Assessing the (anti)-inflammatory potential of diets.

PURPOSE OF REVIEW: It is accepted that several chronic diseases are associated with inflammation. Dietary habits and the consumption of certain nutrients have been shown to influence inflammation, reflected by inflammatory cytokines. In this narrative review, we discuss currently developed tools to assess the inflammatory potential of diets and compare them with established tools. RECENT FINDINGS: Four new indices were recently developed. The Inflammatory Score of the Diet is a modified version of the established Dietary Inflammatory Index. The novel Empirical Dietary Inflammatory Index works without previous dietary intake assessment and the Anti-Inflammatory Diet Index was specifically developed in a northern European population. The Dietary and Lifestyle Inflammation Scores addresses additional confounders. The informative value of dietary indices relies on the accuracy and completeness of dietary intake assessment. SUMMARY: Dietary inflammatory indices are important tools to assess, compare and validate the inflammatory potential of diets across populations without the need for biomarker assessments. They allow to investigate associations between an (anti)-inflammatory diet with disease risk and course. Although the Dietary Inflammatory Index remains the most used index worldwide, currently developed indices allow more flexibility, have a different focus or simplify assessment. Additional foods, that were recently shown to modulate inflammation, but are not (fully) considered yet, may deserve more attention in the future.

Impact of sarcopenia on 1-year mortality in older patients with cancer.

OBJECTIVES: sarcopenia is common especially in hospitalised older populations. The aim of this study was to assess the prevalence of sarcopenia, defined as low skeletal mass and muscle strength, and its impact on 1-year mortality in older patients with cancer. METHODS: skeletal muscle mass was estimated using bioelectric impedance analysis and related to height2 (SMI; Janssen et al. 2002). Grip strength was measured with the JAMAR dynamometer and the cut-offs suggested by the European Working Group on Sarcopenia in Older People (EWGSOP) were applied. One-year mortality was assessed by telephone follow-up and the local cancer death registry. RESULTS: of the 439 consecutively recruited cancer patients (60-95 years; 43.5% women), 119 (27.1%) had sarcopenia. Of the patients with sarcopenia, 62 (52.5%) died within 1 year after study entry compared to 108 (35.1%) patients who did not have sarcopenia (P = 0.001). In a stepwise, forward Cox proportional hazards analysis, sarcopenia (HR = 1.53; 95% CI: 1.034-2.250; P < 0.05), advanced disease (HR = 1.87; 95% CI: 1.228-2.847; P < 0.05), number of drugs/day (HR = 1.11; 95% CI: 1.057-1.170; P < 0.001), tumour diagnosis (overall P < 0.05) and Karnofsky index (HR = 0.98, 95% CI: 0.963-0.995; P < 0.05) associated with 1-year mortality risk. The factors sex, age, co-morbidities and involuntary 6-month weight loss ≥5% were insignificant. CONCLUSIONS: sarcopenia was present in 27.1% of older patients with cancer and was independently associated with 1-year mortality. The fact that sarcopenia was nearly as predictive for 1-year mortality as an advanced disease stage underlines the importance of preservation of muscle mass and function as a potential target of intervention in older patients with cancer.

Effects of a Short-Term Vegan Challenge in Older Adults on Metabolic and Inflammatory Parameters-A Randomized Controlled Crossover Study.

SCOPE: A long-term vegan diet carries the risk of insufficient protein and micronutrient intake for older adults. However, even a short-term (48 h) vegan diet exerts positive metabolic effects in younger adults. In this study, we investigate the feasibility and effects of a short-term vegan challenge on metabolic and inflammatory markers in older adults. METHOD AND RESULTS: In this randomized controlled crossover-study, 30 healthy older adults (≥65 years) are assigned to either a 48 h ad libitum vegan or omnivorous diet. During the vegan diet, participants exhibit lower protein (p = 0.001) and fat intake as well as higher carbohydrate and dietary fiber intake, resulting in a lower caloric intake (all p < 0.001). Insulin concentrations (p = 0.042) and insulin resistance (p = 0.036) decline only after the vegan diet. The study observes reductions in serum glucose (p < 0.001), triglyceride (p = 0.005), and hsCRP (p = 0.044) concentrations and weight (p < 0.001), independent of the diet. Participants with low-grade inflammation exhibit notable metabolic improvements after the vegan diet. CONCLUSION: Improvements in insulin homeostasis are observed after the vegan diet, but meeting protein requirements are not feasible during the short-term vegan challenge despite dietary counseling, which warrants concern.

Malnutrition is associated with six-month mortality in older patients admitted to the emergency department with hip fracture.

Background: Hip fractures in older people are a common health problem often associated with malnutrition that might affect outcomes. Screening for malnutrition is not a routine examination in emergency departments (ED). This analysis of the EMAAge study, a prospective, multicenter cohort study, aimed to evaluate the nutritional status of older patients (≥ 50 years) with hip fracture, factors associated with malnutrition risk, and the association between malnutrition and the six-months mortality. Methods: Risk of malnutrition was evaluated using the Short Nutritional Assessment Questionnaire. Clinical data as well as data on depression and physical activity were determined. Mortality was captured for the first six months after the event. To assess factors associated with malnutrition risk we used a binary logistic regression. A Cox proportional hazards model was used to assess the association of malnutrition risk with six-month survival adjusted for other relevant risk factors. Results: The sample consisted of N = 318 hip fracture patients aged 50 to 98 (68% women). The prevalence of malnutrition risk was 25.3% (n = 76) at the time of injury. There were no differences in triage categories or routine parameters measured in the ED that could point to malnutrition. 89% of the patients (n = 267) survived for six months. The mean survival time was longer in those without malnutrition risk (171.9 (167.1-176.9) days vs. 153.1 (140.0-166.2) days). The Kaplan Meier curves and the unadjusted Cox regression (Hazard Ratio (HR) 3.08 (1.61-5.91)) showed differences between patients with and patients without malnutrition risk. In the adjusted Cox regression model, risk of death was associated with malnutrition risk (HR 2.61, 1.34-5.06), older age (70-76 years: HR 2.5 (0.52-11.99); 77-82 years: HR 4.25 (1.15-15.62); 83-99 years: HR 3.82 (1.05-13.88)) and a high burden of comorbidities (Charlson Comorbidity Index ≥3: HR 5.4 (1.53-19.12)). Conclusion: Risk of malnutrition was associated with higher mortality after hip fracture. ED parameters did not differentiate between patients with nutritional deficiencies and those without. Therefore, it is particularly important to pay attention to malnutrition in EDs to detect patients at risk of adverse outcomes and to initiate early interventions.

Frailty is characterized by biomarker patterns reflecting inflammation or muscle catabolism in multi-morbid patients.

BACKGROUND: Frailty development is partly dependent on multiple factors like low levels of nutrients and high levels of oxidative stress (OS) and inflammation potentially leading to a muscle-catabolic state. Measures of specific biomarker patterns including nutrients, OS and inflammatory biomarkers as well as muscle related biomarkers like 3-methylhistidine (3MH) may improve evaluation of mechanisms and the complex networks leading to frailty. METHODS: In 220 multi-morbid patients (≥ 60 years), classified as non-frail (n = 104) and frail (n = 116) according to Fried's frailty criteria, we measured serum concentrations of fat-soluble micronutrients, amino acids (AA), OS, interleukins (IL) 6 and 10, 3MH (biomarker for muscle protein turnover) and serum spectra of fatty acids (FA). We evaluated biomarker patterns by principal component analysis (PCA) and their cross-sectional associations with frailty by multivariate logistic regression analysis. RESULTS: Two biomarker patterns [principal components (PC)] were identified by PCA. PC1 was characterized by high positive factor loadings (FL) of carotenoids, anti-inflammatory FA and vitamin D3 together with high negative FL of pro-inflammatory FA, IL6 and IL6/IL10, reflecting an inflammation-related pattern. PC2 was characterized by high positive FL of AA together with high negative FL of 3MH-based biomarkers, reflecting a muscle-related pattern. Frail patients had significantly lower factor scores than non-frail patients for both PC1 [median: -0.27 (interquartile range: 1.15) vs. 0.27 (1.23); P = 0.001] and PC2 [median: -0.15 (interquartile range: 1.13) vs. 0.21 (1.38); P = 0.002]. Patients with higher PC1 or PC2 factor scores were less likely to be frail [odds ratio (OR): 0.62, 95% CI: 0.46-0.83, P = 0.001 for PC1; OR: 0.64, 95% CI: 0.48-0.86, P = 0.003 for PC2] compared with patients with lower PC1 or PC2 factor scores. This indicates that increasing levels of anti-inflammatory biomarkers and increasing levels of muscle-anabolic biomarkers are associated with a reduced likelihood (38% and 36%, respectively) for frailty. Significant associations remained after adjusting the regression models for potential confounders. CONCLUSIONS: We conclude that two specific patterns reflecting either inflammation-related or muscle-related biomarkers are both significantly associated with frailty among multi-morbid patients and that these specific biomarker patterns are more informative than single biomarker analyses considering frailty identification.

Dietary supplement use in ambulatory cancer patients: a survey on prevalence, motivation and attitudes.

PURPOSE: Patients with cancer often believe dietary supplements (DS) such as micronutrients and botanical products to be health supporting and non-toxic despite growing concerns regarding potential pharmacological interactions. Studies on the prevalence of DS use among patients with cancer are heterogeneous and mainly conducted at university-based cancer centers. This survey focused on a particular cancer patient group treated in an ambulatory setting without regular access to professional nutritional counselling. METHODS: Patients with a history of cancer or hematological malignancy were included in this survey. A self-reported questionnaire was used to evaluate the different aspects of DS use, changes in dietary habits and patients' demographic characteristics. RESULTS: Almost every second patient reported using DS (47.2%). Women (56.3%), patients with an academic degree (56.0%) and non-smokers (84.8%) were more inclined to use DS. Along with magnesium (16.6%), calcium (14.3%), multivitamins (12.0%) and vitamin C (9.4%), use of herbal supplements (12.6%) was common. Women (84.8% vs. 74.9% of men, p = < 0.001) and patients younger than 65 years (84.4% vs. 77.2% of patients > 65 y, p = 0.002) sought dietary advice more often. Support of the immune system was the main reason for DS use (26.4%) and a relevant number of patients (49.6%) reported to have changed their dietary habits following cancer diagnosis. CONCLUSION: DS use is common among patients with cancer treated in an ambulatory setting. This finding should encourage oncologists to implement detailed questioning about DS use and dietary habits to prevent potential interactions and offer substantial advice.

Age-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells.

BACKGROUND: Fatigue is a complex syndrome associated with exhaustion not relieved by sleep. It occurs frequently in older adults in the context of chronic disease and is associated with decreased physical capacity. Whether a mitochondrial dysfunction and therefore an impaired energy production might contribute to the development of fatigue during aging is yet unknown. The aim of this study was to evaluate mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) in older patients with and without fatigue. METHOD: Fatigue was determined according to the Brief Fatigue Inventory. Mitochondrial respiration of freshly isolated PBMCs was investigated by high-resolution respirometry using the Oroboros Oxygraph-O2k. Functional impairment and depressive symptoms were assessed using questionnaires. RESULTS: 23 geriatric patients (77.8 ± 4.9 years; 43.5% female) with fatigue and 22 without fatigue (75.4 ± 5.4 years; 45.5% female) were analyzed. Patients with fatigue exhibited more functional limitations and more depressive symptoms. High-resolution respirometry of intact PBMCs revealed a lower routine (4.82 ± 1.14 pmol/s versus 5.89 ± 1.90 pmol/s, p = 0.041) and maximum (6.55 ± 1.51 pmol/s versus 8.43 ± 3.67 pmol/s, p = 0.013) oxygen consumption rate, resulting in a reduced ATP-linked respiration (4.26 ± 1.00 pmol/s versus 5.09 ± 1.53 pmol/s, p = 0.035) of PBMCs from geriatric patients with fatigue compared to controls without. CONCLUSIONS: This short report shows that in this group of older patients, fatigue is associated with lower PBMC mitochondrial respiration. Whether the impaired mitochondrial respiration is accompanied by a reduced mitochondrial activity in other organs (e.g. muscle) remains to be elucidated.

Associations Between Serum GDF15 Concentrations, Muscle Mass, and Strength Show Sex-Specific Differences in Older Hospital Patients.

Aging is accompanied by a progressive decline of muscle mass and strength and also higher levels of circulating cytokines such as growth differentiation factor 15 (GDF15). Studies evaluating the association of GDF15 with muscle mass and strength are rare. In this analysis, we investigated GDF15 concentrations and their relationship with muscle mass and strength in older men compared with women. GDF15 serum concentrations were measured in 103 (60 years and older) hospital patients and an age-matched control group with an immunosorbent assay. Skeletal muscle mass was determined with the bioelectrical impedance analysis. Grip strength and knee extension strength were assessed and normalized for height. Associations between GDF15 concentrations and muscle mass and strength were evaluated with general linear models. Male patients showed higher levels of GDF15 compared with female patients (p = 0.021). Elevated GDF15 concentrations were associated with lower measures of muscle mass, exclusively in men, after adjustment for age and number of drugs per day. Our results indicate sex differences between associations of GDF15 with muscle mass and strength parameters in a cohort of older hospital patients.

Postprandial dynamics and response of fibroblast growth factor 21 in older adults.

BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition. METHODS: Participants (n = 60 older; n = 60 younger) were randomized to one of four test meals: dextrose, high carbohydrate (HC), high fat (HF) or high protein (HP). Blood was drawn before and 15, 30, 60, 120, 240 min after meal ingestion. Postprandial dynamics were evaluated using repeated measures ANCOVA. FGF21 response was assessed by incremental area under the curve. RESULTS: Fasting FGF21 concentrations were significantly higher in older adults. FGF21 dynamics were affected by test meal (p < 0.001) and age (p = 0.013), when adjusted for BMI and fasting FGF21. Postprandial FGF21 concentrations steadily declined over 240 min in both age groups after HF and HP, but not after dextrose or HC ingestion. At 240 min, FGF21 concentrations were significantly higher in older than in younger adults following dextrose (133 pg/mL, 95%CI: 103, 172 versus 91.2 pg/mL, 95%CI: 70.4, 118; p = 0.044), HC (109 pg/mL, 95%CI: 85.1, 141 versus 70.3 pg/mL, 95%CI: 55.2, 89.6; p = 0.014) and HP ingestion (45.4 pg/mL, 95%CI: 34.4, 59.9 versus 27.9 pg/mL 95%CI: 20.9, 37.1; p = 0.018). FGF21 dynamics and response to HF were similar for both age groups. CONCLUSIONS: The age-specific differences in postprandial FGF21 dynamics and response in healthy adults, potentially explain higher FGF21 concentrations in older age. Furthermore, there appears to be a significant impact of acute and recent protein intake on FGF21 secretion.

The prognostic impact of BIA-derived fat-free mass index in patients with cancer.

BACKGROUND & AIMS: Reduced muscle mass represents one of the top ranked phenotypic criteria for malnutrition proposed by the Global Leadership Initiative on Malnutrition. Although height-indexed fat-free mass (FFMI) thresholds have been proposed as useful surrogate measures of reduced muscle mass, the independent prognostic value of BIA-derived FFMI by bioelectric impedance analysis (BIA) in patients with cancer still needs to be fully explored. METHODS: Data on body mass index (BMI), 6-month percentage of weight loss (%WL), FFMI by BIA and quality of life (QoL by EORTC Quality of Life Questionnaire [EORTC QLQ-C30]) of Italian and German patients observed prospectively until death or censoring were used (N = 1217). Patients were stratified in 5 risk categories according to a robustly validated scoring system based on BMI and %WL. Low FFMI was defined as follows: men, <17 kg/m2; women, <15 kg/m2. RESULTS: Reduced FFMI was found in 234 patients (19.2%). After a median follow-up of 57 months [25th-75th, 31-60], 620 patients (50.9%) had died. The study detected differences in survival between patients presenting with and without reduced FFMI (14.0 months vs. 45.1 months; P < 0.001). The fully-adjusted hazard ratio of mortality for low FFMI was 1.46 [95%CI, 1.18-1.81] (P < 0.001). Low FFMI was also independently associated with reduced QoL: fully-adjusted odds ratio, 1.50 [95%CI, 1.00-2.25] (P = 0.050). CONCLUSIONS: Reduced FFMI by BIA independently predicted survival and was associated with impaired QoL. Altered body composition should always be considered in all patients with cancer as additional phenotypic criterion of poor prognosis and BIA offers the possibility of multiple, noninvasive bedside assessments.

Severe Weight Loss and Its Association with Fatigue in Old Patients at Discharge from a Geriatric Hospital.

Although malnutrition is frequent in the old, little is known about its association with fatigue. We evaluated the relation of self-reported severe weight loss with fatigue and the predictors for fatigue in old patients at hospital discharge. Severe weight loss was defined according to involuntary weight loss ≥5% in the last three months. We determined fatigue with the validated Brief Fatigue Inventory questionnaire. The regression analyses were adjusted for age, sex, number of comorbidities, medications/day, and BMI. Of 424 patients aged between 61 and 98 y, 34.1% had severe weight loss. Fatigue was higher in patients with severe weight loss (3.7 ± 2.3 vs. 3.2 ± 2.3 points, p = 0.021). In a multinomial regression model, weight loss was independently associated with higher risk for moderate fatigue (OR:1.172, CI:1.026-1.338, p = 0.019) and with increased risk for severe fatigue (OR:1.209, CI:1.047-1.395, p = 0.010) together with the number of medications/day (OR:1.220, CI:1.023-1.455, p = 0.027). In a binary regression model, severe weight loss predicted moderate-to-severe fatigue in the study population (OR:1.651, CI:1.052-2.590, p = 0.029). In summary, patients with self-reported severe weight loss at hospital discharge exhibited higher fatigue levels and severe weight loss was an independent predictor of moderate and severe fatigue, placing these patients at risk for impaired outcome in the post-hospital period.

Higher serum levels of fibroblast growth factor 21 in old patients with cachexia.

OBJECTIVE: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. METHODS: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-α were measured with enzyme-linked immunoassays. Cachexia was defined as ≥5% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). RESULTS: We included 103 patients with and without cachexia (76.9 ± 5.2 y of age) and 56 healthy controls (72.9 ± 5.9 y of age). Cachexia was present in 16.5% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 ± 821.3 versus 525.2 ± 560.3 pg/mL; P = 0.012) and the lowest FGF21 levels (293.3 ± 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-α did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total (ß = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (ß = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. CONCLUSIONS: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state.

The impact of malnutrition on quality of life in patients with systemic sclerosis.

BACKGROUND/OBJECTIVES: Our objective was to investigate the prevalence of malnutrition in patients with systemic sclerosis (SSc) and its impact on their quality of life (QoL). SUBJECTS/METHODS: One hundred and twenty-nine patients with SSc underwent clinical evaluation and were screened with the Malnutrition Universal Screening Tool (MUST). Malnutrition was defined as MUST score ≥2.To investigate QoL, all patients completed the Short Form 36 Questionnaire and the Scleroderma Health Assessment Questionnaire. The data were analyzed with IBM SPSS® Statistics by using χ2/Fisher's test, Mann-Whitney U test, correlation, and linear regression analysis. RESULTS: One hundred and twenty-nine patients were included in this study (mean age was 59.1 ± 13.8 years, 90.7% women). The prevalence of malnutrition was 10.9%. Age and disease duration were not significantly different between malnourished and well-nourished patients. All QoL scores (except bodily pain and self-reported health) were significantly impaired in malnourished patients. Furthermore, the Scleroderma Health Assessment Score score which assesses disease-specific QoL was significantly higher in the malnourished patients (1.6 ± 0.73 compared to 0.91 ± 0.61 in well-nourished patients; p = 0.001), reflecting a lower QoL due to disease-specific impairments. CONCLUSIONS: Severe malnutrition in SSc patients is associated with reduced QoL. Standardized nutritional screening should routinely be conducted to identify the risk of malnutrition in order to enable an intervention with multimodal treatment and avoid the serious consequences associated with severe malnutrition.

Comprehensive two-dimensional gas chromatography in combination with pixel-based analysis for fouling tendency prediction.

Fouling tendencies of a series of gas condensates were evaluated using comprehensive two-dimensional gas chromatography with flame ionization detection and sulfur chemiluminescence detection. A pixel-based approach was applied in order to identify parts of the chromatograms which were associated with the reactor coil fouling. Particular emphasis is given in this work to evaluate several feature selection methodologies along with various data preprocessing procedures. It was found that both aspects were crucial for studying the fouling tendencies and, as part of the subsequent partial least squares model development, predominantly the feature selection. Based on the flame ionization detector chromatograms and using the RReliefF algorithm for feature selection, a partial least squares regression model with one latent variable resulted in a root mean square error of the cross-validation of 0.65gdeposit/6h (17%). Based on the sulfur chemiluminescence detector chromatograms, the F-statistics feature selection generated a slightly better partial least squares regression model compared to using RReliefF, thus generating a model using one latent variable with a root mean square error of the cross-validation of 0.81gdeposit/6h (21%). Heavy aromatic compounds and heavy sulfur containing compounds were negatively associated with the fouling rate. Both were crucial in developing a partial least squares model with good prediction power, however, worked independently as predictors.

Quantitative analysis of nitrogen containing compounds in microalgae based bio-oils using comprehensive two-dimensional gas-chromatography coupled to nitrogen chemiluminescence detector and time of flight mass spectrometer.

Insight in the composition of the algae derived bio-oils is crucial for the development of efficient conversion processes and better upgrading strategies for microalgae. Comprehensive two-dimensional gas chromatography (GC×GC) coupled to nitrogen chemiluminescence detector (NCD) and time-of-flight mass spectrometer (TOF-MS) allows to obtain the detailed quantitative composition of the nitrogen containing compounds in the aqueous and the organic fraction of fast pyrolysis bio-oils from microalgae. Normal phase (apolar×mid-polar) and reverse phase column (polar×apolar) combination are investigated to optimize the separation of the detected nitrogen containing compounds. The reverse phase column combination gives the most detailed information in terms of the nitrogen containing compounds. The combined information from the GC×GC-TOF-MS (qualitative) and GC×GC-NCD (quantitative) with the use of a well-chosen internal standard, i.e. caprolactam, enables the identification and quantification of nitrogen containing compounds belonging to 13 different classes: amines, imidazoles, amides, imides, nitriles, pyrazines, pyridines, indoles, pyrazoles, pyrimidines, quinolines, pyrimidinediones and other nitrogen containing compounds which were not assigned to a specific class. The aqueous fraction mostly consists of amines (4.0wt%) and imidazoles (2.8wt%) corresponding to approximately 80wt% of the total identified nitrogen containing compounds. On the other hand, the organic fraction shows a more diverse distribution of nitrogen containing compounds with the majority of the compounds quantified as amides (3.0wt%), indoles (2.0wt%), amines (1.7wt%) and imides (1.3wt%) corresponding to approximately 65wt% of the total identified nitrogen containing compounds.