An analysis of UK Biobank data showed an association between regular glucosamine use and significantly lower risks of seven non-communicable chronic diseases [1].
A common supplement
Glucosamine, a sugar molecule with an amine group (amino sugar), is a supplement used by almost 20% of middle-aged adults in the U.S., U.K., and Australia [2]. It is recommended for osteoarthritis patients to reduce knee pain [3].
Glucosamine has also shown some broader beneficial effects, including on inflammatory responses [4], and it has been linked to reduced risks of cardiovascular disease, type 2 diabetes, lung cancer risks, and all-cause mortality [2,5-7]. However, comprehensive studies on the impact of glucosamine supplementation on non-communicable chronic diseases are lacking.
Given that non-communicable chronic diseases cause around three-quarters of all deaths worldwide and are responsible for a considerable economic burden, and taking into account the preliminary data on glucosamine’s biological mechanisms and positive effects, the researchers examined the impact of regular glucosamine supplementation and its association with the risk of developing major non-communicable chronic diseases.
Large cohort
The authors used a large dataset from the population-based UK Biobank. They only included participants who were free from non-communicable chronic diseases at the beginning of the study and had completed information on medicine use. They obtained the data of 269,033 participants. 52,556 (19.5%) were regular glucosamine users, making it the currently largest cohort with which to analyze this research question.
The participants provided the information regarding glucosamine use through self-reported questionnaires, which weren’t validated in any way. Since the questionnaire was constructed to give simple answers (‘yes’ or ‘no’), the researchers were unable to analyze more detailed information, such as dose-response, impact of duration, or frequency of treatment, or the impact of supplement forms, such as glucosamine sulfate, glucosamine hydrochloride, and N-acetyl-glucosamine.
When glucosamine users were compared to non-users, the researchers noted that “glucosamine users were older, more likely to be female, and had a lower level of socioeconomic deprivation.” They were also more likely to be current or former smokers, “tended to engage in excessive alcohol consumption, exhibit unhealthy dietary patterns, and participate in irregular physical activity.” To remove those differences between the glucosamine and control groups and make those two groups comparable, the researchers employed propensity score matching (PSM). Using this method, they compared 52,525 glucosamine users and 52,525 controls that had comparable characteristics. The data regarding those study populations included a median of almost 14 years of follow-up.
Lower risk of non-communicable chronic diseases
Data analysis, which included false discovery rate correction, showed an association between regular glucosamine use and significantly lower risks of seven non-communicable chronic diseases: esophageal cancer, gout, chronic obstructive pulmonary disease, colorectal cancer, chronic liver disease, heart failure, and coronary heart disease. These associations were robust and persisted when different statistical tools were applied to test their strength. There were also associations between the combination of glucosamine and chondroitin, another supplement often combined with glucosamine, to the risk of non-communicable chronic diseases.
Most of the associations were independent of age and gender. The exceptions involved heart failure, as regular glucosamine use was associated with a 22% lower risk of heart failure in men but not women; and irregular and rapid heart rhythms (atrial fibrillation), in which “regular glucosamine use was related to a 51% higher risk” in people younger than 65.
The authors cautioned that while they observed associations between glucosamine use and the risk of non-communicable chronic diseases, this study is observational and does not prove causal relationships.
However, they also derived a number called the population attributable fraction, which allowed them to quantify, at the population level, what proportion of disease risk may have been prevented by glucosamine use if the relationship is indeed causal. These numbers came out to 12.84% for esophageal cancer, 11.14% for gout, 6.53% for colorectal cancer, 5.67% for chronic obstructive pulmonary disease, 6.54% for chronic liver disease, 6.09% for heart failure, and 4.16% for coronary heart disease.
Many possible mechanisms
While the researchers didn’t experimentally investigate the mechanisms behind he observed association, they speculated on the possible biological processes behind it and discuss it in the light of published studies. For example, they discussed how the connection between glucosamine and reduced risk of cardiovascular diseases can be driven by its ability to help mitigate atherosclerotic lesion formation and its anti-inflammatory effects. The reduced risk of non-communicable chronic diseases can also be linked to glucosamine’s ability to mimic the metabolic effects of a low-carbohydrate diet, its antioxidant properties, or modulation of many cellular processes.
Like every study, this one also has some limitations. While the UK Biobank is a large dataset with many participants, and a plethora of information about each person, some information is not included, such as their reasons for taking glucosamine. If some of the participants took it because of joint discomfort or undiagnosed osteoarthritis, this would change their disease risk and impact the analysis, as participants who had non-communicable chronic diseases at the beginning of he study were excluded.
The results might also have limited generalizability, as the population in the UK Biobank is primarily of European ethnicity and has healthier habits than the general population. Additionally, the authors suspect that glucosamine users might be more conscious about health, introducing another bias. However, they tried to minimize the impact of potential confounding factors by adjusting their analysis.
All in all, the researchers believe that glucosamine is a promising, low-cost, accessible candidate to prevent chronic diseases. Their research suggests that glucosamine benefits might extend beyond joint health, where it is currently employed. However, given that this study cannot establish a causal effect, future research should more directly address causality and establish a better understanding of the molecular processes behind the observed associations.
Literature
[1] He, J., Ma, Y., Jiang, Y., Ji, J., & Song, F. (2025). Regular glucosamine supplementation and risk of age-related chronic diseases: evidence from a propensity score-matched cohort study. Aging clinical and experimental research, 37(1), 259.
[2] Ma, H., Li, X., Zhou, T., Sun, D., Liang, Z., Li, Y., Heianza, Y., & Qi, L. (2020). Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank. Diabetes care, 43(4), 719–725.
[3] Vo, N. X., Le, N. N. H., Chu, T. D. P., Pham, H. L., Dinh, K. X. A., Che, U. T. T., Ngo, T. T. T., & Bui, T. T. (2023). Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review. Pharmacy (Basel, Switzerland), 11(4), 117.
[4] Dalirfardouei, R., Karimi, G., & Jamialahmadi, K. (2016). Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life sciences, 152, 21–29.
[5] Ma, H., Li, X., Sun, D., Zhou, T., Ley, S. H., Gustat, J., Heianza, Y., & Qi, L. (2019). Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank. BMJ (Clinical research ed.), 365, l1628.
[6] Li, G., Zhang, X., Liu, Y., Zhang, J., Li, L., Huang, X., Thabane, L., & Lip, G. Y. H. (2022). Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study. The European respiratory journal, 59(3), 2101399.
[7] Li, Z. H., Gao, X., Chung, V. C., Zhong, W. F., Fu, Q., Lv, Y. B., Wang, Z. H., Shen, D., Zhang, X. R., Zhang, P. D., Li, F. R., Huang, Q. M., Chen, Q., Song, W. Q., Wu, X. B., Shi, X. M., Kraus, V. B., Yang, X., & Mao, C. (2020). Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study. Annals of the rheumatic diseases, 79(6), 829–836.
