Immunonutrition research from Ricochet Nutrition
The research is sound and theoretical advantages are clear, but the most important questions is, does it work in real life? Multiple clinical trials have been conducted and Ricochet Nutrition now has more than 10 years of clinical data to validate the remarkable advantages of optimizing our body’s ability to combat the physiological stress of cancer, chemotherapy and surgery through the use of immunonutrition.

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Clinical evidence for the use of Immunonutrition in surgical patients:
Integrated Role Of Nutrition Post-Hospital Discharge: Summary Of A Scientific Roundtable Discussion
November 4, 2014, Columbus, Ohio, USA


A roundtable discussion was organized by Abbott Nutrition on November 4, 2014 to discuss how nutrition care can be integrated in post-discharge care. This report summarized opinions from leaders in nutrition and healthcare, who presented the current healthcare landscape, examined challenges in post-discharge care, and highlighted the importance of standardized policies for nutrition care in improving health outcomes and reducing healthcare costs. U.S. and global Initiatives and efforts from interdisciplinary healthcare teams, such as the Alliance to Advance Patient Nutrition and the feedM.E. (Malnutrition Awareness and Medical Education) Global Study Group, to address malnutrition and enhance nutrition care for patients in the hospital and community were discussed. In these initiatives, use of oral nutritional supplements (ONS) has been demonstrated as an evidence-based cost effective nutrition intervention for different patient populations. In patients with diabetes, glycemia-targeted specialized nutrition (GTSN) was a successful nutrition therapy in improving patient outcomes and reducing healthcare costs. In summary, nutrition policies by multi-disciplinary coalitions addressing malnutrition should be made to improve patient care in the current healthcare environment. Barriers including the lack of awareness, time, resource, and training should be appraised for successful implementation of standardized nutrition policies.

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Should perioperative immunonutrition for elective surgery be the current standard of care?
Bharadwaj S, Trivax B, Tandon P, Alkam B, Hanouneh I, Steiger E. Gastroenterol Rep (Oxf). 2016 May;4(2):87-95. Epub 2016 Apr 14.


Postoperative infectious complications are independently associated with increased hospital length of stay (LOS) and cost and contribute to significant inpatient morbidity. Many strategies such as avoidance of long periods of preoperative fasting, re-establishment of oral feeding as early as possible after surgery, metabolic control and early mobilization have been used to either prevent or reduce the incidence of postoperative infections. Despite these efforts, it remains a big challenge to our current healthcare system to mitigate the cost of postoperative morbidity. Furthermore, preoperative nutritional status has also been implicated as an independent risk factor for postoperative morbidity. Perioperative nutritional support using enteral and parenteral routes has been shown to decrease postoperative morbidity, especially in high-risk patients. Recently,the role of immunonutrition (IMN) in postoperative infectious complications has been studied extensively. These substrates have been found to positively modulate postsurgical immunosuppression and inflammatory responses. They have also been shown to be cost-effective by decreasing both postoperative infectious complications and hospital LOS. In this review,we discuss the postoperative positive outcomes associated with the use of perioperative IMN, their cost-effectiveness, current guidelines and future clinical implications.

Key words: immunonutrition; infections; postoperative complications; cost-effectiveness; guidelines

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Preoperative Regular Diet of 900 kcal/day vs Balanced Energy High-Protein Formula vs Immunonutrition Formula: Effect on Preoperative Weight Loss and Postoperative Pain, Complications and Analytical Acute Phase Reactants After Laparoscopic Sleeve Gastrectomy.
Obes Surg. 2015 Sep 10. [Epub ahead of print] Ruiz-Tovar J1,2, Zubiaga L3, Diez M3, Murcia A4, Boix E5, Muñoz JL6, Llavero C7; OBELCHE group.


BACKGROUND: Between 2 and 8 weeks before surgery, most bariatric surgery groups establish strict dietary treatments with a total caloric intake of less than 1,000 kcal/day in order to maximize weight loss during this period of time.

METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic sleeve gastrectomy (LSG) was performed. Patients were randomly assigned into 3 groups: those patients receiving a preoperative regular diet of 900 kcal/day (group 1), those receiving a preoperative balanced energy high-protein formula (group 2) and those receiving preoperative Immunonutrition (group 3). Preoperative weight loss, postoperative pain, complications and analytical acute phase reactants were investigated.

RESULTS: Sixty patients were included in the study, 20 in each group. Preoperative excess weight loss was 7.7 % in group 1, 12.3 % in group 2 and 15.3 % in group 3 (p = 0.014). Median postoperative pain was 3.5 in group 1, 3 in group 2 and 2 in group 3 (p = 0.048). C-reactive protein determined 24 h after surgery was significantly lower in group 3 than in the other groups. AST and ALT values were significantly lower in group 3 than in the other groups, without significant differences between groups 1 and 2.

CONCLUSIONS: Preoperative diet with Immunonutrition formulas during 2 weeks achieves a greater preoperative weight loss, lower postoperative pain and lower values of CRP and liver enzymes than high-protein formulas or regular diet, all of them with similar caloric intake.

Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs.
World J Surg Oncol. 2012 Jul 6;10:136. doi: 10.1186/1477-7819-10-136.
Mauskopf JA1, Candrilli SD, Chevrou-Séverac H, Ochoa JB.


BACKGROUND: Oral or enteral dietary supplementation with arginine, omega 3 fatty acids and nucleotides (known as immunonutrition) significantly improve outcomes in patients undergoing elective surgery. The objective of the study was to determine the impact on hospital costs of immunonutrition formulas used in patients undergoing elective surgery for gastrointestinal cancer.

METHODS: US hospital costs of stay with and without surgical infectious complications, and average cost per day in the hospital for patients undergoing elective surgery for gastrointestinal cancer were estimated using data from the Healthcare Cost and Utilization Project’s 2008 Nationwide Inpatient Sample. These costs were then used to estimate the impact of perioperative immunonutrition on hospital costs using estimates of reduction in infectious complications or length of stay from a meta-analysis of clinical trials in patients undergoing elective surgery for gastrointestinal cancer. Sensitivity of the results to changes in baseline complication rates or length of stay was tested.

RESULTS: From the meta-analysis estimates, use of immunonutrition resulted in savings per patient of $3,300 with costs based on reduction in infectious complication rates or $6,000 with costs based on length of hospital stay. Cost savings per patient were present for baseline complication rates above 3.5% or when baseline length of stay and infectious complication rates were reduced to reflect recent US data for those with upper and lower GI elective cancer surgery (range, $1,200 to $6,300).

CONCLUSIONS: Use of immunonutrition for patients undergoing elective surgery for gastrointestinal cancer is an effective and cost-saving intervention.

Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials.
Surg Oncol. 2012 Jun;21(2):e87-95. doi: 10.1016/j.suronc.2012.01.002. Epub 2012 Feb 6.
Zhang Y1, Gu Y, Guo T, Li Y, Cai H.


BACKGROUND: To improve the clinical outcome, immunonutrition (IN) was usually used in the patients undergoing elective gastrointestinal cancer surgery. However, its effectiveness remains uncertain.

METHODS: Randomized controlled trials (RCTs) published between 1995 and 2011 were identified and extracted by two reviewers independently from electronic databases, including PubMed, EMBASE, and Cochrane Library. The quality of included trials was assessed according to the handbook for Cochrane reviewer (V5.0.1). Statistical analysis was carried out with RevMan software.

RESULTS: Nineteen RCTs involving a total of 2331 patients were included in our meta-analysis. The results showed perioperative IN significantly reduced length of hospital stay (WMD, -2.62; 95% CI, -3.26 to -1.97; P < 0.01) and morbidity of postoperative infectious complication (RR, 0.44; 95% CI, 0.32 to 0.60; P < 0.01) compared with standard diet. Moreover, perioperative IN also significantly decreased morbidity of postoperative non-infectious complication in comparison with standard diet (RR, 0.72; 95% CI, 0.54 to 0.97; P = 0.03).

CONCLUSION: Perioperative IN is effective and safe to reduce postoperative infection, non-infection complication and length of hospital stay.

Application of perioperative immunonutrition for gastrointestinal surgery: a meta-analysis of randomized controlled trials.
Asia Pac J Clin Nutr. 2007;16 Suppl 1:253-7.
Zheng Y1, Li F, Qi B, Luo B, Sun H, Liu S, Wu X.


The aim of this study was to evaluate clinical and economic validity of perioperative immunonutrition and effect on postoperative immunity in patients with gastrointestinal cancers. Immunonutrition diet supplemented two or more of nutrients including glutamine, arginine, omega-3 polyunsaturated fatty acids and ribonucleic acids. A meta-analysis of all relevant clinical randomized controlled trials (RCTs) was performed. The trials compared perioperative immunonutrition diet with standard diet. We extracted RCTs from electronic databases: Cochrane Library, MEDLINE, EMBASE, SCI and assessed methodological quality of them according handbook for Cochrane reviewer in June 2006. Statistical analysis was performed by RevMan4.2 software. Thirteen RCTs involving 1269 patients were included. The combined results showed that immunonutrition had no significant effect on postoperative mortality (OR =0.91, p= 0.84). But it had positive effect on postoperative infection rate (OR =0.41, p<0.00001), length of hospital stay (WMD=-3.48, p<0.00001). Furthermore, it improved immune function by increasing total lymphocytes (WMD=0.40, p<0.00001), CD4 levels (WMD=11.39, p<0.00001), IgG levels (WMD=1.07, p=0.0005) and decreasing IL6 levels (WMD=-201.83, p<0.00001). At the same time, we did not found significant difference in CD8, IL2 and CRP levels. There were no serious side effects and two trials found low hospital cost. In conclusion, perioperative diet adding immunonutrition is effective and safe to decrease postoperative infection and reduce length of hospital stay through improving immunity of postoperative patients as compared with the control group. Further prospective study is required in children or critical patients with gastrointestinal surgery.

Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients.
Crit Care Med. 1997 Sep;25(9):1489-96.
Senkal M1, Mumme A, Eickhoff U, Geier B, Späth G, Wulfert D, Joosten U, Frei A, Kemen M.


OBJECTIVE: To determine if early postoperative feeding of patients with upper gastrointestinal malignancy, using an enteral diet supplemented with arginine, dietary nucleotides, and omega-3 fatty acids (IMPACT, Sandoz Nutrition, Bern, Switzerland) results in an improved clinical outcome, i.e., reduced infectious and wound complications and decreased treatment costs when compared with an isocaloric, isonitrogenous control diet.

DESIGN: A prospective, randomized, placebo-controlled, double-blind, multicenter trial of the clinical outcome and a retrospective cost-comparison analysis.

PATIENTS: Of 164 patients enrolled in the study, 154 patients were eligible for analysis. They were admitted to the intensive care unit after upper gastrointestinal surgery for cancer and they received an enteral diet via needle catheter jejunostomy. Infectious complications were defined as sepsis or systemic inflammatory response syndrome, pneumonia, urinary tract infection, central venous catheter sepsis, wound infection, and anastomotic leakage. The complication events were prospectively divided into two groups: early (postoperative days 1 to 5) and late (after the fifth postoperative day) postoperative complications. The treatment costs of each complication were analyzed and compared in both groups.

INTERVENTIONS: Patients were randomized to receive either the immunonutritional diet (n = 77) or an isocaloric and isonitrogenous placebo diet (n = 77). Enteral feeding was initiated 12 to 24 hrs after surgery, starting with 20 mL/hr and advanced to a target volume of 80 mL/hr by postoperative day 5.

MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse gastrointestinal symptoms were recorded on a daily basis. Both groups tolerated early enteral feeding well, and the rate of tube feeding-related complications was low. Postoperative complications occurred in 17 patients in the immunonutrition group vs. 24 patients in the control group (NS). Further, in the early phase (postoperative day 1 to 5), complications occurred to a similar extent in both groups (12 patients in the immunonutritional group vs. 11 patients in the control group). However, in the late phase (after postoperative day 5), considerably fewer patients in the experimental diet group experienced complications compared with the control group (5 vs. 13, p < .05). In addition, the frequency rate of complicating events were recorded in each group. In the experimental diet group, a total of 22 complicating events were recorded vs. a total of 32 events in the placebo diet group (NS). However, the occurrence of late complicating events, i.e., complicating events after the fifth postoperative day, was significantly reduced in the immunonutrition group when compared with the control group (8 vs. 17 events, p < .05). The total costs for the treatment of the complications were 83,563 German marks in the experimental diet group vs. 122,430 German marks in the control group, resulting in a cost-reduction of 38,867 German marks. (At the end of December 1995, the conversion rate from German marks to U.S. dollars was 1.4365 German marks to $1.00.)

CONCLUSIONS: Early enteral feeding with an arginine, dietary nucleotides, and omega-3 fatty acids supplemented diet, as well as an isonitrogenous, isocaloric control diet (placebo) were well tolerated in patients who underwent upper gastrointestinal surgery. In patients who received the supplemented diet, a significant reduction in the frequency rate of late postoperative infectious and wound complications was observed. Thereby, the treatment costs were substantially reduced in the immunonutrition group as compared with the control group

J Visc Surg. 2015 Aug;152 Suppl 1:S14-7. doi: 10.1016/S1878-7886(15)30005-9.
Mariette C1.


Based on a grade A level of evidence, immunonutrition should be given to all patients operated on for a digestive cancer 5 to 7 days prior to surgery whatever could be the patient nutritional status. Immunonutrition should be continued in the postoperative phase in malnourished patients for 5 to 7 days or until patients are able to recover oral feeding covering at least 60% of their needs.

Post-operative enteral immunonutrition for gynecologic oncology patients undergoing laparotomy decreases wound complications.
Gynecol Oncol. 2015 Jun;137(3):523-8. doi: 10.1016/j.ygyno.2015.04.003. Epub 2015 Apr 16.
Chapman JS1, Roddy E2, Westhoff G1, Simons E3, Brooks R1, Ueda S1, Chen L4.


OBJECTIVES: The aim of this study is to determine if peri-operative immune modulating dietary supplements decrease wound complications in gynecologic oncology patients undergoing laparotomy.

METHODS: In July 2013 we instituted a practice change and recommended pre- and post-operative oral immune modulating diets (IMDs) to patients undergoing laparotomy. We retrospectively compared patients who received IMDs to those who did not for the study period July 2012 to June 2014. Our outcome of interest was the frequency of Centers for Disease Control surgical site infections (CDC SSIs).

RESULTS: Of the 338 patients who underwent laparotomy during the study period, 112 (33%) received IMDs post-operatively. There were 89 (26%) wound complications, including 69 (78%) CDC SSI class 1, 7(8%) class 2 and 13(15%) class 3. Patients receiving IMDs had fewer wound complications than those who did not (19.6% vs. 33%, p=0.049). After controlling for variables significantly associated with the development of a wound complication (ASA classification, body mass index (BMI), history of diabetes mellitus or pelvic radiation, length of surgery and blood loss) consumption of IMDs remained protective against wound complications (OR 0.45, CI 0.25-0.84, p=0.013) and was associated with a 78% reduction in the incidence of CDC SSI class 2 and 3 infections (OR=0.22, CI 0.05-0.95, p=0.044).

CONCLUSIONS: Post-operative IMDs are associated with fewer wound complications in patients undergoing laparotomy for gynecologic malignancy and may reduce the incidence of CDC SSI class 2 and 3 infections.

Clinical evidence for use of immunonutrition in cancer and chemotherapy patients:
Immunonutrition improves functional capacities in head and neck and esophageal cancer patients undergoing radiochemotherapy: a randomized clinical trial.
Clin Nutr. 2014 Apr;33(2):204-10. doi: 10.1016/j.clnu.2013.06.008. Epub 2013 Jun 20.
Vasson MP1, Talvas J2, Perche O2, Dillies AF3, Bachmann P4, Pezet D5, Achim AC6, Pommier P7, Racadot S4, Weber A8, Ramdani M8, Kwiatkowski F9, Bouteloup C10.


BACKGROUND & AIMS: Malnutrition is frequent in head and neck (HN) and esophageal cancer patients and aggravated by radiochemotherapy (RCT), increasing morbi-mortality and treatment toxicity. Our goal was to investigate the effect of immunonutrition consisting of an arginine, omega-3 fatty acid, nucleotides-enriched diet on nutritional status, and functional capacity in HN or esophageal cancer patients undergoing RCT.

METHODS: 37 patients were randomized in a double-blind clinical trial. 5 days before and until the end of RCT (5-7 weeks), they received either an Immunomodulating Enteral Nutrition (IEN) or an isonitrogenous, isoenergetic Standard Enteral Nutrition (SEN). Anthropometrical parameters, nutritional risk index (NRI), serum albumin, plasma antioxidant capacity, and functional capacity were recorded between the beginning and the end of RCT.

RESULTS: A significant gain in total body weight (+2.1 ± 3.1 kg) was observed in IEN patients. Albuminemia and NRI were improved concomitantly in IEN malnourished patients. Plasma antioxidant capacity was improved (+100 ± 13 μM EqTrolox) in IEN patients. Functional capacity measured by WHO Performance Status and Karnofsky index was maintained in IEN patients but significantly reduced in SEN patients.

CONCLUSIONS: These preliminary data show that immunonutrition could improve the nutritional status together with functional capacity in HN and esophageal cancer patients undergoing RCT.

Immunonutrition before and during radiochemotherapy: improvement of inflammatory parameters in head and neck cancer patients.
Support Care Cancer. 2012 Dec;20(12):3129-35. doi: 10.1007/s00520-012-1444-5. Epub 2012 Mar 28.
Machon C1, Thezenas S, Dupuy AM, Assenat E, Michel F, Mas E, Senesse P, Cristol JP.


PURPOSE: Inflammatory, angiogenic and oxidative stress markers have been explored in head and neck squamous cell carcinoma (HNSCC) patients before and during radiochemotherapy. Furthermore, the effects of an oral supplementation containing amino acids, ω-3 fatty acids, ribonucleic acids, vitamins, and antioxidants on biological markers and acute toxicities were investigated.

METHODS: Thirty-one patients with non-metastatic stage III or IV HNSCC treated with concomitant radiochemotherapy were recruited. A nutritional support (Oral Impact) was given during 5 days before each cycle of chemotherapy. Biological samples were collected at baseline, after 5 days of oral supplementation and before the last cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines determination and urinary isoprostanes levels were used as inflammatory and oxidative stress biomarkers. Toxicities were followed up during radiochemotherapy.

RESULTS: At baseline, median levels of inflammatory (CRP 9.8 mg/l [0.8-130.1], IL-6 4.2 pg/ml [0.7-126.5]), pro-angiogenic (VEGF 229.5 pg/ml [13.1-595.9]) and pro-oxidative stress (urinary isoprostanes 118 pmol/mmol creatinine [51-299]) markers were increased. Decrease in CRP (p = 0.002) and α-1 acid glycoprotein (p = 0.020) levels were observed after 5 days of oral supplementation. During radiochemotherapy, no significant variation of inflammatory markers was reported, and a low incidence of severe acute mucositis was noted.

CONCLUSIONS: Stage III or IV HNSCC patients are characterised by a pro-inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could improve this inflammatory state and could prevent severe acute mucositis

An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.
Nutr Cancer. 2015 Aug-Sep;67(6):912-20. doi: 10.1080/01635581.2015.1053495. Epub 2015 Jul 2.
Nakamura K1, Sasayama A, Takahashi T, Yamaji T.


Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

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