Glucosamine is widely used by older adults seeking support for aging joints, but new research raises concerns about its use among people with mild cognitive impairment. The supplement was associated with faster progression to dementia in that group, though the study could not prove that glucosamine caused the change.

Researchers at the University of Florida investigated how glucosamine might affect dementia risk and mortality. Their work combined medical record analysis, laboratory mouse models and examinations of healthy human brains and brains affected by Alzheimer’s disease.

Published in Nature Metabolism, the study focused on glycosylation, a natural process in which brain cells attach small sugar chains to proteins. These chains help proteins fold properly, move to the correct locations within cells and connect with other proteins.

“You can think of these sugar chains as the labels and fittings on a machine part — they help a protein fold correctly, get shipped to the right place in the cell and connect with its partners,” senior author Ramon Sun, Ph.D., professor of biochemistry and molecular biology in the College of Medicine at University of Florida, told Fox News Digital. “The right amount is essential.”

Glucosamine is a naturally occurring compound made from sugar and an amino acid group, according to Neil Levin, senior nutrition education manager at Now, an Illinois manufacturer of glucosamine supplements. It is concentrated in cartilage, the connective tissue that cushions joints.

The compound is also part of larger molecules that help cartilage retain water while maintaining strength and elasticity. “Support for aging joints is the primary reason people take glucosamine as a dietary supplement,” Levin told Fox News Digital.

According to Sun, the body has an internal checkpoint that regulates how many sugar chains it produces. Supplemental glucosamine bypasses that initial checkpoint and rapidly increases the supply of material available for making the chains.

Researchers analyzed records from thousands of patients with dementia, including Alzheimer’s disease, and patients with mild cognitive impairment. They then narrowed their examination to people who were taking glucosamine.

Among patients with mild cognitive impairment, glucosamine use was not associated with a change in mortality risk. However, those taking the supplement were 25% more likely to progress to dementia, while glucosamine users who already had dementia showed higher mortality than similar people who did not use it.

The researchers also examined brain tissue for clues that might explain the association. “We found an excess of sugar chains on proteins in the Alzheimer’s brain,” Sun said.

Many of the affected proteins help nerve cells communicate, but Sun said excessive sugar chains may interfere with their function. He compared the process to covering a key with so much wax that it remains the same key but can no longer fit properly into its lock.

Researchers also followed the processing of glucosamine in mice and compared its effects in healthy brains with those affected by disease resembling Alzheimer’s. “In our experiments, normal mice given glucosamine showed no increase in these sugar chains and no change in a memory test,” Sun said.

“But in mice with Alzheimer's-like disease, where the production line was already running too hot, glucosamine increased the sugar chains further and worsened performance on a memory test.” The different findings led researchers to emphasize that healthy brains and brains affected by dementia may respond differently.

The research carries significant limitations because it relied on medical records, which may not include every supplement a patient used. Records also may not reliably show the product, dose, brand, duration or consistency of glucosamine use.

“Health records tell us what was documented, not everything a person took,” Sun said. “Over-the-counter supplements are not always recorded, and records don't reliably capture dose, brand or how consistently someone took it.”

Levin noted that glucosamine users may differ in arthritis, pain, mobility, frailty and medication use. Because the observational study examined past records, it could identify an association but could not establish that glucosamine caused Alzheimer’s disease or cognitive decline.

“The finding should therefore be treated as a safety signal that warrants controlled human research, but it did not — could not — reach a conclusion that glucosamine causes Alzheimer’s disease,” Levin said. Researchers called for a carefully designed clinical trial to evaluate glucosamine’s impact on cognitive decline among patients with dementia.

The study did not examine cognitively healthy people and does not suggest glucosamine poses a risk to people taking it for joint health. Sun said the current evidence is not strong enough to recommend any supplement for slowing Alzheimer’s disease.

“A brain affected by dementia and a healthy brain are different biological environments, and we shouldn't assume a supplement behaves the same way in both,” Sun said. He advised people with cognitive impairment or dementia to discuss glucosamine with a doctor before starting or stopping the supplement.