Desirable Side Effect of Glucosamine: It may lower lung cancer risk
Tina Kaczor, ND, FABNO
September 19, 2011
One very interesting study was published in a recent issue of Cancer Causes & Control. In it, Theodore Brasky and colleagues tell us that taking glucosamine sulphate may significantly lower risk of lung cancer.
This paper analyzed data that are being collected through the VITamins And Lifestyle Trial. (VITAL). For this particular paper, data from a total of 76,904 men and women who live in western Washington were analyzed. Ages ranged from 50-76 years old at the time of enrollment (October 2000-December 2002).
The study participants were queried on their use of glucosamine and chondroitin as part of a 24-page questionnaire given at time of entry to the VITAL epidemiological study. Usage of glucosamine and chondroitin, and the frequency of usage, in the prior ten-year period was queried. Usage was categorized as nonuser, low use (<4 days/week or <3 years), or high use( ≥4 days/week and ≥3 years). Dosage was not asked about. The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to ascertain lung cancer diagnoses.
Among these nearly 77,000 people, 808 lung cancers were identified. Those people who took glucosamine four or more times a week for three or more years had a 51% lower risk of developing adenocarcinoma of the lungs (HR, 0.49; 95% CI: 0.27-0.90; p trend <0.01). Taking chondroitin did not provide this benefit. The benefit did not change if someone was taking non-steroidal anti-inflammatory drugs (NSAIDs) or smoked.
Glucosamine is a commonly used nutritional supplement typically taken for sore joints. We rarely think of it for any other use outside of treating osteoarthritis. This large epidemiological study gives us reason to look at other unexpected benefits from this simple molecule. The risk of lung adenocarcinoma was cut by about half in those taking glucosamine. This is a remarkable reduction of risk that could have a huge impact on lung cancer incidence, and by extension mortality, if it is valid. The authors note in their conclusion that this degree of reduction in adenocarcinoma is consistent with prior studies looking at the use of NSAID’s and risk of developing lung cancer.
But unlike NSAID’s, glucosamine has no known toxicity.
Lung cancer is the leading cause of cancer deaths in the United States. In 2010, lung cancer caused 157,300 deaths. More deaths than fro breast, colorectal and prostate cancers combined. Cancers arising from lung tissues are broadly divided into Non-Small Cell Lung Cancers and Small Cell Lung Cancer (NSCLC). Adenocarcinoma is a type of NSCLC and accounts for the majority of lung cancer diagnoses (30-40% of all cases). 
This is not the first inverse association of glucosamine and/or chondroitin intake with incident lung cancer to be published. The VITAL study is an ongoing observational study aimed at investigating associations of dietary supplement use on cancer risk.  Data from the VITAL study first suggested this association in 2009. In the first analysis of these data, any use of glucosamine or chondroitin in the prior ten years was associated with a significant 26% and 28% decrease in lung cancer risk respectively. In this earlier assessment of the VITAL data, glucosamine and chondroitin were also associated with 27% and 35% lower risks of colorectal cancer as well, respectively. The current study was designed to update this earlier analysis. It added one year to the observational data, elucidated the effects of frequency/duration of use, accounted for other anti-inflammatory factors and tracked histology of the lung cancers.
So, if glucosamine lowers the risk of developing adenocarcinoma of the lungs, one must wonder how could it be doing this? One hypothesis looks at the role of glucosamine as an anti-inflammatory compound. The role of inflammation in lung cancer development is well established, and is certainly corroborated by the reduction of risk with NSAID use.  Glucosamine’s anti-inflammatory effects include inhibiting interleukin-1β (IL-1β) stimulation of nuclear factor kappa B (NF-kB), thus reducing the expression of over 400 cancer-related genes downstream from the NF-kB promoter region.  Other anti-tumor actions of glucosamine include inhibiting matrix metalloproteinases (MMP’s) and suppression of nitric oxide production. The ability of glucosamine to lessen MMP production appears to be through inhibiting phosphorylation of mitogen-activated protein kinase (MAPK), a well studied pathway of cellular growth. In addition, MMP’s are integral to the degradation of the extracellular matrix in cancerous growths. This degradation of the stroma is necessary for angiogenesis and metastatic spread of cancers. Perhaps glucosamine preserves the integrity of the stroma much like it preserves the joints? The mechanisms of possible anti-tumor effects are speculative, and are perhaps an academic exercise only in the face of the impressive evidence from the VITAL study.
Glucosamine certainly has proven fairly reliable in relieving joint pain clinically. Perhaps this study tips the scale for its recommendation more commonly for patients with joint pain. Importantly, there is no reason to think it would affect an established lung cancer diagnosis, as prevention and treatment of cancer are two different molecular processes. Nonetheless, this study has me reassessing how aggressively I will treat osteoarthritis in my patients. If this is the added benefit of glucosamine, the cost/benefit analysis has been changed.
Limitations: Like any observational study, there is the possibility that glucosamine use is indicative of other lifestyle choices that can affect lung cancer risk. For example, it is possible that those taking glucosamine were more likely to try giving up some of the most common food triggers of inflammation, such as dairy or wheat, thus lowering overall inflammation. Since this study was in the Seattle area, where there is an abundance of naturopathic physicians and other natural medicine practitioners, it is also possible that inflammation was modified using other diets, agents outside of the 20 natural agents that were queried, or through mind-body practices not accounted for as confounders. Indeed, while the use of glucosamine for joint pain is common knowledge, its use implies that these participants were actively addressing their health through more natural means. Whether this means improving digestion through probiotics or being more mindful of how stress plays a role in your well being, practices that improve overall health may also bring down inflammation. While the VITAL findings are intriguing, further studies are needed to corroborate these findings.
Please note: This newsletter is only a slightly modified version of f a review written about by Tina Kaczor, ND, FABNO. Tina’s review will appear in an upcoming issue of The Natural Medicine Journal.
Brasky Theodore M., Lampe Johanna W., Slatore Christopher G., White Emily. Use of glucosamine and chondroitin and lung cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Causes & Control : CCC. 2011;22:1333-1342.
White E, Patterson RE, Kristal AR, et al. VITamins And Lifestyle cohort study: study design and characteristics of supplement users. Am J Epidemiol 2004;159:83–93
Satia Jessie A., Littman Alyson, Slatore Christopher G., Galanko Joseph A., White Emily. Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study Cancer Epidemiology Biomarkers & Prevention. 2009;18:1419-1428.
Schottenfeld D, Beebe-Dimmer J. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 2006;56:69–83.
Largo MA, Alvarez-Soria, J, Diez-Ortego E, et al. Glucosamine inhibits IL-1 β-induced NFκB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2003;11:290–8.
Nakamura H., Shibakawa A., Tanaka M., Kato T., Nishioka K.. Effects of glucosamine hydrochloride on the production of prostaglandin E2, nitric oxide and metalloproteases by chondrocytes and synoviocytes in osteoarthritis. Clinical and experimental rheumatology. 2004;22:293-299.
d'Abusco Anna Scotto S., Calamia Valentina, Cicione Claudia, Grigolo Brunella, Politi Laura, Scandurra Roberto. Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes. Arthritis research & therapy. 2007;9:R104+