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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
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The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.
Draxler, A, Franzke, B, Kelecevic, S, Maier, A, Pantic, J, Srienc, S, Cellnigg, K, Solomon, SM, Zötsch, C, Aschauer, R, et al
Redox biology. 2023;61:102640
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Aging is associated with a decline in physiological and physical function resulting in reduced physical activity, all of which are driving factors to the onset of chronic diseases and physical impairment. Older adults are often deficient in micronutrients, specifically vitamin D, which has been shown to have detrimental effects on the immune system, inflammatory and healing processes of fractured bones and also cardiovascular health beyond other musculoskeletal effects. The aim of this study was to investigate the effect of different vitamin D regimens in older individuals during an ongoing strength training period of 10 weeks while receiving vitamin D supplementation at the recommended level of 800 IU per day vs. a single dose of 50.000 IU per month. The data presented in this paper are part of the NutriAging Vitamin D study. The study was a randomised placebo-controlled double-blind trial which recruited one hundred community-dwelling women and men (aged 65–85 years). Participants were randomly allocated into three intervention groups, either the control group, the vitamin D daily (VDD) or the vitamin D monthly group (VDM). Results showed that oxidative stress might have played a role in the detrimental progress on chromosomal stability parameters since the protective effect of GSH (reduced glutathione) was reduced in all study groups at the end of the intervention, but the least reduction occurred in the VDD group. Authors concluded that a supplementation with the recommended dose of 800 IU vitamin D per day might be more advantageous when it comes to chromosomal stability parameters in older, formerly untrained participants undergoing demanding resistance exercise for 10 weeks.
Abstract
Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.
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Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.
Porto, AA, Gonzaga, LA, Benjamim, CJR, Valenti, VE
Nutrients. 2023;15(8)
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L-citrulline is a non-essential amino acid that acts as a precursor to L-arginine. L-arginine is a semi-essential amino acid used for nitric oxide production which is crucial for maintaining physiological function and immune regulation. Previous research has shown that L-citrulline and L-arginine supplementation may offer antioxidant and anti-inflammatory benefits in reducing exercise-related oxidative stress and inflammation. This systematic review and meta-analysis included seven randomised controlled trials to investigate the effect of L-citrulline and L-arginine on antioxidants, oxidative stress, and inflammatory and anti-inflammatory markers. This systematic review and meta-analysis showed no significant improvements in oxidative stress and inflammation followed by the supplementation of L-citrulline and L-arginine before exercise. However, further robust studies that include different dosages and exercise intensities are required to assess the beneficial effects of L-citrulline and L-arginine supplements to support physical exercise-induced oxidative stress and inflammation due to the heterogeneity of the included studies. Healthcare professionals can use the results of this study to understand the potential benefits of L-citrulline and L-arginine supplementation in people prone to producing proinflammatory cytokines.
Abstract
The repercussions on oxidative and inflammatory stress markers under the effects of arginine and citrulline in response to exercise are not fully reached. We completed a systematic review to investigate the effects of L-Citrulline or L-Arginine on oxidative stress and inflammatory biomarkers following exercise. EMBASE, MEDLINE (PubMed), Cochrane Library, CINAHL, LILACS, and Web of Science databases were used to record the trials. This study includes randomized controlled trials (RCTs) and non-RCTs with subjects over 18 years old. Those under the intervention protocol consumed L-Citrulline or L-Arginine, and the controls ingested placebo. We recognized 1080 studies, but only 7 were included (7 studies in meta-analysis). We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], p = 0.24, and heterogeneity = 0%. In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], p = 0.16, and heterogeneity = 0%. For the "L-Citrulline" subgroup we observed a subtotal = 0.00 [-0.67, 0.67], p = 1.00, and heterogeneity was not applicable. No differences were observed between groups (p = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], p = 0.68, and heterogeneity = 0%). In the "L-Arginine" sub-group, we found a subtotal = -3.90 [-14.18, 6.38], p = 0.46, and heterogeneity was not applicable. For the "L-Citrulline" subgroup, we reported a subtotal = -0.22 [-1.60, 1.16], p = 0.75, and heterogeneity was not applicable. No differences were observed between groups (p = 0.49), and I² = 0%), inflammatory markers (subtotal = 8.38 [-0.02, 16.78], p = 0.05, and heterogeneity = 93%. Tests for subgroup differences were not applicable, and anti-inflammatory markers (subtotal = -0.38 [-1.15, 0.39], p = 0.34 and heterogeneity = 15%; testing for subgroup differences was not applicable). In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.
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Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection.
Townsend, L, Dyer, AH, McCluskey, P, O'Brien, K, Dowds, J, Laird, E, Bannan, C, Bourke, NM, Ní Cheallaigh, C, Byrne, DG, et al
Nutrients. 2021;13(7)
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Persistence of symptoms following COVID-19 infection is known as long COVID and occurs in up to a third of sufferers and can last for as long as 6 months post infection. Tiredness and reduced capacity to exercise are characteristic of long COVID, however why these symptoms persist in a handful of patients is unknown. Vitamin D deficiency is gaining attention for its potential to improve symptoms of tiredness, however there are few studies examining its relationship with long COVID. This observational study of 149 patients who had been diagnosed with COVID-19 aimed to determine the relationship between symptoms of long COVID, inflammation in the body and vitamin D levels. The results showed that fatigue was common, but there was no association between vitamin D levels and fatigue, inflammation, or capacity to exercise. Interestingly women were more likely to experience fatigue in this study. It was concluded that fatigue and reduced exercise capacity are independent of vitamin D in those who have had COVID-19. This study could be used by healthcare professionals to understand symptoms of long COVID, and that vitamin D may not be effective for those symptoms.
Abstract
The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30-49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.
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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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Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial.
Moro, T, Tinsley, G, Longo, G, Grigoletto, D, Bianco, A, Ferraris, C, Guglielmetti, M, Veneto, A, Tagliabue, A, Marcolin, G, et al
Journal of the International Society of Sports Nutrition. 2020;17(1):65
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Adequate nutrition is important for elite athletes, as nutrient availability influences energy expenditure, body composition, performance and exercise-induced immune responses. Time-restricted eating (TRE) is a form of intermittent fasting that has received much interest in recent years. Previous research of TRE suggested beneficial effects on performance in untrained individuals, by allowing weight loss whilst maintaining muscle functions. These qualities are of interest for endurance cyclists hence the authors of this study sought to investigate the impact of TRE in elite cyclists. Sixteen under-23 year old, elite cyclists were randomly assigned to eat within a TRE window of 8-hr or 15hr window during a 4-week, high-level endurance training phase. Both groups consumed their full estimated energy needs and markers such as fat and fat-free mass, VO2 max, basal metabolism, blood counts, anabolic hormones and inflammatory markers were measured. As a result, TRE produced weight loss, improved body composition and increased peak power output in relation to body weight without compromising aerobic performance. Furthermore, the TRE pattern proved helpful in mitigating some of the exercise-induced suppressions of the immune system. The authors concluded that TRE could be considered as part of a performance nutrition plan in endurance athletes. Particularly where there is a need to reduce body fat mass or for the management of training-induced depression of the immune system and associated respiratory infection susceptibility. This can be of clinical relevance in the support of endurance athletes.
Abstract
BACKGROUND Although there is substantial interest in intermittent fasting as a dietary approach in active individuals, information regarding its effects in elite endurance athletes is currently unavailable. The present parallel randomized trial investigated the effects of a particular intermittent fasting approach, called time-restricted eating (TRE), during 4 weeks of high-level endurance training. METHODS Sixteen elite under-23 cyclists were randomly assigned either to a TRE group or a control group (ND). The TRE group consumed 100% of its estimated daily energy needs in an 8-h time window (from 10:00 a.m. to 6:00 p.m.) whilst energy intake in the ND group was distributed in 3 meals consumed between 7:00 a.m. and 9:00 p.m. Fat and fat-free mass were estimated by bioelectrical impedance analysis and VO2max and basal metabolism by indirect gas analyzer. In addition, blood counts, anabolic hormones (i.e. free testosterone, IGF-1) and inflammatory markers (i.e. IL-6, TNF-α) were assessed. RESULTS TRE reduced body weight (- 2%; p = 0.04) and fat mass percentage (- 1.1%; p = 0.01) with no change in fat-free mass. Performance tests showed no significant differences between groups, however the peak power output/body weight ratio (PPO/BW) improved in TRE group due to weight loss (p = 0.02). Free testosterone and IGF-1 decreased significantly (p = 0.01 and p = 0.03 respectively) in TRE group. Leucocyte count decreased in ND group (p = 0.02) whilst the neutrophils-to-lymphocytes ratio (NLR) decreased significantly (p = 0.03) in TRE group. CONCLUSIONS Our results suggest that a TRE program with an 8-h feeding window elicits weight loss, improves body composition and increases PPO/BW in elite cyclists. TRE could also be beneficial for reducing inflammation and may have a protective effect on some components of the immune system. Overall, TRE could be considered as a component of a periodized nutrition plan in endurance athletes. TRIAL REGISTRATION This trial was retrospectively registered at clinicaltrials.gov as NCT04320784 on 25 March 2020.
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Four weeks of probiotic supplementation reduces GI symptoms during a marathon race.
Pugh, JN, Sparks, AS, Doran, DA, Fleming, SC, Langan-Evans, C, Kirk, B, Fearn, R, Morton, JP, Close, GL
European journal of applied physiology. 2019;119(7):1491-1501
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Gastrointestinal (GI) symptoms are common in athletes participating in marathon running. The purpose of this study was to evaluate the effects of probiotic supplementation on GI symptoms and markers of GI permeability and damage during marathon training and racing. 24 runners took part in this double-blind, randomised trial. Participants took a probiotic supplement containing 25 billion organisms (Lactobacilli and bifidobacterial) or placebo for 4 weeks prior to the marathon race. Blood samples were taken before supplementation, pre and post marathon. Participants also completed a questionnaires regarding GI symptoms. All runners experienced GI symptoms during the marathon. Runners supplementing with probiotics reported fewer and less severe GI symptoms, both in training and during the race, and also showed increased performance during the race compared to the placebo group. There was no association between GI symptoms and markers of GI permeability and damage, although both were increased post-race in all participants. The authors conclude that athletes participating in endurance events, where GI symptoms are common and likely to affect performance, could consider probiotic supplementation in the weeks prior to competition.
Abstract
PURPOSE To evaluate the effects of probiotic supplementation on gastrointestinal (GI) symptoms, circulatory markers of GI permeability, damage, and markers of immune response during a marathon race. METHODS Twenty-four recreational runners were randomly assigned to either supplement with a probiotic (PRO) capsule [25 billion CFU Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium bifidum (CUL20), and Bifidobacterium animalis subs p. Lactis (CUL34)] or placebo (PLC) for 28 days prior to a marathon race. GI symptoms were recorded during the supplement period and during the race. Serum lactulose:rhamnose ratio, and plasma intestinal-fatty acid binding protein, sCD14, and cytokines were measured pre- and post-races. RESULTS Prevalence of moderate GI symptoms reported were lower during the third and fourth weeks of the supplement period compared to the first and second weeks in PRO (p < 0.05) but not PLC (p > 0.05). During the marathon, GI symptom severity during the final third was significantly lower in PRO compared to PLC (p = 0.010). The lower symptom severity was associated with a significant difference in reduction of average speed from the first to the last third of the race between PLC (- 14.2 ± 5.8%) and PRO (- 7.9 ± 7.5%) (p = 0.04), although there was no difference in finish times between groups (p > 0.05). Circulatory measures increased to a similar extent between PRO and PLC (p > 0.05). CONCLUSION Probiotics supplementation was associated with a lower incidence and severity of GI symptoms in marathon runners, although the exact mechanisms are yet to be elucidated. Reducing GI symptoms during marathon running may help maintain running pace during the latter stages of racing.
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Proprietary Milk Protein Concentrate Reduces Joint Discomfort While Improving Exercise Performance in Non-Osteoarthritic Individuals.
Ziegenfuss, TN, Kerksick, CM, Kedia, AW, Sandrock, J, Raub, B, Lopez, HL
Nutrients. 2019;11(2)
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Osteoarthritis is the most common joint disorder of the different forms of arthritis. Key symptoms associated with osteoarthritis include the onset of pain, development of various disabilities such as increased difficulty with climbing stairs, walking and other activities of daily living. The aim of this study was to examine the impact of ingesting a concentrated milk protein derived from the milk produced by hyperimmunized cows on alleviating pain (discomfort) and function with and without an external physical stimulus in non-osteoarthritic participants. The study was a randomized, double-blind, placebo-controlled investigation using two parallel supplementation groups (milk protein concentrate group n = 24 and placebo group n = 34) that spanned eight weeks. Results indicate that treatment with proprietary milk protein concentrate resulted in greater improvements in several components within the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) assessment, walking performance, as well as self-reported levels of pain, discomfort, stiffness and stability. Authors conclude that daily doses of proprietary milk protein concentrate yielded improvements in several components and it was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.
Abstract
Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE To examine the impact of MicroLactin®, a proprietary milk protein concentrate, on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m², n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m², n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or MicroLactin® (ML) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS Distance covered in the 6-min walking significantly improved 9% in ML versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of ML improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, ML also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS In comparison to placebo, daily doses of MicroLactin® yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.
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The effects of bovine colostrum supplementation on in vivo immunity following prolonged exercise: a randomised controlled trial.
Jones, AW, March, DS, Thatcher, R, Diment, B, Walsh, NP, Davison, G
European journal of nutrition. 2019;58(1):335-344
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Upper respiratory tract symptoms (URS) are the most common ailment reported by athletes to medicine clinics at major sporting events. The main aim of this study was to investigate the effects of bovine colostrum (COL) supplementation on the induction of invivo immune responses to a novel antigen, diphenylcyclopropenone (DPCP) [a topically administered experimental drug], following prolonged exercise. The study is a double-blind randomised placebo-controlled trial which recruited 34 healthy male participants aged between 18 and 45 years. The participants were randomly assigned to one of the two groups: COL group (n = 17) or placebo group (n = 17). Results indicate that COL did not significantly affect the overall response to the novel antigen, DPCP, but COL supplementation induced greater sensitivity of antigen-specific memory recalled 4 weeks following the initial sensitisation. Authors conclude that their findings may suggest a nutritional strategy to counter exercise-induced immunodepression assessed via an established, clinically relevant in vivo marker of immunity.
Abstract
BACKGROUND Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction, but there is a lack of research with clinically relevant in vivo measures. AIM: To investigate the effects of COL supplementation on in vivo immunity following prolonged exercise using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS In a double-blind design, 31 men were randomly assigned to COL (20 g/day) or placebo (PLA) for 58 days. Participants ran for 2 h at 60% maximal aerobic capacity on day 28 and received a primary DPCP exposure (sensitisation) 20 min after. On day 56, participants received a low-dose-series DPCP challenge to elicit recall of in vivo immune-specific memory (quantified by skinfold thickness 24 and 48 h later). Analysis of the dose-response curves allowed determination of the minimum dose required to elicit a positive response (i.e., sensitivity). RESULTS There was no difference in summed skinfold thickness responses between COL and PLA at 24 h (p = 0.124) and 48 h (p = 0.405). However, sensitivity of in vivo immune responsiveness was greater with COL at 24 h (p < 0.001) and 48 h (p = 0.023) with doses ~ twofold greater required to elicit a positive response in PLA. CONCLUSIONS COL blunts the prolonged exercise-induced decrease in clinically relevant in vivo immune responsiveness to a novel antigen, which may be a mechanism for reduced illness reports observed in the previous studies. These findings also suggest that CHS sensitivity is highly relevant to host defence.
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Influence of combined functional resistance and endurance exercise over 12 weeks on matrix metalloproteinase-2 serum concentration in persons with relapsing-remitting multiple sclerosis - a community-based randomized controlled trial.
Proschinger, S, Joisten, N, Rademacher, A, Schlagheck, ML, Walzik, D, Metcalfe, AJ, Oberste, M, Warnke, C, Bloch, W, Schenk, A, et al
BMC neurology. 2019;19(1):314
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Multiple Sclerosis (MS) is a degenerative autoimmune neuroinflammatory disease where the blood-brain barrier is compromised, causing inflammation. Regular exercise has been shown to support psychomotor symptoms and improve mobility. This trial examines the effects of resistance and endurance exercise in 64 patients, aged 18-45 years, with relapsing-remitting MS (RRMS). The patients are divided into an exercise group and a passive group. The exercise group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks. Blood samples will be taken to measure proteolytic matrix metalloproteinases (MMP) as an indicator of neurological inflammation. Secondary measures will also be taken to evaluate patient-reported outcomes regarding gait, sleep, depression, anxiety, fatigue, and quality of life. The study is currently ongoing, so the results are not yet published. From an ethical perspective the passive group will also be offered the opportunity to perform the same exercises at the end of the trial.
Abstract
BACKGROUND The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS. METHODS In this two-armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0-4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6. DISCUSSION To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology. TRIAL REGISTRATION DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform.