Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults.

BACKGROUND: Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals. OBJECTIVES: To investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults. DESIGN: Randomized controlled trial. SETTING: Exercise laboratory on the Health Sciences campus of an urban university. PARTICIPANTS: 99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults. INTERVENTION: 6-month structured physical activity with or without a protein and vitamin D nutritional supplement. MEASUREMENTS: Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention. RESULTS: At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively). CONCLUSIONS: These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Physical Performance and Serum 25(OH)vitamin D Status in Community Dwelling Old Mobility Limited Adults: A Cross-Sectional Study.

OBJECTIVES: To examine the potential association between serum 25(OH) vitamin D and the performance on the Short Physical Performance Battery (SPPB) including the sub-components; five repeated chair stands test, 4 meters walk test and balance in older mobility-limited community-dwelling men and women. DESIGN: A cross sectional study was performed in American and Swedish subjects who were examined for potential participation in a combined exercise and nutrition intervention trial. Logistic regression analysis and linear regression analyses were performed to evaluate the association for 25(OH)D with the overall score on the SBBP, chair stand, gait speed and balance. PARTICIPANTS: Community-dwelling (mean age 77.6 ± 5.3 years) mobility limited American (n=494) and Swedish (n=116) females (59%) and males. MEASUREMENTS: The SPPB (0-12 points) includes chair stand (s), gait speed (m/s) and a balance test. Mobility limitation i.e., SPPB score ≤ 9 was an inclusion criterion. A blood sample was obtained to measure serum 25(OH)vitamin D concentrations. RESULTS: No clear association of 25(OH)D with SPPB scores was detected either when 25(OH)D was assessed as a continuous variable or when categorized according to serum concentrations of <50, 50-75 or <75 nmol/L. However, when analyzing the relationship between 25(OH)D and seconds to perform the chair stands, a significant quadratic relationship was observed. Thus, at serum levels of 25(OH)D above 74 nmol/L, higher concentrations appeared to be advantageous for the chair stand test, whereas for serum levels below 74 nmol/L this association was not observed. CONCLUSION: This cross- sectional study lacked clear association between serum 25(OH)D and physical performance in mobility limited adults. A potentially interesting observation was that at higher serum levels of 25(OH)D a better performance on the chair stand test was indicated.

Effect of Structured Physical Activity and Nutritional Supplementation on Physical Function in Mobility-Limited Older Adults: Results from the VIVE2 Randomized Trial.

OBJECTIVES: The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). DESIGN: All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). SETTING: Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. PARTICIPANTS: Mobility-limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. MEASUREMENTS: Primary outcome was gait speed assessed by the 400M walk. RESULTS: 149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean 25(OH)D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. CONCLUSION: Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.

Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women.

BACKGROUND: The present study aimed to describe the relationship between self-reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women. METHODS: Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression. RESULTS: Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not. CONCLUSIONS: In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations.

Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

Sarcopenia and fragility fractures.

Sarcopenia, a reduction in muscle mass and muscle function, is considered one of the hallmarks of the aging process. Current views consider sarcopenia as the consequence of multiple medical, behavioural and environmental factors that characterize aged individuals. Likewise bone fragility is known to depend on several pathogenetic mechanisms leading to bone mass loss and reduction of bone strength. Muscle weakness, fear of falls, falls and subsequent fractures are associated to concurrent sarcopenia and osteoporosis and lead to restricted mobility, loss of autonomy and reduced life expectancy. The skeletal and the muscular organ systems are tightly intertwined: the strongest mechanical forces applied to bones are, indeed, those created by muscle contractions that condition bone density, strength, and microarchitecture. Not surprising, therefore, the decrease in muscle strength leads to lower bone strength. The degenerative processes leading to osteoporosis and sarcopenia show many common pathogenic pathways, like the sensitivity to reduced anabolic hormone secretion, increased inflammatory cytokine activity and reduced physical activity. Thus they may also respond to the same kind of treatments. Basic is life-style interventions related to exercise and nutrition. Sufficient vitamin D levels are of importance for both bone and muscle, primarily provided by sun exposure at younger age, and by supplementation at older age. Resistance training several times per week is crucial, and to be effective adequate access to energy and proteins is necessary.

Adipose tissue fatty acids and insulin sensitivity in elderly men.

AIMS/HYPOTHESIS: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. METHODS: In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n = 795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas-liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. RESULTS: Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r = -0.14), as were 16:1 n-7 (r = -0.15), 20:3 n-6 (r = -0.31), 20:4 n-6 (r = -0.38), 22:4 n-6 (r = -0.37) and 22:5 n-3 (r = -0.24; p < 0.001 for all). Some minor SFAs were positively correlated; 12:0 (r = 0.46), 14:0 (r = 0.32), 17:0 (r = 0.21) and 18:0 (r = 0.41; p < 0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r = 0.10, p < 0.01) and 18:3 n-3 (r = 0.16, p < 0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r = -0.11, p < 0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r = -0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. CONCLUSIONS/INTERPRETATION: Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.

Nutritional support and risk status among cancer patients in palliative home care services.

GOAL OF WORK: The aim of this study was to investigate the nutritional risk status and use of nutritional support among cancer patients enrolled in palliative home care services. Differences in the use of nutritional support in relation to nutritional, social and clinical factors, as well as survival were also investigated. PATIENTS AND METHODS: Structured telephone interviews were conducted with cancer patients enrolled in all 21 palliative home care services in the Stockholm region. An interview guide was designed to investigate topics related to the patient's nutritional situation. MAIN RESULTS: Interviews with 621 patients were analysed. Sixty-eight percent of the patients were scored as at nutritional risk according on a modified version of NRS-2002. Nutritional support was used by 55% of the patients, with oral nutritional supplements most common and 14% using artificial nutrition. Use of nutritional support was related to low BMI and severe weight loss and was more common in patients with shorter survival times. CONCLUSIONS: These findings demonstrate that nutritional support is used to treat already malnourished patients with shorter survival time, rather than to prevent malnutrition. A more structured approach to nutritional issues for patients in palliative phases, which considers life expectancy and psycho-social aspects of nutritional issues, could help identify potential candidates for nutritional support.

Food habits and appetite of elderly women at the time of a femoral neck fracture and after nutritional and anabolic support.

OBJECTIVE: To study appetite and food choices in lean elderly women at the time of a femoral neck fracture and after 6 months of nutritional and anabolic intervention. SUBJECTS AND METHODS: Forty-five nondemented women >70 years of age (mean +/- SD: 83 +/- 5 years) with a recent hip fracture and body mass index <24 kg/m2 (mean: 20.5 +/- 2.3) were interviewed about their appetite and dietary habits prior to fracture. The patients were randomized to treatment with a protein-rich liquid supplement (PR; 200 kcal and 20 g protein day(-1)) alone or in combination with nandrolone decanoate injections (PR/N) 25 mg i.m. every third week or to a control group (C). A second interview was conducted 6 months later. RESULTS: Reduced appetite before the fracture was reported by 60%. Half of the patients did not have dessert with any of their daily meals, one-third used low-fat margarines and one-third drank water with their meals. The estimated mean daily energy intake was 6.4 +/- 1.2 MJ (1541 +/- 304 kcal) indicating that three of four subjects did not meet their energy needs. At 6 months, 40% reported reduced appetite. There was no difference in the change of appetite between the three randomized groups. Still, half of the subjects appeared to not meet their energy needs. Protein intake increased in the PR and PR/N groups, in contrast to the controls (P = 0.002). CONCLUSION: Reduced appetite and insufficient energy intake was recorded in lean elderly women with a femoral neck fracture. Nutritional supplementation alone or in combination with an anabolic steroid increased protein intake without adversely affecting appetite.

The effect of nutritional intervention in elderly subjects residing in group-living for the demented.

OBJECTIVES: We studied the nutritional status and the effects of nutritional intervention on body weight, cognition and activities of daily life (ADL)-function in demented individuals. DESIGN: Controlled non-randomised study. SETTING: Group-living for demented elderly (GLD), ie community assisted housing. SUBJECTS AND INTERVENTIONS: Twenty-two residents living in one of two units (GLD-I), received oral liquid supplements (1720 kJ/410 kcal/day) and the personnel of the GLD-I were given nutritional education. Fourteen residents in the other unit (GLD-C) served as controls. After 6 months 21 (83 (4) y, 81% women) and 12 (85 (4) y, 100% women) of the participants, respectively, were re-examined according to body mass index (BMI, kg/m2), cognitive function (Mini Mental State Examination (MMSE, 0-30 p) and Clinical Dementia Rating Scale (CDR) and the Katz' ADL index. RESULTS: Body mass index (BMI) < or =20 was found in 19% of the participants and 44% had BMI< or =23. BMI correlated with MMSE (r=0.43, P<0.01). The weight of the residents in the intervention group increased by 3.4 (3) kg (P=0.001) at follow-up, whereas the weight remained unchanged in the control group. The cognitive function was low at the start in both groups, ie MMSE approximately 9 and no apparent positive effect of the nutritional intervention was seen. In addition, the ADL functions appeared to deteriorate in both groups. CONCLUSIONS: Being underweight was common among demented elderly in group-living and was related to low cognitive capacity. Five months of oral supplementation, along with education of personnel, was followed by a weight gain. In this study the nutritional treatment did not affect the rate of decline in cognitive function or Katz' ADL index. SPONSORSHIP: Supported by grants from the Swedish National Board of Health and Social Welfare. Semper Foods AB provided the liquid supplements.

Treatment of protein-energy malnutrition in chronic nonmalignant disorders.

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes.

Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people.

Essential fatty acid (FA) deficiency, which may accompany protein-energy malnutrition (PEM), has been associated with impaired inflammatory reactions. We evaluated this relationship by analysing FA profiles and delayed cutaneous hypersensitivity in 20 malnourished elderly non-cancer patients and in 20 age-matched control patients. As indicated by serum cholesterol and serum triglycerides, the lipid levels were decreased by about one-third in the subjects with PEM. In comparison with the controls, there was a reduction in the omega 3 FA (e.g. eicosapentanoate) in total serum lipids (mg l-1) and serum phospholipids (%) of 40% and 47%, respectively. Reductions in serum omega 6 FA (e.g. linoleate and arachidonate) levels corresponded to the drop in total FA concentrations (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished patients. The magnitude of the skin reaction was positively correlated (P < 0.05) to the concentrations of eicosapentanoate in serum lipids and serum phospholipids, as well as to the linoleate concentration in total serum lipids. Six of the malnourished patients took part in a nutritional intervention programme for 3 months. In parallel with an improvement in the nutritional status there was a 35% increase (P < 0.05) in the total omega 3 FA serum concentration. Negative skin tests became positive and the median skin induration enlarged threefold (P < 0.05). Thus, deficiency of omega 3 FA might be one factor contributing to cutaneous anergy in elderly malnourished patients.