Glucosamine Linked To Alzheimer's Progression?

[00:00:00]A supplement you may be taking has been shown to increase Alzheimer's disease morbidity.

[00:00:07]>> Wait. What?

[00:00:08]>> Yes. A supplement that millions of people take for their joints has actually been shown to accelerate the negative effects of Alzheimer's disease and lead to more mortality.

[00:00:17]>> through social media? Shocking. Shocking news. Welcome to Talking with Docs. I'm Dr. Brad Weening.

[00:00:21]>> I'm Dr. Paul Saladino.

[00:00:23]>> This is pretty pretty interesting study.

[00:00:25]Now, I came across this article. I was like shocked, scared, thrilled, excited to share it. You were underwhelmed.

[00:00:32]>> Yeah, so so So, we're like Abbott and Costello. And I'm definitely more of the skeptic. I'm like, you know, show me the evidence.

[00:00:39]>> Yeah. But, I would say also unfortunately, if I really believe it, I'm like, "Hey, look at this good evidence." You know, like we all are, right? We're all biased. But, I recognize that in myself.

[00:00:47]>> Should we tell them what it is?

[00:00:48]>> Yeah, I think we should.

[00:00:48]>> Okay. Well, I'm Dr. Paul Saladino. Have we done this yet?

[00:00:51]>> I did my part.

[00:00:51]>> Oh. All right.

[00:00:52]>> We're talking about >> Welcome to Talking with Docs.

[00:00:54]>> Yeah.

[00:00:55]Glucosamine.

[00:00:56]>> Hey, we said that together.

[00:00:57]>> Yeah. 1.2 billion dollars in yearly sales. There are a lot of people probably watching this video right now that either have taken, are taking, or know someone that's taking glucosamine.

[00:01:07]>> That's everyone.

[00:01:08]>> Like two degrees of separation probably.

[00:01:09]>> Everyone knows someone taking it or has taken it or considered taking it or taken it in the past.

[00:01:13]>> Anyone that's ever gone to Costco, [clears throat] saw that five-gallon bucket of glucosamine, thought, "I might need that."

[00:01:19]>> It's everywhere.

[00:01:20]>> need that."

[00:01:21]>> And people take it for their joints, right?

[00:01:25]And the evidence for joint health is >> It's not great.

[00:01:29]>> Okay. Definitely, glucosamine does not rebuild cartilage, all right? But, now, this paper, which was in a good journal, Nature Metabolism, >> Yes.

[00:01:38]>> hyperglycosylation is a metabolic driver of Alzheimer's disease.

[00:01:43]>> Okay.

[00:01:44]>> Boom.

[00:01:44]>> Okay. Is it a randomized controlled trial?

[00:01:46]>> No.

[00:01:47]>> Okay.

[00:01:47]>> However, it's a very interesting study that was multi-pronged.

[00:01:52]>> Yes. [clears throat] >> They did They had an animal model.

[00:01:56]There's an actual animal model.

[00:01:57]>> Do you >> me to break the prongs as we go or wait till the end?

[00:01:59]>> Wait till the end.

[00:01:59]>> Okay.

[00:02:00]>> I'll just describe it quickly.

[00:02:01]>> Okay. Yeah.

[00:02:02]>> They did They looked at animal model >> model, yeah.

[00:02:04]>> mouse model of Alzheimer's disease.

[00:02:06]>> Yes.

[00:02:06]>> know how you could tell a mouse >> I I looked deeper.

[00:02:09]>> Did you? How would you tell if a mouse had Cuz there's a dead one in my pool every other week.

[00:02:13]>> Okay, so those are probably the ones with Alzheimer's.

[00:02:15]>> So, they actually did mouse memory studies. So, when mice meet each other >> Yes.

[00:02:20]>> right? They remember. And then if you introduce that mouse to the same mouse again >> Yeah.

[00:02:24]>> they will [clears throat] behave differently. But if there are two mice, one that they've met and one that they haven't met, they'll actually spend less time with the mouse that they've met.

[00:02:31]And that's how they determined that mouse memory was either increased or decreased.

[00:02:36]>> a validated mouse memory model.

[00:02:37]>> This Yeah, this leads into my some of my objections.

[00:02:40]>> All right. And then they found that like cosolation, which is basically taking a sugar molecule and adding it onto a protein molecule, which is a fundamental biochemical pathway that happens in the human body and is necessary for everything from like nerves communicating with each other and just about every metabolic pathway in the body. It's important. But they found that in the mice with Alzheimer's disease, this was occurring more.

[00:03:03]>> That's right.

[00:03:03]>> Okay. And when they gave mice with Alzheimer's disease the glucosamine >> Yes.

[00:03:11]>> their memory was worse. So, they deteriorated.

[00:03:13]>> Yes, so they recognized that mouse >> Yeah.

[00:03:15]>> that they had met before less.

[00:03:18]>> So, the validated mouse memory model.

[00:03:20]That's what you're talking about.

[00:03:20]>> Yeah. It's kind of like 50 First Dates kind of. That's what happens to them.

[00:03:24]>> Yeah. The poor mice.

[00:03:25]>> Yeah.

[00:03:25]>> I mean, I've never done mice animal models personally, but this is a validated model for memory.

[00:03:29]>> Right.

[00:03:29]>> They also looked at cadaveric brains >> Right.

[00:03:32]>> of humans >> Yes.

[00:03:34]>> with Alzheimer's disease >> Yes.

[00:03:36]>> and without Alzheimer's disease. Now, they looked at hundreds of these brains.

[00:03:39]>> No, they looked at six.

[00:03:40]>> Okay. They looked at six of these brains.

[00:03:41]>> Three in each group.

[00:03:42]>> Three in each group. And that's all you need when you do cadaveric study.

[00:03:45]>> Well, said no one. But, you know what?

[00:03:47]A, it's it still it supported >> Yeah.

[00:03:51]>> their hypothesis.

[00:03:52]>> The hyper glycosylation occurring in the Alzheimer's disease as opposed to the normals.

[00:03:56]>> And I think you can recognize doing postmortem brain molecular studies is complicated. So, it's hard to get large numbers.

[00:04:02]>> god, they use some serious technology to do it.

[00:04:04]>> So, it's not just I'm knocking the methods. I'm it's a little bit of a grain of salt.

[00:04:07]>> Okay. And then the third prong is they looked at clinical databases.

[00:04:12]>> Yes.

[00:04:12]>> And they looked at like 50,000 people, identified the ones that were taking glucosamine, had Alzheimer's disease compared to those who were not taking glucosamine, who had Alzheimer's disease, and found an increased mortality and morbidity, so worsening of the Alzheimer's in the group that was taking glucosamine.

[00:04:29]>> Yeah, and their conclusion was to the tune of about 25% I think.

[00:04:32]>> 25% increase, yeah.

[00:04:33]>> And so, like we always talk about, um this is association, not causation. So, you there's a lot of variables you can't control for. It's a it's an electronic database, so it's hard to know, you know, how much glucosamine were they actually taking? Were they taking it every day? Um do they have other variables in their lives that led to the dementia? And does someone that takes glucosamine, do they already do other things that may have either positive or negative effects on this outcome? So, >> Confounding variables, for sure.

[00:04:58]>> Human studies are difficult to do. So, anyway, you take all that together.

[00:05:01]>> Take all that together and they said that, "Hey, listen.

[00:05:05]Glucosamine seems to increase the deterioration of Alzheimer's disease and actually increase mortality." So, they found like a biochemical explanation for it, shh demonstrated with their animal model, postmortem studies, >> Yeah.

[00:05:22]>> and some clinical data. Is it a randomized control trial? No.

[00:05:25]>> No.

[00:05:26]>> Is it enough to convince me not to use glucosamine in anyone that is at risk for Alzheimer's disease or has Alzheimer's disease? Yes.

[00:05:34]>> Okay, so so I like that. What's interesting about glucosamine is a couple of things. So, glucosamine, do you know glucosamine? We make glucosamine.

[00:05:40]>> Yes, naturally.

[00:05:41]>> Like every day, all the time.

[00:05:42]>> Collagen, cartilage, connective tissue.

[00:05:44]>> And so, part of me thought, well, if we need it so badly, you know, why why don't we just make more of it? Well, you know, if you think from an evolutionary perspective, you know, glucosamine is mostly implicated in your your cartilage Yeah, your cartilage, your your connective tissue, so your tendons, your ligaments, and even some of the lining like your synovial lining, and extracellular matrix, but it doesn't really provide like a survival benefit in the moment. And that's probably why our bodies haven't said, "Well, guess what? We're going to make a whole bunch extra glucosamine cuz we're having breakdown products." Um so that's the first thing. Second thing is, when you take glucosamine by mouth, it does not get absorbed as glucosamine like we've talked about before. You want good skin, you don't eat skin. If you want good cartilage, you don't eat cartilage. If you want good bone, you don't eat bone.

[00:06:26]>> do. They take shark cartilage.

[00:06:27]>> I know they do, but it it almost makes no sense. So glucosamine gets broken down, the the meta- the metabolites get absorbed, and then some of that glucosamine metabolic byproducts could end up as glucosamine, but there's no way to really direct it. It doesn't work like that. Your knee doesn't say, "Hey, come here cuz you took some glucosamine."

[00:06:45]So, that's probably why glucosamine doesn't have a greater effect in the first place.

[00:06:50]>> yeah, as a good friend of ours and colleague says, because it doesn't work for joint cartilage.

[00:06:56]>> Nizar Zehr. Yeah.

[00:06:57]>> For sorry, rebuilding a joint.

[00:06:59]>> And so for me, normally when people ask me in the office, "Hey, should I take glucosamine?" I'm like, "Listen, you know, 20% maybe, you know, hard to tease out exactly what the placebo benefit would be, but if you feel like it helps, and you stop taking it, and you feel worse, then I would say normally if you're young and healthy, I think you could take it. The risk is financial.

[00:07:17]>> Fair.

[00:07:18]>> Cuz we didn't really know about this, but now, to be honest, I'm I'm with you.

[00:07:21]Like now with this new information, if I had a risk of dementia, or if I had early cognitive decline, or if I had a loved one that had that, >> or a mouse, >> or a mouse that was taking this, I would be like, "You know what? I think there's minimal benefit." It's not like you're taking like something for heart failure, or for to save your life. You know, we're not sure if there's a benefit, and there's a potential risk. So, for me, I think it's a no-brainer, actually. Like that, no pun intended on that.

[00:07:46]>> It actually does cross the blood I didn't think it did cross the blood brain barrier, but it does. Cuz you're taking this thing for your knee and it's getting into your brain.

[00:07:54]>> And so, I looked into that. I'm like, what does it do in the brain? Why is it even there? So, it doesn't make specific structures, but that kind of um shock absorptive value in the extracellular matrix and some of the other processes, that's what glucosamine is for. So, yeah, my take home is study's not bad. I think there's probably something there like almost every paper that you read and you're like, I'm so tired of saying this, "Hey, further studies required."

[00:08:15]But, I think further study is required.

[00:08:17]But, in the short term, if you have cognitive decline or dementia, Alzheimer's, or someone you care about or love them has that, I would have a thoughtful discussion with them about whether they should keep taking it.

[00:08:26]>> You know what? It changed It changes my practice. Cuz before I'd always tell people, "Go for it. It probably won't help, but it doesn't do any harm." Now, there's a caveat to that. Actually, there is some evidence that it can do harm in certain populations.

[00:08:38]>> And I would see more and more in the office I'm having conversations actually about dementia, about Alzheimer's, either in my patient or my patient's loved one saying, "Yeah, I'm dealing with this at home." It is a a rapidly growing complicated problem.

[00:08:51]>> Difficult for the patient, difficult for the caregiver.

[00:08:53]>> Yeah.

[00:08:54]>> But, you know what? The other thing that I found interesting was that it might inform further treatments because now we've kind of learned this this hyper glycosylation process does play a role, not just those tau proteins, not just inflammation. You know, there's a lot of things been implicated in Alzheimer's disease. Here's something else now, and maybe we can learn more about it and direct some therapies that can help prevent the progression or prevent the occurrence of Alzheimer's disease.

[00:09:19]>> Yeah, and adding the sugar to the amino acids, they think this is part of what maybe is the type 3 diabetes, you know, people with elevated blood sugars leading. And just to be clear, glycosylation is very different than glycation. So, we talk about something called advanced um glycation end products. So, typically um certain kinds of foods as well as cooking methods, like particularly grilling, lead to these things that can cause chronic inflammation. It's a very, very different process. It's when it happens without an enzyme. It's not enzyme regulated. So, um AGES are very bad.

[00:09:47]Glycosylation is necessary, but when it happens uncontrolled, >> Looks like hyper-glycosylation in the brain is implicated in Alzheimer's.

[00:09:54]>> Now Now you know, we thought it was super interesting. It's definitely We see it on a regular basis. We talk about glucosamine all the time. Now you know, if you like this video, please like it.

[00:10:01]Subscribe to our channel. Share it with someone that's like, "You know what?

[00:10:04]Should I be taking this glucosamine?"

[00:10:06]>> Especially someone who says, "I can't remember if I took it today."

[00:10:09]Could be a total problem. But this is going to be in the headlines. You're going to see this on the news soon that oh boy, glucosamine causes Alzheimer's.

[00:10:16]Doesn't cause Alzheimer's, but it has been implicated in progressing the disease.

[00:10:20]>> There you go.

[00:10:21]>> Remember, you are in charge of your own health. See you next time.