Bobbi Langkamp-Henken

Glutamine Prevents Parenteral Nutrition-Induced Increases in Intestinal Permeability

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. This study evaluated changes in rat jejunal permeability and histology after total parenteral nutrition (TPN) or TPN supplemented with glutamine. Lactulose and mannitol were used to measure jejunal permeability, and fixed stained histologic specimens were used to measure mucosal dimensions. After the insertion of central venous catheters, 18 male rats were randomly divided into three groups: CHOW, saline infusion with a standard laboratory rat diet ad libitum; TPN; and GLN, 2% L-glutamine-supplemented TPN. The TPN and GLN groups received isocaloric, isovolumic, and isonitrogenous feedings. After 7 days of infusion, a laparotomy was performed, and lactulose and mannitol were instilled into the lumen of a 25-cm ligated segment of jejunum. Urine was collected for 5 hours and assayed for lactulose, mannitol, and creatinine. The jejunum was harvested, and wet weight, villus height, mucosal thickness, and villus width were measured. Intestinal permeability to lactulose and the lactulose to mannitol ratio significantly increased after TPN compared with CHOW, and these effects were prevented with the addition of glutamine to the TPN solution. Jejunal villus height and mucosal thickness significantly decreased following TPN but were not significantly different from CHOW when glutamine was added to the TPN solution. These data suggest that TPN was associated with increased jejunal permeability and that glutamine, when added to the TPN solution, prevented this effect. In addition, glutamine reduced TPN-associated atrophy of the jejunum.

Arginine and immunity: a unique perspective

Arginine functions in the body as a free amino acid, a component of most proteins, and the substrate for several non-protein, nitrogen-containing compounds, many of which function in immunity. Although arginine is synthesized in the body, it is not made in sufficient quantities to support growth or meet metabolic requirements during periods of stress. Based on the biochemical and physiological role of arginine in maintaining health and immunity, arginine is being added at pharmacologic concentrations to enteral formulas to boost immune function. Unfortunately, animal and human studies that investigate enteral arginine supplementation as the single variable do not show clear immunologic benefit. The inconsistent effects of arginine supplementation on immune function are due to numerous factors, such as the amount and timing of arginine supplementation, the animal species or strain of species, and the experimental model. Systematic study is required to determine whether a basal dietary intake of arginine is required to maintain immune function during health and how much arginine is required to meet metabolic requirements during periods of growth or stress.

Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis

Implementation of zinc interventions for subjects suspected of being zinc-deficient is a global need, but is limited due to the absence of reliable biomarkers. To discover molecular signatures of human zinc deficiency, a combination of transcriptome, cytokine, and microRNA analyses was applied to a dietary zinc depletion/repletion protocol with young male human subjects. Concomitant with a decrease in serum zinc concentration, changes in buccal and blood gene transcripts related to zinc homeostasis occurred with zinc depletion. Microarray analyses of whole blood RNA revealed zinc-responsive genes, particularly, those associated with cell cycle regulation and immunity. Responses of potential signature genes of dietary zinc depletion were further assessed by quantitative real-time PCR. The diagnostic properties of specific serum microRNAs for dietary zinc deficiency were identified by acute responses to zinc depletion, which were reversible by subsequent zinc repletion. Depression of immune-stimulated TNFα secretion by blood cells was observed after low zinc consumption and may serve as a functional biomarker. Our findings introduce numerous novel candidate biomarkers for dietary zinc status assessment using a variety of contemporary technologies and which identify changes that occur prior to or with greater sensitivity than the serum zinc concentration which represents the current zinc status assessment marker. In addition, the results of gene network analysis reveal potential clinical outcomes attributable to suboptimal zinc intake including immune function defects and predisposition to cancer. These demonstrate through a controlled depletion/repletion dietary protocol that the illusive zinc biomarker(s) can be identified and applied to assessment and intervention strategies.

Invited Review: Immunologic Structure and Function of the Gastrointestinal Tract

Host defenses within the gastrointestinal tract exclude bacteria and other intraluminal substances, which if released into the systemic circulation, would be toxic to the body. This is accomplished via complex interactions between these external pathogens and local immune responses and nonimmunologic processes. In addition to the mechanical and chemical barriers of the nonimmunologic defense system within the gastrointestinal tract, there is an effective immunologic barrier composed of aggregated and nonaggregated lymphoid cells. Gut-associated lymphoid tissue protects the intestinal mucosa from invading pathogens by intricate pathways of antigen processing. Gut-associated lymphoid tissue also transfers protection to other secretory sites within the body through the common mucosal immune system. The integrity of both the immunologic and nonimmunologic barriers may be affected by any number of pathologic insults as well as by nutritional influences. This article reviews the structural and functional characteristics of this complex and critically important host defense system. Specific nutrient requirements of the immunologic processes are discussed.

Comparing nutrient intake from food to the estimated average requirements shows middle- to upper-income pregnant women lack iron and possibly magnesium

OBJECTIVE To determine whether nutrient intake from food alone was adequate across trimesters for middle- to upper-income pregnant women when compared with estimated average requirements (EAR), and to determine whether food intake exceeded the tolerable upper intake level (UL) for any nutrient. DESIGN Observational study in which pregnant women completed 3-day diet records each month during their pregnancy. Records were analyzed for nutrient content, and usual intake distributions were determined. SUBJECTS/SETTING Subjects were low-risk women in their first trimester of pregnancy (living in middle- to upper-income households). Ninety-four women were recruited, and sixty-three participated. STATISTICAL ANALYSIS PERFORMED Nutrient intake data were adjusted to achieve normality by using a power transformation. A mixed model method was used to assess trends in intake over time, and to estimate mean intake and within-subjects and between-subjects variance. The usual intake distribution for each nutrient was determined and compared with the EAR and UL. RESULTS The probabilities of usual nutrient intake from food being less than the EAR were highest for iron (.91), magnesium (.53), zinc (.31), vitamin B6 (.21), selenium (.20), and vitamin C (.12). Women were not at risk of exceeding the UL from food intake for any nutrient studied. APPLICATIONS/CONCLUSIONS Study participants did not consume adequate amounts of iron from food to meet the needs of pregnancy, and therefore iron supplementation is warranted in this population. Intake of magnesium was suboptimal using the EAR as a cut-point for adequacy.

Arginine Supplementation Is Well Tolerated but Does Not Enhance Mitogen-Induced Lymphocyte Proliferation in Elderly Nursing Home Residents with Pressure Ulcers

BACKGROUND Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. METHODS Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. RESULTS Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. CONCLUSIONS Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.

Nutritional Formula Enhanced Immune Function and Reduced Days of Symptoms of Upper Respiratory Tract Infection in Seniors

Objectives: To assess whether an experimental nutritional formula, given as a supplement, would reduce days of symptoms of upper respiratory tract infection (URTI) and affect antibody and lymphocyte proliferative responses to influenza vaccine.

Nutritional formula improved immune profiles of seniors living in nursing homes

OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long‐term care facilities.

Immune Function Is Impaired With a Mini Nutritional Assessment Score Indicative of Malnutrition in Nursing Home Elders With Pressure Ulcers

BACKGROUND Malnutrition is prevalent in elders with pressure ulcers and is associated with increased morbidity and mortality. This study compared nutritional status, assessed by the Mini Nutrition Assessment (MNA), to immune function in nursing home elders with pressure ulcers. METHODS Nutritional status was assessed in nursing home residents (>65 years) with a stage II or more severe pressure ulcer. Subjects were classified as well nourished, at risk of malnutrition, or malnourished according to MNA score. Blood was drawn to assess whole blood mitogen-induced lymphocyte proliferation and neutrophil respiratory burst. Delayed-type hypersensitivity to 3 antigens was measured. MNA status was compared with immune parameters using the Kruskall-Wallis test. RESULTS Of the 24 subjects (23 men, 1 woman) who completed the study protocol, only 4 (17%) were classified as well nourished, whereas 7 (29%) were at risk and 13 (54%) were malnourished according to MNA score. Whole blood lymphocyte proliferation was significantly lower in the malnourished vs at risk subjects with both pokeweed (median [25th, 75th percentile], 0.6 [0.3, 0.9] vs 1.8 [1.2, 2.1] disintegrations per minute [dpm]/cell, p < .05); and concanavalin A (1.7 [0.9, 2.0] vs 2.8 [2.6, 3.9] dpm/cell, p < .05) mitogens. Neutrophil respiratory burst normalized to a young control was significantly lower in malnourished subjects vs well-nourished subjects (0.8 [0.5, 0.9] vs 1.4 [1.0, 1.7], p < .05). Total induration to 3 skin-test antigens was 13.4 +/- 4.6, 3.5 +/- 2.6, and 3.8 +/- 1.8 (mean +/- SEM) for well-nourished, at risk, and malnourished, respectively (p = .059). CONCLUSIONS Immune function is impaired with an MNA score indicative of malnutrition in nursing home elders with pressure ulcers.

Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students

BACKGROUND Acute psychological stress induced by academic exams is associated with dysregulated gastrointestinal and immune function. OBJECTIVE We examined whether supplementation with galactooligosaccharides reduced gastrointestinal dysfunction and the percentage of days with cold or flu in academically stressed undergraduate students. DESIGN In a randomized, double-blind study, subjects (n = 427) received 0, 2.5, or 5.0 g galactooligosaccharides for 8 wk around the time of fall final exams. Levels of stress and cold or flu symptom intensity (SI; 0 = not experiencing to 3 = severe) were recorded daily. The SI from 9 cold or flu symptoms was summed with 1 d of cold or flu defined as a sum >6. The Gastrointestinal Symptom Response Scale was completed weekly. RESULTS Stress was positively related to diarrhea, indigestion, and reflux syndromes and with abdominal pain, average daily cold or flu SI score, and the percentage of days with cold or flu. Gastrointestinal symptom scores for diarrhea (P = 0.0298), constipation (P = 0.0342), abdominal pain (P = 0.0058), and indigestion (P = 0.0003) syndromes were lower after galactooligosaccharide supplementation. The cold or flu SI score was affected by galactooligosaccharides and stress (P < 0.0001); 2.5 g was associated with a lower SI score across all levels of stress, but 5.0 g was protective only at lower levels of stress. The percentage of days with cold or flu was associated with galactooligosaccharides within different body mass index categories (P = 0.0002), wherein a 40% reduction in the percentage of days with cold or flu was observed in normal-weight individuals with 5.0 g galactooligosaccharides. This effect was not observed in overweight or obese individuals. CONCLUSIONS Acute psychological stress was directly related to symptoms of gastrointestinal dysfunction and cold or flu. Galactooligosaccharide supplementation reduced these symptoms and the number of days with cold or flu. This trial was registered at clinicaltrials.gov as NCT01137760.