51 replies to this topic

[blood]

Ristow apparently has suggested a dose of 3-5 gm/day glucosamine for life extension purposes (if this dailymail.co.uk article is to be believed):
 

Could a popular arthritis supplement be the key to a longer life?
 
In two large-scale human studies, people who took glucosamine lived longer than others – but Dr Ristow said more research is needed to prove its effectiveness.
 
He added: ‘This may be considered a valid option, and yes, I have started taking glucosamine myself.
 
‘There is no definite proof of the effectiveness of glucosamine in humans.
 
‘But the chances are good – and since unlike most other potentially lifespan-extending drugs there are no known relevant side-effects of glucosamine supplementation, I would tend to recommend this supplement.’
 
Dr Ristow advised people should take a daily tablespoon of glucosamine powder, mixed in water, or alternatively, 3g to 5g a day in capsule form.
 
Diabetics should speak to their doctor first, and people with shellfish allergies, or those on the blood-thinning drug warfarin, should be cautious.

Nice summary of what's known & not known from Vince Giuliano: Glucosamine for longevity

Edited by blood, 15 December 2014 - 12:41 PM.

[albedo]

...
Nice summary of what's known & not known from Vince Giuliano: Glucosamine for longevity

 

 

Thanks. I just wonder if what reported in the summary helps putting at rest the (admittedly not well researched) hints to an increased risk of prostate cancer spread when using chondroitin sulfate (e.g. see here and here). As CS and GS  are typically taken together for joints help would it be possible the anti proliferative effect of GS (reported in the article, specifically for the prostate cancer (*)) limits the risk of CS? I am still not taking both CS and GS for the reasons already mentioned but might reconsider.

 

(*)

... In the present study, we found d-glucosamine inhibited the activity of p70S6K and the proliferation of DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. d-Glucosamine decreased phosphorylation of p70S6K, and its downstream substrates RPS6, and eIF-4B, but not mTOR and 4EBP1 in DU145 cells, suggesting that d-glucosamine induced inhibition of p70S6K is not through the inhibition of mTOR.  In addition, d-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR.  These findings suggest that d-glucosamine can inhibit growth of cancer cells through dephosphorylation of p70S6K....

 

[YOLF]

Very interesting, I've switched to bulk powder for my GS intake recently... I had been wanting to ditch the CS for a while now and couldn't remember why, but this looks like another reason to keep taking it separate.

[ta5]

Int J Mol Med. 2016 Dec 28.
Effect of glucosamine on expression of type II collagen, matrix metalloproteinase and sirtuin genes in a human chondrocyte cell line.
Igarashi M1, Sakamoto K1, Nagaoka I1.
Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, the effects of GlcN on genes related to cartilage metabolism are still unknown. In the present study, to elucidate the chondroprotective action of GlcN on OA, we examined the effects of GlcN (0.1-10 mM) on the expression of the sirtuin (SIRT) genes as well as type II collagen and matrix metalloproteinases (MMPs) using a human chondrocyte cell line SW 1353. SW 1353 cells were incubated in the absence or presence of GlcN. RT-PCR analyses revealed that GlcN markedly increased the mRNA expression of type II collagen (COL2A1). By contrast, the levels of MMP-1 and MMP-9 mRNA were only slightly increased by GlcN. Furthermore, western blot analyses revealed that GlcN significantly increased the protein level of COL2A1. Importantly, GlcN enhanced the mRNA expression and protein level of SIRT1, an upstream-regulating gene of COL2A1. Moreover, a SIRT1 inhibitor suppressed GlcN-induced COL2A1 gene expression. Together these observations suggest that GlcN enhances the mRNA expression and protein level of SIRT1 and its downstream gene COL2A1 in chondrocytes, thereby possibly exhibiting chondroprotective action on OA.
PMID: 28035358

[zorba990]

Ristow apparently has suggested a dose of 3-5 gm/day glucosamine for life extension purposes (if this dailymail.co.uk article is to be believed):

Could a popular arthritis supplement be the key to a longer life?

In two large-scale human studies, people who took glucosamine lived longer than others – but Dr Ristow said more research is needed to prove its effectiveness.

He added: ‘This may be considered a valid option, and yes, I have started taking glucosamine myself.

‘There is no definite proof of the effectiveness of glucosamine in humans.

‘But the chances are good – and since unlike most other potentially lifespan-extending drugs there are no known relevant side-effects of glucosamine supplementation, I would tend to recommend this supplement.’

Dr Ristow advised people should take a daily tablespoon of glucosamine powder, mixed in water, or alternatively, 3g to 5g a day in capsule form.

Diabetics should speak to their doctor first, and people with shellfish allergies, or those on the blood-thinning drug warfarin, should be cautious.

Nice summary of what's known & not known from Vince Giuliano: Glucosamine for longevity

Thanks. This part is particularly interesting

"10. N-acetyl-glucosamine has a different mechanism of action from D-glucosamine – The last paragraph in the discussion section of this paper mentions that another group has shown a lifespan extending effect of N-acetyl-glucosamine, but the mechanism of life span extension is by inhibiting the hexosamine pathway, not via AMPK."

[tunt01]

 

Thanks. This part is particularly interesting

"10. N-acetyl-glucosamine has a different mechanism of action from D-glucosamine – The last paragraph in the discussion section of this paper mentions that another group has shown a lifespan extending effect of N-acetyl-glucosamine, but the mechanism of life span extension is by inhibiting the hexosamine pathway, not via AMPK."

 

 

Very good point.  I think this is worth looking at more closely.  Overactive hexosamine pathway occurs in diabetes and leads to microvascular complications.

[Kalliste]

 

Glucosamine promotes osteoblast proliferation by modulating autophagy via the mammalian target of rapamycin pathway.

(PMID:29334671)

• Abstract
• Citations
• Related Articles
• Data
• BioEntities
• External Links

Lv C ¹ , 

Wang L ¹ , 

Zhu X ¹ , 

Lin W ¹ , 

Chen X ¹ , 

Huang Z ¹ , 

Huang L ¹ , 

Yang S ²

Affiliations

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie [12 Jan 2018, 99:271-277]

Type: Journal Article
DOI: 10.1016/j.biopha.2018.01.066

Abstract

Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The results showed that glucosamine had a biphasic effect on the viability of hFOB1.19 osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell proliferation, whereas at high concentrations (>0.8 mM) it induced apoptosis. The autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas the promotion of cell proliferation by low concentrations of glucosamine was significantly suppressed by 3-MA. Autophagy was examined by western blot detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62 and by immunofluorescence analysis of autophagosomes. Glucosamine activated autophagy in a time- and concentration-dependent manner. Investigation of the underlying mechanism showed that glucosamine inhibited the phosphorylation of m-TOR in a concentration-dependent manner within 48 h, and rapamycin significantly inhibited the phosphorylation of m-TOR. These results demonstrated that glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for osteoporosis.

http://europepmc.org...ct/med/29334671

[YOLF]

well, apparently the life extension effects of glucosamine were abolished with the addition of antioxidants.
 

So it sounds like Glucosamine acts as a senolytic in the same way that calorie restriction does and NAC and BHA(was it?) prevented senolytic action. Presumably, these types of antioxidants would lead to a greater incidence of various disease states, except for the ones they treat. 

[YOLF]

http://europepmc.org...ct/med/29334671

 

So what's the human equivalent of the low dosage? This stuff is really cheap in powder and 1g pill form.

[Kalliste]

To be honest I don't know. I take between 400mg-1200mg a day along with MSM.

So what's the human equivalent of the low dosage? This stuff is really cheap in powder and 1g pill form.

 

[Harkijn]

The brand I have been taking for many years now advises two tablets daily, totaling 1500mgs of glucosamine. Most days I take only one tablet.

[normalizing]

So it sounds like Glucosamine acts as a senolytic in the same way that calorie restriction does and NAC and BHA(was it?) prevented senolytic action. Presumably, these types of antioxidants would lead to a greater incidence of various disease states, except for the ones they treat. 

 

can you explain this. what do you mean they will cause diseases but will treat some of them??

[normalizing]

just found this; https://www.medicaln...cles/319766.php

 

very interesting! whats the take on n acetyl glucosamine vs plain glucosamine? which is better idea to be used with more bioavailiblity especially in the brain??

[YOLF]

can you explain this. what do you mean they will cause diseases but will treat some of them??

Cause might have been too strong of a word. Perhaps contribute? So save a cell that should die and it could become senescence resistant. Antiox early in life is probably great, but at some point it may lead to the accumulation of damage where those antiox don't active the right enzymes for DNA repair and intercellular digestion etc. NAC under certain conditions and at certain dosages promoted some types of cancer.Senolytics would seem to be the safest of the lifeextension bunch in a broad sense as nothing bad will likely occur as a result of senescent cell removal at any time during the standard period of aging that we affectionately refer to as life.

[normalizing]

what are examples of senolytics? anything thats easily available?

[YOLF]

what are examples of senolytics? anything thats easily available?

Quercetin has been delineated as a senolytic. Apigenin and a variety of other flavonoids have been shown to have similar activity. Some also activate p53, so there's a lot of crossover from things we're already used to taking for life extension.

[normalizing]

oh i know of quercetin, luteolin and apigenin. all of them are present naturally in most foods and herbs and they have very low if any bioavailability. although on the market they sell formulations now with enhanced bioavailability it seems it might actually be bad if you sustain high plasma levels of those things which makes sense if the body naturally gets rid of them so easily to begin with

[YOLF]

I don't know. I take metaquercetin and I haven't had any side effects since I stopped taking it with vitamin C (it also extends the longevity of  Vit C and some other antiox's). Taking quercetin in a pure unconjugated form at 1g is fine, though I don't experience the same energy boost from meta as I do from pure quercetin. Not sure which is better actually. when attached to long lasting lipids they start developing an affinity for things that use fat. Not sure how much that's true with the indigestible polysorbate 80 that's used in the RevGenetics product... But it's the kind of thing that you can feel working. Fewer senescence resistant cells and more antiox recycling means more energy, though they do come back everyday unfortunately, so the area needs more delineation as there is too much complexity right now to know exactly what to do for who and we don't exactly have home mass spectrometers in our kitchens to put just the right amount of everything in our meal supplements... 

Edited by YOLF, 07 May 2018 - 03:00 AM.

[ironfistx]

Here, is the amount of NAG you use going to be based upon effects?  Is 1g every day unlike 2g every other day?  How about this statement that glucosamine prevents cartilage rebuilding?  Wouldn't that defeat the reason of taking it?  How is NAG not the same?

[Kevnzworld]

Glucosamine may reduce overall death rates as effectively as regular exercise, study suggests

https://www.scienced...01201171726.htm

[Guest]

Glucosamine may reduce overall death rates as effectively as regular exercise, study suggests

https://www.scienced...01201171726.htm

 

 

I don't want to dismiss their findings; but reading into the (free) direct paper, the press release seems to be overselling the results:

 

https://www.jabfm.org/content/33/6/842

 

 

The 39% reduction in overall mortality was not after correction for all available confounders, but just for age. The true results reported in the study is a reduction in total mortality of 27% and CVD mortality of 58%

 

Note though, that the study population was smaller compared to previous studies (about 16.600 in this study vs. 77.000. vs. 500.000 previously) and only 658 taking glucosamine are included (some of them in combination with chondroitin). That's not that many, to do some multi-variate analysis on. The range of factors corrected for is smaller than in previous studies.

 

On da' plus side, and in contrast to previous studies, they excluded people that just recently started supplementing. This could potentially explain the larger effect size - i.e. long term use vs. a mixture of long-term and short-term use in other studies.

 

 

 

The connection to exercise is of course superficial. They do not imply, that the health benefits are based on the same mechanisms. So don't stop exercising regularly (similarly, you wouldn't stop exercising, just because you started a healthy diet instead of McDonald's).

Edited by Guest, 07 December 2020 - 12:33 AM.

[Florin]

This study claims that glucosamine use reduces all-cause mortality by 15%. The study also controlled for chondroitin use, and as far as I know, it's the first to do so.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study
https://ard.bmj.com/content/79/6/829
 

In this large population-based cohort study involving 495 077 individuals, we found that regular glucosamine use was significantly associated with a 15% lower risk of total mortality and 18% for CVD mortality; 6% for cancer mortality; 27% for respiratory mortality and 26% for digestive mortality.

Glucosamine and chondroitin supplements are often taken together in a single daily supplements, and it is therefore possible that our observed associations are driven by either of these supplements. To address this issue, we performed sensitivity analyses examining the associations of glucosamine use alone (excluding participants who took chondroitin) with all-cause and cause-specific mortality. We found that the estimates did not change substantially. Therefore, it is likely that glucosamine use may reduce the risk of mortality, regardless of the co-administration of chondroitin.