A University of Florida-led study reported an association between use of the joint-health supplement glucosamine and a higher risk of progressing from mild cognitive impairment to dementia, as well as higher mortality among patients already diagnosed with Alzheimer’s disease and related dementias. The researchers emphasized that the findings do not prove glucosamine causes cognitive decline and said the results should be tested in clinical trials.
New research from the University of Florida suggests that glucosamine, a widely available over-the-counter supplement often used for joint pain, may be associated with faster progression of neurodegenerative disease. The findings, published June 9, 2026 in Nature Metabolism, draw on an analysis of deidentified UF Health electronic health records collected between 2012 and 2024, alongside laboratory work in mouse models and analyses of post-mortem human brain tissue. Using Artificial Intelligence methods, the researchers examined UF Health records for patients diagnosed with Alzheimer’s disease and related dementias (ADRD) or mild cognitive impairment (MCI). They reported that 1,896 patients with ADRD and 2,750 patients with MCI said they were taking glucosamine—about 8% of each group. After accounting for factors including age, sex and demographics, glucosamine use was associated with a 25% higher likelihood that patients with MCI would later develop dementia. The analysis also found glucosamine use was linked to a 25% increase in mortality risk among patients already diagnosed with ADRD; the researchers reported no similar mortality increase among patients with MCI. Senior author Ramon C. Sun, a University of Florida scientist affiliated with the McKnight Brain Institute, said the work adds to evidence that metabolic changes may contribute to neurodegenerative disease. “In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias such as Lewy body or frontotemporal dementia,” Sun said. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.” The study also pointed to a biological pathway that may help explain the association. The team reported evidence that a protein “sugar-tagging” process—glycosylation—appears excessively active in Alzheimer’s disease, and they argued this pathway may represent a potential therapeutic target. Co-author Matthew S. Gentry, chair of the University of Florida’s Department of Biochemistry and Molecular Biology, called the electronic health record findings “provocative,” while stressing the limitations of observational data. “While it’s an association and not proof of causality, it does raise an important clinical question that now deserves much more attention,” Gentry said. In experiments in genetically modified mice, the researchers reported that oral glucosamine supplementation increased sugar attachment to proteins and worsened social-memory performance, while chemically reducing the sugar-tagging activity improved memory. They also reported higher levels of sugar attachment to proteins in Alzheimer’s brain specimens compared with healthy control samples from a UF brain bank. The researchers said clinical trials would be needed to determine whether glucosamine directly influences dementia risk or survival, and whether any effects vary by disease stage.
