Scientists hunting for clues to Alzheimer’s progression didn’t expect to find them in a bottle of joint supplements, but a study published in June suggests glucosamine, taken by roughly 20 percent of Americans, may be worsening cognitive decline in brains that are already affected.
The findings appear to apply only to people who already have mild cognitive impairment (MCI) or Alzheimer’s disease.
“If you are a healthy person taking glucosamine for joint pain, our findings are not about you, and there is no reason to be alarmed or to throw out your supplement,” Ramon Sun, senior author of the study and director of the University of Florida’s Center for Advanced Spatial Biomolecule Research, told The Epoch Times.
The concern is specific to brains already affected by Alzheimer’s. “In that setting, glucosamine appears to feed the very process driving the disease, and in our data those patients had worse outcomes.”
Glucosamine Use Linked to Higher Risk
The study, recently published in Nature Metabolism, combined patient records, advanced brain imaging, human tissue samples, and Alzheimer’s disease mouse models.
Sun’s team examined clinical records from the University of Florida Health System from more than 4,600 patients diagnosed with either MCI or dementia between 2012 and 2024. About 8 percent reported using glucosamine.
Glucosamine use was associated with a 25 percent higher chance of progressing from mild cognitive impairment to dementia, as well as a 25 percent increased risk of death within 10 years among patients who already had dementia.
Sun and his colleagues describe the findings as preliminary and say testing in human trials is the next necessary step before drawing firm conclusions about cause and effect.
How Glucosamine May Affect the Brain
Glucosamine contributes to a chemical reaction that often goes into overdrive in Alzheimer’s disease. Just as diabetes is a disease caused by the body being unable to metabolize sugar, recent studies have also found evidence that the same may be happening in the brain during Alzheimer’s disease.
One way the brain metabolizes sugar is by tagging it to proteins, a process known as glycosylation. Hyperglycosylation, the excessive buildup of sugar-protein chains, may act as a primary metabolic driver of Alzheimer’s disease pathology rather than just a byproduct.
“This sugar-tagging system appears to be overactive,” study co-author Matt Gentry, chair of the University of Florida’s Department of Biochemistry and Molecular Biology, told The Epoch Times. “The Alzheimer’s brain is adding too many of these sugar structures, and this seems to contribute to the disease rather than protect against it.”
Glucosamine is a naturally occurring type of sugar molecule that can also feed into the glycosylation process.
In animal models, researchers found that supplemental glucosamine increased glycosylation and was associated with worsening Alzheimer’s disease pathology.
Brain tissue samples from Alzheimer’s disease patients had higher glycosylation levels than healthy controls, suggesting the dysfunction may actively drive disease progression rather than simply result from it.
“Our findings suggest that metabolic changes in the brain are important in Alzheimer’s progression,” Sun said. “Fixing this metabolic problem might be a helpful addition to existing treatments focused on brain plaques and tangles.”
A Reversible Pathway?
Sun noted that the pathway’s potential reversibility is the “encouraging side” of the findings. “The important point is that the pathway runs in both directions,” he said. “If feeding it makes things worse, turning it down should help, and that is what we saw.”
When the team reduced glycosylation in mice, both genetically and with a drug-like inhibitor, their memory improved. The discovery adds to existing research, pointing to insulin resistance and impaired glucose metabolism as potential drivers of Alzheimer’s disease. The study authors described Alzheimer’s as a “manifestation of diabetes.”
That framing opens up the possibility of new therapeutic strategies incorporating lifestyle modifications and the use of antidiabetic medications as potential tools to slow cognitive decline.
Discovery Points to a New Treatment Strategy
Sun noted that the benefit his team observed in mice came through a completely separate route from the amyloid plaques and tau tangles, the hallmarks the field has focused on for years. “We improved function without changing either of those,” he said. “So this pathway is a target in its own right, and one that could potentially be combined with existing therapies rather than replace them.”
“The finding supports a larger shift in how we think about Alzheimer’s, not only as a disease of plaques and tangles but as a disease of metabolism,” Sun added. “That view is opening up new ways to understand it and, I hope, new ways to treat it.”
The practical challenge, Sun emphasized, is developing a drug that shuts down this pathway while still crossing into the brain, which is the hard part of any neurological medicine. “That is one of the directions we are now pushing, alongside work to identify exactly which patients are most affected,” he noted. “It is a question that still needs a proper clinical trial to settle.”