A widely used joint supplement may be doing more than just soothing creaky knees - it might also be speeding up the path to dementia. Researchers at the University of Florida have found that glucosamine, the popular over-the-counter joint pain remedy, is associated with a 25% higher likelihood that people with mild cognitive impairment will progress to Alzheimer’s disease.

Published June 9 in Nature Metabolism, the study analyzed UF Health records from 2012 to 2024 using AI, focusing on patients with Alzheimer’s or mild cognitive impairment. Among 2,750 MCI patients and 1,896 Alzheimer’s patients who reported taking glucosamine - about 8% of each group - the supplement was linked to a 25% increase in dementia progression risk for MCI patients and a 25% increase in mortality for those already diagnosed with Alzheimer’s.

The researchers, led by Ramon Sun, Ph.D., director of the Center for Advanced Spatial Biomolecule Research, also identified a potential mechanism: glucosamine may overactivate a sugar-tagging pathway in the brain, disrupting protein function. Experiments in genetically modified mice showed glucosamine worsened social memory deficits, while reducing sugar-tagging activity improved memory. Human brain tissue from the UF Neuromedicine Brain and Tissue Bank confirmed higher levels of sugar attachment to proteins in Alzheimer’s samples.

“In the United States, there are about 7 million people living with Alzheimer’s and millions more with related dementias,” Sun said. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.” The findings don’t prove causation, the team cautions, but they raise enough eyebrows to warrant clinical trials. As study co-author Matt Gentry, Ph.D., put it: “The electronic health record data are very provocative. While it’s an association and not proof of causality, it does raise an important clinical question.”