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.
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.
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.
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.
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•Following plant-based diet was associated with lower levels of oxidative stress and inflammation.•Mediterranean diet reduced levels of lipid peroxidation and oxidative DNA damage.•DASH diet lowered levels of lipid peroxidation and increased nitric oxide levels.•Western diets were associated with higher oxidative stress and inflammation levels.•The overall quality of dietary intervention studies was low to moderate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible ...individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated with IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes, and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and have weak evidence. This review summarises the current knowledge on the complex interactions between diet, microbiome and epigenetics in IBD. Whereas an overabundance of calories and some macronutrients increase gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, and D, folic acid, beta carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, an anti-inflammatory dietary pattern as a complex intervention approach has become popular in recent years. Hence, exclusive enteral nutrition in paediatric Crohn's disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet (SCD), the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet and, most recently, the Mediterranean diet have shown strong anti-inflammatory properties and show promise for improving disease symptoms. More work is required to evaluate the role of individual food compounds and complex nutritional interventions with the potential to decrease inflammation as a means of prevention and management of IBD.
The worldwide rise of obesity has provoked intensified research to better understand its pathophysiology as a means for disease prevention. Several biomarkers that may reflect various ...pathophysiological pathways that link obesity and cardiometabolic diseases have been identified over the past decades.
We summarize research evidence regarding the role of established and novel obesity-related biomarkers, focusing on recent epidemiological evidence for detrimental associations with cardiometabolic diseases including obesity-related cancer. The reviewed biomarkers include biomarkers of glucose-insulin homeostasis (insulin, insulin-like growth factors, and C-peptide), adipose tissue biomarkers (adiponectin, omentin, apelin, leptin, resistin, and fatty-acid-binding protein-4), inflammatory biomarkers (C-reactive protein, interleukin 6, tumor necrosis factor α), and omics-based biomarkers (metabolites and microRNAs).
Although the evidence for many classical obesity biomarkers, including adiponectin and C-reactive protein (CRP), in disease etiology has been initially promising, the evidence for a causal role in humans remains limited. Further, there has been little demonstrated ability to improve disease prediction beyond classical risk factors. In the era of "precision medicine," there is an increasing interest in novel biomarkers, and the extended list of potentially promising biomarkers, such as adipokines, cytokines, metabolites, and microRNAs, implicated in obesity may bring new promise for improved, personalized prevention. To further evaluate the role of obesity-related biomarkers as etiological and early-disease-prediction targets, well-designed studies are needed to evaluate temporal associations, replicate findings, and test clinical utility of novel biomarkers. In particular, studies to determine the therapeutic implications of novel biomarkers beyond established metabolic risk factors are highly warranted.
IMPORTANCE: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. OBJECTIVE: To ...examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. EXPOSURE: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. MAIN OUTCOMES AND MEASURES: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. RESULTS: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio HR, 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001). CONCLUSIONS AND RELEVANCE: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.
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.
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-1β, 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).
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The objective of this study was to develop a scoring system (NutriGrade) to evaluate the quality of evidence of randomized controlled trial (RCT) and cohort study meta-analyses in nutrition research, ...building upon previous tools and expert recommendations. NutriGrade aims to assess the meta-evidence of an association or effect between different nutrition factors and outcomes, taking into account nutrition research–specific requirements not considered by other tools. In a pretest study, 6 randomly selected meta-analyses investigating diet–disease relations were evaluated with NutriGrade by 5 independent raters. After revision, NutriGrade was applied by the same raters to 30 randomly selected meta-analyses in the same thematic area. The reliability of ratings of NutriGrade items was calculated with the use of a multirater κ, and reliability of the total (summed scores) was calculated with the use of intraclass correlation coefficients (ICCs). The following categories for meta-evidence evaluation were established: high (8–10), moderate (6–7.99), low (4–5.99), and very low (0–3.99). The NutriGrade scoring system (maximum of 10 points) comprises the following items: 1) risk of bias, study quality, and study limitations, 2) precision, 3) heterogeneity, 4) directness, 5) publication bias, 6) funding bias, 7) study design, 8) effect size, and 9) dose-response. The NutriGrade score varied between 2.9 (very low meta-evidence) and 8.8 (high meta-evidence) for meta-analyses of RCTs, and it ranged between 3.1 and 8.8 for meta-analyses of cohort studies. The κ value of the ratings for each scoring item varied from 0.32 (95% CI: 0.22, 0.42) for risk of bias for cohort studies and 0.95 (95% CI: 0.91, 0.99) for study design, with a mean κ of 0.66 (95% CI: 0.53, 0.79). The ICC of the total score was 0.81 (95% CI: 0.69, 0.90). The NutriGrade scoring system showed good agreement and reliability. The initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, ...possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.
In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.
After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.
The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
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•Liver cancer rates are increasing in Western countries, possibly due to increases in obesity, diabetes, and physical inactivity.•Previous evidence was not convincing to support an ...effect of physical activity on liver cancer.•We found that physical activity reduced the risk of hepatocellular carcinoma by about 45%.
To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).
We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).
In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.
These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.
In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint ...effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors--healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated.
After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend<0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend<0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend<0.0001) for rectal cancer, respectively (P-difference by cancer sub-site=0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index.
Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advanced Glycation End Products (AGEs) have been positively correlated with inflammation in adults, while inconsistent evidence is available in children. We evaluated the association between urinary ...AGEs, measured by fluorescence spectroscopy, and biomarkers of subclinical inflammation in 676 healthy children/adolescents (age 11.8 ± 1.6 years, M ± SD) from the Italian cohort of the I.Family project. Urinary fluorescent AGEs were used as independent variable and high-sensitivity C-reactive protein (hs-CRP) was the primary outcome, while other biomarkers of inflammation were investigated as secondary outcomes. Participants with urinary AGEs above the median of the study population showed statistically significantly higher hs-CRP levels as compared to those below the median (hs-CRP 0.44 ± 1.1 vs. 0.24 ± 0.6 mg/dL, M ± SD p = 0.002). We found significant positive correlations between urinary AGEs and hs-CRP (p = 0.0001), IL-15 (p = 0.001), IP-10 (p = 0.006), and IL-1Ra (p = 0.001). At multiple regression analysis, urinary AGEs, age, and BMI Z-score were independent variables predicting hs-CRP levels. We demonstrated for the first time, in a large cohort of children and adolescents, that the measurement of fluorescent urinary AGEs may represent a simple, noninvasive, and rapid technique to evaluate the association between AGEs and biomarkers of inflammation. Our data support a role of AGEs as biomarkers of subclinical inflammation in otherwise healthy children and adolescents.