A widely used joint supplement taken by millions of older adults for arthritis pain has been linked to accelerated cognitive decline, new research suggests, raising urgent questions about the safety of a remedy that many patients buy without prescription.
Glucosamine, sold over-the-counter in pharmacies and supermarkets across the UK, is a staple of self‑care for osteoarthritis. In the UK Biobank – one of the country’s largest health databases – roughly one in five participants report taking it regularly. Across the Atlantic, about 40 million Americans use it each year to ease joint inflammation and pain. Yet despite this popularity, official guidelines in Britain have long been cautious: the National Institute for Health and Care Excellence (NICE) does not recommend glucosamine for osteoarthritis, citing inconsistent trial results and a lack of strong evidence of meaningful benefit. GPs no longer prescribe it on the NHS, deeming it not cost‑effective. Some patients do report mild relief, particularly with glucosamine sulphate at 1500 mg daily, but the effects are considered modest.
Study links supplement to faster decline and higher death risk
Now a study published in Nature Metabolism by neuroscientists at the University of Florida suggests the supplement may be doing more harm than good for those already on the path to dementia. Using artificial intelligence to analyse anonymised UF Health records from 2012 to 2024, the team identified patients diagnosed with Alzheimer’s disease and related dementias, or with mild cognitive impairment (MCI) – a stage often preceding Alzheimer’s. Among these patients, about eight per cent reported using glucosamine, representing 1,896 individuals with established dementia and 2,750 with MCI.
After adjusting for age, sex and demographics, the data showed that those with MCI who took glucosamine faced a 25 per cent greater likelihood of progressing to Alzheimer’s disease compared with non‑users. For patients already living with dementia, the same supplement was linked to a 25 per cent increase in mortality risk. Notably, this higher death rate was not seen among the MCI group, suggesting the supplement’s effects may become more dangerous as the disease advances.
Senior author Ramon Sun, director of the Center for Advanced Spatial Biomolecule Research, said: “A lot of these people actively take an over‑the‑counter supplement that could be making their disease progression worse.” Co‑author Matt Gentry, chair of the university’s Department of Biochemistry and Molecular Biology, acknowledged the data are preliminary: “While it’s an association and not proof of causality, it does raise an important clinical question that now deserves much more attention.”
The findings add to a complex picture. Earlier large‑scale studies, including some using UK Biobank data, had suggested that regular glucosamine use might be linked to a lower risk of dementia, including Alzheimer’s and vascular dementia. The University of Florida researchers stress that their work is observational and does not prove cause and effect; human clinical trials are needed before any definitive conclusions on safety can be drawn.
How glucosamine may fuel the disease
To understand what might be happening inside the brain, the team investigated a metabolic pathway that is already known to be dysregulated in Alzheimer’s. The process involves attaching sugar molecules to cellular proteins – a kind of “sugar‑tagging” that becomes overly active in the disease. Glucosamine, a naturally occurring sugar‑related compound, can cross the blood‑brain barrier. Once inside the brain, it appears to feed into this aberrant pathway, providing raw material for excessive sugar attachment.
Experiments in genetically modified mice confirmed the effect. When the animals were given glucosamine, the sugar‑tagging of proteins increased significantly and their recognition memory – the ability to remember previously encountered objects or situations – worsened. Crucially, when the scientists chemically blocked the attachment process, the mice’s memory function improved.
Analysis of human brain tissue from the UF Neuromedicine Brain and Tissue Bank provided further evidence. Samples from Alzheimer’s patients showed markedly elevated levels of sugar attachment to proteins compared with healthy controls. The team believes this metabolic dysfunction may actively drive disease progression rather than merely accompany it.
Senior author Sun said: “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.”
Context and cautions for users
The supplement is classified as a dietary supplement by the US Food and Drug Administration, meaning it is regulated less strictly than medicines. In the UK, Glucosamine is sold in sulphate and hydrochloride forms, and while generally considered safe, it carries some side effects: mild gastrointestinal issues such as nausea, indigestion and diarrhoea, heartburn and bloating. Those with shellfish allergies should be cautious, as many products are derived from shellfish. It may also interact with blood‑thinning medication like warfarin – increasing bleeding risk – and could affect blood sugar levels in people with diabetes, requiring careful monitoring.
The researchers emphasise that their findings are preliminary. Gentry noted: “The electronic health record data are very provocative,” but cautioned that they show an association, not proof. The study does, however, add weight to the growing recognition that what we put into our bodies can have unintended consequences for brain health – and that for some of the most vulnerable patients, a common joint pain remedy may be doing far more harm than good. No definitive recommendation can yet be made; the team calls for clinical trials to determine whether glucosamine should be avoided by people with cognitive impairment.