Association between glucosamine use and albuminuria in the UK: a cohort and Mendelian randomisation study.

Abstract

BACKGROUND: Glucosamine is a commonly used 'over the counter' dietary supplement. Previous research has identified an association between glucosamine use and several positive health outcomes. However, a plausible biological mechanism for these associations has not yet been identified, meaning the causality of these relationships remains unclear. A protective effect of glucosamine on the vascular endothelium has been suggested as one such possible mechanism. Albuminuria is an early marker of endothelial dysfunction within the kidney and is associated with progression of kidney disease and adverse cardiovascular outcomes. In order to provide insights into the potential biological mechanisms underlying a protective association of glucosamine use with health outcomes, we evaluated evidence for an association between glucosamine use and albuminuria in UK Biobank (N=436 200). METHODS: Univariable and multivariable ordinal logistic regression were performed to evaluate evidence for an association between self-reported glucosamine use and albuminuria (measured as urine albumin creatinine ratio (uACR) categories). As a secondary analysis, we performed Mendelian randomisation (MR) to demonstrate the difficulties in inferring causality in this relationship using currently available data, using summary genetic data from UK Biobank and CDKGen (N=67 452). RESULTS: We found that people who used glucosamine were more likely to be in a lower uACR group (OR 0.81, 95% CI 0.80 to 0.83, p<2.2×10-16). This association was robust to sensitivity analyses and was maintained after adjustment for age, sex and measures of obesity. In our MR analysis, we found little evidence for an association of genetically proxied glucosamine use on albuminuria (change in log uACR (mg/g) per SD change in genetic liability=1.11, 95% CI -3.01 to 5.23, p=0.60). CONCLUSIONS: We found that detectable albuminuria was common in UK Biobank participants and we are the first to show that use of glucosamine supplements was associated with lower levels. Though this fits with a plausible biological role of the vascular endothelium in a potential protective effect of glucosamine use on many health outcomes, whether this relationship is causal or confounded remains unclear. We further discuss the inherent difficulties in using genetic instruments to proxy supplement use in MR analyses and highlight the need for a genome-wide association study of measured circulating glucosamine levels.