A widely used supplement marketed to reduce joint pain may be linked to faster progression of Alzheimer’s disease, according to a new study from the University of Florida.
The study found that people with mild cognitive impairment who reported taking glucosamine were more likely to progress to dementia than those who did not take the supplement. Researchers also found evidence suggesting that glucosamine may interact with biological processes in the brain that are already impaired in Alzheimer’s disease.
The findings were published on June 9th. natural metabolismis based on extensive analysis of patient health records combined with advanced imaging studies of human brain tissue and mouse models of Alzheimer’s disease.
Although the results do not prove that glucosamine causes dementia, which needs to be confirmed in clinical trials, the researchers say the study adds to growing evidence that metabolic dysfunction plays an important role in neurodegenerative diseases.
“About 7 million people in the United States have Alzheimer’s disease, and millions more have related dementias such as Lewy body dementia and frontotemporal dementia,” said senior author Dr. Ramon Sun, director of the Center for Advanced Spatial Biomolecular Research and associate director of innovation at the University of California’s McKnight Institute for Brain Research. “Many of these people are actively taking over-the-counter supplements that can worsen the progression of the disease.”
Glucosamine use and risk of dementia
Because glucosamine is widely available and frequently used by older adults to support joint health, researchers wanted to see if glucosamine could have an impact on Alzheimer’s disease and related dementias (ADRD).
The research team, in collaboration with co-investigators Dr. Yi Guo and Dr. Jiang Bian, used artificial intelligence to analyze anonymized UF health records collected between 2012 and 2024. They focused on patients diagnosed with ADRD or mild cognitive impairment (MCI).
Researchers found that glucosamine use was relatively common among these patients. A total of 1,896 ADRD patients and 2,750 MCI patients reported taking supplements, representing approximately 8% of each group.
After taking into account factors such as age, gender and demographics, the analysis showed that glucosamine use was associated with a 25% higher chance that people with MCI would later develop dementia.
Researchers also observed that glucosamine use was associated with a 25% increased risk of death in people who were already diagnosed with ADRD. A similar increase was not seen in MCI patients, suggesting that the effects of supplements may vary depending on the stage of the disease.
Potentially important metabolic pathways
The study also pointed to specific biological processes that may help explain this association.
Researchers have identified evidence that protein and sugar tagging pathways are overactive in Alzheimer’s disease. According to the research team, this pathway could represent a new target for future treatments.
“Our findings suggest that metabolic changes significantly contribute to the progression of Alzheimer’s disease, and furthermore, addressing metabolic abnormalities may be an important complement to approaches focused on Alzheimer’s disease plaques and Alzheimer’s disease,” Sun said.
This discovery was made possible by advanced spatial analysis techniques developed in Sun’s lab.
“This technology allows us to examine the thousands of molecules produced when the body breaks down food and drugs, revealing complex pathways that would otherwise be hidden,” Sun said.
Effects of glucosamine on the brain
To investigate further, researchers turned to glucosamine. This is because glucosamine is a naturally occurring sugar-related molecule that can cross the blood-brain barrier. Once in the brain, it can contribute to biochemical pathways involved in building complex sugar structures on proteins. Commercially available glucosamine supplements are often manufactured from materials such as seashells and corn.
The results of this study suggest that the effects of glucosamine may be highly dependent on the biological environment in which it acts.
“Electronic medical record data is very provocative,” said study co-author Dr. Matt Gentry, chair of the university’s Department of Chemistry and Molecular Biology. “While this is an association and not proof of causation, it does raise important clinical questions and now deserves more attention.”
Gentry says Alzheimer’s brains may be particularly susceptible to disruptions in this pathway compared to healthy brain tissue.
Mouse studies and human brain tissue findings
Experiments using genetically modified mice further supported this hypothesis.
Researchers found that glucosamine significantly increases the binding of sugar molecules to proteins within cells. Mice given glucosamine also showed worsened deficits in social memory, the ability to recognize and remember other individuals.
When scientists chemically reduced the activity of this sugar tag, memory improved.
The team then worked with Stefan Prokop, MD, to examine human brain tissue taken from the UF Neuromedicine Brain and Tissue Bank. Compared to healthy control samples, Alzheimer’s disease brain specimens showed significantly higher levels of sugar binding to proteins.
The researchers say that, taken together, these findings suggest that this metabolic abnormality is not simply a consequence of Alzheimer’s disease, but may actively contribute to it.
“Proteins are the molecular machinery of the cell, and many of them need to be sugar-tagged in the right way in order to fold correctly and move to the right place to do their job,” Gentry said. “What we found in Alzheimer’s disease is that this sugar-tagging system appears to be overactive. The Alzheimer’s brain is adding too many of these sugar structures, and this appears to be contributing to the disease rather than preventing it.”
