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      Effect of dietary omega-3 fatty acid supplementation on frailty-related phenotypes in older adults: a systematic review and meta-analysis protocol

      protocol
      1 , 2 , 3 , 1 , 2 , 3
      BMJ Open
      BMJ Publishing Group
      frailty, omega-3, older adults

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          Abstract

          Introduction

          The beneficial effect of dietary omega-3 supplementation in younger adults or older people with acute or chronic disease is established. Knowledge is now needed about the effect in medically stable older people. The objective of this study is to examine and assess the evidence for a role of dietary omega-3 polyunsaturated fatty acid (PUFA) supplementation in older adults on (1) muscle mass and muscle strength, (2) inflammatory biomarkers and (3) physical activity.

          Methods and analysis

          A systematic review and data synthesis will be conducted of randomised controlled trials in older people not recruited for any given disease diagnosis. Placebo-controlled studies reporting interventions involving dietary supplementation of omega-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid will be included. Outcomes must include changes from baseline to last available follow-up for one or more of the following: muscle mass, inflammatory biomarkers, physical activity, walking speed, weight change, hand grip strength or muscle strength. Once the search strategy has been carried out, two independent researchers will assess relevant papers for eligibility. Articles up until 31 December 2017 in any language will be included. We will provide a narrative synthesis of the findings from the included studies. Studies will be grouped for meta-analysis according to the outcome(s) provided. Where studies have used the same type of intervention, with the same outcome measure, we will pool the results using a random effects meta-analysis, with standardised mean differences for continuous outcomes and risk ratios for binary outcomes, and calculate 95% CI and two-sided p values for each outcome.

          Ethics and dissemination

          No research ethics approval is required for this systematic review as no confidential patient data will be used. The results of this systematic review will be disseminated through publication in an open-access peer-reviewed journal and through conference presentations.

          PROSPERO registration number

          CRD42017080240.

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          Most cited references23

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          Nutritional determinants of frailty in older adults: A systematic review

          Background Frailty is a geriatric syndrome that affects multiple domains of human functioning. A variety of problems contributes to the development of this syndrome; poor nutritional status is an important determinant of this condition. The purpose of this systematic review was to examine recent evidence regarding the association between nutritional status and frailty syndrome in older adults. Methods PubMed, Web of Science, and Scopus electronic databases were searched using specific key words, for observational papers that were published during the period from 2005 to February 2017 and that studied the association or relationship between nutritional status and frailty in older adults. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was followed to assess the quality of the included articles. Results Of the 2042 studies found, nineteen met the inclusion criteria. Of these studies, five provided data on micronutrients and frailty, and reported that frailty syndrome is associated with low intakes of specific micronutrients. Five studies provided data on macronutrients and frailty, and among those studies, four revealed that a higher protein intake was associated with a lower risk of frailty. Three studies examined the relationship between diet quality and frailty, and showed that the quality of the diet is inversely associated with the risk of being frail. Two studies provided data on the antioxidant capacity of the diet and frailty, and reported that a high dietary antioxidant capacity is associated with a lower risk of developing frailty. Finally, seven studies evaluated the relationship between scores on both the Mini Nutritional Assessment (MNA) and the MNA-SF (Short Form) and frailty, and revealed an association between malnutrition and/or the risk of malnutrition and frailty. Conclusions This systematic review confirms the importance of both quantitative (energy intake) and qualitative (nutrient quality) factors of nutrition in the development of frailty syndrome in older adults. However, more longitudinal studies on this topic are required to further understand the potential role of nutrition in the prevention, postponement, or even reversion of frailty syndrome. Electronic supplementary material The online version of this article (doi:10.1186/s12877-017-0496-2) contains supplementary material, which is available to authorized users.
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            Inflammation and frailty in older women.

            To evaluate relationships between white blood cell (WBC) count and interleukin-6 (IL-6) and prevalent frailty. Cross-sectional study. Two population-based studies, the Women's Health and Aging Studies (WHAS) I and II, Baltimore, Maryland. Five hundred fifty-eight women aged 65 to 101 from WHAS I and 548 women aged 70 to 79 from the merged WHAS I and II cohorts. Frailty was determined using validated screening criteria. WBC counts and IL-6 levels were measured using standard laboratory methods. Odds ratios (ORs) for frailty were evaluated across tertiles of baseline WBC counts and IL-6 levels, adjusting for age, race, education, body mass index, and smoking status. In WHAS I, those in the top tertile of WBC count and IL-6 had ORs of 4.25 (95% confidence interval (CI)=1.89-9.58) and 3.98 (95% CI=1.76-9.00), respectively, for frailty (both P<.001). In the combined models, participants in the top tertile of WBC count had an OR of 3.15 (95% CI=1.34-7.41), adjusting for IL-6 (P<.01), and those in the top tertile of IL-6 had an OR of 2.81 (95% CI=1.19-6.64), adjusting for WBC count (P<.05). Furthermore, participants in the top tertiles of WBC count and IL-6 had an OR of 9.85 (95% CI=3.04-31.99), and those in the middle/top tertiles had an OR of 5.40 (95% CI=1.83-15.92) (P<.001, trend test) for frailty. These results were validated in the merged WHAS I and II. Higher WBC counts and IL-6 levels were independently associated with prevalent frailty in community-dwelling older women.
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              Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women

              Summary Background & aims Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). Methods Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13C6-phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting. Results Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0–2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0–4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05). Conclusions In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2018
                17 May 2018
                : 8
                : 5
                : e021344
                Affiliations
                [1 ] NIHR Nottingham BRC , Nottingham, UK
                [2 ] departmentArthritis Research UK Pain Centre , University of Nottingham , Nottingham, UK
                [3 ] departmentDivision of Rheumatology, Orthopaedics and Dermatology, School of Medicine , University of Nottingham , Nottingham, UK
                Author notes
                [Correspondence to ] Dr Joanne Stocks; joanne.stocks@ 123456nottingham.ac.uk
                Author information
                http://orcid.org/0000-0002-7800-6002
                http://orcid.org/0000-0003-1141-4471
                Article
                bmjopen-2017-021344
                10.1136/bmjopen-2017-021344
                5961576
                29773704
                6f1eb530-1293-4ef1-8fd4-107e35d2daca
                © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

                History
                : 21 December 2017
                : 27 March 2018
                : 06 April 2018
                Funding
                Funded by: National Institute for Health Research Nottingham Biomedical Research Centre;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000341, Arthritis Research UK;
                Categories
                Geriatric Medicine
                Protocol
                1506
                1698
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                Medicine
                frailty,omega-3,older adults
                Medicine
                frailty, omega-3, older adults

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