Counteracting Age-related Loss of Skeletal Muscle Mass: a clinical and ethnological trial on the role of protein supplementation and training load (CALM Intervention Study): study protocol for a randomized controlled trial

Rasmus Leidesdorff Bechshøft, Søren Reitelseder, Grith Højfeldt, Josué Leonardo Castro-Mejía, Bekzod Khakimov, Hajar Fauzan Bin Ahmad, Michael Kjær, Søren Balling Engelsen, Susanne Margrete Bølling Johansen, Morten Arendt Rasmussen, Aske Juul Lassen, Tenna Jensen, Nina Beyer, Anja Serena, Frederico Jose Armando Perez-Cueto, Dennis Sandris Nielsen, Astrid Pernille Jespersen, Lars Holm, Rasmus Leidesdorff Bechshøft, Søren Reitelseder, Grith Højfeldt, Josué Leonardo Castro-Mejía, Bekzod Khakimov, Hajar Fauzan Bin Ahmad, Michael Kjær, Søren Balling Engelsen, Susanne Margrete Bølling Johansen, Morten Arendt Rasmussen, Aske Juul Lassen, Tenna Jensen, Nina Beyer, Anja Serena, Frederico Jose Armando Perez-Cueto, Dennis Sandris Nielsen, Astrid Pernille Jespersen, Lars Holm

Abstract

Background: Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle Mass (CALM) to investigate the impact of lifestyle changes on physical and functional outcomes as well as everyday practices and habits in a qualitative context.

Methods: We will randomize 205 participants older than 65 years to be given 1 year of two daily nutrient supplements with 10 g of sucrose and 20 g of either collagen protein, carbohydrates, or whey. Further, two groups will perform either heavy progressive resistance training or light load training on top of the whey supplement.

Discussion: The primary outcome of the CALM Intervention Study is the change in thigh cross-sectional area. Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals.

Trial registration: ClinicalTrials.gov NCT02034760 . Registered on 10 January 2014. ClinicalTrials.gov NCT02115698 . Registered on 14 April 2014. Danish regional committee of the Capital Region H-4-2013-070. Registered on 4 July 2013. Danish Data Protection Agency 2012-58-0004 - BBH-2015-001 I-Suite 03432. Registered on 9 January 2015.

Keywords: Elderly; Gut microbiome; Muscle; Plasma metabolome; Protein; Strength training; Whey.

Figures

Fig. 1
Fig. 1
Hypothesized improvements over time with different interventions. Black lines mark the expected effect of per-protocol analysis: HRTW (solid line), LITW (long-dashed line), WHEY (short-dashed line), COLL (dashed-dotted line), and CARB (dotted line) interventions when analyzed per protocol. The gray line marks the expected effect intention-to-treat analysis of HRTW. CARB carbohydrate supplementation group, COLL collagen supplementation group, HRTW heavy resistance training with whey supplementation, LITW light-intensity training with whey supplementation, WHEY whey supplementation
Fig. 2
Fig. 2
Spectrum of outcome variables. In the interdisciplinary Counteracting Age-related Loss of Skeletal Muscle Mass Intervention Study, we are investigating the entire spectrum of possible impacts of the intervention by applying objective, quantitative measures of the body and subjective, qualitative investigations of the participants
Fig. 3
Fig. 3
Participant flow. Ntotal represents the expected number of inclusions in each group. Nacute represents the expected number of participants who will complete the measurements of fractional synthesis rate at 0 and 12 months. COLL Collagen supplementation, CARB Carbohydrate supplementation, WHEY Whey supplementation, LITW Light intensity resistance training and whey supplementation, HRTW Heavy resistance training and whey supplementation
Fig. 4
Fig. 4
Magnetic resonance imaging analysis. We place slices as shown for analysis of cross-sectional area of the m. quadriceps femoris muscle and analyze slices 3 (counting in distal to proximal direction) and 4 for all subjects, and we use slice 4 for primary outcome evaluation. We fix the placement of slices in absolute distances, but we measure the femur length on dual-energy X-ray absorptiometric scans from the lateral tibial plateau (0 %) to the top of the greater trochanter (100 %) to report the relative placement of slices. Currently, placement of slice 3 ranges from 27 % to 36 % and slice 4 from 40 % to 54 % of the femoral length, depending on the height of the participant

References

    1. National Institute on Aging, National Institutes of Health (NIH), World Health Organization. Global health and aging. NIH Publication 11-7737. Washington, DC: NIH; October 2011. . Accessed 27 Jul 2016.
    1. Population Division, Department of Economic Affairs, United Nations . World population prospects: the 2015 revision. Geneva, Switzerland: United Nations; 2015.
    1. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56. doi: 10.1093/gerona/56.3.M146.
    1. Rosenberg IH. Summary comments. Am J Clin Nutr. 1989;50:1231–3.
    1. Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol. 2000;89:81–8.
    1. Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol. 2000;88:1321–6.
    1. Gallagher D, Ruts E, Visser M, Heshka S, Baumgartner RN, Wang J, et al. Weight stability masks sarcopenia in elderly men and women. Am J Physiol Endocrinol Metab. 2000;279:E366–75.
    1. Skelton DA, Greig CA, Davies JM, Young A. Strength, power and related functional ability of healthy people aged 65-89 years. Age Ageing. 1994;23:371–7. doi: 10.1093/ageing/23.5.371.
    1. Landi F, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, et al. Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study. Clin Nutr. 2012;31:652–8. doi: 10.1016/j.clnu.2012.02.007.
    1. Friedman EM, Ryff CD. Living well with medical comorbidities: a biopsychosocial perspective. J Gerontol B Psychol Sci Soc Sci. 2012;67:535–44. doi: 10.1093/geronb/gbr152.
    1. da Silva AT, de Oliveira Duarte YA, Ferreira Santos JL, Wong R, Lebrão ML. Sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) versus dynapenia as a risk factor for mortality in the elderly. J Nutr Health Aging. 2014;18:751–6. doi: 10.1007/s12603-014-0540-2.
    1. Morley JE, Abbatecola AM, Argiles JM, Baracos V, Bauer J, Bhasin S, et al. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12:403–9. doi: 10.1016/j.jamda.2011.04.014.
    1. Deutz NEP, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33:929–36. doi: 10.1016/j.clnu.2014.04.007.
    1. Cruz-Jentoft AJ. Perspective: Protein and exercise for frailty and sarcopenia: still learning. J Am Med Dir Assoc. 2013;14:69–71. doi: 10.1016/j.jamda.2012.09.024.
    1. Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, et al. Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. J Gerontol A Biol Sci Med Sci. 2015;70:57–62. doi: 10.1093/gerona/glu103.
    1. Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, et al. Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol. 2009;587(Pt 1):211–7. doi: 10.1113/jphysiol.2008.164483.
    1. Kumar V, Atherton PJ, Selby A, Rankin D, Williams J, Smith K, et al. Muscle protein synthetic responses to exercise: effects of age, volume, and intensity. J Gerontol A Biol Sci Med Sci. 2012;67:1170–7. doi: 10.1093/gerona/gls141.
    1. Tieland M, Dirks ML, van der Zwaluw N, Verdijk LB, van de Rest O, de Groot LCPGM, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2012;13:713–9. doi: 10.1016/j.jamda.2012.05.020.
    1. Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330:1769–75. doi: 10.1056/NEJM199406233302501.
    1. Bartali B, Frongillo EA, Bandinelli S, Lauretani F, Semba RD, Fried LP, et al. Low nutrient intake is an essential component of frailty in older persons. J Gerontol A Biol Sci Med Sci. 2006;61:589–93. doi: 10.1093/gerona/61.6.589.
    1. Beasley JM, Shikany JM, Thomson CA. The role of dietary protein intake in the prevention of sarcopenia of aging. Nutr Clin Pract. 2013;28:684–90. doi: 10.1177/0884533613507607.
    1. Beasley JM, Wertheim BC, LaCroix AZ, Prentice RL, Neuhouser ML, Tinker LF, et al. Biomarker-calibrated protein intake and physical function in the Women’s Health Initiative. J Am Geriatr Soc. 2013;61:1863–71. doi: 10.1111/jgs.12503.
    1. Tieland M, van de Rest O, Dirks ML, van der Zwaluw N, Mensink M, van Loon LJC, et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2012;13:720–6. doi: 10.1016/j.jamda.2012.07.005.
    1. Zhu K, Kerr DA, Meng X, Devine A, Solah V, Binns CW, et al. Two-year whey protein supplementation did not enhance muscle mass and physical function in well-nourished healthy older postmenopausal women. J Nutr. 2015;145:2520–6. doi: 10.3945/jn.115.218297.
    1. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE Study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16:740–7. doi: 10.1016/j.jamda.2015.05.021.
    1. Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, et al. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 2005;19:422–4.
    1. Pennings B, Groen B, de Lange A, Gijsen AP, Zorenc AH, Senden JMG, et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab. 2012;302:E992–9. doi: 10.1152/ajpendo.00517.2011.
    1. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, et al. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2012;108:1780–8. doi: 10.1017/S0007114511007422.
    1. World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), United Nations University (UNU) Protein and amino acid requirements in human nutrition: report of a joint FAO/WHO/UNU expert consultation. WHO technical report series 935. Geneva, Switzerland: WHO; 2007.
    1. Devries MC, Breen L, Von Allmen M, MacDonald MJ, Moore DR, Offord EA, et al. Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men. Physiol Rep. 2015;3(8):e12493. doi: 10.14814/phy2.12493.
    1. Pennings B, Boirie Y, Senden JMG, Gijsen AP, Kuipers H, Van Loon LJC. Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr. 2011;93:997–1005. doi: 10.3945/ajcn.110.008102.
    1. Volpi E, Campbell WW, Dwyer JT, Johnson MA, Jensen GL, Morley JE, et al. Is the optimal level of protein intake for older adults greater than the recommended dietary allowance? J Gerontol A Biol Sci Med Sci. 2013;68:677–81. doi: 10.1093/gerona/gls229.
    1. Christensen AI, Davidsen M, Ekholm O, Pedersen PV, Juel K. Danskernes sundhed – den nationale sundhedsprofil 2013 [in Danish] Copenhagen: Sundhedsstyrelsen; 2014.
    1. Pedersen AN, Christensen T, Matthiessen J, Knudsen VK, Rosenlund-Sørensen M, Biltoft-Jensen A, et al. Danskernes kostvaner 2011-2013 [in Danish] Søborg, Denmark: DTU Fødevareinstituttet; 2015.
    1. Pedersen AN, Cederholm T. Health effects of protein intake in healthy elderly populations: a systematic literature review. Food Nutr Res. 2014;58:23364. doi: 10.3402/fnr.v58.23364.
    1. Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14:542–59. doi: 10.1016/j.jamda.2013.05.021.
    1. Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR. Role of dietary protein in the sarcopenia of aging. Am J Clin Nutr. 2008;87:1562S–6S.
    1. European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies Scientific opinion on dietary reference values for protein. EFSA J. 2012;10(2):2557. doi: 10.2903/j.efsa.2012.2557.
    1. Berner LA, Becker G, Wise M, Doi J. Characterization of dietary protein among older adults in the United States: amount, animal sources, and meal patterns. J Acad Nutr Diet. 2013;113:809–15. doi: 10.1016/j.jand.2013.01.014.
    1. Areta JL, Burke LM, Ross ML, Camera DM, West DWD, Broad EM, et al. Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol. 2013;591(Pt 9):2319–31. doi: 10.1113/jphysiol.2012.244897.
    1. Paddon-Jones D, Campbell WW, Jacques PF, Kritchevsky SB, Moore LL, Rodriguez NR, et al. Protein and healthy aging. Am J Clin Nutr. 2015;101:1339S–45S.
    1. Bollwein J, Diekmann R, Kaiser MJ, Bauer JM, Uter W, Sieber CC, et al. Distribution but not amount of protein intake is associated with frailty: a cross-sectional investigation in the region of Nürnberg. Nutr J. 2013;12:109. doi: 10.1186/1475-2891-12-109.
    1. Mamerow MM, Mettler JA, English KL, Casperson SL, Arentson-Lantz E, Sheffield-Moore M, et al. Dietary protein distribution positively influences 24-h muscle protein synthesis in healthy adults. J Nutr. 2014;144:876–80. doi: 10.3945/jn.113.185280.
    1. Pérez-Cueto FJA, Aschemann-Witzel J, Shankar B, Brambila-Macias J, Bech-Larsen T, Mazzocchi M, et al. Assessment of evaluations made to healthy eating policies in Europe: a review within the EATWELL Project. Public Health Nutr. 2012;15:1489–96. doi: 10.1017/S1368980011003107.
    1. Abe T, Mitsukawa N, Thiebaud RS, Loenneke JP, Loftin M, Ogawa M. Lower body site-specific sarcopenia and accelerometer-determined moderate and vigorous physical activity: the HIREGASAKI study. Aging Clin Exp Res. 2012;24:657–62.
    1. American College of Sports Medicine Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009;41:687–708. doi: 10.1249/MSS.0b013e3181915670.
    1. Campos GER, Luecke TJ, Wendeln HK, Toma K, Hagerman FC, Murray TF, et al. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones. Eur J Appl Physiol. 2002;88:50–60. doi: 10.1007/s00421-002-0681-6.
    1. Holm L, Reitelseder S, Pedersen TG, Doessing S, Petersen SG, Flyvbjerg A, et al. Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity. J Appl Physiol. 2008;105:1454–61. doi: 10.1152/japplphysiol.90538.2008.
    1. Arnarson A, Gudny Geirsdottir O, Ramel A, Briem K, Jonsson PV, Thorsdottir I. Effects of whey proteins and carbohydrates on the efficacy of resistance training in elderly people: double blind, randomised controlled trial. Eur J Clin Nutr. 2013;67:821–6. doi: 10.1038/ejcn.2013.40.
    1. Sipilä S, Suominen H. Effects of strength and endurance training on thigh and leg muscle mass and composition in elderly women. J Appl Physiol. 1995;78:334–40.
    1. Kryger AI, Andersen JL. Resistance training in the oldest old: consequences for muscle strength, fiber types, fiber size, and MHC isoforms. Scand J Med Sci Sports. 2007;17:422–30. doi: 10.1111/j.1600-0838.2006.00575.x.
    1. Stewart VH, Saunders DH, Greig CA. Responsiveness of muscle size and strength to physical training in very elderly people: a systematic review. Scand J Med Sci Sports. 2014;24:e1–10. doi: 10.1111/sms.12123.
    1. King AC. Interventions to promote physical activity by older adults. J Gerontol A Biol Sci Med Sci. 2001;56(Spec No 2):36–46. doi: 10.1093/gerona/56.suppl_2.36.
    1. King AC, Castro C, Wilcox S, Eyler AA, Sallis JF, Brownson RC. Personal and environmental factors associated with physical inactivity among different racial-ethnic groups of U.S. middle-aged and older-aged women. Health Psychol. 2000;19:354–64. doi: 10.1037/0278-6133.19.4.354.
    1. King AC, Haskell WL, Taylor CB, Kraemer HC, DeBusk RF. Group- vs home-based exercise training in healthy older men and women: a community-based clinical trial. JAMA. 1991;266:1535–42. doi: 10.1001/jama.1991.03470110081037.
    1. Perri MG, Martin AD, Leermakers EA, Sears SF, Notelovitz M. Effects of group- versus home-based exercise in the treatment of obesity. J Consult Clin Psychol. 1997;65:278–285. doi: 10.1037/0022-006X.65.2.278.
    1. Daley AJ, Maynard IW. Preferred exercise mode and affective responses in physically active adults. Psychol Sport Exerc. 2003;4:347–56. doi: 10.1016/S1469-0292(02)00018-3.
    1. MinimPy 0.3. . Accessed 27 Jul 2016.
    1. Saghaei M, Saghaei S. Implementation of an open-source customizable minimization program for allocation of patients to parallel groups in clinical trials. J Biomed Sci Eng. 2011;4:734–9. doi: 10.4236/jbise.2011.411090.
    1. Brzycki M. A practical approach to strength training. 1. Grand Rapids, MI: Masters Press; 1989.
    1. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1998;85:115–22.
    1. Fuller NJ, Hardingham CR, Graves M, Screaton N, Dixon AK, Ward LC, et al. Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison. Int J Obes. 1999;23:1295–302. doi: 10.1038/sj.ijo.0801070.
    1. Maden-Wilkinson TM, Degens H, Jones DA, McPhee JS. Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles. J Musculoskelet Neuronal Interact. 2013;13:320–8.
    1. Farrell M, Richards JG. Analysis of the reliability and validity of the kinetic communicator exercise device. Med Sci Sports Exerc. 1986;18:44–9. doi: 10.1249/00005768-198602000-00009.
    1. Bassey EJ, Short AH. A new method for measuring power output in a single leg extension: feasibility, reliability and validity. Eur J Appl Physiol. 1990;60:385–90. doi: 10.1007/BF00713504.
    1. Reid KF, Fielding RA. Skeletal muscle power: a critical determinant of physical functioning in older adults. Exerc Sport Sci Rev. 2012;40:4–12. doi: 10.1097/JES.0b013e31823b5f13.
    1. Jones CJ, Rikli RE, Beam WC. A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport. 1999;70:113–9. doi: 10.1080/02701367.1999.10608028.
    1. Rikli RE, Jones CJ. Development and validation of criterion-referenced clinically relevant fitness standards for maintaining physical independence in later years. Gerontologist. 2013;53:255–67. doi: 10.1093/geront/gns071.
    1. Bergström J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975;35:609–16. doi: 10.3109/00365517509095787.
    1. Andreoli A, Scalzo G, Masala S, Tarantino U, Guglielmi G. Body composition assessment by dual-energy X-ray absorptiometry (DXA) Radiol Med. 2009;114:286–300. doi: 10.1007/s11547-009-0369-7.
    1. Nana A, Slater GJ, Stewart AD, Burke LM. Methodology review: using dual-energy X-ray absorptiometry (DXA) for the assessment of body composition in athletes and active people. Int J Sport Nutr Exerc Metab. 2015;25:198–215. doi: 10.1123/ijsnem.2013-0228.
    1. Marinangeli CPF, Kassis AN. Use of dual X-ray absorptiometry to measure body mass during short- to medium-term trials of nutrition and exercise interventions. Nutr Rev. 2013;71:332–42. doi: 10.1111/nure.12025.
    1. Leslie WD, Adler RA, El-Hajj Fuleihan G, Hodsman AB, Kendler DL, McClung M, et al. Application of the 1994 WHO classification to populations other than postmenopausal Caucasian women: the 2005 ISCD Official Positions. J Clin Densitom. 1994;2006(9):22–30.
    1. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–41. doi: 10.1002/jbmr.5650090802.
    1. Castro-Mejía JL, Muhammed MK, Kot W, Neve H, Franz CMAP, Hansen LH, et al. Optimizing protocols for extraction of bacteriophages prior to metagenomic analyses of phage communities in the human gut. Microbiome. 2015;3:64. doi: 10.1186/s40168-015-0131-4.
    1. Khakimov B, Motawia MS, Bak S, Engelsen SB. The use of trimethylsilyl cyanide derivatization for robust and broad-spectrum high-throughput gas chromatography-mass spectrometry based metabolomics. Anal Bioanal Chem. 2013;405:9193–205. doi: 10.1007/s00216-013-7341-z.
    1. Khakimov B, Amigo JM, Bak S, Engelsen SB. Plant metabolomics: resolution and quantification of elusive peaks in liquid chromatography-mass spectrometry profiles of complex plant extracts using multi-way decomposition methods. J Chromatogr A. 2012;1266:84–94. doi: 10.1016/j.chroma.2012.10.023.
    1. Savorani F, Rasmussen MA, Mikkelsen MS, Engelsen SB. A primer to nutritional metabolomics by NMR spectroscopy and chemometrics. Food Res Int. 2013;54:1131–45. doi: 10.1016/j.foodres.2012.12.025.
    1. Savorani F, Kristensen M, Larsen FH, Astrup A, Engelsen SB. High throughput prediction of chylomicron triglycerides in human plasma by nuclear magnetic resonance and chemometrics. Nutr Metab (Lond) 2010;7:43. doi: 10.1186/1743-7075-7-43.
    1. Petersen M, Dyrby M, Toubro S, Engelsen SB, Nørgaard L, Pedersen HT, et al. Quantification of lipoprotein subclasses by proton nuclear magnetic resonance-based partial least-squares regression models. Clin Chem. 2005;51:1457–61. doi: 10.1373/clinchem.2004.046748.
    1. Wolfe RR, Chinkes DL. Isotope tracers in metabolic research: principles and practice of kinetic analysis. 2. Hoboken, NJ: Wiley-Liss; 2005.
    1. Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One. 2014;9:e113637. doi: 10.1371/journal.pone.0113637.
    1. Simonsick EM, Fan E, Fleg JL. Estimating cardiorespiratory fitness in well-functioning older adults: treadmill validation of the long distance corridor walk. J Am Geriatr Soc. 2006;54:127–32. doi: 10.1111/j.1532-5415.2005.00530.x.
    1. Maruish ME. User’s manual for the SF-36v2 Health Survey. 3. Lincoln, RI: QualityMetric Incorporated; 2011.
    1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Dowd KP, Harrington DM, Donnelly AE. Criterion and concurrent validity of the activPALTM professional physical activity monitor in adolescent females. PLoS One. 2012;7:e47633. doi: 10.1371/journal.pone.0047633.
    1. Dahlgren G, Carlsson D, Moorhead A, Häger-Ross C, McDonough SM. Test-retest reliability of step counts with the ActivPALTM device in common daily activities. Gait Posture. 2010;32:386–90. doi: 10.1016/j.gaitpost.2010.06.022.
    1. Grunert KG, Dean M, Raats MM, Nielsen NA, Lumbers M. A measure of satisfaction with food-related life. Appetite. 2007;49:486–93. doi: 10.1016/j.appet.2007.03.010.
    1. World Health Organization (WHO) Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO consultation. Geneva, Switzerland: WHO; 1999.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—a metadata driven methodology and workflow process for providing translational research informatict support. J Biomed Inform. 2009;42:377–81. doi: 10.1016/j.jbi.2008.08.010.
    1. Holm L, Olesen JL, Matsumoto K, Doi T, Mizuno M, Alsted TJ, et al. Protein-containing nutrient supplementation following strength training enhances the effect on muscle mass, strength, and bone formation in postmenopausal women. J Appl Physiol. 2008;105:274–81. doi: 10.1152/japplphysiol.00935.2007.
    1. Danmarks Statistik. Danmark i tal 2015 [in Danish]. . Accessed 27 Jul 2016.
    1. Mathar T, Jansen YJFM. Health promotion and prevention programmes in practice. how patient’s health practices are rationalised, reconceptualised and reorganised. Bielefeld, Germany: transcript Verlag; 2010.
    1. Jespersen AP, Bønnelycke J, Eriksen HH. Careful science? Bodywork and care practices in randomised clinical trials. Sociol Health Illn. 2014;36:655–69. doi: 10.1111/1467-9566.12094.

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