167 replies to this topic

[Heisok]

I never try to advise others what to do, and that is not my intent here..

 

For many years, I have been taking 1.5 grams of Glucosamine HCL split into morning, and afternoon doses. For around 30 days, I have been taking 1.5 grams Glucosamine Hcl in the A.M. 750 mg of Glucosamine Hcl in the afternoon, and 2 grams of Glucosamine Sulfate before bed. The total intake of Glucosamine is 4.25 grams.

 

I have been eating some level of Ketogenic macros for years now.  I have not noticed any hypoglycemia or other signs of lack of energy mentally nor physically. We ride well over an hour 5-6 days a week of combined dirt and paved trail bicycle riding. I resistance train twice a week. No issues so far. I eat about 5 or so tablespoons of C8 Mct, and enough other saturated fat to bring me  to 3,000 or more calories per day given the lack of Carbs.

 

I do not think that Glucosamine can completely block most blood glucose, as our bodies seem to want some sort of equilibrium.

 

I would love to see a study where Glucosamine can completely eliminate blood Glucose? Is there one? Autopsies I guess

 

Maybe, Crazy, stupid , irresponsible, but I am doing OK for now. I have not decided yet if I will create a cycling schedule for Glucosamine to lessen the prodding of my body towards too much Autophagy (if that is even possible) I will report if anything changes

 

Thanks.

 

 

Edited by Heisok, 26 July 2019 - 12:49 AM.

[Guest]

Although it's a little far fetched, I'm posting 2 studies that I found concerning immuno effects of GS. The first one:

 

"Immunosuppressive Effects of Glucosamine" (2002)

http://www.jbc.org/c...7/42/39343.long

 

experiments with transplanting organs onto mice, noting that Glucosamine (but not other amino-sugars) at very high conentrations acts as an effective immuno-supressive agent comparable to standard pharmacological treatment. The plasma level was more than 100 times higher than normal GS concentrations in bio-availability studies and should be impossible to achieve by oral intake.

 

 

A similar observation was made in humans transplant patients:

"Glucosamine Activates T Lymphocytes in Healthy Individuals and may Induce GVHD/GVL in Stem Cell Transplanted Recipients" (2011)

https://benthamopen....OTRANSJ-5-1.pdf

 

Though depending on the patient situation GS paradoxily either increased immune function and risk of rejection in several patients or suppressed immune function and saved a patient. The dose was just 1,25 g per day.

 

 

So if you're in a situation that requires immuno-supression you might be careful using any amount of GS. Vice-versa a very high dose (much more than 1,5 g by oral intake) might have the opposite effect and make you prone to infection.

 

 

 

As for the mice-autopagy study: the human equivalent of 3 gram per day by injection requires more oral intake. While about 90%-95% of GS is absorbed in the GI-tract, the first pass effect of the liver leads to a plasma-availability of 20%-26%. If this is directly translatable (not factoring in the leveling off of the plasma-level-curve with increasing doses in one sitting), you'd need to take 12g - 15g to achieve the same results, i.e. much stronger AP than fasting. It might be a good idea not to do this 365 days a year - although I personally think that 1,5 g is too conservative as a steady-state dose.

Edited by Guest, 05 August 2019 - 04:15 AM.

[BieraK]

As for the mice-autopagy study: the human equivalent of 3 gram per day by injection requires more oral intake. While about 90%-95% of GS is absorbed in the GI-tract, the first pass effect of the liver leads to a plasma-availability of 20%-26%. If this is directly translatable (not factoring in the leveling off of the plasma-level-curve with increasing doses in one sitting), you'd need to take 12g - 15g to achieve the same results, i.e. much stronger AP than fasting. It might be a good idea not to do this 365 days a year - although I personally think that 1,5 g is too conservative as a steady-state dose.

 So, sublingual could be a better option?

[Female Scientist]

I also get a jittery/crashing feeling from both glucosamine and ALA, as William S. does. Just wanted to mention because I'll bet it's a "thing" and I wanted to record my Plus 1 here. ...my glucose tolerance seems to be weird in a very specific way, and always has been. I've never been able to tolerate morning sugar intake at all...a pancake breakfast will send me to bed with crushing fatigue within an hour of eating. I've had several Glucose Tolerance Tests, and in each one my glucose crashes very quickly - much more quickly than usual metabolism, following consumption. Otherwise, my fasting glucose is normal (90 or less). I don't have the background to analyze it, but I'm 51 years old and pretty tuned in to my physical response to food and supplements. As a speculative theory, perhaps William and I share a specific genetic SNP that impacts our glucose metabolism, and these types of supplements only increase our fast glucose metabolism?

[Izan]

Are there more reports/experiences on this?

[YOLF]

I also get a jittery/crashing feeling from both glucosamine and ALA, as William S. does. Just wanted to mention because I'll bet it's a "thing" and I wanted to record my Plus 1 here. ...my glucose tolerance seems to be weird in a very specific way, and always has been. I've never been able to tolerate morning sugar intake at all...a pancake breakfast will send me to bed with crushing fatigue within an hour of eating. I've had several Glucose Tolerance Tests, and in each one my glucose crashes very quickly - much more quickly than usual metabolism, following consumption. Otherwise, my fasting glucose is normal (90 or less). I don't have the background to analyze it, but I'm 51 years old and pretty tuned in to my physical response to food and supplements. As a speculative theory, perhaps William and I share a specific genetic SNP that impacts our glucose metabolism, and these types of supplements only increase our fast glucose metabolism?

Have you lodged your experience with FAER? The FDA Adverse Event Reporting people? That's important and I doubt that it'll result in the stuff being removed from the market, but may lead to publications on the topic.

[QuestforLife]

I also get a jittery/crashing feeling from both glucosamine and ALA, as William S. does. Just wanted to mention because I'll bet it's a "thing" and I wanted to record my Plus 1 here. ...my glucose tolerance seems to be weird in a very specific way, and always has been. I've never been able to tolerate morning sugar intake at all...a pancake breakfast will send me to bed with crushing fatigue within an hour of eating. I've had several Glucose Tolerance Tests, and in each one my glucose crashes very quickly - much more quickly than usual metabolism, following consumption. Otherwise, my fasting glucose is normal (90 or less). I don't have the background to analyze it, but I'm 51 years old and pretty tuned in to my physical response to food and supplements. As a speculative theory, perhaps William and I share a specific genetic SNP that impacts our glucose metabolism, and these types of supplements only increase our fast glucose metabolism?

Well morning is the time the body is the most insulin sensitive, so you'd expect faster glucose clearance. Put the competition of glucosamine into your blood as well, and that might explain the 'sugar crash' feeling.

[William Sterog]

I also get a jittery/crashing feeling from both glucosamine and ALA, as William S. does. Just wanted to mention because I'll bet it's a "thing" and I wanted to record my Plus 1 here. ...my glucose tolerance seems to be weird in a very specific way, and always has been. I've never been able to tolerate morning sugar intake at all...a pancake breakfast will send me to bed with crushing fatigue within an hour of eating. I've had several Glucose Tolerance Tests, and in each one my glucose crashes very quickly - much more quickly than usual metabolism, following consumption. Otherwise, my fasting glucose is normal (90 or less). I don't have the background to analyze it, but I'm 51 years old and pretty tuned in to my physical response to food and supplements. As a speculative theory, perhaps William and I share a specific genetic SNP that impacts our glucose metabolism, and these types of supplements only increase our fast glucose metabolism?

I also have a weird relationship with sugar. It really causes me brain fog and tiredness. That is one of the reasons why I lean towards low-carb.

[Heisok]

Has anybody else taken their blood glucose readings around their sugar crash, potential hypoglycemic symptoms? Please share.

 

For me, I am ending my trial of daily glucosamine sulfate, added to the 1,500 mgs glucosamine hcl which I have taken for many years. I was taking 2,000 mgs of the sulfate  around 10 pm each evening. I end up very hungry the following day which causes me to need to eat my first solid food by about 9 am. Usually, I can get by with my fatty coffee until as late as 1 pm.

 

Yes maybe a little jittery, almost hypoglycemic feelings.  Thing is, I measure my B.G. at those times, and whenever I feel like it during the day, and it has been high 80's to high 90's. Maybe it has something to do with the combination with caffeine? Anybody notice needing less caffeine? I monitor the calories which I consume closely, and believe I am eating about the same. Also my weight is within the about 3 to 5 lb range which it varies by on any given day, so I do not believe that I am simply hungry from eating less.

 

 

 

Edited by Heisok, 14 August 2019 - 10:47 PM.

[GABAergic]

how long does glucosamine takes to work? ive been using it for months now, i still do not get benefit for various joint pains. i use the sulfate version. i sure hope by end of the year it helps with my joints or i might switch to kratom, which helped enormously with my joint pain in the past. the only reason i stopped it is because its frowned upon. that stuff worked like charm tho.

Edited by GABAergic, 15 August 2019 - 02:04 AM.

[Guest]

Some curious results.... I recently had a small surgical procedure, and wondered, if I should take glucosamine during the healing process. GS is anti-inflammatory - so it might reduce wound healing (e.g. fish oil seems to do just that). Luckily there are several studies, that are demonstrating the opposite in rats and mice (GS enhances healing). But during my read-up I also found a study that looked at bio-markers for skin-aging:

 

"Efficacy of Glucosamine Sulphate in Skin Ageing: Results from an ex vivo Anti-Ageing Model and a Clinical Trial" (2017)

 

https://www.karger.c...FullText/450832

 

 

where it seems, that GS indeed improves those biomarkers in humans. Biomarkers for wound healing are at least not worse than before. It should be noted though, that the dose used is 250 mg per day - that is oddly small, given that even the standard dose in common supplements is 1500 mg per day (and that still is likely sub-optimal).

[Guest]

This very recent study is not about autophagy or about CRC but gives an indication of the safety and effectiveness of supplementing GS. 466.000  healthy people were followed over a number of years. The GS users had significantly less CVD incidence:

https://www.ncbi.nlm...pubmed/31088786

 

To lend some credibility to the recent CVD results of Glucosamine: there is a controlled study in rabbits, that escaped my attention, investigating the effects of GS on atherosclerosis:

 

Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis. (2009)

https://www.physiolo...eart.00142.2009

 

 

They got some impressive results. A short outline of the study directly from the paper:

 

"In this study, 45 white adult New Zealand male rabbits were used with a mean ± SE weight of 3.0 ± 0.3 kg. Briefly, all rabbits were allowed to adapt to the facilities for 1 wk, and they were then separated into three groups of 15 animals each: a control group of healthy rabbits fed with standard chow (control); a group of rabbits with chronic antigen-induced arthritis and atherosclerosis (AIA-AT); and a group of rabbits (AIA-AT + GS) with chronic induced arthritis and atherosclerosis that received GS with their food (GS, 500 mg/kg/day). To induce atherosclerosis, the rabbits were fed a hypercholesterolemic diet of 2% cholesterol and 6% peanut oil throughout the study. After starting the diet (2 wk), an endothelial lesion was induced in both femoral arteries by the intravascular instillation of nitrogen gas under general anesthesia. To induce AIA, animals were given two intradermal injections of 4 mg ovalbumin in Freund's complete adjuvant, 14 days apart, beginning the same week as the hyperlipidemic diet. After the second injection (5 days), 1 ml of ovalbumin (5 mg/ml in 0.9% NaCl) was injected in both knee joints on a weekly basis over the following 4 wk. Animals were then killed 6 wk after the beginning of the atherogenic diet."

 

 

The subsequent analysis revealed a strong anti-inflammatory effect and strong supression of CVD despite an atherogenic diet and lesion inducing procedure:

 

 

 

 

 

CRP is depicted by the black bars in the image above. Other inflammatory markers - COX2, NFkB - are equally supressed:

 

 

 

 

 

 

And most importantly, the rabbits did not develop atherosclerotic lesions:

 

 

 

 

 

It has to be noted, that the rabbits received a really high dose of Glucosamine - in human terms and depending on allometric scaling 15 g to 30 g per day in their diet. So unless you got a really high risk of CVD, a dose closer to the equivalent of 6 g per day used in the mice longevity study might be a better move. I don't think that there would be much of a risk though using the high dose - except side effects of course (at 15 g per day there should be some: like GI-issues or short term Keto-adaption issues, as even a smaller dosis in mice and rats increased keton bodies substantially) and the bad taste. At least rodents being fed even higher doses long term didn't show any serious side effects - so no disease states developed and no tissue changes.

Edited by Guest, 26 September 2019 - 06:57 PM.

[StevesPetMacaque]

Interesting. Anecdotally, glucosamine has a fairly strong anti-anxiety effect in me (Hip, an active forum member, likes NAG for this reason). Anxiety can be driven in part by metabolic issues (specifically, lactic acidosis in the brain), so perhaps improved mitochondrial efficiency is an explanation.

 

Some people have asked about the differences between glucosamine and NAG. Aside from those mentioned previously, these are binding targets for various lectins. In particular, NAG is a target of wheat germ agglutinin, whereas glucosamine isn't. I found a nice table for the sugars bound by various lectins, but a quick search isn't turning it up. If anyone is interested, I can dig a little harder when I get out of the office.

[Slobec]

https://www.ncbi.nlm...les/PMC5848858/

[BieraK]

It has to be noted, that the rabbits received a really high dose of Glucosamine - in human terms and depending on allometric scaling 15 g to 30 g per day in their diet. So unless you got a really high risk of CVD, a dose closer to the equivalent of 6 g per day used in the mice longevity study might be a better move. I don't think that there would be much of a risk though using the high dose - except side effects of course (at 15 g per day there should be some: like GI-issues or short term Keto-adaption issues, as even a smaller dosis in mice and rats increased keton bodies substantially) and the bad taste. At least rodents being fed even higher doses long term didn't show any serious side effects - so no disease states developed and no tissue changes.

This looks interesting. Glucosamine increases ketone bodies? This could works, again, as an fasting booster, for getting the same benefits of 5 days fasting in less time. I'm getting tired to wait to the third day of fasting (By doing a Fasting mimicking diet, less than 800 kcal a day with 45% complex carbs, 45% mufas, no protein of any type) for feeling okay and getting the full benefits. 

I did a quick search on pubmed and was unable to find something related to glucosamine and ketones. Do you have those studies or remember the titles?

Edited by BieraK, 12 October 2019 - 04:51 AM.

[Slobec]

https://www.ncbi.nlm...les/PMC5848858/

...actually, article is about autophagy. Salicylic acid is cheap, effective, safe.

[YOLF]

Try swallowing salicylic acid instead of aspirin... much more acidic, or at least much more heartburn. Not so with excipient free aspirin. The acetyl group makes all the difference and you'll see the difference in your face if you get the dosage right. Acetylsalicylic acid is definitely better than salicylic acid for anti aging. 

[ironfistx]

how long does glucosamine takes to work? ive been using it for months now, i still do not get benefit for various joint pains. i use the sulfate version. i sure hope by end of the year it helps with my joints or i might switch to kratom, which helped enormously with my joint pain in the past. the only reason i stopped it is because its frowned upon. that stuff worked like charm tho.

 

Isn't that hallucinogenic?

[Zisos]

In this study https://www.ncbi.nlm...les/PMC3988823/ the authors found that "Antioxidants prevent GlcN-mediated life span extension". This is an extremely important finding. Many people take all sorts of antioxidants. For example, I take NAC and Glutatheine. Both strong antioxidants. So, I will get no "life span extension" by also taking Glucosamine.

It would be very useful if anyone can suggest a way of reaping the benefits of both : antioxidants and Glucosamine.

Most likely, we would need to take these intermittently. But the question is, what time frames would be appropriate? 

-Taking them at diferent times of the same day?

-Maybe one or two weeks on Glucosamine and a similar timeframe for antioxidants?

-All the time Glucosamine, but some weeks without antioxidants?

 

Any ideas will be greately appreciated

[micro2000]

If I'm reading this correctly, the antioxidant + glucosamine study was only done with C. elegans. Not something I would extrapolate to humans.

[aribadabar]

If I'm reading this correctly, the antioxidant + glucosamine study was only done with C. elegans. Not something I would extrapolate to humans.

 

And rightfully so.

[brundall]

Some pretty impressive latest findings on Glucosamine

 

Conclusions Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

 

https://ard.bmj.com/...dis-2020-217176

 

 

[Guest]

Some pretty impressive latest findings on Glucosamine

 

Conclusions Regular glucosamine supplementation was associated with lower incidence of type 2 diabetes after controlling for a broad range of co-factors. The potential ability to prevent diabetes seems to be mediated by controlling background inflammation.

 

https://pubmed.ncbi....h.gov/31988063/

[Onur]

How many grams of glucosamine per day is recommended?

[Guest]

Unfortunately I got little time for extensive elaboration currently.


My statements below are based on a recent and very good study, that investigated the effects of Glucosamine on autophagy:
https://www.tandfonl...27.2019.1632104



GS it turns out does both: upregulating autophagy and inhibiting it at the same time


1. It gradually lowers acidification of the lysosome. Thereby lowering the rate of AP-degredation.

2. At the same time it eventually causes a strong inhibition of MTORC1. This results in a massive surge in formation of AP-vesicles in their experiments.


Now, a sizeable increase of the rate of AP-vesicle creation does no good, if they do not get cleared eventually.


GS elemination half life is 15 hours in humans. And we know for mice, that their half life is about 3-5 hours.


Mice taking the human equivalent of about 6 gram of GS spread out in their food get sizeable benefits (see the mice lifeextension study for starting GS in 23 month old animals - that's old age in people). The typical dose in people in the prospective cohort study is 1,5 gram a day. Therefore roughly in line with the different rate of metabolism. This dose appears to be small enough, that

a) the rate of slowdown of degradation is not really relevant

and / or

b) that the 15 hours of half life are a sufficient time-course to let sligthly impaired AP-degredation take on the increased AP-activity


Note, that the level of GS on AP-vesicle creation and lysosome de-acidification in the mice in the recent study is dose-dependend.



I'd say:

if you take 3 gram in the morning you don't need to be concerned

if you take a high dose, 9 gram or 15 gram a day, it could be advisable, to take 2 break days (e.g. Sat+Sun) out of precaution


15 gram means massive upregulation of the rate of AP-vesicle formation - but also a bigger degree of inhibition of AP-vesicle clearance


I personally start Mondays at 3 gram, finis Friday at 15 gram and take Sat+Sun off.

Edited by Guest, 02 September 2020 - 09:26 PM.

[Guest]

One slightly interesting head-to-head comparison of Glucosamine and Rapamycin:

 

 

https://sci-hub.st/h...753332217361425

 

 

note: this is an invitro-study - so don't take the absolute effects as a measure; the comparison of relative levels of MTOR-inhibition to Rapamycin is the more interesting part.

 

The researchers were bathing cells in a 0,6 mM solution of Glucosamine for 48 hours continously and did the same for 100 nM of Rapa. Both exposure is difficult if not impossible to achieve in-vivo in humans. The concentration of Glucosamine was 6000 times the Rapa one. That sound insane, but not so much if you look at what humans can take: if you take 6 gram of Glucosamine daily, the Rapamycin equivalent based on this study would be 1 mg. Which makes taking Glucosamine much cheaper.

 

 

The interesting graph is this one:

 

 

 Gluscoamsms.bmp   2.08MB   15 downloads

 

 

at the concentrations mentioned, Glucosamine and Rapamycin result in the same level of MTOR supression. Note, that Glucosamine doesn't supress MTORC2 - so you can take it daily. But as outlined above, it's probably still a good idea not to take a high dose (such as 6 grams or more) every day.

Edited by Guest, 23 September 2020 - 05:46 PM.

[aribadabar]

the typical dose in people in the prospective cohort study is 1,5 gram a day.


I personally start Mondays at 3 gram, finis Friday at 15 gram and take Sat+Sun off.

 

Why have you settled on min 3g per day dose?

Is 1.5g/d waste of time with negligible effect?
 

[William Sterog]

I reintroduced Glucosamine and Chondroitin after abandoning the keto diet, and I find that they don't mess with my sugar levels anymore. I have found that they almost completely eliminate my chronic rhinitis, that I have been suffering for years, but they also cause some mild headache in the back of my head.

I investigated the issue and I found this:

Glucosamine has an antiallergic effect in mice with allergic asthma and rhinitis

https://pubmed.ncbi....h.gov/28558148/

I have also bought a mix of Glucosamine, Chondroitin, MSM and Hyaluronic Acid, since I was unable to find G + C alone this time. I have not opened this new bottle yet, and I hope that those things further contribute to the anti-inflammatory effects without disrupting the benefits on autophagy.

Edited by William Sterog, 25 September 2020 - 12:00 PM.

[Guest]

Why have you settled on min 3g per day dose?

Is 1.5g/d waste of time with negligible effect?
 

 

 

it's not clear cut; but there are is various reasoning behind a dose that goes beyond the 1,5 g commonly taken for joint support:

 

- first: the 1,5 g was never scientifically validated; Rottapharma literally came up with that recommendation out of the blue in the early 90s and due to it's subsequent prevalence in "natural medicine" circles its what is most commonly used and therefore most human data on effects and safety is available

 

- the mice in the life-extension study took a much higher dose (for humans somwhere around +-6 g depending on your favorite method of scaling)

 

- in 3 prospective cohort studies (one analysis looking at the Washington vital-study, one recent Spanish study, the US-health professional study) a higher intake of GS was associated with better anti-cancer effects (dose-depended effect)

 

- in animal data for rabbits and mice, a much higher equivalent dose than 1,5 g of oral intake in humans demonstrated profound benefits for cardiovascular health; literally almost stopping animal-models of atherosclerosis

 

- the in-vivo data for profound autophagy in animals also employed a considerably greater dose than 1,5 g by oral intake for people

 

 

It is true, that there is no human data available for taking 6 g or more a day for years. Nonetheless, GS administered in rats and dogs for 1 year at a much larger dose (scaled for people about 27 g per day; every day) did not result in any notable side effects or negative histological/tissue alterations.

 

 

All in all the evidence for longevity effects and side effects (or lack thereof) in people is much more developed than for rapamycin in people. Based on 1,5 g there appears to be a substantial safety margin above it. Researcers literally failed to find an LD50 for mice. There is one study that tried to figure it out; but could only register that the highest dose administered - the equivalent of 150 g by oral intake in people in one sitting - did not result in any dead mice and is reportedly "well tolerated" (in mice).

[Danniel]

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/