Individuals with Alzheimer’s disease who consumed the common supplement glucosamine were 25% more likely to die within five years compared to those who did not take it.
This is the main conclusion of a recent study that my colleagues and I published in the journal Nature Metabolism.
Glucosamine, a sugar molecule, is marketed as an over-the-counter treatment for joint pain and arthritis. More than 40 million Americans use it annually.
Our research also found that glucosamine impacted individuals in the earliest phase of memory loss, known as mild cognitive impairment. Those in this initial stage of dementia who took glucosamine were 25% more likely to progress to full Alzheimer’s disease.
Our study utilized anonymized medical records from the University of Florida Health system to analyze patients with Alzheimer’s disease.
We examined 24,000 patients with dementia and 41,000 with mild cognitive impairment, comparing those who took glucosamine to those who did not.
We further conducted experiments on mice engineered to exhibit Alzheimer’s-like symptoms to explore the potential mechanism through which glucosamine affects the brain.
Our findings revealed that blocking the enzyme responsible for producing sugars like glucosamine alleviated dementia symptoms in mice. Conversely, giving glucosamine to these mice exacerbated memory loss.
In healthy mice, however, the supplement had no effect.
Why it matters
The Food and Drug Administration classifies glucosamine as a dietary supplement, not a prescription drug. Consequently, it is available over the counter without requiring a doctor’s consultation.
Glucosamine is an amino sugar composed of glucose and an amino acid called glutamine, which the body uses to construct new cells.
Since glucosamine is not deemed an essential nutrient, there is no recognized condition of glucosamine deficiency.
Nonetheless, people take the supplement based on anecdotal evidence suggesting it enhances joint health, particularly in the knees.
For over ten years, my research team and I at the University of Florida have investigated how the brain utilizes and processes sugar and the issues that arise with this process in people with Alzheimer’s disease.
A less commonly known issue with Alzheimer’s disease is the buildup of excess sugar coatings on brain cells and proteins.
Normally, brain cells and proteins have short chains of sugar on their surface called N-glycans, which help guide new proteins into their three-dimensional shapes and allow them to attach to other proteins.
In individuals with Alzheimer’s, these sugar chains accumulate in inappropriate areas, causing the proteins beneath them to malfunction, which results in memory loss and cell death. This phenomenon is known as hyperglycosylation.
With approximately 7.2 million Americans aged 65 and older living with Alzheimer’s disease, we estimated that many are also taking glucosamine for joint health.
We hypothesized that this sugar amine might contribute to cognitive decline.
Previous studies have associated glucosamine supplements with a lower risk of dementia in cognitively healthy individuals. Our research does not contradict these reports but rather refines them.
Although glucosamine appears to be safe and possibly protective for a healthy brain, it could be detrimental for a brain already experiencing cognitive decline.
What still isn’t known
Since our study relied on patient records rather than a controlled human experiment, it cannot definitively prove that glucosamine accelerates cognitive decline; it only suggests a correlation.
To definitively answer this question, a study randomly assigning glucosamine to some patients but not others would be required. However, if glucosamine potentially increases dementia risk, it would be unethical to administer it to patients.
Moreover, we still do not know if the potential harm of glucosamine to the brains of people with memory issues depends on the dosage, the brand of the supplement, or how long it is taken.
We also do not know whether this finding is applicable to other forms of dementia.
What’s next
To determine whether glucosamine directly causes cognitive decline, a clinical trial could be conducted on patients who previously took glucosamine and then stopped. About 8% of dementia patients in our database fall into this category.
We hope to track them over several years to see if discontinuing the supplement slows their cognitive decline.
Related: An Early Clue to Alzheimer’s May Appear as Young as 45, Study Finds
We are also examining compounds that block the N-glycan molecule and reduce sugar buildup on brain cells to determine if this could slow or reverse Alzheimer’s disease.
Additionally, we intend to investigate whether other supplements that the body metabolizes similarly to glucosamine pose similar risks for brains undergoing cognitive decline.
The Research Brief offers a concise overview of intriguing academic research.
Ramon Sun, Associate Professor of Biochemistry and Molecular Biology, University of Florida
This article is republished from The Conversation under a Creative Commons license. Read the original article.
