BACKGROUND: Preventing metabolic syndrome (MetS) and frailty in older adults is crucial for healthy aging. The association between MetS and physical frailty is well-documented, with low-grade inflammation as potential explanation. However, the association between MetS and frailty as a multidimensional concept, and the association of low-grade inflammation with presence of MetS and frailty, is yet unclear. Therefore, we examined these associations low-grade inflammation in a large cohort of community-dwelling older adults.METHODS: This cross-sectional study was performed among adults aged ≥ 65 years enrolled in the Dutch Lifelines population cohort. MetS was defined according to the Joint Interim Statement of 2009. Frailty was measured by the Groningen Frailty Indicator (GFI), which consists of 15 self-reported items on both physical and psychosocial functioning, with a score ≥ 4 indicating presence of frailty. The association between MetS and its five components and frailty was assessed using logistic regression models. Low-grade inflammation was represented by high-sensitivity C-reactive protein (hsCRP) level. The association of hsCRP level with presence of MetS and frailty was assessed using multinomial logistic regression in a sub-cohort with available hsCRP measurements.RESULTS: Of 11,552 adults (52.1% women) included, the prevalences of MetS and frailty were 28% and 15%, respectively. MetS was positively associated with frailty after adjusting for relevant covariates (OR: 1.37; 95% CI: 1.22-1.53). MetS components elevated blood pressure was most strongly associated with frailty. In the sub-cohort of 3896 participants, high hsCRP was associated with presence of MetS and frailty (OR: 1.31; 95% CI: 1.15-1.51), and MetS alone (OR: 1.44; 95% CI: 1.33-1.56), but not to frailty alone. A higher hsCRP level was associated with a higher score on the physical domain of frailty (b: 0.06; 95% CI: 0.03-0.08).CONCLUSIONS: Presence of MetS is associated with presence of frailty indicated by a multidimensional index in a large group of Dutch older adults. Low-grade inflammation, indicated by plasma hsCRP level, was found to be associated with both presence of MetS and frailty and presence of MetS alone. Increased hsCRP levels were associated with the physical component of frailty, but not with frailty as a multidimensional concept.
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Background and aims: Observational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.Methods: In this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.Results: Administration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.Conclusion: This study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.Keywords: biomarkers; diet; glucoraphanin; hormesis; inflammation; nutrients; phenotypic flexibility; sulforaphane.
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Background: A chronic low-grade infammatory profle (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for efects of nutritional supplementation on CLIP is limited. Aim To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein afected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. Methods: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4–9) and a body mass index of 20–30 kg/m2 were randomly allocated to two daily servings of active (n=137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n=151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH) D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. Results: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p=0.006 and p<0.001, respectively). For IL-6 a signifcant time × treatment interaction (p=0.046) was observed, with no signifcant change over time in the active group (p=0.155) compared to control (signifcant increase p=0.012). IL-8 showed an overall signifcant decrease (p=0.03). The change in pre-albumin was a signifcant predictor for changes in IL-6 after 13 weeks. Conclusions: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations
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Background: Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. Methods: In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). Results: There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. Conclusion: 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.
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ObjectivesChronic systemic low grade inflammation is associated with the age-related loss of muscle mass. Resistance exercise has been suggested to reduce or lower chronic systemic low grade inflammation. However, systemic chronic low-grade inflammation may adversely affect the adaptive response to exercise training. We investigated the effect of resistance exercise training on systemic chronic low-grade inflammation in older adults. In addition, we studied the association between systemic chronic low-grade inflammation and the adaptive response to exercise training.Design/setting/participantsFrail and pre-frail older adults (61 subjects) performed 24 weeks of progressive resistance exercise training. Frailty was assessed using the Fried frailty criteria.MeasurementsLean body mass (DXA), strength (1RM), circulating levels of IL-1β, IL-6, IL-8 and TNF-α were measured prior to exercise training, after 12 weeks of training, and after 24 weeks of training.ResultsProlonged progressive resistance exercise training did not affect circulating levels of IL-6, IL-8 and TNF-α. However, exercise training led to a small but significant increase of 0.052 pg/mL in IL-1β. Higher circulating levels of TNF-α, IL-8 and IL-6 during the training period were negatively associated with strength gains for the leg press. A doubling of plasma TNF-α, IL-8 or IL-6 resulted in reduced strength gains for leg press with coefficients of −3.52, −3.42 and −1.54 respectively. High levels of circulating TNF-α were also associated with decreased strength gains for the leg extension (coefficient −1.50). Inflammatory cytokines did not appear to have an effect on gains in lean mass.ConclusionOur findings suggest that increased levels of plasma cytokines (TNF-α, IL-6 and IL-8) are associated with lower strength gains during resistance exercise training.
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The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NMon ILCs and other components of the serosal immune systemare scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NMmay lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NMon the serosal immune system.
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Introduction:The recently published 2018 ESPEN Guidelines on Clinical Nutrition in the Intensive Care Unit [1] represents a valuable revision of the 2006 Enteral Nutrition Guidelines [2] and the 2009 Parenteral Nutrition Guidelines [3] published earlier by this European group. The guidelines committee members have done an excellent job in putting thismanuscript together, providing directives that are clear, concise, brief, and most importantly, transparent. They included only studies published since 2000 for use in their meta-analyses, commenting that this time of transition heralded a new era in the literature involving higher quality randomized control trials (RCTs) and methodologic innovations such as trial registry. Not mentioned (but felt by many within the nutrition community) was the sense that this particular time was a tipping point, following the publication of Van den Berghe’s seminal paper on intensive insulin therapy [4]. Studies published in nutrition prior to this date were felt to reflect an older more antiquated style of management that was less effective. These authors utilized the persistent inflammation catabolism syndrome (PICS) system where four parameters (the patient, intervention, controls, and outcomes) are clearly described, which in turn direct the questions that the guideline committee members were to address. Quality of evidence was assessed by GRADE methodology, and a cut-off date of August 2017 for data entry from the literature was clearly identified. Not all of the recommendations were based on RCTs. The authors are to be commended in that they provided recommendations based on Level 4 low-quality evidence, in areas where RCTs were not available, clearly taking advantage of the group of experts on the committee to provide practical guidance for clinicians where there was a paucity of literature to support evidence-based practices.
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Low-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial [RCT] 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score [DAS28] ≤ 5.1, RCT 1, n = 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2, n = 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3, n = 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6-12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.
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Circulating sex hormone levels have been linked to a wide range of cardiovascular risk factors in men, but studies on incident CVD have been inconclusive [1]. Recent data from meta-analyses show an increase in CVD risk with low testosterone in elderly men and no association with estradiol levels [2,3]. To clarify the role of sex hormones in male CVD risk, we examined the cross-sectional and longitudinal associations between endogenous sex hormones and subclinical atherosclerosis in a population-based cohort of middle-aged and older men.
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Acne vulgaris is considered one of the most common medical skin conditions globally, affecting approximately 85% of individuals worldwide. While acne is most prevalent among adolescents between 15 to 24 years old, it is not uncommon in adults either. Acne addresses a number of different challenges, causing a multidimensional disease burden. These challenges include clinical sequelae, such as post inflammatory hyperpigmentation (PIH) and the chance of developing lifelong disfiguring scars, psychological aspects such as deficits in health related quality of life, chronicity of acne, economic factors, and treatment-related issues, such as antimicrobial resistance. The multidimensionality of the disease burden stipulates the importance of an effective and timely treatment in a well organised care system. Within the Netherlands, acne care provision is managed by several types of professional care givers, each approaching acne care from different angles: (I) general practitioners (GPs) who serve as ‘gatekeepers’ of healthcare within primary care; (II) dermatologists providing specialist medical care within secondary care; (III) dermal therapists, a non-physician medical professional with a bachelor’s degree, exclusively operating within the Australian and Dutch primary and secondary health care; and (IV) beauticians, mainly working within the cosmetology or wellness domain. However, despite the large variety in acne care services, many patients experience a delay between the onset of acne and receiving an effective treatment, or a prolonged use of care, which raises the question whether acne related care resources are being used in the most effective and (cost)efficient way. It is therefore necessary to gain insights into the organization and quality of Dutch acne health care beyond conventional guidelines and protocols. Exploring areas of care that may need improvement allow Dutch acne healthcare services to develop and improve the quality of acne care services in harmony with patient needs.
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