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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 82414

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Prof. Dr. Matteo Cesari

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Guest Editor

1. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
2. Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Interests: frailty; sarcopenia; geriatric medicine; integrated care; healthy ageing
Special Issues, Collections and Topics in MDPI journals

Dr. Emanuele Marzetti

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Guest Editor

Department of Geriatrics, Neurosciences and Orthopaedics, Policlinico Universitario Agostino Gemelli, Rome, Italy
Interests: Muscle function; Skeletal Muscle; Geriatrics; Frailty; Sarcopenia; Mitochondria; Biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The maintenance of optimal musculoskeletal health is increasingly recognized as a key element for promoting overall health and fostering independent living in advanced age. Growing evidence indicates that nutrition, together with an active lifestyle, plays a central role in supporting musculoskeletal health both during aging and in the setting of specific disease conditions. This Special Issue of Nutrients, entitled “Nutrition for Musculoskeletal Health”, welcomes the submission of manuscripts reporting the findings of original research or reviewing the existing literature on the subject. The topics of interest may be explored in various disciplines (e.g., nutritional sciences, geriatrics, internal medicine, sports medicine, public health, rheumatology, oncology, cardiology, orthopedics). Reports from basic science up to clinical and population research will be considered suitable for inclusion in the Special Issue. Articles presenting results (either positive or negative) from clinical trials testing specific nutritional interventions will be given special consideration.

Potential topics include, but are not limited to:

Impact of specific dietary patterns on musculoskeletal health
Effects of nutritional interventions on sarcopenia, osteoporosis, and osteosarcopenia
Nutritional interventions targeting the musculoskeletal system in the setting of specific disease conditions
Nutraceutical interventions with an impact on musculoskeletal health during aging or in the context of specific disease conditions
Description of mechanisms whereby nutrition impact musculoskeletal health
Gut microbiota and musculoskeletal health

We therefore invite you to submit your latest original research or review articles that fall within the overarching theme of this Special Issue.

Dr. Matteo Cesari
Dr. Emanuele Marzetti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Sarcopenia
Osteosarcopenia
Osteoporosis
Frailty
Fragility
Fracture
physical function
diet
nutraceutical
macronutrients
micronutrients

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Published Papers (10 papers)

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Research

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10 pages, 706 KiB

Open AccessArticle

Determinants of Adherence in Time-Restricted Feeding in Older Adults: Lessons from a Pilot Study

by Stephanie A. Lee, Caroline Sypniewski, Benjamin A. Bensadon, Christian McLaren, William T. Donahoo, Kimberly T. Sibille and Stephen Anton

Nutrients 2020, 12(3), 874; https://doi.org/10.3390/nu12030874 - 24 Mar 2020

Cited by 42 | Viewed by 6812

Abstract

Time-restricted feeding (TRF) is a type of intermittent fasting in which no calories are commonly consumed for approximately 12–18 hours on a daily basis. The health benefits of this eating pattern have been shown in overweight adults, with improvements in cardiometabolic risk factors as well as the preservation of lean mass during weight loss. Although TRF has been well studied in younger and middle-aged adults, few studies have evaluated the effects of TRF in older adults. Thus, the goal of this study was to evaluate older-adult perspectives regarding the real-world advantages, disadvantages, and challenges to adopting a TRF eating pattern among participants aged 65 and over. A four-week single-arm pre- and post-test design was used for this clinical pilot trial TRF intervention study. Participants were instructed to fast for approximately 16 h per day with the daily target range between 14 and 18 h. Participants were provided with the TRF protocol at a baseline visit, along with a pictorial guide that depicted food items and beverages that were allowed and not allowed during fasting windows to reinforce that calorie-containing items were to be avoided. The trial interventionist called each participant weekly to promote adherence, review the protocol, monitor for adverse events, and provide support and guidance for any challenges faced during the intervention. Participants were instructed to complete daily eating time logs by recording the times at which they first consumed calories and when they stopped consuming calories. At the end of the intervention, participants completed an exit interview and a study-specific Diet Satisfaction Survey (Table 1) to assess their satisfaction, feasibility, and overall experience with the study intervention. Of the 10 participants who commenced the study (mean age = 77.1 y; 6 women, 4 men), nine completed the entire protocol. Seven of the ten participants reported easy adjustment to a 16-hour fast and rated the difference from normal eating patterns as minimal. Eight participants reported no decrease in energy during fasting periods, with greater self-reported activity levels in yardwork and light exercise. Adverse events were rare, and included transient headaches, which dissipated with increased water intake, and dizziness in one participant, which subsided with a small snack. The findings of the current trial suggest that TRF is an eating approach that is well tolerated by most older adults. Six participants, however, did not fully understand the requirements of the fasting regimen, despite being provided with specific instructions and a pictorial guide at a baseline visit. This suggests that more instruction and/or participant contact is needed in the early stages of a TRF intervention to promote adherence. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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12 pages, 980 KiB

Open AccessArticle

Identification of a Circulating Amino Acid Signature in Frail Older Persons with Type 2 Diabetes Mellitus: Results from the Metabofrail Study

by Riccardo Calvani, Leocadio Rodriguez-Mañas, Anna Picca, Federico Marini, Alessandra Biancolillo, Olga Laosa, Laura Pedraza, Jacopo Gervasoni, Aniello Primiano, Giorgia Conta, Isabelle Bourdel-Marchasson, Sophie C. Regueme, Roberto Bernabei, Emanuele Marzetti, Alan J. Sinclair and Giovanni Gambassi

Nutrients 2020, 12(1), 199; https://doi.org/10.3390/nu12010199 - 12 Jan 2020

Cited by 30 | Viewed by 6997

Abstract

Diabetes and frailty are highly prevalent conditions that impact the health status of older adults. Perturbations in protein/amino acid metabolism are associated with both functional impairment and type 2 diabetes mellitus (T2DM). In the present study, we compared the concentrations of a panel of circulating 37 amino acids and derivatives between frail/pre-frail older adults with T2DM and robust non-diabetic controls. Sixty-six functionally impaired older persons aged 70+ with T2DM and 30 age and sex-matched controls were included in the analysis. We applied a partial least squares-discriminant analysis (PLS-DA)-based analytical strategy to characterize the metabotype of study participants. The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 94.1 ± 1.9% for frail/pre-frail persons with T2DM and 100% for control participants. Functionally impaired older persons with T2DM showed higher levels of 3-methyl histidine, alanine, arginine, glutamic acid, ethanolamine sarcosine, and tryptophan. Control participants had higher levels of ornithine and taurine. These findings indicate that a specific profile of amino acids and derivatives characterizes pre-frail/frail older persons with T2DM. The dissection of these pathways may provide novel insights into the metabolic perturbations involved in the disabling cascade in older persons with T2DM. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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15 pages, 1846 KiB

Open AccessArticle

Gut Microbial, Inflammatory and Metabolic Signatures in Older People with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study

by Anna Picca, Francesca Romana Ponziani, Riccardo Calvani, Federico Marini, Alessandra Biancolillo, Hélio José Coelho-Júnior, Jacopo Gervasoni, Aniello Primiano, Lorenza Putignani, Federica Del Chierico, Sofia Reddel, Antonio Gasbarrini, Francesco Landi, Roberto Bernabei and Emanuele Marzetti

Nutrients 2020, 12(1), 65; https://doi.org/10.3390/nu12010065 - 26 Dec 2019

Cited by 114 | Viewed by 6153

Abstract

Physical frailty and sarcopenia (PF&S) share multisystem derangements, including variations in circulating amino acids and chronic low-grade inflammation. Gut microbiota balances inflammatory responses in several conditions and according to nutritional status. Therefore, an altered gut-muscle crosstalk has been hypothesized in PF&S. We analyzed the gut microbial taxa, systemic inflammation, and metabolic characteristics of older adults with and without PF&S. An innovative multi-marker analytical approach was applied to explore the classification performance of potential biomarkers for PF&S. Thirty-five community dwellers aged 70+, 18 with PF&S, and 17 nonPF&S controls were enrolled. Sequential and Orthogonalized Covariance Selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables, was applied. The SO-CovSel model with the best prediction ability using the smallest number of variables was built using seven mediators. The model correctly classified 91.7% participants with PF&S and 87.5% nonPF&S controls. Compared with the latter group, PF&S participants showed higher serum concentrations of aspartic acid, lower circulating levels of concentrations of threonine and macrophage inflammatory protein 1α, increased abundance of Oscillospira and Ruminococcus microbial taxa, and decreased abundance of Barnesiellaceae and Christensenellaceae. Future investigations are warranted to determine whether these biomediators are involved in PF&S pathophysiology and may, therefore, provide new targets for interventions. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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13 pages, 596 KiB

Open AccessCommunication

Dietary Protein and Physical Activity Interventions to Support Muscle Maintenance in End-Stage Renal Disease Patients on Hemodialysis

by Floris K. Hendriks, Joey S.J. Smeets, Frank M. van der Sande, Jeroen P. Kooman and Luc J.C. van Loon

Nutrients 2019, 11(12), 2972; https://doi.org/10.3390/nu11122972 - 5 Dec 2019

Cited by 24 | Viewed by 6893

Abstract

End-stage renal disease patients have insufficient renal clearance capacity left to adequately excrete metabolic waste products. Hemodialysis (HD) is often employed to partially replace renal clearance in these patients. However, skeletal muscle mass and strength start to decline at an accelerated rate after initiation of chronic HD therapy. An essential anabolic stimulus to allow muscle maintenance is dietary protein ingestion. Chronic HD patients generally fail to achieve recommended protein intake levels, in particular on dialysis days. Besides a low protein intake on dialysis days, the protein equivalent of a meal is extracted from the circulation during HD. Apart from protein ingestion, physical activity is essential to allow muscle maintenance. Unfortunately, most chronic HD patients have a sedentary lifestyle. Yet, physical activity and nutritional interventions to support muscle maintenance are generally not implemented in routine patient care. To support muscle maintenance in chronic HD patients, quantity and timing of protein intake should be optimized, in particular throughout dialysis days. Furthermore, implementing physical activity either during or between HD sessions may improve the muscle protein synthetic response to protein ingestion. A well-orchestrated combination of physical activity and nutritional interventions will be instrumental to preserve muscle mass in chronic HD patients. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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13 pages, 639 KiB

Open AccessArticle

Malnutrition as a Strong Predictor of the Onset of Sarcopenia

by Charlotte Beaudart, Dolores Sanchez-Rodriguez, Médéa Locquet, Jean-Yves Reginster, Laetitia Lengelé and Olivier Bruyère

Nutrients 2019, 11(12), 2883; https://doi.org/10.3390/nu11122883 - 27 Nov 2019

Cited by 148 | Viewed by 8391

Abstract

This study aims to explore the association between malnutrition diagnosed according to both the Global Leadership Initiative of Malnutrition (GLIM) and the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria and the onset of sarcopenia/severe sarcopenia, diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criterion, in the sarcopenia and physical impairment with advancing age (SarcoPhAge) cohort during a four-year follow-up. Adjusted Cox-regression and Kaplan-Meier curves were performed. Among the 534 community-dwelling participants recruited in the SarcoPhAge study, 510 were free from sarcopenia at baseline, of whom 336 had complete data (186 women and 150 men, mean age of 72.5 ± 5.8 years) to apply the GLIM and ESPEN criteria. A significantly higher risk of developing sarcopenia/severe sarcopenia during the four-year follow-up based on the GLIM [sarcopenia: Adjusted hazard ratio (HR) = 3.23 (95% confidence interval (CI) 1.73–6.05); severe sarcopenia: Adjusted HR = 2.87 (95% CI 1.25–6.56)] and ESPEN [sarcopenia: Adjusted HR = 4.28 (95% CI 1.86–9.86); severe sarcopenia: Adjusted HR = 3.86 (95% CI 1.29–11.54)] criteria was observed. Kaplan-Meier curves confirmed this relationship (log rank p < 0.001 for all). These results highlighted the importance of malnutrition since it has been shown to be associated with an approximately fourfold higher risk of developing sarcopenia/severe sarcopenia during a four-year follow-up. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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12 pages, 1929 KiB

Open AccessArticle

Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model

by Mudan Cai and Eun Jin Yang

Nutrients 2019, 11(11), 2644; https://doi.org/10.3390/nu11112644 - 4 Nov 2019

Cited by 16 | Viewed by 3627

Abstract

Hochu-ekki-to (Bojungikgi-Tang (BJIGT) in Korea; Bu-Zhong-Yi-Qi Tang in Chinese), a traditional herbal prescription, has been widely used in Asia. Hochu-ekki-to (HET) is used to enhance the immune system in respiratory disorders, improve the nutritional status associated with chronic diseases, enhance the mucosal immune system, and improve learning and memory. Amyotrophic lateral sclerosis (ALS) is pathologically characterized by motor neuron cell death and muscle paralysis, and is an adult-onset motor neuron disease. Several pathological mechanisms of ALS have been reported by clinical and in vitro/in vivo studies using ALS models. However, the underlying mechanisms remain elusive, and the critical pathological target needs to be identified before effective drugs can be developed for patients with ALS. Since ALS is a disease involving both motor neuron death and skeletal muscle paralysis, suitable therapy with optimal treatment effects would involve a motor neuron target combined with a skeletal muscle target. Herbal medicine is effective for complex diseases because it consists of multiple components for multiple targets. Therefore, we investigated the effect of the herbal medicine HET on motor function and survival in hSOD1^G93A transgenic mice. HET was orally administered once a day for 6 weeks from the age of 2 months (the pre-symptomatic stage) of hSOD1^G93A transgenic mice. We used the rota-rod test and foot printing test to examine motor activity, and Western blotting and H&E staining for evaluation of the effects of HET in the gastrocnemius muscle and lumbar (L4–5) spinal cord of mice. We found that HET treatment dramatically inhibited inflammation and oxidative stress both in the spinal cord and gastrocnemius of hSOD1^G93A transgenic mice. Furthermore, HET treatment improved motor function and extended the survival of hSOD1^G93A transgenic mice. Our findings suggest that HET treatment may modulate the immune reaction in muscles and neurons to delay disease progression in a model of ALS. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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19 pages, 1826 KiB

Open AccessArticle

Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan

by Claudia Romano, Giovanni Corsetti, Vincenzo Flati, Evasio Pasini, Anna Picca, Riccardo Calvani, Emanuele Marzetti and Francesco Saverio Dioguardi

Nutrients 2019, 11(6), 1367; https://doi.org/10.3390/nu11061367 - 18 Jun 2019

Cited by 28 | Viewed by 6079

Abstract

An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for “optimal” nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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10 pages, 3500 KiB

Open AccessArticle

Lactate Stimulates a Potential for Hypertrophy and Regeneration of Mouse Skeletal Muscle

by Yoshitaka Ohno, Koki Ando, Takafumi Ito, Yohei Suda, Yuki Matsui, Akiko Oyama, Hikari Kaneko, Shingo Yokoyama, Tatsuro Egawa and Katsumasa Goto

Nutrients 2019, 11(4), 869; https://doi.org/10.3390/nu11040869 - 17 Apr 2019

Cited by 41 | Viewed by 9304

Abstract

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups. CTX was injected into right tibialis anterior (TA) muscle before the oral administration of sodium lactate (five days/week for two weeks) to the mice. Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse TA skeletal muscle. Oral administration of lactate also facilitated the recovery process of CTX-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. Mouse myoblast-derived C2C12 cells were differentiated for five days to form myotubes with or without lactate administration. C2C12 myotube formation with an increase in protein content, fiber diameter, length, and myo-nuclei was stimulated by lactate. These observations suggest that lactate may be a potential molecule to stimulate muscle hypertrophy and regeneration of mouse skeletal muscle via the activation of muscle satellite cells. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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17 pages, 711 KiB

Open AccessFeature PaperReview

Poor Oral Health as a Determinant of Malnutrition and Sarcopenia

by Domenico Azzolino, Pier Carmine Passarelli, Paolo De Angelis, Giovan Battista Piccirillo, Antonio D’Addona and Matteo Cesari

Nutrients 2019, 11(12), 2898; https://doi.org/10.3390/nu11122898 - 29 Nov 2019

Cited by 158 | Viewed by 17062

Abstract

Aging is accompanied by profound changes in many physiological functions, leading to a decreased ability to cope with stressors. Many changes are subtle, but can negatively affect nutrient intake, leading to overt malnutrition. Poor oral health may affect food selection and nutrient intake, leading to malnutrition and, consequently, to frailty and sarcopenia. On the other hand, it has been highlighted that sarcopenia is a whole-body process also affecting muscles dedicated to chewing and swallowing. Hence, muscle decline of these muscle groups may also have a negative impact on nutrient intake, increasing the risk for malnutrition. The interplay between oral diseases and malnutrition with frailty and sarcopenia may be explained through biological and environmental factors that are linked to the common burden of inflammation and oxidative stress. The presence of oral problems, alone or in combination with sarcopenia, may thus represent the biological substratum of the disabling cascade experienced by many frail individuals. A multimodal and multidisciplinary approach, including personalized dietary counselling and oral health care, may thus be helpful to better manage the complexity of older people. Furthermore, preventive strategies applied throughout the lifetime could help to preserve both oral and muscle function later in life. Here, we provide an overview on the relevance of poor oral health as a determinant of malnutrition and sarcopenia. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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30 pages, 2296 KiB

Open AccessReview

Role of Citrate in Pathophysiology and Medical Management of Bone Diseases

by Donatella Granchi, Nicola Baldini, Fabio Massimo Ulivieri and Renata Caudarella

Nutrients 2019, 11(11), 2576; https://doi.org/10.3390/nu11112576 - 25 Oct 2019

Cited by 55 | Viewed by 8732

Abstract

Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders. Full article

(This article belongs to the Special Issue Nutrition for Musculoskeletal Health)

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