

 

Albeit this study is a little strange:

 

- they say, that each group got n = 10 mice; that should make 11% or 55% results impossible... it maybe just a typo

 

- GS is anti-inflammatory; so why does it seem to aid fighting off infections? If anything I would have expected that it downregulates immunity, as is sometimes discussed for caloric restriction.

 

 

really? there were reports by people on here using NAG and helping with inflamation issues. the product itself claims better gastrointestinal health. im surprised nobody cares to study NAG further. perhaps the other forms are widely available and cheaper and easier to deal with i assume. but in your opinion wouldnt NAG still have the same benefits as plain glucosamine? from what i have read, it has better absorption, especially in the brain, than plain one.

 

[BieraK]

Yes as I know NAG is anti-inflammatory and crosses the BBB, however it does not works like Glucosamine in sense as imitating the effects of a low carb diet.

I don't see the problem of taking both, this is something I need to read more (the differences between GlcN and NAG).

 

Well, perhaps 12 or 16 hours of fasting is not enough for boosting AP even with Glucosamine, but if we could at least have the benefits of a 5 day fasting in two days that could be a powerful anti-aging regimen. Even a exercise boosting regimen. I have done several fasting mimicking diets (FMD) cycles and it is so powerful, erases inflammation, gives you a sense of wellbeing, some pains are gone, you feel like a new one. I have done resistance training while fasting, and again, the majority of my long-term and more notorious gains are the gains from the FMD and refeed. I explain this by autophagy, HGH increase and the stem cell proliferation after refeeding.

 

So two days of low calories from complex carbs like the FMD, plus Glucosamine+Niacin could give us the benefits of a 5 day fasting by boosting autophagy and reducing the time needed for entering into ketosis. The problem with fasting is that you need to empty all the glycogen stores, thats why you need to the third day of the FMD for feeling mentally clear. 

 

Sadly I don't have nor Glucosamine nor a Ketone meter with me for now, so I can't do the experiment for now.

 

 

 

 

Edited by BieraK, 24 May 2019 - 08:21 PM.

[William Sterog]

"So two days of low calories from complex carbs like the FMD..."

You mean low calories and all of them obtained from fat, right? I think that the FMD is ketogenic in nature.

[BieraK]

FMD eliminates simple carbs and protein both animal and veg protein like beans. Complex carbs like green veggies are used with MUFAS like olive oil, pistacho, almonds, nuts and so on in a 50/50 ratio. The original Prolon diet uses things like rice bars and oat.

You can do it strictly keto (just eating olives, avocado, olive oil, nuts), but basically consuming a low calorie diet from healthy fats and complex carbs will lead you into ketosis. FMD is like a mix of a vegan ketogenic diet+extreme calorie restriction (800 kcal a day, however I have tried with less like 300 kcal).

 

So I mean two days of a low calorie diet like the FMD using Glucosamine+Niacin for boosting autophagy. So my hypothesis is that with such intervention you don't need to stay 5 days of the week in a restricted diet waiting for the third day when you enter into full ketosis. In my experience FMD is works better if you do it every month. If you could enter into full ketosis in two days and getting both the Human Growth Hormone effects and autophagy from fasting, then this could be used for weigh training. As I said before FMD is excellent for increasing muscle mass, after the refeeding stem cells proliferate and do the job of rejuvenating muscle and other tissues.

 

My idea is to boost fasting like 16:8, 5:2 or FMD with Glucosamine+Niacin. However I don't know if this will work I have never tested this and als idk if the combination is safe. Also look into the 5:2 diet, this "protocol" of Niacin+Glucosamine looks perfect for using it with such fasting schedule.

Edited by BieraK, 24 May 2019 - 10:51 PM.

[GABAergic]

so it has to be a 5 day fast? that will not work well for someone who is already too skinny. there are dozen of articles on positive findings concerning intermittent fasting, but i havent seen any on 5 day fasts so far. so you actually believe 12 hours is doing absolutely nothing?

Edited by GABAergic, 25 May 2019 - 03:32 AM.

[smithx]

He's talking about this diet:

 

 

"A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan"

https://www.scienced...550413115002247

[GABAergic]

everyone seems to promote their own diet. each year a new diet fad comes along. this study is from 2015 maybe it was a big discussion back then. but after that we have the ketogenic diet, medatrenian diet, intermittent fasting diet, caloric restriction has always been around and im not sure whats the latest though. but regardless, anyone can find positive studies like one you posted, for any of the diets they follow. im not really intrigued by the study you posted from 2015 though

[ironfistx]

Look, we're talking 3g a day pushed into two doses at 12pm and 6pm, taken separate from food?  Are we including chondroitin in the combination?

[GABAergic]

there was this study concerning diabetes https://www.ncbi.nlm...pubmed/16339923 but like the liver issue study, it seems to be a special case, maybe

 

anyway, i was looking more into it and it seems it is one of the most used by seniors in the US supplement out there. if in fact it extends lifespan, we should be seeing most seniors now to live longer than usual. you guys would think right.

Edited by GABAergic, 29 May 2019 - 03:09 AM.

[ironfistx]

How come whenever I post details people criticize the post?  lol.  You just want science and no actual usage?

there was this study concerning diabetes https://www.ncbi.nlm...pubmed/16339923 but like the liver issue study, it seems to be a special case, maybe

 

anyway, i was looking more into it and it seems it is one of the most used by seniors in the US supplement out there. if in fact it extends lifespan, we should be seeing most seniors now to live longer than usual. you guys would think right.

 

Yeah, agree.

[Heisok]

I am only semi-literate Science wise. I also tend to rely on those who are literate, and then have a quick look myself to see if something jumps out. This includes those posting here, and elsewhere. Actual uses by many is important, but there seems to be a Scientific process to look at such information for effect. Has this been done for those taking the doses which seem to be common in the products. The original poster indicates yes for tumors. 1,500 mg divided in 2 doses. The original topic starter indicated a benefit at 3,000 mg per day, but that 3,000 mg twice a day was not proportionately better. I guess, that results were not twice as good. They also indicated that there were some observational studies in post #1.

 

Post #32:

As outlined in the glucosamine and cancer thread:

 

there are very well controlled for, prospective cohort studies, with 10th of thousands of participants. Those have good statistical power, delivering highly statistical significant results AFTER accounting for dozens of confounding factors. In addition the reduction in relative risk calculated for total mortality and cancer (for users of glucosamine vs. non-users) is not small, but huge. That's still not a scientific proof for a causal relationship! But at least it's not just anecdotal evidence."

 

Post #33:

"Their main findings:

- GS got an elimination half-life of about 15 hours in humans

- an oral doses up to 1,5 gram in on sitting is readily absorbed and increases plasma concentration of GS proportionally compared to 0,75 gram

- oral intake of 3 gram of GS in one sitting did result in a less than proportional increase in plasma levels

This indicates, that you might want to spread out taking a GS intake of 3 gram or more per day - i.e. a little in the morning and a little in the evening - to get the most out of it."

 

Post #51:

 

"the cancer studies indeed indicate a dose-response-relationship - it might be sufficient to just up the amount taken. If absorption levels off, if taken at 3 grams or more at once, it should still be possible to take it 1 or 2 hours apart. The powdered version of GS might be better for that purpose, as you can sprinkle it into drinks or on food."

 

Post #1:

 

"In 3 observational studies low dose glucosamine (about 1500 mg a day - I mean low dose, because the dose at which side effects occur is more than 10 times; in contrast to metformin and rapamycin) appeared to exert stupifyingly large tumor supressor effects of about 50% reduction in cancer death for long term consumers of frequent (i.e. daily) glucosamine. This is another plausible point for the narrative: in recent years there is emerging consensus, that many cancers are actually driven by mutant mitochondria"

 

I have taken a Glucosamine/Chondroitin product for many years. In addition to 1,500 mg Glucosamine it has Chondroitin Sulfate, MSM and a Boswellia Extract. I might add  1,500 mg of Glucosamine split into 2 doses.

Edited by Heisok, 29 May 2019 - 08:29 PM.

[Preventionisthekey]

I am only semi-literate Science wise. I also tend to rely on those who are literate, and then have a quick look myself to see if something jumps out. This includes those posting here, and elsewhere. Actual uses by many is important, but there seems to be a Scientific process to look at such information for effect. Has this been done for those taking the doses which seem to be common in the products. The original poster indicates yes for tumors. 1,500 mg divided in 2 doses. The original topic starter indicated a benefit at 3,000 mg per day, but that 3,000 mg twice a day was not proportionately better. I guess, that results were not twice as good. They also indicated that there were some observational studies in post #1.

 

Post #32:

As outlined in the glucosamine and cancer thread:

 

there are very well controlled for, prospective cohort studies, with 10th of thousands of participants. Those have good statistical power, delivering highly statistical significant results AFTER accounting for dozens of confounding factors. In addition the reduction in relative risk calculated for total mortality and cancer (for users of glucosamine vs. non-users) is not small, but huge. That's still not a scientific proof for a causal relationship! But at least it's not just anecdotal evidence."

 

Post #33:

"Their main findings:

- GS got an elimination half-life of about 15 hours in humans

- an oral doses up to 1,5 gram in on sitting is readily absorbed and increases plasma concentration of GS proportionally compared to 0,75 gram

- oral intake of 3 gram of GS in one sitting did result in a less than proportional increase in plasma levels

This indicates, that you might want to spread out taking a GS intake of 3 gram or more per day - i.e. a little in the morning and a little in the evening - to get the most out of it."

 

Post #51:

 

"the cancer studies indeed indicate a dose-response-relationship - it might be sufficient to just up the amount taken. If absorption levels off, if taken at 3 grams or more at once, it should still be possible to take it 1 or 2 hours apart. The powdered version of GS might be better for that purpose, as you can sprinkle it into drinks or on food."

 

Post #1:

 

"In 3 observational studies low dose glucosamine (about 1500 mg a day - I mean low dose, because the dose at which side effects occur is more than 10 times; in contrast to metformin and rapamycin) appeared to exert stupifyingly large tumor supressor effects of about 50% reduction in cancer death for long term consumers of frequent (i.e. daily) glucosamine. This is another plausible point for the narrative: in recent years there is emerging consensus, that many cancers are actually driven by mutant mitochondria"

 

I have taken a Glucosamine/Chondroitin product for many years. In addition to 1,500 mg Glucosamine it has Chondroitin Sulfate, MSM and a Boswellia Extract. I might add  1,500 mg of Glucosamine split into 2 doses.

 

 

Thank you for your post ! people like you really help this community

[Guest]

To add to the theory, that Glucosamine is not just a CR-mimetic or Keto-Diet mimetic, but exerts it effect by induction of autophagy:

 

Glucosamine Extends the Lifespan of Caenorhabditis elegans via Autophagy Induction (2018)

https://www.jstage.j...G-2018_002/_pdf

 

this paper tries to disentangle the regulatory effects of Glucosamine by investigating certain genes associated with dietary restriction and observing the life-extension effects in nematodes.

 

Quote from the paper:

"Recently, another group reported the longevity effect of GlcN on nematodes and mice.39) They suggest that the effect was caused by impaired glucose metabolism; however, the involvement of autophagy was not discussed. Here, we clearly showed that the longevity effect of GlcN required an autophagy gene, atg-18. However, unlike functional food factors and calorie restriction, the longevity genes sir-2.1 and daf-16 were not required for GlcN-induced lifespan extension."

 

 

That's a very interesting find!

 

 

There are several papers that demonstrate, that Sirtuins (and the nematod version sir-2.1) are required for Resveratrol and Caloric Restriction to activate autophagy and most of their life extension effects, e.g.

 

"Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy."

https://www.nature.c...cles/cddis20098

 

 

Glucosamine only requires that the basic machinery of autophagy is not disabled - similar to Rapamycin. As the mice-lifeextension-study concluded, GS is not exerting its effect via the nutrient sensing hexosamine-mechanism. This nematode paper is another indicator, that GS is targeting AP directly, just as Rapamycin. It's not just a Keto-mimic/CR-mimic. In the AP-mice study GS caused a much stronger AP-response than a 48-hour fast (the equivalent of several days in people) at the people-equivalent of about 3 gram injected GS per day (that requires probably more in oral consumption). This is plausible if it targets AP directly - via AMPK, mTOR and/or different channels - but not if it's just crypto-Keto/CR.

 

 

Unlike fasting or caloric restricition, GS probably directly targets autophagy mediators. This might be the reason, why Glucosamine is much better than fasting for activating autophagy.

Edited by Guest, 10 June 2019 - 05:46 PM.

[GABAergic]

you are just assuming, as you say "probably" that GS directly targets autophagy mediators and fasting does not. really, you dont know this and whatever you posted doesnt prove it. something tells me that natural ways of inducing autophagy like fasting which have been with humans and animals on this planet since the birth of the planet are more reliable than some synthetic non-vitamin supplement that was invented in the 70s for veterinary medicine.

Edited by GABAergic, 10 June 2019 - 07:07 PM.

[Guest]

Yes, I'm using the qualifier "probably" as we still have no final evidence as we got for Rapamycin. And unlike you - GABA - who constantly is using the weakest of evidence to make strong and completely unfounded claims ("GS causes liver damage" etc. etc.)

 

 

The study I just posted gives a good indication, that GS is not using indirect AP-activation mechanisms that run through nutrient-sensing channels. As GS in mice is demonstrating stronger AP than fasting and doesn't use the hexosamine action in the mice-lifeextension-study this is a good indicator (though not yet proof) that it does not rely upon a metabolic response to activate AP.

 

 

I don't follow your line of argumentation though ("appeal to nature"). Rapamycin reliably activates AP and very strongly. Much stronger than "natural" fasting. Also GS is not "invented". It's part of your body, produced in minuscule amounts in your body every day and part of shell fish and insects. Since about 500 Million years.

[ironfistx]

So not eating produces autophagy but not eating and glucosamine forms better autophagy?

Edited by ironfistx, 10 June 2019 - 11:16 PM.

[Guest]

So not eating produces autophagy but not eating and glucosamine forms better autophagy?

 

well, if you believe these previously posted results for autophagy in mice:

 

 

 

 

... it seems, that the total area (meaning volume in 3D) of autophagosomes and autolysomes in GS-treated mice is much larger than in fasted mice. This indicates, that much more cell components get recycled under GS-exposure - and/or larger cell components such as mitochondria. Note that the difference in area is considerably bigger than the difference in number of AP-vesicles per cell. So if you're only doing it for AP (and not other benefits of multi-day fasting) it seems as if you could skip fasting entirely. Also you can't fast for 365 days - but you can take GS for 365 days. Note though, that the result above is unlikely to be achieved using the commonly 1,5 gram used by oral ingestion. Somewhere above 3 gram/day is probably needed.

Edited by Guest, 11 June 2019 - 10:15 AM.

[GABAergic]

guest at least i looked at the negative profile of this unlike you. if someone didnt know better, they would think you are working for a company promoting glucosamine on here because most of your talk seems like a good advertisement for people to buy it. i would appreciate if you also look at the negative profile, but at this point im convinced you wont and im the bad guy for posting a single negative study i have found. boowhoo

[Guest]

I'm a tenured college teacher in a completely unrelated field - I got no financial interest and don't advertise for any company or product (for GS I recommend to just take the cheapest you can find online). But I know statistics and am used to read into original papers and do some more comprehensive research before making definitive and bold statements.

 

If you can find substantiated side effects for GS I would be happy to read up about it.

 

But what you are posting are claims not backed up by studies that have much relevance (anecdotal evidence vs. well controlled for cohort studies; in-vitro vs. RCTs in humans; or just plain "it's not natural, therefore it's bad").

 

 

Does GS sound too good to be true? Sure. That's why I opened this discussion initially to gather some feedback. But so far I don't see any evidence to the contrary.

 

 

I think your energy would be better spend on substances as NAD+ or C60, that are far more speculative and with some limited theory/evidence of harmful effects (at least on the same level as the evidence that is in favour of those).

[brosci]

So if glucosamine is seemingly anti-aging, and glycine is seemingly anti-aging, and we do need some level of amino acids in our diet to support exercise / fitness. Is bone broth a sort of superfood as the natural source of these compounds?

[GABAergic]

i would say insects are probably the best superfood you can eat as they contain lots of those plus omega 3s https://www.google.c...sects superfood

Edited by GABAergic, 12 June 2019 - 12:03 AM.

[William Sterog]

What about chondroitin? My supplement have both. Do you think it will make the treatment more effective, less effective or equally effective?

[William Sterog]

Am I the only one who gets insanely hungry with Glucosamine + Chondroitin? It is fucking crazy how much I eat when I take this supplement. I am very thin, so it is not like this is necessarily a problem, but it still worries me a little. 

[ironfistx]

Do we need to take it on an empty stomach?

 

Why aren't old people living forever if they take glucosamine?

[BieraK]

So not eating produces autophagy but not eating and glucosamine forms better autophagy?

Use it conjunction  

 

To add to the theory, that Glucosamine is not just a CR-mimetic or Keto-Diet mimetic, but exerts it effect by induction of autophagy:

 

Glucosamine Extends the Lifespan of Caenorhabditis elegans via Autophagy Induction (2018)

https://www.jstage.j...G-2018_002/_pdf

 

this paper tries to disentangle the regulatory effects of Glucosamine by investigating certain genes associated with dietary restriction and observing the life-extension effects in nematodes.

 

Quote from the paper:

"Recently, another group reported the longevity effect of GlcN on nematodes and mice.39) They suggest that the effect was caused by impaired glucose metabolism; however, the involvement of autophagy was not discussed. Here, we clearly showed that the longevity effect of GlcN required an autophagy gene, atg-18. However, unlike functional food factors and calorie restriction, the longevity genes sir-2.1 and daf-16 were not required for GlcN-induced lifespan extension."

 

 

That's a very interesting find!

 

 

There are several papers that demonstrate, that Sirtuins (and the nematod version sir-2.1) are required for Resveratrol and Caloric Restriction to activate autophagy and most of their life extension effects, e.g.

 

"Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy."

https://www.nature.c...cles/cddis20098

 

 

Glucosamine only requires that the basic machinery of autophagy is not disabled - similar to Rapamycin. As the mice-lifeextension-study concluded, GS is not exerting its effect via the nutrient sensing hexosamine-mechanism. This nematode paper is another indicator, that GS is targeting AP directly, just as Rapamycin. It's not just a Keto-mimic/CR-mimic. In the AP-mice study GS caused a much stronger AP-response than a 48-hour fast (the equivalent of several days in people) at the people-equivalent of about 3 gram injected GS per day (that requires probably more in oral consumption). This is plausible if it targets AP directly - via AMPK, mTOR and/or different channels - but not if it's just crypto-Keto/CR.

 

 

Unlike fasting or caloric restricition, GS probably directly targets autophagy mediators. This might be the reason, why Glucosamine is much better than fasting for activating autophagy.

 

This reinforces my idea that Glucosamine + Niacin could be an effective intervention to accelerate the effects of fasting, or to enter ketosis faster.

Edited by BieraK, 24 June 2019 - 09:57 AM.

[BieraK]

Bodybuilders often use Glucosamine to decrease or avoid joint damage. Is not it supposed then that in the light of these studies glucosamine should avoid or decrease muscle growth from weight training + protein?

[QuestforLife]

Bodybuilders often use Glucosamine to decrease or avoid joint damage. Is not it supposed then that in the light of these studies glucosamine should avoid or decrease muscle growth from weight training + protein?

 

Not if autophagy can increase the quality of muscle cells.

 

I.e. a suitable regime might be eat protein and lift weights to build muscle, then sleep/fast/take an autophagy inducer to clean out cells, break down what needs to be broken down, and get ready for more growth.

 

It is not that growth leads to aging or that autophagy leads to muscle wasting, it is that either one without the other is harmful in the long run.

[ironfistx]

Yes as I know NAG is anti-inflammatory and crosses the BBB, however it does not works like Glucosamine in sense as imitating the effects of a low carb diet.
I don't see the problem of taking both, this is something I need to read more (the differences between GlcN and NAG).
 
Well, perhaps 12 or 16 hours of fasting is not enough for boosting AP even with Glucosamine, but if we could at least have the benefits of a 5 day fasting in two days that could be a powerful anti-aging regimen. Even a exercise boosting regimen. I have done several fasting mimicking diets (FMD) cycles and it is so powerful, erases inflammation, gives you a sense of wellbeing, some pains are gone, you feel like a new one. I have done resistance training while fasting, and again, the majority of my long-term and more notorious gains are the gains from the FMD and refeed. I explain this by autophagy, HGH increase and the stem cell proliferation after refeeding.

 
You're saying you got gains while training and fasting?
 

So two days of low calories from complex carbs like the FMD, plus Glucosamine+Niacin could give us the benefits of a 5 day fasting by boosting autophagy and reducing the time needed for entering into ketosis. The problem with fasting is that you need to empty all the glycogen stores, thats why you need to the third day of the FMD for feeling mentally clear. 
 
Sadly I don't have nor Glucosamine nor a Ketone meter with me for now, so I can't do the experiment for now.

 
Seriously?  I feel good after a day of fasting.  You need multiple days to feel mentally clear?  I mean you in general, not you specifically.

Edited by ironfistx, 24 June 2019 - 10:40 PM.

[Preventionisthekey]

Does n acetyl glucosamine provide the same result ? or we need to take glucosamine hcl or sulfate

[GABAergic]

i was taking acetyl form because from what i read its more bioavailable and passes the blood brain barrier better, but people here say there arent many studies to say its better or worse than generic glucosamine. if you ask me, i think its the best form because its harder to find and more expensive AND any acetyl form of a supplement is always more bioavailable not just for the brain but whole body as well