PERSPECTIVE
             Perspective:VeganDietsforOlderAdults?
             APerspectiveOnthePotentialImpactOnMuscle
             MassandStrength
                            ´ 1                   1                 2,3                            1
             JacinthaDomic, PolGrootswagers, LucJCvanLoon,             andLisetteCPGMdeGroot
             1Division of HumanNutritionandHealth,WageningenUniversity,Wageningen,TheNetherlands;2DepartmentofHumanBiology,SchoolofNutritionand
             Translational Research in Metabolism (NUTRIM),MaastrichtUniversityMedicalCentre+,Maastricht,TheNetherlands;and3InstituteofSportsandExercise
             Studies,HANUniversityofAppliedSciences,Nijmegen,TheNetherlands
               ABSTRACT
             Consumers are increasingly encouraged to consume more plant-based foods and lower their consumption of foods from animal origin.
             Concurrently, older adults are recommended to consume an adequate amount of high-quality dietary protein for the prevention of age-related
             muscleloss. In the current Perspective article, we discuss why it may not be preferred to consume a vegan diet at an older age. Our perspective is
             basedontheproposedlowerbioavailabilityandfunctionality of proteins in a vegan diet due to the matrix of the whole-food protein sources, the
             lower essential amino acid (EAA) content, and specific EAA deficiencies in proteins derived from plant-based foods. We propose that a vegan diet
             increasestheriskofaninadequateproteinintakeatanolderageandthatcurrentstrategiestoimprovetheanabolicpropertiesofplant-basedfoods
             are not feasible for many older adults. We provide recommendations for further research to substantiate the remaining knowledge gaps regarding
             theconsequencesofavegandietonskeletalmusclemassandstrengthatanolderage. AdvNutr2022;13:712–725.
                StatementofSignificance: To our knowledge, this is the first article that provides an evidence-based perspective regarding the potential
                impact of a vegan diet on muscle mass and strength in older adults. The current perspective is highly relevant considering the envisaged
                shifts towards sustainable dietary guidelines.
             Keywords: plant-basedfood,animal-basedfood,plant-baseddiet,aging,protein,sustainablefood
             Introduction                                                       such as improving cardiovascular risk factors (6–9). These
             Several countries are adapting to dietary guidelines that          indications are promising for several subgroups of the adult
             recommend increasing the consumption of plant-based                population. However, the consequences of consuming a
             foods and thereby lowering the consumption of animal-              vegan diet at an older age on skeletal muscle mass and
             basedfoods(1,2).Thistransitiontowardsplant-basedeating             strength remain unknown. Concurrently, the loss of muscle
             is primarily driven by environmental factors and is endorsed       massandstrengthwithintheagingpopulationisanemerging
             by the EAT-Lancet commission and the European Unions              public health concern (10).
             call for Europe-widesustainabledietaryguidelinesbeforethe             Theage-relatedlossofmusclemassandstrengthbecomes
             endof2030(3,4).                                                    apparent approximately in the fifth decade of life and may
                Plant-baseddietscanbeclassifiedaccordingtotherelative           result in sarcopenia. Sarcopenia is a muscle disorder that is
             contribution of animal- and plant-based foods within the           characterized by low muscle strength in combination with
             diet. A vegan diet is considered the strictest plant-based diet    low muscle mass or quality (11). In community-dwelling
             andexcludesallfoodsfromanimalorigin(5).Theincreased                older adults, the estimated prevalence of sarcopenia ranges
             consumption of fruits and vegetables that concur with a            from 9.9% to 40.4% depending on the definition used (12).
             vegan diet may improve the dietary intake of important             Sarcopeniaincreasestheriskforfrailty, falls, hospitalization,
             nutrients and bioactive compounds. In accordance, vegan            impaired recovery, and mortality (11, 13). As such, in view
             diets have been associated with potential health benefits,         of the envisaged transition towards more plant-based dietary
                      
             712       C TheAuthor(s)2022.PublishedbyOxfordUniversityPressonbehalfoftheAmericanSocietyforNutrition.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
                 CommonsAttributionLicense(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is
                                                                                  properly cited. Adv Nutr 2022;13:712–725; doi: https://doi.org/10.1093/advances/nmac009.
                    guidelines, it is urgently needed to underscore the potential                                         (MPS) and inhibits muscle protein breakdown via various
                    impact of a vegan diet on muscle mass and strength at an                                              pathways. The balance between MPS and muscle protein
                    older age.                                                                                            breakdown(i.e.,muscleproteinturnover)determinesmuscle
                         TheaimofthecurrentPerspectivearticleistodiscussthe                                               maintenance, loss, or growth. When MPS exceeds break-
                    potential consequences of a vegan diet on muscle mass and                                             downconsistently,thisleadstotheaccretionofnewlysynthe-
                    strength in adults aged 65 y and older. Thereby, we extend                                            sized muscleproteinsandeventuallymusclegrowth(18,19).
                    our evaluation from data on isolated plant-based protein                                                  Theability of a protein source to alter muscle protein bal-
                    sourcestowardstheimpactofconsumingwholemealsand anceisdependentonitsdigestionandabsorption,splanchnic
                    diets. This whole-diet, or so-called holistic, approach has                                           amino acid uptake, plasma amino acid availability, the
                    gained more emphasis in the recent years as it considers all                                          transportation of amino acids to the muscle, the subsequent
                    food component interactions within meal matrices (14, 15).                                            uptake of amino acids by the muscle, and intramuscular
                    Burdandcolleagues(15)recentlyhighlightedtheimportance                                                 signalling (20). Furthermore, the EAA content of a protein
                    of such an approach when assessing the effects of dietary                                             sourceispivotalforthepostprandialstimulationofMPS(21–
                    interventions, focusing on meals and diets rather than single                                         25).Whenaproteinsourcelacks1EAA,allotheraminoacids
                    food sources, since food components interact differently                                              appear to be oxidized rather than used for MPS (26). It is
                    whenconsumedaspartofamealratherthaninisolation.                                                       suggested that EAAs themselves may function as nutritional
                         The current article 1) provides a short overview of                                              signals with the potential to directly stimulate MPS and
                    the current status of knowledge regarding dietary protein                                             inhibit protein breakdown. For example, the EAA leucine
                    recommendations for older adults, 2)discussesthequality isshowntohavetheabilitytostimulateMPSbyactivating
                    and functionality of both isolated plant-based proteins and                                           the mammalian target of rapamycin complex 1 (mTORC1)
                    proteins within a vegan meal, 3) highlights why current                                               pathway,andsubsequentlyactivatingmRNAtranslation(22,
                    strategies to improve the anabolic properties of a vegan diet                                         27, 28).
                    maynotbefeasible for older adults, 4) explains that a vegan                                               Older adults are recommended to consume sufficient
                    diet increases the risk of an inadequate protein intake in                                            high-quality protein to maintain muscle mass and physical
                    olderadults,5)providesanoverviewoftheexistingevidence                                                 function and to support healthy aging (13, 16, 17, 29). The
                    regarding vegan diets and the potential impact on muscle                                              RDA for dietary protein is 0.8 g/kg body weight per day
                    mass and strength in older individuals, and 6) provides                                               [g/(kg·d)] for all adults aged 18 y and older (30). However,
                    suggestions for future research regarding this aspect.                                                thecurrentRDAisprimarilyobtainedfromnitrogenbalance
                                                                                                                          studies in young adults and may not be representative for
                    CurrentDietaryProteinRecommendationsfor                                                               older individuals (13, 31). Older adults have been observed
                    OlderAdults                                                                                           to exhibit lower sensitivity to protein consumption, known
                    Aneffectivestrategytoattenuatetherateofdeclineinmuscle                                                as age-related anabolic resistance. As such, older adults
                    massandstrengthwithadvancingageisamplephysical may require a higher dose of protein intake to adequately
                    activity combined with sufficient intake of high-quality di-                                          stimulate MPS (13). Expert groups emphasize that a daily
                    etaryprotein(16,17).Dietaryproteincontainsindispensable                                               dietary protein intake of 0.8 g/(kg·d) is too low for the main-
                    nutrients called essential amino acids (EAAs) that are vital                                          tenanceofmusclemassinindividualsaged≥65 y, and have
                    for maintenance of muscle mass and strength throughout                                                repeatedly proposed to increase the RDA for older adults
                    life. The consumption of dietary protein induces hyper-                                               to approximately 1.0–1.2 g/(kg·d), with specific attention to
                    aminoacidemia, which stimulates muscle protein synthesis                                              timingandqualityoftheconsumedprotein(13,16,17,29).
                    SupportedbyagrantfromtheRegioDealFoodvalley(162135).                                                  TheProteinQualityofaVeganDiet
                    LJCvLhasreceivedresearchgrants,consultingfees, speaking honoraria, or a combination of                The quality of a protein source (i.e., a whole-food product
                    these for research on the impact of exercise and nutrition on muscle metabolism, which                or protein in its isolated form) relates to its ability to meet
                    include funding from companiesthatproducedairy,meat,and/orplant-derivedproteins.Afull                 metabolic demandsandtosupportgrowthandmaintenance
                    overviewonresearchfundingisprovidedat:https://www.maastrichtuniversity.nl/l.vanloon.
                    LCPGMdGandPGhavereceivedgrantsforresearchontheimpactofnutrition(andexercise)                          of body protein mass (32). The quality of a protein source
                    onmusclemetabolism,fromtheDutchgovernment(ZonMw),theEuropeanUnion(H2020),                             is determined by its EAA content, the digestibility of
                    andTopInstituteFoodandNutrition,whichpre-competitivelyincludesfundingfromfood                         the protein, and subsequent bioavailability of the protein-
                    industry (small and medium sized enterprises and larger enterprises). LCPGMdG is an editor on
                    AdvancesinNutrition but played no role in the Journals evaluation of the manuscript.                 derived amino acids. The bioavailability of an amino acid
                    Authordisclosures: The authors report no conflict of interest.                                        is the proportion of the consumed amino acid that is fully
                    Perspective articles allow authors to take a position on a topic of current major importance or       digestedandabsorbed(31,33–35).Together,allthesefactors
                    controversy in the field of nutrition. As such, these articles could include statements based on
                    authoropinionsorpointofview.OpinionsexpressedinPerspectivearticlesarethoseofthe                       contribute to the functionality of the protein—that is, the
                    authorandarenotattributabletothefunder(s)orthesponsor(s)orthepublisher,Editor,or                      ability of the amino acids within the protein to serve their
                    Editorial Board of AdvancesinNutrition. Individuals with different positions on the topic of a        purpose after absorption, for example, to synthesize new
                    Perspective are invited to submit their comments in the form of a Perspectives article or in a
                    Letter to the Editor.                                                                                 proteins in the body or to serve their role in the regulation
                    AddresscorrespondencetoJD(e-mail:jacintha.domic@wur.nl).                                              of neurotransmission or fluid balance.
                    Abbreviations used: ANF, antinutritional factor; DIAAS, Digestible Indispensable Amino Acid               The recommended method to evaluate protein quality is
                    Score; EAA, essential amino acid; en%, % of energy; MPC, milk protein concentrate; MPS,
                    muscleproteinsynthesis; PDCAAS,ProteinDigestibility Corrected Amino Acid Score.                       amino acid scoring. Until recently, the Protein Digestibility
                                                                                                                                                      Aperspectiveonvegandietsforolderadults                         713
              Corrected Amino Acid Score (PDCAAS) was the recom-                   consumedwithinavegandiet,suchasmeatanalogues,nuts,
              mendedmeanstoexpressthequalityofaproteinsource.The                   andseeds, are not yet available.
              PDCAASwascalculatedbasedonasinglevalueoffecalcrude                      Todate,mostresearchintoDIAASexclusivelyfocused
              proteindigestibility.Thisfactorwascriticizedandconsidered            on raw and isolated food products and proteins (36, 39,
              as a major shortcoming and led to the adoption of a new              40).Proteinconcentrates(≥25%protein)andisolates(≥90%
              amino acid scoring method, the Digestible Indispensable              protein) are derived by the removal of nonprotein con-
              Amino Acid Score (DIAAS). The DIAAS differs from the                 stituents. Taking it a step further, proteins can be processed
              PDCAAS by using true ileal amino acid digestibility for              via enzymatic hydrolyzation to provide protein hydrolysates
              each individual EAA instead of a single fecal crude protein          (41). Subsequently, any effects of other food components on
              digestibility value for evaluating the quality of a protein          the bioavailability of the protein-derived amino acids are
              source,sincethisreflectsthebioavailabilityoftheEAAsmore              excluded. However,proteinsandfoodproductsaregenerally
              accurately (31). A short explanation of the DIAAS can be             consumed as part of a meal rather than in their isolated
              foundinText Box 1.                                                   form and it is essential to consider the interplay between
                                                                                   food components within such a meal that may affect amino
                                                                                   acid bioavailability and subsequently their functionality (32,
                Text Box 1                                                         42, 43). Taking these factors into account, in the following
                TheDIAAS                                                           paragraphs we separately discuss that 1)theproteinquality
                The DIAAS is currently the recommended method by                   of most isolated plant-based foods and proteins is inferior
                the FAO to evaluate the protein quality of a food, meal,           to those of animal origin and 2)thequalityofveganmixed
                ordiet. TheDIAASisbasedontheEAAcompositionof                       meals and diets is uncertain and that calculating its DIAAS
                the food source and the ileal digestibility of each EAA.           basedonblendingisolatedfoodsourcesdoesnotaccountfor
                The DIAAS of a protein source is determined by its                 the food component interaction(s) within a single meal or
                mostlimiting digested EAA. As the DIAAS of a protein               within a specific diet.
                source increases, the quality of that protein source
                increases. The DIAAS classification is as follows: <75,            Isolatedplant-basedfoodsandproteinsexhibitinferior
                no quality claim; 75–99, high-quality protein; ≥100,               proteinqualitycomparedwithanimal-basedfoodsand
                excellent-quality protein. A DIAAS ≥100 indicates that             proteins
                the protein source has no limiting EAA. These foods                Protein quality and amino acid content vary widely among
                maybeusedascomplementarysources to foods with a                    animal- and plant-based foods and proteins. The amino
                lower DIAAS to achieve better protein quality in a diet            acid profile of most animal-based foods and proteins can be
                (31).                                                              considered complete, meaning that these foods and proteins
                                                                                   do not exhibit a limiting amino acid, and their DIAAS
                 TheDIAASisacknowledgedasthebestmethodcurrently                    often reflects excellent protein quality (Figure 1A). On the
              available to assess protein quality, but still exhibits several      other hand, the plant-based foods and proteins from which
              limitations that are essential to consider when evaluating           dataregardingproteindigestibilityarecurrentlyavailableare
              the protein quality of a vegan diet (34, 36). One of these           frequently limiting in 1 or more EAA, resulting in lower
              limitations is that the true ileal digestibility of the EAA          DIAAS,andshowahighheterogeneityregardingtheiramino
              does not always accurately reflect bioavailability when it           acid profiles (40, 44–48). Gorissen et al. (44)observedthat
              comes to dietary protein sources that have undergone a               plant-basedproteinisolatesexhibit,onaverage,an11%lower
              certaindegreeofprocessing(e.g.,atthemanufacturerorheat               EAAcontentthananimal-basedproteinisolates,withawide
              treatment while cooking at home). This is mainly the issue           variety in EAA profiles between the different plant-based
              for the amino acids lysine, methionine, cysteine, threonine,         protein isolates. Specifically, the EAA contents of oat, lupin,
              and tryptophan (34, 37, 38). According to Batterham (38),            wheat, and hemp exhibit an EAA content below the amino
              the ratio of retained lysine to the ileal digestible lysine in       acid requirements as established by the WHO (49)andtheir
              pigs was only 0.36 after consuming a cottonseed meal. The            EAAcontentsdisplay21%,21%,22%,23%,and23%oftotal
              ratios were higher after consuming a meat and a soybean              protein, respectively. On the other hand, soy, brown rice,
              meal (0.60 and 0.75). For methionine, these values were              pea, corn, and potato do meet the amino acid requirements
              0.38 for the cottonseed meal and 0.45 for both the meat              established by the WHO and display 27%, 28%, 30%, 32%,
              andthesoybeanmeal.Itwasconcludedthatheatprocessing                   and 37% of EAAs from total protein. Plant-based foods
              affects the availability, but not the digestibility of these amino   andproteins show particularly high heterogeneity regarding
              acids,andassuch,thatthetrueilealdigestibilityofthese methionine and lysine contents. Interestingly, plant-based
              amino acids overestimates their availability, especially in          foods that are high in methionine often appear to be low in
              mealsthatexhibitalowerproteinquality.Anotherlimitation               lysine and vice versa (44). An incomplete EAA profile results
              is that the DIAAS does not provide insight on how the                in an increased oxidation of the other EAAs. Consequently,
              absorbed amino acids stimulate downstream physiological              these EAAswillnotbecomeavailableforMPS(26).
              targets (i.e., its functionality), such as the stimulation of MPS       Another notable difference in EAA content between
              (39). Furthermore, the DIAAS values of many foods that are           isolated animal-based foods and proteins and those of
                        ´
              714 Domicetal.
            FIGURE1 AnoverviewoftheDIAASasdeterminedusingtheadultreferencevaluesforseveralplant-andanimal-basedfoodproducts
            (A) and plant-based food blends (B). Data derived from Herreman et al. (40) (supplementary data). DIAAS, Digestible Indispensable Amino
            Acid Score.
            plantoriginisthatisolatedplant-basedfoodsandproteins presented in Figure 1. All but 1 of the animal-based foods
            generally exhibit a lower proportion of the anabolic EAA        assessed in their study contained protein of excellent quality
            leucine (44). The leucine content of the plant-based protein    (DIAAS ≥100). With respect to the plant-based foods, the
            isolates observed by Gorissen et al. (44) varied from 5.1% in   DIAAS values as calculated with the adult reference values
            hemp to 13.5% in corn, with an average leucine content of       ranged from 43 to 125, with only soy and potato showing
            7.1%±0.8%.Theanimal-basedproteinisolatesinthatstudy             excellent protein quality. Pea and lupin both showed a
            exhibited a higher average leucine content of 8.8% ± 0.7%.      DIAASof83,indicatinghighproteinquality.Theremaining
            Zaromskyte et al. (50) recently found that in older adults      plant-basedfoodswerenotclassifiedashighorexcellent
            specifically, the leucine content of isolated proteins appears  proteinqualityasaresultoftheirlowDIAASvalues(40).An-
            to play an important role in the postprandial regulation of     otherstudycalculatedthattheDIAASvaluesforseitan,tofu,
            MPS. It should be noted, however, that in the context of        soya milk, and pea emulsion containing pea protein isolate
            mixed meals, the regulatory role of leucine on MPS remains      were,respectively, 28, 97, 117, and 60, again emphasizing the
            uncertain. It has been observed that whole eggs (containing     high heterogeneity in protein quality between plant-based
            18 g protein and 17 g fat) elicit a greater MPS response        foods(47).
            whencomparedwitheggwhites(18gprotein,0gfat)in                      Thedifferenceinaminoaciddigestibilitybetweenisolated
            youngindividuals, despite a similar plasma leucine response     animal- and plant-based protein was recently illustrated
            (51). Although the mechanism behind this finding remains        in healthy young males (52). In that study, Pinckaers and
            unclear,othercomponentswithinthefoodmatrixofamixed              colleagues (52) observed significantly greater increases in
            meal, as discussed in more detail below, may also modulate      plasma EAA, leucine, lysine and methionine concentrations
            the MPS response rather than aminoacidemia alone. An            after the ingestion of 30 g of milk protein concentrate
            importantnotiononthisisthatthisobservationwasmadein             (MPC) compared with a similar amount wheat protein
            youngindividualsandtheregulatoryroleofleucineinMPS hydrolysate. A smaller, but still significant, increase in these
            appearstobelessevidentatayoungerage(50).Assuch,the              plasma EAA values was observed after the consumption
            specific role of leucine within the context of mixed meals in   of MPC as compared with a blend containing both MPC
            older individuals requires further research.                    and wheat protein hydrolysate, illustrating improvements
               Herreman et al. (40) combined information from dif-          in EAA availability with increasing quality of the pro-
            ferent datasets to calculate the DIAAS of 17 foods and a        tein source. Similar findings were observed in older men
            number of food blends. Several of these DIAAS values are        (53).
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