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Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.
Wauters, L, Van Oudenhove, L, Accarie, A, Geboers, K, Geysen, H, Toth, J, Luypaerts, A, Verbeke, K, Smokvina, T, Raes, J, et al
Gut microbes. 2022;14(1):2031695
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Previous research has shown a bidirectional relationship between the gut and psychological stress, which could be mediated by intestinal permeability followed by an immune and inflammatory response. However, the exact mechanisms of this relationship are yet to be elucidated. This randomised, double-blind, placebo-controlled trial evaluated the beneficial effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress markers during a public speech in healthy students. Participants consumed either milk containing Lactobacillus rhamnosus CNCM I-3690 or acidified milk twice daily for four weeks to assess subjective and objective stress markers and markers of intestinal permeability. Lactobacillus rhamnosus CNCM I-3690 reduced the stress-induced hyperpermeability to mannitol and subjective stress markers (State-Trait Anxiety Inventory/ STAI). A subgroup of healthy students with stress-induced cortisol >P90 of baseline showed a reduction in perceived stress score following Lactobacillus rhamnosus CNCM I-3690 intervention. To evaluate the additional effects of Lactobacillus rhamnosus CNCM I-3690 on stress and gut health, further robust studies are needed. Healthcare professionals can use the findings of this study to understand the anxiolytic effects of Lactobacillus rhamnosus CNCM I-3690.
Abstract
Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.
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Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial.
Wang, J, Chang, E, Jiang, Y
European journal of physical and rehabilitation medicine. 2022;58(4):558-564
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Stroke refers to a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. It has the characteristics of rapid onset, high morbidity, high mortality, and high disability. After a stroke, various dysfunction can be caused, and dysphagia is one of the most common symptoms. The acidity of vitamin C can promote the secretion of saliva by stimulating the tongue, which can accelerate the swallowing action, thereby improving the swallowing function. The aim of this study was to explore the effects of vitamin C stimulation on the rehabilitation process, Nourishment State Index and immune function indicator of stroke patients with dysphagia. This study is a randomised controlled trial which enrolled 120 participants with dysphagia. The participants were randomly assigned into control group and vitamin C stimulation group, with 60 cases in each group. Results show that vitamin C acid stimulation significantly improves rehabilitation, and the Nourishment State Index and Immune Function Index of stroke patients with dysphagia. Authors conclude that Vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote post-operative recovery of patients. Thus, vitamin C stimulation therapy can be widely used in stroke rehabilitation management.
Abstract
BACKGROUND Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. AIM: The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. DESIGN This is a prospective cohort study. SETTING This study was conducted at our hospital. POPULATION We analyzed stroke patients with dysphagia. METHODS A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG. RESULTS Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group. CONCLUSIONS Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management. CLINICAL REHABILITATION IMPACT Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.
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Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.
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Coping Strategies Influence Cardiometabolic Risk Factors in Chronic Psychological Stress: A Post Hoc Analysis of A Randomized Pilot Study.
Armborst, D, Bitterlich, N, Alteheld, B, Rösler, D, Metzner, C, Siener, R
Nutrients. 2021;14(1)
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Chronic psychological stress is increasingly recognized as a significant contributor to mental and physiological disorders in modern societies. The individual response to chronic stressors and resulting disorders depends on numerous factors. The aim of this study was to investigate the cardiometabolic risk profile in participants with ‘high’ and ‘very high’ chronic stress loads and the impact of positive and negative coping factors used. This study is a post hoc analysis of a randomised pilot study. For this analysis, baseline data were available for 62 chronic psychologically stressed participants, of whom 61 participants (43 women and 18 men) were included in the intention-to-treat (ITT) population. Results indicate that: - perceiving high chronic stress is significantly associated with the criteria of the metabolic syndrome. - on the contrary, a very high perceived chronic stress load seemed to be rather associated with mental health risk than with cardiometabolic risk. - inflammation and oxidative stress markers significantly correlated with cardiometabolic risk parameters. - stress load can be coped with in diverse ways and that the coping strategy is crucial for cardiometabolic risk. Authors conclude that long-term studies are necessary to examine further adaptations to chronic stress and to evaluate individual stress-management strategies.
Abstract
Chronic psychological stress can result in physiological and mental health risks via the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal activity and emotion-focused coping strategies. The impact of different stress loads on cardiometabolic risk is poorly understood. This post hoc analysis of a randomized pilot study was conducted on 61 participants (18-65 years of age) with perceived chronic stress. The Perceived Stress Questionnaire (PSQ30), Psychological Neurological Questionnaire (PNF), anthropometric, clinical and blood parameters were assessed. Subjects were assigned to 'high stress' (HS; PSQ30 score: 0.573 ± 0.057) and 'very high stress' (VHS; PSQ30 score: 0.771 ± 0.069) groups based on the PSQ30. Morning salivary cortisol and CRP were elevated in both groups. Visceral adiposity, elevated blood pressure and metabolic syndrome were significantly more frequent in the HS group vs. the VHS group. The fatty liver index (FLI) was higher (p = 0.045), while the PNF score was lower (p < 0.001) in the HS group. The HS group was comprised of more smokers (p = 0.016). Energy intake and physical activity levels were similar in both groups. Thus, high chronic stress was related to visceral adiposity, FLI, elevated blood pressure and metabolic syndrome in the HS group, while very high chronic stress was associated with psychological-neurological symptoms and a lower cardiometabolic risk in the VHS group, probably due to different coping strategies.
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Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.
Song, SJ, Wang, J, Martino, C, Jiang, L, Thompson, WK, Shenhav, L, McDonald, D, Marotz, C, Harris, PR, Hernandez, CD, et al
Med (New York, N.Y.). 2021;2(8):951-964.e5
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Studies on model organisms show that foetal development can be modulated by microbial products from the pregnant mother’s microbiota, and early colonisation is critical for immune system development. However, natural transmission and colonisation of maternal microbes is impaired by caesarean section (CS) delivery. The aim of this study was to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. This study is a large observational study of 177 infants born to 174 mothers. Physicians assessed healthy mothers who were set to deliver vaginally or by scheduled CS. Results demonstrate that microbial differences associated with delivery mode can be reduced by exposure to a vaginal microbial source at birth. In fact, birth mode significantly differentiated infant gut and skin microbiome development, and that seeding worked to adjust the trajectory of CS-delivered infants through partial restoration of microbiome features associated with a vaginal delivery. Authors conclude that restoring natural exposures at birth may be one way to reduce the risk of CS-associated diseases such as obesity, asthma, allergies, and immune disfunctions. However, randomised clinical trials on large cohorts are needed to gain conclusive evidence for microbial restoration at birth improving health outcomes.
Abstract
BACKGROUND Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
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Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME).
Lupo, GFD, Rocchetti, G, Lucini, L, Lorusso, L, Manara, E, Bertelli, M, Puglisi, E, Capelli, E
Scientific reports. 2021;11(1):7043
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Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME) is a severe multisystemic disease. The main symptom is persistent unexplained fatigue, it has inflammatory symptoms, is characterized by an abnormal immune response and dysfunction of energy metabolism. Recent studies suggest strong correlations between dysbiosis and other conditions such as intestinal disorders, autoimmune conditions, cancer and several neurological disorders. In the case of CFS/ME, some studies have shown an altered composition of the gut and oral microbiomes. In this study the oral and intestinal bacterial composition of CFS/ME patients were analysed and compared to a group of relatives and to a control population outside the families. This was to identify a possible effect of lifestyle habits and a microbial profile of CFS/ME syndrome. The study showed significant variations in both the intestinal and oral bacteria composition between CFS/ME patients, their relatives and external controls. There is a lot of interesting detail about the levels of specific bacteria in each group. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.
Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe multisystemic disease characterized by immunological abnormalities and dysfunction of energy metabolism. Recent evidences suggest strong correlations between dysbiosis and pathological condition. The present research explored the composition of the intestinal and oral microbiota in CFS/ME patients as compared to healthy controls. The fecal metabolomic profile of a subgroup of CFS/ME patients was also compared with the one of healthy controls. The fecal and salivary bacterial composition in CFS/ME patients was investigated by Illumina sequencing of 16S rRNA gene amplicons. The metabolomic analysis was performed by an UHPLC-MS. The fecal microbiota of CFS/ME patients showed a reduction of Lachnospiraceae, particularly Anaerostipes, and an increased abundance of genera Bacteroides and Phascolarctobacterium compared to the non-CFS/ME groups. The oral microbiota of CFS/ME patients showed an increase of Rothia dentocariosa. The fecal metabolomic profile of CFS/ME patients revealed high levels of glutamic acid and argininosuccinic acid, together with a decrease of alpha-tocopherol. Our results reveal microbial signatures of dysbiosis in the intestinal microbiota of CFS/ME patients. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.
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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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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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A Large Randomized Trial: Effects of Mindfulness-Based Stress Reduction (MBSR) for Breast Cancer (BC) Survivors on Salivary Cortisol and IL-6.
Lengacher, CA, Reich, RR, Paterson, CL, Shelton, M, Shivers, S, Ramesar, S, Pleasant, ML, Budhrani-Shani, P, Groer, M, Post-White, J, et al
Biological research for nursing. 2019;21(1):39-49
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Breast cancer survivors (BCS) often experience physiological and psychological stressors related to their diagnosis and treatment, and a disruption of cortisol function can affect cancer risk and progression. Increased levels of the stress hormone cortisol and interleukin-6 (IL-6), a pro-inflammatory immune mediator, have been associated with acute and chronic stress levels. Mindfulness-Based Stress Reduction (MBSR) is a clinical stress-reducing program, which has been found to decrease psychological and physical symptoms associated with stress. The purpose of this randomised study, involving 299 BCS, was to evaluate the efficacy of MBSR in reducing cortisol and IL-6 levels, compared to a usual-care control treatment. Statistically significant reductions in cortisol levels were seen after the delivery of the MBSR program at both time points (week 1 and 6), and at week 6 only for IL-6. There was no significant difference in change in cortisol or IL6 levels over time between the MBSR and the usual-care groups. An association was observed between levels of IL-6 and psychological and physical symptoms and quality of life, but not for cortisol. The authors conclude that MBSR can alleviate the stress response in the short term for breast cancer survivors.
Abstract
Breast cancer survivors (BCS) often experience psychological and physiological symptoms after cancer treatment. Mindfulness-based stress reduction (MBSR), a complementary and alternative therapy, has reduced subjective measures of stress, anxiety, and fatigue among BCS. Little is known, however, about how MBSR affects objective markers of stress, specifically the stress hormone cortisol and the pro-inflammatory cytokine interleukin-6 (IL-6). In the present study, BCS ( N = 322) were randomly assigned to a 6-week MBSR program for BC or usual-care control. Measurements of cortisol, IL-6, symptoms, and quality of life were obtained at orientation and 6 weeks. Cortisol and IL-6 were also measured prior to and after the MBSR(BC) class Weeks 1 and 6. The mean age of participants was 56.6 years and 69.4% were White non-Hispanic. Most had Stage I (33.8%) or II (35.7%) BC, and 35.7% had received chemotherapy and radiation. Cortisol levels were reduced immediately following MBSR(BC) class compared to before the class Weeks 1 and 6 (Wilcoxon-signed rank test; p < .01, d = .52-.56). IL-6 was significantly reduced from pre- to postclass at Week 6 (Wilcoxon-signed rank test; p < .01, d = .21). No differences were observed between the MBSR(BC) and control groups from baseline to Week 6 using linear mixed models. Significant relationships with small effect sizes were observed between IL-6 and both symptoms and quality of life in both groups. Results support the use of MBSR(BC) to reduce salivary cortisol and IL-6 levels in the short term in BCS.
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Effects of a polysaccharide-based multi-ingredient supplement on salivary immunity in non-elite marathon runners.
Roca, E, Cantó, E, Nescolarde, L, Perea, L, Bayes-Genis, A, Sibila, O, Vidal, S
Journal of the International Society of Sports Nutrition. 2019;16(1):14
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Competing in very strenuous events such as marathons imposes severe metabolic stress and causes acute responses that may negatively alter the immune system. The aim of this study is to determine the impact of Advanced Ambrotose© complex powder (AA) on the levels of salivary secretory Immunoglobulin A (sIgA) [an antibody that plays a critical role in mucosal immunity], pro-inflammatory chemokines and anti-inflammatory proteins before and after running a marathon in non-elite marathoners. The study recruited 41 male participants which were randomly assigned to one of the two groups. Twenty participants (48%) received AA supplementation prior to the race (AA group), whilst the rest did not receive AA supplementation. Supplementation was received for 15 days prior to the marathon. Results indicate that there were no significant differences in age, weight, height, and training were found between runners who received AA supplementation and those who did not. However, findings show significant changes in salivary biomarkers of immune function in healthy, non-elite athletes before and after a strenuous exercise. Authors conclude that AA supplementation produces changes in salivary immunity that may have a positive effect on immunity before and after a marathon.
Abstract
BACKGROUND Extreme exercise may alter the innate immune system. Glycans are involved in several biological processes including immune system regulation. However, limited data regarding the impact of glycan supplementation on immunological parameters after strenuous exercise are available. We aimed to determine the impact of a standardized polysaccharide-based multi-ingredient supplement, Advanced Ambrotose© complex powder (AA) on salivary secretory Immunoglobulin A (sIgA) and pro- and anti-inflammatory protein levels before and after a marathon in non-elite runners. METHODS Forty-one male marathon runners who completed the 42.195 km of the 2016 Barcelona marathon were randomly assigned to two study groups. Of them, n = 20 (48%) received the AA supplement for 15 days prior the race (AA group) and n = 21 (52%) did not receive any AA supplement (non-AA group). Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, pro-inflammatory chemokines (Gro-alpha, Gro-beta, MCP-1) and anti-inflammatory proteins (Angiogenin, ACRP, Siglec 5) were determined using commercially ELISA kits in saliva supernatant. Biochemical parameters, including C-reactive protein, cardiac biomarkers, and blood hemogram were also evaluated. RESULTS Marathon runners who did not receive the AA supplement experienced a decrease of salivary sIgA and pro-inflammatory chemokines (Gro-alpha and Gro-beta) after the race, while runners with AA supplementation showed lower levels of anti-inflammatory chemokines (Angiogenin). Gro-alpha and Gro-beta salivary levels were lower before the race in the AA group and correlated with blood leukocytes and platelets. CONCLUSIONS Changes in salivary sIgA and inflammatory chemokines, especially Gro-alfa and Gro-beta, were observed in marathon runners supplemented with AA prior to the race. These findings suggested that AA may have a positive effect on immune response after a strenuous exercise.