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Vegan diet reduces neutrophils, monocytes and platelets related to branched-chain amino acids - A randomized, controlled trial.
Lederer, AK, Maul-Pavicic, A, Hannibal, L, Hettich, M, Steinborn, C, Gründemann, C, Zimmermann-Klemd, AM, Müller, A, Sehnert, B, Salzer, U, et al
Clinical nutrition (Edinburgh, Scotland). 2020;39(11):3241-3250
Abstract
BACKGROUND Vegan diet (VD) has improved inflammatory activity in patients with rheumatoid arthritis (RA) in several small controlled trials. The underlying mechanism remains widely unclear. We investigated the effect of a VD in comparison to a meat-rich diet (MD) on markers of inflammation (which have been shown to be relevant in patients with RA) in healthy volunteers. METHODS 53 healthy, omnivore subjects were randomized to a controlled VD (n = 26) or MD (n = 27) for 4 weeks following a pre-treatment phase of a one week controlled mixed diet. Primary parameters of interest were sialylation of immunoglobulins, percentage of regulatory T-cells and level of interleukin 10 (IL10). Usual care immune parameters used in patients with RA and amino acid serum levels as well as granulocytes and monocytes colony stimulating factor (GM-CSF) serum levels were secondary parameters. RESULTS In the VD group, total leukocyte, neutrophil, monocyte and platelet counts decreased and after four weeks they were significantly lower compared to the MD group (ANCOVA leukocytes p = 0.003, neutrophils p = 0.001, monocytes p = 0.032, platelets p = 0.004). Leukocytes, neutrophils, monocytes, and platelets correlated with each other and likewise conform with serum levels of branched-chain amino acids, which were significantly lower in the VD compared to the MD group. The primary parameters did not differ between the groups and BMI remained stable in the two groups. CONCLUSION Four weeks of a controlled VD affected the number of neutrophils, monocytes and platelets but not the number or function of lymphocytes. The relation with branched-chain amino acids and GM-CSF suggests a mode of action via the mTOR signaling pathway. REGISTERED AT http://www.drks.de (German Clinical Trial register) at DRKS00011963.
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Hemostatic and Anti-Inflammatory Effects of Carbazochrome Sodium Sulfonate in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Trial.
Luo, Y, Zhao, X, Releken, Y, Yang, Z, Pei, F, Kang, P
The Journal of arthroplasty. 2020;(1):61-68
Abstract
BACKGROUND Postoperative recovery after total knee arthroplasty (TKA) is associated with postoperative anemia, allogeneic transfusion, and stress immune responses to surgery. Carbazochrome sodium sulfonate (CSS) reduces bleeding through several mechanisms. We assessed the effect of CSS combined with tranexamic acid (TXA) on postoperative anemia, blood transfusion, and inflammatory responses. METHODS This study was designed as a randomized, placebo-controlled trial of 200 patients undergoing unilateral primary TKA. Patients were divided into 4 groups: group A received TXA plus topical and intravenous CSS; group B received TXA plus topical CSS only; group C received TXA plus intravenous CSS only; group D received TXA only. RESULTS Total blood loss in groups A (609.92 ± 221.24 mL), B (753.16 ± 247.67 mL), and C (829.23 ± 297.45 mL) was lower than in group D (1158.26 ± 334.13 mL, P < .05). There was no difference in total blood loss between groups B and C. We also found that compared with group D, the postoperative swelling rate, biomarker level of inflammation, visual analog scale pain score, and range of motion at discharge in groups A, B, and C were significantly improved (P < .05). No thromboembolic complications occurred. There were no differences in transfusion rate, intraoperative blood loss, platelet count, or average length of stay among the 4 groups (P > .05). CONCLUSION CSS combined with TXA was more effective than TXA alone in reducing perioperative blood loss and inflammatory response and did not increase the incidence of thromboembolism complications.
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Selenoprotein P in Myocardial Infarction With Cardiogenic Shock.
Büttner, P, Obradovic, D, Wunderlich, S, Feistritzer, HJ, Holzwirth, E, Lauten, P, Fuernau, G, de Waha-Thiele, S, Desch, S, Thiele, H
Shock (Augusta, Ga.). 2020;(1):58-62
Abstract
BACKGROUND Reperfusion strategies in acute myocardial infarction (AMI) may result in ischemia reperfusion injury characterized by increased oxidative stress, inflammation, and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock (CS). Many anti-oxidative and immune regulatory processes depend on selenium which in large proportions is bound to circulating selenoprotein P (SelP). Individual SelP patterns may therefore be associated with inflammatory response and possibly mortality in patients with CS post AMI. METHODS In the randomized Intra-Aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. In a predefined biomarker substudy of 147 patients, we analyzed SelP levels 1 and 3 days following randomization. Samples were compared with healthy controls and associations with the unspecific inflammatory marker C-reactive protein (CRP) were analyzed. RESULTS Compared with controls SelP levels in patients with infarct-related CS were markedly higher (2.7-fold at day 1 and 5.7-fold at day 3 following AMI, all P < 0.001). Thirty-day mortality was significantly higher in patients with SelP levels above the 75th percentile at day 3 following AMI (26% vs. 46%, P = 0.045). SelP was significantly proportionally correlated with CRP 1 (R = 0.762, P < 0.0001) and 3 days (R = 0.777 P < 0.0001) following AMI. CONCLUSION SelP levels are significantly increased post AMI with CS. Higher SelP levels are associated with increased CRP levels indicative for inflammatory processes. Future studies should focus on the characterization of SelP profiles following AMI and the identification of pathomechanisms affected by SelP.
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Association between Subcutaneous Adipose Tissue Inflammation, Insulin Resistance, and Calorie Restriction in Obese Females.
Sbierski-Kind, J, Mai, K, Kath, J, Jurisch, A, Streitz, M, Kuchenbecker, L, Babel, N, Nienen, M, Jürchott, K, Spranger, L, et al
Journal of immunology (Baltimore, Md. : 1950). 2020;(1):45-55
Abstract
The worldwide epidemic of overweight and obesity has led to an increase in associated metabolic comorbidities. Obesity induces chronic low-grade inflammation in white adipose tissue (WAT). However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal overweight or obese female subjects who either underwent CR for 3 mo followed by a 4-wk phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and s.c. WAT (SAT). The TCR repertoire was analyzed by next-generation sequencing and cytokine levels were determined in SAT. Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp. We found that insulin resistance correlates significantly with a shift toward the memory T cell compartment in SAT. TCR analysis revealed a diverse repertoire in SAT of overweight or obese individuals. Additionally, whereas weight loss improved systemic insulin sensitivity in the intervention group, SAT displayed no significant improvement of inflammatory parameters (cytokine levels and leukocyte subpopulations) compared with the control group. Our data demonstrate the accumulation of effector memory T cells in obese SAT and an association between systemic glucose homeostasis and inflammatory parameters in obese females. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR-induced weight loss.
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The Effect of a Multivitamin and Mineral Supplement on Immune Function in Healthy Older Adults: A Double-Blind, Randomized, Controlled Trial.
Fantacone, ML, Lowry, MB, Uesugi, SL, Michels, AJ, Choi, J, Leonard, SW, Gombart, SK, Gombart, JS, Bobe, G, Gombart, AF
Nutrients. 2020;12(8)
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Vitamins and minerals are essential for a healthy immune system. The prevalence of vitamin and mineral deficiencies increases with age, and this may contribute to age-related decline of the immune system. The aim of this study was to investigate whether a daily multivitamin and mineral (MVM) supplement could improve the immune function of older people. 42 healthy adults aged between 55 and 75 took part in this single-centre, two-armed, parallel, randomised, double-blinded study. Half of the group was given a MVM supplement called Redoxon Vita Immune (VI) containing the vitamins A, D, E, C, B6, B12 and folate plus iron, copper, zinc and selenium daily for 12 weeks, whilst the other half was given placebo tablets for 12 weeks. Participants were instructed to avoid certain foods high in vitamins and minerals such as oily fish, red meat, liver, and citrus fruits during the study period. Blood and saliva samples were taken from all participants at the beginning and end of the study period, to measure vitamin and mineral status and markers of immune function. Participants also kept a diary to record any illnesses or symptoms. At the end of the study, participants given the MVM supplement had increased their blood levels of vitamin C by 126% and zinc by 43%. There was no significant change in blood levels of vitamin D. There was no significant difference in the potential of blood to kill the introduced bacteria Staphylococcus aureus, or in neutrophil activity, nor were there any significant changes in blood levels of cytokines and chemokines. Participants taking the supplement did however report a shorter length, and lower severity of illnesses compared to those taking the placebo. The authors concluded that their findings support further research to test whether MVM supplementation can improve immune outcomes in older adults.
Abstract
Older adults are at increased risk for vitamin and mineral deficiencies that contribute to age-related immune system decline. Several lines of evidence suggest that taking a multi-vitamin and mineral supplement (MVM) could improve immune function in individuals 55 and older. To test this hypothesis, we provided healthy older adults with either an MVM supplement formulated to improve immune function (Redoxon® VI, Singapore) or an identical, inactive placebo control to take daily for 12 weeks. Prior to and after treatment, we measured (1) their blood mineral and vitamin status (i.e., vitamin C, zinc and vitamin D); (2) immune function (i.e., whole blood bacterial killing activity, neutrophil phagocytic activity, and reactive oxygen species production); (3) immune status (salivary IgA and plasma cytokine/chemokine levels); and (4) self-reported health status. MVM supplementation improved vitamin C and zinc status in blood and self-reported health-status without altering measures of immune function or status or vitamin D levels, suggesting that healthy older adults may benefit from MVM supplementation. Further development of functional assays and larger study populations should improve detection of specific changes in immune function after supplementation in healthy older adults. Clinical Trials Registration: ClinicalTrials.gov #NCT02876315.
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Stratifying cellular metabolism during weight loss: an interplay of metabolism, metabolic flexibility and inflammation.
Tareen, SHK, Kutmon, M, de Kok, TM, Mariman, ECM, van Baak, MA, Evelo, CT, Adriaens, ME, Arts, ICW
Scientific reports. 2020;10(1):1651
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Obesity is a public health concern as it has been linked to cardiovascular diseases, type 2 diabetes and metabolic syndrome. The aim of this study was to identify and analyse expression profiles of individuals clustered by cellular metabolism centring on metabolic flexibility. This study clustered gene expression samples from a weight loss study (Yoyo study’ - Clinical Trial ID: NCT01559415) into two clusters, based on 291 genes associated with cellular metabolic fexibility. The study covers two diets: a low-calorie diet (LCD) and a very low-calorie diet (VLCD). All the participants of the study were Caucasian with a BMI between 28kg/m2 and 35 kg/m2, aged between 32 and 67 years old. Findings showed that the majority of the individuals had their metabolism associated genes downregulated after weight loss and weight maintenance, but also had an upregulation of immune system associated genes. Furthermore, individuals who had changed their metabolic profiles in response to caloric restriction had a significant retention of lost weight compared to individuals which had not changed their cluster membership. Authors conclude that their findings indicate possible cross-talk between cellular metabolism and inflammation.
Abstract
Obesity is a global epidemic, contributing significantly to chronic non-communicable diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. Metabolic flexibility, the ability of organisms to switch between metabolic substrates, is found to be impaired in obesity, possibly contributing to the development of chronic illnesses. Several studies have shown the improvement of metabolic flexibility after weight loss. In this study, we have mapped the cellular metabolism of the adipose tissue from a weight loss study to stratify the cellular metabolic processes and metabolic flexibility during weight loss. We have found that for a majority of the individuals, cellular metabolism was downregulated during weight loss, with gene expression of all major cellular metabolic processes (such as glycolysis, fatty acid β-oxidation etc.) being lowered during weight loss and weight maintenance. Parallel to this, the gene expression of immune system related processes involving interferons and interleukins increased. Previously, studies have indicated both negative and positive effects of post-weight loss inflammation in the adipose tissue with regards to weight loss or obesity and its co-morbidities; however, mechanistic links need to be constructed in order to determine the effects further. Our study contributes towards this goal by mapping the changes in gene expression across the weight loss study and indicates possible cross-talk between cellular metabolism and inflammation.
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Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients.
Al-Sharif, FM, Abd El-Kader, SM, Neamatallah, ZA, AlKhateeb, AM
African health sciences. 2020;20(2):897-902
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Asthma is a common condition characterised by attacks of obstruction, chronic inflammation and hyper-responsiveness of the airways. Obesity increases severity of asthmatic symptoms through mechanical, anatomical and/or inflammatory mechanisms. 80 adults with asthma were randomly allocated to a weight reduction programme, including aerobic exercise and a calorie reduced diet, or control group with no intervention. After 3 months, body mass index (BMI) reduced significantly in the intervention group (from 31.7 to 27.9). This was associated with significant reductions in the pro-inflammatory markers TNF-alpha, interleukin-6 and interleukin-8, and significant increases in CD4 and CD8 cell counts (important immune cells). There were no changes in the control group in any of the parameters and the results were statistically significantly better in the intervention compared to the control group. The authors conclude that weight reduction improved immunological and inflammatory markers in obese asthma patients.
Abstract
BACKGROUND Activation of immunological and systemic inflammation markers are common in obesity and asthma. OBJECTIVE The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients. MATERIAL AND METHODS Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B). RESULTS The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences. CONCLUSION Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.
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Safety and efficacy of herbal extracts to restore respiratory health and improve innate immunity in COVID-19 positive patients with mild to moderate severity: A structured summary of a study protocol for a randomised controlled trial.
Rangnekar, H, Patankar, S, Suryawanshi, K, Soni, P
Trials. 2020;(1):943
Abstract
OBJECTIVES Primary Objective • To assess the efficacy of herbal extracts in boosting innate immunity of patients with COVID-19 infection. Secondary Objectives • To assess the efficacy of herbal extracts in restoring respiratory health • To assess the efficacy of Cap. IP in early recovery of patients and decline in viral load • To assess the safety of herbal extracts TRIAL DESIGN This is a single centre, randomized, 2-arm, parallel group, double blind, 1:1 ratio, controlled, exploratory trial with a study period of 30 days from the day of enrolment. PARTICIPANTS Patients attending the COVID treatment centre at Yashwantrao Chavan Memorial Hospital, Nehrunagar, Pimpri, Pune, India were screened for their participation in the study. Patients who were known COVID-19 positive (with positive RT-PCR), eligible and willing were enrolled in the study. INTERVENTION AND COMPARATOR The intervention in the trial has a background in 'Ayurved'. Intervention Arm: Two capsules, Investigational Product (IP) - 1 - 400mg and Investigational Product - 2 - 450mg, containing herbal extracts (a blend of water and CO2 extracts) of Shunthi (Zingiber officinale (Ginger), Vidanga (Embelia ribes), Yashtimadhu (Glycyrrhiza glabra), Haritaki (Terminalia chebula), Guduchi (Tinospora cordifolia), Shatavari (Asparagus racemosus), Aamalaki (Emblica officinalis), Pippali (Piper longum) and calcined Zinc, Shankha bhasma. Placebo Arm: Edible starch ~ 450 mg. The look and feel of IP and of Placebo boxes were very similar. Patients are to take two capsules (one each of IP-1 and IP-2) twice a day for 15 days, and from the 16th day, one capsule of IP-2 twice a day up-to day 30. Capsules are to be administered orally with plain water. The IP is to be taken with all other concomitant medicines prescribed by the treating physician/doctor. The dose of each component in the IP is very safe to administer. The investigational products are registered products with the Indian Government and have been used for more than 6 months in various health conditions but not for COVID-19. MAIN OUTCOMES Primary Outcome: Efficacy of the herbal extracts in COVID 19 positive patients (in declining viral load: time-point: 4 days and early recovery) Secondary Outcomes: Efficacy of the herbal extracts as an immune-modulator - TH1, TH2, Th17, IL6, NK Cells and CD markers; Immunoglobulin IGG (Serum); Immunoglobulin IGM (Serum) - at 30 days. Efficacy of the investigational product in reducing sequela of the disease Safety analysis (Liver Function Test and Kidney Function Test) including serious allergic reaction of: rash, itching/swelling, severe dizziness, trouble breathing. RANDOMISATION An alphanumeric coded set of IP/Placebo containers will be used. Participants will be automatically randomized to two groups in the ratio 1:1. BLINDING (MASKING): Participants, caregivers and investigators were blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of more than 60 and up to 75 patients were to be enrolled in the study into the two groups, considering drop-outs. 72 were enrolled with 37 into the intervention group and 35 into the placebo group. TRIAL STATUS Protocol number: CoviQuest-01 Protocol version number: 1.2 Protocol Date: 1st July 2020 The recruitment period is completed for the trial. Date of 1st patient enrolment was 11th Aug 2020 and the last patient was enrolled on 3rd of September 2020. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. Last Participant's last follow-up is scheduled on 5th October 2020 TRIAL REGISTRATION The trial was prospectively registered with the CTRI (Clinical Trial Registry of India). Registration number is CTRI/2020/07/026570 . Registered on 14 July 2020 FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Immune recovery markers in a double blind clinical trial comparing dolutegravir and raltegravir based regimens as initial therapy (SPRING-2).
Blanco, JR, Alejos, B, Moreno, S
PloS one. 2020;(1):e0226724
Abstract
BACKGROUND Multiple T-cell marker recovery (MTMR: CD4+ T-cells >500 cel/mm3 plus CD4+% >29% plus CD4+/CD8+ ratio >1) has been proposed as the most complete level of immune reconstitution. In this study we quantified differences in the CD4+/CD8+ ratio, CD4+% recovery and MTMR after starting HIV-1 treatment with dolutegravir (DTG) vs. raltegravir (RAL) plus a NRTI backbone. METHODS Exploratory post-hoc analysis of the SPRING-2 study, a randomized double-blind clinical trial comparing DTG and RAL as third agents in naive HIV-infected patients at 100 sites in Canada, USA, Australia, and Europe. Percentage differences and corresponding precision based on 95% confidence intervals (CI) and p-values were calculated for i) CD4+/CD8+ ratio normalization, ii) CD4+% normalization, and iii) the achievement of MTMR. RESULTS A total of 822 participants were analyzed (411 in each group). No statistically significant differences in the proportion of patients who reached a CD4+/CD8+ ratio ≥0.5 & ≥1 at w48 & w96 were observed. At w96, the proportion of patients with a CD4+/CD8+ ratio ≥1 was similar (30.43% DTG vs. 29.57% RAL). No differences were observed in the mean increase in CD4+/CD8+ ratio from baseline at both w48 & w96. Similarly, no significant differences in the CD4+/CD8+>29% were observed at w96 (72.95% DTG vs 69.28% RAL). The proportion of patients attaining MTMR criteria was also similar in the DTG group and the RAL group at w48 (20.33% vs. 18.26%; difference 2.07 (95%CI (-3.67;7.81) P = 0.481 and w96 (28.70% vs. 27.13; difference 1.56 (95%CI -5.22;8.34) P = 0.652). CONCLUSION After comparing DTG and RAL, no differences on immune recovery markers were observed.
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Yeast Beta-Glucan Supplementation Downregulates Markers of Systemic Inflammation after Heated Treadmill Exercise.
Zabriskie, HA, Blumkaitis, JC, Moon, JM, Currier, BS, Stefan, R, Ratliff, K, Harty, PS, Stecker, RA, Rudnicka, K, Jäger, R, et al
Nutrients. 2020;(4)
Abstract
Aerobic exercise and thermal stress instigate robust challenges to the immune system. Various attempts to modify or supplement the diet have been proposed to bolster the immune system responses. The purpose of this study was to identify the impact of yeast beta-glucan (Saccharomyces cerevisiae) supplementation on exercise-induced muscle damage and inflammation. Healthy, active men (29.6 ± 6.7 years, 178.1 ± 7.2 cm, 83.2 ± 11.2 kg, 49.6 ± 5.1 mL/kg/min, n = 16) and women (30.1 ± 8.9 years, 165.6 ± 4.1 cm, 66.7 ± 10.0 kg, 38.7 ± 5.8 mL/kg/min, n = 15) were randomly assigned in a double-blind and cross-over fashion to supplement for 13 days with either 250 mg/day of yeast beta-glucan (YBG) or a maltodextrin placebo (PLA). Participants arrived fasted and completed a bout of treadmill exercise at 55% peak aerobic capacity (VO2Peak) in a hot (37.2 ± 1.8 °C) and humid (45.2 ± 8.8%) environment. Prior to and 0, 2, and 72 h after completing exercise, changes in white blood cell counts, pro- and anti-inflammatory cytokines, markers of muscle damage, markers of muscle function, soreness, and profile of mood states (POMS) were assessed. In response to exercise and heat, both groups experienced significant increases in white blood cell counts, plasma creatine kinase and myoglobin, and soreness along with reductions in peak torque and total work with no between-group differences. Concentrations of serum pro-inflammatory cytokines in YBG were lower than PLA for macrophage inflammatory protein 1β (MIP-1β) (p = 0.044) and tended to be lower for interleukin 8 (IL-8) (p = 0.079), monocyte chemoattractment protein 1 (MCP-1) (p = 0.095), and tumor necrosis factor α (TNF-α) (p = 0.085). Paired samples t-tests using delta values between baseline and 72 h post-exercise revealed significant differences between groups for IL-8 (p = 0.044, 95% Confidence Interval (CI): (0.013, 0.938, d = -0.34), MCP-1 (p = 0.038, 95% CI: 0.087, 2.942, d = -0.33), and MIP-1β (p = 0.010, 95% CI: 0.13, 0.85, d = -0.33). POMS outcomes changed across time with anger scores in PLA exhibiting a sharper decline than YBG (p = 0.04). Vigor scores (p = 0.04) in YBG remained stable while scores in PLA were significantly reduced 72 h after exercise. In conclusion, a 13-day prophylactic period of supplementation with 250 mg of yeast-derived beta-glucans invoked favorable changes in cytokine markers of inflammation after completing a prolonged bout of heated treadmill exercise.