Therapeutic Nutrition In the Oncology Population


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Therapeutic Nutrition In the Oncology Population

  1. 1. Therapeutic Nutrition In the Oncology Population Suzanne Dixon, MPH, MS, RD Oncology Nutrition Specialist & Epidemiologist Cancer Nutrition Info, LLC
  2. 2. Why is Nutrition Such a Battleground? <ul><li>May be the only aspect of care with which family & friends feel they can help </li></ul><ul><li>May be the only thing over which the individual with cancer still feels a sense of control </li></ul><ul><li>People want to help & everyone ‘knows’ nutrition </li></ul><ul><li>These conflicting agendas cause much anxiety and tension </li></ul>
  3. 3. Why Should We Care About Nutrition? <ul><li>20 to 40% of cancer patient deaths are related to cancer-induced or treatment related malnutrition </li></ul><ul><li>Site of treatment: </li></ul><ul><ul><li>GI tract and/or pelvic region: diarrhea, lactose intolerance, malabsorption, weight loss </li></ul></ul><ul><ul><li>Head & Neck: xerostomia, superficial ulceration in the field of radiation, bleeding, pain, mucositis, weight loss </li></ul></ul><ul><li>Mucositis during chemotherapy ~ 40%, </li></ul><ul><li>Mucositis during chemoradiation ~ 100% </li></ul><ul><li>Effect of symptoms on dietary intake profound: ~ 60% of H&N & GI patients lose weight upon beginning treatment </li></ul>
  4. 4. Nutrition Intervention Works! <ul><li>The Good News… </li></ul><ul><li>Getting Help With Nutrition WORKS!! Recent study comparing usual care with intensive diet intervention (seeing a dietitian) showed that people who see a dietitian do better! 1 </li></ul><ul><li>Population: GI & H&N </li></ul><ul><li>1 British Journal of Cancer 2004;91:447-452. </li></ul>
  5. 5. Cachexia vs. Anorexia <ul><li>Anorexia: ‘Lack of Appetite’ & ‘Involuntary Decline in Food Intake’ </li></ul><ul><ul><ul><li>Anorexia is EFFECT rather than CAUSE of Cachexia </li></ul></ul></ul><ul><li>Cachexia is term to describe the disordered metabolism of diseases including (but not limited to): </li></ul><ul><ul><ul><li>Cancer </li></ul></ul></ul><ul><ul><ul><li>HIV/AIDS </li></ul></ul></ul><ul><ul><ul><li>Sepsis </li></ul></ul></ul><ul><ul><ul><li>Other chronic infections </li></ul></ul></ul><ul><ul><ul><li>Other Inflammatory Conditions </li></ul></ul></ul>
  6. 6. Cytokines Responsible for Metabolic Alterations
  7. 7. Disordered Metabolism
  8. 8. Adequate Education of Family & Care Givers Key <ul><li>May be a fundamental lack of understanding among family members & care givers </li></ul><ul><ul><li>Symptoms </li></ul></ul><ul><ul><li>Physical sensations of ‘starving’ </li></ul></ul><ul><li>Forcing the issue is often counterproductive </li></ul><ul><li>Must be addressed before the crisis point </li></ul>
  9. 9. Treatment Nutrition Goals <ul><li>Phase 1: Getting Through Treatment ( Primary Goals ) </li></ul><ul><ul><li>Prevent or correct nutritional deficiencies </li></ul></ul><ul><ul><li>Minimize short-term and long-term treatment side effects </li></ul></ul><ul><ul><li>Improve tolerance to treatment </li></ul></ul><ul><ul><li>Enhance quality of life during treatment </li></ul></ul><ul><ul><li>Help achieve and maintain optimal body weight </li></ul></ul><ul><ul><li>Educate family members about special nutrition needs </li></ul></ul><ul><ul><li>Evaluate the risks and benefits of nutrition-related CAM (supplements, vitamins, minerals, herbs); consider medication interaction issues! </li></ul></ul>
  10. 10. Treatment Nutrition Goals <ul><li>Phase 2: Cancer Fighting Nutrition For Life ( Secondary Goals ) </li></ul><ul><ul><li>Maintain healthy weight </li></ul></ul><ul><ul><li>Incorporate healthy nutrition habits for long-term health </li></ul></ul><ul><ul><li>Maximize cancer preventive potential of the diet (minimize recurrence risk) </li></ul></ul><ul><ul><li>Evaluate the risks and benefits of nutrition-related CAM (supplements, vitamins, minerals, herbs); consider medication interaction issues! </li></ul></ul>
  11. 11. Addressing Primary Clinical Nutrition Intervention Goals
  12. 12. Screening Vs. Assessment <ul><li>SCREENING </li></ul><ul><li>To detect possibility of nutrition risk </li></ul><ul><li>Provide information to determine if follow-up is required </li></ul><ul><li>All oncology patients in all settings require screening </li></ul><ul><li>Screen must be simple & self-administered </li></ul><ul><li>Screen determines whether patient is referred to specialist (RD) </li></ul><ul><li>If screening detects need for more intensive assessment & intervention, arrange for this immediately </li></ul><ul><li>If referral unnecessary, document screen & re-screen at follow-up </li></ul><ul><li>ASSESSMENT </li></ul><ul><li>More intensive & thorough </li></ul><ul><li>Includes intervention, follow-up, intervention, follow-up, etc. </li></ul>
  13. 13. The Who & How of Screening <ul><li>Generally, nursing staff performs screen: In-home & Outpatient </li></ul><ul><li>May simply provide & collect form to/from patient & return it to the office for screening score & further intervention planning </li></ul><ul><li>Different clinics & home care companies use different methods for patient referral </li></ul><ul><ul><li>Forms handed to dietitian prior to scoring </li></ul></ul><ul><ul><li>Forms scored & referrals made by nursing/medical staff </li></ul></ul><ul><li>Referral must be made if patient is classified at risk </li></ul><ul><li>Dietitian may keep & store screening forms, but it will need to be in permanent medical record </li></ul><ul><li>Best Tool: Patient-Generated Subjective Global Assessment (PG-SGA) </li></ul>
  14. 14. Screening Tool Fundamentals <ul><li>SCREENING TOOL </li></ul><ul><li>PG-SGA = Patient Generated Subjective Global Assessment </li></ul><ul><li>Despite the name, PG-SGA is a good screening tool </li></ul><ul><li>PG-SGA is validated for use in oncology populations </li></ul><ul><li>Easy to administer & score </li></ul><ul><li>ITEMS ON A NUTRITION SCREEN </li></ul><ul><li>Weight History & Percent Weight Change </li></ul><ul><li>Food Intake: Has It Changed? </li></ul><ul><li>Symptoms </li></ul><ul><li>Functional Status </li></ul><ul><li>Disease & stage </li></ul><ul><li>Metabolic demand </li></ul><ul><li>Physical exam </li></ul>
  15. 15. PG-SGA Scoring & Optimal Intervention <ul><li>PG-SGA Score Guides Nutrition Intervention </li></ul><ul><li>Not At Risk: Additive Score = 0 to 1 </li></ul><ul><ul><li>No intervention required at this time; continue to screen at follow up visits </li></ul></ul><ul><li>Stage A/Low Risk: Additive Score = 2 to 3 </li></ul><ul><ul><li>Well nourished, but may still be at risk; intervention includes education by dietitian or nurse, with pharmacologic nurse or physician triage as indicated by symptom survey </li></ul></ul><ul><li>Stage B/Moderately Malnourished: Additive Score = 4 to 8 </li></ul><ul><ul><li>Moderately malnourished, requires dietitian intervention working in conjunction with nurse, physician, and medical care team as indicated by the symptom check-off for pharmacologic management </li></ul></ul><ul><li>Stage C/Severely Malnourished: Additive Score = 9 or greater </li></ul><ul><ul><li>Critical need for symptom mgmt and other nutrition intervention. Requires interdisciplinary team discussion to address all aspects affecting nutritional status and discussion of non-oral nutrition options including enteral or parenteral nutrition as dictated by gut function </li></ul></ul>
  16. 16. From Screening To Assessment <ul><li>AFTER SCREEN INDICATES RISK, FULL ASSESSMENT: </li></ul><ul><li>Weight History & Percent Weight Change; Consider IBW </li></ul><ul><li>Appearance, behavior, mental health </li></ul><ul><li>Age & Gender </li></ul><ul><li>Functional status (Karnofsky Score, ECOG Score, etc.) </li></ul><ul><li>GI, oral cavity, head & neck region, cancer type & location </li></ul><ul><li>Intake: Diet History & 24-Hour Recall </li></ul><ul><ul><li>FFQ generally NOT appropriate in the clinical setting </li></ul></ul><ul><ul><li>Diet records are impractical </li></ul></ul><ul><li>Biochemical parameters: Albumin, Prealbumin, Transferrin, Hematocrit, Hemoglobin, RBP, glucose, CRP, Serum Creatinine </li></ul><ul><li>Medications & Planned Treatment </li></ul><ul><li>Psychosocial?? Financial?? </li></ul>
  17. 17. Symptoms Affecting Nutrition Status <ul><li>Diarrhea </li></ul><ul><li>Sore Mouth </li></ul><ul><li>Dry Mouth </li></ul><ul><li>Altered Taste/Smell </li></ul><ul><li>Constipation </li></ul><ul><li>Lack of Appetite </li></ul><ul><li>Fullness/Early Fullness </li></ul><ul><li>Fluid status (ascites, edema) </li></ul><ul><li>Dumping Syndrome </li></ul><ul><li>Nausea/Vomiting </li></ul><ul><li>Other Pain </li></ul>
  18. 18. Nutrition Can Help Manage Symptoms <ul><li>KEY: START EARLY </li></ul><ul><li>Specific Diet Modifications Will Help Minimize Nutrition-Related Side Effects </li></ul><ul><li>Each Side Effect Has Numerous Approaches for Mgmt </li></ul><ul><li>Nutrients/Food will PROFOUNDLY Affect The Body </li></ul><ul><li>Written Materials Alone May Not Be Sufficient </li></ul>
  19. 19. Some Patients Must Have Enteral Support <ul><li>Nutrition ‘tricks’ (and there are dozens) may be useful for non-acute patients </li></ul><ul><li>For others, enteral support is a must </li></ul><ul><li>Screening & Assessment will help identify those requiring more aggressive intervention </li></ul><ul><li>Some populations need enteral support preemptively (H&N, Stomach, other GI…) </li></ul>
  20. 20. When Is Initiation of Enteral Nutrition Indicated? <ul><li>Actual or anticipated inability to meet 50% of needs for 7 or more days </li></ul><ul><li>Contributes to Quality/Length of life in meaningful way </li></ul><ul><li>Can improve tolerance to treatment and/or ultimate outcome </li></ul><ul><li>Patient wants it </li></ul><ul><li>A functioning gut (to some degree) is present </li></ul><ul><li>Is not contraindicated </li></ul><ul><ul><li>Obstruction? </li></ul></ul><ul><ul><li>Gastroparesis? </li></ul></ul><ul><ul><ul><li>May be able to by-pass with a J-tube </li></ul></ul></ul><ul><ul><ul><li>Is there hypomotility of the small intestine as well? </li></ul></ul></ul><ul><ul><li>Nausea/Vomiting? </li></ul></ul><ul><ul><ul><li>Often can get around this if using a J-tube </li></ul></ul></ul>
  21. 21. Beginning Enteral Feeding <ul><li>Use HBE to determine Calorie Needs </li></ul><ul><li>Males: BEE = 66.5+(13.7xW{kg})+(5.0xH{cm})-(6.8xA{yrs}) </li></ul><ul><li>Females: BEE = 655+(9.6xW{kg})+(1.9xH{cm})-(4.7xA{yrs}) </li></ul><ul><li>(Quick & Easy: 35-50 kcal/kg for hypermetabolic patients) </li></ul><ul><li>Protein Needs </li></ul><ul><li>1.3 to 1.5 grams/kg body weight (IBW or Adjusted IBW) </li></ul><ul><li>Adjusted IBW = (Actual BW - IBW) x (0.25 to 0.4) + IBW </li></ul><ul><li>IBW: Males = 106 lbs + 6 lbs/inch + 10%; Females = 100 lbs + 5 lbs/inch + 10% </li></ul><ul><li>Fluid Needs </li></ul><ul><li>1500 mL for first 20 kg of body weight + 20 mL per kg for </li></ul><ul><li>each kg over 20 kg </li></ul>
  22. 22. Basic Points For Enteral Feeding <ul><li>SELECT FORMULA CONSIDERING: </li></ul><ul><li>Osmolality (280 to 350 mOsm ideal for J-feeds); Albumin?? </li></ul><ul><li>Calories per cc </li></ul><ul><li>Malabsorption (Specialty Formulas, MCT oil) </li></ul><ul><li>Account for free water & supplement liberally as needed </li></ul><ul><li>ROUTE OF ADMINISTRATION </li></ul><ul><li>Will G-Tube Be Tolerated? </li></ul><ul><li>Is J-Tube Necessary? (can bypass nausea & high obstructions) </li></ul><ul><li>Begin slowly; always, Always, ALWAYS use pump with J-Tubes </li></ul><ul><li>Gravity Feed/Bolus </li></ul><ul><ul><li>Bolus feeding: 250 - 300 mL over 15 minutes, followed by 25-60 mL water; at least 3 hours b/w each bolus feeding </li></ul></ul>
  23. 23. Trouble Shooting for Enteral Feeding Problems
  24. 24. Addressing Secondary Clinical Nutrition Intervention Goals
  25. 25. Healing 101: No Judging <ul><li>Why judge? It should be clear why a client is doing a specific approach! </li></ul><ul><li>Don’t take it personally! </li></ul><ul><li>Compliment client on initiative - Do NOT indicate disdain </li></ul><ul><li>Don’t forget the power of ‘self-help’ </li></ul>
  26. 26. Healing 102: Everyone is Unique <ul><li>The story of the medical student and loss of compassion </li></ul><ul><li>Use science but be compassionate </li></ul><ul><li>Don’t betray your own principles but DO be flexible </li></ul><ul><li>Never say never! </li></ul>
  27. 27. Healing 103: Nocebo Effect <ul><li>What about YOUR expectations? </li></ul><ul><li>Your power is greater than you believe or know </li></ul><ul><li>Don’t betray your own principles but DO be honest & compassionate </li></ul><ul><li>Never say never! </li></ul>
  28. 28. First Do No Harm <ul><li>Discouragement of a harmless or potentially beneficial intervention may constitute harm (must consider all aspects including psychological, emotional, socioeconomic, etc) </li></ul><ul><li>Nutrients & Food Have The Ability To PROFOUNDLY Affect Our Bodies, On Many Levels </li></ul><ul><li>For the Client, “Food & Nutrition Are POWER, And YOU Control That Power By Choices!” </li></ul>
  29. 29. Think About This <ul><li>If you think you don’t need to think about this, you’re missing the boat </li></ul><ul><li>A Few Nutrients of Interest: </li></ul><ul><ul><li>Capsaicin </li></ul></ul><ul><ul><li>Coenzyme Q-10 </li></ul></ul><ul><ul><li>Eicosapentaenoic Acid (EPA) (Omega-3s) </li></ul></ul><ul><ul><li>Glutamine </li></ul></ul><ul><ul><li>Ginger </li></ul></ul><ul><ul><li>Milk Thistle </li></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Zinc </li></ul></ul>
  30. 30. <ul><li>Weight loss and malnutrition have been shown to lead to: </li></ul><ul><li>Decreased treatment tolerance </li></ul><ul><li>Longer hospital stays </li></ul><ul><li>Decreased quality of life </li></ul><ul><li>Reduced life expectancy </li></ul><ul><li>Regaining lost weight is difficult, so early nutritional intervention is critical </li></ul><ul><li>Useful interventions include omega-3 fats (EPA/DHA) </li></ul>The Implications: 1 Andreyev, et al, 1998. 2 Ottery 1996. 3 O’Gorman P, et al, 1998, Andreyev, 1998. 4 Albrecht and Canada 1996, Ottery 1995.
  31. 31. <ul><li>Early Intervention With Specialized Nutrition: </li></ul><ul><li>Recent studies have shown that specialized ingredients help improve outcomes: </li></ul><ul><ul><li>Omega-3 fatty acids (EPA/DHA) </li></ul></ul><ul><ul><ul><li>Help prevent muscle and fat breakdown </li></ul></ul></ul><ul><ul><ul><li>Help improve appetite </li></ul></ul></ul><ul><ul><ul><li>Help restore metabolic balance </li></ul></ul></ul><ul><ul><li>Standard supplements do not contain EPA/DHA or high levels of essential amino acids </li></ul></ul>Solutions: 1 Barber, et al, 2001; Tisdale, et al, 2003; Wigmore, et al, 1997. 2 Borsheim, et al, 2002; Tipton, et al, 1999; Shaw, et al, 1988.
  32. 32. Omega-3 fatty acids (EPA/DHA) have been shown to reverse weight loss & increase LBM – may improve treatment tolerance Weight and Lean Body Mass in Patients with Advanced Pancreatic Cancer Following Administration of an EPA-Enriched Nutritional Supplement Source: Barber MD, et al, 1999. Prospective study completed in 20 pancreatic cancer patients experiencing weight loss. Patients consumed an average of 1.9 cans/day of a nutritional supplement containing 1.1g EPA/can in addition to normal food intake for 7 wks.
  33. 33. Mean Change in Physical Activity Level Following 8 Weeks of Oral Supplementation Karnofsky Performance Status Following Supplementation with EPA-Enriched Supplement Source: Moses, et al, 2001 examined a subset of a large randomized trial conducted in pancreatic cancer patients and compared the intake of nutritional supplements with and without EPA (1.1g – 2.2g/day) and the effects on total energy expenditure and physical activity level. Source: Barber MD, et al, 1999. Prospective study in 20 patients with pancreatic cancer experiencing ongoing weight loss. Patients consumed average 1.9 cans/day of a nutritional supplement containing 1.1g EPA/can along with normal intake for 7 weeks. Nutritional supplements enriched with omega-3 fatty acids (EPA/DHA) have been shown to improve quality of life and performance status
  34. 34. Source: Voss AC, et al, 2003. Voss, et al, examined survival rates in pancreatic cancer patients from 2 different studies. In one study patients received an omega-3 fatty acid nutritional supplement containing 1.1g EPA/can and in the other a supplement containing no omega-3. Impact of EPA Supplement on Survival Nutritional supplements enriched with omega-3 fatty acids (EPA/DHA) have been shown to increase life expectancy
  35. 35. “ Best Bet” Complementary Cancer Therapies <ul><li>Eicosapentaenoic Acid (EPA) (Omega-3s) </li></ul><ul><ul><li>Essential fatty acid with potential roles in inflammation, immunity, cachexia </li></ul></ul><ul><ul><li>May help decrease cachexia </li></ul></ul><ul><ul><li>May improve chemotherapy effectiveness/enhance immune function </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>May have anticoagulant activity so use with caution if platelets low or on coagulation therapy </li></ul></ul><ul><ul><li>Generally well tolerated (up to 0.3 g EPA+DHA/kg body weight/day), but diarrhea possible </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>Minimum dose of 2.2 mg EPA per day (best to avoid coagulation complications) </li></ul></ul><ul><ul><li>Two new products on the market Prosure & Resource Support </li></ul></ul>
  36. 36. What Is Glutamine? <ul><li>Neutral, gluconeogenic nonessential amino acid </li></ul><ul><li>Stored primarily in skeletal muscle (75%) and liver (25%) </li></ul><ul><li>Nitrogen carrier between tissues </li></ul><ul><li>Primary energy source for rapidly proliferating cells (e.g. intestinal epithelium, activated lymphocytes, & fibroblasts) </li></ul><ul><li>May be conditionally essential; depleted in stress states (e.g. surgery, sepsis, & cancer) </li></ul><ul><li>Appears to be synthesized in muscle tissue in substantial amounts </li></ul><ul><li>Plasma concentrations are quite high, second only to alanine </li></ul><ul><li>Needed for renal acid-base balance </li></ul>
  37. 37. Why Glutamine For Oncology? <ul><li>Neuropathy </li></ul><ul><li>Arthralgias </li></ul><ul><li>Myalgias </li></ul><ul><li>Diarrhea </li></ul><ul><li>Enteritis & GI Mucosal Damage </li></ul><ul><li>Stomatitis </li></ul><ul><li>Muscle Mass Preservation?? </li></ul>
  38. 38. Glutamine For Neuropathy: Physiology & Possible Mechanisms of Action <ul><li>Role in circulating nerve growth factor levels </li></ul><ul><ul><li>increased peripheral neuropathy concurrent with declining serum nerve growth factor concentrations </li></ul></ul><ul><ul><li>animal models: glutamine up-regulates nerve growth factor mRNA </li></ul></ul><ul><ul><li>ongoing studies are examining nerve growth factor concentrations in banked serum </li></ul></ul>
  39. 39. Glutamine For Neuropathy: Physiology & Possible Mechanisms of Action <ul><li>Role in pain perception in the cerebral cortex </li></ul><ul><ul><li>glutamine is a precursor amino acid for excitatory neurotransmitters such as glutamate and GABA </li></ul></ul><ul><ul><li>glutamine into astrocytes and converted to glutamate (glutamine synthetase), then released into synapse </li></ul></ul><ul><ul><li>some glutamate in neurotransmitter capacity, but some used for neuronal energy requirements </li></ul></ul><ul><ul><li>hypothesized that high systemic glutamine concentrations may down-regulate conversion of glutamine to glutamate </li></ul></ul>
  40. 40. Glutamine For Arthralgias/Myalgias: Physiology & Possible Mechanisms of Action <ul><li>Role in metabolic stress states </li></ul><ul><ul><li>Glutamine freely released from skeletal muscles in states of metabolic distress </li></ul></ul><ul><ul><li>Advanced malignant disease results in muscle glutamine depletion and weight loss </li></ul></ul><ul><ul><li>Stress hormones induce decreased muscle glutamine concentrations, even in healthy adults </li></ul></ul><ul><ul><li>Intracellular glutamine concentrations  more than 50% under metabolic stress </li></ul></ul><ul><ul><li>Glutamine is known to preserve glutathione concentrations; glutathione is needed for intracellular redox status </li></ul></ul>
  41. 41. Glutamine For Arthralgias/Myalgias: Physiology & Possible Mechanisms of Action <ul><li>Role in metabolic stress states </li></ul><ul><ul><li>Previous research suggests that during periods of metabolic stress, approximately 15 to 35 grams of supplemental glutamine may be needed to preserve muscle glutamine concentrations, provide fuel for cells with rapid turnover, and improve overall nitrogen balance. </li></ul></ul><ul><ul><li>Glutamine is vital as energy for rapidly proliferating cells, it may be extracted from muscles and supplied to other cells at the expense of muscle and connective tissue integrity </li></ul></ul><ul><ul><li>Altered redox status and resultant oxidative damage may also play a role in pain syndromes </li></ul></ul>
  42. 42. Glutamine For Diarrhea/Enteritis: Physiology & Possible Mechanisms of Action <ul><li>Role in provision of energy, nutrients, cellular building blocks to enterocytes </li></ul><ul><ul><li>Well-documented that glutamine is preferred fuel for GI tract </li></ul></ul><ul><ul><li>Three potential mechanisms through which glutamine appears to exert positive effects on GI tissue: </li></ul></ul><ul><ul><ul><ul><li>Primary cellular fuel of enterocytes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Precursor for nucleotides needed for cell regeneration </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Source of glutathione, an endogenous anti-oxidant system </li></ul></ul></ul></ul>
  43. 43. Glutamine For Diarrhea/Enteritis: Physiology & Possible Mechanisms of Action <ul><li>Cell, Animal, & Human Studies Demonstrate: </li></ul><ul><ul><li>Glutamine is documented as preferential fuel for enterocytes, esp. during stress </li></ul></ul><ul><ul><li>Controls glycogen synthesis in enterocytes </li></ul></ul><ul><ul><li>Decreases protein degradation in enterocytes </li></ul></ul><ul><ul><li>Demonstrated to enhance gut cell mass </li></ul></ul><ul><ul><li>Demonstrated to increase height of mucosal villi </li></ul></ul><ul><ul><li>Demonstrated to increase numbers of mucosal villi </li></ul></ul><ul><ul><li>Decreases bacterial translocation under stress </li></ul></ul>
  44. 44. Glutamine For Muscle Mass Maintenance: Physiology & Possible Mechanisms of Action <ul><li>Role in weight loss for HIV/AIDS </li></ul><ul><ul><li>Loss of body cell mass (BCM) correlates with length of survival in this, and other, populations </li></ul></ul><ul><ul><li>Hypothesized that glutamine, which is conditionally essential, may be rate-limiting for repletion of BCM </li></ul></ul><ul><ul><li>Muscles synthesize glutamine & release into circulation </li></ul></ul>
  45. 45. Glutamine For Muscle Mass Maintenance: Physiology & Possible Mechanisms of Action <ul><li>Role in weight loss for HIV/AIDS </li></ul><ul><ul><li>Tissues that consume glutamine extract as needed from circulation </li></ul></ul><ul><ul><li>During stress and inflammation, consumption of glutamine exceeds ability of skeletal muscle to supply this amino acid </li></ul></ul><ul><ul><li>Blood & muscle glutamine concentrations decrease and muscle breaks down to satisfy needs </li></ul></ul>
  46. 46. Glutamine For Muscle Mass Maintenance: Research Evidence <ul><li>Study </li></ul><ul><li>Shabert et al. 1999 </li></ul><ul><ul><li>40 grams glutamine/day in divided doses </li></ul></ul><ul><ul><li>26 patients total </li></ul></ul><ul><ul><li>Double-blind, placebo controlled (glycine as control) </li></ul></ul><ul><ul><li>Over 3 months: glutamine group gained 2.2 kg vs. 0.3 in control (1.8 kg BCM vs. 0.4 kg BCM) </li></ul></ul><ul><li>Given common etiology between wasting seen in HIV/AIDS and wasting seen in cancer cachexia, it may be possible to enhance lean body mass retention throughout cancer treatment with glutamine </li></ul>
  47. 47. “ Best Bet” Complementary Cancer Therapies <ul><li>Glutamine </li></ul><ul><ul><li>Amino Acid </li></ul></ul><ul><ul><li>May help with diarrhea/GI symptoms & sore mouth/throat </li></ul></ul><ul><ul><li>May help decrease mucositis (5-FU) </li></ul></ul><ul><ul><li>May help decrease radiation enteritis </li></ul></ul><ul><ul><li>May help With Aching Muscles/Nerves (Taxol) </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>No major side effects, some minor side effects </li></ul></ul><ul><ul><li>Do not take if you have poor kidney and/or liver function </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>10 grams glutamine powder, three times per day, dissolved in liquid (research has been done with Cambridge Nutraceuticals-Baxter Pharmaceuticals & Glutasolve by Novartis) </li></ul></ul>
  48. 48. Think About This <ul><li>Looking at a summary of some other potentially important interventions: </li></ul><ul><li>A Few Nutrients of Interest: </li></ul><ul><ul><li>Capsaicin </li></ul></ul><ul><ul><li>Coenzyme Q-10 </li></ul></ul><ul><ul><li>Eicosapentaenoic Acid (EPA) (Omega-3s) </li></ul></ul><ul><ul><li>Glutamine </li></ul></ul><ul><ul><li>Ginger </li></ul></ul><ul><ul><li>Milk Thistle </li></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><li>Zinc </li></ul></ul>
  49. 49. Capsaicin Taffy Recipe (For Sore Mouth) 1 cup sugar 3 / 4 cup light corn syrup 2 / 3 cup water 1 tablespoon cornstarch 2 tablespoons butter or margarine 1 teaspoon salt 2 teaspoons vanilla 1 1 / 2 teaspoons cayenne pepper Combine all ingredients except vanilla and cayenne pepper and cook over medium heat stirring constantly, to 256°F (use candy thermometer). Remove from heat, stir in vanilla and cayenne pepper. When cool enough to handle, pull taffy. When stiff, cut into strips, then pieces and wrap. From: Journal of Pain and Symptom Management 1995;10(3): 245
  50. 50. “ Best Bet” Complementary Cancer Therapies <ul><li>Coenzyme Q10 </li></ul><ul><ul><li>Antioxidant </li></ul></ul><ul><ul><li>May protect heart muscle from damage during treatment with certain chemotherapy regimens (adriamycin) </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>Appears to be safe when used in reasonable dose </li></ul></ul><ul><ul><li>It acts as an antioxidant and some experts believe antioxidants are counterproductive during radiation therapy; data is mixed concerning antioxidants during radiation therapy, but overall suggests moderate use is ok </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>30 mg two times daily </li></ul></ul>
  51. 51. “ Best Bet” Complementary Cancer Therapies <ul><li>Ginger </li></ul><ul><ul><li>Food spice that also has medicinal properties </li></ul></ul><ul><ul><li>Taken as tea or root may help alleviate nausea </li></ul></ul><ul><ul><li>Also try 'natural' ginger ales </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>Can act as mild anti-coagulant </li></ul></ul><ul><ul><li>Use with caution if low platelets or are on anti-coagulant medications (e.g. coumadin, heparin, etc.) </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>Chopped/dried extracts for tea, taken 2-3 times daily </li></ul></ul><ul><ul><li>940 mg once daily of powdered ginger root for nausea prevention </li></ul></ul><ul><ul><li>250 mg of powder taken 4 times daily for nausea mgmt </li></ul></ul>
  52. 52. “ Best Bet” Complementary Cancer Therapies <ul><li>Milk Thistle </li></ul><ul><ul><li>May help protect the liver from damaging effects of chemotherapy; may protect kidney & other organs </li></ul></ul><ul><ul><li>May help the liver regenerate & recover after damage </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>Appears very safe for use in cancer patients; not much data on use in those with liver involvement </li></ul></ul><ul><ul><li>Mild nausea is a reported side effect </li></ul></ul><ul><ul><li>Mild anti-coagulant; use with caution if platelets are low </li></ul></ul><ul><ul><li>May reduce effectiveness of oral contraceptives </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>140 mg standardized to 70-80% silymarin, 3 times daily </li></ul></ul><ul><ul><li>Phosphatidylcholine-bound silymarin, 100 mg 3 to 4 times daily </li></ul></ul>
  53. 53. “ Best Bet” Complementary Cancer Therapies <ul><li>Probiotics </li></ul><ul><ul><li>“ Healthy Bacteria” in yogurt & other fermented foods </li></ul></ul><ul><ul><li>May have selective immune modulating activity </li></ul></ul><ul><ul><li>May decrease rates of ‘opportunistic’ infections </li></ul></ul><ul><ul><li>May decrease diarrhea, mucositis, improve nutrient absorption </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>Not many downsides however… </li></ul></ul><ul><ul><li>Dietary supplement products are poorly regulated and contamination is possible (yogurt & other fermented dairy are good options) </li></ul></ul><ul><ul><li>May need to be avoided in severe immune compromise (e.g. BMT populations) </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>Unknown </li></ul></ul>
  54. 54. “ Best Bet” Complementary Cancer Therapies <ul><li>Zinc </li></ul><ul><ul><li>May help restore sense of taste during radiation therapy to head/neck region </li></ul></ul><ul><ul><li>May take up to 1 month for noticeable effect </li></ul></ul><ul><li>Downside: </li></ul><ul><ul><li>Short term use improves immune function, long term use may suppress immune function </li></ul></ul><ul><ul><li>DO NOT USE if on cisplatin as zinc may increase toxicity </li></ul></ul><ul><li>Dose: </li></ul><ul><ul><li>30 - 50 mg daily elemental zinc daily (~135 - 220 mg zinc sulfate, divided into three doses) </li></ul></ul>
  55. 55. Use the Resources That Are Available To Evaluate CAM <ul><li>Herbal/Supplement Resources (websites) : </li></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> ( </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> & </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li> </li></ul></ul>
  56. 56. Use the Resources That Are Available To Evaluate CAM <ul><li>Look at the Herbal/Supplement Resources (books) : </li></ul><ul><ul><li>Mosby’s Handbook of Herbs & Natural Supplements </li></ul></ul><ul><ul><li>German Commission E Monographs </li></ul></ul><ul><ul><li>The Health Professional’s Guide to Popular Dietary Supplements </li></ul></ul><ul><ul><li>The Honest Herbal & Herbs of Choice </li></ul></ul><ul><ul><li>Herbal Drugs and Phytopharmaceuticals </li></ul></ul><ul><ul><li>The Encyclopedia of Medicinal Plants </li></ul></ul><ul><ul><li>Integrative Medicine: Your Quick Reference Guide </li></ul></ul><ul><ul><li>PDR for Herbal Medicines </li></ul></ul><ul><ul><li>Herbal Medicinals: A Clinician’s Guide </li></ul></ul><ul><ul><li>H erbal Medicines: A Guide for Healthcare Professionals </li></ul></ul><ul><ul><li>The American Pharmaceutical Association Practical Guide to Natural Medicines </li></ul></ul><ul><ul><li>Rational Phytotherapy: A Physican’s Guide to Herbal Medicine </li></ul></ul><ul><ul><li>Many, many journals also available </li></ul></ul>
  57. 57. Does Nutrition Matter for Survival?
  58. 58. Findings of Special Interest <ul><li>Body Weight, ER status & Risk of Death After Breast Cancer: </li></ul><ul><ul><li>1997 Int J Epidemiol : 1169 early stage breast cancer cases </li></ul></ul><ul><ul><li>Lower # estrogen receptors assoc w/ hazard ratio of 1.8 </li></ul></ul><ul><ul><li>Highest BMI vs. lowest BMI (quartiles) assoc w/ a hazard ratio of 2.5!! </li></ul></ul><ul><li>Diet & Body Weight & Risk of Death After Breast Cancer: </li></ul><ul><ul><li>1998 Breast Cancer Res Treat : 472 early stage breast cancer cases, diet data collected & patients followed </li></ul></ul><ul><ul><li>Higher consumption of butter, margarine, lard, beer, red meat, liver, bacon increases likelihood of dying AFTER diagnosis of breast cancer </li></ul></ul><ul><ul><li>HIGHER body weight (as measured by BMI) assoc w/ higher risk of death AFTER diagnosis of breast cancer </li></ul></ul>
  59. 59. Findings of Special Interest <ul><li>Zinc Supplements For Taste Changes: </li></ul><ul><ul><li>1998 Cancer : 20 head and neck cancer cases randomized to 45 mg zinc sulfate, 3 times daily or placebo </li></ul></ul><ul><ul><li>Those receiving zinc supplement: less worsening sense of taste when compared to placebo </li></ul></ul><ul><ul><li>Those receiving zinc recovered their sense of taste faster after treatment </li></ul></ul><ul><li>Saturated Fat & Risk of Death After Prostate Cancer: </li></ul><ul><ul><li>1999 Eur Urol : 384 confirmed prostate cancer cases </li></ul></ul><ul><ul><li>Diet data collected & patients followed </li></ul></ul><ul><ul><li>Higher consumption of saturated fat increases likelihood of dying AFTER diagnosis of prostate cancer </li></ul></ul>
  60. 60. Findings of Special Interest <ul><li>Diet & Risk of Death After Stomach Cancer Diagnosis: </li></ul><ul><ul><li>2000 Nutr Cancer : 877 confirmed stomach cancer cases </li></ul></ul><ul><ul><li>Diet data collected & patients followed </li></ul></ul><ul><ul><li>Higher consumption of tofu & raw vegetables decreases likelihood of dying AFTER diagnosis of stomach cancer </li></ul></ul><ul><li>Processed Tomato Products & Prostate Cancer: </li></ul><ul><ul><li>2001 JNCI : 32 men w/ prostate cancer fed 3/4 cup tomato sauce daily for 3 weeks; serum & prostate lycopene concentrations, PSA, oxidative damage assessed pre- and post-intervention </li></ul></ul><ul><ul><li>Post-intervention: serum & prostate lycopene significantly increased; oxidative damage & PSA significantly decreased </li></ul></ul>
  61. 61. Findings of Special Interest <ul><li>Fasting Insulin & Breast Cancer Recurrence Risk: </li></ul><ul><ul><li>2002 Journal of Clin Onc : 512 women with early stage breast cancer (T1-T3, N0-N1, M0) w/o known diabetes followed prospectively </li></ul></ul><ul><ul><li>Highest vs. Lowest quartile had twice the risk of distant recurrence & death </li></ul></ul><ul><ul><li>Insulin associated w/ BMI and BMI a known risk factor </li></ul></ul><ul><li>AHCC ® & Hepatocellular Carcinoma (HCC) </li></ul><ul><ul><li>2002 J Hepatol : 222 people with confirmed HCC </li></ul></ul><ul><ul><li>By self choice: assigned to surgical resection vs. surgical resection plus AHCC ® and followed for a time ranging between 2 months to 10 years </li></ul></ul><ul><ul><li>Intervention vs. Normal Care: </li></ul></ul><ul><ul><li>34% vs. 66% recurrence </li></ul></ul><ul><ul><li>80% vs. 53% survival </li></ul></ul>
  62. 62. Findings of Special Interest <ul><li>Avemar ® & Colorectal Cancer </li></ul><ul><ul><li>2003 Br J Cancer : 176 people, Dukes A-D colorectal cancer diagnosis </li></ul></ul><ul><ul><li>By self choice: assigned to regular treatment vs. regular treatment plus Avemar ® and followed for 30-34 months </li></ul></ul><ul><ul><li>Intervention vs. Normal Care: </li></ul></ul><ul><ul><li>3% vs. 17% recurrence </li></ul></ul><ul><ul><li>7% vs. 23% new metasases </li></ul></ul><ul><ul><li>31% vs. 64% progression </li></ul></ul><ul><ul><li>75% vs. 54% survival </li></ul></ul><ul><li>Lycopene & Advanced Prostate Cancer </li></ul><ul><ul><li>2003 BJU Int : 54 men randomized to orchidectomy or orchidectomy + lycopene and followed for 2+ years </li></ul></ul><ul><ul><li>PSA of 78% of supplemented group returned to normal vs. only 40% in orchidectomy alone group </li></ul></ul><ul><ul><li>Normal bone scans in 25% of supplemented group vs only 15% of orchidectomy alone group having normal scans </li></ul></ul><ul><ul><li>2 years after intervention: 87% of supplemented group alive vs. 78% of orchidectomy alone group </li></ul></ul>
  63. 63. Findings of Special Interest <ul><li>Diet, Insulin & Risk of Death After Breast Cancer: </li></ul><ul><ul><li>2004 Cancer Epidemiol Biomarkers Prev : 603 women with breast cancer asked about diet & had blood samples collected </li></ul></ul><ul><ul><li>Higher level of insulin = worse survival </li></ul></ul><ul><ul><li>Higher protein & lower fat = better survival </li></ul></ul><ul><ul><li>Higher intake of sweets and sugar = worse survival </li></ul></ul><ul><li>Breast Cancer & Health Behavior Changes </li></ul><ul><ul><li>2004 Eur J Clin Nutr : 354 Finnish & Australian women diagnosed with breast cancer surveyed about experiences & choices </li></ul></ul><ul><ul><li>One-third reported changing diet & exercise habits </li></ul></ul><ul><ul><li>Both populations reported high need for diet & lifestyle counseling </li></ul></ul><ul><ul><li>Both populations reported this need as unrecognized by physicians </li></ul></ul>
  64. 64. Nutrition For Prevention of Recurrence: Fantasy or Reality? <ul><li>Consider the research and there is A LOT of it!! </li></ul><ul><li>So many things are not in our control, encourage your clients to take advantage of the things that are! </li></ul><ul><li>Nutrition & Diet are powerful tools that one can use in the journey to regain and maintain health after a cancer diagnosis. </li></ul>
  65. 65. Remember This Truth… <ul><li>Nutrients & Food Have The Ability To PROFOUNDLY Affect Our Bodies, On Many Levels </li></ul><ul><li>Food Is POWER Over Disease Risk, And WE Control It! </li></ul>
  66. 66. Let Food Be Your Medicine And Medicine Be Your Food - Hippocrates, 337 BC
  67. 67. References <ul><li>Isenring E, Bauer J, Capra S. The scored Patient-generated Subjective Global Assessment (PG-SGA) and its association with quality of life in ambulatory patients receiving radiotherapy. Eur J Clin Nutr . 2003;57: 305-9. </li></ul><ul><li>Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Nutritional deterioration in cancer: the role of disease and diet. Clin Oncol (R Coll Radiol). 2003;15:443-50. </li></ul><ul><li>Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr. 2002;56:779-85. </li></ul><ul><li>Capra S, Ferguson M, Ried K. Cancer: impact of nutrition intervention outcome--nutrition issues for patients. Nutrition. 2001;17:769-72. </li></ul><ul><li>Ottery FD. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition. 1996;12:S15-9. </li></ul><ul><li>FD Ottery, Patient-generated subjective global assessment of nutritional status. Nutritional Oncology . 1996;2(8-9). </li></ul><ul><li>Decker G, Bagyi JJ. Nutrition Interventions to Impact Clinical Practice (monograph). Minneapolis, MN: Novartis Nutrition, 2003. </li></ul>
  68. 68. References <ul><li>8. Evans MA, Shronts EP. Intestinal fuels: glutamine, short-chain fatty, and dietary fiber. Journal of the American Dietetic Association . 1992;92:1239-1246,1249. </li></ul><ul><li>9. Fox AD, Kripke SA, De Paula J, Berman JM, Settle RG, Rombeau JL. Effect of glutamine supplemented enteral diet on methotrexate induced enterocolitis. JPEN: Journal of Parenteral & Enteral Nutrition. 1988;12:325-331. </li></ul><ul><li>10. Klimberg M. The Clauce H. Organ, Jr. Honorary Lectureship: Glutamine, cancer, and its therapy. American Journal of Surgery . 1996;172:418-424. </li></ul><ul><li>11. Klimberg VS. How glutamine protects the gut during irradiation. ICCN . 1996;3:21. </li></ul><ul><li>12. Klimberg VS. Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation. Archives of Surgery . 1990;125:1040-1045. </li></ul><ul><li>Muscaritoli M, Micozzi A, Conversano L, Martino P, Petti MC, Cartoni C, Cascino A, Rossi-Fanelli F, et al. Oral glutamine in the prevention of chemotherapy induced gastrointestinal toxicity. European Journal of Cancer . 1997;33:319-320. </li></ul><ul><li>14. Savarese, D., Al-Zoubi, A., Boucher, J. Glutamine for irinotecan diarrhea. Journal of Clinical Oncology . 2000;18:450-451. </li></ul>
  69. 69. References 15. Anderson P, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer. 1998;83:1433-1439. 16. Skubitz K, Anderson P. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. Journal of Laboratory and Clinical Medicine. 1996;127:223-228. 17. Levy MH, Rosen SM, Ottery FD, Hermann J. Supportive care in oncology. Current Problems in Cancer . 1992;16:329-418. 18. Slavin JL. Implementation of dietary modifications. American Journal of Medicine. 1999;106:46S-49S, discussion 50S-51S. 19. Savarese D, Boucher J, Corey B. Glutamine treatment of paclitaxel-induced myalgias and athralgias. Journal of Clinical Oncology. 1998;12:3918-3919. 20. Boyle FM, Wheeler HR, Shenfield GM. Glutamine ameliorates experimental vincristine neuropathy. Journal of Pharmacology & Experimental Therapy. 1996;279:410-415. 21. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. British Journal of Anaesthesia . 2000;84(3):367-371.
  70. 70. References 22. Burton A. Chemoprevention: eat ginger, rub on pomegranate. Lancet Oncol . 2003;4:715. 23. Sharma SS, Gupta YK. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale). J Ethnopharmacol . 1998;62:49-55. 24. Ripamonti C, Zecca E, Brunelli C, Fulfaro F, Villa S, Balzarini A, Bombardieri E, De Conno F. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer . 1998;82:1938-1945. 25. Ertekin MV, Koc M, Karslioglu I, Sezen O. Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. Int J Radiat Oncol Biol Phys . 2004;58:167-74. 26. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. American Journal of Gastroenterology. 1998;93:139-43. 27. Ladas EJ, Kelly KM. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? J Altern Complement Med . 2003;9: 411-16. 28. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine . 1998. 3rd ed. Berlin, Germany: Springer-Verlag.
  71. 71. References <ul><li>29. Eaton S, Skinner R, Hale JP, Pourfarzam M, Roberts A, Price L, Bartlett K. Plasma coenzyme Q(10) in children and adolescents undergoing doxorubicin therapy. Clinica Chimica Acta . 2000;302:1-9. </li></ul><ul><li>30. Cortes EP, Gupta M, Chou C, Amin VC, Folkers K. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treatment Reports . 1978;62:887-89. </li></ul><ul><li>31. Folkers K, Liu M, Watanabe T, Porter TH. Inhibition by adriamycin of the mitochondrial biosynthesis of coenzyme Q10 and implication for the cardiotoxicity of adriamycin in cancer patients. Biochemical & Biophysical Research Communications . 1977;77:1536-42. </li></ul><ul><li>Burns CP, Halabi S, Clamon GH, Hars V, Wagner BA, Hohl RJ, Lester E, Kirshner JJ, Vinciguerra V, Paskett E. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clinical Cancer Research . 1999;5:3942-3947. </li></ul><ul><li>33. Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ. 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. Gut . 2003; 52:1479-86. </li></ul>
  72. 72. References 34. Hardman WE. Omega-3 fatty acids to augment cancer therapy. J Nutr . 2002; 132: 3508S-3512S. 35. Boik J. Natural Compounds in Cancer Therapy. 2001. 1 st ed. Princeton, MN: Oregon Medical Press, LLC. 36. Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci . 2003;23: 4315-23. 37. Kasdan ML, Lewis K, Bruner A, Johnson AL. The nocebo effect: do no harm. J South Orthop Assoc . 1999; 8: 108-13. 38. Flaten MA, Simonsen T, Olsen H. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom Med . 1999;61:250-55. 39. Spiegel H. Nocebo: the power of suggestibility. Prev Med . 1997;26:616-21. 40. Hahn RA. The nocebo phenomenon: concept, evidence, and implications for public health. Prev Med . 1997;26:607-11.
  73. 73. References 41. Schweiger A, Parducci A. Nocebo: the psychologic induction of pain. Pavlov J Biol Sci . 1981;16:140-3. 42. Spriet A, Spriet C, Larousse C, Chigot D, Roux M, Simon P. Methodology and results of a survey of adverse reactons to a drug in private practice. Eur J Clin Pharmacol . 1977;11:181-92. 43. Newman SC, Lees AW, Jenkins HJ. The effect of body mass index and oestrogen receptor level on survival of breast cancer patients. Int J Epidemiol . 1997;26:484-90. 44. Hebert JR, Hurley TG, Ma Y. The effect of dietary exposures on recurrence and mortality in early stage breast cancer. Breast Cancer Res Treat . 1998;51:17-28. 45. Fradet Y, Meyer F, Bairati I, Shadmani R, Moore L. Dietary fat and prostate cancer progression and survival. Eur Urol .1999;35:388-91. 46. Meyer F, Bairati I, Shadmani R, Fradet Y, Moore L. Dietary fat and prostate cancer survival. Cancer Causes Control . 1999;10:245-51. 47. Huang XE, Tajima K, Hamajima N, Kodera Y, Yamamura Y, Xiang J, Tominaga S, Tokudome S. Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer. Nutr Cancer . 2000;38:30-36.
  74. 74. References 48. Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van Breemen R, Ashton D, Bowen PE. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst . 2001;93:1872-79. 49. Spriet A, Spriet C, Larousse C, Chigot D, Roux M, Simon P. Methodology and results of a survey of adverse reactons to a drug in private practice. Eur J Clin Pharmacol . 1977;11:181-92. 50. Newman SC, Lees AW, Jenkins HJ. The effect of body mass index and oestrogen receptor level on survival of breast cancer patients. Int J Epidemiol . 1997;26:484-90. 51. Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int . 2003;92:375-8;discussion 378. 52. Salminen E, Bishop M, Poussa T, Drummond R, Salminen S. Dietary attitudes and changes as well as use of supplements and complementary therapies by Australian and Finnish women following the diagnosis of breast cancer. Eur J Clin Nutr . 2004;58:137-44.
  75. 75. References <ul><li>53. Smith RF, Wilmore DW. Glutamine nutrition and requirements. J Parenter Enteral Nutr 1990;14:94S-99S. </li></ul><ul><li>54. Windmeuller HG. Glutamine utilization by the small intestine. Adv Enzymol 1982;53:201-237. </li></ul><ul><li>55. Chipponi JX, Bleier JC, Santi MT, Rudman D. Deficiencies of essential and conditionally essential nutrients. Am J Clin Nutr 1982;35:1112-1116. </li></ul><ul><li>De Santis S, Pace A, et al. Patients treated with antitumor drugs displaying neurologic deficits are characterized by a low circulating level of nerve growth factor. Clin Cancer Res 2000;6:90-95. </li></ul><ul><li>57. Gwag BJ, Sessler, et al. Endogenous glutamate levels regulate nerve growth factor mRNA expression in the rat dentate gyrus. Mol Cell 1999;7:425-430. </li></ul><ul><li>58. Vahdat L, Papadopoulos K, et al. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 2001;7:1192-1197. </li></ul><ul><li>59. Kandel E, Schwartz J, Jessell T (eds.). Principles of Neural Science, 3 rd Edition. Norwalk, CT: Appleton & Lange, 1991. </li></ul><ul><li>60. Roberg B, Torgner IA, Kvamme E. Inhibition of glutamine transport in rat brain mitochondria by some amino acids and tricarboxylic acid cycle intermediates. Neurochem Res 1999;24:809-814. </li></ul>
  76. 76. References <ul><li>Daikhim Y, Yudkoff M. Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr 2000;130:1026S-1031S. </li></ul><ul><li>62. Fraser CL, Arieff AI. Hepatic encephalopathy. New Engl J Med 1985;313:865-873. </li></ul><ul><li>63. Brown SA, Goringe A, Fegan C et al. Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplantation 1998;22:281-284. </li></ul><ul><li>64. Vante JP, et al. Plasma amino acid profiles in sepsis and stress. Ann Surg 1989;209:57-62. </li></ul><ul><li>65. Boyle FM, et al. Glutamate ameliorates experimental vincristine neuropathy. J Pharmacol Exp Therap 1996;279:410-415. </li></ul><ul><li>Boyle FM, et al. Prevention of experimental paclitaxel neuropathy with glutamate. Proceedings AACR 1996;37:290. </li></ul><ul><li>67. Askanazi J, et al. Muscle and plasma amino acids following injury: influence of intercurrent infection. Ann Surg 1980;192:78-85. </li></ul><ul><li>68. Furst P, et al. Influence of amino acid supply on nitrogen and plasma amino acid metabolism in severe trauma. Acta Chir Scand 1979;494:136-138. </li></ul>
  77. 77. References <ul><li>69. Hammarqvist F, Ejesson B, Wernerman J. Stress hormones initiate prolonged changes in the muscle amino acid pattern. Clinical Physiology 2001;21:44-50 </li></ul><ul><li>70. Furst P, et al. Evidence for a nutritional need for glutamine in catabolic patients. Kidney Int 1989;36:5287-5292. </li></ul><ul><li>Klimberg VS, Souba WW, Salloum RM, et al. Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res 1990;48:319-323. </li></ul><ul><li>72. Jensen J, et al. Dietary glutamine prevents chronic radiation enteropathy. Ann Surg Oncol 1993;1:157-163. </li></ul><ul><li>73. Yoshida S, Matsui M, et al. Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg 1998;227:485-91. </li></ul><ul><li>74. Wilmore DW. Metabolic support of the gastrointestinal tract: potential gut protection during intensive cytotoxic therapy. Cancer 1997;79:1794-1803. </li></ul><ul><li>75. Klimberg VS, Souba WW, et al. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990;66:62-68. </li></ul><ul><li>76. Klimberg S. Prevention of radiogenic side effects using glutamine-enriched elemental diets. Recent Results Cancer Res 1991;121:283-855. </li></ul>
  78. 78. References <ul><li>77. Souba WW, Klimberg VS, Copeland EM 3 rd . Glutamine nutrition in the management of radiation enteritis. JPEN 1990;14:106S-108S. </li></ul><ul><li>Jensen JC, Schaefer R, et al. Prevention of chronic radiation enteropathy by dietary glutamine. Ann Surg Oncol 1994;1:157-163. </li></ul><ul><li>79. Cao Y, Feng Z, et al. Glutamine enhances gut glutathione production. JPEN 1998;22:224-227. </li></ul><ul><li>80. Bai MX, Jiang ZM, et al. Effects of alanyl-glutamine on gut barrier function. Nutrition 1996;12:793-796. </li></ul><ul><li>81. Robinson MK, Ziegler TR, Wilmore DW. Overview of intestinal adaptation and its stimulation. Eur J Pediatr Surg 1999;9:200-206. </li></ul><ul><li>82. Wilmore DW, Schloerb PR, Ziegler TR. Glutamine in the support of patients following bone marrow transplantation. Curr Opin Clin Nutr Metab Care 1999;2:323-327. </li></ul><ul><li>83. Argiles JM, Lopez-Soriano. The role of cytokines in cancer cachexia. Med Res Rev 1999; 19: 223-248. </li></ul><ul><li>Barber MD, Ross JA, Fearon KC. Disordered metabolic response with cancer and its management. World J Surg; 2000; 24: 681-689. </li></ul><ul><li>85. Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS Jr. NF- B-Induced loss of MyoD messenger RNA: Possible role in muscle decay and cachexia. Science 2000; 289: 2363-2366. </li></ul>
  79. 79. References <ul><li>86. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A. Failure to regulate TNF-Induced NF-B and cell death responses in A20-deficient mice. Science 2000; 289: 2350-2354. </li></ul><ul><li>87. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A. Failure to regulate TNF-Induced NF-B and cell death responses in A20-deficient mice. Science 2000; 289: 2350-2354. </li></ul><ul><li>Marian M. Cancer cachexia: Prevalence, mechanisms, and interventions. Support Line 1998; XX: 3-12. </li></ul><ul><li>89. Tisdale MJ. Protein loss in cancer cachexia. Science 2000; 289: 2293-2294. </li></ul><ul><li>90. P.D. McCallum & C.G. Polisena (Eds.). The Clinical Guide to Oncology Nutrition , 2000. Chicago: The American Dietetic Association. </li></ul><ul><li>91. Anderson, P., et al. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-1439. </li></ul><ul><li>92. Skubitz, K. and Anderson P. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. Journal of Laboratory and Clinical Medicine 1996;127:223-228. </li></ul><ul><li>93. Levy M.H., Rosen, S.M., Ottery, F.D., Hermann, J. Supportive care in oncology. Current Problems in Cancer 1992;16(6):329-418. </li></ul>
  80. 80. References 94. Shabert JK, Winslow C, Lacey JM, Wilmore DM. Glutamine-anti-oxidant supplementation increases body cell mass in AIDS patients with weight loss: A randomized, double-blind controlled trial. Nutrition 1999;15:860-864.