Researchers at the University of Florida cross-referenced twelve years of medical records with analyzes of human brains and experiments in mice. A worrying signal, but which does not yet allow us to confirm that glucosamine directly accelerates the disease.
Does this joint supplement hide an unexpected risk?
Glucosamine is commonly used to try to relieve pain related to osteoarthritis. Available without a prescription, it is particularly common among seniors. But could it have an effect on an already weakened brain?
To find out, researchers at the University of Florida used artificial intelligence to analyze deidentified medical records from UF Health between 2012 and 2024. They identified 24,481 people with Alzheimer’s or related dementia and 41,884 with mild cognitive impairment, characterized by measurable memory difficulties but not yet significantly disrupting daily life.
In both groups, around 8% took glucosamine: 1,896 people in the first and 2,750 in the second.
After controlling for age, gender, and demographic characteristics, people with mild cognitive impairment taking glucosamine had 25% more likely to progress to dementia.
In patients already suffering from Alzheimer’s or related dementia, taking the supplement was also associated with
a 25% increase in mortality risk. This association was not found in people with only mild cognitive impairment.
For Ramon Sun, director of the Center for Advanced Spatial Biomolecule Research at the University of Florida, the signal is therefore worth studying: “Many of these people are actively taking an over-the-counter supplement that could worsen the progression of their disease.”
In the brain, a biological track begins to emerge
The researchers didn’t stop at medical records. They also sought to understand how glucosamine could act on a diseased brain.
The lead concerns glycosylation, a mechanism which consists of attaching structures made up of sugars to certain proteins. This step is normal and essential for the functioning of cells. But in the brains studied in people with Alzheimer’s, this system seems particularly active.
Glucosamine can cross the blood-brain barrier and fuel these metabolic pathways.
- In mice genetically modified to reproduce certain aspects of Alzheimer’s, researchers observed an increase in this binding of sugars to proteins after administration of glucosamine. The animals also showed worsening “social memory” difficulties. Conversely, when scientists chemically blocked this process, memory improved.
- Analyzes of human brains provided another element: this fixation of sugary structures was significantly greater in samples from people with Alzheimer’s than in controls.
Matt Gentry, co-author of the study, explains: “What we found in Alzheimer’s disease is that this sugar labeling system seems to be overactive. The Alzheimer’s brain adds too many of these sugary structures, and this appears to contribute to the disease rather than protect it.”.
Should we stop glucosamine? Not so fast…
The result is intriguing, but it does not support the conclusion that glucosamine causes dementia.
The study is retrospective: the researchers observed data already present in medical records, without experimentally controlling the intake of the supplement. Some consumption may also not have been recorded.
In other words, other factors could help explain the observed association.
Matt Gentry emphasizes this distinction: “This is an association and not proof of causation, but it raises an important clinical question that now deserves much more attention.”.
It is therefore not possible, based on this study alone, to say that everyone taking glucosamine increases their risk of dementia. Rather, the results suggest that
the brain already affected by a neurodegenerative disease could be particularly vulnerable to this metabolic disturbance.
A new avenue for understanding Alzheimer’s?
For researchers, the interest of this work ultimately goes beyond glucosamine. They highlight the possible role of
brain metabolism in the progression of Alzheimer’s, in addition to research devoted to amyloid plaques and tau proteins.
Ramon Sun summarizes their hypothesis: “Our results suggest that impaired metabolism contributes significantly to the progression of Alzheimer’s disease and that correcting this metabolic defect could be an important complement to approaches focused on Alzheimer’s-associated plaques and tangles.”.
But an essential step is still missing: a controlled clinical trial in humans. This alone will make it possible to determine whether glucosamine really accelerates the disease and, possibly, in which patients.
In the meantime, the authors recommend that people with mild cognitive impairment or dementia discuss their glucosamine use with their doctor. A simple precaution, without giving in to alarm, while research is still trying to understand this unexpected signal.