New research has found an association between taking glucosamine, and a higher likelihood of progressing from mild cognitive impairment to Alzheimer’s disease. 

The study, by neuroscientists at University of Florida, also found that people with Alzheimer’s disease who took a regular glucosamine supplement were 25% more likely to die within a specified time frame than those who didn’t. 

The findings are based on a large retrospective analysis of patients’ records as well as supporting data from advanced imaging technology used to scan human brain specimens and Alzheimer’s disease mouse models.

The Florida team cautions that the results are preliminary and require validation in a human clinical trial, but says they provide another piece of a much bigger mechanistic picture involving metabolic dysregulation and neurodegeneration, according to the study published today in Nature Metabolism.

“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,” said senior author Ramon Sun, Ph.D., director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation of UF’s McKnight Brain Institute. “A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.”

As glucosamine is widely available and commonly used by older people for joint health, researchers set out to investigate whether it could have any effect in Alzheimer’s disease and related dementias, known as ADRD.

With collaborators Yi Guo, Ph.D., and Jiang Bian, Ph.D., the team used artificial intelligence to comb deidentified UF Health records from 2012 to 2024 for patients diagnosed with either ADRD or mild cognitive impairment, or MCI. They found that a significant proportion — 8% — of both types of patients reported taking glucosamine: 1,896 with ADRD and 2,750 with MCI.

After controlling for age, sex and demographics, the analysis showed that glucosamine use was associated with a 25% higher likelihood of progression from mild cognitive impairment to dementia.

In addition, researchers found that taking glucosamine was associated with a 25% increase in mortality risk, or the likelihood of death within a specified time frame, among ADRD patients. For the MCI group, there was no such impact, suggesting the impact of glucosamine may be greater in patients with established dementia.

Notably, said Sun, researchers revealed that a metabolic process in which a protein and sugar-tagging pathway is overactive in Alzheimer’s could be a new target for intervention.

“Our results suggest that altered metabolism is a significant contributor to Alzheimer’s progression and, in addition, addressing the metabolic defect could be an important complement to approaches focused on Alzheimer’s plaques and tangles,” Sun said.

The findings suggest that glucosamine’s impact may depend on biological context, with the Alzheimer’s brain appearing more vulnerable to this metabolic pathway than the nondiseased brain, said Matt Gentry, Ph.D., chair of UF’s Department of Biochemistry and Molecular Biology and a study co-author.

“The electronic health record data are very provocative,” Gentry said. “While it’s an association and not proof of causality, it does raise an important clinical question that now deserves much more attention.”