Effect Of Diet On Loss And Preservation Of Lean Body Mass .

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Effect of Diet on Loss and Preservation of Lean Body Massin Aging Dogs and CatsDottie Laflamme, DVM, PhD, DACVNFloyd, [email protected] cats showed that apparently healthyGlossary of Abbreviationscats lose approximately one-third of theirSarcopenia may be defined as an ageCKD: Chronic Kidney DiseaseLBM between about 10 and 15 years ofrelated loss of lean body mass (LBM)LBM: Lean Body Massage.3 This was confirmed in a longitudinalunrelated to disease. It is a long-termDHA: Docosahexaenoic Acidstudy following mature and geriatric catsprocess that becomes evident later ineIF2 : Eukaryotic Initiativeover an eight-year period, wherein meanlife, it has a complex and multifactorialFactor 2αLBM decreased by 34%.4 In aging dogs,etiology, and it increases the risks forEPA: Eicosapenaenoic Acidthere was approximately a 10% loss inmorbidity and mortality. Dietary factorsPI3K: PhosphatidylinositolLBM and corresponding increase in fatplay a role in minimizing this age-related3-Kinasemass.6,10 These effects appeared to beloss of LBM. Specifically, increased intake PTH: Parathyroid Hormonemore pronounced in dogs beginning atof protein and vitamin D has shown benefits.RDA: Recommended Dailyage 8 to 9 years. Lifelong limited feedingOther nutrients that appear to be importAllowanceor increased dietary protein intake reducedant are those related to acid/base balanceor delayed this age-related loss of LBM.6,10 Another longituand inflammation. Most of the research into sarcopenia hasdinal study in Labrador Retrievers confirmed loss of LBMbeen done in humans and rodent models, but some aspectswith age and identified that the longest-lived dogs in thehave been confirmed in dogs or cats. More research is neededstudy experienced the slowest loss of LBM.7 Similar resultsto determine optimum nutrient levels to reduce or preventwere observed in cats.4 As with humans, loss of LBM insarcopenia in aging dogs and cats.dogs and cats is associated with increased mortality.4,7,10Muscle and lean body mass (LBM) are determined byEtiology of Sarcopeniathe balance between the rates of de novo protein synthesisThe etiology of sarcopenia is multifactorial and complex.and protein degradation. During growth, protein synthesisElderlypeople, especially those who are sarcopenic, haveexceeds degradation and muscle mass increases, while inabluntedanabolic response to nutritional stimuli, such asmature subjects protein synthesis and degradation areamino acids and insulin.11 Some of the factors involved inroughly equal so that muscle mass remains constant. Withage this balance is lost and LBM decreases, leading to sarco- sarcopenia include altered protein turnover with decreasedmuscle protein synthesis, due in part to decreased funcpenia, which may be defined as an age-related loss of LBMtionality of the mTOR pathway, and a relative increase inunrelated to disease.Sarcopenia is a lifelong process that becomes evident later protein catabolism; chronic low-grade inflammation withincreased cytokines such as TNF and IL-6; mitochondrialin life, and it has a complex and multifactorial etiology.1 Indysfunction; increased oxidative stress; insulin resistance;most cases, the loss of LBM is offset by an increase in fat mass,and altered neuromuscular junction structure and function.11-13resulting in little or no change in body weight. The ageRegardless of the mechanisms, the result is a decreaserelated loss of LBM occurs in all species evaluated to date,in endogenous protein synthesis, possibly coupled withincluding humans, dogs and cats.2-7In cachexia, a 15% reduction in LBM interferes with organic increased protein catabolism, leading to decreased musclemass and strength.and physiological functions, while a decrease beyond 30%8Although exercise is the most efficient therapy for managis usually fatal. Although there is no agreed upon cutoff toing sarcopenia, it is recognized that nutrition also plays adefine sarcopenia, one study identified sarcopenia as a 3%role in the development and management of this condition.loss in muscle mass or a 40% loss of grip strength over a9Specifically, adequate dietary protein, specific amino acidsthree-year timeframe.Functional measures of muscle strength are not conducted and vitamin D have been shown to play a role. Proteinsupplementation coupled with exercise achieves the bestin dogs or cats, but significant loss of LBM has been demonresults in sarcopenic people.14 Other dietary factors thatstrated in aging dogs and cats. A cross-sectional study ofAbstractCOMPANION ANIMAL NUTRITION SUMMIT MAY 3-5, 2018 CHARLESTON, SOUTH CAROLINA41

may be important include nutrients impacting metabolism,inflammatory mediators and acid/base balance.Role of Diet in SarcopeniaProtein:Insufficient protein intake can contribute to loss of LBM.Multiple studies have confirmed lower protein intakes wereassociated with increased risk for sarcopenia in elderlypeople.15-18 Likewise, in dogs and cats, lower protein intakewas associated with greater loss of LBM.6,19-21 Dietary proteinsupports both endogenous protein turnover and gluconeogenesis. When dietary protein intake is inadequate, mammalswill gradually deplete proteins from their LBM, particularlyskeletal muscle, to support these metabolic functions.15,21Aging impacts the physiological response to protein intake.Muscle protein synthesis in response to protein intake isattenuated in older people compared to younger people.12,13Increasing the amount of protein consumed may help toovercome this anabolic resistance. For example, muscleprotein synthesis was stimulated in young adults with 10gof whey protein, but older men required 20g whey proteinto achieve similar protein synthesis.22 It appears that therecommended daily allowance (RDA) (0.8g/kg bodyweight),which was established using data from young adult men,is not adequate to maintain nitrogen balance nor preservemuscle mass in elderly people.12 Although not universallyaccepted, there is a growing consensus that older peopleshould consume more protein. Daily intake of at least 1.0to 1.2g/kg body weight is recommended, an increase of50% over the RDA.17,23-25The amount of protein that is “adequate” for dogs and catsalso remains controversial. Traditionally, nitrogen balancestudies were used to determine minimum protein requirements. However, nitrogen balance studies do not accountfor maintenance of muscle mass, and multiple studies haveindicated that the amount of protein required to maintainLBM or protein turnover far exceeds that needed to maintainnitrogen balance.15,21,26-30 For example, cats need only about1.5g protein/kg body weight to maintain nitrogen (protein)balance but need over 5g protein/kg body weight to maintainLBM.21 Dogs required about three times more protein to maintainprotein/DNA ratios (an indicator of protein reserves) comparedto that needed to maintain nitrogen balance, and old dogsneeded 50% more protein than young dogs regardless of themeasure used.27 As in humans, greater protein intake helpsreduce the age-related loss of LBM in dogs and cats.6,16,20Specific types of protein and amino acids also can impactLBM. “Fast” proteins, such as whey, contribute to greaterendogenous protein synthesis compared to “slow” proteins,such as casein. Whey, a soluble protein, is rapidly digestedand absorbed. Casein protein clots in the stomach, delayinggastric emptying and slowing uptake of the amino acids.31The greatest anabolic effect of protein appears dependenton reaching a threshold concentration. Rapidly absorbed42proteins achieve this threshold, while slower absorption ofthe same amino acids fails to achieve the threshold, resultingin less protein synthesis.31 In healthy young adults, postprandial protein synthesis was increased 68% by whey butonly 31% by casein. Although casein protein reduced protein catabolism to a greater extent compared to whey, netprotein balance was more positive for the whey protein.31Similar findings were observed in old rats, in elderly menand following exercise.32,33Whey protein is rich in branched-chain amino acids including leucine, which is recognized to have important regulatoryactions on protein turnover. Among other functions, leucinereduces proteolysis and enhances protein synthesis.13,34Whey protein also triggers insulin release, which promotesprotein synthesis.22,34 When the effect of whole whey proteinwas compared to an infusion equivalent to its essentialamino-acid content, the intact whey protein resulted ingreater muscle protein accrual.35Based on the numerous studies showing beneficial effectsfrom either leucine or whey protein on muscle protein synthesis, studies in sarcopenic humans have been conductedusing leucine-enriched whey protein (along with vitamin D)supplements.36,37 In the first of these multicenter trials, elderlysarcopenic subjects received a supplement containing 20gwhey protein (including 3g leucine), 800IU vitamin D anda mixture of vitamins, minerals and fiber twice daily, or theyreceived an isocaloric placebo containing carbohydrates,fat and some trace elements. The baseline protein intakein both groups averaged 1.0g protein/kg body weight daily.Over the 13-week study, the treated group showed significantly greater improvement in the chair-stand test, indicatinggreater strength and balance, and also in muscle mass.36Another study evaluated subjects given a once daily supplement containing 22g whey protein, 9g essential amino acids, and100IU vitamin D compared to those receiving a placebo, whileboth groups underwent a similar exercise program for 12weeks.37 The treated group showed significant improvementsin muscle mass and muscle strength. In addition, the treatedgroup showed reduced body fat, improved fat distribution,increased insulin-like growth factor, and reduced C-reactiveprotein, an inflammatory mediator.37The amino acid lysine also may impact LBM. Studies inswine and rats show that lysine deficiency leads to increasedprotein degradation and decreased protein synthesis inmuscle, whereas supplementation with lysine decreasedmuscle protein degradation.38,39Since lysine is limited (low relative to requirements) in manyvegetable-source proteins, supplementation may be mostimportant for vegetarians or for those whose diets are basedon vegetable-source proteins. A study in young adult dogsfed diets containing mixtures of corn gluten or poultry as theprotein sources evaluated changes in LBM and body fat, andchanges in the 20S proteasome of the ubiquitin proteasomepathway involved in protein catabolism.19 While most dogsCOMPANION ANIMAL NUTRITION SUMMIT MAY 3-5, 2018 CHARLESTON, SOUTH CAROLINA

lost LBM, those with the highest lysine intake gained LBM.In dogs fed 12% protein diets, there appeared to be aninverse linear correlation between lysine intake and LBMloss. Further, the 20S proteasome was decreased in dogsfed the high-lysine diet, suggesting a reduction in proteincatabolism via this mechanism. This is consistent withpigs, where lysine-deficient diets trigger upregulation ofthis catabolic pathway.39Similarly, in aging cats, lysine appears to protect LBM. Onepublished study in aging cats evaluated the impact of dietscontaining protein ranging from 6.87 to 10.22g/100Kcal,and lysine (lysine:calorie ratio) ranging from 2.71 to 6.30on changes in LBM. Although there were limitations to thestudy, it showed that increasing dietary lysine, independentof total protein, helped reduce loss of LBM in aging cats.40Vitamin D:Multiple epidemiological studies have identified an association between low serum vitamin D concentrations andan increased prevalence of sarcopenia in aging people.9,14,41Coupled with low vitamin D were increased concentrationsof parathyroid hormone (PTH), which also has been associated with loss of muscle mass and strength.9Vitamin D metabolites can influence muscle cell metabolismby mediating gene transcription as well as by other mechanisms.9 Vitamin D affects the transcription rate of thousandsof genes, including insulin receptors.42 Activation of insulinreceptors contributes to increased muscle protein synthesis,and supplemental vitamin D results in increased vitamin Dreceptors within muscle.14,43 In aged rats, vitamin D deficiencyreduced the rate of protein synthesis by 40% compared tovitamin-D replete rats.42 In both rodents and humans,vitamin D deficiency induced greater body fat and intramuscular lipids, a finding linked with compromised neuromuscular function.14 Intramuscular fat also may contributeto reduced protein synthesis via activation of eukaryoticinitiation factor 2alpha (elF2α).42 Activated elF2α inhibitsinitiation of protein translation and the rate of proteinsynthesis. Whether this specific mechanism applies tohumans, dogs or cats remains to be determined.Low serum vitamin D may impact muscle function viaPTH, which can be increased due to lack of inhibition fromvitamin D. PTH increases intracellular calcium concentrations, which may disrupt muscle structure or function. PTHalso may stimulate release of inflammatory mediators suchas IL-6. Elevated IL-6 in aging humans is associated withlower muscle mass and strength.9 Independent of PTH,studies have shown an inverse association between serumvitamin D and IL-6 and between intramuscular vitamin Dreceptor density and intramuscular IL-6 in aging humans.14Studies in humans evaluating vitamin D supplementationhave generally yielded beneficial results with improvementsin muscle strength as well as muscle mass.14,37 These effectswere primarily observed in individuals with initially lowserum vitamin D concentrations, which is common in sarcopenia. Provision of vitamin D along with supplementalprotein may yield the best results, but additional research isneeded.14,36,37 Currently, data on vitamin D supplementationto preserve LBM in dogs or cats is lacking.Acid/Base Balance:Acidosis is associated with increased protein catabolism,negative nitrogen balance and muscle protein wasting.It appears to promote muscle pro