Markers Of Inflammation In Adults Research Articles

Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial.

In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D). Out of 88 participants who were recruited, 49 adults with prediabetes or well-controlled T2D (HbA1c: 6.6 ± 0.7% [mean ± SD]) who were treated with diet and/or metformin were eligible for inclusion. Participants were randomised to receive 2 g/day of carnosine or a matching placebo for 14 weeks. We measured serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), adiponectin, leptin, adipsin, serpin, and resistin levels at baseline and after 14 weeks. The trial was registered at clinicaltrials.gov (NCT02917928). Forty-one participants (M = 29/F = 12) aged 53 (42.6, 59.3) years [median (IQR)] completed the trial. After 14 weeks of supplementation, changes in pro- and anti-inflammatory cytokine and adipokine levels did not differ between the carnosine and placebo groups (p > 0.05 for all). The results remained unchanged after adjustment for confounders including age, sex, and anthropometric measures (e.g., body fat percentage and visceral adipose tissue). In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D.

Exploring the associations of tobacco smoking and serum cotinine levels with selected inflammatory markers in adults with HIV in South Africa

This study examined the associations between tobacco smoking and serum cotinine levels, an objective biochemical measure of tobacco smoke exposure, with markers of inflammation, i.e., interferon-gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2) and tumour necrosis factor-alpha (TNF-α) in people living with HIV (PLWH).These specific markers were selected because of their hypothesised associations with smoking, PLWH and their outcomes. In a random sample of ≥ 18-year-old PLWH receiving care at 17 public healthcare facilities across the Western Cape Province in South Africa, data collection included self-reported smoking history, and serum levels of cotinine and selected inflammatory markers. The inflammatory marker data were log transformed because of the skewedness of their distribution. Linear regression models (1) adjusted for age and gender, and (2) fully adjusted for age, gender, current alcohol use, body mass index and CD4 counts were used to examine the associations between smoking tobacco or serum cotinine and inflammatory markers. Level of significance was p < 0.05. Among 749 PLWH who were mainly women (79%), the mean age was 38.5 (8.9) years and similar when stratified by smoking status. Serum cotinine levels exhibited a striking discrepancy, with a median of 154 ng/mL among current smokers, in stark contrast to the consistent median values of 10 ng/mL observed among past and never smokers. In regression models adjusted for age and gender, current smoking and frequent smoking were associated with lower IL-2 but higher TNF-α. Log-cotinine exhibited associations with IFN-γ, IL-10, and TNF-α, while cotinine levels ≥ 10 ng/mL compared to < 10 ng/mL were associated with higher IFN-γ and TNF-α. In fully adjusted models, log-cotinine and cotinine levels ≥ 10 ng/mL displayed significant associations with higher IFN-γ and lower IL-2. This study underscores the importance of investigating the interplay between smoking tobacco or serum cotinine levels with pro-inflammatory cytokines in PLWH. It signals the need for comprehensive research to unravel the potential synergistic impacts of smoking tobacco and HIV infection on chronic inflammation and immune dysregulation, shedding light on critical avenues for intervention and management strategies.

Loneliness Gets Under the Skin: A Scoping Review Exploring the Link Between Loneliness and Biological Measures of Inflammation.

Research suggests that systemic inflammation may link loneliness to adverse health outcomes, yet there is a gap in comprehensively reviewing recent evidence on the relationship between loneliness and biological measures of inflammation in adults. This scoping review synthesizes current research to address the question: Is there a definitive link between loneliness and biological markers of inflammation in adults? Following the methods outlined by Arksey and O'Malley, we developed a protocol, defined our research question, and systematically searched PubMed, CINAHL, Embase, and Scopus for English-language studies conducted from 2018 to 2023 exploring the relationship between loneliness and biomarkers of inflammation in adults. Twelve studies meeting the inclusion criteria displayed heterogeneity in terms of sample characteristics, loneliness scales, and inflammatory biomarkers. The UCLA Loneliness Scale, in various forms, emerged as the predominant tool for measuring loneliness, while C-reactive protein and interleukin-6 were the most frequently evaluated inflammatory biomarkers. Notably, all 12 studies reported an association between loneliness and at least 1 biological marker of inflammation. Research consistently associates loneliness with poor health outcomes in aging adults, but the underlying mechanisms remain unclear. This scoping review suggests that inflammation may serve as a pathway linking loneliness to adverse health outcomes. However, the variability across studies highlights the need for standardized measurement methods and a consideration of both the duration and extent of loneliness. Enhancing our understanding of how loneliness affects systemic inflammation may help clarify why loneliness is associated with negative health outcomes.

Wheat germ supplementation has modest effects on gut health markers but improves glucose homeostasis markers in adults classified as overweight: A randomized controlled pilot study

Wheat germ (WG), a by-product of flour milling, is rich in bioactive substances that may help improve health complications associated with increased adiposity. This study investigated the effects of WG on gut health, metabolic, and inflammatory markers in adults classified as overweight. We hypothesized that WG, because of its many bioactive components, would improve gut health and metabolic, and inflammatory markers in overweight adults. Forty adults (18-45 years old) and with a body mass index between 25 and 30 kg/m2 participated in this single-blinded randomized controlled pilot study. Participants consumed the study supplements containing 30 g of either cornmeal (control, CL) or WG daily for 4 weeks. Primary outcome variables were gut health markers including gut microbiota, gut integrity markers, and fecal short-chain fatty acids, whereas secondary outcome variables included metabolic and inflammatory parameters assessed at baseline and at the end of supplementation. Thirty-nine participants (n = 19 and 20 for CL and WG group, respectively) completed the study. The genus Faecalibacterium was significantly higher in the WG group compared to CL post-supplementation but no significant changes in other gut health markers, short-chain fatty acids, inflammatory markers, and lipid profiles were observed. Compared with baseline, WG improved markers of glucose homeostasis including insulin (P = .02), homeostatic model assessment of insulin resistance (P = .03), glycated hemoglobin (P = .07), and the pro-inflammatory adipokine, resistin (P = .04). However, these parameters after intervention were not different with control. Our findings suggest that WG supplementation have modest effects on gut health but may provide an economical option for individuals to improve glycemic control.

Effects of low-carbohydrate diets, with and without caloric restriction, on inflammatory markers in adults: a systematic review and meta-analysis of randomized clinical trials.

Low-carbohydrate diets (LCDs) have gained interest due to their favorable effects on health outcomes, such as inflammation. However, further research is needed to ascertain the overall effects of LCDs on inflammatory parameters, but at the same time considering weight loss and calorie intake. Thus, a systematic review and meta-analysis of randomized clinical trials was performed to investigate the effects of LCDs compared with low-fat diets (LFDs), with and without caloric restriction, on inflammatory markers in adults. PubMed, Scopus, and Web of Science were searched through March 2022 to select intervention studies addressing LCDs vs. LFDs, in which the following circulating inflammatory markers were used: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL-6). Analyses were conducted comparing LCDs vs. LFDs through weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (95% CIs) using random effects models. The systematic review and meta-analysis included a total of 51 studies with a total sample of 4,164 adults, with or without other chronic diseases. Intervention durations ranged from 2-144 weeks. LCDs, compared with LFDs, significantly decreased body weight [WMD = -1.35%, p = 0.001], CRP [SMD = -0.1, p = 0.03], and IL-6 [SMD = -0.15, p = 0.09]. However, LCDs did not significantly decrease TNF-α [SMD = -0.02, p = 0.7] compared to LFDs. In conclusion, LCDs have a beneficial effect on markers of inflammation by decreasing CRP and IL-6; this effect has an association with weight loss. However, LCDs were not more effective than LFDs in decreasing TNF-α.

The Role of Probiotics in Managing Glucose Homeostasis in Adults with Prediabetes: A Systematic Review and Meta-Analysis.

The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; p = 0.03; I2 = 76.13%, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (SMD -0.27; 95% CI -0.45, -0.09; p < 0.001; I2 = 0.50%, p = 0.36) and improve the levels of high-density lipoprotein cholesterol (HDL) (SMD -8.94; 95% CI -14.91, -2.97; p = 0.003; I2 = 80.24%, p < 0.001), when compared to the placebo group. However, no significant difference was observed in fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-α, and body mass index. Subgroup analyses showed that probiotics significantly reduced HbA1c in adults with prediabetes in Oceania, intervention duration of ≥3 months, and sample size <30. Collectively, our meta-analysis revealed that probiotics had a significant impact on reducing the levels of HbA1c and HOMA-IR and improving the level of HDL in adults with prediabetes, which indicated a potential role in regulating blood glucose homeostasis. However, given the limited number of studies included in this analysis and the potential for bias, further large-scale, higher-quality randomized controlled trials are needed to confirm these findings. This trial is registered with CRD42022358379.

The effect of dietary interventions on inflammatory biomarkers among people with multiple sclerosis: A protocol for systematic review and meta-analysis of randomized controlled trials.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration, which has a profound impact on the quality of life. Dysregulated inflammatory processes are a major driver of MS progression, with many areas of research being dedicated to modulating inflammation in people with MS. Several dietary patterns have been associated with improvements in inflammatory biomarkers; although, the findings have been inconsistent. Thus, this study aims to evaluate the effects of dietary interventions on inflammatory markers in adults with MS. Electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, and Cochrane/Central, will be searched. Screening, selection, and extraction of data, along with quality assessment of included studies, will be done by two separate reviewers, and any potential conflicts will be settled through discussion. Two reviewers will independently assess the risk of bias in included studies using the Cochrane Risk of Bias Tool. If plausible, the results will be synthesized and pooled for meta-analysis. The overall quality of evidence of each study will be evaluated using the NutriGRADE tool, which is a modification to the Grading Recommendations Assessment, Development, and Evaluation (GRADE) developed specifically for nutrition research. Studies have demonstrated conflicting results regarding the effects of dietary interventions on serum levels of inflammatory biomarkers among people with MS. Thus, it is expected that the planned systematic review and meta-analysis will yield robust evidence on the effects of diet on inflammatory profile in the setting of MS.

Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections

We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. We included 738 episodes between 2017 and 2022, split into a derivation (n=450) and validation cohort (n=288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1β in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC=0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC=0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model=0.97 vs. AUC CSF leukocytes=0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n=19) or low-fat diet (n=23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P=.010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P=.016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population.

The Mediating Effect of Central Obesity on the Association between Dietary Quality, Dietary Inflammation Level and Low-Grade Inflammation-Related Serum Inflammatory Markers in Adults

To date, few studies have explored the role of central obesity on the association between diet quality, measured by the health eating index (HEI), inflammatory eating index (DII), and low-grade inflammation-related serum inflammatory markers. In this paper, we use the data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES) to explore this. Dietary intakes were measured during two 24-h dietary recall interviews and using USDA Food Pattern Equivalence Database (FPED) dietary data. Serum inflammatory markers were obtained from NHANES Laboratory Data. Generalized structural equation models (GSEMs) were used to explore the mediating relationship. Central obesity plays a significant mediating role in the association between HEI-2015 and high-sensitivity C-reactive protein (hs-CRP), mediating 26.87% of the associations between the two; it also mediates 15.24% of the associations between DII and hs-CRP. Central obesity plays a mediating role in 13.98% of the associations between HEI-2015 and white blood cells (WBC); it also mediates 10.83% of the associations between DII and WBC. Our study suggests that central obesity plays a mediating role in the association of dietary quality with low-grade inflammation-related serum inflammatory markers (hs-CRP and WBC).

Cardiorespiratory Fitness and Bone Turnover Markers in Adults With Metabolic Syndrome: The Mediator Role of Inflammation.

The relationship between inflammatory markers and bone turnover in adults is well known, and a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5 ± 5.0years, 62.7% women) were included in the analysis. CRF was measured by the 6-min walking test. Serum interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP), and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy X-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers, and bone turnover markers, controlling for sex, lean mass, and fat mass. Boot-strapped mediation procedures were performed, and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r = .228, p = .044) and osteocalcin levels (r = .296, p = .009). Furthermore, CRF was positively correlated with IL-1β levels (r = .340, p = .002) and negatively correlated with hsCRP levels (r = -.335, p = .003), whereas IL-1β levels were positively correlated with P1NP levels (r = .245, p = .030), and hsCRP levels were negatively correlated with P1NP levels (r = -.319, p = .004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (percentage of mediation = 39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.

Efficacy and safety of a new mometasone furoate nasal spray formulation in patients with acute rhinosinusitis: a randomized clinical trial

Common inflammatory airway disorders, such as seasonal and perennial allergic rhinitis, acute sinusitis, and nasal polyposis, can have a significant impact on patient health and quality of life. Intranasal corticosteroids are recommended as part of treatment plans for each of these illnesses because they reduce inflammation and thus symptoms. In order to compare the efficacy and safety of a new nano formulation of mometasone furoate nano-nasal spray (MF-NNS) with a commercially available nasal spray called mometasone furoate nasal spray (MFNS) for the treatment of allergic rhinitis, 20 rhinitis patients were enrolled in this randomized controlled trial (10 to 50 years). Patients were given 50 mcg MF-NNS doses in the morning and evening. This regimen was administered as a nasal spray for a 3-week efficacy and safety phase. The primary endpoints changed from baseline in the subjects’ congestion as determined by the physicians’ assessment of allergic rhinitis. Analysis of variance was used to evaluate all efficacy end points. More clinical trials have shown that MF-NNS reduces both objective and subjective markers of inflammation in adults, adolescents, and children.

Meals That Differ in Nutrient Composition and Inflammatory Potential Do Not Differentially Impact Postprandial Circulating Cytokines in Older Adults above a Healthy Weight.

In this exploratory study, mixed meals specifically formulated to differ in inflammatory potential were tested to determine whether they could differentially impact circulating levels of inflammatory markers in adults above a healthy weight. Complete data were analyzed from 11 adults (6 males and 5 females) aged 54–63 years with median BMI of 30.0 (27.1–31.6) kg/m². In a crossover study design, each participant consumed an isocaloric (2.2 MJ) meal with either a low (Anti-meal), moderate (Neutr-meal), or high (Pro-meal) inflammatory potential. Fasting and postprandial blood samples were analyzed for plasma levels of IL-6, IL-1β, TNF-α, IL-10, and metabolic makers. Postprandial plasma IL-6, IL-1β, TNF-α, and IL-10 incremental areas under the curve (iAUC) were not different between the three meals (p > 0.05). There was a trend of an increase in IL-6 with time in all three meals, but no changes were obvious for the other measured cytokines. The Pro-meal induced an increased postprandial iAUC for triglycerides compared to the Anti-meal and Neutr-meal (p = 0.004 and p = 0.012, respectively). Single meals, regardless of their theoretical inflammatory potential, did not substantially shift circulating inflammatory markers, suggesting that longer-term dietary patterns are important rather than single dietary exposures in the pathology of metabolic conditions.

Blunted rest-activity rhythm is associated with increased white blood-cell-based inflammatory markers in adults: an analysis from NHANES 2011-2014

ABSTRACT Circadian rhythm disruption is associated with immune system disturbance and has been observed in many health problems where chronic-inflammation acts as a major contributor. We aim to examine whether rest-activity circadian rhythm is associated with chronic inflammation using white blood-cell-based inflammatory indices including white blood cell (WBC) count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). We analyzed the data from 8089 adults (age≥20) with at least 4 days of validated accelerometer recordings and a valid WBC count from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings. In the models adjusting multiple covariates, a one-quantile increase in relative amplitude (i.e. more robust circadian rhythm) was associated with 1 × 108 cells/L decrease in WBC number (95% CI: 5 × 107 to 1.5 × 108, P < .001), 7 × 107 cells/L decrease in neutrophils (95% CI: 3 × 107 to 1.1 × 108, P = .003) and 15.2 × 109 /L decrease in SII (95% CI: 6 × 109 /L to 20 × 109/L, P = .019). Consistent results were also observed for the association of M10 value and L5 value with these inflammatory indices. Our results indicated that blunted rest-activity circadian rhythm is associated with increased white blood-cell-based inflammatory indices in adults, suggesting interventions aiming at enhancing circadian rhythm by lifestyle programs may be a novel approach to improve the general health.

Effects of Probiotic Supplementation on Inflammatory Markers and Glucose Homeostasis in Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Several studies have revealed the effect of probiotic supplementation in patients with type 2 diabetes (T2DM) on the amelioration of low-grade inflammation, which plays an important role in the pathogenesis of T2DM. However, the effects of the clinical application of probiotics on inflammation in individuals with T2DM remain inconsistent. This study aims to investigate the comprehensive effects of probiotics on inflammatory markers in adults with T2DM. Methods: PubMed, Embase, Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) exploring the effect of probiotic supplementation on inflammatory markers in individuals with T2DM through March 11, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We used a random-effects model to calculate the standardized mean difference (SMD) between the probiotic supplementation and control groups. Results: Seventeen eligible studies were selected with a total of 836 participants, including 423 participants in probiotic supplementation groups and 413 participants in control groups. Our study demonstrated that compared with the control condition, probiotic intake produced a beneficial effect in reducing the levels of plasma inflammation markers, including tumour necrosis factor-α (TNF-α) (SMD [95% CI]; −0.37 [−0.56, −0.19], p < 0.0001) and C-reactive protein (CRP) (SMD [95% CI]; −0.21 [−0.42, −0.01], p = 0.040), while it had no effect on the plasma interleukin-6 (IL-6) level (SMD [95% CI]; −0.07 [−0.27, 0.13], p = 0.520). In addition, our results support the notion that probiotic supplementation improves glycaemic control, as evidenced by a significant reduction in fasting blood glucose (FPG), HbA1c and HOMA-IR (SMD [95% CI]: −0.24 [−0.42, −0.05], p = 0.010; −0.19 [−0.37, −0.00], p = 0.040; −0.36 [−0.62, −0.10], p = 0.006, respectively). Conclusion: Our study revealed some beneficial effects of probiotic supplementation on improving inflammatory markers and glucose homeostasis in individuals with T2DM. Probiotics might be a potential adjuvant therapeutic approach for T2DM.

Phenylalanine and COVID-19: Tracking disease severity markers

BackgroundAlthough there are several severity predictors for COVID-19, none are specific. Serum levels of phenylalanine were recently associated with increased inflammation, higher SOFA scores, ICU admission, and mortality rates among non-COVID-19 patients. Here, we investigated the relationship between phenylalanine and inflammatory markers in adults with COVID-19. MethodsWe assessed adults with COVID-19 at hospital admission for clinical and laboratory data. Nuclear magnetic resonance spectroscopy measured serum levels of phenylalanine and other amino acids of its metabolomic pathway. Flow Cytometry measured serum levels of IL-2, IL-4, IL-6, Il-10, TNF-α, and IFN-γ. Linear regression models adjusted for potential confounders assessed the relationship between serum levels of phenylalanine and inflammatory cytokines. ResultsPhenylalanine and tyrosine were significantly lower in mild disease as compared to moderate and severe groups. Linear regression models showed that phenylalanine is independently and positively associated with disease severity regardless of the cytokine analyzed and after adjustment for potential confounders. In addition, mild cases showed consistently lower serum phenylalanine levels within the first ten days from disease onset to hospital admission. ConclusionsPhenylalanine is a marker of disease severity. This association is independent of the time between the onset of symptoms and the magnitude of the inflammatory state.

Ergothioneine supplementation in people with metabolic syndrome (ErgMS): protocol for a randomised, double-blind, placebo-controlled pilot study

BackgroundErgothioneine is a naturally occurring metabolite of histidine found in many foods and in high amounts in mushrooms. In vivo, ergothioneine acts as an antioxidant and is widely distributed in most mammalian tissues. While ergothioneine is sold as a dietary supplement for its antioxidant and anti-inflammatory properties, to date there are no published intervention trials examining its health benefits in humans. The aim of this work was to develop a study protocol for a pilot interventional trial that will establish the primary and secondary outcomes, and the power required, for a definitive randomised controlled trial to test the hypothesis that ergothioneine supplementation is beneficial for people with metabolic syndrome.MethodsWe have designed the ErgMS study as a single-centre, randomised, double-blind, placebo-controlled, 3-arm parallel, pilot intervention trial, which aims to supplement participants with either placebo, 5 or 30 mg/day ergothioneine for 12 weeks. Measurements of metabolic syndrome risk factors, serum markers of oxidative stress (lipid peroxidation), inflammation, blood platelet function and liver function will take place at baseline, and after 6 weeks and 12 weeks of supplementation. In addition, we will examine if there are any changes in the serum metabolome in response to ergothioneine supplementation. Linear regression and two-way ANOVA will be utilised to analyse the association between ergothioneine and measured variables.DiscussionThe ErgMS study will be the first study to address the question does ergothioneine supplementation have health benefits for people with metabolic syndrome. Study results will provide preliminary data as to which dose may improve inflammatory markers in adults with metabolic syndrome and will inform dose and primary outcome selection for a definitive randomised controlled trial.Trial registrationISRCTN, ISRCTN25890011 Registered February 10th, 2021

Improved diet quality is associated with decreased concentrations of inflammatory markers in adults with uncontrolled asthma

Asthma has become one of the major public health challenges, and recent studies show promising clinical benefits of dietary interventions, such as the Dietary Approaches to Stop Hypertension (DASH) diet. The objective of this study was to examine whether changes in diet quality are associated with changes in inflammatory markers important in asthma pathophysiology. In this exploratory study in patients with poorly controlled asthma participating in a randomized controlled trial of a DASH intervention study, changes in concentrations of a broad panel of serum proteins (51-plex Luminex assay, Affymetrix) were determined, and their relation to diet quality (DASH score) assessed by combining data of both intervention and usual-care control groups. Second, the relation between the serum proteins, other biomarkers of inflammation and nutrition, and Asthma Control Questionnaire (ACQ) was assessed. During the first 3 mo, diet quality (DASH scores) were inversely associated (P<0.05, false discovery rate P<0.09) with serum concentrations of a large number serum proteins, reflecting not only general proinflammatory markers such as IL-1β, transforming growth factor α (TGF-α), and IL-6 (r = -0.31 to -0.39) but also a number of proteins associated with asthmatic conditions, specifically several T-helper (Th) 2 (Th2; r = -0.29 to -0.34) and Th17 (r = -0.4) associated cytokines and growth factors. Monokine induced by gamma/chemokine (C-X-C motif) ligand 9 (CXCL9) (MIG/CXCL9), a T-cell attractant induced by IFN-γ previously linked to asthma exacerbations, appeared to be the marker most consistently associated with DASH diet quality for the entire 6-mo study period (r = -0.40 and -0.30 for 0-3 and 3-6 mo, respectively, and standardized coefficient loadings -0.13 in the partial least squares analyses). Decreases in 19 serum protein concentrations were also correlated with improved asthma control during the 6-mo study period. Our data in adult patients with poorly controlled asthma suggest that dietary changes, like the introduction of DASH, may have beneficial effects on reducing inflammatory status. This trial was registered at http://www.clinicaltrials.gov as NCT01725945.

Association of vitamin D status with metabolic and inflammatory factors in adults with obesity

Introduction: Obesity and vitamin D deficiency are both have become major public health challenges worldwide which are associated with an increased risk of metabolic diseases. The aim of this study was to investigate the association between vitamin D status with metabolic and inflammatory markers in adults with obesity. Materials and Methods: In this case-control study, 90 obese subjects with vitamin D deficiency were selected as the case group and 90 obese subjects with adequate vitamin D status were selected as the control group. Demographic, anthropometric, and dietary data were collected for each participant. Then, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and fasting serum concentrations of glucose (FBS), insulin, total cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c) and triglyceride (TG) as metabolic factors and serum levels of high-sensitivity C-reactive protein (hs-CRP) as inflammatory marker were measured in the participants. Results: The obese subjects with vitamin D deficiency had higher serum concentrations of TC (p=0.001), LDL-C (p=0.003), hs-CRP (p=0.004), parathyroid hormone (p=0.001), and HOMA-IR (p=0.020) compared to the counterparts in the vitamin D sufficiency group. Likewise, vitamin D deficient subjects were at higher risk for having hypercholesrolemia (OR: 2.7, p=0.012), high LDL-c (OR: 2.34, p=0.017), and high hs-CRP (OR: 1.97, p=0.032) than vitamin D sufficient subjects, after controlling for confounders. Conclusion: vitamin D deficiency in obese subjects was found to be strongly related to higher risk of metabolic and inflammatory disorders.

The association of child maltreatment and systemic inflammation in adulthood: A systematic review.

IntroductionChild maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults.MethodsA pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting.ResultsForty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field.ConclusionsThere is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.