Glucosamine significantly reduces risk of lung cancer and lung cancer mortality

https://erj.ersjournals.com/content/59/3/2101399

by birriel • 4 years ago

161 107 4 years ago

erj.ersjournals.com

abcc82• 4 years ago

Interesting study, but it needs replication. A 15% reduction in cancer incidence is a rather large reduction, assuming this result is replicated in a different, ideally non-European cohort.

dudus• 4 years ago

It had almost half a million subjects. Isn't that enough replication?

abcc82• 4 years ago

It isn't the most diverse cohort so a body such as the WHO might or might not choose to make recommendations based on this single finding.

rootusrootus• 4 years ago

Shouldn't we want replication even if the sample size seems large, to rule out experimental errors or other flaws in the work?

refurb• 4 years ago

This is true. That’s a very large effect.

But as others have stated it’s observational, not an interventional study. Thus less rigorous.

jugg1es• 4 years ago

I love when you see such a huge study yield significant results.

jcoq• 4 years ago

There have been other studies with similar results but the main drawback of these population analyses is that glucosamine use is more likely in people with healthy lifestyles.

Other supplements have shown benefits in these sorts of studies without standing up to more exacting experiment design.

So potentially interesting results but nothing worth getting invested in.

DantesKite3• 4 years ago

It would be cool if someone made a dashboard of studies complete with their listed interventions to find out which were the most effective for preventing cancer and reducing cancer mortality.

uncomputation• 4 years ago

examine.com has a lot of good studies referenced.

ttrmw• 4 years ago

Not quite what you asked for, but this is a nice resource for at a glance assessment of supplements:

https://www.informationisbeautiful.net/visualizations/snake-...

DantesKite3• 4 years ago

This is great. Thank you very much for the recommendation.

phendrenad2• 4 years ago

According to a google search, "the only natural food sources are shellfish shells from shrimp, lobster and crabs". So I wonder if you can see a significant effect in people who eat a lot of shrimp.

TaylorAlexander2• 4 years ago

Well if it is truly only in the shells, then probably not!

MengerSponge• 4 years ago

A lot of shrimp recipes have you cook the shells in oil for extra flavor. This one is a personal favorite:

https://www.seriouseats.com/spanish-style-garlic-shrimp-gamb...

Seriously. Get some good shrimp, some garlic, and go to town on some crusty bread. It's one of the recipes I'd still eat even if it took time off my life, it's just so damn good.

pcthrowaway• 4 years ago

Interesting, I'm vegan and the glucosamine I've ordered has claimed to be sourced from a fungus. Perhaps the fungus isn't edible (hence, it's not a natural food source)

MaximumYComb• 4 years ago

The fungus probably isn't normally eaten. Shrimp shells aren't exactly a treat.

KennyBlanken• 4 years ago

I find it difficult to believe that it has "significant" health benefits. Glucosamine has never shown significant health benefits, only minor ones: https://examine.com/supplements/glucosamine/

I find it extremely difficult to trust an all-Chinese research team on a substance heavily used in "traditional chinese medicine", for two reasons:

"TCM" is the invention of Mao, who needed to look like he was doing something to provide medical care for billions: https://slate.com/technology/2013/10/traditional-chinese-med...

...and the CCP has been pushing it very heavily: https://www.economist.com/leaders/2017/08/31/china-is-rampin...

Or more simply put, it's utter tripe that was passed off to peasants to keep them from rioting over having essentially no healthcare system.

culi3• 4 years ago

Glucosamine has never shown significant health benefits, only minor ones

... This is a bit of a ridiculous argument to make when looking at the data. First of all, they only have 8 categories, only 2 of which have more than 2 studies cited. Second of all, imagine if you only studied the effects of aspirin on addiction. I'm assuming you'd find little to no effect. And if Examine had a list of addiction-related effects you'd also be like "look aspirin is weak, how can it suddenly be strong?". The listed effects on examine all have to do with pain relief which likely has little in common with the mechanism of action for lung cancer

I find it extremely difficult to trust an all-Chinese research team

This is published in a (European) journal with an H-index of 255.[0] The journal is reputable so are you just asserting you can't trust Chinese scientists to study ingredients used in TCM?

"TCM" is the invention of Mao

This is very false. Even the article you link only says Mao "heavily invested" in it. You know who else is heavily investing in traditional medicine? The World Health Organization. Which currently has a decades long plan to support and fund and increase the role that complementary medicines play in non-industrialized countries[1][2]

[0] https://www.scimagojr.com/journalsearch.php?q=18458&tip=sid&...

[1] https://www.who.int/health-topics/traditional-complementary-...

[2] https://www.who.int/publications/i/item/9789241506096

Chris20482• 4 years ago

You know who else is heavily investing in traditional medicine? The World Health Organization

That's not the best argument if you are trying to debunk CCP conspiracies: https://www.bbc.com/news/world-asia-52088167

koboll• 4 years ago

Why exactly does glucosamine only having a minor effect on pain, collagen degradation, joint function, etc. preclude it from having an effect on cancer outcomes?

Obviously this should be replicated and if not replicable, should be dismissed. But it's perplexing to dismiss it out of hand because its effects weren't strong enough for an array of other totally unrelated health outcomes.

phkahler2• 4 years ago

Not sure you should reject TCM categorically. That's where we got statins from. You dont even need an Rx to lower cholesterol, just use red yeast rice - works a charm and even has the same side effects.

lvturner2• 4 years ago

And a in part a leukemia treatment, https://en.wikipedia.org/wiki/Arsenic_trioxide

and ephedrine..

I don't put much stock in the reasons behind why a lot of TCM works, but dismissing the whole thing out of hand is folly, because essentially you are saying plants have no medicinal value and massage is a waste of time.

I would push for more scientific rigour within TCM to come up with better models of why some of this stuff works instead, which to the best of my understanding isn't even a particularly controversial statement in many TCM circles.

grumple• 4 years ago

Source for TCM playing a role in statin development? https://en.wikipedia.org/wiki/Discovery_and_development_of_s...

lovemenot• 4 years ago

artemisinin against malaria too

civilized• 4 years ago

https://www.tylervigen.com/spurious-correlations

tirwander• 4 years ago

Murders By Steam....

Gatsky3• 4 years ago

These results from observational studies almost never replicate in randomized studies. It's because people who decide to take glucosamine (or not) also do lots of other confounding things, like visit the doctor more, or have higher salaries, or don't live with people who smoke etc. It's been shown many times you can't really adjust for these things. Epidemiologists love doing these studies, because they are comparatively easy. The hardest part is the data sharing agreement with whatever registry you are using. You don't even need to leave your desk to collect any data.

mrfusion• 4 years ago

Good advice in general but it’s worth reading to see what confounders they tried to correct for. There’s still information to be gleaned.

This part caught my eye:

A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history.

SoftTalker• 4 years ago

A family history of lung cancer could simply mean a family history of smoking, which was much more common a few generations ago than it is today.

adtac• 4 years ago

The real question is: why is anything other than randomised studies allowed to be published in the first place?

derbOac• 4 years ago

Not questioning the need for RCTs, but they have their own issues. Like, let's say you do a RCT and it shows an effect, but then in a large epi observational study there isn't any? There would be some problems to work out.

RCTs are great but can have problems with generalizability to real-world conditions. Ideally you'd study both.

Gatsky3• 4 years ago

I guess it's ok to publish uninteresting and probably false things. This could be a fairly accurate description of biomedical science to be honest. It's annoying when it ends up on HN for example, or in the health section of a tabloid newspaper.

In theory, these observational findings could suggest treatments that should be evaluated in a randomised trial. I am not actually sure this is true however, it is possible they are less useful than selecting interventions for further testing in some other way. Anecdotally, folk remedies may have a higher hit rate for selecting treatments for proper evaluation. This is often surprising - eg a precursor to aspirin is found in the Willow tree, which has been used as a medicine for thousands of years. Another example is the foxglove plant from which the heart drug digoxin is derived, which was used as a herbal medicine predating modern medicine.

yCombLinks• 4 years ago

Observational studies are far cheaper and easier, and are actually very useful for a lot of situations.

WalterSear2• 4 years ago

Published, or publicized?

All science needs to be published. Pilot studies, observational studies, quasi-experimental studies. Otherwise, we don't have the information we need to create randomized control trials.

However, I'd strongly support keeping all that science from being publicized.

dragonwriter• 4 years ago

The real question is: why is anything other than randomised studies allowed to be published in the first place?

Because things other than randomized studies produce the results that generate the funding for randomized studies.

jryb• 4 years ago

One answer: anyone can start a journal, there are no laws or standards. Peer reviewers are busy and don't always have the background to criticize every aspect of a paper.

Another: not all research can or should have randomized studies (like it just wouldn't make sense if you were, say, determining the structure of a protein). So drawing the line as to what does and doesn't need a specific approach is blurry, and really, can only be enforced during the peer review process, or by the editor.

On the other hand, this kind of work can still serve as a hypothesis generator. Someone else will read this, think, "well they did this all wrong!" and perform a better study that clearly demonstrates whether it has an effect or not.

gnicholas• 4 years ago

This is a good point. I was recently having a conversation with a non-scientist (I am not one either) about two different studies. One was an RCT that found no effect for a treatment, and the other was a "case control, test-negative" design study that found a beneficial effect. My friend said the latter was as good as an RCT because it also has a control arm.

But when I looked up what "case control, test-negative" means, I found that it is observational, and there is no intervention provided to any of the individuals. Some of the recent discussions of the design indicate that it is understood by scientists, but can mislead laypeople, who assume that its conclusions are much more robust than they actually are.

We should definitely continue to do research of many types, partly as a way to figure out where to spend the time/money to do RCTs (which are more expensive than other types of analysis). But we need people reporting on studies to be very clear up-front when they are not describing an RCT. They should say what the study's conclusion means, versus what it would mean if there were a similar 'finding' in an RCT. Otherwise people will not understand that they are being told a weak conclusion, not realizing there is a strong conclusion that has gone unmentioned.

gumby2• 4 years ago

Not everything can be done with a randomized controlled study. For some fields (quantum mechanics, volcanology, climate change, paleontology...) most studies can't be randomized, much less blind. This is also true of longitudinal studies: you can't fully control anyone's exercise and diet over months, much less decades.

Yet we want to do research in these areas. So we have to make do with what's possible.

Rastonbury• 4 years ago

Because academics and primary consumers of these studies understand their uses and limitations. Not all science has to be groundbreaking new discoveries, simply trying to replicate an existing study or exact same methodology on different cohort is perfectly fine.

The problem is when it gets printed in mainstream press who sensationalize and then posted to reddit/hn where people go 'duh this is obvious, this is a dumb thing to study', 'sample too small', 'not controlling for income/confounding'.

astrange• 4 years ago

You can't do randomized studies for things like nutrition if the question is "does eating red meat for a decade increase the risk of cancer". Nobody's going to comply with it.

fellow_human2• 4 years ago

With all the common sense replies explaining why, I guess this was not the real question at all.

dukeofdoom4• 4 years ago

I agree with that. You can see this in Ontario COVID statistics.

People that did not take the vaccine, despite all the pressure, tend to be healthier as population. They kind of self selected by being self confident in their health and not worrying about dying from COVID. The triple vaccinated in Ontario are now the highest risk of getting COVID. They too self selected, by tending to be older with pre existing health problems, and worried enough to get boosters.

https://covid-19.ontario.ca/data?fbclid=1

ImPostingOnHN2• 4 years ago

does that include the people who died after not taking the vaccine?

asking because you only linked to the homepage of a general data portal which itself reports its no longer being updated,

versus to a study supporting what you're saying

ramraj07• 4 years ago

You are right that people who take vaccines and who do not probably bifurcate along other lines as well. But you’re doing everything even more of a disservice by speculating the dimensions as if it’s established fact. Maybe the unvaccinated aren’t healthier they’re just liars? Also any self respecting study would control for the simple demographics like age so your hypothesis would be quite moot if the study was done with any rigor.

triceratops2• 4 years ago

The triple vaccinated in Ontario are now the highest risk of getting COVID

I don't understand how the source you shared supports this claim*. If anything, it shows the opposite - you're at far higher risk of death if you're unvaccinated. And that's after considering the fact that unvaccinated people are likely to be younger and fitter.

The unvaccinated have, at best, half as many deaths per 100k as those who are fully vaccinated + booster (in reality, the two lines mostly track each other). Which sounds good, until you realize that the unvaccinated make up only 9% of the population. 33% of the deaths coming from 9% of the population - healthier, they are not. Delusional, would be more correct.

* I'm assuming "getting COVID" here means "having serious consequences from an infection" as opposed to merely being infected. The vaccinated make up the vast majority of the population, so it's obvious that they are also at the highest risk of being infected by COVID. There are very few unvaccinated people left for the virus to infect.

vcdimension3• 4 years ago

Actually, you're wrong about that. According to this Cochrane systematic review, RCT's and observational studies are usually in close agreement: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.MR...

rich_sasha• 4 years ago

Hmm, that would be interesting, except it seems they only considered 14 studies. They find in 11 of these observational studies match the results of RCTs.

Im sure this will be different in areas where there is no public awareness of a risk factor vs ones where there are. Eg healthy diets select for people who care about their health, so it's not so infomative, vs something where the link is not publicly known (so that the observational study is already somewhat blind/randomized).

Gatsky3• 4 years ago

Well no, I’m not wrong. That article you linked is a review of reviews comparing RCTs and observational studies for medical interventions, primarily surgical studies or pharmacological treatments with well characterised effects. Observational studies of supplements and nutritional interventions on the other hand have a very poor track record of RCT validation.

gojomo2• 4 years ago

Such a review is necessarily limited to topics which have both an RCT and an observational study.

As such, the general bias against publishing non-significant results could mean the conditions for being able to even try such a review risk biasing the review towards exaggerating agreement.

(It also seems the Cochrane review here may itself only be considering other reviews - a metameta analysis of sorts – which might also be influenced by a selection bias, if there’s any chance at all that researchers choosing work, & then publication decisions, prefer to address questions where there’s more agreement, rather than less-attention-catching mixed results.)

The most convincing evidence here would be how strongly preregistered RCT results, whether ever published or not, tend to match earlier observational studies. It doesn’t appear to me that this Cochrane review is focused on that.

stoorafa• 4 years ago

You’re right that there is non-random allocation to the exposure (taking glucosamine), but this is something that can be addressed to an extent with a bit of statistics.

I was disappointed to see the authors didn’t take the additional step of doing propensity score matching or weighting to account for propensity to take glucosamine.

Here’s a good reference about propensity score matching: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144483/

JoelMcCracken2• 4 years ago

I wonder, does anyone know of a good guide for lay persons that explains how to understand scientific studies?

Even something that details the difference between a population study and randomized controlled trials.

Jedd• 4 years ago

Ben Goldacre's book 'Bad Pharma' has a good discussion around this, especially in terms of caveats and gotchas to watch out for with such studies.

It might be more 'lay person' than you are looking for, but it's an excellent read for myriad other reasons, so you wouldn't be wasting your time (IMO).

jnwatson• 4 years ago

Interesting. I‘ve been taking a glucosamine supplement for several years since I saw a study that correlates it with overall reduced mortality.

thebigspacefuck• 4 years ago

Me too. I’m still here!

lvturner2• 4 years ago

Confirmation bias?

throwaway2902• 4 years ago

Perhaps the causality here is that if you care about reducing own mortality, then your general course is action ends up reducing your mortality. It would be difficult to tell if it's glucosamine that's the cause, or some other thing a person of the kind that takes glucosamine would do (or all of such things in combination).

Spooky23• 4 years ago

I can’t speak for people, but I did notice meaningful improvement in my dog’s joint pain when we provided glucosamine supplements.

Inflammation is correlated with many conditions, so I would not be surprised to see other correlations, or that it was combined with other inflammation reducing agents.

mellavora• 4 years ago

I was taking it, but then I died

ck2• 4 years ago

If you are allergic to shellfish you are going to have a fun time finding out with conventional glucosamine.

Note there is a version made from corn but more expensive and you have to look for it (I think it's called "GreenGrown"). I think it's chemically identical?

clumsysmurf• 4 years ago

The problem with glucosamine is that it reliably increases intraocular pressure.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350357/

agumonkey• 4 years ago

Is there research to engineer ways so that we can use blood as delivery only in some areas ? I know it sounds stupid but maybe toying with timings so that chemicals never live long enough to reach upper body / brain ? or maybe microcapsules that only dissolve in certain biological environment ?

db65edfc7996• 4 years ago

Specifically targeting compounds is an active area of research. Example: all oncotherapies are essentially just poison. The trick is to deliver the toxin to the 0.001% of cells in the body that are cancerous.

It is amusing you should say ways that avoid reaching the brain. The blood-brain barrier impedes a large number of therapeutics from entering the brain. It is incredibly difficult to engineer the constraints of something that: is potent enough to have an effect, can survive in the blood, cross into the brain, targets the cells of interest, has a meaningful half-life, does not decompose into something toxic, etc.

voisin• 4 years ago

Does it raise it enough to cause issues? What are the issues associated with increased pressure?

manceraio• 4 years ago

Increases the risk of glaucoma.

https://www.nei.nih.gov/learn-about-eye-health/eye-condition....

aaaaaaaaaaab• 4 years ago

Literally the first Google result for "eye pressure" is about glaucoma. So go figure.

pseudoramble• 4 years ago

I'm unfamiliar with glucosamine aside from the quick search and comments I read now. Neat that they see a correlation, but are there any theories about why this would be the case? Do the lungs use glucosamine somehow?

telecuda• 4 years ago

Related, glucosamine treats had a quick positive impact on the mobility of my aging dog. I recommend these: https://stratfordrx.com/products/max-strength-joint-support-...

bottled_poe• 4 years ago

Anecdotal, but I had a conversation about smoking with a med science professor many years ago. He said something along the lines of “as long as you don’t eat seafood your risk is low”. I was baffled.. looks like there is some truth to it.

copperx• 4 years ago

The risk of what is low?

jacobmischka• 4 years ago

Based on the title and reference to smoking, I imagine he means the risk of lung cancer.

Galaxity• 4 years ago

Seafood is a main source of glucosamine so shouldn't it be "as long as you DO eat seafood your risk is low"?

hirenj2• 4 years ago

Glucosamine is both a precursor metabolite and major component of complex carbohydrates in the cell.

Glucosamine (GlcN) gets acetylated to form GlcNAc, which is found in pretty much all the complex carbohydrate types in humans. It’s also the main component of the chitin shells on our insect/crustacean friends.

You can also find GlcN in glycosaminoglycans (GAGs), in heparan sulfates (transformed from GlcNAc to an N-sulfated GlcN by the NDSTs) as a prerequisite for further sulfation. The pattern of sulfation on these sugars is important for determining the bioactivity and interactions for each of the GAGs. For example, the sulfation pattern on heprarin is important to tune to avoid HITT while still maintaining anticoagulant activity.

DantesKite3• 4 years ago

Any concerns about glucosamine raising eye pressure? And also, if NAG is a component of GAGs, doesn’t that mean taking an NAG supplement could contribute towards increased ocular pressure as well?

Or are the chemical pathways in the body too dissimilar for that to happen?

hirenj2• 4 years ago

If there’s a connection, it might be via hyaluronan, another glycan polymer, which is abundant in the vitreous humor in the eye. I don’t know much about how it’s regulated.

Generally, I don’t think we know enough about how metabolite levels translate to specific complex carb levels because there’s a relatively complex set of intermediate steps which themselves can be regulated.

AlexanderNull• 4 years ago

This is hardly the first time that Glucosamine use is associated with lower cancer/mortality risks:

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

https://pubmed.ncbi.nlm.nih.gov/33219063/ - Glucosamine/Chondroitin and Mortality in a US NHANES Cohort

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175750/ - Use of Glucosamine and Chondroitin and Lung Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870876/ - Glucosamine Use and Risk of Colorectal Cancer: Results from the Cancer Prevention Study II Nutrition Cohort

https://cancerci.biomedcentral.com/articles/10.1186/1475-286... - Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling (in vitro)

https://www.pharmacytoday.org/article/S1042-0991(17)30735-1/... - Glucosamine and chondroitin decrease colorectal cancer risk

Some of those still showed significant correlation even when accounting for NSAID use however there have been other studies where the correlation significance disappears when accounting for NSAIDs: https://www.nature.com/articles/s41598-018-20349-6

Mortality reduction with glucosamine has been directly shown in more controlled studies on other organisms such as nematodes and mice, but may do so through a path that hasn't been shown to work in humans: https://www.nature.com/articles/ncomms4563

And in an actual double blind study glucosamine (+ chondroitin) use was found to lower serum levels of C-reactive protein in men and women: https://journals.plos.org/plosone/article?id=10.1371/journal... (small sample size)

fellow_human2• 4 years ago

Glucosamine is taken a lot by runners as its promoted as a suppliment that helps cartilidge in the knees. Runners are unlikely to be current smokers and more likely to be working their lungs in a healhty way.

Glucosamine significantly reduces risk of lung cancer and lung cancer mortality

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