Should I take glucosamine?

This is not just some random data fishing result. Even before the results of the two glucosamine papers this year, longevity researcher James Clement wrote in "The Switch", that glucosamine is "an autophagy inducer in a pathway separate fron mTOR-inhibiting." That is big, since autophagy seems to be responsible for most of the benefit from fasting and CR, but almost all autophagy that we know is activated via mTOR.

That means that you have a clear prior that it should increase your healthspan (but as with all autophagy inducers, like resveratrol or cold showers, don't take it after exercise, since it dulls the response). The prior together with the study results working out as expected is a very good sign for a rationalist IMHO.

Unfortunately glucosamine has at least one significant negative effect as well (see e.g examine.com). It is similar to glucose, so can disrupt blood sugar stability.

Our biology is complex. Don't take substances just because of correlations. Strive to know why they work. If you are going to take glucosamine, do it when you want to be catabolic for a while (it has 15h half life), take it together with fat (I have fish oil and quercetin in my notes for reasons I forget - probably blood sugar results from the detailed notes on examine.com) and know if you are in a risk group for diabetes 2, because it might mess slightly with your blood sugar.

The above is from my personal research notes. I don't take glucosamine yet, but believe I will start. I am not a health professional, just a hobbyist.

A much larger cohort study was published just before the Dana King paper:

https://ard.bmj.com/content/79/6/829

They have adjusted for a wide variety of factors and concluded there was a 15% overall reduction in mortality associated with glucosamine supplementation.

h/t https://lemire.me/blog/2020/07/25/science-and-technology-links-july-25th-2020/

Daniel Lemire covers medical developments in his blog, it is well worth following.

Glucosamine is used by people with arthritis to reduce joint pain with activity. It would not be used by a group to ill to be active i.e. if you are healthy enough to worry about taking glucosamine you probably aren’t going to die this year. This result is purely selection bias obtained by data mining.

As you said, it's a cohort study. The cohorts are pretty different (gluco/condro users were more white, educated, non-smorkers, physically active than non-users, though pretty older in comparisons) and the adjustment could be skewed by the small number of users. But, it's mostly harmless and the effect size looks promising. Personally I'd make a quick review of the literature to decide whether to commit to taking the supplement and set up an alert on Pubmed.

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Correlation does not imply causation. There is a clear correlation between the decline in piracy and global warming. Subsidizing pirates won't solve the climate crisis however. On a more serious note, glucosamine is usually a treatment for mild to moderate arthrosis. People who use it are likely the kind of people that take care of themselves and thinks good health is important.

Look for other differences between the two groups and you'll likely find something else there that is more likely to increase your lifespan.

All cause mortality? I very much doubt it'll protect you from car accidents or bear attacks.

Far more likely that people that people that take such supplements do so as they're health conscious and any perceived benefits are halo effect.

Eat a balanced diet, include skin, bone and shellfish and you'll get more than enough of both plus lots of other nutrients.