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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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Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.
Goncalves-Mendes, N, Talvas, J, Dualé, C, Guttmann, A, Corbin, V, Marceau, G, Sapin, V, Brachet, P, Evrard, B, Laurichesse, H, et al
Frontiers in immunology. 2019;10:65
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This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in a sample of 38 deficient elderly persons, over 65-year olds, could improve influenza seroprotection and immune response. Vitamin D is known to both potentiate the innate immune response and inhibit the adaptive system, and so potentially modulate vaccination response. The participants were randomised into two arms: vitamin D supplementation group (D) and placebo group (P). The D group received 100,000 IU/15 days of cholecalciferol over a 3-month period after which both groups were given the influenza vaccine, and their blood was evaluated 28 days later. Several immune biomarkers were analysed including plasma cytokine profiles, phagocyte ROS production, and lymphocyte cells phenotyping to determine if Vitamin D enhanced immune response to the vaccination. No differences were found in serum ROS and antibody markers. However, Vitamin D supplementation did promote a higher TGFβ plasma level in response to influenza vaccination. Taken together, these results suggest that vitamin D supplementation is not an effective way to improve antibody response to influenza vaccine in deficient elderly people.
Abstract
Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.
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Daily Nutritional Supplementation with Vitamin D₃ and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial.
Ashenafi, S, Amogne, W, Kassa, E, Gebreselassie, N, Bekele, A, Aseffa, G, Getachew, M, Aseffa, A, Worku, A, Hammar, U, et al
Nutrients. 2019;11(1)
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Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD3) deficiency. VitD3 together with phenylbutyrate (PBA) can induce an antimicrobial peptide called cathelicidin which has anti-viral properties. VitD3 and PBA can also enhance autophagy, a physiological process known to enhance destruction of intracellular viruses. The aim of this double-blind, placebo-controlled trial was to evaluate whether vitD3 + PBA could reduce viral replication and restore immune and nutritional status in HIV infection. 173 previously untreated HIV patients were randomised to receive either 5000 IU vitD3 and 500 mg PBA or placebos for 16 weeks with follow-up of a further 8 weeks. Most subjects had low plasma vitD3 levels at baseline which increased significantly in the vitD3 + PBA group compared with placebo at weeks 4, 8 and 16, indicating good compliance and response to the treatment. There were no statistical differences in any of the measured outcomes, including viral load, CD4 cells, CD8 cells and body mass index, between treatment and placebo group at any point during the study and follow-up.
Abstract
Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD₃) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD₃ (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, n = 197) and per-protocol (n = 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D₃ levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4⁺ (median 410 cells/µL), and elevated CD8⁺ (median 930 cells/µL) T cell counts. Most subjects were vitD₃ deficient at enrolment, but a gradual and significant improvement of vitD₃ status was demonstrated in the vitD₃ + PBA group compared with placebo (p < 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4⁺ or CD8⁺ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD₃ + PBA for 16 weeks was well-tolerated and effectively improved vitD₃ status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.
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A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold.
Ramalingam, S, Graham, C, Dove, J, Morrice, L, Sheikh, A
Scientific reports. 2019;9(1):1015
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The common cold is a viral upper respiratory tract infection which affects adults and children worldwide, often multiple times a year. A large number of viruses cause these infections, making targeted antiviral treatment impractical. This small, randomised, controlled pilot trial (not blinded) of 68 adults aimed to assess the impact of salt-water nasal washing and throat gargling as many times as required (on average 3 times a day for 5 days) within 48 hours of symptom on-set on study recruitment and retention, as well as acceptability, symptom duration and viral shedding. The researchers found that nasal irrigation and gargling with a saline solution was acceptable to study participants. Illness duration was shortened by 1.9 days in the intervention arm, with significant reductions in the duration of runny nose, blocked nose, sneezing, cough and hoarseness of voice. The average quality of life score was also higher in the intervention arm, although this failed to reach significance. Viral shedding was higher in the intervention arm, with over the counter medication use 36% lower. There was also a lower rate of infection spread within households for the intervention arm. The authors call for a larger, placebo controlled trial to confirm these findings. Nutrition Practitioners supporting immunity in relation to the common cold virus may want to discuss the use of saline nasal irrigation with their clients as a simple measure to reduce symptoms and spread.
Abstract
There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log10/day (p = 0.04). We hence need a larger trial to confirm our findings.
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Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial.
Loesche, MA, Farahi, K, Capone, K, Fakharzadeh, S, Blauvelt, A, Duffin, KC, DePrimo, SE, Muñoz-Elías, EJ, Brodmerkel, C, Dasgupta, B, et al
The Journal of investigative dermatology. 2018;138(9):1973-1981
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Chronic plaque psoriasis is an immune-mediated disease of the skin and joints. A growing appreciation of the role of the innate immune system in psoriasis pathogenesis stems from the prominent role of inflammatory cytokines and cells associated with innate immunity in the disease and associations observed between psoriasis and genetic variations involved in innate immunity. The aim of this study was to assess changes of the skin microbiome in the setting of a longitudinal phase 3b study of patients receiving up to 2 years of ustekinumab therapy. Results show that prior to treatment, there were minor, body-site specific differences in microbial diversity and composition when comparing lesional with non-lesional skin. Microbial heterogeneity was greater in lesional skin than non-lesional skin. During ustekinumab treatment, the composition of microbiota diverged further between lesional and non-lesional skin across body sites. The divergence observed between lesional and non-lesional skin during ustekinumab treatment varied by body site. Authors conclude that their findings may help inform future study design and it may also have medically relevant implications for diagnostics and therapeutics involving the skin microbiome.
Abstract
Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.
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Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial.
Savino, F, Garro, M, Montanari, P, Galliano, I, Bergallo, M
The Journal of pediatrics. 2018;192:171-177.e1
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The causes of infant colic are unknown, but growing evidence shows a possible link with the gut microbiome. Increased inflammation has also been found in infants with colic, and this could be linked to dysbiosis. This double-blind, placebo-controlled clinical trial investigated whether supplementation with the probiotic Lactobacillus reuteri (L reuteri) DSM 17938 could reduce the crying time and modify inflammation in a group of infants with colic. Infants enrolled in the trial were less than 12 weeks old, with a healthy birth weight and predominantly breastfed. Infants with colic were given either 5 million colony-forming units (CFU) of L reuteri DSM 17938 or a placebo daily for 1 month. Crying times were significantly shortened among infants with colic given the probiotic, whilst the concentration of transcription factors for cells that help to regulate the immune system increased significantly. Infants treated with the probiotic showed an increase in the percentage of Lactobacillus and a decrease in the inflammatory marker faecal calprotectin. The authors concluded that their findings support the hypothesis that dysbiosis and inflammation may contribute to the onset of infant colic.
Abstract
OBJECTIVES To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic. STUDY DESIGN A double-blind, placebo-controlled randomized trial was conducted in primary care in Torino from August 1, 2015 to September 30, 2016. Patients suffering from infantile colic were randomly assigned to receive daily oral L reuteri (1 × 108 colony forming unit) or placebo for 1 month. Daily crying times were recorded in a structured diary. FOXP3 and RORγ messenger RNA in the peripheral blood was assessed with real-time TaqMan reverse transcription polymerase chain reaction. Gut microbiota and fecal calprotectin were evaluated. RESULTS After infants with colic were supplemented with L reuteri DSM 17938 for 30 days, crying times were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (74.67 ± 25.04 [IQR = 79] minutes /day vs 147.85 [IQR = 135] minutes /day [P = .001]). The FOXP3 concentration increased significantly (P = .009), resulting in decreased RORγ/FOXP3 ratios: 0.61 (IQR = 0.60) at day 0 and 0.48 (IQR = 0.28) at day 30 (P = .028). Furthermore, the probiotic increased the percentage of Lactobacillus (P = .049) and decreased fecal calprotectin (P = .0001). CONCLUSIONS Infants with colic treated with L reuteri for 30 days had a significantly decreased crying time and an increased FOXP3 concentration, resulting in a decreased RORγ/FOXP3 ratio. The treatment reduced fecal calprotectin. TRIAL REGISTRATION ClinicalTrials.gov: NCT00893711.
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Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge.
Mandile, R, Picascia, S, Parrella, C, Camarca, A, Gobbetti, M, Greco, L, Troncone, R, Gianfrani, C, Auricchio, R
Alimentary pharmacology & therapeutics. 2017;46(4):440-446
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A gluten-free diet is currently the only reliable therapeutic approach for coeliac disease (CD), an immune-mediated condition where eating gluten causes intestinal inflammation. Hydrolysing wheat flour with a sourdough enriched with lactobacilli and fungal proteases has been shown to be effective in reducing the gluten in the bread baked with it to less that 10ppm (which should be safe for CD patients). This randomised prospective study was designed to confirm the lack of an immunological response to the hydrolysed gluten in CD patients, both in vitro and in vivo. 20 CD patients who were in clinical remission and had followed a gluten-free diet (GFD) for at least three years were enrolled into this study and randomised to receive either natural wheat (10g gluten per day) or hydrolysed wheat (10g hydrolysed gluten per day) for three days. In vitro studies using intestinal cells from three of the study participants showed that the hydrolysed gluten did not elicit an immune response, whilst the natural gluten did. In vivo, there were no statistically significant increases in immune reactivity in the hydrolysed gluten patients, and no-one in this group experienced any symptoms. In the natural wheat group significant increases in immune reactivity to gluten were seen although only one person experienced symptoms (abdominal pain). The authors conclude that wheat flour hydrolysed with an enriched sourdough may be an alternative for the CD patient’s diet.
Abstract
BACKGROUND A gluten-free diet is currently the only reliable therapeutic strategy that is approved for coeliac disease (CD). For many patients, however, compliance remains inadequate. AIM: To investigate the immunogenicity of wheat flour that was pre-treated with selected lactobacilli and fungal proteases (hydrolysed wheat gluten) in coeliac patients. METHODS The immunogenicity of hydrolysed wheat gluten was evaluated both in vitro in intestinal T cell lines (TCLs) and in vivo in treated CD patients after a short-term gluten challenge. Twenty treated CD patients were enrolled and equally randomised into two groups. The patients ate bread that was prepared with hydrolysed wheat flour or natural wheat flour (10 g of gluten/d for 3 days). The interferon (INF)-γ responses to natural gliadin and a 33-mer peptide were assessed by the enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) both before and 6 days after the start of the challenge. RESULTS Hydrolysed wheat was not able to activate the TCLs from the coeliac intestinal mucosa. Consistent with the in vitro results, no significant increase in INF-γ secretion was observed in patients who consumed hydrolysed wheat flour. Conversely, the consumption of natural wheat gluten mobilised INF-γ secreting cells in the blood (P<.05). CONCLUSIONS We confirm that fermentation of wheat flour with sourdough lactobacilli and fungal proteases is capable of abolishing the T cell immunogenicity of gluten in coeliac patients. Our data also validate the short-term oral challenge as a useful tool for testing the efficacy of novel therapeutic approaches.
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Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort).
Singh, S, Bhansali, A
BMC dermatology. 2016;16(1):12
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As an immune-mediated chronic inflammatory skin condition, psoriasis is associated with obesity, metabolic syndrome, diabetes, and cardiovascular disease. Medications capable of sensitising insulin, such as Metformin and Pioglitazone, have also shown benefits in improving factors associated with metabolic syndrome and psoriasis. This single-centre, parallel-group, randomised, open-label with blinded endpoint evaluated the effects of Metformin with Pioglitazone and placebo in psoriatic patients. Patients with mild-to-moderate psoriasis were randomised to a topical treatment cohort to take 1000 mg metformin daily or 30 mg pioglitazone or placebo groups for 12 weeks. Each participant received a topical ointment containing 5% coal tar during the treatment period. The Metformin and Pioglitazone groups showed significant improvements in psoriasis and metabolic syndrome parameters, such as fasting plasma glucose, total cholesterol, and triglyceride levels, after 12 weeks of treatment. The treatment with metformin resulted in significant improvements in weight, BMI, waist circumference, FPG, triglycerides, and total cholesterol, while the treatment with pioglitazone resulted in significant improvements in FPG, triglycerides, systolic and diastolic blood pressure, cholesterol levels, and LDL cholesterol levels. There was no significant improvement in inflammatory cytokine levels in any group. For further evaluation of the beneficial effects of insulin-sensitising drugs in patients suffering from psoriasis and metabolic syndrome, more robust studies are needed. The study results can be used by healthcare professionals to better understand how insulin-sensitising drugs may decrease the risk of diabetes, cardiovascular disease, and psoriasis in psoriasis patients with metabolic syndrome.
Abstract
BACKGROUND Increased prevalence of metabolic syndrome (MS) is observed in psoriasis. Metformin has shown improvement in cardiovascular risk factors while pioglitazone demonstrated anti proliferative, anti-inflammatory and anti angiogenic effects. Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS). METHODS Single centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS. RESULTS Statistically significant improvement was observed in Psoriasis Area and Severity Index (PASI), Erythema, Scaling and Induration (ESI) and Physician global assessment (PGA) scores in pioglitazone (p values - PASI = 0.001, ESI = 0.002, PGA = 0.008) and metformin groups (p values - PASI = 0.001, ESI = 0.016, PGA = 0.012) as compared to placebo. There was statistically significant difference in percentage of patients achieving 75 % reduction in PASI and ESI scores in metformin (p value - PASI = 0.001, ESI = 0.001) and pioglitazone groups (p vaue - PASI = 0.001, ESI = 0.001). Significant improvement was observed in fasting plasma glucose (FPG) and triglycerides levels in metformin and pioglitazone arms. Significant improvement was noted in weight, BMI, waist circumference, FPG, triglycerides and total cholesterol after 12 weeks of treatment with metformin while pioglitazone showed improvement in FPG, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and LDL cholesterol levels. There was no difference in pattern of adverse drug reaction in three groups. CONCLUSION Insulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients. TRIAL REGISTRATION CTRI Registration Number: CTRI/2011/12/002252 . Registered on 19/12/2011.
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Effect of the Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSanTM, on Symptoms, Fatigue and Quality of Life in Patients with Crohn's Disease in a Randomized Single-Blinded Placebo Controlled Study.
Therkelsen, SP, Hetland, G, Lyberg, T, Lygren, I, Johnson, E
PloS one. 2016;11(7):e0159288
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AndoSanTM is a medicinal mushroom supplement based on Agaricus Blazei Murrill (ABM), but also contains Hericium erinaceus (lion’s mane, 14.7%) and Grifola frondosa (Maitake, 2.9), and contains immune modulatory beta-glucans as well as other bioactive compounds. This single-centre randomised two-armed patient-blinded study was designed to determine whether daily oral intake of AndoSanTM could improve clinical symptoms, fatigue and quality of life in patients with Crohn’s Disease (CD). Patients received either AndoSanTM 60ml per day or placebo for 21 days and were evaluated before start of treatment and at day 14 and 21. Outcome measures were the Crohn’s Disease Activity Index (SCDAI), the self-reported health-related quality of life (HRQoL), a fatigue questionnaire, blood parameters and faecal calprotectin (a marker for intestinal inflammation). 25 patients in each study arm completed the trial and were included in study analysis. There was a statistically significant improvement inf SCDAI in the AndoSanTM group, in particular for number of liquid stools and pain, but not the placebo group, although the difference between the groups was not statistically significant. There were no statistically significant differences for fatigue, quality of life, blood tests or calprotectin. No adverse effects were reported. The authors conclude that AndoSanTM could be safe to complement conventional medication to relieve symptoms in CD patients.
Abstract
BACKGROUND Ingestion of AndoSanTM, based on the mushroom Agaricus blazei Murill, has previously shown an anti-inflammatory effect through reduction of pro-inflammatory cytokines in healthy individuals and patients with Crohn's disease (CD). In this randomized single-blinded placebo-controlled study we examined whether intake of AndoSanTM also resulted in clinical effects. METHODS AND FINDINGS 50 patients with symptomatic CD were randomized for oral daily consumption of AndoSanTM or placebo for a 21-day experimental period, in this per-protocol study. Patients reported validated scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSanTM group (n = 25) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.52 (4.64-6.40), 4.48 (3.69-5.27) and 4.08 (3.22-4.94) (p<0,001). We found significant improvements in symptom score for both genders in the AndoSanTM group, and no significant changes in the placebo (n = 25) group. There were however no significant differences between the groups (p = 0.106), although a marginal effect in symptom score for men (p = 0.054). There were comparable improvements in physical, mental and total fatigue for both groups. HRQoL versus baseline were at day 21 improved for bodily pain and vitality in the AndoSanTM group and for vitality and social functioning in the placebo group. No crucial changes in general blood samples and fecal calprotectin were detected. CONCLUSIONS The results from this single-blinded randomized clinical trial shows significant improvement on symptoms, for both genders, in the AndoSanTM group, but no significant differences between the study groups. The results on fatigue, HRQoL, fecal calprotectin and blood samples were quite similar compared with placebo. The patients did not report any harms or unintended effects of AndoSanTM. CD patients with mild to moderate symptoms may have beneficiary effects of AndoSanTM as a safe supplement in addition to conventional medication. TRIAL REGISTRATION ClinicalTrials.gov NCT01496053.
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Effect of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™, on Symptoms, Fatigue and Quality of Life in Patients with Ulcerative Colitis in a Randomized Single-Blinded Placebo Controlled Study.
Therkelsen, SP, Hetland, G, Lyberg, T, Lygren, I, Johnson, E
PloS one. 2016;11(3):e0150191
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AndoSanTM is a medicinal mushroom supplement based on Agaricus Blazei Murrill (ABM), but also contains Hericium erinaceus (lion’s mane, 14.7%) and Grifola frondosa (Maitake, 2.9), and contains immune modulatory beta-glucans as well as other bioactive compounds. This single-centre randomised two-armed patient-blinded study was designed to determine whether daily oral intake of AndoSanTM could improve clinical symptoms, fatigue and quality of life in patients with mild to moderate ulcerative colitis (UC). Patients received either AndoSanTM 60ml per day or placebo for 21 days and were evaluated before start of treatment and at day 14 and 21. Outcome measures were a modified Clinical Activity Index (CAI)), the self-reported health-related quality of life (HRQoL), a fatigue questionnaire, blood parameters and faecal calprotectin (a marker for intestinal inflammation). 24 patients in the AndoSanTM arm and 26 in the placebo arm completed the trial and were included in study analysis. Compared with baseline only the patients in the AndoSan™ group reported significant reductions of symptoms, fatigue and quality of life which were significantly better than in the placebo group. There were no significant changes in blood parameters in either group. There was no change in calprotectin in the AndoSanTM group but a significant worsening in the placebo group. No adverse effects were reported. A limitation of the study is that it was only blinded to the patients but not to the investigators. The authors conclude that AndoSan™ may be beneficial as a supplement to conventional medication in patients with mild to moderate UC.
Abstract
BACKGROUND Ingestion of AndoSan™, based on the mushroom Agaricus blazei Murill, has previously been shown to exhibit anti-inflammatory effects because of reduction of pro-inflammatory cytokines in healthy individuals and patients with ulcerative colitis. In this randomized single-blinded placebo controlled study we examined whether intake of AndoSan™ also resulted in clinical effects. METHODS AND FINDINGS 50 patients with symptomatic ulcerative colitis were block-randomized and blinded for oral daily intake of AndoSan™ or placebo for the 21 days' experimental period. The patients reported scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSan™ group (n = 24) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.88 (4.92-6.83), 4.71 (3.90-5.52) (p = 0.002) and 4.50 (3.70-5.30) (p = 0.001). Corresponding improved mean scores (±SD) for total fatigue were 16.6 (5.59), 14.1 (4.50) (p = 0.001) and 15.1 (4.09) (p = 0.023). These scores in the placebo group (n = 26) were not improved. When comparing the two study groups using mixed model statistics, we found significant better scores for the AndoSan™-patients. HRQoL for dimensions bodily pain, vitality, social functioning and mental health improved in the AndoSan™ group. There were no alterations in general blood samples and fecal calprotectin. CONCLUSIONS Beneficiary effects on symptoms, fatigue and HRQoL from AndoSan™ consumption were demonstrated in this per-protocol study, supporting its use as a supplement to conventional medication for patients with mild to moderate symptoms from ulcerative colitis. The patients did not report any harms or unintended effects of AndoSan™ in this study. TRIAL REGISTRATION ClinicalTrials.gov NCT01496053.