Every so often, a scientific article hits the press, causing patients to question their supplement regimens. We’ve recently seen it with long-term melatonin use and increased risks of heart failure and mortality. Now, a new study has raised questions about glucosamine, a popular supplement used for arthritis and joint health, and its possible link to Alzheimer’s disease (AD).
How can a joint supplement impact brain health? Glucosamine readily crosses the blood-brain barrier, where it can be incorporated into brain glycans. Complex carbohydrate metabolism, including glycan biosynthesis, is essential for normal brain function. While glycosylation is critical for neuronal health, excessive glycan production or impaired glycan processing may contribute to neurodegeneration.
The Study
A study published in Nature Metabolism assessed hyperglycosylation as a pathological driver of AD, employing multiple experimental approaches to provide supporting evidence:
- Hyperglycosylation in brain tissue: Advanced imaging revealed hyperglycosylation in vulnerable brain regions in AD brain tissue compared with healthy human brain tissue. These findings were validated in AD mouse brain samples, allowing researchers to use experimental mouse models to evaluate the effects of glucosamine.
- AD mice given glucosamine show deficits: AD mice with genetic knockout of glycan biosynthetic enzymes showed improved cognition compared to those with intact glycan biosynthesis, establishing hyperglycosylation as a pathologic contributor. Glucosamine supplementation increased glycosylation in AD mouse brain samples, and mice showed poorer social memory performance. Healthy mice given glucosamine did not show cognitive deficits or hyperglycosylation.
- Glucosamine’s impact on dementia patients: Researchers performed a retrospective analysis using electronic health records from the University of Florida Health System. They identified over 50,000 patients with mild cognitive impairment (MCI) and AD-related dementia and selected those with documented glucosamine supplementation for at least 1 year. Glucosamine use was associated with a higher progression from MCI to AD and 25% increased mortality in AD-related populations.
The researchers concluded that these findings support the mechanism of hyperglycosylation as a driver of AD progression. The evidence suggests that glucosamine’s harmful effects may vary according to the existing neurometabolic state.
In many cases, the underlying condition may contribute more to health risks than the supplements used to treat it. For example, glucosamine is commonly taken for arthritis, a chronic inflammatory condition.
Conclusions
The study suggests that the healthy brain may possess an inherent resilience to glucosamine exposure, as no adverse effects were observed in the non-diseased mouse model. However, glucosamine was not evaluated in cognitively healthy human populations for comparison.
Continued research into dietary supplements is essential, particularly because many over-the-counter products are perceived as inherently safe. At the same time, it’s important to interpret new findings carefully. Observational studies can identify associations, but they do not establish cause and effect. As a result, reported links should prompt further investigation rather than definitive evidence that a supplement causes a particular health outcome.
In many cases, the underlying condition may contribute more to health risks than the supplements used to treat it. For example, glucosamine is commonly taken for arthritis, a chronic inflammatory condition. Chronic inflammation and reduced physical activity, both common in arthritis, are established risk factors for cognitive decline and may confound the observed association between glucosamine use and AD.
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Reference
Hawkinson, T.R., Liu, Z., Ribas, R.A. et al. Hyperglycosylation is a metabolic driver of Alzheimer’s disease. Nat Metab 8, 1410–1425 (2026). https://doi.org/10.1038/s42255-026-01538-4
