I Was Always Skeptical of This Supplement. Now There's an Alzheimer's Connection.
Over the years, clients have often asked me about glucosamine and chondroitin for their arthritis pain. Some said their doctors recommended it.
I always suspected the recommendation was less about overwhelming evidence and more about having something to offer — something that seemed harmless. Doctors know that patients don’t like to leave their office without options to try.
As it turns out, the “harmless” part may deserve a second look.
A Brief History of This Popular Joint Supplement
For decades, glucosamine and chondroitin were the go-to over the counter recommendation for joint pain.
Orthopedists often suggested the combination, and millions of people added it to their daily supplement routine hoping for relief.
Then the evidence started to wobble.
Large clinical trials, including the landmark GAIT study, found that while some people with moderate-to-severe knee pain reported benefit, glucosamine and chondroitin performed no better than placebo for most participants.
The combination came under particular scrutiny, since glucosamine is typically derived from shellfish, posing a risk for those with allergies.
Gradually, many orthopedists stopped recommending it but millions of people kept taking it anyway.
Here’s my unofficial theory: if glucosamine had delivered on its promise, we’d know by now. We’d be buying it the way we buy protein powder and creatine — flying off shelves, backed by decades of undeniable results.
Instead, it lingered in that uncertain middle ground of supplements that might help, probably don’t hurt, and give patients something to do.
The Surprising Alzheimer’s Connection
Glucosamine is an amino sugar found in cartilage.
Researchers led by Dr. Tara Hawkinson analyzed thousands of U.S. health records and found something unexpected:
Accelerated Disease Progression: People who were diagnosed with Mild Cognitive Impairment (MCI) butroutinely took glucosamine were 25% more likely to progress all the way to full-blown Alzheimer’s disease than those who didn’t take the supplement.
Worse Survival Rates: In patients who’d already been diagnosed with Alzheimer’s disease or a related dementia, taking glucosamine for at least one year after their diagnosis was associated with a 25% increase in overall mortality risk.
The mechanism appears to involve protein glycosylation, a process in which sugar molecules attach to proteins.
Dr. Hawkinson’s team found that excessive glycosylation seemed to be a significant driver of Alzheimer’s disease progression, and that glucosamine may worsen this already overactive “sugar-tagging pathway” in the Alzheimer’s brain.
I found this all particularly interesting because Alzheimer’s is now being referred to as “Type 3 Diabetes.”Glucosamine can cross the blood-brain barrier and influence glycosylation.
Dr. Ramon Sun, a fellow researcher on the study, went so far as to say that a lot of people are unknowingly taking an over-the-counter supplement that may be making their disease progression worse.
This was an observational retrospective study, meaning it identified correlation, not causation.
The researchers took it another step further and tested glucosamine in mice with Alzheimer’s disease.
It increased protein glycosylation and social memory worsened.
Suppressing glycosylation improved memory.
Examination of post-mortem Alzheimer’s brain tissue showed much higher levels of protein glycosylation than in non-Alzheimer’s control brains.
The convergence of human data, animal studies, and post-mortem tissue analysis makes this finding harder to dismiss as a single observational study.
The researchers were direct enough to include the word “driver” in their paper’s title —“Hyperglycosylation is a metabolic driver of Alzheimer’s disease“— bold language for scientists who are typically cautious about making claims.
Glucosamine isn’t the first seemingly benign supplement or medication to be linked to cognitive concerns.
Proton pump inhibitors, commonly taken for acid reflux, and diphenhydramine (the active ingredient in Benadryl and many sleep aids) have both been associated with increased dementia risk in research studies.
The pattern is worth noting: medications and supplements we assume are safe because they’re widely used and available over the counter don’t always get the same rigorous long-term safety scrutiny as prescription drugs.
Now what?
If you’re taking glucosamine for joint pain and have no cognitive concerns, this research doesn’t necessarily mean you should stop. The joint health evidence is mixed but not alarming for most people.
However, if you or someone you love has been diagnosed with mild cognitive impairment or Alzheimer’s disease, or has a strong family history, this is worth discussing with your doctor--maybe starting with, “Is glucosamine actually alleviating my pain?”
You’d be astounded if you knew how many people have told me they have continued procedures and pills despite thinking they didn’t make a difference.
If you’re looking for an alternative, there’s a promising option worth knowing about: cucumber extract. Seriously!
It’s plant-derived and requires only 1/135th the dosage of glucosamine and chondroitin to produce roughly double the benefit.
In a 2018 randomized trial, cucumber extract (10mg twice daily) was tested against glucosamine and chondroitin (1,350mg twice daily) in patients with moderate knee osteoarthritis. After 180 days, the cucumber extract group saw a 70% reduction in symptoms, compared to 33% in the glucosamine-chondroitin group — nearly double the effect.
The researchers concluded, “The use of 10 mg CSE, twice daily, was effective in reducing pain related to moderate knee OA and can be potentially used in the management of knee pain, stiffness, and physical functions related to OA.”
A caveat of my own: this was one study with 122 participants, and two of the researchers involved were affiliated with the company that makes the cucumber extract. Promising, not proven.....
Ask questions and stay skeptical!
What’s Proven To Keep Joints Healthy?
If we’re tossing the supplements in the trash, where does that leave your aching joints?
Your joints are avascular, meaning they don’t have a direct blood supply to deliver nutrients and clear out waste. They rely on a mechanism calledsynovial fluid diffusion.
The way to pump life-giving fluid, oxygen, and nutrients into your joint capsule is to actively move it through its full, loaded range of motion.
If you want healthy knees, hips, and shoulders as you age, you need:
Progressive Strength Training: Building the musculaturearoundthe joint to absorb the impact of daily life so your cartilage doesn’t have to.
Stabilizer Activation: Actively training the smaller, neglected stabilizer muscles that keep your joints tracking perfectly, preventing the structural friction that causes wear-and-tear—the most common joint issue I see.
Consistent, Varied Movement: Moving through multi-directional planes of motion every day to keep the joint capsule lubricated and mobile.
Instead of a daily pill, prescribe yourself the right kinds of movement.
You’ll love the side effects!
