Effects of Exercise and Omega-3-Supplemented, High-Protein Diet on Inflammatory Markers in Serum, on Gene Expression Levels in PBMC, and after Ex Vivo Whole-Blood LPS Stimulation in Old Adults.

Inflammaging is related to cell senescence and reflects an erratic immune system, which promotes age-associated diseases. Exercise and nutrition, particularly omega-3 fatty acids, are able to affect inflammation. Therefore, we examined the effects of an 8-week exercise and dietary intervention on the inflammatory response in community-dwelling old adults. All participants received weekly vibration and home-based resistance exercise. Furthermore, participants were randomized to either a control, high-protein (1.2-1.5 g/kg), or high-protein, omega-3-enriched (2.2 g/day) diet. Before and after treatment, inflammatory markers in fasting serum and after whole-blood ex vivo lipopolysaccharide (LPS) stimulation were assessed. Gene expression levels of inflammatory markers were quantified in peripheral blood mononuclear cells (PBMC). Sixty-one participants (age: 70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein, omega-3-enriched diet decreased circulating anti-inflammatory interleukin (IL-) 10 and IL-1 receptor antagonist (IL-1RA). Sex-stratified analyses showed also significantly reduced pro-inflammatory markers in men with a high-protein, omega-3-enriched diet. Gene expression of IL-1RA was significantly reduced after both protein-enriched diets compared with controls. In comparison to a high-protein diet, exercise alone showed lower LPS-induced release of c-c motif chemokine ligand-2 (CCL-2), which tended to be more pronounced in men compared with women. Eight weeks of a high-protein, omega-3-enriched diet combined with exercise decreased circulating anti-inflammatory markers, and pro-inflammatory markers in men. A high-protein diet attenuated anti-inflammatory markers on gene expression level in PBMC. Exercise alone resulted in a lower pro-inflammatory response to LPS-exposure in whole-blood cultures.

Effects of an Omega-3 Supplemented, High-Protein Diet in Combination with Vibration and Resistance Exercise on Muscle Power and Inflammation in Old Adults: A Pilot Randomized Controlled Trial.

BACKGROUND: Inflammaging is considered to drive loss of muscle function. Omega-3 fatty acids exhibit anti-inflammatory properties. Therefore, we examined the effects of eight weeks of vibration and home-based resistance exercise combined with a whey-enriched, omega-3-supplemented diet on muscle power, inflammation and muscle biomarkers in community-dwelling old adults. METHODS: Participants were randomized to either exercise (3x/week, n = 20), exercise + high-protein diet (1.2-1.5 g/kg, n = 20), or exercise + high-protein and omega-3-enriched diet (2.2 g/day, n = 21). Muscle power (watt/m2) and chair rise test (CRT) time (s) were assessed via CRT measured with mechanography. Furthermore, leg strength (kg/m2) and fasting concentrations of inflammatory (interleukin (IL-) 6, IL-10, high-mobility group box-1 (HMGB-1)) and muscle biomarkers (insulin-like growth factor (IGF-) 1, IGF-binding protein-3, myostatin) were assessed. RESULTS: Sixty-one participants (70.6 ± 4.7 years; 47% men) completed the study. According to generalized linear mixed models, a high-protein diet improved leg strength and CRT time. Only IGF-1 increased with additional omega-3. Sex-specific analyses revealed that muscle power, IL-6, IL-6/IL-10 ratio, and HMGB-1 improved significantly in the male high-protein, omega-3-enriched group only. CONCLUSION: Vibration and home-based resistance exercise combined with a high-protein, omega-3-enriched diet increased muscle power and reduced inflammation in old men, but not in old women. While muscle biomarkers remained unchanged, a high-protein diet combined with exercise improved leg strength and CRT time.

Malnutrition in Older Adults-Recent Advances and Remaining Challenges.

Malnutrition in older adults has been recognised as a challenging health concern associated with not only increased mortality and morbidity, but also with physical decline, which has wide ranging acute implications for activities of daily living and quality of life in general. Malnutrition is common and may also contribute to the development of the geriatric syndromes in older adults. Malnutrition in the old is reflected by either involuntary weight loss or low body mass index, but hidden deficiencies such as micronutrient deficiencies are more difficult to assess and therefore frequently overlooked in the community-dwelling old. In developed countries, the most cited cause of malnutrition is disease, as both acute and chronic disorders have the potential to result in or aggravate malnutrition. Therefore, as higher age is one risk factor for developing disease, older adults have the highest risk of being at nutritional risk or becoming malnourished. However, the aetiology of malnutrition is complex and multifactorial, and the development of malnutrition in the old is most likely also facilitated by ageing processes. This comprehensive narrative review summarizes current evidence on the prevalence and determinants of malnutrition in old adults spanning from age-related changes to disease-associated risk factors, and outlines remaining challenges in the understanding, identification as well as treatment of malnutrition, which in some cases may include targeted supplementation of macro- and/or micronutrients, when diet alone is not sufficient to meet age-specific requirements.

Altered Adiponectin Response in Older Women Following Dextrose and High-Fat Dietary Challenges.

SCOPE: Despite its beneficial properties, higher adiponectin concentrations are paradoxically associated with mortality in advanced age. Several mechanisms are being discussed. However, little is known about postprandial regulation of adiponectin in older adults. We assessed age-specific differences of the adiponectin response to different test meals considering potential determinants. METHODS AND RESULTS: Older (n = 20) and younger (n = 22) women are randomized to a dextrose (DEX) or high-fat (HF) dietary challenge. Postprandial adiponectin and fibroblast growth factor 21 (FGF21) concentrations are measured before and 60, 120, 240 min after ingestion. We assessed postprandial changes and group differences using linear mixed models controlled for possible determinants. In younger women, postprandial adiponectin remains stable after both test meals. In contrast, adiponectin increases following DEX and decreases after HF in older women, irrespective of control variables. Postprandial adiponectin is positively associated with malondialdehyde and inversely associated with interleukin-6 following DEX and also negatively associated with metabolic parameters after both test meals. In older women, elevated postprandial FGF21 concentrations are associated with a higher adiponectin response (ß = 30.7, 95% CI 10.6-50.8, p = 0.007). CONCLUSIONS: Adiponectin response is associated with type of dietary challenge, age, and FGF21 response. Age-group differences are partly attributable to metabolic parameters and oxidative stress.

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.

Anti-Inflammatory Diets and Fatigue.

Accumulating data indicates a link between a pro-inflammatory status and occurrence of chronic disease-related fatigue. The questions are whether the observed inflammatory profile can be (a) improved by anti-inflammatory diets, and (b) if this improvement can in turn be translated into a significant fatigue reduction. The aim of this narrative review was to investigate the effect of anti-inflammatory nutrients, foods, and diets on inflammatory markers and fatigue in various patient populations. Next to observational and epidemiological studies, a total of 21 human trials have been evaluated in this work. Current available research is indicative, rather than evident, regarding the effectiveness of individuals' use of single nutrients with anti-inflammatory and fatigue-reducing effects. In contrast, clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms. Nonetheless, further research is needed to clarify conflicting results in the literature and substantiate the promising results from human trials on fatigue.

Translation and Cultural Adaptation of the Scored Patient-Generated Subjective Global Assessment: An Interdisciplinary Nutritional Instrument Appropriate for Dutch Cancer Patients.

BACKGROUND: Assessment of malnutrition is important in cancer patients. The Scored Patient-Generated Subjective Global Assessment (PG-SGA), an instrument that enables interdisciplinary assessment of malnutrition and its risk factors, was not available in Dutch. OBJECTIVE: Translation and cultural adaption of the original English PG-SGA to the Dutch setting. METHODS: The PG-SGA was translated and culturally adapted, following the International Society for Pharmacoeconomics and Outcomes Research principles. Perceived content validity, comprehensibility, and difficulty were explored among a multidisciplinary sample of healthcare professionals and their cancer patients. Content validity, comprehensibility, and difficulty were operationalized by calculating item and scale indices. On scale level, indices of 0.80 to 0.90 were considered acceptable, and indices of 0.90 or greater were considered excellent. RESULTS: Consensus was reached on 91 and 8 differences in the forward and back translations, respectively. Scale Content Validity Index was 0.89. Scale Comprehensibility Index and Scale Difficulty Index of the patient-generated component of the PG-SGA were 0.99 and 0.96, respectively. Scale Comprehensibility Index and Scale Difficulty Index of the professional component were 0.81 and 0.55, respectively. CONCLUSIONS: Translation and cultural adaptation of the PG-SGA according to the International Society for Pharmacoeconomics and Outcomes Research principles resulted in a Dutch version that maintained the purpose, meaning, and format and have acceptable content validity. Now a Dutch version of the PG-SGA is available that is considered comprehensible and easy by patients, and comprehensible and relevant by professionals. However, the professional component was considered difficult by the PG-SGA-naive professionals, which indicates a need for training. IMPLICATIONS FOR PRACTICE: A similar systematic approach for future translations of the PG-SGA is recommended, to safeguard cultural equivalence.

Occurrence and distribution of psychoactive compounds and their metabolites in the urban water cycle of Berlin (Germany).

The occurrence and distribution of six psychoactive compounds (primidone, phenobarbital, oxazepam, diazepam, meprobamate, and pyrithyldione) and a metabolite of primidone (phenylethylmalonamide) were investigated in wastewater treatment plant (WWTP) effluents, surface water, groundwater of a bank filtration site, raw and final drinking water, and in groundwater affected by former sewage irrigation. Primidone and its metabolite phenylethylmalonamide were found to be ubiquitous in environmental water samples in Berlin. Maximum concentrations of 0.87 and 0.42 µg/L, respectively, were encountered in WWTP effluents. Both compounds are apparently not removed when passaging through the different compartments of the water cycle and concentrations are only reduced by dilution. Phenobarbital was present at nearly every stage of the Berlin water cycle with the exception of raw and final drinking water. The highest concentrations of phenobarbital (up to 0.96 µg/L) were measured in groundwater influenced by former sewage irrigation. Oxazepam was only present in WWTP effluents and surface waters (up to 0.18 µg/L), while diazepam was not detected in any matrix. Due to their withdrawal from the German market years ago, the pharmaceuticals meprobamate and pyrithyldione were only found in sewage farm groundwater (up to 0.50 and 0.04 µg/L, respectively) and, in case of meprobamate, also in decade old bank filtrate (0.03 µg/L). Our results indicate a high persistence of some of the investigated compounds in the aquatic system. As a consequence, these pollutants may potentially reach drinking water resources via bank filtration if present in WWTP effluents and/or surface waters in partly closed water cycles such as Berlin's.

Occurrence of psychoactive compounds and their metabolites in groundwater downgradient of a decommissioned sewage farm in Berlin (Germany).

PURPOSE: Psychoactive compounds-meprobamate, pyrithyldione, primidone, and its metabolites, phenobarbital, and phenylethylmalonamide-were detected in groundwater within the catchment area of a drinking water treatment plant located downgradient of a former sewage farm in Berlin, Germany. The aim of this study was to investigate the distribution of the psychoactive compounds in anoxic groundwater and to assess the risk of drinking water contamination. Groundwater age was determined to achieve a better understanding of present hydrogeological conditions. METHODS: A large number of observation and production wells were sampled. Samples were analyzed using solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry. Groundwater age was estimated using the helium-tritium ((3)He-(3)H) dating method. RESULTS: Concentrations of psychoactive compounds up to 1 µg/L were encountered in the contamination plume. Generally, concentrations of phenobarbital and meprobamate were the highest. Elevated concentrations of the analytes were also detected in raw water from abstraction wells located approximately 2.5 km downgradient of the former sewage farm. Concentrations in the final drinking water were below the limit of quantification owing to dilution. The age of shallow groundwater samples ranged from years to a decade, whereas groundwater was up to four decades old at 40 m below ground. Concentrations of the compounds increased with groundwater age. CONCLUSIONS: Elevated concentrations of psychoactive drugs indicate a strong persistence of these compounds in the environment under anoxic aquifer conditions. Results suggest that the heritage of sewage irrigation will affect raw water quality in the area for decades. Therefore, further monitoring of raw and final drinking water is recommended to ensure that contaminant concentrations remain below the health-based precautionary value.