Glucosamine is a compound naturally occurring in the human body and found in high concentrations in joints and cartilage. Glucosamine supplements are primarily used as a joint health supplement and are typically derived from shellfish. A few studies suggest glucosamine may provide minor cognitive benefits, though no clinical trials have tested whether glucosamine can prevent age-related cognitive decline or dementia. Glucosamine supplements are generally regarded as safe, though some drug interactions are known.
No clinical trials have tested whether glucosamine can prevent age-related cognitive decline or dementia. Our search identified:
Several large observational studies utilizing data from the UK Biobank have examined whether glucosamine use may be associated with improving cognitive function or lowering dementia risk [1; 2; 3; 4; 5; 6]. A study that included 482,766 participants from the UK Biobank reported that regular use of glucosamine was associated with better performance on reasoning and reaction time, but not on memory [6]. Another analysis of the UK Biobank cohort including 258,841 participants reported that people with genetic variants associated with glucosamine use had significantly higher cognitive performance and fluid intelligence scores, even after controlling for factors such as osteoarthritis and body mass index [1]. Another UK Biobank study of 494,814 participants between the ages of 40 and 70 reported that glucosamine users had a significantly lower risk of dementia (of any cause), Alzheimer’s disease, and vascular dementia, after following these participants for almost nine years [4]. However, not all observational studies have shown a significant association between glucosamine use and lower dementia risk. A UK Biobank study of ~290,000 middle- to old-aged participants reported that glucosamine intake was not significantly associated with dementia or Parkinson’s disease [2].
While the data are encouraging overall, there are some limitations to these types of observational studies. Because the data come from a cohort study and not a clinical trial with a placebo control, it is not possible to prove that glucosamine is responsible for the improvement in cognitive performance or lowering of dementia risk.
In preclinical testing, glucosamine had positive effects on cognitive tasks and memory in small mammals [7; 8; 9]. There are several potential ways glucosamine may protect the brain. In small mammals and invertebrates, glucosamine promotes generation of mitochondria? [10]. Cell culture studies also suggest that glucosamine inhibits inflammation? [11; 12; 13].
No clinical trials have reported whether glucosamine can improve cognitive function or slow decline in people with dementia. In an analysis of clinical records from the University of Florida Health system with over 50,000 patients diagnosed with Alzheimer’s disease-related dementia, patients who had documented glucosamine usage for at least one year following a dementia diagnosis had a 25% higher risk of mortality based on a 10-year survival analysis [14]. However, a newer observational study that evaluated the National Alzheimer’s Coordinating Center cohort found that glucosamine use was not significantly associated with the risk of dementia (of any cause) or Alzheimer’s disease, and the study did not find a significant association between glucosamine use and mortality [15]. Without a randomized placebo-controlled clinical trial, it is not possible to definitively determine whether glucosamine treatment improves or harms cognitive function in people with dementia.
Glucosamine is generally considered safe, though much of the safety data comes from studies in people with osteoarthritis. Several large meta-analyses of randomized controlled trials reported that glucosamine was as safe as placebo [16; 17; 18]. However, a clinical trial of patients with osteoarthritis reported that glucosamine treatment for three months increased intraocular pressure, the fluid pressure of the eye [19]. It is not yet clear if glucosamine treatment may affect glaucoma risk, or if glucosamine may be harmful in glaucoma patients.
Some drug interactions with glucosamine are known. Glucosamine should not be used if you take warfarin, anisindione, or dicumarol, as the combination may raise your risk of bruising and bleeding [20]. Glucosamine may also reduce the effectiveness of acetaminophen (Tylenol), certain chemotherapy drugs (doxorubicin, etoposide, and teniposide), and diabetes drugs (glimepiride, glyburide, insulin, pioglitazone, and rosiglitazone) [21]. Some glucosamine products also contain manganese, so excessive supplementation of such products may lead to manganese overdose.
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
Glucosamine supplements are available in capsule or tablet forms and are typically manufactured by processing shells of shrimp, lobsters, and crabs. Vegans/vegetarians and people with shellfish allergies may use glucosamine supplements derived from fungi (Aspergillus niger) or fermented corn [22]. Clinical studies have used daily doses ranging from 900 to 1,500 mg, orally [16; 23]. Glucosamine sulfate appears to be superior to glucosamine hydrochloride, the latter of which was reported to be ineffective for osteoarthritis in clinical studies [24].
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