Effects of Dietary Patterns on Biomarkers of Inflammation and Immune Responses: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Altered immune cell phenotype and chronic inflammation are key features shared by various chronic diseases. Evidence from nutritional interventions aimed at alleviating inflammation could be a promising approach for the prevention of adverse health outcomes. We therefore aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize the recent evidence on the effects of dietary patterns on inflammatory and immune-related biomarkers in humans. PubMed, Medline, and Web of Science databases were searched for publications up to October 2020. In total, 22 RCTs were included in the meta-analysis conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Mediterranean diet appeared as the dietary pattern that showed the most prominent reductions of inflammatory biomarkers such as IL-6 [mean difference (MD): -1.07 pg/mL (95% CI: -1.94, -0.20); I2: 96%], IL-1ß [MD: -0.46 pg/mL (95% CI: -0.66, -0.25); I2: 0%], and C-reactive protein [MD: -1.00 mg/L (95% CI: -2.02, 0.01); I2: 100%]. No substantial effects were observed for the additional dietary patterns studied in intervention research, including the Dietary Adherence to Stop Hypertension diet, and the vegetarian or vegan diets. Future large-scale multifactorial intervention studies are warranted to allow direct comparison of various dietary patterns in relation to a range of biomarkers reflecting multiple inflammatory and immune-related pathways.

Determinants of elevated chemerin as a novel biomarker of immunometabolism: data from a large population-based cohort.

OBJECTIVE: Chemerin is a novel inflammatory biomarker suggested to play a role in the development of metabolic disorders, providing new avenues for treatment and prevention. Little is known about the factors that predispose elevated chemerin concentrations. We therefore aimed to explore a range of lifestyle-associated, dietary, and metabolic factors as potential determinants of elevated chemerin concentrations in asymptomatic adults. DESIGN: We used cross-sectional data from a random subsample of 2433 participants (1494 women and 939 men) aged 42-58 years of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. METHODS: Random forest regression (RFR) was applied to explore the relative importance of 32 variables as statistical predictors of elevated chemerin concentrations overall and by sex. Multivariable-adjusted linear regression was applied to evaluate associations between selected predictors and chemerin concentrations. RESULTS: Results from RFR suggested BMI, waist circumference, C-reactive protein, fatty liver index, and estimated glomerular filtration rate as the strongest predictors of chemerin concentrations. Additional predictors included sleeping duration, alcohol, red and processed meat, fruits, sugar-sweetened beverages (SSB), vegetables, dairy, and refined grains. Collectively, these factors explained 32.9% variation of circulating chemerin. Multivariable-adjusted analyses revealed linear associations of elevated chemerin with metabolic parameters, obesity, longer sleep, higher intakes of red meat and SSB, and lower intakes of dairy. CONCLUSIONS: These findings come in support of the role of chemerin as a biomarker characterizing inflammatory and metabolic phenotypes in asymptomatic adults. Modifiable dietary and lifestyle-associated determinants of elevated chemerin concentrations require further evaluation in a prospective study setting.

Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies.

INTRODUCTION: Oxidative stress and inflammation are known to play a critical role in ageing and chronic disease development and could therefore represent important targets for developing dietary strategies for disease prevention. We aimed to systematically review the results from observational studies and intervention trials published in the last 5 years on the associations between dietary patterns and biomarkers of oxidative stress and inflammation. METHODS: A systematic search of the PubMed, MEDLINE and Web of Science (January 2015 to October 2020) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of selected studies was evaluated based on the NUTRIGRADE and BIOCROSS assessment tools. RESULTS: In total, 29 studies among which 16 observational studies and 13 intervention studies were found eligible for review. Overall, results indicated an inverse association between plant-based diets - the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet - and oxidative stress and proinflammatory biomarkers. In observational studies, inverse associations were further revealed for the vegetarian diet, the USDA Healthy Eating Index (HEI) - based diet and the paleolithic diet, whereas a positive association was seen for western and fast food diets. Quality assessment suggested that majority of dietary intervention studies (n = 12) were of low to moderate quality. CONCLUSIONS: This study provides evidence that the plant-based dietary patterns are associated with lowered levels of oxidative stress and inflammation and may provide valid means for chronic disease prevention. Future large-scale intervention trials using validated biomarkers are warranted to confirm these findings.

Effects of High and Low Protein Diets on Inflammatory Profiles in People with Morbid Obesity: A 3-Week Intervention Study.

Nutritional interventions in morbidly obese individuals that effectively reverse a pro-inflammatory state and prevent obesity-associated medical complications are highly warranted. Our aim was to evaluate the effect of high (HP) or low (LP) protein diets on circulating immune-inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), chemerin, omentin, leptin, total adiponectin, high molecular weight adiponectin, and fetuin-A. With this aim, 18 people with morbid obesity were matched into two hypocaloric groups: HP (30E% protein, n = 8) and LP (10E% protein, n = 10) for three weeks. Biomarkers were measured pre and post intervention and linear mixed-effects models were used to investigate differences. Consuming HP or LP diets resulted in reduced CRP (HP: -2.2 ± 1.0 mg/L, LP: -2.3 ± 0.9 mg/L) and chemerin (HP: -17.9 ± 8.6 ng/mL, LP: -20.0 ± 7.4 ng/mL), with no statistically significant differences by diet arm. Participants following the LP diet showed a more pronounced decrease in leptin (-19.2 ± 6.0 ng/mL) and IL-6 (-0.4 ± 0.1 pg/mL) and an increase in total adiponectin (1.6 ± 0.6 µg/mL). Changes were also observed for the remaining biomarkers to a smaller degree by the HP than the LP hypocaloric diet, suggesting that a LP hypocaloric diet modulates a wider range of immune inflammatory biomarkers in morbidly obese individuals.

Intra-individual reproducibility of galectin-1, haptoglobin, and nesfatin-1 as promising new biomarkers of immunometabolism.

BACKGROUND: Galectin-1, haptoglobin, and nesfatin-1 have recently emerged as promising biomarkers implicated in immunometabolism. However, whether single blood measurements of these analytes could be suitable for large-scale human studies has not yet been evaluated. METHODS: The concentrations of galectin-1, haptoglobin, and nesfatin-1 were measured over a 4-month period in 207 healthy adults with median age of 56.7 years. Biomarker intra-individual reproducibility was assessed based on calculation of intraclass correlation coefficients (ICCs) and examining Bland-Altman plots. RESULTS: The overall ICCs were excellent for nesfatin-1 (ICC: 0.89 (95% CI: 0.86, 0.92), and good for galectin-1 and haptoglobin (ICCs: 0.70 (95% CI: 0.61, 0.77) and 0.67 (95% CI: 0.57, 0.74), respectively). Bland-Altman plots supported a high level of agreement between repeated biomarker measurements. CONCLUSIONS: Assay measurements of galectin-1, haptoglobin, and nesfatin-1 showed good to excellent within-subject reproducibility over a 4-month period, indicating that they may serve as feasible and reliable biomarkers for assessing metabolic inflammation in population research.

Effects of plant and animal high protein diets on immune-inflammatory biomarkers: A 6-week intervention trial.

BACKGROUND & AIMS: Pro-inflammatory biomarkers are well-established contributors to insulin resistance and represent valid targets for diabetes management and prevention. Yet, little is known whether nutrition could play a role in modulating various aspects of immune-inflammatory responses. Our aim is to assess the effect of isocaloric animal and plant protein dietary interventions on selected biomarkers representing various immune-inflammatory pathways. METHODS: We enrolled 37 participants with type 2 diabetes (age 64 ± 6 years, body mass index 30.2 ± 3.6 kg/m2, glycated hemoglobin 7.0 ± 0.6%) who underwent an either high-animal protein (AP) or high-plant protein (PP) diet (30 E% protein, 40 E% carbohydrates, 30 E% fat) for 6-weeks. Clinical examinations were performed at beginning and end of the study. Levels of pro-inflammatory adipokines [chemerin, progranulin], cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), transforming growth factor beta 1 (TGF-ß1)], and proteins [calprotectin, lactoferrin and growth differentiation factor 15 (GDF-15)] were determined in blood serum using enzyme-linked immunosorbent assay. RESULTS: Chemerin and progranulin concentrations decreased following AP and PP diets. TGF-ß1 increased in AP and decreased in PP, whereas calprotectin increased in PP and decreased in AP. No statistically significant differences in the concentrations of IL-6, TNF-α, suPAR, lactoferrin and GDF-15 could be seen in either of the protein diet arms. CONCLUSIONS: These results suggest that both AP and PP diets may effectively reduce the levels of the pro-inflammatory adipokines chemerin and progranulin. The effects on the additional immune-inflammatory biomarkers seem to be more complex. CLINICAL TRIAL REGISTRY NUMBER: NCT02402985 (ww.clinicaltrials.gov).

Cytokines for evaluation of chronic inflammatory status in ageing research: reliability and phenotypic characterisation.

BACKGROUND: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes. RESULTS: Overall, the majority of cytokines were above the limit of detection (in at least 85.3% of the samples). Cytokines IL-6, IL-8, TNF-α, IL-10, IL-13, and IFN-γ showed overall good to fair reliability (ICC > 0.40), whereas IL-1ß, IL-2, IL-4, and IL-12p70 showed poor reliability (ICC < 0.40). The reliability estimates were not substantially influenced by participants' age, sex, obesity and C-reactive protein (CRP) levels. As expected, cytokine concentrations were elevated with advanced age most pronouncedly for IL-6, IL-8, Il-2, IFN- γ, and TNF-α. No major associations with metabolic phenotypes were observed for most cytokines, with the exception of a positive association between IL-6 and TNF-α with body mass index and CRP (ρ: 0.36; ρ: 0.20; ρ: 0.53; ρ: 0.22, respectively), and IFN-γ and IL-10 with CRP (ρ: 0.23 and ρ: 0.19, respectively). CONCLUSIONS: Single measurements of selected cytokines using MSD platform, including IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ have shown to be representative of an individual's average level over time and could be suitable for use in prospective epidemiological and clinical studies. Such studies are highly warranted to characterize associations of cytokines with phenotypes and diseases associated with ageing.