HLA genes, haplotype, and supertype related to HIV-1 susceptibility and AIDS progression
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-signs-new-contract-with-cepiec-china-for-distribution-of-open-access-books-20210319",title:"IntechOpen Signs New Contract with CEPIEC, China for Distribution of Open Access Books"},{slug:"150-million-downloads-and-counting-20210316",title:"150 Million Downloads and Counting"},{slug:"intechopen-secures-indefinite-content-preservation-with-clockss-20210309",title:"IntechOpen Secures Indefinite Content Preservation with CLOCKSS"},{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"}]},book:{item:{type:"book",id:"5413",leadTitle:null,fullTitle:"Thermoelectrics for Power Generation - A Look at Trends in the Technology",title:"Thermoelectrics for Power Generation",subtitle:"A Look at Trends in the Technology",reviewType:"peer-reviewed",abstract:"Thermoelectrics for Power Generation - A Look at Trends in the Technology is the first part of the InTech collection of international community works in the field of thermoelectric power generation. The authors from many counties have presented in this book their achievements and vision for the future development in different aspects of thermoelectric power generation. Remarkably, this hot topic unites together efforts of researchers and engineers from all continents of our planet. 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\r\n\tPolyimide is nowadays fully acknowledged as one of the most efficient polymers in many industries for its excellent thermal, electrical and mechanical properties, as well as for its easy processability. Particularly, in the Electronic and Electrical Engineering industries, polyimide is widely used for decades thanks to its very good dielectric and insulating properties at high electric field and high temperature up to 250°C in long term-service.
\r\n\t
\r\n\tSince its discovery in the mid-50’s, a wide range of applications from low to high voltage appeared, putting polyimide as a key material to design more performing and reliable electrical devices and systems. On another hand, polyimide appears also essential for the development of new electronic devices where further considerations such as high power density, integration, higher temperature, thermal conduction management, energy storage, reliability or flexibility are required in order to sustain the growing electrical energy consumption needs of the global society.
\r\n\tConsequently, polyimide materials have and will have to face new exciting fundamental, technological and environmental challenges among which:
\r\n\t• a better understanding of its intrinsic electrical properties to identify current limitations and propose new advanced device designs,
\r\n\t• the development of innovative composites and nanocomposites structuration to tailor its physical properties by involving classical and original nanoparticles such as graphene layer, carbon nanotubes, metal, silicates, nitrides, etc.,
\r\n\t• the development of polyimide composites for energy storage, thermal management, reinforced nanodielectrics and corona-resistant nanocomposites,
\r\n\t• the development of new low and ultra-low dielectric constant polyimide for microelectronics (fluorinated polyimides, nanoporous, mesoporous),
\r\n\t• the development of new higher temperature reliable polyimide (high glass transition, high degradation temperature),
\r\n\t• the emergence of solvent-free processes to fit with environmental purposes
\r\n\tMoreover, many challenges regarding the aging mechanisms understanding under single or multiple constraints and the realistic lifetime prediction using robust physical modelling is a ubiquitous questioning in most of the electronic industries.
\r\n\tThis book will target to review both the state-of-the-art and new researches on Polyimide for Electronic and Electrical Engineering Applications. It will present interdisciplinary chapters on the state of knowledge of each topic under consideration through a combination of overviews and original unpublished research. Chapter proposals related to one of the following topics and their keywords (but not only restricted to them) are very welcome to be submitted for this book publication project:
\r\n\t• General Considerations and Technological Processes of Polyimide for Electronics and Electrical Systems
\r\n\tProcessability, Photosensitive and non-photosensitive polyimide, Curing temperature,
\r\n\tSpin-coating, Dip-coating, Extruded enameled wires, Other casting methods
\r\n\t• Polyimide in Microelectronic Applications
\r\n\tDielectric properties, Intermetal layer, Ultra Large-Scale Integration (ULSI), Low-k dielectrics, Fluorinated polyimide, Nanoporous polyimide, Flexible substrates, Thin film transistors, LCD devices, sensors and actuators (gas, humidity, pressure, tactile…)
\r\n\t• Polyimide in Medium and High Voltage Applications
\r\n\tElectrical insulation properties (conduction, breakdown), Digital isolators, Power electronics and devices, Power modules, Power integration, Passivation, Packaging, High voltage power systems, Enameled wires for fed-inverter rotating machine
Human leukocyte antigen (HLA) complex, which refers to a group of closely linked genes on the short arm of the sixth human chromosome, is considered the most polymorphic genetic marker that has so far been reported in the human. HLA plays a significant role in the immune response, particularly in antiviral immunity. Although HLA and genetic predisposition to various autoimmune diseases have been separately studied for the past 40 years, the evaluation of the correlation between the two was initiated only within the last 10 years. In recent years, research on HLA polymorphisms and susceptibility to various infectious diseases has attracted significant attention owing to the critical role of HLA in diseases such as SARS and hepatitis B. In particular, HLA polymorphism, HIV, and genetic predisposition to AIDS have emerged as research areas of immense clinical significance.
Human immunodeficiency virus (HIV) infection is able to perturb and alter gene expression through several mechanisms that can, lastly, cause acquired immunodeficiency syndrome (AIDS) Figure 1. Meanwhile, associations between disease parameters and the genetic makeup of the host and virus may be crucial in determining the outcome of HIV-1 infection.
HIV virus is formed by a diploid single strand RNA genome enclosed in a truncated cone capsid with a phospholipidic bilayer envelope, containing the proteins that allow the virus entry into the cells. The HIV-1 infection is mediated by interaction between the proteins of the viral envelope, leukocyte receptor, and coreceptor. This interaction causes the membranes fusion and the uncoating of the virion core. The viral RNA is reverse transcribed in DNA which enters in the nucleus where the integrase enzyme catalyzes the insertion of the viral genome into the genome of the host cell. The expression of integrated viral genome is controlled by the RNA-binding proteins tat and rev. A set of RNAs are transported from the nucleus to the cytoplasm, where they can be translated or packaged. The new core proteins localize near the cell membrane, while the envelope mRNA is translated at the endoplasmic reticulum (ER) and subsequently the envelope proteins are placed on the cell membrane. Finally, the capsid proteins are assembled with the viral genomic RNA, and an immature virion begins to bud from cell surface.
According to Joint United Nations Programme on HIV/AIDS, there were approximately 40 million HIV-infected people worldwide at the end of 2004. Limiting the susceptibility to HIV, predicting the course of AIDS, and reversing it are some of the challenging tasks that need to be addressed urgently. Existing data demonstrates that the susceptibility to HIV differs among individuals, and significant differences exist in the disease progression in HIV-infected persons. In general, it takes less than 10 years from the time of HIV infection to the manifestation of typical AIDS symptoms. However, a small subset of HIV-infected people (0.8%) are asymptomatic for over 10 years. According to a number of studies, the HLA complex is considered as the most noteworthy genetic marker that is closely related to AIDS progression and highlights the differences in genetic susceptibility of HIV-infected individuals.
Epidemiological survey: Worldwide epidemiological surveys indicate that there is a close relationship between HIV/AIDS and HLA. Although global research reports at different times have demonstrated the involvement of HLA in the differential susceptibility to HIV, the individual HLA locus has not been validated to correlate with HIV infection or AIDS progression. For example, some reports indicate a correlation between HIV susceptibility and HLA-B*35 in ethnic groups of Han. However, findings of research on Caucasian individuals did not agree with this notion. HLA-B*07, found among people of African descent, is considered to correlate with the susceptibility to HIV, but the similar correlation has not been reported among people of other ethnic groups. Research on other ethnic groups indicates that HLA-B*18 and the HLA-A2 either influence HIV-1 infectivity or act as protective genes that inhibit the incidence of AIDS. The homozygous HLA-G 14-bp nsertion/deletion genotype is associated with higher viral load, lower CD4 cell count, and increased mortality compared with HLA-G 14-bp carriers.
Considering the limitation of the small population evaluated, polymorphisms outside the peptide binding region of the HLA class I molecule can play a key role in HIV progression through interaction with other immune-relevant receptors. Some results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect. HLA-A-restricted Gag-specific responses can impose selection pressure on HIV. Vaidya et al analyzed the associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP in untreated subjects. The results show that the effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, while HLA-B*97 is more broadly associated with HIV-1 viral load during primary infection. In HIC (HIV controllers, a unique group of infected individuals who are able to control HIV naturally), HLA-B*57 and the amount of ultrasensitive viral load seem to play a role in the HIV-specific CD8+ T cell responses. Some results provide support for the role of HLA-B*51-restricted CTLs and functional avidity in the control of early HIV-1 infection. HALS (HIV/Highly active antiretroviral therapy-associated lipodystrophy syndrome) is associated with combined low-expression TS (thymidylate synthase) and MTHFR (methylene-tetrahydrofolate reductase) associated with high activity polymorphisms but not with HLA-B*40:01 carriage in Caucasian patients with long-term exposure to stavudine. For details, see Table 1.
Richard et al characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. They found that HIV peptides presented by higher expressed HLA-C alleles were more likely to elicit CTL responses than peptides presented by low expression HLA-C allotypes, such that higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. It is also pointed out that HLA-C and HLA-E collaborate to keep the HIV-1 virus at bay. HLA-C can present antigens to CTL, and it is able to inhibit NK cell lysis, but for some reason it is normally expressed on the cell surface at levels approximately 10-fold less than most HLA-A and HLA-B allotypes. The mechanisms that regulate HLA-C expression and the link between this molecule and HIV infection are not yet completely understood. Maybe a new miRNA targeting sequences identified on HLA-C gene and the low level of affinity between
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
Han Ethnicity | \n\t\t\tB*35 | \n\t\t\t- | \n\t\t
Zambian | \n\t\t\tA*02-Cw*16, A*23-B*14, A*23-Cw*07(FP) | \n\t\t\tB*57, B*39, A*30-Cw*03(SP) | \n\t\t
European | \n\t\t\tA1-Cw7-B8-DR3, A24(FP) | \n\t\t\t- | \n\t\t
Yi Ethnicity | \n\t\t\tB*07, B*35, B*46 | \n\t\t\tB*55, B*44, B*78 | \n\t\t
Kenya | \n\t\t\tA*29, Cw*07, Cw*08 (HT) | \n\t\t\tB*18(LT) | \n\t\t
Kenya | \n\t\t\tA*2301 | \n\t\t\tA2/6802 supertype(LT) | \n\t\t
Argentina | \n\t\t\tA*24, B*18, B*39 | \n\t\t\tB*44, B*55 | \n\t\t
African-American | \n\t\t\tDQB1*0201 | \n\t\t\tDQB1*0303 | \n\t\t
Caucasian | \n\t\t\tDQB1*0603, DRB1*04 | \n\t\t\tDQB1*0303 | \n\t\t
European | \n\t\t\tA*29, B*22, DR*11(FP) | \n\t\t\tB*14, Cw*08(SP) | \n\t\t
Caucasian | \n\t\t\tHeterozygous HLA locus, Type I | \n\t\t\tB*35, Cw*04 | \n\t\t
American | \n\t\t\tB*54, B*55, B*56 | \n\t\t\t- | \n\t\t
American | \n\t\t\t- | \n\t\t\tB*18(LT) | \n\t\t
Male Caucasian Homosexuals | \n\t\t\tB*35 | \n\t\t\tA2 supertype | \n\t\t
Zimbabwean | \n\t\t\tHLA-G 14-bp insertion/deletion | \n\t\t\t\n\t\t |
European-American | \n\t\t\tHLA-C low expression | \n\t\t\tHLA-C high expression | \n\t\t
HLA genes, haplotype, and supertype related to HIV-1 susceptibility and AIDS progression
FP, fast progression; SP, slow progression; HT, high transmission; LT, low transmission
Jabri and his colleagues used two strains of HIV-1 and HIV-2 to infect peripheral blood cells with different HLA antigenic specificities, and reported that no single HLA antigen was capable of preventing both types of HIV infection. For example, HLA-B52 showed susceptibility to HIV-1 viral strains, whereas it was not susceptible to HIV-2 viral strains. HLA-B58 showed susceptibility to HIV-2 viral strains, but it was not susceptible to HIV-1 viral strains. HLA-B44 influenced the immune function only against certain HIV-1/2 strains. It is still therefore still ambiguous whether different HLA phenotypes influence the susceptibility to and
HLA-G variant expression has a considerable impact on the control of HIV replication, an effect that seems to be mediated primarily by the protein specificity of CD4(+) T cell responses to HIV Gag and Nef. Numerous studies have been conducted, aimed at observing the expression of the molecule HLA-G in the early stage of infection by HIV and its progression. In 2004, Derrien and colleagues demonstrated that during HIV-1 infection the HLA-G1 isoform was down regulated by a Vpu dependent mechanism, which recognizes a double lysine residues in 4 and 5 positions of the C terminus. The HLA-G1 isoform has the major ability to present viral peptides to CD8+ T lymphocytes; therefore, the recognition of HIV-1 infected cells by CD8+ T lymphocytes could depend on the expression of HLA-G1.More results show that HLA-G Treg plays an important role for balancing by stander immune activation and anti-viral immune activity in HIV-1 infection and suggest that the loss of these cells during advanced HIV-1 infection may contribute to immune dysregulation and HIV-1 disease progression. The connection between miRNA, HLA-G expression, and HIV-1 also needs to be further explored because it can reveal novel information about HIV-1 control of the immune system.
Statistical analysis of the correlation between HLA gene polymorphism and HIV infection or AIDS susceptibility: Previously published research findings have been analyzed to evaluate the diversity in the correlation of HLA with HIV/AIDS susceptibility. Meta-analysis was anticipated to identify the common features. Research articles that satisfy the selection criteria were retrieved and the original data in the documents were processed and analyzed, wherein B35, B62, DR5, and DR11 were identified as genes that facilitate HIV-1 susceptibility and/or occurrence of AIDS, while A10, B18, B27, B5, and DR1 were identified as protective genes against HIV-1 infection and/or occurrence of AIDS. Since meta-analysis is an observational study, variations are likely to be introduced in each step of the analysis, and the results need to be validated by testing in laboratories with a large sample size.
Infection receptors: HIV combines with the CD4 molecule and other coreceptors to invade T cells during infection. HIV susceptibility is affected when the above-mentioned receptors have natural defects or mutations. So far, it has been verified that receptors of chemotactic factors (CCR35 and CXCR4) are coreceptors for HIV-1. When HIV-1 infects target cells, the viruses that combine with CD4 molecules combine with coreceptors in order to enter the target cells. In high-risk populations with close contact to infected individuals but no infection, approximately one-third of the CCR5 alleles undergo deletion mutation; for instance, deletion of 32 bases of CCR5 genes (referred to as CCR5Δ32 mutation), which results in a natural immunity of the organism against HIV-1 infection at the gene level. The mutation and polymorphism changes of alleles not only influence the ability of HIV-1 to infect the target cells, but also change the onset and progression of AIDS. It is possible that HLA participates in HIV invading process through similar means, and affects AIDS progression. However, there are no validated reports on HLA’s direct participation in HIV-1 infection by acting as the receptor, so far. Therefore, the susceptibility theory, which suggests that HLA acts as a receptor, needs to be subjected to further scientific scrutiny.
HLA molecules selection pressure: The antigen-binding groove of HLA molecules combine with a specific epitope of the HIV protein (For example, gap 120), inducing the generation of helper T cells and cytotoxic T cells. In particular, CD8+ cytotoxic T lymphocytes can kill infected CD4+ T lymphocyte in a direct manner, which can influence virus replication, transmission, and AIDS progression. HLA molecules can employ different epitopes for the same molecule, and stimulate generation of CTLs featuring different quantities as well as specific properties, which has been confirmed in previous studies. Therefore, this can better explain the differences in AIDS progress when individuals with certain HLA phenotypes infected with HIV.
During viral infection, some viruses undergo degradation by cellular proteasome complex, and the cytosolic antigenic peptides are carried into the ER. In this organelle, the peptides are captured by HLA I molecules and then exposed on the cell surface, triggering the cytotoxic activity of the circulating CD8+ T lymphocytes, as described previously. The HIV has devised different ways to evade the immune response including a Nef-dependent mechanism that downregulates the HLA I expression, thus avoiding the recognition of the infected cells by CD8+ T lymphocytes (Fig2). Selectively, Nef alters the expression of HLA-A and -B by recognition of a sequence (Y320SQAASS) present on the cytoplasmic tail of these HLA molecules accelerating their endocytosis from the plasma membrane and blocking the transport of newly synthesized MHC class I molecules to the cell surface. Nef maintains the expression of HLA-C -G and -E unchanged, in order to inhibit the innate response of the natural killer cells (NK). Furthermore, the gp41 protein of the viral envelope upregulates the synthesis of IL-10 by monocytes; in turn, as mentioned before, this cytokine increases the expression of HLA-G molecules to control immune response and facilitate infection.
The HIV has devised different ways to evade the immune response, including a Nef-dependent mechanism that downregulates the HLA I expression, thus avoiding the recognition of the infected cells by CD8+ T lymphocytes. Selectively, Nef alters the expression of HLA-A and -B by recognition of a sequence (Y320SQAASS) present on the cytoplasmic tail of these HLA molecules accelerating their endocytosis from the plasma membrane and blocking the transport of newly synthesized MHC class I molecules to the cell surface. Nef maintains the expression of HLA-C, -G, and -E unchanged, in order to inhibit the innate response of the natural killer cells (NK). NU: nucleus; GO: golgi apparatu
Meanwhile, under the influence of CTLs that are induced by HLA, mutation of HIV can occur. For example, TW10 peptide fragment (TAILQEQIAW) of gap protein in the HIV-1 virus, has a specific mutation on the residue 242 in the individuals with HLA-B57 or B58 and can revert to the wild type after the viruses detach from HLA-B57 or B58 molecules. This HIV mutation can cause functional loss of specific CTL, and enable HIV to adapt to the HLA environment and overcome the immune responses, resulting in HIV susceptibility of specific HLA types as well as a rapid progression of AIDS. Children of mothers with AIDS who have similar HLA genes are at a higher risk of being infected with HIV, and they tend to progress to AIDS in a shorter time. The possible reason for this is that the HIV of the mother might have adapted to the HLA environment in the host, and the virus replication increases when HLA similarity is high between the mother and child, which in turn makes it is easier for HIV to propagate and lead to a faster progression of AIDS. But sometimes specific mutation of HIV can also lead to a decrease in its virulence, enabling a reduced susceptibility of individuals towards HIV and a slower progression of AIDS.
Supported by grants from the State Key Development Program for Basic Research of China (No.2003CB515509 and 2009CB522401) and from National Natural Scientific Foundation of China(No.81070450 and 30470751) to Dr. X.-Y.Z.
Muscle mass and strength have been linked to overall health and mortality [1, 2], and improvements in skeletal muscle properties and the prevention of muscle wasting with disuse/atrophy are essential for all individuals, particularly inactive older adults [3]. Sarcopenia is characterized by the loss of skeletal muscle mass and physical function (muscle strength or physical performance) with advancing age [4, 5, 6]. It is associated with physical disability, poor quality of life, and increased mortality in older adults [5]. Although the loss of muscle mass and physical function is associated with aging, rates of decline vary across the population [7]. Therefore, modifiable behavioral factors, such as diet, may influence the development of sarcopenia. Since a poor diet and nutritional status are common among the elderly [8, 9, 10], improvements in these factors may contribute to the prevention and treatment of sarcopenia, thereby promoting better health in later life for this population [11].
The term
While there is growing evidence linking healthier diets with greater muscle strength and better physical performance outcomes in older adults, limited information is currently available on how diet quality influences sarcopenia in older adults [11, 18]. A recent systematic review concluded that the number of longitudinal studies was too small to reach concrete conclusions; however, there is growing evidence for the benefits of adhering to a Mediterranean diet [19, 20, 21]. The next section summarizes current epidemiological evidence for the relationship between diet quality and sarcopenia in older adults.
The world’s population is getting older [22]. Based on a 2017 report, the number of adults aged 60 years and older will increase worldwide, from 962 million (or one in eight individuals) in 2017 to 2.1 billion (one in five) by the middle of the 21st century [23]. Several environmental and lifestyle factors may modify the aging process [24], including physical activity [25, 26] and diet [27, 28, 29].
A large number of observational and intervention studies have used a single-nutrient approach to investigate the relationship between diet and muscle health in aging. However, difficulties are associated with isolating the influence of one dietary component on health outcomes from other components as well as obtaining a clearer understanding of how dietary components interact within a whole diet to affect health outcomes. Previous studies using a whole-diet approach were conducted to clarify the role diet quality plays in muscle health with aging [30, 31, 32, 33].
Two main methods of defining diet quality—
We reviewed nutritional epidemiology studies on the role of diet quality in muscle health and function in older adults (Table 1). Only eight studies reported a relationship between diet quality (i.e., the amount of nutrients consumed and/or the uptake of specific nutrients from foods) and sarcopenia components [38, 39, 40, 41, 42, 43, 44, 45]. Five of these studies were cross-sectional, while three were longitudinal. Study sample sizes ranged between 156 and 2983 participants. The majority of studies were conducted in a community setting (e.g., a nursing home or care facility) and with participants whose mean age ranged between 65 and 75 years.
Reference | Population | Study design | Diet quality (DQ) | Physical function | |
---|---|---|---|---|---|
Robinson et al. (2008) [38] | n = 2983 community-dwelling men (n = 1569) and women (n = 1414), 65.7 ± 2.9 years (men) 66.6 ± 2.7 years (women) | Cross-sectional | Administered FFQ based on EPIC Questionnaire 18, pertaining to the 3-month period preceding the interview. | Men and women with high prudent diet scores had stronger grip strengths. | |
Martin et al. (2011) [39] | n = 628 community-dwelling men (n = 348) and women (n = 280), 67.8 ± 2.5 years (men) 68.1 ± 2.5 years (women) | Cross-sectional | Administered FFQ pertaining to the 3-month period preceding the interview Data-driven: PCA. A “prudent” dietary pattern was identified. | In women, a higher prudent diet score was associated with a shorter 3-m walk time, shorter chair-rise time, and better balance. | |
Bollwein et al. (2013) [40] | n = 192 community-dwelling men and women, 83 ± 4 years | Cross-sectional | Administered FFQ of the German part of the EPIC study. Dietary indices: Adherence to a Mediterranean dietary pattern was assessed using the MED score | A relationship was observed between a high MED score and lower risk of a slow walking speed. | |
Rahi et al. (2014) [41] | n = 156 community-dwelling men (n = 94) and women (n = 62) with type 2 diabetes, 74.3 ± 4.2 years (men) 75.0 ± 4.2 years (women) | Longitudinal | Three non-consecutive 24-h dietary recalls. Dietary indices; DQ was evaluated at recruitment using the Canadian Healthy Eating Index (C-HEI). | Good DQ was combined with stable or increased physical activity, and muscle strength losses were minimal in diabetic older males. | |
Hashemi et al. (2015) [42] | n = 300 elderly men and women (55 years old and older), 66.8 ± 7.2 years | Cross-sectional | Three major dietary patterns (DP) were identified. a. DP1, Mediterranean b. DP2, Western c. DP3, Mixed | Participants in the highest tertile of DP1 had a lower odds ratio for sarcopenia than those in the lowest tertile. | |
Granic et al. (2016) [43] | n = 791 men (n = 302) and women (n = 489), living either at home or in a care facility, 68.7 ± 0.3 years | Longitudinal | Three dietary patterns were identified. a. DP1, High Red Meat b. DP2, Low Meat c. DP3, High Butter | Men in DP1 had worse overall hand grip strength and slower timed up and go than those in DP2. Women in DP3 had slower timed up and go than those in DP2. Men in DP3 had a steeper decline in hand grip strength than those in DP1. | |
Perälä et al. (2016) [44] | n = 1072 participants, elderly men and women, 61.3 ± 0.2 years | Longitudinal | Dietary indices: The | Women in the highest fourth of the NDS had a 5-point higher Senior Fitness Test score on average than those in the lowest fourth. | |
Suthutvoravut et al. (2020) [45] | n = 1241 community-dwelling men (n = 646) and women (n = 595), 74.6 ± 5.5 years | Cross-sectional | Three dietary patterns were identified. a. DP1, high factor loading for fish, tofu, vegetables, and fruits b DP2, high factor loading for fish, rice, and miso soup c. DP3, high factor loading for noodles | Men with the lowest tertile of the DP1 score had a higher likelihood of being sarcopenic. Women with the lowest tertile of the DP2 score had a moderate likelihood of being sarcopenic. |
Summary of diet quality and physical function in older adults.
Robinson et al. examined the relationship between diet quality and grip strength in older men and women [38]. A food frequency questionnaire (FFQ) based on the European Prospective Investigation of Cancer (EPIC) questionnaire was used to assess the subject’s diet. They used the FFQ that contained 129 foods and food groups and assessed the average frequency of the consumption of the listed foods over the three months preceding the interview. Nutrient intake for each food item consumed was calculated by multiplying the nutrient content listed in the UK national food composition database or manufacturer composition data. The 129 foods listed in the FFQ were divided into 54 food groups based on similarity and nutrient compositions. The PCA of the reported weekly consumption frequencies of these food groups was used to define diet patterns. The
Martin et al. investigated the relationship between diet and physical performance (measured using a short physical performance battery) in a group of men and women living in West Hertfordshire who were part of the Hertfordshire Cohort Study [39]. Nutrient intake for each food item consumed was calculated by multiplying the nutrient content listed in the UK national food composition database or manufacturer composition data. Higher prudent diet scores were related to shorter three-meter walk times and shorter chair-rise times in women. Additionally, inverse relationships were observed between physical function and the consumption of vegetables, whitefish, shellfish, and oily fish. These findings indicate that a relationship exists between diet variations in community-dwelling older women and differences in physical performance. However, further studies are needed to clarify the role of diet variations in physical performance, particularly in men.
Bollwein et al. examined whether the risk of frailty was significantly reduced in participants who scored in the highest quartile for Mediterranean diet consumption (MED) [40]. This scoring is an alternative to the MED scoring used by Fung et al. [46], who adapted the original MED score used by Trichopoulou et al. [47] for a non-Mediterranean population. They combined FFQ foods into nine nutritional characteristics, classified as either beneficial (vegetables, legumes, fruits, unrefined cereals, nuts, fish, high monounsaturated fatty acid [MUFA]/saturated fatty acid [SFA] foods, and moderate alcohol consumption) or detrimental (red and processed meats) to health, to calculate the score, and found an inverse correlation between a low walking speed and MED scores. Moreover, a relationship was observed between high diet quality (high MED score) and slow walking speed in older men and women.
Rahi et al. investigated the relationship between diet quality and muscle strength changes over three years in diabetic participants aged 67 to 84 years [41]. Diet quality was evaluated at recruitment using the validated Diet Quality Index-Canada and nine-item Canadian Healthy Eating Index (C-HEI) [48]. Diet quality was calculated using data from the mean of three, non-consecutive, 24-hour dietary recalls collected using the five-step, multiple-pass method [49]. The C-HEI has nine components. The first four components evaluate the extent to which respondents meet age and gender-based recommendations for the number of portions eaten from each of the four groups of Canada’s Food Guide (grain products, vegetables and fruits, milk and alternatives, and meat and alternatives). The next four items reflect Canadian nutritional recommendations for moderation: the daily percentage of energy from total fat, the daily percentage of energy from saturated fat, cholesterol intake (mg), and sodium intake (mg). The final component, dietary variety (adapted from the Dietary Diversity Score), was assessed as the daily consumption of at least one food from each food group. The findings obtained indicated that the combination of a high diet quality with stable or increased physical activity minimized muscle strength losses in diabetic older males over the three-year follow-up period.
Hashemi et al. investigated whether adherence to a particular dietary pattern was associated with sarcopenia among elderly adults in a district of Teheran, Iran [42]. A semiquantitative FFQ was used to survey the dietary intake of 300 randomly-selected older men and women. They evaluated the dietary patterns of participants using PCA. Participants in the highest tertile of the Mediterranean dietary pattern had a lower odds ratio for developing sarcopenia than those in the lowest tertile. In contrast, adherence to the Western dietary pattern (characterized by the high consumption of sugar, soy, and fast foods) and mixed dietary pattern (characterized by the high consumption of animal proteins, potatoes, and refined grains) did not affect the odds of developing sarcopenia. These findings suggested that Mediterranean diet adherence was associated with a lower odds ratio for the development of sarcopenia among older Iranian individuals.
Granic et al. examined the relationship between previously established dietary patterns and declines in muscle strength and physical performance among older adults [43]. In total, 791 participants were followed for five years to detect changes in grip strength and timed up and go test (TUG) scores. Trained research nurses kept a detailed record of food intake on the previous day for each participant on two different days of the week, at least one week apart. Each food had a unique food code (>2000), and intakes were entered into a Microsoft Access-based dietary data system, then further grouped into 118 food groups based on McCance and Widdowson’s composition of foods [50, 51]. These 118 groups were combined into 33 food groups based on food/nutrient composition similarities and then classified as either absent or present in each participant’s food intake. Participants were divided into three groups: dietary pattern 1 (DP1; high red meat); dietary pattern 2 (DP2; low meat); and dietary pattern 3 (DP3; high butter). The findings obtained showed that men in DP1 had worse overall grip strength, whereas those in DP3 had steeper grip strength declines than those in DP2. Additionally, TUG scores were significantly longer for men in DP1 and women in DP3 than those in DP2. Therefore, diets high in red meats, potatoes, gravy, and butter appear to adversely affect muscle strength and physical performance in later life.
Perälä et al. researched whether the consumption of a healthy Nordic diet for 10 years was associated with improved physical performance measures [44]. After the diets of 1072 participants (mean age 67 years) had been examined using a validated 128-item FFQ, the
Suthutvoravut et al. investigated the relationship between dietary patterns and sarcopenia in a sample of older community-dwelling Japanese adults [45]. The sample included 1241 older adults aged 65 years and older who were not eligible for long-term care. Dietary intake by participants was assessed using the brief self-administered diet history questionnaire. Dietary patterns were identified using both PCA and Japanese diet scores (soybeans and soybean products, fish, vegetables, pickles, mushrooms, seaweeds, and fruits). Participants were classified into three groups: dietary pattern 1 (DP1; high factor loading for the consumption of fish, tofu, vegetables, and fruits found in typical Japanese side dishes); dietary pattern 2 (DP2; high factor loading for fish, rice, and miso soup found in typical Japanese main dishes); and dietary pattern 3 (DP3; high factor loading for noodles). The findings obtained showed that men with the lowest tertile DP1 score had a higher likelihood of being sarcopenic, while women with the lowest tertile DP2 score had a moderate likelihood of being sarcopenic. Additionally, low adherence to Japanese dietary patterns increased with the prevalence of sarcopenia in both genders.
Many traditional regional diets may have similar benefits to those described here. We then focused on diets with demonstrated effects on muscle mass, reported by randomized controlled trials that investigated diet quality using precise parameters. For example, the traditional diets of Korea and China may be beneficial for preventing sarcopenia in the populations of these countries. Healthier diets are higher in plant-based food and lower in animal-based foods than Western diets. Further epidemiological studies are needed to investigate the relationship between healthy diets and development of sarcopenia throughout the world, particularly in developing countries.
Skeletal muscle is a dynamic, plastic tissue with a mass that is regulated by the balance between the rates of muscle protein synthesis and breakdown. Adopting an appropriate dietary strategy is crucial for facilitating an anabolic response that may prevent muscle wasting with atrophy by suppressing the breakdown of muscle protein. An adequate nutrient intake is essential for maintaining and improving muscle properties. Many supplements have been proposed to enhance muscle mass and strength. More than 50% of adults in the United States take some form of dietary supplement to improve their health or well-being [52]. However, there is no scientific evidence for the effectiveness of many of these supplements. In some cases, their use has been linked to serious adverse side effects. This section summarizes the effects of several popular nutritional supplements when administered under strict dietary controls, either alone or in combination with other supplements.
In a randomized study, Tieland et al. examined the effects of 24 weeks of dietary protein supplementation on muscle mass, strength, and physical performance in a sample of frail older adults [53]. This study included 65 frail participants who were allocated to either the daily protein supplementation group (15 g protein consumed at breakfast and lunch) or placebo group (0 g protein at breakfast and lunch). Participants recorded their food intake for three days with the help of trained dieticians. Dietary intake data were coded (the type of food, time of intake, and amount), and energy and macronutrient intakes were calculated using a food-calculation system from the 2006 Dutch food composition database. The findings obtained indicated that skeletal muscle mass did not change in either the protein or placebo group following the 24-week intervention. However, leg extension strength increased more in the protein group than in the placebo group. Furthermore, physical performance significantly improved (from 8.9 to 10.0 points) in the protein group, but not in the placebo group. Therefore, while dietary protein supplementation appeared to improve physical performance in frail older adults, it did not increase their skeletal muscle mass.
Kim et al. investigated whether protein-energy supplementation prevented functional declines in frail older adults with a low socioeconomic status [54]. In that study, 84 frail elderly participants were assigned to either an intervention or control group. The intervention group received two 200-ml cans of commercial liquid formula (an additional 400 kcal of energy, 25 g of protein, 9.4 g of essential amino acids, and 400 ml of water) each day for 12 weeks, while the control group did not. Dietary intake was assessed in three, non-consecutive 24-hour recall sessions (one face-to-face and two by telephone; weekday and weekend ratio of 2:1) to show the nutritional status. The same research dietitian coded dietary data, and a nutrient analysis was performed using CAN-Pro 3.0. No significant changes were observed in grip strength in either group; however, physical functioning, usual gait speed, and TUG scores were significantly better in the protein group than in the control group. Therefore, protein-energy supplementation administered to frail older adults with a low socioeconomic status appeared to reduce the progression of functional decline.
Veronese et al. investigated whether 12 weeks of oral magnesium supplementation improved physical performance in healthy older women [55]. In that study, 124 participants were grouped into either a treatment group (300 mg of magnesium/day) or control group (no treatment). A dietary assessment was examined by a modified method including an estimated three-day record and a questionnaire about the frequency that participants generally ate certain foods. They used the data from the previous month as a reference and calculated the macronutrients and micronutrients of usual food intake by a national food composition table. After 12 weeks of supplementation with magnesium, the treatment group had significantly higher total short physical performance battery scores, chair-stand times, and four-minute walking speeds than the control group. These findings indicated that magnesium supplementation prevented or delayed age-related physical performance declines.
Roma et al. examined the effects of PUFA supplementation on the parameters of body composition, muscle strength, and physical performance in the elderly [56]. Fifty participants were randomly assigned to a PUFA-treated group (receiving 1.3 g of PUFA and 10 mg of vitamin E) or control group (receiving 11 mg of vitamin E). Participants were assessed using the mini nutritional assessment (composed of six questions related to decreased food intake in the three months before the test) and a 12-question survey on diet (number of meals consumed and consumption of protein, fruits, vegetables, and liquids) and the ability to feed themselves. No significant between-group differences were observed in muscle mass, grip strength, or TUG scores. Therefore, the 12-week PUFA supplementation did not appear to affect the parameters evaluated in elderly individuals with a decreased muscle mass.
Bauer et al. sought to test the hypothesis that a specific oral nutritional supplement may improve selected sarcopenia measures [57]. The active group (n = 184) consumed a vitamin D and leucine-enriched whey protein nutritional supplement twice daily for 13 weeks. The control group (n = 196) consumed an iso-caloric control product twice daily for 13 weeks. A dietary assessment was completed at baseline and week 13 using three-day prospective diet records for two weekdays and one weekend day. Additional energy and protein intakes from both supplements were added to habitual three-day intakes to assess total intake. The active group gained more appendicular muscle mass and performed better in the chair-stand test than the control group. These findings demonstrated that specific nutritional supplementation alone may benefit geriatric patients, particularly those unable to exercise.
Porter et al. investigated whether participants following an enhanced protein regimen have greater functional status improvements and better lean muscle mass preservation than control group participants [58]. In that study, 67 obese older adults were randomly assigned to either a traditional weight loss regimen (control group) or one with a higher protein intake at each meal (protein group). Control group participants were prescribed a 500-kcal deficit diet (15% protein, 30% fat, and 55% carbohydrate), which met the recommended dietary allowance (RDA) for protein intake (0.8 g/kg of body weight). Protein group participants were also prescribed a 500-kcal deficit, but with a macronutrient distribution of 30% protein, 30% fat, and 40% carbohydrate, for a total prescribed protein intake of 1.2 g/kg. Both groups exhibited significant weight loss at the six-month endpoint. However, while both groups had improved muscle function, the Short Physical Performance Battery response was greater in the protein group than in the control group. These findings indicated that functionally limited obese adults undergoing a six-month weight loss intervention that included a meal-based protein enhancement lost similar amounts of weight, but had better functional improvements than the control group.
Only one of the studies used an iso-caloric control supplement to investigate the efficacy of a vitamin D and leucine-enriched whey protein nutritional supplement (not combined with exercise) for attenuating sarcopenia. To produce the most useful data, future studies that investigate whether a simple nutrient supplement contributes to the prevention of sarcopenia will need to use dietary control in a sample of more than 100 elderly participants. Evidence from two
Reference | Population | Diets | Nutritional intervention | Changes in muscle mass and strength | Physical function |
---|---|---|---|---|---|
Tieland et al. (2012) [53] | n = 65 frail elderly subjects | 1935 kcal/day, 49% CHO, 35% fat, 16% protein (1.0 g protein/kg/day) | 15 g protein × twice/day for 24 wks vs. non protein × twice/day for 24 wks | No change in muscle mass in both groups Significant increase in muscle strength in both groups. | Significantly improved physical performance in the protein group, but not in the control group |
Kim et al. (2013) [54] | n = 84 frail elderly subjects, 78.7 ± 5.8 years | 896 kcal/day (0.7 g protein/kg/day) | 400 kcal (25 g protein, 9.4 g amino acids, 56 g carbohydrate, 9 g lipids, micronutrients)/day for 12 wks vs. non-supplemental control | No change in hand grip strength in both groups | Significantly improved physical functioning, usual gait speed, and timed up-and-go in the protein group, but not in the control group |
Veronese et al. (2014) [55] | n = 124 elderly women, 71.5 ± 5.2 years | 1490 kcal/day (383 mg magnesium/day) | 300 mg magnesium/day for 12 wks vs. non-supplemental control | No change in hand grip strength in both groups | Significantly improved Short Physical Performance Battery score, chair-stand times, and 4-m walking speeds in the magnesium group, but not in the control group |
Roma et al. (2015) [56] | n = 50 elderly subjects, 74.9 ± 7.9 years | Mini Nutritional Assessment score 24.1 ± 3.1 points | 1.3 g omega-3 fatty acids/day for 12 wks vs. non-supplemental control | No differences in muscle mass or hand grip in both groups | No differences in timed up-and-go in both groups |
Bauer et al. (2015) [57] | n = 380 sarcopenic primarily independent-living older adults, 77.7 ± 6.9 years | 1612 kcal/day (1.0 g protein/kg/day) | 800 IU vitamin D + 20 g whey protein +3 g leucine twice/day for 13 wks (active) vs. iso-caloric control | Significantly higher appendicular muscle mass in the active group than in the control | Significantly improved chair-stand test in the active group from those in the control group |
Porter et al. (2016) [58] | n = 67 obese older adults with a Short Physical Performance Battery (SPPB) score of 4–10, 68.2 ± 5.6 years | 1458 kcal/day, 55% CHO, 30% fat, 15% protein (0.8 g protein/kg/day) | 30 g protein × 3 times/day for 6 mo vs. non-supplemental control | No differences in lean body mass or hand grip in both groups | Significantly improved total and chair-stand scores in the protein group from those in the control group |
Summary of effects of nutrient supplementation for attenuating sarcopenia.
A number of conditions, such as recovery from injury or illness or space flight, require prolonged periods of muscle disuse (i.e., unloading) in otherwise healthy individuals, resulting in the progressive loss of skeletal muscle mass that impairs functional strength, reduces the basal metabolic rate, and increases body fat mass. Therefore, prolonged muscle disuse is a significant health concern, particularly in aging populations. While nutrition is an important factor regulating muscle mass, the development of effective nutritional strategies that attenuate muscle loss during periods of muscle disuse warrants further efforts. Table 3 shows an overview of studies that have assessed the efficacy of nutritional interventions for attenuating muscle disuse atrophy under controlled diet quality.
Reference | Population | Diets | Nutritional intervention | Changes in muscle mass | Loss of strength |
---|---|---|---|---|---|
Paddon-Jones et al. (2004) [61] | n=13 young males, Bed rest (28 days) | 2487 kcal/day, 59% CHO, 27% fat, 14% protein (1.0 g protein/kg/day) | 30 g carbohydrate +16.5 g EAA vs. non-supplemental control | Leg lean mass maintained in EAA, but lost in the control | Significantly lower decrease of 11% in EAA than in the control (23% down) |
Trappe et al. (2007) [62] | n = 24 young women, Bed rest (60 days) | 1557 kcal/day, 56% CHO, 30% fat, 14% protein (1.0 g protein/kg/day) | 1.0 (low), 1.6 (high) g/kg body mass/day dietary protein | Greater loss of quadriceps femoris muscle volume in high protein (24%) vs. low protein (21%) | 19 ~ 33% decreased for the supine square in both groups |
Ferrando et al. (2010) [63] | n = 21 elderly, Bed rest (10 days) | (0.8 g protein/kg/day) | 15 g × 3 times/day EAA vs. the non-supplemental control | ~6% decrease in leg lean mass in both groups | Better functional capacity in EAA than in control |
Deutz et al. (2013) [64] | n=19 older adults, Bed rest (10 days) | 1900 kcal/day (0.8 g protein/kg/day) | 3 g/day HMB vs. non-supplemental control, 5 days prior to bed rest | Leg lean mass maintained in HMB, but lost in control | No difference in the knee extensor in both groups |
Dirks et al. (2014) [65] | n = 23 elderly men, One-legged immobilization (5 days) | 2150 kcal/day, 51% CHO, 33% fat, 16% protein (1.1 g protein/kg/day) | 9.3 g carbohydrate +20.7 g protein +3.0 g fat twice/day vs. the non-supplemental control | 1.5 ~ 2.0% decrease in quadriceps CSA in both groups | 8.3 ~ 9.3% decrease in maximal muscle strength in both groups |
English et al. (2016) [66] | n=19 middle-aged adults, Bed rest (10 days) | 2111 kcal/day, 55% CHO, 30% fat, 15% protein (1.1 g protein/kg/day) | 4.5 g × 3 times/day leucine vs. 4.5 g × 3 times/day alanine | 5.3 ~ 6.9% reduction in leg lean mass in both groups | Significantly smaller decrease of 7% in leucine than in alanine (15% down) with knee extensor peak torque |
Holloway et al. (2019) [67] | n = 20 young men, One-legged immobilization (8 days) | 2521 kcal/day (1.0 g protein/kg/day) | 23.7 g × 3 times/day amino acids vs. 23.7 g × 3 times/day maltodextrin (iso-caloric control) | Significantly lower decrease of 3.1% in amino acids than in control (2.4% down) in quadriceps muscle volume | No difference in both groups in peak leg isometric torque |
Summary of effects of nutritional interventions on muscle mass and strength during a period of muscle disuse.
Paddon-Jones et al. examined whether supplementation with essential amino acids and carbohydrates offset the catabolic response to 28 days of bed rest [61]. Thirteen healthy male participants were randomly assigned to either the experimental or control groups. The control group consumed nutritionally mixed meals three times a day. The experimental group consumed the same meals plus 30 g of carbohydrate and 16.5 g of essential amino acids three times a day. The Harris-Benedict equation was used to estimate daily caloric requirements, according to the following formula: daily energy requirement (kcal) = [66 + (13.7 × kg) + (5 × cm) – (6.8 × yr)] × 1.3 (activity factor for bed rest). Participants were placed on a three-day rotating diet with daily nutrient intake evenly distributed between the three meals. The findings obtained revealed that the experimental group maintained lean leg mass throughout bed rest (+0.2 kg), whereas the control group lost mass (−0.4 kg). In addition, strength loss was more pronounced in the control group (exp group, −8.8 kg; cont group, −17.8 kg). Therefore, supplementation with essential amino acids and carbohydrates during bed rest appeared to provide an anabolic stimulus that ameliorated lean muscle mass loss in an otherwise catabolic environment. However, it currently remains unclear whether additional energy intake contributed to these findings.
Trappe et al. investigated whether nutritional countermeasures, consisting of additional protein and free leucine, reduced volume and strength losses in lower-limb skeletal muscle during 60 days of simulated weightlessness [62]. Young women were assigned to either the bed rest group (control) or the bedrest plus a nutrition countermeasure group (intervention). Dietary staff prepared all meals for both groups. These meals contained controlled amounts of total energy and macronutrients. The findings obtained demonstrated that thigh muscle (quadriceps femoris) volume decreased in both the control (−21%) and intervention groups (−24%). Moreover, both groups exhibited similar large decreases in isometric and dynamic (centric force, eccentric force, power, and work) muscle strength for the supine squat (−19% to −33%). Therefore, the nutrition countermeasure did not appear to be effective at offsetting volume or strength losses in lower-limb muscles. Furthermore, exercise countermeasures may need to be modified to protect the calf muscles of participants.
Ferrando et al. examined the effects of an increasing protein intake (through essential amino acid supplementation) in older individuals subjected to 10 days of bed rest on their lean body mass and muscle function [63]. Participants received either a placebo or 15 g of essential amino acids, three times a day throughout 10 days of bed rest. The placebo was a non-caloric diet soda. During diet stabilization and bed rest, subjects consumed a lacto-ovo vegetarian diet providing the RDA for protein (0.8 g/kg of protein per day). The diet consisted of a three-day rotation based on the Harris-Benedict equation designed to maintain body weight throughout the study. An activity factor of 1.3 was used to estimate daily energy requirements during bed rest. The findings obtained indicated that essential amino acids did not affect the maintenance of total or leg lean muscle mass. However, stair ascent power and standing plantar flexion appeared to be maintained with essential amino acid supplementation. Therefore, increasing protein intake above the RDA may preserve muscle function in elderly individuals during compulsory inactivity. However, this protocol may need to be operated under iso-caloric nutritional interventions.
Deutz et al. attempted to clarify whether beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, was capable of attenuating muscle decline in healthy older adults during 10 days of bed rest [64]. Healthy older adults were randomly assigned to a control group or HMB group (Ca-HMB, 1.5 g twice daily, total 3 g/day). Participants were fed a metabolically controlled diet for diet stabilization, providing the RDA for protein intake (0.8 g protein/kg of body weight per day). Total calorie needs were estimated using the Harris–Benedict equation for resting energy expenditure. An activity factor of 1.35 was used to estimate daily energy requirements during bedrest. The study protocol significantly decreased total lean body mass in the control group. In contrast, the treatment with HMB prevented these declines in all but one participant in the HMB group. However, differences in functional parameters were not observed between the two groups. These findings indicated that HMB supplementation contributed to the preservation of muscle mass during 10 days of bed rest. Further studies using larger samples and iso-calorie conditions for nutritional interventions are needed to clarify the preventative effects of HMB on the acute decline in muscle mass.
Dirks et al. investigated whether protein supplementation preserved muscle mass during a short period of limb immobilization [65]. Healthy older men were subjected to five days of one-legged knee immobilization using a full-leg cast with or without the twice-daily administration of a dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat). Weighted dietary intake records were completed by participants for the five-day immobilization period and on a separate consecutive five-day occasion, either before or after the immobilization period. Immobilization decreased the quadricep cross-sectional area by 1.5 and 2.0%, and muscle strength by 8.3 and 9.3% in the control and protein groups, respectively. These findings indicated that dietary protein supplementation (~20 g twice daily) did not attenuate muscle loss during short-term muscle disuse in healthy older men.
English et al. investigated whether leucine protects skeletal muscle health during bed rest [66]. In that study, a group of middle-aged adults were randomly assigned to a leucine group (4.5 g leucine × 3 times/day) or alanine group (4.5 g alanine × 3 times/day). Participants were fed controlled isoenergetic diets with protein intake evenly distributed across three daily meals for diet stabilization. Daily energy requirements were estimated using the Harris-Benedict equation. An activity factor of 1.3 was used during the bedrest period. The findings obtained indicated that while leg lean mass significantly decreased in both groups, leucine supplementation protected knee extensor peak torque more than in the alanine group. Therefore, leucine supplementation appeared to protect muscle health during relatively brief periods of physical inactivity. The parameters of this study allowed for the strict control of diets and nutritional supplementation under energy-matched conditions; therefore, leucine supplementation may help protect muscle function in muscle disuse atrophy.
Holloway et al. examined the safety, tolerability, and atrophy-mitigating effects of a novel amino acid composition (containing essential amino acids and arginine, glutamine, and N-acetylcysteine) during single-limb immobilization [67]. Twenty young men were randomly assigned to receive either the amino acid mixture or an energy-matched, non-amino acid-containing placebo three times a day (two hours after breakfast, lunch, and dinner) for consecutive days. Diets were designed to achieve an energy balance, and meal plans included protein derived from dairy sources held constant at 1.0 g/kg/day. The reduction in the cross-sectional area of the quadriceps muscle was significantly lower in the amino acid group than in the placebo group. However, immobilization resulted in similar relative declines in peak torque in both groups. These findings indicated that the daily consumption of an amino acid mixture (three times a day for 28 days) attenuated muscle atrophy, and are bolstered by the use of well-controlled diets and nutritional supplementation with energy-matched conditions.
A number of human studies examined the effects of nutritional interventions on muscle mass and strength during a period of muscle disuse [68, 69]. Due to insufficient dietary control, these studies were not sufficient to clarify the nutritional value of such supplements. Despite these deficits, many studies have reported the efficacy of nutritional supplementation for preventing the loss of muscle mass and strength during a period of muscle disuse
In this chapter, we (a) summarized nutritional epidemiology evidence related to sarcopenia from recent systematic reviews; (b) reviewed the role nutrient supplementation plays in attenuating sarcopenia through dietary control; (c) provided evidence for the efficacy of nutrient supplementation for treating disuse muscle atrophy under controlled diet quality conditions.
Dietary patterns of adequate quality for older adults (i.e., ensuring a sufficient intake of beneficial foods, such as fruits, vegetables, whole grain products, fish, nuts, and low-fat foods) are useful for preventing sarcopenia. While the Mediterranean diet has been touted as a healthy diet, other diets (healthy Nordic or traditional Asian diets) also help prevent sarcopenia in older adults.
Vitamin D and leucine-enriched whey protein supplement may be useful for attenuating sarcopenia in geriatric patients, particularly in those unable to exercise.
Further studies are needed to clarify the effects of protein and amino acid supplementation on muscle mass and strength.
Based on the strong evidence linking nutrition to muscle mass and function, nutrition plays a crucial role in both the prevention and management of sarcopenia. Further high quality studies, particularly those using large sample sizes, controlled diet quality, and iso-caloric placebo supplementation, are needed to provide a clear understanding of the dose and duration effects of nutrients on muscle atrophy.
The authors declare no conflict of interest.
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