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Researchers from the University of Florida have reported a possible link between glucosamine—a widely used over-the-counter supplement for joint health—and an increased risk of cognitive decline progression. The study was published in the journal Nature Metabolism.

Glucosamine is a naturally occurring compound found in cartilage. It is commonly taken to relieve joint pain and manage osteoarthritis because it is believed to reduce inflammation and support cartilage structure. However, the new findings raise questions about its potential effects on brain health.

The researchers analyzed health records from the University of Florida Health system covering the period from 2012 to 2024. Using artificial intelligence tools, they identified patients with mild cognitive impairment, dementia, and Alzheimer's disease.

Approximately 8% of patients experiencing cognitive decline were taking glucosamine. The analysis found that these individuals had about a 25% higher risk of progressing from mild cognitive impairment to dementia and Alzheimer’s disease compared with those who did not use the supplement. They also showed an approximately 25% higher risk of mortality.

The authors emphasize that the findings demonstrate an association rather than a proven cause-and-effect relationship. Nevertheless, they consider the results clinically important and worthy of further investigation.

A key focus of the study was glucosamine’s potential influence on protein glycosylation—the process by which sugar molecules are attached to proteins. While glycosylation is essential for normal protein function, excessive activity of this pathway may contribute to disease.

According to the researchers’ hypothesis, this process may become overactive in Alzheimer’s disease, promoting the formation of abnormal protein structures, including amyloid plaques and tau tangles.

Experiments in genetically modified mice showed that glucosamine administration increased the addition of sugar groups to proteins and was associated with impaired memory performance. Conversely, suppressing this process led to improvements in cognitive function.

Additional analyses of human brain tissue samples also revealed increased glycosylation activity in patients with Alzheimer’s disease.

The researchers conclude that metabolic disturbances may play a more significant role in dementia progression than previously recognized and could represent a promising new target for future therapeutic interventions