COLON

Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial

K C H Fearon¹, M F von Meyenfeldt², A G W Moses¹, R van Geenen³, A Roy⁴, D J Gouma³, A Giacosa⁵, A Van Gossum⁶, J Bauer⁷, M D Barber¹, N K Aaronson⁸, A C Voss⁹, M J Tisdale¹⁰

¹ Royal Infirmary of Edinburgh, Edinburgh, UK
² University Hospital of Maastricht, Maastricht, the Netherlands
³ Academisch Medisch Centrum, Amsterdam, the Netherlands
⁴ Centre Hospitalier de l’University de Montreal, Montreal, Canada
⁵ Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
⁶ Universite de Bruxelles Erasme, Brussels, Belgium
⁷ The Wesley Hospital, Brisbane, Australia
⁸ Antonie van Leeuwen Hoek Ziekenhuis, Amsterdam, the Netherlands
⁹ Ross Products Division, Abbott Laboratories, Columbus, Ohio, USA
¹⁰ Aston University, Birmingham, UK

Correspondence to:
Correspondence to:
Professor K C H Fearon, Department of Clinical and Surgical Sciences (Surgery), Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK;
k.fearon{at}ed.ac.uk

Aim: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer.

Methods: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein ± 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial.

Results: At enrolment, patients’ mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight ( weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM ( LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group.

Conclusion: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.

Keywords: cachexia; pancreatic cancer; quality of life; eicosapentaenoic acid; n-3 fatty acids; nutritional support; weight; lean body mass; cytokines

Abbreviations: EPA, eicosapentaenoic acid; PIF, proteolysis inducing factor; LBM, lean body mass; TBW, total body water

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Nutritional therapy for cancer cachexia

R F Grimble
Gut 2003 52: 1391-1392. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• August, D. A., Huhmann, M. B., the American Society for Parenteral and Enteral Nu, (2009). A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation. JPEN J Parenter Enteral Nutr 33: 472-500 [Full Text]  
• Fetterman, J. W. Jr., Zdanowicz, M. M. (2009). Therapeutic potential of n-3 polyunsaturated fatty acids in disease. Am J Health Syst Pharm 66: 1169-1179 [Abstract] [Full Text]  
• Bozzetti, F., Mariani, L. (2009). Defining and Classifying Cancer Cachexia: A Proposal by the SCRINIO Working Group. JPEN J Parenter Enteral Nutr 33: 361-367 [Abstract] [Full Text]  
• Prado, C. M.M., Baracos, V. E., McCargar, L. J., Reiman, T., Mourtzakis, M., Tonkin, K., Mackey, J. R., Koski, S., Pituskin, E., Sawyer, M. B. (2009). Sarcopenia as a Determinant of Chemotherapy Toxicity and Time to Tumor Progression in Metastatic Breast Cancer Patients Receiving Capecitabine Treatment. Clin. Cancer Res. 15: 2920-2926 [Abstract] [Full Text]  
• Tisdale, M. J. (2009). Mechanisms of Cancer Cachexia. Physiol. Rev. 89: 381-410 [Abstract] [Full Text]  
• Al-Majid, S., Waters, H. (2008). The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise.. Biol Res Nurs 10: 7-20 [Abstract]  
• Radbruch, L., Strasser, F., Elsner, F., Goncalves, J. F., Loge, J., Kaasa, S., Nauck, F., Stone, P., the Research Steering Committee of the European As, (2008). Fatigue in palliative care patients -- an EAPC approach. Palliat Med 22: 13-32 [Abstract]  
• Nourissat, A., Mille, D., Delaroche, G., Jacquin, J. P., Vergnon, J. M., Fournel, P., Seffert, P., Porcheron, J., Michaud, P., Merrouche, Y., Chauvin, F. (2007). Estimation of the risk for nutritional state degradation in patients with cancer: development of a screening tool based on results from a cross-sectional survey. Ann Oncol 18: 1882-1886 [Abstract] [Full Text]  
• Acharyya, S., Guttridge, D. C. (2007). Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome. Clin. Cancer Res. 13: 1356-1361 [Abstract] [Full Text]  
• Loprinzi, C. L., Barton, D. L., Sloan, J. A. (2006). Whose Opinion Counts?. JCO 24: 5183-5185 [Full Text]  
• Hutton, J. L, Martin, L., Field, C. J, Wismer, W. V, Bruera, E. D, Watanabe, S. M, Baracos, V. E (2006). Dietary patterns in patients with advanced cancer: implications for anorexia-cachexia therapy.. Am. J. Clin. Nutr. 84: 1163-1170 [Abstract] [Full Text]  
• Strasser, F., Luftner, D., Possinger, K., Ernst, G., Ruhstaller, T., Meissner, W., Ko, Y.-D., Schnelle, M., Reif, M., Cerny, T. (2006). Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients With Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial From the Cannabis-In-Cachexia-Study-Group. JCO 24: 3394-3400 [Abstract] [Full Text]  
• Fearon, K. C.H., Barber, M. D., Moses, A. G., Ahmedzai, S. H., Taylor, G. S., Tisdale, M. J., Murray, G. D. (2006). Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia. JCO 24: 3401-3407 [Abstract] [Full Text]  
• McCarty, M. F., Block, K. I. (2006). Toward a Core Nutraceutical Program for Cancer Management. Integr Cancer Ther 5: 150-171 [Abstract]  
• Fearon, K. C, Voss, A. C, Hustead, D. S, for the Cancer Cachexia Study Group, (2006). Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am. J. Clin. Nutr. 83: 1345-1350 [Abstract] [Full Text]  
• Mantovani, G., Maccio, A., Madeddu, C., Gramignano, G., Lusso, M. R., Serpe, R., Massa, E., Astara, G., Deiana, L. (2006). A Phase II Study with Antioxidants, Both in the Diet and Supplemented, Pharmaconutritional Support, Progestagen, and Anti-Cyclooxygenase-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia/Cachexia and Oxidative Stress.. Cancer Epidemiol. Biomarkers Prev. 15: 1030-1034 [Abstract] [Full Text]  
• Morley, J. E, Thomas, D. R, Wilson, M.-M. G (2006). Cachexia: pathophysiology and clinical relevance.. Am. J. Clin. Nutr. 83: 735-743 [Abstract] [Full Text]  
• Siddiqui, R., Pandya, D., Harvey, K., Zaloga, G. P. (2006). Nutrition Modulation of Cachexia/Proteolysis. Nutr Clin Pract 21: 155-167 [Abstract] [Full Text]  
• Tisdale, M. J. (2006). Clinical Anticachexia Treatments. Nutr Clin Pract 21: 168-174 [Abstract] [Full Text]  
• Yavuzsen, T., Davis, M. P., Walsh, D., LeGrand, S., Lagman, R. (2005). Systematic Review of the Treatment of Cancer-Associated Anorexia and Weight Loss. JCO 23: 8500-8511 [Abstract] [Full Text]  
• Gordon, J.N., Green, S.R., Goggin, P.M. (2005). Cancer cachexia. QJM 98: 779-788 [Abstract] [Full Text]  
• Wilcock, A. (2005). Cachexia and omega-3 polyunsaturated fatty acids: the beginning of the end or the end of the beginning?. Palliat Med 19: 500-502  
• Jatoi, A. (2005). {Omega}-3 Fatty Acid Supplements for Cancer-Associated Weight Loss. Nutr Clin Pract 20: 394-399 [Abstract] [Full Text]  
• Mattox, T. W. (2005). Treatment of Unintentional Weight Loss in Patients With Cancer. Nutr Clin Pract 20: 400-410 [Abstract] [Full Text]  
• Davis, M. P. (2005). Eicosapentaenoic Acid: The Answers Are Not All In. JCO 23: 3854-3854 [Full Text]  
• Jatoi, A., Loprinzi, C. L., Rowland, K., Dakhil, S. (2005). In Reply:. JCO 23: 3854-3855 [Full Text]  
• Broekhuizen, R, Wouters, E F M, Creutzberg, E C, Weling-Scheepers, C A P M, Schols, A M W J (2005). Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 60: 376-382 [Abstract] [Full Text]  
• Jatoi, A., Loprinzi, C., Rowland, K., Dakhil, S. (2005). In Reply:. JCO 23: 2872-2873 [Full Text]  
• Gordon, J N, Trebble, T M, Ellis, R D, Duncan, H D, Johns, T, Goggin, P M (2005). Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 54: 540-545 [Abstract] [Full Text]  
• Mantovani, G., Madeddu, C., Maccio, A., Gramignano, G., Lusso, M. R., Massa, E., Astara, G., Serpe, R. (2004). Cancer-Related Anorexia/Cachexia Syndrome and Oxidative Stress: An Innovative Approach beyond Current Treatment. Cancer Epidemiol. Biomarkers Prev. 13: 1651-1659 [Abstract] [Full Text]  
• Jatoi, A., Rowland, K., Loprinzi, C. L., Sloan, J. A., Dakhil, S. R., MacDonald, N., Gagnon, B., Novotny, P. J., Mailliard, J. A., Bushey, T. I.L., Nair, S., Christensen, B. (2004). An Eicosapentaenoic Acid Supplement Versus Megestrol Acetate Versus Both for Patients With Cancer-Associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Effort. JCO 22: 2469-2476 [Abstract] [Full Text]  
• Grimble, R F (2003). Nutritional therapy for cancer cachexia. Gut 52: 1391-1392 [Full Text]