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

Royal Infirmary of Edinburgh, Edinburgh, UK.
Gut (Impact Factor: 14.66). 11/2003; 52(10):1479-86.
Source: PubMed


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.
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.
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 (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta 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.
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.

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    • "Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are long-chain n-3 fatty acids with immune-modulating and anti-inflammatory properties that may counteract the effects of inflammatory cytokines on muscle proteolysis (Whitehouse et al. 2001) and may alleviate muscle protein anabolic resistance. Earlier studies showed maintenance of lean body mass and improvement of performance status, appetite, and weight (Barber et al. 1999; Gogos et al. 1998; Wigmore et al. 2000), but subsequent larger trials found no benefit from EPA on lean mass (Fearon et al. 2003, 2006; Dewey et al. 2007; Jatoi et al. 2004). Since then, positive outcomes on lean mass or muscle have been reported (Murphy et al. 2011a; Ryan et al. 2009; van der Meij et al. 2010; Weed et al. 2011), which might be explained by better compliance and precise quantitation of muscle mass. "
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    • "Dietary recommendations can significantly increase oral caloric and protein intake (Ovesen et al., 1993). Several studies evaluating the role of oral nutritional supplementation among patients with pancreatic cancer demonstrated improvement in weight and appetite (Fearon et al., 2003; Bauer and Capra, 2005). Oral supplementation with compounds such as L-Carnitine and omega-3 fatty acids may have benefits as well (Barber et al., 1999; Kraft et al., 2012). "
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    • "The likelihood of the association of IL-17 production with nutritional impairment is high, due to the role of IL-17 as a marker of systemic inflammation. It was previously reported that the key mechanisms leading to cancer cachexia, in which nutritional impairment is a major clinical issue, are mostly immune reactions caused by chronic inflammation and that treatment with a COX-2 inhibitor or a specific nutrient formula is effective (18,19). "
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