Immune-enhancing Nutrients Research Articles

COVID-19: A Review of Immune-enhancing Nutrients and Supplements

COVID-19: A Review of Immune-enhancing Nutrients and Supplements

Dairy-Derived and Egg White Proteins in Enhancing Immune System Against COVID-19.

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.

ASPEN-FELANPE Clinical Guidelines: Nutrition Support of Adult Patients with Enterocutaneous Fistula

Background: the management of patients with enterocutaneous fistula (ECF) requires an interdisciplinary approach and poses a significant challenge to surgeons, gastroenterologists, intensivists, wound/stoma care specialists, and nutrition support clinicians. Available guidelines for optimizing nutritional status in these patients are often vague, based on limited and dated clinical studies, and typically rely on individual or institutional experience. Specific nutrient requirements, appropriate route of feeding, role of immune-enhancing nutrients, and use of somatostatin analogs in the management of patients with ECF remain a challenge for the clinician. The purpose of this clinical guideline is to develop recommendations for the nutritional care of adult patients with ECF. Methods: a systematic review of the best available evidence to answer a series of questions regarding clinical management of adults with ECF was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. An anonymous consensus process was used to develop the clinical guideline recommendations prior to peer review and approval by the A.S.P.E.N. and FELANPE Board of Directors. Questions: in adult patients with enterocutaneous fistula: 1) What factors best describe nutritional status? 2) What is the preferred route of nutritional therapy (oral diet, EN or PN)? 3) What protein and energy intake provide best clinical outcomes? 4) Is fistuloclysis associated with better outcomes than standard care? 5) Are immune-enhancing nutrients associated with better outcomes? 6) Does the use of somatostatin provide better outcomes than standard medical therapy? 7) When is home parenteral nutrition support indicated?

Nutrition Practices in Hematopoietic Stem Cell Transplantation (HSCT): A Comparison between Guidelines and Clinical Practice

Background Several professional societies have established nutrition guidelines for patients undergoing HSCT. We surveyed HSCT programs to understand how these compare with clinical practice. Methods Qualitative surveys were emailed to HSCT dietitians. Surveys addressed malnutrition screening; dietary recommendations including nutrition support, graft-versus-host disease (GVHD), immune enhancing nutrients, and prebiotics/probiotics; and nutrition-related preventive care screening. Results Twenty adult programs (19 United States (US), 1 Australia) and 3 pediatric programs (3 US) responded. Annual volume across the 22 US programs was 5405 patients, representing 25% of all transplants in the US. Nineteen programs (83%) follow guidelines for nutrition screening and fourteen for nutrition therapy in the inpatient setting (Table 1); six (26%) follow guidelines for screening and therapy in the outpatient setting. All programs adhere to food safety recommendations and 5 (22%) have additional institutional precautions. However, only 2 programs (9%) report frequent adherence to guidelines for use of enteral nutrition. While there are no guidelines for GVHD diet and uncertainty over alternative nutrition practices, 8 programs (35%) follow a stepwise GVHD diet; 4 (17%) allow immunonutrition supplements; 2 (9%) allow prebiotics, and 7 (30%) allow probiotics after the resolution of neutropenia. With regard to adherence to preventive screening recommendations, only 4 programs (17%) screen for diabetes, 6 (26%) screen for hyperlipidemia, and none screen for abdominal obesity. There are no guidelines for vitamin D deficiency screening, but 10 programs (43%) screen for this. Discussion Wide variations in nutrition practices exist across HSCT programs. Similarly, with the exception of food safety recommendations, there are also wide variations in adherence to established nutrition guidelines. The use of enteral nutrition and preventive screening is particularly varied. Efforts are needed to understand barriers to guideline implementation and their correlation to patient outcomes. Further research is needed regarding new interventions such as immunonutrition, prebiotics, and probiotics.

Effect of immune-enhancing enteral nutrition formula enriched with plant-derived n-3 fatty acids on natural killer cell activity in rehabilitation patients.

BACKGROUND/OBJECTIVESEnteral nutrition formulas with immune-enhancing nutrients, such as n-3 fatty acids, may manage patients' nutritional status and pathophysiological processes. The aim of our study was to investigate natural killer (NK) cell activity alterations and related cytokine changes resulting from feeding with soybean oil-containing enteral nutrition formula (control group) and plant-derived n-3 fatty acid-enriched enteral nutrition formula.SUBJECTS/METHODSSubjects participated for 14 consecutive days and consumed enteral formula containing canola and flaxseed oil (n3EN, test group) in nonsurgical patients hospitalized for rehabilitation. Blood samples were collected on the first day and 14 days after the consumption of each formula daily, and anthropometric parameters were collected. Hematology and biochemical values were analyzed, and NK cell activities and serum cytokine concentration were measured. A total of sixty subjects were included in the analysis, excluding dropouts.RESULTSNo significant differences were found in biochemical parameters. The n3EN group's NK cell activities at effector:tumor cell ratios of 10:1, 5:1, 2.5:1 and 0.625:1 were significantly higher than those of the control group after two weeks (P < 0.05). However, there were no statistically significant differences in serum cytokine interleukin (IL)-12, interferon-γ, IL-1β, IL-6 and tumor necrosis factor-α values between the two groups.CONCLUSIONSIn conclusion, this study elucidates the beneficial effects of plant-derived n-3 fatty acid supplementation in enteral formula on NK cell activity.

Immunonutrition and Amino Acids

Loss of body protein?mostly from skeletal muscles?is the most characteristic sign of critical illness. The most common immune-enhancing nutrients for favorable Compensatory Anti-inflammatory Response Syndrome (CARS) are glutamine, arginine, poly-unsaturated fatty acid, some trace elements and probiotics. Glutamine is an essential amino acid with an important role it fuels the proliferation of cells and acts as a precursor to antioxidant glutathione. The conflicting results of glutamine trials are largely related to its dosage and duration of treatment. However, its overall effects, when parenterally or enterally supplied, are thought to be helpful in immune-enhancing and decreasing infectious complications. Arginine is also conditionally essential and has an important role in the synthesis of anabolic hormones and in the activation of T lymphocytes. It also is converted to citrulline and nitric oxide, the latter is a potent intracellular signaling molecule. Leucine and citrulline are common in the mechanism of action and are mediated by the mTOR signaling pathway. Both leucine- and citrulline-enriched diets have been proven to increase nutritional status in various experimental models of injury. However, there are conflicting data about when they were supplied to the critically ill patients. The role of the most immune-modulating nutrients have not been fully discovered thus far. For critically ill patients, basic support with macro-nutrients should come first, followed by other specially provided nutrients, such as immunonutrients.

Nutritional Considerations After Gastrectomy and Esophagectomy for Malignancy

This article reviews various methods of assessing and managing post-gastrectomy or esophagectomy patients from a nutritional standpoint, by examining recent research focusing on assessment models, components of enteral feeding, timing of feeding, safety of enteral nutrition (EN) vs total parenteral nutrition (TPN), appetite stimulants, alternative treatments, and long-term care. Pre-, peri-, and post-operative nutrition represent a major prognostic indicator in patients undergoing a gastrectomy or esophagectomy for malignant cancer. An accurate initial nutrition assessment to determine risk, followed by close monitoring pre-operatively and early enteral feeding post-operatively, has been shown to have the most beneficial effects. The optimal delivery route for nutrition involves the use of EN with immune enhancing nutrients while avoiding TPN. In practice, TPN is reserved for patients with post-operative complications that delay enteral feeding for an extended time. While megace is commonly used as an appetite stimulant, the hormone ghrelin is another novel, safe, and efficacious treatment to improve appetite, increase by mouth (PO) intake, and minimize loss of weight and lean body mass. Although use of ghrelin is not yet common practice, as more studies are published, we predict that this will become a more common treatment. While complementary and alternative therapies are commonly employed in this patient population, more research needs to be done before incorporation into our mainstay of treatment. Long term, these patients continue to be at nutritional risk and therefore should be followed to optimize weight maintenance and prevent micronutrient deficiencies.

Glutamine as an Immunonutrient

Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.

Potential Antitumor Activity of a Low-Molecular-Weight Protein Fraction from Grifola frondosa Through Enhancement of Cytokine Production

Edible mushrooms contain an abundance of immune-enhancing nutritients. Some of these compounds, referred to as biological response modifiers (BRMs), have been used in biological therapies for cancer treatment. We obtained a low-molecular-weight protein fraction (MLP-Fraction) from the fruiting body of the maitake mushroom Grifola frondosa by multiple sequential steps, including ethanol precipitation, DEAE-exchange chromatography, and gel filtration. The effect of the MLP-Fraction on the immune system was determined using normal mice. This resulted in a simultaneous increase in splenocyte proliferation and production of cytokines such as interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-10, IL-12, and interferon (IFN)-gamma. The expression levels of IFN-gamma and IL-12 in antigen-presenting cells (APCs) and the activation of natural killer (NK) cells, macrophages, and dendritic cells were observed. These results suggest a mechanism in which NK cells are activated through cytokines produced by APCs. We also confirmed the possibility that the MLP-Fraction acts as a BRM using colon-26 carcinoma-bearing mice. This fraction enhanced the production of IL-12 and IFN-gamma by splenocytes in tumor-bearing mice and clearly showed an inhibitory effect on tumor cell growth.

Can immune-enhancing nutrients reduce postoperative complications in patients undergoing esophageal surgery?

Postoperative infection of esophageal neoplasm surgery is the major cause of prolonged postoperative hospitalization, as well as morbidity. The clinical benefits of administering immune-enhancing nutrients (IEN) to critically ill patients and those undergoing elective surgery were clarified. However, the benefits of preoperative administration of IEN for patients with esophageal cancer remain unclear. The present study was designed to clarify the clinical efficacy of administration of IEN prior to esophageal surgery. A total of 123 patients undergoing esophagectomy in single institute were retrospectively investigated. All patients received postoperative enteral nutrition by use of ordinal nutrients. Preoperative IEN were also given to 84 patients (IEN group), while the other 39 received an ordinary diet (control). Postoperative courses and laboratory data were compared between the two groups. The incidences of infectious complications in the IEN and control groups were 18% and 38%, respectively (P < 0.05). Pneumonia developed in 5 (6%) IEN and 7 (18%) control patients (P < 0.05). Postoperative hospitalization was shorter in the IEN group (P < 0.01). Prealbumin levels, retinal binding protein levels and the lymphocyte count were significantly higher in the IEN group on postoperative day 3. These results suggest that preoperative administration of IEN in patients undergoing esophagectomy reduces infectious complications, mainly pneumonia, and shortens postoperative hospitalization.

Sex differences in response to immunonutrition in sepsis

Background Cell-mediated immune response is superior in females compared to males. Whether sex differences influenced mortality in sepsis while on immune-enhancing nutrients was investigated. Materials and Methods Seventy-two non-orchitectomized male and non-oophorectomized female rats ( n = 36/group) were randomized into four groups. Rats were fed either an immune-enhancing diet or control diet for five days. Sepsis was induced with caecal ligation and puncture (CLP). An additional group of orchitectomized and oophorectomized rats ( n = 36/group) were divided into four groups; fed either an immune-enhancing or control diet of one month, then following castration. Sepsis was induced with CLP. The influence of immune-enhancing nutrients on the effect of the rat's sex on mortality rates and serum cytokines were compared. Results Non-orchitectomized male rats had a decreased mortality (88.9% vs. 16.7%) on immune-enhancing diet. Low mortality among non-oophorectomized female rats persisted, on immune-enhancing diet (27.8% vs. 11.1%). Orchitectomized rats demonstrated reduced mortality (88.8% vs. 50%) on immune-enhancing diet. Oophorectomized rats showed a similar trend (55.6% vs. 44.4%). Orchitectomy increased mortality in spite of immune-enhancing diet (50% vs. 16.7%). Oophorectomy increased mortality on immune-enhancing diet (44.4% vs. 11.1%). Circulating IL-1β was higher in non-oophorectomized female rats on control diet compared to immune-enhancing diet. Non-orchitectomized male and non-oophorectomized female rats had similar increases in IL-10 on immune-enhancing diet. Conclusions Mortality rates on immunonutrition were less in male than female rats following sepsis. Orchitectomy did not confer an advantage for septic rats. Sex hormone was more important than immunonutrition in septic female rats.

Enteral Nutrition by Endoscopic Means; I. Techniques, Indications, Types of Enteral Feed

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.

Enteral feeding.

In this review, topics with scientific strength, topical interest, and controversy were selected. Over the past 50 years, malnutrition has become increasingly recognized as a cause of increased morbidity and mortality in hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the most appropriate form of nutritional therapy for hospital patients. Since then, parenteral nutrition has been replaced by enteral nutrition as the best way of delivering nutrients to hospital patients. The timing of enteral nutrition has been debated. Should it be instituted early, within the first 24 hours? In addition, enteral nutrition containing immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for critically ill patients. The relative merits of enteral versus total parenteral nutrition continue to be debated. Questions about possible complications related to enteral nutrition have been raised. Patients are at risk of nosocomial pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition increases intestinal oxygen consumption. Steroids are often used to treat Crohn disease, but because of undesirable side effects, various techniques have been used to reduce steroid dependency. Enteral nutrition has been advocated as a way of reducing steroid dependency. Finally, enteral nutrition is routinely used to feed demented patients and those in a vegetative state. It is not clear whether this practice alters outcome or quality of life.

Enteral feeding

In this review, topics with scientific strength, topical interest, and controversy were selected. Over the past 50 years, malnutrition has become increasingly recognized as a cause of increased morbidity and mortality in hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the most appropriate form of nutritional therapy for hospital patients. Since then, parenteral nutrition has been replaced by enteral nutrition as the best way of delivering nutrients to hospital patients. The timing of enteral nutrition has been debated. Should it be instituted early, within the first 24 hours? In addition, enteral nutrition containing immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for critically ill patients. The relative merits of enteral versus total parenteral nutrition continue to be debated. Questions about possible complications related to enteral nutrition have been raised. Patients are at risk of nosocomial pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition increases intestinal oxygen consumption. Steroids are often used to treat Crohn disease, but because of undesirable side effects, various techniques have been used to reduce steroid dependency. Enteral nutrition has been advocated as a way of reducing steroid dependency. Finally, enteral nutrition is routinely used to feed demented patients and those in a vegetative state. It is not clear whether this practice alters outcome or quality of life.

Immune-modulatory actions of arginine in the critically ill.

Current trials of immune-enhancing diets suggest several beneficial clinical effects. These products are associated with a reduction in infectious risk, ventilator days, ICU and hospital stay. However, methodological weaknesses limit the inferences we can make from these studies. Furthermore, improvements in outcomes were largely seen in surgical patients and in patients who tolerated critical amounts of formula. We propose that the beneficial findings cannot easily be extrapolated to other patient populations since there is suggestion from clinical trials that the sickest patients, especially those with severest appearances of sepsis, shock and organ failure may not benefit or may even be harmed. In these conditions we hypothesize that systemic inflammation might be undesirably intensified by immune-enhancing nutrients like arginine in critically ill patients. In this paper, we review the purported effects of arginine on the immune system and organ function to understand the scientific rationale for its inclusion into enteral feeding products. We conclude that patients with the most severe appearances of the systemic inflammatory response syndrome should not receive immune-enhancing substrates which may aggravate systemic inflammation and worsen clinical outcomes.

Should immunonutrition become routine in critically ill patients? A systematic review of the evidence.

Several nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear. To examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients. The databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review. A total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality. Methodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently. Twenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score. Immunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.

The Best of the Best—1997

For future annual updating of this list, we invite your suggestions addressed to the Editor of the Archives of Surgery at the office listed in the JOURNAL. Articles may originate in any publication. Our hope is that this list will be helpful to you in staying abreast of important practice-related innovations. For 1997 our choices are as follows, in random order: • Turner RR, Ollila DW, Krasne DL, et al. Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg. 1997;226:271-278. The authors evaluated 103 patients with breast cancer by examining their sentinel lymph node and nonsentinel nodes following completion of a level I and II axillary dissection. Patients had a median age of 55 years and had primary tumors of a median size of 1.8 cm (58%, T1; 40%, T2; 2%, T3). Examination of nodes included immunohistochemical staining. Overall, metatastic disease was noted in 42% of patients. Only 1 patient who was sentinel node negative (1.7%) and had undergone routine staining of nodal specimens (hematoxylin-eosin) was actually node positive on examination of all her axillary nodes and when the immunohistochemical processing was used, the probability of nonsentinel node involvement was less than 0.1%. This indeed validates the concept as set forth by the John Wayne Cancer Institute Group. • ten Cate J, for The Columbus Investigators. Low molecular weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med. 1997;337:657-662. The value of low-molecular-weight heparin in the treatment of patients with pulmonary embolism or previous episodes of thromboembolism was studied in more than 1000 patients in a multiinstitutional study. Randomly assigned patients with symptomatic venous thromboembolism were treated with fixed-dose, subcutaneous, low-molecular-weight heparin or adjusted-dose, intravenous, unfractionated heparin. Treatment with oral coumarin was started concomitantly and continued for 12 weeks. The outcome events studied included recurrent venous thromboembolism, major bleeding, and death. Fixed-dose, subcutaneous, lowmolecular-weight heparin proved as effective and safe as adjusted-dose, intravenous, unfractionated heparin in all categories. • Heslin MJ, Latkany L, Lung D, et al. A prospective randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg. 1997; 226:567-580. In an attempt to decrease morbidity, mortality, and length of stay in patients with upper gastrointestinal tract cancer, 195 individuals were randomized to an immune-enhancing feeding formula given via a jejunostomy tube or to intravenous crystalloid following curative resection. The feedings were begun within 24 hours and included supplemental nutrients. Despite receiving considerably more protein, carbohydrate, lipids, and immuneenhancing nutrients, the complication rate, mortality rate, and median length of hosFrom the Department of Surgery, University of California, Davis-East Bay, Oakland. SPECIAL ARTICLE