Brasky TM, Lampe JW, Slatore CG, White E. Use of glucosamine and chondroitin and lung cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Causes Control. 2011;22:1333-1342.
Researchers queried participants on their use of glucosamine and chondroitin as part of a 24-page questionnaire at time of entry to the VITAL epidemiological study (between October 2000 and December 2002). The questionnaire asked about usage and frequency of usage of glucosamine and chondroitin in the prior 10-year period. 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 queried. The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to ascertain lung cancer diagnoses.
A total of 76,904 men and women in 13 western Washington state counties, corresponding to the SEER Seattle-Puget Sound catchment area. Age range was 50–76 years old at the time of enrollment (October 2000–December 2002).
Using SEER data, researchers identified 808 lung cancers. Glucosamine users in the high use category had a significantly lower risk of developing adenocarcinoma of the lungs (HR=0.49; 95% CI=0.27–0.90; P<0.01). This association was not found with chondroitin use, nor was it modified by non-steroidal anti-inflammatory drug (NSAID) use or smoking status.
Glucosamine is commonly used for joint support, and it has attracted very little interest for any other use outside of osteoarthritic pain. This large epidemiological study gives us reason to look at other unexpected benefits to this simple molecule. The risk of lung adenocarcinoma was cut approximately in half in those taking glucosamine at least 4 times per week for 3 years. 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 NSAIDs and risk of developing lung cancer. Unlike NSAIDs, glucosamine has no known toxicity.
The risk of lung adenocarcinoma was cut approximately in half in those taking glucosamine at least 4 times per week for 3 years.
Lung cancer is the leading cause of cancer deaths in the United States, where 157,300 lung cancer deaths are estimated to have occurred in 2010 alone. This is more than 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, a type of NSCLC, accounts for the majority of lung cancer diagnoses (30–40% of all cases).1
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.2 Data from the VITAL study first suggested this association in 2009, when any use of glucosamine or chondroitin in the prior 10 years was associated with a significant lowering of lung cancer risk (HR=0.74; 95% CI=0.58–0.94; and HR=0.72; 95% CI=0.54–0.96, respectively). In this preliminary assessment of the VITAL data, glucosamine and chondroitin were associated with a lower risk of colorectal cancer as well (HR=0.73; 95% CI=0.54–0.98; and HR=0.65; 95% CI=0.45–0.93, respectively).3 The current study was designed to update this analysis. It added 1 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.4 Glucosamine’s anti-inflammatory effects include inhibiting interleukin-1β (IL-1β) stimulation of nuclear factor kappa B (NF-kB), thus reducing the expression of more than 400 cancer-related genes downstream from the NF-kB promoter region.5 Other antitumor actions of glucosamine include inhibiting matrix metalloproteinases (MMPs) and suppressing nitric oxide production.6 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.7 In addition, MMPs 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 antitumor 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 supplementation with glucosamine 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.
Because this is an observational study, there is the possibility that glucosamine use is indicative of other lifestyle choices that affect lung cancer risk. For example, it is possible that those taking glucosamine are 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 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.
For more research involving integrative oncology, click here.
1. Lung cancer. E Medicine Health Web site. http://www.emedicinehealth.com/lung_cancer/article_em.htm. Accessed October 3, 2011.
2. 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
3. Satia JA, Littman A, Slatore CG, Galanko JA, White E. Associations of herbal and specialty supplements with lung and colorectal cancer risk in the VITamins And Lifestyle Study. Cancer Epidemiol Biomarkers Prev. 2009;18:1419-1428.
4. 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.
5. Largo MA, Alvarez-Soria, J, Diez-Ortego E, et al. Glucosamine inhibits IL-1-?induced NF?B activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2003;11:290-298.
6. 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. Clin Exp Rheumatol. 2004;22:293-299.
7. d'Abusco AS, Calamia V, Cicione C, Grigolo B, Politi L, Scandurra R. Glucosamine affects intracellular signalling through inhibition of mitogen-activated protein kinase phosphorylation in human chondrocytes. Arthritis Res Ther. 2007;9:R104.