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.

Download full-text


Available from: Dirk J Gouma,
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues. A greater contribution of gluconeogenesis to glucose production may limit amino acid availability for muscle protein synthesis, further aggravating muscle loss. In the context of inter-dependence between glucose and protein metabolism, the present review summarizes the current state of knowledge on alterations that may lead to muscle wasting in human cancer. By highlighting the similarities with T2D, a disease that has been more extensively studied, the objective of this review is to provide a better understanding of the pathophysiology of cancer cachexia and to consider potential treatments usually targeted for T2D. Nutritional approaches aimed at stimulating protein anabolism might include specially formulated food with optimal protein and amino acid composition. Because the gradual muscle loss in T2D may be attenuated by diabetes treatment, anti-diabetic drugs might be considered in cachexia treatment. Metformin emerges as a choice candidate as it acts both on reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated tumour suppressor properties in multiple cancer types. Such a multimodal approach to slow or reverse muscle wasting in cachexia warrants further investigation.
    Applied Physiology Nutrition and Metabolism 06/2014; 39(6). DOI:10.1139/apnm-2013-0369 · 2.34 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.
    Frontiers in Physiology 03/2014; 5:88. DOI:10.3389/fphys.2014.00088 · 3.53 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cell mechanisms mediating this relationship have not been elucidated. Th17 cells, which produce the proinflammatory cytokine interleukin 17 (IL-17), have been recognized as one of the key factors in the regulation of inflammatory bowel disease and rheumatoid arthritis. This study demonstrated that, in patients with various types of gastrointestinal cancer, IL-17 production was correlated with myeloid-derived suppressor cell (MDSC) levels and with markers for nutritional impairment, immune suppression and chronic inflammation. IL-17 was significantly higher in patients with various types of gastrointestinal cancer compared to normal volunteers. In addition, IL-17 levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio (NLR) and significantly inversely correlated with cell-mediated immune response indicators [lymphocyte phytohemagglutinin (PHA)-blastogenesis and IL-12 induction] and patient nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism contributing to disease progression through enhancement of immune suppression or cachexia. Controlling the activation of Th17 cells may prove to be a valuable strategy for the treatment of gastrointestinal cancer patients.
    Molecular and Clinical Oncology 07/2013; 1(4):675-679. DOI:10.3892/mco.2013.134
Show more