Category: Orthopedics
Posted: 6/27/2026 by Brian Corwell, MD
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Should patients with mild cognitive impaired take glucosamine for their knee pain?
Glucosamine is one of the most commonly used dietary supplements in the US.
It is an amino sugar. Made from glucose and the amino acid glutamine.
Approximately 5% of the general adult population reported using glucosamine in the prior week, with higher rates among older adults — up to 9% of elderly men and 7% of elderly women.
Several studies have investigated glucosamine use and risk of Alzheimer’s disease. This literature has suggested either no association or even a protective association (Zhou et al., 2023 & Zheng et al.2023).
A study published this month in Nature Metabolism found a different association.
The research team used AI to comb deidentified health records (65,000) in the University of Florida health system for patients diagnosed with either Alzheimer’s disease and related dementias (ADRD) or mild cognitive impairment (MCI).
24,000 patients with dementia and 41,000 with MCI.
They compared people who took glucosamine with those who didn’t.
Data collected from 2012 to 2024.
8% of both groups of patients reported taking glucosamine. They attempted to control for features such as age, sex and other demographics.
In those with MCI, glucosamine use was associated with a 25% higher likelihood of progression to dementia. There was no increased mortality in this group.
In the ADRD group, glucosamine was associated with a 25% increase in mortality risk (<5 years).
The study found no adverse effects on cognitively healthy adults
If true, these findings suggest that the danger of glucosamine supplementation is unique to the biological environment of an already vulnerable or diseased brain.
The mechanism suggested involves hyperglycosylation.
Glucosamine crosses the BBB and acts as a fuel source adding excessive sugar tagging to proteins thereby affecting proper protein functioning.
To further test this, researchers investigated normal mice or mice engineered with Alzheimer’s symptoms, Feeding glucosamine to the Alzheimer’s mice severely worsened their memory deficits. There was no effect on the healthy mice.
Interestingly, they then chemically blocked the sugar-tagging enzyme that makes sugars like glucosamine and this reversed the cognitive decline (improved dementia symptoms).
They then looked at post-mortem tissue samples of human Alzheimer’s brains and found they possessed a heavy, abnormal accumulation of these sugars as compared to healthy control brains.
As usual, this study needs to be further investigated in an ethically constructed interventional trial before firm conclusions can be made from this association
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).
