The association between regular glucosamine use and risk of dementia

By Pooja Toshniwal PahariaApr 3 2023Reviewed by Lily Ramsey, LLM

In a recent study published in the BMC Medicine Journal, researchers assessed the association between daily glucosamine consumption and the risk of new-onset dementia.

Study: Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study. Image Credit: Farion_O/Shutterstock.com

Background

The characteristic progressive cognitive impairments in dementia and lowered capacity to perform routine activities increase the health burden on the affected individuals and their health systems. Given the lack of effective pharmacological therapies for dementia, identifying modifiable factors with protective effects against dementia has garnered interest.

Glucosamine, an extensively used non-mineral, non-vitamin supplement for joint pain and osteoarthritis, reportedly has anti-neuroinflammatory and neuroprotective properties.

Of note, a study reported the relationship between glucosamine consumption and improved cognitive function, possibly due to its influence on energy metabolism and the involvement in the O-linked N-acetylglucosaminylation of proteins. However, data on the relationship between glucosamine consumption and the risk of dementia are limited.

About the study

In the prospective cohort study, researchers assessed any-cause dementia, vascular dementia, and Alzheimer's disease (AD) development risks in glucosamine consumers and non-consumers.

The study compared 55,794 United Kingdom (UK) Biobank participants, aged 40 to 70 years, with new-onset dementia data and no history of dementia. Individuals were recruited from 22 sites across the United Kingdom, including Scotland, Wales, and England, from 2006 to 2010.

For further testing of the causal relationship between glucosamine usage and dementia, a two-sample Mendelian randomization (MR) analysis was performed utilizing genome-wide association study (GWAS) summary-level data. In addition, the team explored the probable modifying effects of various known risk factors, including the apolipoprotein E (APOE ε4) genotypes for dementia.

Cox proportional hazard-type modeling was performed, and the hazard ratios (HR) were calculated. Data were adjusted for age, sex, level of education, ethnicity, education, income, Townsend deprivation index (TDI), body mass index (BMI), fruit and vegetable consumption, smoking habits, alcohol consumption, physical activity, comorbidities, medications, and dietary supplements. Comorbidities were assessed using the Elixhauser comorbidity index.

Data were analyzed via digital questionnaires, physical evaluation, in-person interviews, and hospitalization and death records. The team obtained genome-wide association studies' data from observational cohorts comprising primarily Europeans. Diagnoses were based on the international classification of diseases, tenth revision (ICD-10) codes.

Digital assessments and pair-matching tests were performed to assess memory and reaction time. The team excluded 1,298 individuals who withdrew from the study, 224 individuals with prior dementia history, 6,171 individuals with missing data on glucosamine usage, and 15,339 lacking genotyping data.

Results and discussion

In total, 494,814 individuals were considered for the final analysis, among whom the mean participant age was 57 years, 54% were women, and 19% (n=94,259) of participants documented glucosamine usage at baseline.

During the nine-year follow-up (median) period, 2,458, 924, and 491 cases of any-cause dementia, AD, and vascular dementia, respectively, were reported. The HR values for glucosamine consumers for any-cause dementia, vascular dementia, and AD were 0.8, 0.7, and 0.0, respectively.

The positive but inverse association between the use of glucosamine and Alzheimer's disease was stronger among participants aged <60 years compared to individuals aged >60 years, and the associations were not modified by the apolipoprotein E genotype.

Single-variable Mendelian randomization analysis findings indicated a causal association between glucosamine use and a lower risk of dementia. Multivariable Mendelian randomization analysis findings showed that glucosamine use prevented dementia after data were controlled for vitamin and/or chondroitin supplementation and osteoarthritis, with HR values for any-cause dementia, vascular dementia, and AD being 0.9, 0.7, and 0.8, respectively.

The single variable analysis, multivariable inverse variance weighted (MV-IVW), and sensitivity analysis yielded similar findings. Excluding individuals reporting outcomes within two years of follow-up, individuals using chondroitin, and those with missing data, the association between glucosamine usage and any-cause dementia, vascular dementia, and AD persisted.

In the follow-up period, among individuals without dementia, 19,763, 19,654, and 19,082 deaths were reported as competing events for vascular dementia, AD, and all-cause dementia, respectively. The competing risks analysis findings were consistent with Cox proportional hazard-type modeling.

Passing through the blood-brain barrier (BBB), glucosamine may enter the hippocampus, cortex, and striatum. The stronger influence of glucosamine on AD patients aged <60 years, compared to the elderly, may be related to the gradually progressing hippocampal atrophy and lowering of cortical density with advancing age, decreasing the number of brain cell membrane receptors, and lowered sensitivity to medications.

Glucosamine may simulate low-carbohydrate diets by reducing glycolysis, increasing the catabolism of amino acids, and may reverse intestinal microbial dysbiosis.

Conclusions

Overall, the study findings provide evidence for potential causal relationships between glucosamine usage and a lower risk for dementia. Daily glucosamine usage was associated with a 15.0% lower risk of any-cause dementia, 17.0% for Alzheimer's disease, and 26.0% for vascular dementia. The APOE genotype did not modify the association.

Glucosamine use was associated with improved cognitive functions, with a higher reasoning score and faster reaction speed among glucosamine users compared to non-users. Glucosamine may also prevent dementia, irrespective of chondroitin supplementation. Randomized controlled trials (RCTs) must be conducted in the future to validate the study findings.