Glucosamine Supplementation Correlates with Lower All Cause Mortality

An analysis of a large study population here shows that glucosamine supplementation results in about a 15% reduction in mortality, a sizable effect size in the context of what is known of the effects of lifestyle choices and supplementation on aging. Glucosamine is used as an anti-inflammatory intervention, but there is at best only mixed evidence for it to actually do much good as a treatment for specific inflammatory conditions such as arthritis. It is nonetheless widely used, hence the ability to see outcomes in sizable group of people. The effect on mortality is certainly an interesting outcome, given the lack of robust and compelling evidence for specific benefits.

Glucosamine is a non-vitamin, non-mineral specialty supplement commonly used to manage osteoarthritis and joint pain. Although the effectiveness of glucosamine supplementation for osteoarthritis and joint pain remains controversial, several human, animal, and laboratory studies have suggested that glucosamine may have anti-inflammatory properties, which could decrease the risk of multiple diseases. In this large-scale prospective cohort study of nearly half a million UK adults, we evaluated the association between regular glucosamine supplement use and mortality from all causes, cardiovascular disease (CVD), cancer, respiratory disease, and digestive disease.

At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years, 19,882 all-cause deaths were recorded, including 3,802 CVD deaths, 8,090 cancer deaths, 3,380 respiratory disease deaths and 1,061 digestive disease deaths. The hazard ratios associated with glucosamine use were 0.85 for all-cause mortality, 0.82 for CVD mortality, 0.94 for cancer mortality, 0.73 for respiratory mortality and 0.74 for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers.

Glucosamine and chondroitin supplements are often taken together in a single daily supplements, and it is therefore possible that our observed associations are driven by either of these supplements. To address this issue, we performed sensitivity analyses examining the associations of glucosamine use alone (excluding participants who took chondroitin) with all-cause and cause-specific mortality. We found that the estimates did not change substantially. Therefore, it is likely that glucosamine use may reduce the risk of mortality, regardless of the co-administration of chondroitin.

Several potential mechanisms could explain the inverse association between glucosamine use and mortality. First, nuclear factor-κB (NF-κB) has been implicated in several diseases, such as inflammation-related CVD and cancers. Glucosamine use may affect inflammation by inhibiting the transcription factor NF-κB from translocating to the nucleus, reducing inflammation and thus lowering related mortality. Aside from reducing inflammation, an animal study reported that glucosamine use could trigger a mimic response of a low carbohydrate diet, via reducing glycolysis and increasing amino acid catabolism in mice. This could explain the linkage between glucosamine use and its protective effect, as population-based studies found that low carbohydrate diets are indeed related to a reduced risk of mortality.