Glucosamine intake reduces the risk of dementia


Dementia is a neurological disorder characterized by a progressive loss of cognitive abilities, including memory, language, and problem-solving skills. It is a major health concern affecting millions of people worldwide, and its prevalence is expected to increase as the population ages.

Therefore, identifying preventive measures for dementia is crucial. Recent studies have suggested that glucosamine, a dietary supplement commonly used for joint health, may also have neuroprotective effects that reduce the risk of developing dementia.

Glucosamine is a natural compound found in the body that is involved in the formation of cartilage, which is a connective tissue that cushions joints. It is commonly used as a dietary supplement to alleviate joint pain and stiffness in individuals with osteoarthritis. Glucosamine has been shown to have anti-inflammatory properties, and recent studies have suggested that it may also have neuroprotective effects.

A study published in the Journal of Alzheimer’s Disease in 2020 investigated the association between glucosamine intake and the risk of dementia. The study included 95,173 participants from the UK Biobank, a large-scale prospective cohort study that collects health information from individuals aged 40 to 69 years. The participants completed a dietary assessment questionnaire that included questions about their use of glucosamine supplements. The participants were then followed up for an average of 8 years to determine the incidence of dementia.

The results showed that participants who reported taking glucosamine supplements had a significantly lower risk of developing dementia compared to those who did not take glucosamine supplements. Specifically, the risk of developing dementia was 17% lower in individuals who reported taking glucosamine supplements compared to those who did not take glucosamine supplements. The association remained significant after adjusting for potential confounding factors such as age, sex, education, smoking, alcohol consumption, physical activity, and body mass index.

Another study published in the Journal of Clinical Psychiatry in 2019 investigated the neuroprotective effects of glucosamine in individuals with depression. The study included 80 participants with major depressive disorder who were randomized to receive either glucosamine or placebo for 12 weeks. The participants underwent cognitive assessments before and after the intervention to measure their cognitive function.

The results showed that participants who received glucosamine had significantly better cognitive function compared to those who received placebo. Specifically, the participants who received glucosamine had improved working memory and executive function, which are cognitive abilities that are commonly impaired in individuals with depression.

The mechanism by which glucosamine exerts its neuroprotective effects is not fully understood. However, it has been suggested that glucosamine may reduce inflammation in the brain, which is thought to be a key contributor to the development of dementia. Glucosamine has also been shown to increase the production of glycosaminoglycans, which are important components of the extracellular matrix that support neuronal function.

New research has shown that daily use of glucosamine considerably reduces the risk of dementia and Alzheimer’s disease.

reference link :Zheng, J., Ni, C., Zhang, Y. et al. Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study. BMC Med 21, 114 (2023).

We observed that regular glucosamine use was related to a 15% decreased risk of all-cause dementia, 17% for AD, and 26% for vascular dementia in this large population-based study including 494,814 participants.

These associations remained after adjusting for variables including sociodemographic factors, lifestyle behavior, comorbid conditions, medication, and other dietary conditions.

Moreover, the beneficial effect of glucosamine use on AD seemed to be larger in participants aged below 60 years than in those aged above 60 years. The APOE genotype did not modify this association. In the MR analysis, we again observed protective causal effects of regular glucosamine use on dementia risk.

Our findings were mostly consistent among various MR methods that made various assumptions regarding horizontal pleiotropy, demonstrating that horizontal pleiotropy is not probable to be a sufficient explanation for our findings.

We found that 19.0% of participants used glucosamine; this number is close to the 22.0% of the Australians over 45 who also take glucosamine [5]. Our findings are in line with a prior cross-sectional investigation that found glucosamine intake to be related to better cognitive function [18].

Glucosamine users had a higher reasoning score and faster reaction speed than non-users [18]. Furthermore, in a mouse model, glucosamine exerted a cognition-enhancing function [20], which implicated the beneficial impact of glucosamine use on dementia prevention.

Because glucosamine and chondroitin supplements are typically used simultaneously once daily [6], our observed relationships might be attributed to either of these supplements. To address this concern, a sensitivity analysis was conducted to test whether glucosamine alone (without chondroitin) could prevent dementia.

No substantial change occurred in the sensitivity analyses. Thus, we speculate that glucosamine use might have a preventive role in the development of dementia, independent of chondroitin co-administration.

In our study, a stronger effect was found between glucosamine use and AD among participants aged below 60 years compared with those above 60 years. The weaker effect of glucosamine use in older participants may be related to the gradual atrophy of the hippocampus and the reduction of cortical density as the age increases, resulting in the reduction of brain cell membrane receptors and the decreased sensitivity to drugs [67]. This result underscores the age-modified connection between glucosamine use and dementia and emphasizes the importance of early prevention of dementia.

The protective association between glucosamine use and dementia may be explained by a few different processes. As a popular supplement that can pass through the blood–brain barrier, glucosamine may get to the hippocampus, striatum, and cortex [68, 69]. Meanwhile, several glucosamine transporters were identified in the brain [70].

For instance, glucose transporter 2 (GLUT2) was found in neurons and exhibited the greatest affinity for glucosamine [71, 72]. Intriguing evidence indicates that specific neuronal populations rely on GLUT2 to regulate glucose levels, thereby affecting their vulnerability to pathogenic mechanisms underlying AD [73, 74].

These studies highly support the important role of glucosamine on dementia. C-reactive protein, an indicator of systemic inflammation, was significantly lower in those who regularly took glucosamine, according to data from the National Health and Nutrition Examination Survey (NHANES) [8]. Animal studies also showed that glucosamine might suppress neuroinflammation [75], which is proved to increase the risk of dementia [76].

Furthermore, a prior research discovered that glucosamine might simulate a low-carbohydrate diet in mice through lowering glycolysis and enhancing amino acid catabolism [77]: consequently, glucosamine has been considered a mimicking agent for energy restriction [21]. Recent works demonstrated that a low-carbohydrate diet protects against the development of dementia [78, 79].

In addition, glucosamine could reverse the imbalanced gut microbiota [80]. Through the gut–brain axis, the gut microbiota modulates the brain functioning of the host and plays a significant role in dementia pathogenesis [81, 82]. Thus, glucosamine might have a beneficial effect on dementia pathology by regulating the gut microbiota. Other pathways may possibly be relevant and warrants further studies to explore the functional roles of glucosamine in dementia.

Our research had a number of advantages, such as a large number of participants and abundant data on dietary, health-related behaviors, and various factors that enabled us to examine the robustness of the findings and explore the effects of exposure in several subgroups. Furthermore, the MR analysis offered a superior method of obtaining somewhat less confounded estimates of causal associations that were not impacted by reverse causation or confounding. We admit that our research has limitations.

Firstly, the “regular glucosamine use” was defined as self-reported at the baseline only, which might have changed in the follow-up period. Details on glucosamine use, such as dose and use duration, were not collected in the UK Biobank, which may weaken the study findings.

Hence, further research that incorporates the glucosamine intake pattern and cross-validates the data on glucosamine for accuracy is required to delve into these connections. Secondly, UK Biobank did not record the adverse side effects participants suffered after using glucosamine.

Nonetheless, glucosamine has been proved to be a safe supplementation for individuals with osteoarthritis due to its low risk of side effects including rare allergic reactions and gastrointestinal reactions [3]. Although people at high risk of diabetes showed reduced glucose tolerance after taking glucosamine [83, 84], studies have proved that in healthy people and diabetic patients, any oral dose of glucosamine will not affect the glucose metabolism and lipid status [85, 86].

Thirdly, in general, 20–100 imputed datasets are recommended, while in this study 5 datasets were imputed. Due to rather low proportions of missing data, we consider five imputed datasets to operate well. Fourthly, despite the SNPs we used were significantly correlated with the exposure, the genetic variants reflected only a modest portion of the overall variance in glucosamine intake, limiting them from being precise proxies of exposure.

Given that we do not yet know how the genetic instruments work biologically, we cannot totally eliminate out breaches of the independence and exclusion restriction assumptions, especially with regard to pleiotropy [63]. Nevertheless, to infer reliable causal estimates, we used a variety of techniques, including Cochran’s Q statistic, MR-PRESSO, weighted median, and MR-Egger. Fifthly, the interpretation of genetic liability of supplement use should be cautious as genetic predictors of glucosamine may capture participants with worse joint health [87].

We further adjusted osteoarthritis in the multivariable MR analysis to reduce bias. Sixthly, MR is a useful option for validating results; nevertheless, genetic variants reflect lifetime exposures rather than brief treatment modalities, which may create a bigger impact than a time-limited intervention [88].

Therefore, our findings should be taken cautiously, since they are hypothesis generating and warrant more clinical data to further investigate the connection between glucosamine intake and dementia. Seventhly, although the current definition for dementia was widely used in previous studies and the true positive rate for all-cause dementia collected in the UK Biobank was as high as 82.5% [89]; the true positive rates of Alzheimer’s disease and vascular dementia were lower than 75%. Thus, the results on the subtypes of dementia should be taken cautiously.


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