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Glucosamine Supplementation Reduces All-Cause Mortality: Study (lifespan.io)
279 points by mrfusion 14 days ago | hide | past | favorite | 148 comments



If you are interested in digging into this stuff, and what really works medically/scientifically based on reviewed evidence and sources such as Cochrane Reviews, I can't recommend Dr Stanfields youtube channel high enough: https://www.youtube.com/c/DrBradStanfield/videos

Also here is his video on Sulforaphane which Glucosamine activates. He goes into detail as to how this mechanism works. Because of his video/latest research presented I changed to taking Broccomax because you need Myrosinase to actvite the SGS for it's full effect, he goes into detail on this here: https://www.youtube.com/watch?v=qAb1eQbRAe0

Cochrane Review he uses as his primary source: https://www.cochrane.org/CD007176/LIVER_antioxidant-suppleme...


Interesting, I've just used examine.com in the past. It's pretty reliable/decent and lower friction than a YT channel. Here is what Examine has on Glucosamine:

https://examine.com/supplements/glucosamine/


Is a Cochrane review really a primary source? They're meta-analysis, which I'd think of as secondary.

In the case linked, the analysis seems pretty unequivocally to not support supplementing:

"We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing."

Did I miss something?


The op talks about sulforaphane but then links to an article about vitamin a and e(I don't know why) They're totally different chemicals that work through completely different pathways.

And a study on vitamin a and e etc doesn't tell you much about other supplements. Just like how a study on does whether or not statins are associated with reduced mortality tells you little about whether or not ACE inhibitors are associated with reduced mortality.

Also I don't think op meant primary source as in primary vs secondary sources but meant in the sense of "this doctor primarily uses Cochrane as his source for information"


Vitamin E research also ends up being a bit YMMV: most commercially available Vitamin E is one form only, alpha tocopherol... except Vit E is 8 different forms: 4 tocopherols and 4 tocotrienols.

The research that has been done so far basically indicates alpha tocopherol-only supplementation aligns identically with unspecified-Vitamin-E-is-bad research.


Thank you for a very curious channel, I'm going to watch it all. Why does the doctor look so weird anyway? I mean his eyes - sort of a crazy gaze. Isn't he blind or something? Or is that an effect of a medication he takes?


This is a video where he uses natural light and his eyes look normal. It is just bad lighting. https://www.youtube.com/watch?v=5kzaj-_vr1w


he seems to never blink

Do you take Broccomax in addition to standard Glucosamine supplements? Or is Broccomax by itself sufficient?


Glucosamine supplementation looked decidedly unimpressive a decade ago and I don’t imagine anything has changed since.

https://sciencebasedmedicine.org/?s=glucosamine

Still, I took a look at Dr Stanfield’s youtube channel (because nothing says “primary source” like a YT link):

    As a side note, here's all the supplements I currently take (affiliate links):
    WAKE UP:
    • Sulforaphane 8mg ( https://amzn.to/… )
    • Niacin 50-500mg ( https://amzn.to/… ) - start low to help with flushing
    WORKOUT:
    • Creatine 2.5g before & after ( https://amzn.to/… )
    BREAKFAST:
    • Vitamin K2 MK-7 90μg ( https://amzn.to/… )
    • Vitamin D3 3,000 IU ( https://amzn.to/… )
    • Omega-3 (DHA/EPA) two capsules ( https://amzn.to/… )
    • Trans-Resveratrol 500mg ( https://amzn.to/… or https://cntr.click/… )
    • Pterostilbene 150mg ( https://amzn.to/… )
    • Collagen 10g ( https://amzn.to/… )
    LUNCH:
    • Niacin 50-500mg ( https://amzn.to/… )
    • Trimethylglycine (TMG) 750mg ( https://amzn.to/… or https://cntr.click/… )
    NIGHT (one hour before sleeping):
    • Metformin 1 gram (only on non-workout days)
    • Melatonin 500mcg ( https://amzn.to/… )
    • Magnesium Taurate 125mg ( https://amzn.to/… )
    ONCE I can afford it (will take in the morning):
    • Nicotinamide Mononucleotide (NMN) 1 gram ( https://amzn.to/… or https://cntr.click/… )
Yeah, no. Oversold supplements for the neurotic well are a longtime health grift. 1PPM of actual science and medicine, diluted in 999,999PPM of ego-pampering, holy-rolling religion, and wishful anti-aging crap.

BTW, here’s what your own Cochrane link says, which suggests you didn’t even bother to read it yourself:

“The current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases.”

IANAD, but I advise you apply some skepticism to that burn ASAP.


The paper this is based on, which might be a better link: https://ard.bmj.com/content/79/6/829


The study says the participants were 62% female, overwhelmingly ate more vegetables and supplements, exercised more than the control group, were mostly white, as well as self reported glucosamine supplementation - without dosage information. Overall it might be more indicative of wealth, education, and fitness than the effect of glucosamine. The paper itself says it’s not able to differentiate the effect from lifestyle changes:

> Third, regular glucosamine use may be a marker for a healthy lifestyle, but it is hard to distinguish the confounding effects of a healthy lifestyle from the impact of regular supplementations in an observational study. Although we had carefully adjusted for potential confounding lifestyle-related factors in our analyses, we could not exclude the possibility that the results were confounded by unmeasured lifestyle-related factors. In general, with the current observational study design the possibility of residual confounding due to imprecise measurements or unknown factors cannot be excluded for all findings in our study, despite our careful adjustment of all measured confounders.


The confounders are, as you point out, incredible.


The last time I did googling on efficiency of glucosamine (several years ago, to combat runner's knee) I only found clinical trials sponsored by companies which produce glucosamine. Who's sponsoring this study?

That is possible but the large sample size may help. The study involved roughly a half million people with around one hundred thousand supplementing with glucosamine. With that many people and these big numbers the results are rather strong.


Sampling addresses variance, not confounding factors.

If the sample is not representative of the broader population, then in no way will any amount of sampling correct that error.

Observational studies often involve quite large samples, but they remain unreliable because it is extremely difficult to address all possible confounding factors. Experimental intervention is the gold standard for a reason, and absent the ethical or practical impossibility of experimentation, should be used here.


In large studies, both true causal and true non-causal associations get stronger -- size gives no protection from confounding.


I've been supplementing glucosamine along with a large amount of other things for awhile now. I'm not too bullish on it in humans, but it doesn't seem like it hurts, and is definitely cheap: https://nearcyan.com/supplements

My latest favorites that I'm a bit more hopeful for are glycine, spermadine, and rapamycin.


On Rapamycin: "The known adverse effects caused by sirolimus and marketed analogs at the doses used in transplant regimens, especially the increased risk of infection due to immunosuppression, as well as dose-dependent metabolic impairment, make it unlikely that chronic, long-term treatment with sirolimus could become a widely used anti-aging agent."

Sounds more than a little dangerous, unless you have an illnes like Lupus that activates mTOR, and even then I'd be nervous taking this drug without expert medical supervision!

On the upside, my partner has a Lupus-like autoimmune disease, so this drug will be an interesting one to track.


Yeah, I have it in a different section on my page mostly for that reason. It's not something I'd ever encourage people to 'just take', in the way I might some simple vitamins or minerals or so on that they might need.

Personally, I do think it can likely be taken pretty safely if monitored reasonably, and I am pretty hopeful for it as well. But it's true it's a serious drug so it shouldn't be messed around with as if it's a game.


Interesting you take rapamycin and a bunch of other stuff thats supposed to extend lifespan. I wish to see if you live longer but I'll probably die first lol.

Serious questions: have you experimented with calorie restriction? Clearly thats THE method that works in every species. Second question: do you battle with depression? My current hypothesis is that any life extending drug will also inevitably lead to depression given the links shown between the sirt1 pathway and depression (also potentially as an evolutionary check but that's just me throwing ideas out).


Yes, I generally have been doing quite a bit of intermittent fasting, fasting, and caloric restriction. But not very strictly so, only sometimes.

I have before, but I would say it's not too bad right now.


Interesting. I'll keep following you to see how things progress!

How are you getting rapamycin?

I'm interested in it's benefits for autoimmune diseases but it seems quite expensive (in the US).


Some doctors will prescribe it for off-label use, but this is pretty rare. It's possible to purchase it from overseas websites as it is not scheduled, but this is technically not legal, and it will still cost quite a bit out-of-pocket. With that said, it can definitely be potentially dangerous, and dosing+frequency would have to carefully be paid attention to, as well as monitoring results via blood tests imo, and having done extensive research and so on. I wouldn't suggest anyone just purchases it to experiment with it without being very careful and having a high appetite for risk. But other things like glycine or spermadine or vitamin D or magnesium I'm much happier to gleefully suggest to people.


Any other advice for folks? What do you think of NR?


I personally don't buy that NR does much. I think there's some interesting hints that we're getting close to finding out useful things, but I haven't found much that personally convinced me about NR and those related to it. Agree with what I hear on podcasts like Peter Attia about it, but I think maybe some day soon we'll find something promising in that area.

It's a hard area to give advice in since everyone is different, so I can't really offer much besides that I think for the best return, someone has to spend a lot of time doing their own research and testing and so on to find out what works for them


Do you take each Vitamin individually, or do you take a multivitamin?

Do you make an effort to get large doses of these things from food first?


Individually. Sometimes a few things are combined when a good option is available, but generally multivitamins don't give me what I want in the doses that I want.

Since I tested all of my blood metrics beforehand, it's unlikely the market would have a 'perfect' vitamin for me. Especially since most of what I like to take isn't technically a vitamin.

My diet is currently pretty un-optimized, so although I would prefer to consume a lot of things via diet, it's not guaranteed at all. But the extra bio-availability and such is likely nice


Id be curious what it would look like if you tested your blood now, stopped taking them all, and radically modified your died, what kind of results you would get in a couple weeks.

Daily intake of, tomato juice, kefir, sardines, salmon, spinach, sunflower seeds, pumpkin seeds, pistachio, eggs. You could probably get a whole days worth of food into a snack, a salad, and a soup.


I wish it was easier to do intensive tracking of everything like that, but it's definitely a lot of work. Some supplements I have very clear before+after results, with the only probable cause being the supplement (e.g. vitamin D or magnesium), but a lot of others are hard to test, control for, find biomarkers for, etc.

I do know there are a few people in the area that log literally every substance they eat in terms of grams, and then correlate it with all of their blood metrics, and use that to try to optimize each blood metric for what correlates with the lowest mortality rate. It's interesting, but this stuff is unfortunately a lot of work for average people to attempt. Here's a great example: https://twitter.com/Nearcyan/status/1282042301980835842


I wonder why we need to supplement glucosamine (e.g. to treat arthritis) when it is synthesised by the body from glucose in one of our basic metabolic pathways. I could only imagine this becomes a problem unless a) the enzymes responsible stop working or b) if the glucose gets shunted off to some other purpose.

It’s also funny that chondroitin supplementation does the job too, because it actually contains no glucosamine, but contains monosaccharides that are derived from glucosamine (N-acetyl Galactosamine).

I think there’s probably a very interesting answer to these metabolic questions that could shed a lot of light onto the phenotypes of aging. That said, I don’t know what evidence is out there for systemic lack of e.g. glycosaminoglycans in aged populations, or even in arthritic cohorts.


In absence of good, hard, scientific evidence of effects above and beyond placebo, I’m gonna go with “Cos it’s easy to bottle and it’s easy to sell”.

And profitable too, I have no doubt. Thanks to Orrin Hatch, US supplement peddlers don’t even have to prove their products are safe, never mind effective:

https://en.wikipedia.org/wiki/Dietary_Supplement_Health_and_...

I bet the oft-reviled Big Pharma (who, amusingly enough, are some of the biggest manufactures of supplements too) just wish all their products could enjoy such lax standards of regulation. Meanwhile, to everyone else, I wholeheartedly recommend The Poison Squad:

https://www.pbs.org/wgbh/americanexperience/films/poison-squ...

https://www.penguinrandomhouse.com/books/312067/the-poison-s...


I've given glucosamine to my dogs for years, and I can clearly notice a difference in their joint health and how stiff and sore they are after long runs ('long-run': 15-25 miles, measured on GPS collars). When I run out of glucosamine, or just drop off of giving it to them for whatever reason, I see them fall back pretty quickly. And when I restart them on it, I notice a response in a few days.

I also give give them fish oil pills, but I've never been able to notice a difference.


Purely anecdotal data but a I know a good number of dogs and cats that had really good results supplementing with glucosamine. As for me personally and few other friends and family, glucosamine supplements didn't have much of a noticeable effect.


Probably because we, humans, don't move as much as cats and dogs.

This matches glucosamine's effect on me pretty well. I have a genetic joint condition that makes any repetitive motion cause damage and pain. Glucosamine (4500mg/day) is provably the one thing that lets me have a normal career (carefully chosen job still). If I stop taking it for a few days, that's a problem. I stepped up to that dosage, noticing clear improvements a week or so after each increase.

I couldn't run 15 miles though! Walking 1km is risky even on a good day, even with glucosamine.


Fish oil is more of a natural anti-inflammatory than a fix for the problem.


Would you be so kind to tell me

1. The amount and frequency of glucosamine you give to your dog

2. The size of your dog (kg/pound)


I give 500mg per day. My two dogs are 55 and 65 lbs. The amazon product number I use is: B00V45IQF6. They have dosage info on the label for different sized dogs.

Anecdote: glucosamine had a moderately positive effect for my dogs, but CBD oil (at a low dosage -- 5-10mg/day for ~65lbs of dog) has been incredibly helpful.


Like others, I give my dogs glucosamine and it seems to have clear health benefits, but I have tried numerous dosages for myself and when I consume any meaningful amount it gives me absolutely wretched headaches about a day or two after consumption. Something to be aware if you start taking glucosamine and get headaches, it’s probably the glucosamine.


Perhaps you have some undiagnosed shellfish allergy?

FWIW, I've noticed iHerb has started selling shellfish-free glucosamine.


I had that thought but have never formally tested it. I do eat an above-average amount of crab, clams, scallops, shrimp (tail on), etc... and I always feel great afterwards. Obviously a glucosamine tablet is far more concentrated, so I could very well be allergic.

I’ll definitely checkout that brand though!


This title is not the title of the study.

"Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study"

This does not mean it reduces all cause mortality. This is correlation, not causation.

To take this further, there might be no limit to what you could correlate to some degree with all-cause mortality, especially since it might be heavily correlated to financial status, which would correlate to an enormous amount of other behaviors (eating avocados, owning a swimming pool, having a high ceiling, having your own bathroom, having a gym membership, organic food, name brand laundry soap, not taking public transportation, better healthy insurance, smoking habits, coffee quality, living in a low crime area, etc etc). Determining cause and effect takes a lot of control variables.


"The UK Biobank used a baseline touch screen questionnaire to assess several potential confounders: sociodemographic characteristics (age, sex, ethnicity, Townsend Deprivation Index, education and average total annual household income), lifestyle behaviours (smoking status, alcohol consumption, physical activity, body mass index (BMI) and vegetable and fruit consumption), health conditions (CVD (myocardial infarction, angina or stroke), respiratory disease (chronic obstructive pulmonary disease or emphysema), cancer, digestive disease (liver failure, cirrhosis or alcoholic liver disease), dementia, depression, longstanding illness, hypertension, diabetes and high cholesterol), drug use (chondroitin, aspirin and other non-steroidal anti-inflammatory drug (NSAID) use), vitamin supplementation (vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, multivitamin and folic acid) and mineral and other dietary supplementation (calcium, iron, zinc, selenium and fish oil)). "


Still, the authors accept correlation as a potential objection, despite doing their best to control for it. I suppose they need a randomised controlled study or something to be more certain.

"Third, regular glucosamine use may be a marker for a healthy lifestyle, but it is hard to distinguish the confounding effects of a healthy lifestyle from the impact of regular supplementations in an observational study. Although we had carefully adjusted for potential confounding lifestyle-related factors in our analyses, we could not exclude the possibility that the results were confounded by unmeasured lifestyle-related factors. In general, with the current observational study design the possibility of residual confounding due to imprecise measurements or unknown factors cannot be excluded for all findings in our study, despite our careful adjustment of all measured confounders."


They tried to control for as much as they could, but that doesn't make the title accurate. The authors don't claim what the title says.


> This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.

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


I am guessing they didn't control for lifestyle, etc. Someone who takes glucosamine either works out heavily and supplements (and probably watches their diet), or had joint surgery, and falls into the first group to some degree.

Edit: Yea, reading the study, I don't see anything about controlling for fitness level. Running and caring about one's diet alone would account for this effect without glucosamine.


> Edit: Yea, reading the study, I don't see anything about controlling for fitness level.

They specifically control for the following lifestyle factors: "smoking status, alcohol consumption, physical activity, body mass index (BMI) and vegetable and fruit consumption."

(Ctrl+f for "covariates")

In the conclusion, they acknowledge: "Although we had carefully adjusted for potential confounding lifestyle-related factors in our analyses, we could not exclude the possibility that the results were confounded by unmeasured lifestyle-related factors."

But if someone "works out heavily and supplements," that should show up in self reported physical activity, and indirectly in BMI.


But if someone "works out heavily and supplements," that should show up in self reported physical activity, and indirectly in BMI.

Well, not to nitpick, but people with high muscle mass can easily end up with an "obese" BMI even if they have very low body fat. And it also doesn't take very many hours of working out per week to get jacked if you're doing heavy weightlifting and supplementing.

No idea if such people are common enough to skew the results of this study significantly, but it still makes me wonder a bit.


Even body builders will have a hard time of getting to obese levels of BMI most of them are in the “overweight” range usually around 26-27.

And no people like this aren’t common at all.


Sure, some (not a huge fraction, I'm guessing single digit percentage) of very physically active people are poorly modeled by BMI but it shouldn't matter if they are explictly handling these covariates.

It's more an issue if there is something they haven't accounted for, as they point out.


I missed that. Thanks a lot for the correction.


I don't see "other supplements" in that list; surely they had to control for that as well?


Awesome!, thanks for the tip `(Ctrl+f for "covariates")`


> Yea, reading the study, I don't see anything about controlling for fitness level.

Doesn't table 2 and 3 show that they examined a bunch of relevant covariates including physical activity, smoking, alcohol use, diabetes, hypertension, cholesterol, statin and aspirin use? It's at least "something" at the very least and I'm not sure how you missed it if you were actually reading the study because it's very hard to miss.


"because it's very hard to miss". Haha rub it in, fair enough.


So it's just another crappy observational study, which is about all we ever get on human nutrition. This is low quality on the evidence-based medicine scale.


I've been a big fan of N-Acetyl Glucosamine (aka NAG), which is one of the most underlooked safe supplement to deal with autoimmune disease. Could it be the same as the mobility supplements with Glucosamine?


The bit questioning its usefulness in addressing arthritis is pretty much bullshit, as it's working for my parents and even my cat - Who went from dragging himself around to going all jumpy within DAYS of having it mixed in with the food.

Glucosamine + Chondrotin + MSM - This supplement combination is ideal.


The evidence for Glucosamine alone to do much about arthritis is poor. Glucosamine + Chondrotin + MSM is a different matter entirely and is not the same as what the author is speaking about.

Yes, we started giving Glycoflex to our dogs every day going back decades.

I do indeed note that my minor (RSI related) joint issues almost immediately disappear when I take that stuff. It seems indeed quite beneficial.


What dosage do you take and how long does the pain relief last?


I take Glucosamine / Chondroitine Complex 500/100mg. One or 2 per day.

It's hard to say how long, it does take a day or 2 to kick in (when I said "immediately" I meant within a couple days when I start taking it. I probably shouldn't have used that term.)

I'm not very strict with medication so I tend to stop it when I don't have issues.

But especially in my elbows where I only have mild pain it seems to help a lot. In my wrists it doesn't as much, but I think the pain there is not totally joint-related.


Indeed, I'm also having RSI issues and would like to know

I wonder if humans used to eat more bones ... I had a physical anthropology professor who studied an ancient site in east Africa where it appeared humans got a fair amount of food from eating leftovers from lions and whatnot, breaking open bones and eating marrow. Basically humans were in between the predators and the vultures.


Yes, and even more recently, the stew pot extracted a lot more than the boneless chicken breast of today.


I was suffering from severe knee pain due to cartilage wear and started taking liquid Glucosamine supplement as per doctor advice since 4 years. Now I'm perfectly OK and run daily.


Quote: "Glucosamine is a polysaccharide that is found naturally in cartilaginous joint tissues, bones, skin, ligaments, and nails"

Why not just eat natural sources like cartilage, bone broth, skin etc ?


Interestingly most sources I could find on the web say categorically that “No natural food sources of glucosamine exist”, while the the supplement is made from sea shells. All resources related to canine health on the other hand mention cartilage, bone marrow and beef trachea as rich in glucosamine... someone is being dishonest there.


Natural source means made by plants.


This so much. Absorption rate could vary quite a bit and it’s nearly impossible to research and find a good source these days due to insane number of supplement manufacturers in the market (I partly blame Amazon for this).


Glucosamine tablets are made from natural sources, usually seafood (e.g. shells of shrimp, lobsters, and crabs).


I’ve heard that in japan (or at least parts of it) they eat shrimp whole, and it’s kind of amusing when visitors bite off the tails.

Also the little “bones” from certain fish I expect do the same.


There's even snacks that are just the fried fish bones. http://seriouseats.com/2011/03/the-nasty-bits-fried-fish-bon...

I wonder if you get enough of it on a highly carnivorous diet -- bone broth, bone marrow etc.


I doubt it as many people mention it has great benefit on dogs, and their diet is pretty much all that.


Probably because those who are old start moving again with lower joint pain.

My 80 year old grandfather is the most fit person I know. Super healthy, but literally lifts rocks and gardens every day.

To contrast other family members are in their 50s with diabetes and heart conditions.

Keeping active is key. Remove peoples joint pain (which is what this supplement is used for) and of course they reduce mortal across the board.


Props to your grandfather. I can barely lift even a small garden.


lol


This is an impossible field to be working in - I know - and it's to do with the way our medical research and treatment systems are set up.

We began as a species focused on making sick people healthy, and it's the way the entire system works. It's near impossible to get studies approved that tackle aging and proactive healthcare with drugs, as they will largely need to look at the effects on people who are healthy now, but will almost assuredly die from dementia, Alzheimer's and heart disease.

I understand why it is the way it is, but it's frustrating to see the system wait until you have heart disease in your 70s before doing something about it.


You do realize the reason people now die of dementia is because medical science and improved standards of living have largely eliminated all the things that used to kill them before they got old enough to develop it? The same goes for cancers.

As for heart disease, that’s largely a product of lifestyle choices: smoking, obesity, inactivity. And doctors already tell their patients to eat healthily and exercise daily, but who wants to hear that when they’re young enough not to feel the consequences, or old enough not to want to change their ways now?

Hence the eternal market for easy, quick magical pills and their silver-tongued salesmen that promise to cure it all.

We began as a species programmed to spot the difference between a zebra and lion on the plains of the Serengeti, and we’ve barely evolved since—if anything, we’re even easier to hack now. Just ask the vampires.


https://examine.com/supplements/glucosamine/

Always used this site when trying to find unbiased information, and also not be to hyped about a single study. However now the effect matrix is hidden behind a paywall.

When talking about joint health: As a young and very active person my biggest problem is overtraining injuries. Wish I knew how to be able to train as much as I would like to, with just a simple supplement or so...


There's always peptides that do work with mouse models but there aren't any decent safety studies on them with humans. I really wish there was a push to get safety and efficacy studies around BPC-157 and other peptides.


Look up Keith Baar. He has some suggestions.


Is it a simple case of pain-free joints enabling one to exercise more?


Every time you move, the body releases adrenaline, so you are not far wrong in your line of thought. The adrenal glands produces around 180 different hormones including adrenaline, so protecting or even attempting to improve their function would be a logical natural pain killing route to take. Hint they are layer upon layer of epithelial cells. Of course other factors like the body attacking itself is also a problem which the adrenal glands alone cant "fix", for example too much sodium increases the Th17 cells to the point they start attacking the body. T cells from Thymus, B cells from bone marrow. However considering civilisations & Religions have existed for over 10,000years dating back to Sumerian times, observation was the only "scientific" methods available at the time, and Religions had to keep their followers healthy for the next attack, so looking into different religious fasting methods could also improve health outcomes. The world record for a water only fast, still in the Guinness book of world records is 382days, carried out in 1971 at the University of Dundee. Having done an 18day water only fast myself and felt like a teenager again, I'd highly recommend investigating it to others. A US movement in the 1950's called the Hygienists and Shelton were big advocates. Also consider the immune system attacks the food we eat, so as our immune cell count falls during a fast, are there still more immune cells now working solely removing damaged cells from the body? Its suggested viruses need carbs as noted by the use of the Keto BCAA Lysine for Cold Sores, bacteria builds biofilms when they go dormant in the body but are not impenetrable to the attacking immune system either. So there seems to be some merit with a water only fast for some, however sudden death is a risk to those with undiagnosed conditions, a bit like we see with some seemingly healthy people dying of covid. Either way, the human body, in fact any lifeform is an extremely complex biochemical and electrical real time puzzle where many chemicals play their part in lengthening life spans or shortening life spans. I wouldnt bet my life on just one supplement, unlike Linus Pauling and Vit C, its effects like all supplements, need to be put in context in the scheme of things keeping us alive, healthy and happy.


Article title is gross overreach, if not outright wrong.

IANAS, but even I know Correlation does not mean Causation. The paper itself only says “associated with”, not “responsible for”. Being an observational study of self-selecting cohorts, even with the authors’ attempts to control the confounders will be massive.

Honestly, this is the standard of reporting I’d expect from yellow-bellied fish wrappers like the Daily Mail. Please do better.


All-Cause Mortality? Is it make you also somehow immune to fire arms for example? Just the title makes the article to view unserious.


>Is it make you also somehow immune to fire arms for example?

No, you have to start off with daily injections of small arms fires (think .22 caliber) in order to begin building immunity. Over time you gain immunity and then can work your way up to larger calibers.


It is a Reddit worthy response, but it immediately made me think of a KungFu movie I saw in the 80s where the monks were trained to withstand gunshots (multiple) to their heart. Now I just cannot find what (incredibly bad but apparently memorable) movie that was!

That was one of the low key funniest things I’ve ever read on hacking news


Hacker News. I’m an idiot. But I stand by the rest!

Reminiscent of the biological testing approach here:

https://xkcd.com/1217/


All cause mortality is just a categorical bucket.


Statistically perhaps? I.e. there surely are chemicals and infections which make you more, hmmm, adventurous. Perhaps it might make you more careful and less likely to get shot.


It's interesting to see that even on HN people don't know the difference between correlation and causation.


Have you read the paper? They adjust for damn near everything including reverse causation. What confounders do you believe the UK biobank data can't account for?


It doesn't matter if you eliminate 10 million confounds. No matter how good your correlation study is, it cannot establish a causation. To do that you need random assignment at the very least.


10 million confounds is a lot to eliminate. Randomization only works because it decreases the probability of a spurious association existing. At some point the number of confounds eliminated would probably be more worthwhile. I'd definitely pay more attention to a study that eliminated 10 million confounds than most randomized controlled trials.

I agree a randomized controlled trial would be nice now. But even that is potentially fraught. For example, someone else mentioned the possibility that glucosamine reduces joint pain, which increases mobility, which increases longevity. Randomizing wouldn't really control for that sort of scenario. And that's not even getting into preregistration, meta-analysis etc.


... and even that gives you the wrong answer if your diagnostic specificity is faulty.

This last is why we keep seeing muddled reports that "antidepressants don't work". Diagnosis of "depression" is a snakepit; the only known way to discern which among at least six conditions you might have, all labeled "depression", is to see what medications work, if any. Imagine trying to conduct a plausible RCT for that.

"Gold standard"? Ha.


Did you reply to the wrong comment?

I replied to "...it cannot establish a causation. To do that you need random assignment at the very least."

Oh, your quoting of "gold standard" really threw me off.

Adjusting for the wrong confounders is one of the ways to create spurious correlations. For example, consider the causal system

    X -> Z <- Y
in which X and Y are random coin tosses (heads=0, tails=1) and Z is their sum. Even though X and Y independent, they will be correlated if you control for Z.

If you want to see it yourself, let's simulate this system in R:

    # Simulate 1000 trials in which X and Y are random coin tosses (T or F)
    # and Z is their sum.
    
    > X <- rnorm(1000) < 0.5
    > Y <- rnorm(1000) < 0.5
    > Z <- X + Y

    # As expected, X and Y are not correlated:
   
    > summary(lm(Y ~ X))

    Call:
    lm(formula = Y ~ X)

    Residuals:
        Min      1Q  Median      3Q     Max 
    -0.6947 -0.6893  0.3053  0.3108  0.3108 

    Coefficients:
                 Estimate Std. Error t value Pr(>|t|)    
    (Intercept)  0.694704   0.025816  26.910   <2e-16 ***
    XTRUE       -0.005455   0.031330  -0.174    0.862    <<< No correlation.
    ---
    Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1

    Residual standard error: 0.4625 on 998 degrees of freedom
    Multiple R-squared:  3.038e-05, Adjusted R-squared:  -0.0009716 
    F-statistic: 0.03032 on 1 and 998 DF,  p-value: 0.8618

    # However, if we include Z as a possible confounder, we create a
    # spurious correlation between X and Y:
    
    > summary(lm(Y ~ X + Z))

    Call:
    lm(formula = Y ~ X + Z)

    Residuals:
          Min        1Q    Median        3Q       Max 
    -2.45e-14 -8.40e-18  2.04e-17  2.04e-17  3.59e-15 

    Coefficients:
                  Estimate Std. Error    t value Pr(>|t|)    
    (Intercept) -3.370e-16  6.292e-17 -5.356e+00 1.05e-07 ***
    XTRUE       -1.000e+00  8.241e-17 -1.213e+16  < 2e-16 ***   <<< Oops!
    Z            1.000e+00  5.873e-17  1.703e+16  < 2e-16 ***
    ---
    Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1

    Residual standard error: 8.582e-16 on 997 degrees of freedom
    Multiple R-squared:      1,     Adjusted R-squared:      1 
    F-statistic: 1.449e+32 on 2 and 997 DF,  p-value: < 2.2e-16


I do not know why you are simulating this system.

Given random x, y, controlling for z = x + y trivially generates a perfect anticorrelation as x = z – y.

Like, I get that you want to make a point, just seems weird to have a numerical solution in 5 lines of code to a problem that was already theoretically solved when you wrote down the problem statement and therefore required exactly 0 equations...?

Also like the theoretical solution clarifies that this happens for arbitrary probability distributions equally, it is not specific to Bernoulli random variables.


I'd guess there's not much cause for it among computer science people. I've noticed this in the past: empirical disciplines are better at this stuff.

Still, I can't quite work out if a biology degree would cause somebody to understand it better..


I mean one of the two dominant frameworks for causal inference is Judea Pearl's directed acyclic graphs / do-calculus, and Pearl is surely a computer scientist.


In my experience, most empirical majors beat you over the head with the chanting of "correlation does not imply causation" pretty much every term. It's too bad that it's one of those things that's not naturally intuitive to people.


What dosage is recommended?


This other study suggests 2000mg per day: https://bjsm.bmj.com/content/37/1/45.short


   Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.
associated, not direct causation


are there dietary sources of glucosamine?


there's no reason to believe macromolecules like glucosamine benefit the body any more than regular, nutritious food. ingested nutrition generally gets broken down into amino acids and the like in the digestive system before it gets distributed to the rest of the body to be reconsistuted into cells and tissue.

cartilage in particular is scaffolding and generally must be constructed by other cells from very basic molecules at anchor points. it's decidedly not like lego blocks of glucosamine and chondroitin that just get assembled together.


As someone that has taken various vitamins and supplements over the years, glucosamine is the one where I truly feel a difference. In my knees, my back stopped cracking when I woke up, and generally just better. Others I take based on blood tests if something is out of whack for a time.


For me too.. And I'm usually extremely sceptical of food supplements and general quackery.

My joints have also been really cracky since I was a child. This seems a bit less but still present with the glucosamine.

But my elbow joints are often sore due to being on the computer way too much and every time I start taking it again it fades in a day or two. I don't think I'm imagining it :) Many other stuff I don't feel much benefit to.


Can I ask your age (or which decade if you prefer!)?


What brand and dosage do you take?


+1. Love to know age, weight and dosages people are taking. (And biological sex, if you feel comfortable.)


Glucosamine supplementation doesn't appear to have harmful effects on humans and is pretty cheap. It may work for some people, so if you have joint issues why not give it a shot?


You raise a good point, but wouldnt taking glucosamine and chondroitin load you up (hopefully) on the base components required to then again make glucosamine and chondroitin locally in one's body?


https://en.wikipedia.org/wiki/Glucosamine#Bioavailability:

“In the first study, glucosamine sulfate was given to healthy volunteers in doses of 750, 1500, or 3000 mg once daily. In the second study, oral glucosamine sulfate capsules (1500 mg) were given daily for two weeks to 12 people with osteoarthritis. Glucosamine concentrations in plasma and synovial fluid increased significantly from baseline levels […] but the levels are still ten- to a hundredfold lower than required to positively affect the cartilage (chondrocytes) to build new tissue”

⇒ the good news is that these molecules make it through the intestines intact, and arrive at the place where they are supposed to help. The bad news seems to be you would need to take huge doses.


It is important to remember the study only saw a correlation between the dietary supplement and mortality. Glucosamine Sulfate is from what I understand the most common form in the supplements on the shelf. Our bodies produce glucosamine naturally.

> Specifically in humans, glucosamine-6-phosphate is synthesized from fructose 6-phosphate and glutamine by glutamine—fructose-6-phosphate transaminase as the first step of the hexosamine biosynthesis pathway -wikipedia


Don't worry. By the time [insert popular news outlet] finds out about this, it'll be a cure all.


Yes - cartilage. If you eat chicken or something like that, eat the cartilage. You can do this on pre-cooked chickens you get from Sam's Club / Costco. If you eat chicken breasts only (which a lot of health-conscious people do), you don't get this benefit.

I talked to Dr.Yang Jwing Ming (one of the few Kung Fu practioners with a Western phd and he said eating cartilage is one of the best ways to help reduce the risk of arthritis. Oh, and pig ears too, but I never tried that, being a Westerner and all.


Westerners have eaten pig ears for centuries.


I would be surprised if I've met anyone in the US who has eaten pig ear nor the chicken feet you see next to them in the hispanic market. And just about everyone would react to the ick factor.

I don't think it's as common as you think: https://en.wikipedia.org/wiki/Pig%27s_ear_(food).


I don't really know of anyone who eats pig ears but chicken feet aren't that weird for the American South.


It's not super-common but it's nothing out of the ordinary either. Many restaurants in Southern Europe, including France, serve dishes such as pig feet, pig snout or pig head.


Also explains how 'Westerners' have been living so long for centuries, especially before the 1960s.


I read research that to reap benefits of these sources ( collagen, etc) your stomach acid needs to be strong enough to break it down- old people have weaker stomach acid so they get wrinkles easier- Supplement apple cider vinegar, lemon juice etc or other fermented foods raises stomach acid strength and raises blood Alkalinity, or so I heard


Another great way to get cartilage is with chicken soup, slow cooked until the gristle liquefies in to the soup. It's more absorbable by the body that way. Chicken fat is great for the skin, too. Easy and cheap to cook - just get a whole hen and simmer it in water in a big pot, or use a crock pot.


Would chicken bone broth have it?



None of those mention Glucosamine. And they seem to be sour grapes articles, not sure why. One of the “myths” they dispel is “bone broth tastes good”.

It does raise some good thoughts on why it’s not a super food.


Quite probably. I am assuming that home-made methods are similar as industrial scale methods (put a bunch of chicken bones and connective tissue in a vat of water, simmer, strain).


Collagen has it too?


Pig ears are absolutely delicious


I really hope at some point in our lifetimes, the deleterious effects of animal protein are pervasively understood by educated Americans to the point where consuming animal parts for their anti-inflammatory benefits would be an oxymoron on par with smoking to prevent cancer. An overwhelming body of scientific evidence suggests that humans are omnivores and not carnivores and the human body evolved to process animal protein on an occasional basis(like alcohol) and not because it’s good for us on a daily basis.


1. Glucosamine is not a protein. 2. The claimed benefit of glucosamine is not anti-inflammation, but providing the building blocks for cartilage repair as synovial fluid is circulated in the joint. 3. It's very difficult to get sufficient protein from a plant based diet, especially when avoiding soy, which raises estrogen.


To people who put too much stock in these "studies", consider this: as of July 2020 we _still_ have no conclusive answer if _eggs_ are good for you or not. What makes you believe this is any different?


Why would eggs, for which there isn't a chemical formula, nor a standard preparation, be easier to study? What even does "good for you" mean?

Don't get confused between mass-media popular "science" and things science can actually do - like measure whether a dozen eggs a day will raise your LDL and HDL (cholesterol) and cause heart disease - and drawing wild conclusions (especially right now) from pre-print articles that are used to sell magazine articles to use as justification to eat chocolate and drink wine under the guise of "it's good for you".


We're still waiting for them to figure out salt.


People who take glucosamine often do so BECAUSE of their active lifestyle, most don't have a use for it otherwise.

This study did not control for lifestyle.

In other news, people who own Peloton shoes likely to live longer...


> Covariates

> The UK Biobank used a baseline touch screen questionnaire to assess several potential confounders: ..., lifestyle behaviours (smoking status, alcohol consumption, physical activity, body mass index (BMI) and vegetable and fruit consumption),

You seem to not have read other comments, where the same complaint is made, and its answers.




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