June 12, 2026, 11:10 am | Read time: 6 minutes
Alzheimer is primarily associated with amyloid and tau deposits. However, there is increasing evidence that metabolic processes could also influence the course of the disease. New research is focusing on the brain’s sugar metabolism. A study describes altered sugar structures as a possible factor and also examined the dietary supplement glucosamine in this context.
The amino sugar glucosamine serves as a building block for cartilage tissue and joint fluid in the body. It is sometimes used as a dietary supplement for joint pain and osteoarthritis. However, it is scientifically controversial, but more on that later.
A new study now concludes that glucosamine could potentially be linked to the progression of Alzheimer’s disease.1 According to the study, the substance could enhance the attachment of certain sugar structures to proteins.
Study on the Role of Sugar Metabolism in Alzheimer’s Disease
The study is not a classic investigation of a dietary supplement. Instead, it focused on the role of sugar metabolism in the brain in Alzheimer’s. Metabolic disorders have been discussed for years as contributing to the development and progression of dementia diseases. However, the metabolism of complex sugar structures has been much less researched.
The focus of the present work was on so-called N-glycosylation. This is a natural, enzyme-controlled process in which sugar chains are attached to proteins—a process important for normal brain function and signal transmission between nerve cells. However, the researchers suspected that excessive N-glycosylation, also called hyperglycosylation, could be more than just a side effect of the disease. According to their hypothesis, it could already contribute to the development of Alzheimer’s and promote the further course of the disease.
To test their assumption, the scientists combined several research approaches.
Details of the Investigation
The scientists examined brain tissue samples from deceased Alzheimer’s patients and healthy control subjects. They used modern imaging techniques to make metabolic products, fats, and sugar structures directly visible in the tissue.
Additionally, the research team analyzed two mouse models established in Alzheimer’s research. Using a special isotope labeling, the scientists were able to trace how increased glycosylation occurs. Is it because the body forms new sugar structures more frequently? Or does it break down existing ones more slowly?
To investigate the biological significance of the observed changes, the researchers specifically intervened in the sugar metabolism. They inhibited the key enzymes of sugar biosynthesis both genetically and with the help of drugs. In another approach, they administered the supplement glucosamine to the mice for two weeks to enhance glycosylation in the brain.
In another part of the investigation, the team analyzed electronic health data from the University of Florida Health Systems. Overall, the scientists had data from more than 50,000 patients with Alzheimer’s-associated dementias and from individuals with mild cognitive impairment. They specifically wanted to find out whether the documented intake of glucosamine is associated with the progression of the disease.
Results of the Investigation
The results suggest that pathologically increased glycosylation could actively drive Alzheimer’s disease. The researchers found significantly elevated levels in both the brains of Alzheimer’s patients and in both mouse models. The brain regions most affected were those crucial for memory and thinking.
The active inhibition of sugar biosynthesis in the Alzheimer’s mice led to an improvement in their performance in behavioral tests. On the other hand, the researchers observed a deterioration in cognitive abilities in the animals when glucosamine was administered, thus enhancing glycosylation. This observation was not confirmed in healthy mice.
The analysis of the health data also revealed anomalies. According to the data, the documented intake of glucosamine in patients with Alzheimer’s-associated dementias led to an increased risk of death. In subjects who already suffered from mild cognitive impairments, the likelihood of developing pronounced Alzheimer’s disease or another form of dementia increased.
Interestingly, the healthy brain seemed to be more resistant: Neither in healthy mice nor in people without a clear dementia diagnosis could the negative effects of glucosamine be observed to this extent.
Study Authors on the Significance of Their Results
In response to a FITBOOK inquiry, the corresponding study author Dr. Ramon Sun, on behalf of the entire team, emphasizes that the results do not speak against glucosamine in general. “For healthy people taking glucosamine for joint complaints, our data shows no warning signal,” he explains. The potential issue, according to the researchers, primarily concerns people whose brains are already affected by Alzheimer’s disease. There, the disease seems to activate a metabolic pathway that could be further stimulated by glucosamine.
At the same time, the researchers caution against overinterpretation. The analysis of patient data can only show correlations, not prove a cause-and-effect relationship. Moreover, results from animal models cannot be directly transferred to humans.
Again, they justify with the mouse experiments that the results should still be taken seriously: There, glucosamine worsened memory performance, while inhibiting the same metabolic pathway improved it. For doctors, it is therefore “reasonable to discuss the intake of glucosamine with patients who have an existing dementia diagnosis individually,” rather than issuing blanket recommendations.
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New, Promising Target for Alzheimer’s Therapies
The authors see particular potential in the newly identified metabolic pathway as a therapeutic target. The fact that the memory performance of the mice improved without affecting amyloid plaques or tau changes suggests that hyperglycosylation “could be an independent and complementary target” for future Alzheimer’s therapies.
As a next step, the scientists consider a clinical study to be sensible. However, in their view, this should not involve administering glucosamine to dementia patients for the first time. Instead, they advocate for a so-called withdrawal study: Patients already taking the supplement could be randomly assigned to either stop or continue using it. This would allow researchers to determine whether discontinuation affects the course of the disease without creating new risks. In parallel, the researchers are reportedly working on agents that aim to specifically inhibit the identified metabolic pathway in the brain.
Also interesting: Dementia – when to see a doctor
Why the Supplement Glucosamine Is Controversial
Even though the study authors found no general contraindications for glucosamine, the effectiveness of the supplement is scientifically disputed. According to consumer protection and expert authorities, there is no convincing scientific evidence for the benefits of glucosamine and chondroitin (a comparable, body-derived polysaccharide available as a dietary supplement) for joint health. Corresponding health-related advertising claims are also not approved in the EU, as they do not meet the requirements of the so-called Health Claims Regulation.2
In addition to the criticized, apparently relatively lax efficacy testing, possible risks and interactions are also described. This concerns, for example, diabetics or people with impaired glucose tolerance, as well as patients taking blood thinners.3 Allergic reactions are also documented. Overall, glucosamine is not recommended without reservation.