The role of EPA in increasing lean body mass in cancer induced weight lose
 
 
 
 
 
 
 
 
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  • Recent research strides have unraveled various mechanisms that underlie the clinical features of this complex condition. Understanding these mechanisms offers new possibilities for improving the nutritional status of patients who are at risk for or are already experiencing cancer-induced weight loss.
  • Pro Sure Medical Presentation Asia

    1. 1. The role of EPA in increasing lean body mass in cancer induced weight lose
    2. 20. Nucleus Central control center that contains genetic information (DNA) Cell Membrane Contains fatty acids
    3. 21. Cytokines Tumor cells produce cytokines 1
    4. 22. 2
    5. 23. <ul><li>AA- (Arachidonic Acid) </li></ul><ul><li>Cytokines bind to cell membrane </li></ul><ul><li>AA is released and metabolized </li></ul>2
    6. 24. 3
    7. 25. AA metabolites stimulate breakup of NF-κB/IκB complex 3
    8. 26. NFκB A transcription factor that is inactive in the cytoplasm when bound to its inhibitor IκB.
    9. 27. IκB A regulatory element that, when attached to NFκB, inactivates this transcription factor
    10. 28. In response to cytokines, IκB splits from NFκB causing NFκB to become active and free to enter the nucleus to “turn on” cytokine genes
    11. 29. 4
    12. 30. 4
    13. 31. 5
    14. 32. 6 Cytokine production results in decreased appetite and food intake and elevated resting metabolic rate (RMR)
    15. 33. Protein Degradation as a Consequence of Inflammation: PIF and GI Malignancy
    16. 34. 1
    17. 35. 2
    18. 36. 3
    19. 37. 4
    20. 43. Evans et al. J Clin Oncol. 1987;5:113
    21. 49. Wigmore. 1996. Nutrition. 12:27s Weight change before and after a median of 3 months supplementation with fish oil in patients with unresectable pancreatic cancer (n=18)
    22. 51. Wigmore. 2000. Nutrition and Cancer. 36:177 Time (months)
    23. 52. Mountain of data to support n-3 clinical efficacy
    24. 53. EPA reduced restenosis after PTCA to comparable levels as aspirin or dipyridamole, as assessed by angiography. Prospective study Max-EPA (for 12-mo) n = 108 with established CAD Nye et al., 1990 Addition of EPA to conventional antiplatelet therapy (aspirin and dipyridamole) reduced restenosis after PTCA, as assessed by quantitative coronary angiography. Prospective RCT EPA 3.2 g/d (for 6-mo) versus control n = 82 with established CAD Dehmer et al., 1988 High levels of serum omega-3 FAs were associated with a reduced risk of CAD-related death. Prospective study Dietary fish consumption (food records and measurements of serum fatty acid composition for 5-yr) n = 415 with established CAD Erkkila et al., 2003 EPA = eicosapentaenoic acid, CAD = coronary artery disease, FA = fatty acid, RCT = randomized placebo-controlled study, PTCA = percutaneous transluminal coronary angioplasty Although fish oil lowered triglyceride levels by 30%, there was minimal CAD change as assessed by angiography and quantified by computer-assistance. Prospective study Fish oil capsules containing 6 g/d omega-3 FAs (for 28-mo) n = 59 with established CAD Sacks et al., 1995 Coronary angiography demonstrated decreased progression or modest regression of CAD with fish oil supplement. Prospective double-blind RCT Fish oil concentrate containing 55% omega-3 FAs at 6 g/d for 3-mo then 3 g/d for 21-mo versus placebo (for 24-mo total) n = 223 with established CAD von Schacky et al., 1999 Coronary angiography and carotid artery ultrasound demonstrated minimal differences between fish oil and placebo groups. Prospective RCT Fish oil oral supplement containing 1.65 g/d omega-3 FAs versus placebo (for 24-mo) n = 171 with established CAD Angerer et al., 2002 Results Design Form of EPA (Length of Treatment) Subjects Authors Table 1: Clinical Trials for EPA Supplementation in Atherosclerotic Cardiovascular Disease
    25. 54. Combination treatment with EPA produced clinical improvement. Prospective study EPA oral supplement with etretinate versus etretinate alone (for 12-wk) Psoriasis (n = 40) Danno et al., 1998 Intravenous omega-3 FAs reduced the area and severity index of psoriatic lesions. Prospective multicenter double-blind RCT Omega-3 FA intravenous lipid emulsion 200 ml/d containing 4.2 g/d EPA versus omega-6 FA lipid emulsion (for 14-d) Psoriasis (n = 83) Mayser et al., 1998 Topical omega-3 FAs improved lesions from baseline but showed no differences from placebo. Prospective multicenter double-blind RCT Omega-3 FA topical 1% or 10% concentration versus placebo (for 8-wk) Psoriasis (n = 52) Henneicke-von Zepelin et al., 1993 EPA improved the number of tender joints and duration of morning stiffness. Prospective double-blind RCT EPA 1.8 g/d versus placebo (for 12-wk) RA (n = 37) Kremer et al., 1985 GLA with or without fish oil reduced the need for NSAIDs and improved patient symptoms. Prospective double-blind placebo-controlled study Fish oil containing 240 mg/d EPA with GLA versus placebo or GLA alone (for 1-yr) RA (n = 49) Belch et al., 1988 Fish oil improved the joint swelling index and duration of morning stiffness. Prospective double-blind crossover RCT Fish oil oral supplement versus coconut oil with crossover design (12-wk treatment periods) RA (n = 16) van der Tempel et al., 1990 EPA produced modest improvements of clinical parameters. Prospective double-blind non-randomized study Max-EPA 15 capsules/d containing 2.7 g/d EPA versus placebo with crossover design (14-wk treatment periods separated by 4-wk washout RA (n = 40) Kremer et al., 1987 Omega-3 FAs induced modest clinical benefits. Prospective double-blind RCT Omega-3 FA oral supplement containing 3.8 g/d EPA with naproxen versus corn oil with naproxen (for 16-wk) RA (n = 67) Kjeldsen et al., 1992 Omega-3 FAs induced modest improvements of some clinical parameters. Prospective multicenter double-blind RCT Omega-3 FA oral supplement 6 capsules/d containing 3.6 g/d omega-3 FAs versus placebo (for 12-wk) RA (n = 51) Faarvang et al., 1994 Fish oil improved clinical parameters, reducing the number of tender joints and the need for NSAIDs. Prospective study Fish oil oral supplement 9 capsules/d containing 130 mg/kg/d omega-3 FAs versus corn oil capsules (for 30-wk) RA (n = 66) Kremer et al., 1995 Omega-3 FAs improved morning stiffness and joint tenderness. Prospective double-blind RCT Omega-3 FA oral supplement 6 capsules/d containing 3.6 g/d omega-3 FAs versus placebo (for 12-wk) RA (n = 51) Nielsen et al., 1992 Fish oil improved clinical parameters in these patients with background dietary omega-6 FA intake of < 10 g/d. Prospective double-blind RCT Fish oil oral supplement 3-6 capsules/d containing 40 mg/kg/d omega-3 FAs versus vegetable oil capsules (for 15-wk) RA (n = 50) Volker et al., 2000 Enteric-coated fish oil capsules helped maintain remission for patients with high risks of relapse. Prospective double-blind RCT Fish oil oral supplement 9 coated capsules/d containing 2.7 g/d omega-3 FAs versus placebo capsules (for 1-yr) IBD--Crohn’s disease (n = 78) Belluzi et al., 1996 EPA produced minimal changes in clinical outcome as assessed by sigmoidoscopy, rectal biopsy, and symptoms. Prospective study Max-EPA versus primrose oil or olive oil placebo (for 6-mo) IBD--ulcerative colitis (n = 43) Greenfield et al., 1993 EPA reduced the need for corticosteroids and decreased serum leukotriene B4 levels but only modestly improved clinical parameters. Prospective blind RCT Hi-EPA fish oil oral supplement 20 ml/d containing 4.5 g/d EPA versus olive oil placebo (for 1-yr) IBD--ulcerative colitis (n = 87) Hawthorne et al., 1992 EPA reduced the need for corticosteroids, decreased rectal dialysate leukotriene B4 levels, and improved histology indices. Prospective multicenter double-blind crossover RCT Max-EPA 18 capsules/d containing 3.24 g/d EPA versus vegetable oil with crossover design (4-mo treatment periods separated by 1-mo washout) IBD--ulcerative colitis (n = 24) Stenson et al., 1992 Fish oil improved disease activity index as based on patient symptoms and sigmoidoscopic appearance. Prospective double-blind crossover RCT Fish oil oral supplement containing 4.2 g/d omega-3 FAs versus placebo with crossover design (4-mo treatment periods) IBD--ulcerative colitis (n = 11) Aslan et al., 1992 Fish oil induced dose-dependent improvement in clinical parameters, including number of tender and swollen joints. Prospective double-blind RCT Fish oil oral supplement with low dose 27 mg/kg/d EPA or high dose 54 mg/kg/d EPA versus olive oil (for 24-wk) RA (n = 49) Kremer et al., 1990 EPA improved clinical outcome measures compared to olive oil placebo. Prospective double-blind crossover RCT Max-EPA 20 g/d versus olive oil placebo with crossover design (17-wk treatment periods) SLE (n = 27) Walton et al., 1991 EPA improved clinical and serological parameters at 3-mo but not at 6-mo. Prospective double-blind crossover RCT Max-EPA versus olive oil placebo with crossover design (3-mo treatment periods) SLE (n = 17) Westberg et al., 1990 EPA only improved serum lipid levels, but results were confounded by carry-over effects even with a 10-wk washout period. Prospective double-blind crossover RCT Max-EPA low dose of 6 g/d or high dose of 18 g/d versus olive oil placebo with crossover design (1-yr treatment periods separated by a 10-wk washout) SLE (n = 26) Clark et al., 1994 Sulfasalazine demonstrated improved disease acrivity over fish oil as assessed by clinical, sigmoidoscopic, histologic, and laboratory parameters. Prospective crossover RCT Fish oil supplement 18 capsules/d containing 3.24 g/d EPA versus sulfasalazine (2-mo treatment periods separated by a 2-mo washout) IBD--ulcerative colitis (n = 10) Dichi et al., 2000 Fish oil improved disease severity as assessed by clinical, sigmoidoscopic, and histologic scores. Prospective double-blind RCT Fish oil extract containing 3.2 g/d EPA versus sunflower oil placebo (for 6-mo) IBD--ulcerative colitis (n = 18) Almallah et al., 1998 Omega-3 FAs helped maintain early remission but demonstrated little long-term benefits as assessed by colonoscopy, histology, and clinical symptoms. Prospective RCT Omega-3 FA oral supplement 5.1 g/d versus placebo (for 2-yr) IBD--ulcerative colitis (n = 64) Loeschke et al., 1996 Omega-3 FAs helped maintain remission for compliant patients, but no differences were observed in the intention-to-treat analysis. Prospective multicenter RCT Concentrated omega-3 FA compound 5 g/d versus placebo or carbohydrate-reduced diet (for 1-yr) IBD--Crohn’s disease (n = 204) Lorenz-Meyer et al., 1996 Omega-3 FAs prolonged remission without observed side effects. Prospective study Omega-3 FA supplement 6 capsules/d containing 162 mg/d EPA (for 3- to 36-mo) SLE (n = 10) Das, 1994 EPA = eicosapentaenoic acid, FA = fatty acid, RCT = randomized placebo-controlled study, SLE = systemic lupus erythematosus, IBD = inflammatory bowel disease, RA = rheumatoid arthritis, NSAIDs = non-steroidal anti-inflammatory drugs, GLA = gamma-linolenic acid Results Design Form of EPA (Length of Treatment) Condition (Subjects) Authors Table 2: Clinical Trials for EPA Supplementation in Autoimmune and Inflammatory Disorders
    26. 55. EPA decreased requirements for mechanical ventilation, improved gas exchange, decreased the length of ICU stay, and reduced the incidence of organ failure. Prospective multicenter double-blind RCT Liquid enteral diet with EPA versus control enteral formula (for 4- to 7-d) ARDS (n = 146) Gadek et al., 1999 Omega-3 FAs failed to reduce the incidence of ARDS and length of hospital stay in patients with severe trauma. Prospective RCT Liquid enteral diet with omega-3 FAs versus control enteral formula (for at least 5-d) ARDS with trauma (n = 43) Mendez et al., 1997 EPA decreased alveolar membrane protein permeability and reduced the presence of chemotactic factors and neutrophils in bronchoalveolar lavage fluid. Prospective double-blind RCT Liquid enteral diet with EPA versus control enteral formula (for 4- to 7-d) ARDS/ALI (n = 67) Pacht et al., 2003 Omega-3 FAs reduced the incidence of SIRS and improved SIRS and MOF scores after severe trauma. Prospective double-blind RCT Liquid enteral diet with omega-3 FAs 2 L/d versus control enteral formula (for 1-mo) SIRS with trauma (n = 29) Bastian et al., 1998 EPA improved survival rates, reduced complications, decreased the severity of graft-versus-host-disease, and lowered serum levels of pro-inflammatory mediators. Prospective RCT EPA oral supplement 1.8 g/d (for 28-wk) versus control SIRS with BMT (n = 16) Takatsuka et al., 2001 Omega-3 FAs reduced serum triglyceride levels and improved lipid profiles in familial hypertriglyceridemia. Prospective study Omega-3 FA oral supplement 2.16-4.32 g/d (for 1-yr) Hypertriglyceridemia (n = 12) Richter et al., 1992 Omega-3 FAs reduced serum triglyceride, VLDL, and chylomicron levels in familial hypertriglyceridemia. Prospective study Omega-3 FA oral supplement 2.16-4.32 g/d (for 1-yr) Hypertriglyceridemia (n = 8) Pschierer et al., 1995 Omacor reduced serum triglyceride concentrations by 45% and improved lipid profiles. Prospective double-blind RCT Omacor capsules 4 g/d containing 85% omega-3 FAs versus placebo (for 4-mo) Hypertriglyceridemia (n = 42) Harris et al., 1997 EPA = eicosapentaenoic acid, FA = fatty acid, RCT = randomized placebo-controlled study, ARDS = acute respiratory distress syndrome, ALI = acute lung injury, SIRS = systemic inflammatory response syndrome, BMT = bone marrow transplantation, MOF = multiple organ failure Results Design Form of EPA (Length of Treatment) Condition (Subjects) Authors Table 3: Clinical Trials for EPA Supplementation in Hypertriglyceridemia (Pancreatitis) and Inflammatory Disorders
    27. 56. Postoperative omega-3 FAs modestly decreased hospital stay, postoperative infection rates, and acute phase reactants in favor of constitutive protein production. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus control enteral formula or TPN (6-h following surgery until discharge) Gastric or pancreatic cancer (n = 260) Gianotti et al., 1997 Postoperative omega-3 FAs reduced hospital stay, infectious/wound complication rates, and PGE2 production. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus control enteral formula or TPN (POD 1 until discharge) Various upper GI cancers (n = 50) Daly et al., 1995 Postoperative omega-3 FAs reduced hospital stay and infectious/wound complication rates. Prospective RCT Liquid enteral diet with omega-3 FAs versus control enteral formula (POD 1 until discharge) Various upper GI cancers (n = 85) Daly et al., 1992 Postoperative omega-3 FAs failed to reduce hospital stay or infectious complications. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus intravenous crystalloid solutions (POD 1 until discharge) Various upper GI cancers (n = 195) Heslin et al., 1997 Postoperative omega-3 FAs improved immunological but not clinical parameters. Prospective double-blind RCT Liquid enteral diet with omega-3 FAs 20-80 ml/h versus control enteral formula (POD 1 until discharge) Various upper GI cancers (n = 42) Kemen et al., 1995 Perioperative omega-3 FAs reduced postoperative infections and complications. Prospective multi-center double-blind RCT Liquid enteral diet with omega-3 FAs 1 L/d versus control enteral formula (for 5-d) Various upper GI cancers (n = 154) Senkal et al., 1999 Postoperative omega-3 FAs decreased late complications after POD 5. Prospective multi-center double-blind RCT Liquid enteral diet with omega-3 FAs 20-80 ml/h versus control enteral formula (POD 1 until discharge) Various upper GI cancers (n = 154) Senkal et al., 1997 Postoperative omega-3 FAs decreased serum TNF-alpha and IL-6 levels. Prospective double-blind RCT Liquid enteral diet with omega-3 FAs versus control enteral formula (POD 1 until discharge) Various upper GI cancers (n = 42) Senkal et al., 1995 Perioperative omega-3 FAs increased constitutive proteins such as prealbumin and decreased inflammatory cytokines such as IL-6. Prospective double-blind RCT Liquid enteral diet with omega-3 FAs 1 L/d versus control enteral formula (for 2-wk) Gastric or colorectal cancer (n = 50) Gianotti et al., 1999 Postoperative omega-3 FAs reduced hospital stay and severity of postoperative infections. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus control enteral formula or TPN (12-h following surgery until discharge) Gastric or pancreatic cancer (n = 166) Braga et al., 1998 EPA = eicosapentaenoic acid, FA = fatty acid, TPN = total parenteral nutrition, RCT = randomized placebo-controlled study, POD = postoperative day, GI = gastrointestinal, TNF-alpha = tumor necrosis factor-alpha, IL-6 = interleukin-6, PGE2 = prostaglandin E2 Postoperative omega-3 FAs reduced hospital stay, severity of postoperative infections, increased constitutive protein levels, and improved immunologic parameters. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus control enteral formula or TPN (12-h following surgery until discharge) Gastric or pancreatic cancer (n = 77) Braga et al., 1995 Postoperative omega-3 FAs reduced severity of postoperative infections, increased constitutive protein levels, and improved monocyte function. Prospective RCT Liquid enteral diet with omega-3 FAs 25 kcal/kg/d versus control enteral formula or TPN (POD 1 until discharge) Gastric or pancreatic cancer (n = 60) Braga et al., 1996b Perioperative omega-3 FAs improved indicators of gut function. Prospective double-blind RCT Liquid enteral diet with omega-3 FAs 1 L/d versus control enteral formula (for 1-wk oral preoperatively and 1-wk jejunal infusion postoperatively) Gastric or colorectal cancer (n = 40) Braga et al., 1996a Results Design Form of EPA (Length of Treatment) Malignancy (Subjects) Authors Table 5: Clinical Trials for EPA Supplementation in Perioperative Nutrition for Gastrointestinal Malignancies
    28. 60. Barber et al. Brit J Nutr. 1999;81:80
    29. 62. Fearon KCH. 2001; Eur J Cancer 37:27S
    30. 63. Fearon KCH. 2001; Eur J Cancer 37:27S
    31. 65. n=30 n=28 n=26 n=22
    32. 69. Moses et al. 2001 Clin Nutr 20:21

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