The effect of an acute aspirin challenge on intestinal permeability in healthy adults with and without prophylactic probiotic consumption: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: Healthy individuals may experience increases in intestinal permeability after chronic or acute use of non-steroidal anti-inflammatory drugs, which may be attenuated by probiotics. This study investigates the effects of an acute aspirin challenge on gastroduodenal barrier function with or without prophylactic probiotic consumption. METHODS: Twenty-nine generally healthy participants (26 ± 6 years) completed a 14-week randomized, double-blind, crossover trial. A probiotic containing 2 Lactobacilli strains or placebo was administered for 3 weeks, with a 4-week washout period between crossover phases. Daily and weekly questionnaires assessing gastrointestinal function were completed for 2 weeks before until 2 weeks after each intervention to assess gastrointestinal function. Gastroduodenal permeability was assessed by urinary excretion of orally administered sucrose after 1, 2, and 3 weeks of each intervention with a 1950 mg-aspirin challenge after 2 weeks of supplementation. Stool samples were collected weekly during supplementation for detection of species of interest. RESULTS: Gastroduodenal permeability increased with aspirin challenge (Week 1: 3.4 ± 0.6 µmol vs Week 2: 9.9 ± 1.0 µmol urinary sucrose; p < 0.05). There were no differences in the change in permeability after the aspirin challenge or gastrointestinal function between interventions. CONCLUSION: The acute aspirin challenge significantly increased intestinal permeability similarly in both groups, and prophylactic probiotic consumption was unable to prevent the loss in this particular model.

Validation of a novel quality of life questionnaire: the Digestion-associated Quality of Life Questionnaire (DQLQ).

BACKGROUND: Few health-related quality of life (QOL) questionnaires are designed specifically for healthy populations and are specific to gastrointestinal (GI) symptoms even though healthy individuals may frequently experience gas, bloating, constipation, diarrhea, and abdominal pain. The purpose of this study was to develop and validate a tool that could assess the impact of GI symptoms on digestion-associated QOL in otherwise healthy individuals. METHODS: After a review of current literature and with input from experienced GI researchers, a 24-item questionnaire was created. The questionnaire was reduced to 9 items with input from focus groups comprised of healthy adults experiencing GI-related symptoms and through variability analysis. The Digestion-associated QOL Questionnaire (DQLQ) was designed to be sensitive to the physical and mental well-being changes that may occur due to GI symptoms. The DQLQ was assessed for internal consistency reliability (Cronbach's alpha; McDonald's omega), test-retest reliability (intraclass correlation coefficient, ICC), and construct validity (Pearson correlations) in a study with healthy, academically stressed, undergraduate students. Convergent validity was evaluated by correlating the DQLQ with gastrointestinal symptom rating scale (GSRS) scores. Divergent validity was assessed by correlating DQLQ scores with stress scores, and bowel satisfaction scores. RESULTS: A total of 594 students (age 18-30 years) completed the DQLQ. Internal consistency reliability was favorable (n = 594; α = 0.84, ω = 0.84). A high level of agreement and correlation between DQLQ scores was found with the test-retest reliability analysis (n = 273; ICC = 0.89). The questionnaire was shown to have good convergent validity through correlation with the GSRS (n = 594; r = 0.54). Divergent validity was also shown to be appropriate by correlating DQLQ scores with stress (n = 592; r = 0.13, p < 0.005), and bowel satisfaction (n = 592; r = 0.18, p < 0.001) scores. CONCLUSION: The DQLQ is a reliable and valid questionnaire for assessing digestion-associated QOL in healthy individuals.

Effect of a Mediterranean diet intervention on gastrointestinal function in Parkinson's disease (the MEDI-PD study): study protocol for a randomised controlled trial.

INTRODUCTION: Constipation is a common and sometimes debilitating non-motor symptom of Parkinson's disease (PD) that can result in intestinal inflammation and microbial dysbiosis. The Mediterranean diet, rich in fermentable fibres and anti-inflammatory phenolic compounds, is associated with reduced risk of developing PD and slower progression of parkinsonism. The Mediterranean diet is often recommended for people with PD; however, no studies to date examine this diet as a therapeutic intervention to modulate gastrointestinal (GI) dysfunction. METHODS AND ANALYSIS: This is a randomised, controlled, parallel study. During a 2-week run-in, participants with PD and constipation symptoms (n=52) will undergo baseline nutritional and neurological assessments and provide a stool sample. Participants will be stratified by sex and Hoehn and Yahr stage and randomised to follow standard of care for constipation (control) or standard of care plus a Mediterranean diet (intervention) for 8 weeks. A study dietitian will provide dietary instruction and weekly follow-up via telephone to both groups to support adherence and monitor adverse events. Questionnaires will assess dietary intake and GI function including stool frequency, form, symptoms and laxative usage. Measurements completed at baseline will be repeated at 4 and 8 weeks of the intervention. The primary outcome is to evaluate the difference between mean change (final-baseline) in Gastrointestinal Symptom Rating Scale (GSRS) constipation syndrome scores for the control versus intervention groups. Secondary outcomes will assess stool frequency and form, weekly GSRS syndrome scores, digestive quality of life, laxative usage, faecal microbial communities and inflammatory markers, anxiety, depression, quality life, body weight and composition, dietary fibre intake and Mediterranean diet adherence. ETHICS AND DISSEMINATION: The study has received University of Florida Institutional Review Board-01 approval (IRB202001333). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04683900.

Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study.

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities. Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples. Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention. Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03851861.

In healthy adults, resistant maltodextrin produces a greater change in fecal bifidobacteria counts and increases stool wet weight: a double-blind, randomized, controlled crossover study.

Dietary fiber stimulates the growth of potentially beneficial bacteria (eg, bifidobacteria), yet most Americans do not meet daily fiber recommendations. Resistant maltodextrin (RMD), a fermentable functional fiber, may help individuals meet total fiber recommendations and potentially increase bifidobacteria. It was hypothesized that fecal bifidobacteria counts/ng fecal DNA would increase after adding 25 g RMD to inadequate fiber diets of healthy adults. In this double-blind, controlled crossover study, 51 participants (26.3 ± 6.8 years, mean ± SD) were randomized to consume 0, 15, and 25 g RMD daily for 3 weeks followed by a 2-week washout. Participants collected all stools for 2 days at weeks 0 and 3 of each intervention for stool wet weight (WW) measurements and fecal bifidobacteria counts. Weekly 24-hour dietary recalls assessed total fiber intake. Only 25 g RMD resulted in a change (final minus baseline) in bifidobacteria that was significant compared with 0 g (0.17 ± 0.09 vs -0.17 ± 0.09 log10[counts], respectively, mean ± SEM, P = .008). Stool WW increased only with 25 g (150 ± 11 vs baseline 121±11 g/d; P = .011). Mean daily total fiber intake (including RMD) was significantly higher (both P< .001) with 15 g (17.8 ± 0.6 g/1000 kcal or 4184 kJ) and 25 g (25.3 ± 1.1 g/1000 kcal) compared with 0 g RMD (8.4±0.4 g/1000 kcal). Mean daily total fiber intakes exceeded recommendations (14 g/1000 kcal) with 15 and 25 g of RMD, and 25 g RMD increased fecal bifidobacteria counts and stool WW, suggesting health benefits from increasing total fiber intake.

Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial.

Background: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2 compared with placebo would result in beneficial effects on MRQLQ scores throughout allergy season in individuals who typically experience seasonal allergies. Secondary outcomes included changes in immune markers as part of a potential mechanism for changes in MRQLQ scores.Design: In this double-blind, placebo-controlled, parallel, randomized clinical trial, 173 participants (mean ± SEM: age 27 ± 1 y) who self-identified as having seasonal allergies received either a probiotic (2 capsules/d, 1.5 billion colony-forming units/capsule) or placebo during spring allergy season for 8 wk. MRQLQ scores were collected weekly throughout the study. Fasting blood samples were taken from a subgroup (placebo, n = 37; probiotic, n = 35) at baseline and week 6 (predicted peak of pollen) to determine serum immunoglobulin (Ig) E concentrations and Treg percentages.Results: The probiotic group reported an improvement in the MRQLQ global score from baseline to pollen peak (-0.68 ± 0.13) when compared with the placebo group (-0.19 ± 0.14; P = 0.0092). Both serum total IgE and the percentage of Tregs increased from baseline to week 6, but changes were not different between groups.Conclusions: This combination probiotic improved rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies; however, the associated mechanism is still unclear. This trial was registered at clinicaltrials.gov as NCT02349711.

Diet quality improves for parents and children when almonds are incorporated into their daily diet: a randomized, crossover study.

The health benefits of nuts may, in part, be due to the fiber that provides substrate for the maintenance of a healthy and diverse microbiota. We hypothesized that consuming almonds would benefit immune status through improving diet quality and modulation of microbiota composition in parents and their children, while improving gastrointestinal function. In a crossover trial, 29 parents (35 ± 0.6 years) and their children (n = 29; 4 ± 0.2 years; pairs) consumed 1.5 and 0.5 oz, respectively, of almonds and/or almond butter or control (no almonds) for 3 weeks followed by 4-week washouts. Parents completed daily questionnaires of stool frequency and compliance with nut intake. The Gastrointestinal Symptom Response Scale was administered weekly. Participants provided stools for microbiota analysis and saliva for secretory immunoglobulin A. Serum antioxidant/proinflammatory balance was determined in parents. From weekly dietary recalls (Automated Self-Administered 24-Hour Dietary Recall), nutrient and energy intake were assessed and Healthy Eating Index-2010 scores were calculated. Consuming almonds increased total Healthy Eating Index score from 53.7 ± 1.8 to 61.4 ± 1.4 (parents) and 53.7 ± 2.6 to 61.4 ± 2.2 (children; P < .001). Minimal changes in gastrointestinal symptoms and no change in stool frequency were noted with the almond intervention. Microbiota was stable at the phylum and family level, but genus-level changes occurred with nut intake, especially in children. No differences were observed for immune markers. Although higher intakes of almonds or longer interventions may be needed to demonstrate effects on immune status, a moderate intake of almonds improves diet quality in adults and their young children and modulates microbiota composition.

Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

OBJECTIVE: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community. METHODS: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing. RESULTS: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo. CONCLUSIONS: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults.

BACKGROUND: Mushrooms are widely cited for their medicinal qualities, yet very few human intervention studies have been done using contemporary guidelines. OBJECTIVE: The aim of this study was to determine whether consumption of whole, dried Lentinula edodes (shiitake) mushrooms could improve human immune function. Primary objectives were to ascertain whether L. edodes consumption would improve γδ-T cell proliferation and activation responses, quantify a dose response, and elicit cytokine secretion patterns. Secondary objectives included determining changes in natural killer T (NK-T) cell proliferation and activation, secretory immunoglobulin A (sIgA) in saliva, and C-reactive protein (CRP) in serum. DESIGN: Fifty-two healthy males and females, aged 21-41 years, participated in a 4-week parallel group study, consuming either 5 or 10 g of mushrooms daily. Each subject had blood drawn before and after 4 weeks of daily L. edodes consumption. Saliva and serum were also collected. Peripheral blood mononuclear cells were cultured in autologous serum for 24 hours or 6 days, stained, and examined by flow cytometry. RESULTS: Eating L. edodes for 4 weeks resulted in increased ex vivo proliferation of γδ-T (60% more, p < 0.0001) and NK-T (2-fold more, p < 0.0001) cells. Both cell types also demonstrated a greater ability to express activation receptors, suggesting that consuming mushrooms improved cell effector function. The increase in sIgA implied improved gut immunity. The reduction in CRP suggested lower inflammation. The pattern of cytokines secreted before and after mushroom consumption was significantly different; consumption resulted in increased interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and IL-1α levels, a decreased macrophage inflammatory protein-1α/chemokine C-C ligand 3 (MIP-1α/CCL3) level, and no change to IL-6, IL-1ß, MIP-1ß, IL-17 and interferon (IFN)-γ levels. CONCLUSIONS: Regular L. edodes consumption resulted in improved immunity, as seen by improved cell proliferation and activation and increased sIgA production. The changes observed in cytokine and serum CRP levels suggest that these improvements occurred under conditions that were less inflammatory than those that existed before consumption.

Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and a lower percentage of academically stressed students reporting a day of cold/flu: a randomised, double-blind, placebo-controlled study.

Acute psychological stress is positively associated with a cold/flu. The present randomised, double-blind, placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students (n 581) who received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu. B. bifidum resulted in a greater proportion of healthy days than placebo (P≤ 0·05). The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo (P< 0·05). There were no effects of B. infantis or L. helveticus compared with placebo on either outcome. A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes. The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep. Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.

Fecal lactic acid bacteria increased in adolescents randomized to whole-grain but not refined-grain foods, whereas inflammatory cytokine production decreased equally with both interventions.

The intake of whole-grain (WG) foods by adolescents is reported to be approximately one-third the recommended intake of 48 g/d. This 6-wk randomized interventional study determined the effect of replacing grains within the diet with refined-grain (RG; n = 42) or WG (n = 41) foods/d on gastrointestinal and immune health in adolescents (aged 12.7 ± 0.1 y). A variety of grain-based foods were delivered weekly to participants and their families. Participants were encouraged to eat 3 different kinds of study foods (e.g., bread, cereals, snacks)/d with goals of 0 g/d (RG) and 80 g/d (WG). Stool samples were obtained during the prebaseline and final weeks to measure bifidobacteria and lactic acid bacteria (LAB) using qPCR. Stool frequency was recorded daily. Blood was drawn at baseline and at final visits for immune markers. Across groups, total-grain intake increased by one serving. The intake of WG was similar at baseline (18 ± 3 g) between groups but increased to 60 ± 5 g in the WG group and decreased to 4 ± 1 g in the RG group. Fecal bifidobacteria increased from baseline with both interventions, but LAB increased (P < 0.05) from baseline [2.4 ± 0.2 log(10) genome equivalents (eq)] to wk 6 (3.0 ± 0.2 log(10) genome eq) in the WG group but not in the RG group (baseline: 2.9 ± 0.2 log(10) genome eq; wk 6: 3.0 ± 0.1 log(10) genome eq). There was no difference in stool frequency, serum antioxidant potential, or in vitro LPS-stimulated mononuclear cell production of inflammatory cytokines between groups. However, across both groups the number of daily stools tended to increase (P = 0.08) by 0.0034 stools/g WG or by 0.2 stools with 60 g WG, mean antioxidant potential increased by 58%, and mean production of TNF-α, IL-1ß, and IL-6 decreased by 24, 22, and 42%, respectively, between baseline and wk 6. Overall, incorporating either WG or RG foods increased serum antioxidant concentrations and decreased inflammatory cytokine production; however, WG study foods had more of an effect on aspects of gastrointestinal health.

Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.

OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.

Regular consumption of concord grape juice benefits human immunity.

γδ T cells are important immune surveillance cells residing in epithelial layers lining the intestine, lung, and reproductive tract. The main objective of this study was to test the hypothesis that consumption of dietary compounds from grapes would modify γδ T-cell function. Other factors related to immune function after grape juice consumption were also tested. A randomized, double-blind, placebo-controlled, parallel intervention was conducted: 100% grape juice made from Concord grapes or a placebo beverage was consumed by 85 individuals daily for 9 weeks. Subjects were asked not to consume other red, blue, and purple fruits during the study. Blood samples, taken at the beginning and the end, were analyzed for γδ T-cell numbers and proliferation, vitamin C, antioxidant capacity, and the ability to protect DNA from strand breaks. Those consuming the grape juice had significantly greater numbers of circulating γδ T cells and higher serum vitamin C levels compared to the placebo by two-way repeated-measure analysis of variance (P < .05). Individuals consuming the placebo had lower serum antioxidant activity, less γδ T-cell proliferation, and increased DNA strand breaks when challenged with H(2)O(2). Analysis of the data by structural equation modeling confirmed that 61% of the variance in biological functions at 9 weeks was due to grape juice consumption. Based on conventional statistical analyses, as well as on sophisticated modeling techniques, regular consumption of purple grape juice in the absence of other red, blue, or purple fruits benefited immunity in healthy, middle-aged human subjects.

Pharmacologic levels of dietary arginine in CB6F1 mice increase serum ammonia in the healthy state and serum nitrite in endotoxemia.

BACKGROUND: Therapeutic or pharmacologic doses of arginine are used to enhance blood flow and immune function despite the lack of dose-response studies and the potential for adverse effects. This study determined the optimal level of oral arginine supplementation required to elevate serum arginine concentrations yet limit adverse effects in healthy and endotoxemic mice. METHODS: Male CB6F1 mice were fed one of the following diets: The standard AIN93G (3 g arginine/100 g of protein) or this diet modified to provide 10 g, 20 g, or 30 g arginine/100 g of protein. On day 14, mice were injected with lipopolysaccharide (endotoxemic) or saline (healthy) and 4 hours later were exsanguinated. RESULTS: Weight gain was reduced 50% in the group fed the 30 g arginine vs standard diet. Serum arginine, ornithine, citrulline, histidine, lysine, serine, threonine, tyrosine, and phenylalanine were greater and glutamate levels were lower in healthy supplemented mice; lipopolysaccharide treatment negated these changes. Serum ammonia concentration was 52% greater in healthy mice fed the 30 g arginine vs standard diet. Serum nitrite and urea were unaffected by supplementation in healthy mice. Serum nitrite was 37% greater in endotoxemic mice fed 30 g vs 10 g arginine, and serum urea was 27% greater in mice fed 20 g or 30 g vs 10 g arginine. CONCLUSIONS: Changes in serum arginine or its metabolites were observed with all of the modified diets; however, a 30-g arginine diet was associated with an initial impairment of growth and potential adverse effects.

Immunity and antioxidant capacity in humans is enhanced by consumption of a dried, encapsulated fruit and vegetable juice concentrate.

The daily consumption of fruits and vegetables is a common dietary recommendation to support good health. We hypothesized that a commercially available encapsulated fruit and vegetable juice powder concentrate (FVJC) could support functional indices of health due to increased intake of various phytonutrients. This was a double-blind, randomized, placebo-controlled investigation of 59 healthy law students who consumed either FVJC or placebo capsules for 77 d. Blood was collected on d 1, 35, and 77 to examine the number of circulating alphabeta- and gammadelta-T cells, cytokine production, lymphocyte DNA damage, antioxidant status, and levels of carotenoids and vitamin C. A log of illnesses and symptoms was also kept. The FVJC group tended to have fewer total symptoms than the placebo group (P < 0.076). By d 77 there was a 30% increase in circulating gammadelta-T cells and a 40% reduction in DNA damage in lymphocytes in the FVJC group relative to the placebo group. Plasma levels of vitamin C and of beta-carotene, lycopene, and lutein increased significantly from baseline in the FVJC group as did plasma oxygen radical absorptive capacity (50%). Interferon-gamma produced by phorbol-stimulated lymphocytes was reduced 70% in the FVJC group, whereas other cytokines (IL-4, IL-6, transforming growth factor beta) were unchanged relative to treatment or time. FVJC consumption during this study period resulted in increased plasma nutrients and antioxidant capacity, reduction in DNA strand breaks, and an increase in circulating gammadelta-T cells.

Arginine supplementation enhances mitogen-induced splenocyte proliferation but does not affect in vivo indicators of antigen-specific immunity in mice.

Arginine is a conditionally essential amino acid with many physiologic roles. Its role in immune function has been one of major focus with conflicting results. Early in vitro immune studies demonstrated increased mitogen-induced lymphocyte proliferation with dietary arginine supplementation; however, not all studies confirmed this effect. Even less is known about the effect of arginine supplementation on in vivo immune responses. To test whether arginine supplementation enhances in vivo indicators of immune function, young female BALB/c mice were fed either the AIN-93G rodent diet (6.4 g arginine/kg diet) or the same diet with 20 g total arginine/kg diet for 15 d before delayed-type hypersensitivity (DTH) testing with 2,4-dinitrofluorobenzene (n = 16-18/diet group). The same mice were challenged with influenza virus A/Port Chalmers/1/73 (H3N2) 15 d later. Mice were killed 3, 6, or 31 d postinfluenza challenge (5-6/diet group on each day). Mitogen-induced splenocyte proliferation, body weight, anti-influenza serum antibody, lung viral titers, and serum arginine were measured. DTH did not differ between diet groups. On d 6 and 31 postchallenge, mitogen-induced proliferation of splenocytes from mice fed the arginine diet was >1.5-fold that of mice fed the control diet (P < 0.05). Body weight and influenza lung viral and serum antibody titers did not differ between diet groups. These data suggest that despite significant enhancement of in vitro mitogen-induced splenocyte proliferation, arginine supplementation does not have a biologically significant effect on antigen-specific in vivo indicators of immune function in this model.

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.

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.