Popular Supplement May Be Linked to Faster Dementia Progression, Study Finds

A new study in Nature Metabolism raises concern that glucosamine, a widely used over-the-counter supplement for joint pain, may be associated with faster Alzheimer’s progression and worse outcomes for people already diagnosed with dementia. The research was led by scientists at the University of Florida and other U.S. institutions.

In a review of medical records collected from 2012 to 2024 in the University of Florida health system, researchers analyzed tens of thousands of patients with different levels of cognitive decline. Among people with mild cognitive impairment, or MCI, glucosamine use was linked to a 25% higher risk of progressing to dementia. Among patients already living with dementia, the supplement was associated with a 25% higher risk of death during follow-up.

The study also examined what appeared to be happening biologically. The team focused on glycosylation, a normal process in which sugar molecules are attached to proteins, and found that brains of Alzheimer’s patients showed what they called hyper-glycosylation. Using metabolic tests, postmortem human brain tissue and mouse models of Alzheimer’s, the researchers reported that glycosylation levels rose as the disease advanced. They wrote that the process seemed driven by increased production of sugar molecules, not slower breakdown, and said hyper-glycosylation may be an active contributor to disease development rather than just a byproduct.

In mice given glucosamine at a dose comparable to a typical human therapeutic dose, glycosylation rose within two weeks and memory and social behavior worsened. When the glycosylation pathway was experimentally reduced, glycosylation levels fell and cognitive performance improved. The authors say the findings justify further study, including a large randomized double-blind clinical trial to test whether glucosamine affects cognitive decline.

Israeli neurologist Dr. Polina Spector of Carmel Medical Center said the study is the first to suggest a possible link, but it does not prove cause and effect because the human data were retrospective and the animal work was primary. She noted that people taking glucosamine may also have other conditions, such as diabetes, that could worsen cognition, and pointed to a 2023 BMC Medicine study that found the opposite, a lower dementia risk among regular users. An editorial accompanying the paper said glycosylation could become a future treatment target for Alzheimer’s.