Consensus Statement Immunonutrition and Exercise.

In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research.

Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

Somatosensory perception of running shoe mass.

Running shoes are often marketed based on mass. A total of 50 young adult males participated across two separate experiments to determine how well they could perceive the relative masses of five different running shoes using hands versus feet. For the foot portion, subjects were blindly fitted with the shoes and asked to rank their masses individually using visual analogue scales (VAS) and verbal rankings. For the hand portion, two different methods were used, one presenting all shoes simultaneously and the other presenting the shoes individually. Verbal accuracy and VAS scores correlated across subjects for the hand and foot, but accuracy in mass perception by the feet was 30% compared to 92% or 63% by the hand (depending on the method). These results indicate the foot perceives mass poorly compared to the hand, and that consumers' perception of shoe mass may come more from handling shoes versus wearing them.

Video laboratories for the teaching and learning of professional ethics in exercise physiology curricula.

Student researchers in physiology courses often interact with human subjects in classroom research but may be unfamiliar with the professional ethics of experimenter-subject interactions. This communication describes experiences related to an interactive video used in exercise science and general biology courses to help students become aware of, sensitive to, and comfortable with implementing professional ethics into their own thinking and behavior as researchers before entering the laboratory. The activity consisted of a filmed exercise physiology experiment complemented with interactive question sheets followed by small- and large-group discussion and culminating with individual student reflections. Student written responses from multiple courses indicated that students were able to 1) identify and consider the ethics of experimenter-subject interactions from the movie, 2) generalize broader ideas of professional ethics from those observations, and 3) consider their observations in terms of future experiments they would be conducting personally and how they should interact with human subjects. A majority of students indicated a positive reaction to the video and identified specific aspects they appreciated. It is hoped that this report will encourage other instructors to consider the use of interactive videos in the teaching and learning of professional ethics related to their courses.

Effects of Echinacea extracts on macrophage antiviral activities.

Type I interferons are a class of cytokines synthesized by leukocytes such as macrophages that limit viral replication. We hypothesized that one mechanism whereby Echinacea spp. extracts may enhance immunity is through modulating interferon-associated macrophage pathways. We used herpes simplex viral infection in the murine macrophage cell line RAW264.7 and monitored virus-induced cell death, interferon secretion, and two intracellular proteins that indicate activation of interferon pathways. Cells were incubated with control media or extracts from four different species (E. angustifolia, E. purpurea, E. tennesseensis, E. pallida). Cells incubated with extracts prior to infection showed very modest enhancement of viability, and no increase in the secretion of interferons alpha or beta as compared to control cells. Virus-infected macrophages treated with extracts from E. purpurea showed a small (<2-fold) induction of guanylate binding protein (GBP) production, but no effect of extracts from other species was observed. In virus-infected cells, all the extracts increased the amount of inducible nitric oxide synthase (iNOS) protein, and this effect varied by type of extraction preparation. Together, these results suggest that any potential antiviral activities of Echinacea spp. extracts are likely not mediated through large inductions of Type I interferon, but may involve iNOS.

Somatosensory Perception of Running Shoe Mass may be influenced by Extended Wearing Time or Inclusion of a Personal Reference Shoe, Depending on Testing Method.

Consumers may purchase running shoes on the basis of their masses, yet little is known about shoe mass perceptual abilities. In this multi-part experiment, four groups of twenty-five young adult males (total n = 100) were challenged to gauge the relative masses of five unfamiliar running shoes. The four groups differed by the length of time they were given to wear the shoes (up to 1 minute versus 5 minutes) and whether or not they were able to use their own personal running shoes as a reference. After wearing each individual pair of shoes, participants provided perceived comfort and heaviness rankings using visual analogue scales (VAS). After wearing all five pairs of unfamiliar shoes, participants gave a verbal ranking of relative shoe mass. Participants also hefted the shoes with their hands and positioned them in order of relative mass. Extended wearing time improved overall verbal ranking accuracy, but did not improve mass perception accuracy as determined by comparing VAS heaviness rankings to actual shoe masses. Conversely, use of a personal reference shoe improved mass perception accuracy as determined by comparing VAS heaviness rankings to actual shoe masses, but did not improve overall verbal ranking accuracy. Hand perceptual scores were similar across the four groups, likely due to a ceiling effect. VAS comfort scores were unrelated to shoe masses. The results suggest that wearing time and reference shoes may influence mass perception by the lower limb in a context-specific manner.

Human blood mononuclear cell in vitro cytokine response before and after two different strenuous exercise bouts in the presence of bloodroot and Echinacea extracts.

The purpose of this multidisciplinary investigation was to characterize cytokine production by human blood mononuclear cells after 2 contrasting exercise bouts (a maximal graded oxygen consumption [VO(2)max] test and 90 min of cycling at 85% of ventilatory threshold [VT]) when stimulated in vitro with extracts from bloodroot (Sanguinaria canadensis), coneflower (Echinacea tennesseensis), or solvent vehicle controls. Blood was sampled pre- and post-exercise. Production of TNF, IL-1beta, and IL-10 were measured at 24, 48, and 72 h, respectively. In the VO(2)max test there was a main effect of exercise such that exercise increased cytokine synthesis and a main effect of stimulant such that bloodroot extracts significantly increased cytokine production compared to other stimulants or controls. In the 90-min bout, there was a main effect of exercise for TNF and IL-1beta (but not IL-10) such that exercise decreased cytokine synthesis and a main effect of stimulant such that bloodroot extracts significantly increased cytokine production compared to other stimulants or controls, with exercisexstimulant interactions for both IL-1beta and IL-10. A similar though weaker effect was seen with Echinacea extracts; subsequent biochemical analyses suggested this was related to alkamide decay during 3 years undisturbed storage at ultralow (-80 degrees C) temperature. In this study, the VO(2)max test was associated with enhanced cytokine production whereas the 90-min cycling at 85% VT was associated with suppressed cytokine production. Bloodroot extracts were able to increase cytokine production in both contexts. Herbal extracts purported to offset exercise-associated effects on immune activity warrant continued investigation.

Echinacea tennesseensis ethanol tinctures harbor cytokine- and proliferation-enhancing capacities.

BACKGROUND: Members of the genus Echinacea are used medicinally to treat upper respiratory infections such as colds and influenza. The aim of the present investigation was to characterize the phytomedicinal properties of the American federally endangered species Echinacea tennesseensis. METHODS: Fifty-percent ethanol tinctures were prepared from roots, stems, leaves, and flowers and tested separately for their ability to influence production of IL-1beta, IL-2, IL-10, and TNF-alpha as well as proliferation by young human adult peripheral blood mononuclear cells (PMBC) in vitro. Tincture aliquots were stored at three different temperatures (4, -20, and -80 degrees C) for 21h before testing. At 1-month post-extraction, tinctures stored at -20 degrees C were tested again for cytokine modulation. Phytochemical analyses were performed using HPLC. RESULTS: Fresh root, leaf, and flower tinctures stimulated PBMC proliferation. Fresh root tinctures alone stimulated IL-1beta, IL-10, and TNF-alpha production. No tinctures modulated IL-2 production. Stem tinctures showed no activity. Storage temperature did not influence any outcomes. Root tinctures maintained their ability to modulate IL-1beta, IL-10, and TNF-alpha production after 1month of storage at -20 degrees C. CONCLUSIONS: These results suggest E. tennesseensis harbors phytomedicinal properties that vary by plant organ, with roots demonstrating the strongest activities.

Herbal supplements and athlete immune function--what's proven, disproven, and unproven?

The purpose of this paper is to critically evaluate current immunological and clinical literature regarding the effects of herbal preparations on athlete immune function. First, we review rates of herbal supplement use by athletes. Second, we use ginseng (Panax ginseng) and coneflower (Echinacea spp.) as models for examining how herbal supplements may influence immune function within the contexts of exercise and sport, while briefly considering several other popular herbal products. Third, we proffer several evidence-based hypotheses to explain apparent discrepancies among the cumulative data, concomitantly advancing a novel conceptual framework which may be useful to understanding herbal supplements and athlete immune function using Echinacea supplements as a model. Fourth, we apply the proposed framework to some prospective data regarding the effects of Echinacea pallida and Echinacea simulata on in vitro cytokine production and cell proliferation in peripheral blood mononuclear cells collected from male collegiate wrestlers and soccer players during training. Fifth and finally, we evaluate the current knowledge on herbal supplements and athlete immune function, identify gaps and limitations in knowledge, and advance several possible options for future research.

Cytokine- and interferon-modulating properties of Echinacea spp. root tinctures stored at -20 degrees C for 2 years.

Echinacea spp. phytomedicines are popular for treating upper respiratory infections. The purpose of this investigation was to examine the immunomodulatory properties of Echinacea tinctures from seven species after being stored at -20 degrees C for 2 years. Two experimental techniques were employed using human peripheral blood mononuclear cells (PBMC). In the first set of experiments, PBMCs were stimulated in vitro with tinctures alone and assayed for proliferation and production of interleukin-10 (IL-10), IL-12, and tumor necrosis factor-alpha (TNF-alpha). In the second set of experiments, subjects were immunized with influenza vaccine. PBMCs from vaccinated individuals were stimulated in vitro with Echinacea tinctures and influenza virus; cytokine production (IL-2, IL-10, and interferon-gamma [IFN-gamma]) was compared prevaccination and postvaccination. In the first experiments, (1) tinctures from E. angustifolia, E. pallida, E. paradoxa, and E. tennesseensis stimulated proliferation and tended to increase IL-10, (2) E. sanguinea and E. simulata stimulated only proliferation, (3) E. purpurea stimulated only IL-10, and (4) none of the extracts influenced IL-12 or TNF-alpha. In the second experiments, (1) tinctures from E. pallida, E. paradoxa, E. sanguinea, and E. simulata diminished influenza-specific IL-2, and (2) none of the extracts influenced influenza-specific IL-10 or IFN-gamma. For in vitro models using Echinacea, immune response may vary based on stimulus (Echinacea alone vs. Echinacea + recall stimulation with virus).

Enhancement of innate and adaptive immune functions by multiple Echinacea species.

Echinacea preparations are commonly used as nonspecific immunomodulatory agents. Alcohol extracts from three widely used Echinacea species, Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, were investigated for immunomodulating properties. The three Echinacea species demonstrated a broad difference in concentrations of individual lipophilic amides and hydrophilic caffeic acid derivatives. Mice were gavaged once a day (for 7 days) with one of the Echinacea extracts (130 mg/kg) or vehicle and immunized with sheep red blood cells (sRBC) 4 days prior to collection of immune cells for multiple immunological assays. The three herb extracts induced similar, but differential, changes in the percentage of immune cell populations and their biological functions, including increased percentages of CD49+ and CD19+ lymphocytes in spleen and natural killer cell cytotoxicity. Antibody response to sRBC was significantly increased equally by extracts of all three Echinacea species. Concanavalin A-stimulated splenocytes from E. angustifolia- and E. pallida-treated mice demonstrated significantly higher T cell proliferation. In addition, the Echinacea treatment significantly altered the cytokine production by mitogen-stimulated splenic cells. The three herbal extracts significantly increased interferon-alpha production, but inhibited the release of tumor necrosis factor-gamma and interleukin (IL)-1beta. Only E. angustifolia- and E. pallida-treated mice demonstrated significantly higher production of IL-4 and increased IL-10 production. Taken together, these findings demonstrated that Echinacea is a wide-spectrum immunomodulator that modulates both innate and adaptive immune responses. In particular, E. angustifolia or E. pallida may have more anti-inflammatory potential.

Disease outbreaks as vehicles for exploring 'engaged citizen' themes through a course on the history of infectious diseases.

Infectious diseases are potential catalysts for exploring 'engaged citizen' or socioscientific themes given their interwoven economic, political, scientific and social dimensions. This article describes how an undergraduate course on the history of infectious diseases was modified to explore the impact of two 'engaged citizen' themes (poverty and technology), and to consider the ramifications of those themes on past, present and future infectious disease outbreaks. Four outbreaks were used as the foundation for the course: plague (1350s), puerperal fever (1840s), cholera (1850s) and syphilis (1930s). The first part of the article describes the general course structure and the role of university-wide 'engaged citizen' themes in its semester-specific construction. The second part of the article demonstrates how poverty and technology 'threads' were explored in each of the four historical contexts, and subsequently how they were considered in current and future contexts; appendices with lesson suggestions are provided. The third and final part of the article discusses how this specific model might be more broadly applied to other microbiology instructional contexts.

PHENETIC COMPARISON OF SEVEN Echinacea SPECIES BASED ON IMMUNOMODULATORY CHARACTERISTICS.

The purpose of the present investigation was to compare similarities and differences in immune response among Echinacea species, which are commonly used to treat upper respiratory infections. The investigation involved two components: acquisition of immunomodulatory data reported here for the first time, and combined phenetic analysis of these data along with previous reports. Experimental data were obtained by stimulating human PBMC in vitro with extracts from Echinacea spp. and assaying production of three cytokines (interleukin-1ß [IL-1ß], interleukin-2 [IL-2], and tumor necrosis factor-α [TNF-α]). Phenetic analyses were employed to compare responses across the entire data set, including UPGMA (Unweighted Pair Group Method with Arithmetic Mean) and neighbor-joining methods. In the immune experiments conducted for this investigation, E. angustifolia, E. paradoxa, E. purpurea, E. simulata, and E. tennesseensis extracts significantly augmented IL-1 ß and TNF-α production, whereas no extracts significantly modulated IL-2. All phenetic methods produced similar dendrograms, revealing two species pairs (E. angustifolia + E. simulata and E. pallida + E.sanguinea) where both species cluster tightly and have similar immune-response profiles. These two species-pairs are maximally dissimilar from each other. The remaining species (E. paradoxa, E. purpurea, and E. tennesseensis) occupy intermediate positions in the dendrogram. Our results suggest that Echinacea spp. act heterogeneously on immune function. The utility of these data for science and industry is discussed.

Adapting an Infectious Diseases Course for "Engaged Citizen" Themes.

This article describes philosophies and perspectives underpinning scientific citizenship-focused curricular changes implemented into a pre-existing undergraduate infectious diseases course. Impetus for the curricular changes was a novel, campus-wide, multidisciplinary "Engaged Citizen" theme for the general education curriculum. The first half of the article describes the larger contexts from which the curricular changes were borne and the resulting instructional model. The second half of the article shares both student and instructor perspectives on the curricular changes and potential application of the model to other science courses.

Changes in immunomodulatory properties of Echinacea spp. root infusions and tinctures stored at 4 degrees C for four days.

BACKGROUND: Phytomedicinal preparations from members of the genus Echinacea are popular worldwide and frequently used to treat upper respiratory infections. With the increasing popularity of herbal medicines, many people are making their own Echinacea extracts at home and storing them at refrigerator (4 degrees C) temperatures. We tested the hypothesis that Echinacea extracts made using homemade methods change in immunomodulatory efficacy with storage at 4 degrees C over a 4-day period. METHODS: Three extract types (50% ethanol tincture, cold water infusion, hot water infusion) from 5 different species (Echinacea angustifolia, E. pallida, E. purpurea, E. sanguinea, E. tennesseensis) were prepared. Four in vitro immune assays (monocyte secretion of TNF-alpha, IL-10, and IL-12; and peripheral blood mononuclear cell proliferation) using human blood were used to test extract efficacy at Days 1 and 4 post-extraction. Two statistical analyses, traditional ANOVA and several statistical models that account for endotoxin effects, were used. RESULTS: Endotoxin was found to significantly impact immune outcomes only in 4-day old cold water infusions and not in all assays. Extracts showed the greatest stimulation in TNF-alpha assays. By extract type, 50% ethanol tinctures produced the most immune stimulation. By species, extracts from E. angustifolia extracts were the most efficacious in our assays; extracts from E. sanguinea showed the least activity overall. CONCLUSIONS: Taken together, these results suggest that: (1) homemade Echinacea extracts are efficacious in modulating immune cell activity in vitro but that their properties change with time during storage at 4 degrees C; and (2) endotoxin effects from extracts may be important considerations in the analysis of immunobiological data.

Age effects on macrophage function vary by tissue site, nature of stimulant, and exercise behavior.

We explored the effects of aging on macrophage function in male BALB/c mice from three age groups: young (2 months), middle-aged (12 months), and old (21 months). Macrophages were collected from alveoli, peritonea, and spleens of each age group. Cells were cultured in vitro with LPS or LPS+IFN-gamma and assayed for production of IL-1, IL-12, NO, and TNF-alpha. Using herpes simplex virus-1, age-related changes in intrinsic antiviral resistance (plaque assay) and extrinsic antiviral resistance (NO and TNF-alpha production) were determined in alveolar and/or peritoneal macrophages. Effects of chronic exercise on age-related macrophage changes were examined. In vitro, macrophages from the alveoli and spleen of older mice generally produced more cytokine and NO compared to younger counterparts. Conversely, macrophages from the peritonea of older mice generally produced less cytokine and NO in vitro compared to younger counterparts. Alveolar macrophages from both old and young mice showed higher intrinsic antiviral resistance to HSV-1 compared to middle-aged mice, while peritoneal macrophages from young mice showed reduced intrinsic resistance compared to those from both middle-aged and old mice. When challenged with HSV-1, a trend towards decreased peritoneal macrophage production of TNF-alpha and decreased alveolar macrophage production of IL-12 with advancing age was found. Chronic moderate exercise tended to reverse age-associated changes in macrophage function in old mice.

Reversing age-associated immunosenescence via exercise.

Decreases in immune responsiveness with age are thought to contribute to the increased incidence and severity of infectious disease among the elderly. Several interventions, including exercise, have been proposed to restore immune function in older populations. The findings from some, but not all studies, support the possibility that exercise may attenuate immunosenescence. In recent years, the role of exercise in modulating immune response has been examined using models that may have clinical relevance, such as the response to vaccines and novel antigens. Taken together, the accumulated data suggest that exercise may be an efficacious therapy for restoring immune function in the elderly. In general, long term exercise interventions appear to show the most promise. Exercise related improvements have been reported with respect to antibody titre, T cell function, macrophage response, alterations of the T(H)1/T(H)2 cytokine balance, the level of pro-inflammatory cytokines, and changes in naïve/memory cell ratio. However, current data is minimal, and many questions remain including: the mechanisms that are involved, the potential clinical impact, the appropriate type or dose of exercise, and whether the benefits extend to all populations including frail, older adults. This review summarizes the major findings of these studies and proposes directions for future exploration.

Ankle Spatting Compared to Bracing or Taping during Maximal-Effort Sprint Drills.

The purpose of this study was to compare the influences of 4 ankle conditions (no support, bracing, taping, taping + spatting; all in football cleats) during 2 maximal-effort field drills (40-yd dash and 34-yd cutting drill) on perceptions of comfort and stability and performance outcomes. Fourteen young adult males participated. Subjects' perceptions of comfort and stability were assessed by visual analogue scales after each drill for each ankle condition. Time-to-completion and post-completion heart rate were recorded. For both drills, significant differences in comfort perception were found such that subjects perceived no support as equivocal to bracing but more comfortable than either taping or spatting + taping. Stability results differed by drill. For the dash, significant differences in stability perception were found such that subjects perceived no support as equivocal to bracing but less stable than either taping or spatting + taping. By contrast, for the cutting drill significant differences in stability perception were found such that subjects perceived their ankles as less stable during the no support condition as compared to all 3 other conditions. Generally, bracing was perceived as equivocal to all 3 other conditions for comfort and stability. There were no significant differences in time-to-completion or heart rate for any comparison. Compared to bracing or taping, spatting + taping (a) did not influence performance time in explosive/sprint-type drills, (b) was perceived as equivalent to taping alone in terms of ankle comfort and stability, and

Age, sex, and ethnicity may modify the influence of obesity on inflammation.

OBJECTIVES: Many medical concerns associated with obesity are due to chronic inflammation, but factors underlying the development or maintenance of obesity-associated inflammation remain unclear. This study investigated how age, sex, and ethnicity may modify the interplay of subclinical inflammation and obesity in nationally representative contexts. METHODS: Using National Health and Nutrition Examination Survey data from 1999 to 2008, we assessed the role of these demographic factors on immunological markers of subclinical inflammation (such as total white blood cell counts, white blood cell subpopulation counts, and C-reactive protein [CRP] levels) in both obese and nonobese individuals. Approximately 9756 individuals were included in the analysis after removing individuals with confounding conditions. RESULTS: The CRP levels, total white blood cell count, and white blood cell subpopulation counts increased with increasing body mass index (BMI). After controlling for BMI, female subjects had greater levels of most inflammatory markers compared with male subjects. After controlling for age, sex, and ethnicity, the following inflammatory markers significantly increased with increasing BMI: CRP and white blood cell, lymphocyte, monocyte, and neutrophil counts. Basophil and eosinophil counts also increased with increasing BMI but not significantly. CONCLUSIONS: Factors, such as age, sex, and ethnicity, may modify the influence of obesity on subclinical inflammation at the population level.