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Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection.
Townsend, L, Dyer, AH, Jones, K, Dunne, J, Mooney, A, Gaffney, F, O'Connor, L, Leavy, D, O'Brien, K, Dowds, J, et al
PloS one. 2020;15(11):e0240784
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Tiredness is a common symptom of Covid-19; however, it is unknown if this fatigue persists once recovered. This observational study of 128 recovered Covid-19 patients aimed to determine if fatigue persisted after recovery and whether severity of disease could predict fatigue. The results showed that post Covid-19 fatigue was reported in more than half of the participants and was particularly pronounced in females and in those with depression. Severity of disease did not predict fatigue. It was concluded that fatigue appears to outlast infection and fatigue was independent of disease severity. This study could be used by health care practitioners to understand that fatigue is common even after recovery from Covid-19 infection and women and sufferers of depression are the most susceptible.
Abstract
Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.
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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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Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
Waqas Khan, HM, Parikh, N, Megala, SM, Predeteanu, GS
The American journal of case reports. 2020;21:e925521
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Coronavirus disease (Covid-19) continues to spread globally and to date there are no proven treatments. Current treatment focuses on the management of the associated acute respiratory distress syndrome (ARDS). There are many studies demonstrating that in severe sepsis and ARDS; Vitamin C reduces systemic inflammation, prevents lung damage, reduces the duration of mechanical ventilation (MV) and the length of intensive care unit (ICU) stay in patients. This is a case report where a critically ill patient received high-dose Vitamin C intravenous (IV) infusions and recovered. A 74 year-old woman with Covid-19, developed ARDS and septic shock. Usual medications were given. She needed MV and deteriorated rapidly. On Day 7 she was administered Vitamin C (11g per 24 hours as a continuous IV infusion). Her clinical condition improved slowly after this. In this case, high dose IV Vitamin C was associated with fewer days on mechanical intervention, a shorter ICU stay and earlier recovery. These results show the importance of further investigation of IV Vitamin C to assess its efficacy in critically ill Covid-19 patients requiring mechanical ventilation and ICU care.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.
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Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome.
Chiscano-Camón, L, Ruiz-Rodriguez, JC, Ruiz-Sanmartin, A, Roca, O, Ferrer, R
Critical care (London, England). 2020;24(1):522
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Sepsis related acute respiratory disease (ARDS) is associated with Covid-19. ARDS patients can present with decreased levels of vitamin C and so by association Covid-19 patients may also have low vitamin C levels. In this cohort study, 18 Covid-19 ARDS patients of which all survived were assessed for vitamin C levels. 17 patients had undetectable levels of vitamin C and one had low levels. It was concluded that more than 90% of the patients in this study had undetectable levels of vitamin C, which may be due to several reasons, such as reduced absorption of vitamin C in the gut and decreased production. Clinicians could use this study to understand the importance of monitoring vitamin C levels in patients with Covid-19.
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Stratifying cellular metabolism during weight loss: an interplay of metabolism, metabolic flexibility and inflammation.
Tareen, SHK, Kutmon, M, de Kok, TM, Mariman, ECM, van Baak, MA, Evelo, CT, Adriaens, ME, Arts, ICW
Scientific reports. 2020;10(1):1651
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Obesity is a public health concern as it has been linked to cardiovascular diseases, type 2 diabetes and metabolic syndrome. The aim of this study was to identify and analyse expression profiles of individuals clustered by cellular metabolism centring on metabolic flexibility. This study clustered gene expression samples from a weight loss study (Yoyo study’ - Clinical Trial ID: NCT01559415) into two clusters, based on 291 genes associated with cellular metabolic fexibility. The study covers two diets: a low-calorie diet (LCD) and a very low-calorie diet (VLCD). All the participants of the study were Caucasian with a BMI between 28kg/m2 and 35 kg/m2, aged between 32 and 67 years old. Findings showed that the majority of the individuals had their metabolism associated genes downregulated after weight loss and weight maintenance, but also had an upregulation of immune system associated genes. Furthermore, individuals who had changed their metabolic profiles in response to caloric restriction had a significant retention of lost weight compared to individuals which had not changed their cluster membership. Authors conclude that their findings indicate possible cross-talk between cellular metabolism and inflammation.
Abstract
Obesity is a global epidemic, contributing significantly to chronic non-communicable diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. Metabolic flexibility, the ability of organisms to switch between metabolic substrates, is found to be impaired in obesity, possibly contributing to the development of chronic illnesses. Several studies have shown the improvement of metabolic flexibility after weight loss. In this study, we have mapped the cellular metabolism of the adipose tissue from a weight loss study to stratify the cellular metabolic processes and metabolic flexibility during weight loss. We have found that for a majority of the individuals, cellular metabolism was downregulated during weight loss, with gene expression of all major cellular metabolic processes (such as glycolysis, fatty acid β-oxidation etc.) being lowered during weight loss and weight maintenance. Parallel to this, the gene expression of immune system related processes involving interferons and interleukins increased. Previously, studies have indicated both negative and positive effects of post-weight loss inflammation in the adipose tissue with regards to weight loss or obesity and its co-morbidities; however, mechanistic links need to be constructed in order to determine the effects further. Our study contributes towards this goal by mapping the changes in gene expression across the weight loss study and indicates possible cross-talk between cellular metabolism and inflammation.
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Weight reduction improves immune system and inflammatory cytokines in obese asthmatic patients.
Al-Sharif, FM, Abd El-Kader, SM, Neamatallah, ZA, AlKhateeb, AM
African health sciences. 2020;20(2):897-902
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Asthma is a common condition characterised by attacks of obstruction, chronic inflammation and hyper-responsiveness of the airways. Obesity increases severity of asthmatic symptoms through mechanical, anatomical and/or inflammatory mechanisms. 80 adults with asthma were randomly allocated to a weight reduction programme, including aerobic exercise and a calorie reduced diet, or control group with no intervention. After 3 months, body mass index (BMI) reduced significantly in the intervention group (from 31.7 to 27.9). This was associated with significant reductions in the pro-inflammatory markers TNF-alpha, interleukin-6 and interleukin-8, and significant increases in CD4 and CD8 cell counts (important immune cells). There were no changes in the control group in any of the parameters and the results were statistically significantly better in the intervention compared to the control group. The authors conclude that weight reduction improved immunological and inflammatory markers in obese asthma patients.
Abstract
BACKGROUND Activation of immunological and systemic inflammation markers are common in obesity and asthma. OBJECTIVE The target of this study was to assess impact of weight reduction on immunological and systemic inflammation markers in obese asthma patients. MATERIAL AND METHODS Eighty asthmatic patients of both sex; their age and body mass index (BMI) mean were 38.72 ± 7.14 year and 32.65 ± 3.18 Kg/m2 respectively. Exclusion criteria included smokers, infections, vaccinations, cancer, surgery, immune system disorders and medications that may influence immune system function as anti-inflammatory medications, analgesics and anti-depressant. All subjects were randomly enrolled in weight reduction group (group A) or control group (group B). RESULTS The main findings in the present study indicated that weight reducing program in group (A) was associated with significant reduction in the mean values of IL6, TNF-α, and IL8 in addition to significant increase in the mean values of CD4 and CD8 cell count . However, findings of group (B) showed no significant changes. Moreover, Comparison between both groups at the end of the study revealed significant differences. CONCLUSION Weight reduction improved immunological and systemic inflammation markers in obese asthma patients.
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The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.
Dzikowski, M, Juchnowicz, D, Dzikowska, I, Rog, J, Próchnicki, M, Kozioł, M, Karakula-Juchnowicz, H
Journal of clinical medicine. 2020;9(11)
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Schizophrenia is a heterogeneous neuroimmune disorder with unknown mechanisms and aetiology. The goal of this clinical study was to compare and evaluate IgG and IgA sensitivity, inflammation, and gut integrity between 52 first episode Schizophrenia patients, 50 chronic Schizophrenia patients, and 60 healthy controls to explain whether there were any associations between these markers. Study results show that antigliadin IgG and IgA antibodies, as well as inflammatory markers such as hs-CRP and IL-6, were significantly higher in the first episodes of schizophrenia and chronic schizophrenia patients when compared to the healthy controls. Schizophrenia risk was 4-7% higher among those with elevated Antigliadin IgG and IgA antibody levels. In addition, smoking cigarettes has been shown to increase the risk of developing schizophrenia. Patients with chronic schizophrenia showed elevated levels of anti-Saccharomyces cerevisiae antibody and soluble CD14, indicating bacterial translocation and immune activation. To understand the mechanisms behind chronic Schizophrenia, which link inflammation, immune responses, and the gut-brain axis, further robust larger studies are necessary. The results of this study can be used by healthcare professionals to understand the relationship between intestinal permeability, inflammation, and food hypersensitivity.
Abstract
Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23-15.39) for AGA IgA and 3.08 (95% CI 1.19-7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.
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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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Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial.
Sim, M, Kim, CS, Shon, WJ, Lee, YK, Choi, EY, Shin, DM
Scientific reports. 2020;10(1):12130
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Oxidative stress indicates a state where excessive reactive oxygen species (ROS) overwhelm the biological antioxidant capacity, leading to disruption of ROS homeostasis and cellular damage. The aim of this study was to investigate the effects of hydrogen-rich water (HW) consumption in healthy adults through the extensive analyses of antioxidant capacity, peripheral blood mononuclear cell subsets and their transcriptome profile and to compare the effects of HW consumption with those of plain water (PW) consumption. This study is a 4-week, parallel-designed, randomized, double-blind, and placebo-controlled trial. The enrolled participants were randomly assigned to either the PW group (n=19) or the HW group (n=22). Results show that four-week consumption of HW induced a substantial increase in the antioxidant capacity and a decrease in oxidative stress of DNAs, although no significant results were found in the comparison of an intervention (HW) and the placebo (PW) group. Furthermore, the frequencies of apoptotic cells were significantly reduced by HW. Authors conclude that consumption of HW may promote biological antioxidant capacity for adults >30 years more than younger individuals.
Abstract
The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.
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Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study.
Souza, PR, Marques, RM, Gomez, EA, Colas, RA, De Matteis, R, Zak, A, Patel, M, Collier, DJ, Dalli, J
Circulation research. 2020;126(1):75-90
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Specialized pro-resolving mediators (SPM) are derived from essential fatty acids and promote resolution of inflammation. The main aim of this study was to establish the relationship(s) between supplement dose, peripheral blood SPM concentrations, and cellular responses using a novel enriched marine oil preparation. This study is a double-blind, randomized, crossover, dose escalation placebo-controlled study in healthy volunteers. Participants (n=22) were randomised to one of eight groups. Results show supplementation with refined marine oils lead to a rapid upregulation of peripheral blood SPM concentrations and reprograming of peripheral blood cell responses to sterile and infectious stimuli, changes that were found to persist after SPM concentrations returned to baseline. Authors conclude that enriched marine oil supplementation leads to a dose-and time-dependent increase of plasma SPM concentrations.
Abstract
RATIONALE Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. OBJECTIVE Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. METHODS AND RESULTS Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo. CONCLUSIONS Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.