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.

Abstract

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1β, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.

Abstract

The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.

Abstract

OBJECTIVE To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. DESIGN Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. MAIN OUTCOME MEASURES The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. RESULTS In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. CONCLUSIONS The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. TRIAL REGISTRATION ClinicalTrials.gov NCT02012790.

Abstract

BACKGROUND Malnutrition is inevitable in patients with Coronavirus Disease 2019 (COVID-19) due to its effect on the gastrointestinal system, immune system, and high metabolic activity. However, the prevalence of malnutrition and its outcomes is uncertain. This study aimed to investigate the prevalence and outcome of malnutrition among patients with COVID-19. METHOD A comprehensive search was conducted in PubMed/Medline; Science direct and LILACS from December 29, 2019 to September, 2020 without language restriction. All observational studies reporting the prevalence of malnutrition were included while case reports and reviews were excluded. The data were extracted with two independent authors with a customized format and the disagreements were resolved by the other authors. The methodological quality of included studies was evaluated using a standardized critical appraisal tool. RESULTS A total of 511 articles were identified from different databases and 27 articles were selected for evaluation after the successive screening. Fourteen articles with 4187 participants were included. The pooled prevalence of malnutrition among hospitalized patients with COVID-19 was 49.11% (95% CI: 31.67 to 66.54). The odd of mortality among patients COVID-19 with malnutrition was 10 times more likely as compared to those who were well-nourished. CONCLUSION The prevalence of malnutrition and mortality associated with malnutrition among COVID-19 hospitalized patients was very high which entails a mitigating strategy by different stakeholders to prevent and manage malnutrition and its outcomes. REGISTRATION This systematic review was registered in Prospero's international prospective register of systematic reviews (CRD42020215396).

Abstract

BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.

Abstract

OBJECTIVES To compare hospitalisation rates, intensive care unit (ICU) admissions and mortality for patients with COVID-19 who were consistently inactive, doing some activity or consistently meeting physical activity guidelines. METHODS We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. We linked each patient's self-reported physical activity category (consistently inactive=0-10 min/week, some activity=11-149 min/week, consistently meeting guidelines=150+ min/week) to the risk of hospitalisation, ICU admission and death after COVID-19 diagnosis. We conducted multivariable logistic regression controlling for demographics and known risk factors to assess whether inactivity was associated with COVID-19 outcomes. RESULTS Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20; 95% CI 1.10 to 1.32), admission to the ICU (OR 1.10; 95% CI 0.93 to 1.29) and death (OR 1.32; 95% CI 1.09 to 1.60) due to COVID-19 than patients who were doing some physical activity. CONCLUSIONS Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.

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.

Abstract

Muscle fatigue and cognitive disturbances persist in patients after recovery from acute COVID-19 disease. However, there are no specific treatments for post-COVID fatigue. Objective: To evaluate the efficacy and safety of the health supplements ImmunoSEB (systemic enzyme complex) and ProbioSEB CSC3 (probiotic complex) in patients suffering from COVID-19 induced fatigue. A randomized, multicentric, double blind, placebo-controlled trial was conducted in 200 patients with a complaint of post-COVID fatigue. The test arm (n = 100) received the oral supplements for 14 days and the control arm (n = 100) received a placebo. Treatment efficacy was compared using the Chalder Fatigue scale (CFQ-11), at various time points from days 1 to 14. The supplemental treatment resulted in resolution of fatigue in a greater percentage of subjects in the test vs. the control arm (91% vs. 15%) on day 14. Subjects in the test arm showed a significantly greater reduction in total as well as physical and mental fatigue scores at all time points vs. the control arm. The supplements were well tolerated with no adverse events reported. This study demonstrates that a 14 days supplementation of ImmunoSEB + ProbioSEB CSC3 resolves post-COVID-19 fatigue and can improve patients' functional status and quality of life.

Abstract

With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.