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The Glucosamine Cancer Prevention Thread

glucosamine cancer longevity

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#1 Guest

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Posted 23 January 2019 - 09:33 PM


I already posted parts of this as a post in an unrelated thread. However, to give a better write up and more convenient place for discussion I’m opening up a new thread to gather ideas and conclusions. This thread is also related to another discussion, but focuses more specifically on the anti-tumor effects:

https://www.longecity.org/forum/topic/69839-glucosamine-promotes-longevity-by-mimicking-a-low-carb-diet

 

 

To summarize the development I give a short overview of the most important results so far:

note: some studies investigated colorectoral cancer (CRC) only, as it is the most common cause of cancer death, after lung cancer (85% caused by smoking, and “easily” avoidable)

 

2010: https://www.ncbi.nlm...pubmed/20410091

https://www.ncbi.nlm...les/PMC2814533/

2011: https://www.ncbi.nlm...les/PMC3175750/

2013: https://www.ncbi.nlm...les/PMC3671752/

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

These are results from the VITAL study, that investigates lot’s of different supplements and their effect on pathology and mortality. 77,673 participating middle aged to older folks where studied for 10 years. A huge variety of factors were analysed (exercise, age, diet etc.) As a results, of the numerous substances, only Gluco/Chon had a notable independent effect on life span:

Mortality was lowered by 13% vs non-takers of gluco/chon; That increased to 38%-49% when users of NSAID (Aspirin, Ibu) were excluded from the analysis. 33% reduction for non-lung/non-colorectoral cancers + lower mortality for other diseases.

Another analysis of VITAL-data found that lung-cancer was reduced by 26/28% (specifically for adenocarcinomas 39%/50% reduced) for gluco/chon and colorectoral cancer (CRC) decreased by 28%/35%.

Follow-up studies on VITAL-data that analysed different amounts of Glucosamine intake found a 61% reduction of lung cancers and 45% reduction in CRC for high-intake users of Gluco (measured by frequency of intake)

 

Weakness of the results: supplement patterns were established just once – at the start of the study

 

 

2014: https://www.ncbi.nlm...les/PMC3988823/

Glucosamine in human-equivalent dosage extends life of already old mice

 

 

2016: https://www.ncbi.nlm...nihms799160.pdf

Another big observational study, observing 68.466 nurses and 27.934 male professionals for 8 years using regularly repeated questionnaires to investigate life style and CRC.

Result: a 25% cancer reduction for users of Gluco/Chon; this increased to 45% for normal weight users (while obese users benefited less for the same intake).

 

Question: why do obese people benefited less?

 

 

2018: https://www.ncbi.nlm...les/PMC5794904/

A smaller Spanish study enrolling 10183 participants to investigate CRC. They calculated a crude reduction of 53% in cases of CRC in gluco/chon consumers.

 

Weakeness: the number of participants and study design did not allow to statistically disentangle the use of NSAID. Only 99 cases in total used gluco/chon and strongly correlated with NSAID use.

My comment: NSAID use was not independently linked to reduced cancer in the other large scale studies; their results could be adjusted for NSAID use and still confer a strong effect. In addition recent quality big randomized controlled trials (RCT) for aspirin and ibuprofen showed little to no cancer prevention effect (primary prevention).

 

 

2018: https://www.ncbi.nlm...pubmed/29411204

113.067 participants of the Cancer Prevention Study II Nutrition cohort, got observed for 10 years to investigate CRC – using regular questionnaires for life style and supplement use.

Result: 17% less cancers for users of Glucosamine

 

Weakeness: some curious inconsistencies in study outcome. Those using glucosamine for a shorter time period got a 32% reduction in cancer cases. Those using it for a longer time period only 10%.

 

 

These are (observational) prospective cohort studies. They can give a suggestion for lines of research – i.e. future research on possible causal relationships for interesting correlations. So far for supplement use the strongest correlation is for glucosamine and cancer. Indeed if we look at large cohort studies or reasonably large RCTs there are – to my knowledge – no studies for any other supplement, that indicate a similar strong association for primary cancer prevention in humans.

 

 

There are no RCTs for cancer and glucosamine. But there are different ideas for explanations for the anti-tumor mechanism of glucosamine, that give a potential anti-cancer effect a plausible narrative:

 

A scientist specializing in energy metabolism (co-author of the mice-paper) suggests a connection to mitochondrial metabolism: http://geroscience.c...ristow-part-ii/

It seems that in-vitro and in-vivo results can proof, that glucosamine exposure in commonly consumed human equivalent doses induces mitohormesis, by preventing cells from relying entirely on glucose metabolism.

 

In addition – and maybe related - numerous in-vitro studies find, that glucosamine decreases inflammation (there are a dozend papers on this; a selection of 2) :

https://www.ncbi.nlm...pubmed/18295395

https://www.ncbi.nlm...pubmed/15922948

 

More in-vitro-studies demonstrate, that Glucosamine can upregulate tumor-supressor genes, causing cell cycle arrest and cell death in cancer cells:

 

https://www.ncbi.nlm...les/PMC5450348/

Glucosamine causes cell-cykle arrest in tumor cells (and up-regluated p21 and p53).

 

https://www.ncbi.nlm...-2407-14-31.pdfk

Glucosamine activates AMPK and in parallel inhibits mTOR.

 

https://www.ncbi.nlm...pubmed/28713921

https://www.ncbi.nlm...pubmed/23606170

Glucosamine increases FOXO1/3/AKT activity, by preventing the inactivation of their transcription factors.

 

https://www.ncbi.nlm.nih.gov/pubmed/20045674

Glucosamine induces autophagy via an mTOR-independent pathway.

 

 

Why are these evolving results for Glucosamine relevant?

 

1. Mortality for cardiovascular disease (CVD) can be almost entirely avoided by life style changes and modern medicine (if not for very unlucky genetics). Even with a perfect life style and perfect genetics the risk for cancer is substantial for current typical life spans (estimates range from 20% to 30% of cancer death in developed countries with no known cause).

 

2. Cancer – unlike (CVD) – is not well treatable. For example the 5-year-survival-rate for CRC is only 60%-65%. Many other cancers – especially Lung – don’t even match that.

 

3. Glucosamine is cheap.

 

4. It’s safe from any (proven) serious side effects - for most there are none at all. For a long time it’s very widely used for (ineffective according to research) joint support. The side effects are established. In placebo studies for Glucosamine use for joint support, side effects are indistinguishable from placebo. Concerns for a possible diabetes promoting effect (caused by a study, that bathed pancreatic cells in a glucosamine doses impossible to achieve by oral ingestion) appear unfounded: https://www.ncbi.nlm...les/PMC3042150/

 

5. No other supplement so far demonstrated a remotely similar magnitude of primary cancer prevention in healthy humans:

- RCTs for aspirin show generally no effect for primary prevention – or if so no effect on total mortality (possibly due to it’s side effects). It appears to be useful for secondary prevention once you are treated for cancer.

- Vitamin D in 2 recently released RCTs did not result in primary cancer prevention. But it increased survival rates in existing cancer cases

metformin decreases cancer in diabetics – a group that is at an elevated risk for cancer; the TAME-trial is going to investigate if similar things can be observed in non-diabetics

 

 

Glucosamine is safer to use than aspirin and metformin and it’s got evidence for primary prevention in non-morbid cohorts of humans.

 

So - what are your thoughts? Is it justified to start taking it? At what dose – 500 mg, 1500 mg, 3000 mg a day? The studies – in-vitro and observational – indicate a dose-dependent respone. If anyone uses metformin or aspirin – shouldn't they use glucosamine too, based on the emerging evidence?

 

 

 


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#2 Kimer Med

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Posted 23 January 2019 - 11:37 PM

Thanks for the detailed info and supporting links.

 

Here's a link to an article that covers some of the same issues:

http://www.anti-agin...-for-longevity/

 

Summarizing: On the longevity side, Glucosamine seems to provide a 6% increase in healthspan (average lifespan) for mice, but no increase in maximum lifespan. Human studies seem to show decreased rates of cancer, and it seems to be safe and free from serious side-effects.

 

Based on that info, it's worth considering adding to my regimen.

 

In terms of dosing, the human studies didn't seem to track it. I'm guessing that means most people were taking "recommended" doses, which are on the order of 1.5g/day. I would probably start at a half or a third of that, and titrate my way up.

 

Should we include Chondroitin as well? The interaction with Aspirin and other NSAIDs is interesting here, too.

 


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#3 QuestforLife

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Posted 24 January 2019 - 10:46 AM

If you look into the work of Thomas Seyfried, who has pioneered the metabolic theory of cancer (following on from Linus Pauling), he uses a ketogenic diet to improve the outcome for cancer sufferers, particularly for brain cancer, which has a very poor outcome with little improvement in 100 years of research.

 

His arguments center around the idea that cancer cells arise from damaged mitochondria and hence do not have the metabolic flexibility to run off fats. This probably explains the benefits of glucosamine in preventing cancer. It will not stop cancer completely, as cancer cells can also survive (but not thrive) off glutamine, but in both prevention and even in treatment, will prove very helpful.

 

But this does also mean that a ketogenic diet will be superior to glucosamine, which will only compete with glucose metabolism, rather than replace it completely with fat and ketones.


Edited by QuestforLife, 24 January 2019 - 10:48 AM.

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#4 Guest

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Posted 24 January 2019 - 10:32 PM

I guess it's still too early to derive conclusions about the relative effectiveness of different supplements and diets that show promising results in bio markers and observational studies.

 

For example: https://www.ncbi.nlm...les/PMC3082009/

 

that is the only study so far that investigates the effect of late-onset metformin supplementation in non-diabetic mice. Started at 15 month of age the mice lived actually just a little shorter average lifes than controls. Only early onset metformin supplementation did extend average life spans. On the other hand feeding 100 weeks - about 23,5 month - old mice glucosamine did extend their life span. Nonetheless a lot of funds are invested into metformin studies (most of them in diabetics of course, but also MILES and TAME in healthy humans), and none into glucosamine cancer/lifespan RCTs or just even animal studies.

 

The metformin results are curious, as gluco and met are supposed to activate similar pathways - changing the mitochondrial metabolism away from glucose.

 

I would be more interested in synergistics: does the secondary cancer prevention effect of aspirin add or distract from a potential primary prevention effect of glucosamine? Can gluco, met and NAG be combined to yield additional anti-cancer potency? 


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#5 QuestforLife

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Posted 25 January 2019 - 10:05 AM

 

The metformin results are curious, as gluco and met are supposed to activate similar pathways - changing the mitochondrial metabolism away from glucose.

 

 

 

Metformin inhibits Complex I of the electron transport chain (which is used by fats and glucose); glucosamine does not affect CxI but competes with ALL glucose for metabolism, whether in mitochondria or cytosol.

 

So quite different effects. Metformin has been reported by many to inhibit exercise performance. I would speculate that in the very old with compromised mitochondria, inhibition of Cx I is a bad idea, but in the young/middle aged who eat too much glucose/carbs, it could be beneficial.  



#6 Guest

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Posted 28 January 2019 - 05:34 PM

It seems that's the beauty of Glucosamine: it appears to be well tolerated in older, healthy humans and in older healthy mice - showing considerable positive effects in both animals.

 

I noticed some inconsistencies concerning dosing though:

 

the mice study used a concentration of 10g/kg of glucosamine in the food. No total oral intake of glucosamine is reported, but we can do some calcluation. Mice eat about 3-5 g of standard mouse feed a day. So total intake of gluco was 30 mg to 50 mg a day. The average body mass is around 30 g (see the mouse study). That translates to 1 mg of gluco per gram of body mass. Using direct scaling that is 70 gram of gluco per day for a 70 kg humans. Using allometric scaling

 

https://www.ncbi.nlm...les/PMC4804402/

 

that translates to 5,7 gram per day.

 

 

We know, that there is a dose depended response in humans. "Frequent intake" as opposed to "occasional" lead to a roughly doubling of the cancer prevention effect. The most common daily (i.e. frequent) dose of glucosamine is 1.5 g . That's below the mouse equivalent intake of 5,7 g. Also there certainly is a dose-dependend effect in mice as well, though it's unclear if more would have been better or not.

 

So: is the effect going to be even more pronounced at a daily intake of 4,5 g (3 pills of 1,5 g a day)? Is that a safe dose for humans (I'd assume yes, given the lack of evidence for side effects so far)?

 

 

EDIT:

to correct an oversight of mine - in the initial topic starter post I'm typing 13% reduced total mortality for gluco/chon. That should have read 17% reduced total mortality. 38%-49% reduced total mortality after adjusting for NSAID use is still correct though.


Edited by Guest, 28 January 2019 - 06:31 PM.

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#7 Daniel Cooper

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Posted 20 February 2019 - 01:37 AM

Back in the 1950s there were a few doctors reporting success in using glucosamine to treat cardiovascular disease.  If it indeed induces autophagy that's not so far fetched.

 

 

 


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#8 Guest

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Posted 13 March 2019 - 09:04 PM

Update:

 

As I wrote in January, the most recent study did find a confusing result - short term use of glucosamine was associated with better anti-cancer effects than long-term use. The free version of that paper is available as of now:

https://www.ncbi.nlm...les/PMC5870876/

 

After some sensitivity analysis, the authors found, that if correcting for previous or current cancer-screening, the association vanished. This result is statistically non-significant though, as the number of non-screened participants did not allow to create a good-enough confidence interval.



#9 Guest

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Posted 21 May 2019 - 04:10 PM

After some additional research on the topic I found something astonishing:

 

there was an active research literature on the use of Glucosamine against cancer in the 1960s and early 1970s. This research appears to be completely forgotten - at least the modern Glucosamine and cancer studies examined in the introduction of this subforum do not reference any of these old studies.

 

Back in the day people were experimenting with mice and rats, administering various dosages of Glucosamine in cancer animals. The unanimous result is, that glucosamine supresses cancer growth in-vivo. The most impressive study I found is this one from 1972 at the University of Chicago:

 

http://cancerres.aac.../4/756.full.pdf

 
a couple of rats (2 controls, 2 18-hour-infusion, 2 40-hour-infusion, 2 40-hour-infusion+5-days) were infused continuously with Glucosamine, just as you would do using chemotherapy, after a tumor was transplanted.
 
After 40 hours of infusing glucosamine and a 5 day reaction time the examined tissue showed interesting changes:
 
- the entire tumor tissue was necrotic - i.e. dead; no more cancer
 
- the liver and kidney tissue showed no relevant changes; i.e. no toxicity of the glucosamine in the organism (unlike your common chemotherapy)
 

 

In addition they noted after administering the glucosamine: "[...]many large, swollen mitochondria and numerous, large, autophagic vacuoles" - in other terms: suddenly autophagy is on overdrive. As I explained here:

 

https://www.longecit...-for-autophagy/

 

there is some evidence, that glucosamine drives autophagy and that this might be connected to the potential anti-tumor effects.

 

 

 

This study has only 5 citations in pubmed and many of the others referenced in this study have none (some of them aren't even available online). For example there's this study from 1980:

https://www.ncbi.nlm...cles/PMC348447/

that tries to explain, why glucosamine is toxic for cancer cells, but non-toxic for all other cell-types in-vivo. But nothing else in terms of follow up.

 

 

What happened? That looks like a better chemotherapy drug than many used today with their horrible side-effects. Those started out as test in rats, too. Why did everyone forget about this literature and did not investigate further?

 

Ironically at the same time (1970s) "alternative medicine" started to promote glusocamine for joint support based on no evidence at all. Without that, there would be no evidence published today, about it's anti-tumor activity (see the studies at the start). And I would not have found this "forgotten" literature.


Edited by Guest, 21 May 2019 - 04:13 PM.

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#10 William Sterog

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Posted 21 May 2019 - 05:11 PM

This is extremely interesting.

#11 Florin

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Posted 24 November 2019 - 03:24 AM

As I mentioned in a supplement stack thread, an analysis of the NHS and HPFS studies claims that glucosamine + chondroitin reduces CRC risk but not glucosamine without chondroitin.

 

Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study.
https://www.ncbi.nlm...pubmed/27357024


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#12 Florin

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Posted 29 July 2020 - 02:39 AM

This study claims that glucosamine use reduces all-cause mortality by 15% but cancer mortality by only a measly 6%. The study also controlled for chondroitin use and is the first to do so, as far as I recall.
 
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.


Edited by Florin, 29 July 2020 - 03:23 AM.


#13 Phoebus

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Posted 10 May 2021 - 01:18 AM

 

 

His arguments center around the idea that cancer cells arise from damaged mitochondria and hence do not have the metabolic flexibility to run off fats. This probably explains the benefits of glucosamine in preventing cancer. It will not stop cancer completely, as cancer cells can also survive (but not thrive) off glutamine, but in both prevention and even in treatment, will prove very helpful.

 

 

 

Latest research shows this is not the case unfortunately (the keto crowd)

 

https://www.technolo...the-body-321879

 

Cancer Cells Switch Sugar for Fatty Acids to Spread Around the Body

 

 

Scientists have uncovered a crucial change in cancer cells that allows them to spread around the body – by switching from sugar to fatty acids to fuel their growth.

Changing their ‘diet’ in this way allows tumour cells to set up shop at new sites where resources such as glucose – their preferred food source – are limited.

Researchers at The Institute of Cancer Research, London, found that a protein called AKR1B10 helps cells adapt the ways in which they get their energy.

When cancer cells have high levels of AKR1B10, it reduces their dependency on sugar and increases their ability to use fatty acids as a fuel source instead.

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#14 QuestforLife

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Posted 10 May 2021 - 10:14 AM

 

Latest research shows this is not the case unfortunately (the keto crowd)

 

https://www.technolo...the-body-321879

 

Cancer Cells Switch Sugar for Fatty Acids to Spread Around the Body

 

 

I guess it is not suprising that cancer cells can adapt to almost anything, even burning fatty acids. Interesting that the protein used reduces ROS to achieve this. 

 

I think if I got cancer I probably would still go low carb, as not all cancer cells are going to be adapted in this way, and the original cancer would need to reach a certain size before it spreads and therefore would still need glucose. 


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