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JAMDA 14 (2013) 642e648 JAMDA journal homepage: www.jamda.com Review Body Weight, Anorexia, and Undernutrition in Older People Stijn Soenen PhD, Ian M. Chapman MD, PhD * Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia a b s t r a c t Keywords: Anorexia of aging body weight appetite health Ideal body weight for maximum life expectancy increases with advancing age. Older people, however, tend to weigh less than younger adults, and old age is also associated with a tendency to lose weight. Weight loss in older people is associated with adverse outcomes, particularly if unintentional, and initial body weight is low. When older people lose weight, more of the tissue lost is lean tissue (mainly skeletal muscle) than in younger people. When excessive, the loss of lean muscle tissue results in sarcopenia, which is associated with poor health outcomes. Unintentional weight loss in older people may be a result of protein-energy malnutrition, cachexia, the physiological anorexia of aging, or a combination of these. The physiological anorexia of aging is a decrease in appetite and energy intake that occurs even in healthy people and is possibly caused by changes in the digestive tract, gastrointestinal hormone concentrations and activity, neurotransmitters, and cytokines. A greater understanding of this decrease in appetite and energy intake during aging, and the responsible mechanisms, may aid the search for ways to treat undernutrition and weight loss in older people. Copyright Ó 2013 - American Medical Directors Association, Inc. In Western countries, there have been substantial increases over recent decades in the number of older people who are overweight or obese, according to standard body mass index (BMI) criteria.1 For example, between 1995 and 2007 to 2008, the percentage of Australians who were obese (BMI of 30 kg/m2) steadily increased from 13% to 31% for 65- to 74-year-olds, and from 6% to 23% for those older than 75 years.2 There is increasing evidence, however, that the adverse effects associated with being overweight or obese by BMI criteria are not as great in older as in younger adults. This is particularly so for life expectancy; in people older than 65 years, a higher BMI is associated with neutral rather than detrimental effects on length of life.1 Consistent with this, body weights associated with maximum life expectancy are higher for older than younger adults. For example, in a 12-year longitudinal study of 324,000 people in the American Cancer Society Cohort, people younger than 75 had a progressive reduction in subsequent life expectancy as baseline BMI increased above 21.9 kg/m2. These adverse effects of increasing body weight weakened, however, with increasing age above 45 years and were absent altogether in those older than 75 years.3 Among 4736 people aged 60 or older followed for an average of 4.5 years in the Systolic Hypertension in the Elderly Program (SHEP), those whose baseline BMI was in the lowest quintile (<23.6 kg/m2) had the highest subsequent mortality, and those within the highest BMI quintile (31 kg/m2) had the lowest mortality.4 The optimum BMI for * Address correspondence to Ian M. Chapman, MD, PhD, Discipline of Medicine, Level 6 Eleanor Harrald Building, Frome Road, Adelaide, SA 5005, Australia. E-mail address: [email protected] (I.M. Chapman). survival in people older than 70 years is probably in the range of 25 to 30 kg/m2, and close to the upper end of that range. There is also evidence that above (so-called) “normal” BMIs (18.5e24.9 kg/m2) may be more beneficial in women than men.5 Of note, in older people, the body weight associated with maximum life expectancy is probably higher than that associated with optimum function and lack of disability. Among 12,725 people aged 65 or older in the Established Populations for Epidemiologic Studies of the Elderly, life expectancy was greatest with a BMI between 25 and 27 kg/m2, but disability-free life expectancy was greatest at a BMI of 24 kg/m2.6 Whereas high BMI values are associated with fewer adverse effects on life expectancy and possibly function in older than young adults, the opposite is probably true for low body weights. There is good evidence that BMI values below approximately 21 to 22 kg/m2 are associated with significant adverse events and increased mortality in older people;4,6,7 BMIs below 18.5 kg/m2 are a particular concern.6 Thus, with increasing age, the U-shaped curve describing the association between BMI and mortality moves to the right, and the curve becomes flatter at higher BMIs.8 Weight Loss in Older People Although optimum body weight for survival is probably higher for older than younger adults, they tend to weigh less. This is documented in population-based, cross-sectional, and longitudinal studies9,10 and is due to a combination of lower peak body weight and weight loss in old age. For example, in the 1997 to 1998 US National 1525-8610/$ - see front matter Copyright Ó 2013 - American Medical Directors Association, Inc. http://dx.doi.org/10.1016/j.jamda.2013.02.004 S. Soenen, I.M. Chapman / JAMDA 14 (2013) 642e648 Health Interview Survey, more people aged 75 years or older were “underweight” (BMI <18.5 kg/m2; 5.0% vs 1.2%) than those aged 45 to 64 years, and substantially fewer were “overweight” (BMI >25 kg/m2; 47.2% vs 63.5%).9 The lower average body weight of older than younger adults is not just because overweight people die earlier, leaving the healthier, more lean ones behind. On average, older people are more likely to lose than gain weight.11,12 For example, 247 community-dwelling American men older than 65 lost on average 0.5% of their body weight per year over 2 years, and 13.1% had involuntary weight loss of 4.0% per annum or more.11 The reasons for such weight loss are multiple and vary between individuals. Unintentional weight loss and associated adverse outcomes in older people may be attributable to protein-energy malnutrition, cachexia, the physiological anorexia of aging, or some combination of these factors. Weight Loss Is Associated With Poor Health Outcomes in Older People Numerous studies have shown that weight loss in older people not resulting from malignancy is associated with poor outcomes, certainly if unintentional, but possibly even when intentional. The prospective Cardiovascular Health Study,12 for example, studied 4714 home-dwelling subjects older than 65 years without known cancer. In the 3 years after study entry, 17% of the subjects lost 5% or more of their initial body weight, compared with 13% who gained 5% or more. The weight-loss group had significant increases in total (2.09-fold increase; 95% confidence interval [CI] 1.67e2.62) and risk-adjusted mortality (1.67-fold increase; 95% CI 1.29e2.15) over the following 4 years compared with the stable weight group, with no increased mortality in the weight-gain group. Increased mortality among those who lost weight occurred irrespective of starting weight and whether or not the weight loss was intentional. In the SHEP study,4 which studied 4736 people aged 60 or older, those subjects who had a weight loss of 1.6 kg per year or more experienced a 4.9 times greater death rate (95% CI 3.5e6.8) than those without significant weight change. Weight gain was also associated with increased mortality, but less so than weight loss (2.4- vs 4.9-fold increase). Of particular note, the adverse association between mortality and weight loss was present even in the subjects who were heaviest at baseline (BMI 31 kg/m2). Subjects with a low baseline weight (BMI <23.6 kg/m2) who lost more than 1.6 kg per year had a mortality rate of 22.6%, almost 20 times greater than the mortality rate of those with a baseline BMI of 23.6 to 28 kg/m2 whose weight remained stable. Thus, the combination of initially low body weight and weight loss is especially bad news for older people. This interaction is a particular concern as the tendency for older people to lose weight is variable, with lean individuals probably most at risk.13 Lean Tissue Loss and Sarcopenia in Older People There are many reasons why weight loss in older people is associated with adverse effects. In some cases, weight loss is attributable to an illness, such as a malignancy, which is mainly responsible for the poor outcome. The loss of body weight after the age of 50 to 60 is disproportionately due to losses of lean body tissue, with average decreases of up to 3 kg of lean body mass, mainly skeletal muscle, per decade after the age of 50.14 When skeletal muscle mass falls too far, sarcopenia results. This has been defined in various ways, often by comparison of skeletal muscle mass with values in young adults (eg, more than 2 standard deviations below the young adult mean as measured by dual-energy X-ray absorptiometry),15 and sometimes also by the coexistence of functional impairments, such as reduced grip strength16 and decreased gait speed.17 The prevalence of 643 sarcopenia increases dramatically as the “young-old” age and is up to 4 times higher in those older than 85 years than in those 70 to 75 years.18 Sarcopenia is an independent predictor of poor gait, falls, fractures, and other disability. In the National Health and Nutrition Examination Survey III (NHANES III), older people with marked sarcopenia were 3.3 times (women) to 4.7 times (men) more likely to have physical disability than those with low-risk skeletal muscle mass.19 For these reasons, a high level of awareness needs to be maintained to detect unintentional weight loss, low body weight, and undernutrition in older people. Weight Loss Programs in Older People Weight loss is often recommended for overweight and obese older adults in the same manner as for younger adults, and for similar increases in body weight and BMI. At any given time, a substantial proportion of older people wish to lose weight and are trying to reduce their energy (food) intake to do so. There is evidence from studies in species as varied as yeast, spiders, mice, and possibly primates that long-term restriction of energy intake by 30% to 60% compared with ad libitum intake prolongs life.20 It might seem, therefore, that reducing food intake to lose weight would be good for most older people. This is not necessarily the case, however. In fact, the opposite may be true. The effects of long-term voluntary energy restriction have not been tested in humans, and the benefits observed in other species may not apply to ours.21 Moreover, marked energy restriction in older adults is likely to lead to a substantial loss of beneficial lean body tissue as well as fat mass and increases the risk of vitamin, mineral, and other dietary deficiencies. Thus, caution should be exercised in recommending weight loss to older people, unless there are definite health problems resulting from the excess weight. Cachexia in Older People Cachexia can also contribute to weight loss and harmful undernutrition in older people. Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. A prominent feature of cachexia is weight loss, but inflammation is also a key component, with an increase in levels of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6. Anorexia, insulin resistance, and increased muscle protein breakdown are also frequently associated with cachexia. Conditions that often afflict older people that are associated frequently with cachexia include cancer, cardiac failure, chronic obstructive pulmonary disease, and chronic renal failure. Although there is often considerable overlap between them, cachexia and malnutrition are not the same. Although all patients with cachexia are malnourished, not all malnourished patients are cachectic.22 Cachexia is distinct from age-related loss of muscle mass, primary depression, hyperthyroidism, malabsorption, and starvation and does not respond readily to increased feeding.23 Recently, the European Society of Clinical Nutrition and Metabolism subclassified cachexia on the basis of severity, into pre-cachexiaddefined as (1) an underlying chronic disease, (2) a systemic inflammatory response, (3) anorexia, and (4) unintentional weight loss over the previous 6 months of less than 5% of usual body weightdand cachexia, defined as (1) to (4) but with weight loss of more than 5%.22 Protein-Energy Malnutrition in Older People Weight loss in older people predisposes to the development of protein-energy malnutrition. This is surprisingly common in developed countries, with up to 15% of community-dwelling and home- 644 S. Soenen, I.M. Chapman / JAMDA 14 (2013) 642e648 bound older people, 23% to 62% of hospitalized patients, and up to 85% of nursing home residents estimated to suffer from proteinenergy malnutrition.24 Protein-energy malnutrition is more likely to develop in the presence of other “pathological” factors, which become more common with increased age (Table 1). Most of these factors are at least partly responsive to treatment, so recognition is important. Social factors that contribute to decreased food intake in the elderly include poverty25; difficulties with shopping, meal preparation, and self-feeding; living alone; social isolation; and loneliness.26 Psychological factors include depression, present in 2% to 10% of community-dwelling older people and a much greater proportion of those in institutions,27 dementia and Alzheimer disease,28 and bereavement. Undernutrition per se, particularly if it produces folate deficiency, may further worsen depression.29 Physical factors include poor dentition and ill-fitting dentures leading to problems with chewing, biting, and swallowing30; immobility (eg, stroke); Parkinson disease; and impaired vision. Medical factors include gastrointestinal disease, malabsorption syndromes, acute and chronic infection, hypermetabolism (ie, hyperthyroidism and chronic obstructive pulmonary disease), micronutrient deficiencies, increased energy requirements, and conditions that cause cachexia, such as cancer and rheumatoid arthritis, by releasing cytokines.24 Older people are major users of medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite, particularly if taken in excess doses or by interaction with other drugs. For example, digoxin and chemotherapy can cause nausea, vomiting, and loss of appetite, and high doses of antacids can deplete phosphate and potassium stores, Table 1 Nonphysiologic Causes of Anorexia in Older Persons Social factors Poverty Inability to shop Inability to prepare and cook meals Inability to feed oneself Living alone/social isolation/lack of social support network Failure to cater to ethnic food preferences in institutionalized individuals Psychological factors Depression Dementia/Alzheimer disease Alcoholism Bereavement Cholesterol phobia Medical factors Cardiac failure Chronic obstructive pulmonary disease Infection Cancer Alcoholism Dysphagia Rheumatoid arthritis Malabsorption syndromes Gastrointestinal symptoms Dyspepsia Helicobacter pylori infection/atrophic gastritis Vomiting/diarrhea/constipation Parkinson disease Hypermetabolism (eg, hyperthyroidism) Medications Anti-infectives Antineoplastics Antirheumatics Nutritional supplements Pulmonary agents Cardiovascular agents Central nervous system agents Gastrointestinal agents leading to muscle weakness and anorexia. Older individuals often take multiple medications that increase the risk of drug interactions that can cause malnutrition. Protein-Energy Malnutrition and Poor Health Outcomes in Older People In older persons, unintentional weight loss of 5% or more over 6 to 12 months is associated with an increased risk of adverse effects, whereas a loss of 10% or more is associated with a particularly high risk of protein-energy malnutrition and poor outcomes. Proteinenergy malnutrition is associated with decreased bone mass, impaired muscle function, anemia, immune dysfunction, reduced cognitive function, poor wound healing, delayed recovery from surgery, and, ultimately, increased morbidity and mortality (Table 2). Protein-energy malnutrition is a strong independent predictor of mortality in elderly people, regardless of their living situation.31 The increased mortality rate in elderly people with protein-energy malnutrition is further increased in the presence of other medical diseases, such as renal failure, cardiac failure, and cerebrovascular disease. For example, the 9-month mortality rate among patients 70 years or older, without cancer, admitted to a Swedish medical ward was 80% in those both malnourished and with cardiac failure, twice that of the malnourished patients without cardiac failure, and more than 4 times that of well-nourished patients without cardiac failure.31 Anorexia of Aging: Reduced Appetite and Energy Intake in Older People All of the previously noted changes can be superimposed on, and tend to exacerbate, the effects of the steady decline in overall appetite and food intake that occurs as healthy adults age. Numerous studies have documented an age-related decline in energy (food) intake in healthy, ambulant, noninstitutionalized people of approximately 30% between 20 and 80 years.32e35 For example, the NHANES III crosssectional study reported a decline in energy intake between the ages of 20 and 80 years of 1321 kcal per day in men and 629 kcal per Table 2 Effects of Weight Loss and Protein-Energy Malnutrition on Function in Older People Y Muscle function Y Muscle relaxation Y Muscle mass Y Muscle strength [ Risk of fracture Y Bone mass [ Incidence of falls Y Functional status Immune dysfunction [ Risk of infection Y Skin hypersensitivity T-cell lymphocytopenia Y Synthesis of interleukin-2 Y Cytolytic cell activity Y Response to influenza vaccination Anemia Poor wound healing Fatigue Pneumonia Delayed recovery from surgery Y Cognitive function Y Cardiac output Y Intravascular fluid (dehydration) [ Incidence of pressure sores Y Maximal breathing capacity [ Hospital admission and length of stay [ Mortality S. Soenen, I.M. Chapman / JAMDA 14 (2013) 642e648 day in women;36 a 7-year New Mexico longitudinal study of 156 persons aged 64 to 91 years reported a decrease of 19.3 kcal per day per year in women and 25.1 kcal per day per year in men;37 and a Swedish longitudinal study of 98 people found an even greater decline of energy intake of 610 kcal per day in men and 440 kcal per day in women between the ages of 70 and 76 years.38 The decline of food intake, and associated decrease in appetite, occurs even in healthy, illness-free adults and is therefore not solely due to aging-associated illnesses. This apparently physiological, agerelated reduction in energy intake has been termed “anorexia of aging.”24 An important component is reduced appetite (decreased hunger). Older people consistently report that they are less hungry than young adults and have increased fullness and early satiation during a meal.33e35,39 On average, older individuals consume smaller meals more slowly, and fewer snacks between meals,24 resulting in overall lower energy intake, and, in some cases, adverse events. For example, in one cross-sectional study of 1247 people aged 60 or older living in Mexico City, anorexia of aging, defined as reporting that they had been eating less in the past 12 months than previously because of loss of appetite, was present in 30% and independently associated with disability and reduced mobility.40 Aging is associated with a reduction in energy expenditure, owing to reduced physical exercise, loss of energy-demanding lean tissue, and reduction in energy intake itself (via the decreased metabolic cost of metabolizing the smaller amount of consumed food). In many individuals, the decrease in daily energy intake is greater than the decrease in energy expenditure, resulting in the loss of body weight during aging, as described previously. One of the mechanisms underlying the decrease in energy intake is a diminished homeostatic regulation of many physiological functions, including the regulation of energy intake. For example, in a landmark study, Roberts et al41 underfed 17 young and old men by 3.17 MJ per day (z750 kcal/day) for 21 days, during which time both the young and old men lost similar amounts of weight. After the underfeeding period, the men were allowed to again eat ad libitum. The young men ate more than at baseline (pre-underfeeding) and quickly returned to normal weight, whereas the old men did not compensate, returned only to their baseline intake, but not above it, and did not regain the weight that they had lost. This indicates that after an anorectic insult (for example, major surgery), older people are likely to take longer than young adults to regain the weight lost, remain undernourished longer, and be more susceptible to subsequent superimposed illnesses, such as infections.41 Mechanisms Responsible for Reduced Appetite and Energy Intake in Older People 645 velocity within visceral neurons and with a reduced sensitivity to gastrointestinal tract distension (for example, impaired receptive relaxation of the gastric fundus,50 probably as a result of increased peripheral and fundic nitric oxide concentrations). As a result, for any given gastric volume, there is more rapid antral filling and distension, slower gastric emptying, and earlier satiety (Table 3).35 Older people may also have lower plasma concentrations of the orexigenic hormone ghrelin than younger adults,34,51 possibly related to the slightly decreased gastric emptying39 and reduced circulating testosterone concentrations,52 as normal aging is accompanied by reductions in circulating androgen levels.53,54 Plasma concentrations of the anorectic hormone leptin in humans often increase with aging, in women to a large extent because of the increased fat mass that also accompanies aging,55 and in men to a large extent because of agerelated decreases in circulating testosterone concentrations.56 In addition, older compared with younger subjects have shown increased small intestinal responses, such as a greater stimulation of phasic pyloric pressure waves by intraduodenal (ID) lipid infusion,57 a greater satiating effect of ID glucose,33 and altered gastrointestinal hormone responses, such as high fasting and postprandial CCK and GLP-1 concentrations, which may contribute to the slowing of gastric emptying mediated by increased pyloric motility.34,35,58e61 Healthy older people seem to retain their sensitivity to the satiating effects of exogenous GLP-161,62 and may even have increased sensitivity to the satiating effects of CCK.42,60 In addition, older people, particularly those who are undernourished, have higher circulating concentrations of CCK than young adults,61 suggesting that these gut hormones, particularly CCK, may contribute to the anorexia of aging. Aging tends to be associated with increased postprandial circulating insulin concentrations,63 mainly attributable to insulin resistance and impaired glucose tolerance,64 which may be influenced by increased adiposity and changes in the incretins GLP-1 and GIP secretion.65 These changes may contribute to reduced appetite. There is also evidence that aging is associated with a reduced opioid feeding drive66 and preliminary evidence from animal studies that aging may be associated with reduced neuropeptide Y (NPY) activity, resulting in a reduced stimulation of energy intake.67 A reduced sensitivity to the orexigen galanin might also contribute to the anorexia of aging; older compared with younger women displayed a reduced growth hormone secretory response to galanin.68 Increased cytokine levels, owing to the “stress” of aging per se, or the amplified stressful effects of other pathologies, may provide an Table 3 Some Endocrine Factors Influencing Feeding and Their Possible Contribution to the Anorexia of Aging Effect of Aging Appetite and energy intake are dependent on central and peripheral mechanisms, the latter including interrelated “intragastric” and “small intestinal” sensory and motor functions, triggered by the interaction with the nutrients ingested. There is evidence that changes at multiple sites, both central and peripheral, contribute to reduced appetite and food intake that accompany normal aging. In young people, appetite and energy intake are suppressed by distension of the distal stomach (antrum) and increased pyloric motility,42 which results in slowing of gastric emptying, and by stimulation of gastrointestinal hormone secretion: cholecystokinin (CCK),43 glucagon like peptide-1 (GLP-1),44 peptide tyrosine tyrosine (PYY),45 and gastric inhibitory polypeptide (GIP).46e48 Feedback signals from peripheral fat cells via leptin, as well as absorption of nutrients from the gut, also contribute to satiation. In older individuals, a diminished suppression of energy intake has been observed.49 Many of the underlying appetite-related mechanisms are affected by healthy aging. Aging is associated with a decline in conduction Factors that stimulate feeding Opioids Y activity not proven in humans NPY no good evidence for role Galanin circulating levels unchanged sensitivity unknown Orexins no good evidence for role Ghrelin circulating levels possibly Y sensitivity unknown Testosterone stimulatory role unconfirmed (? indirect) Yactivity with age possible effects via leptin, ghrelin, and others Factors that inhibit feeding CART possible [ central levels (rodents) CCK [ circulating levels [ CSF levels [ sensitivity to satiating effects GLP-1 few data, possibly [ activity PYY few data, no evidence for role Insulin effect on feeding unconfirmed, no evidence for role Leptin situation complex: circulating levels increase in men (Y testosterone) BUT? leptin resistance Cytokines [ activity likely CART, cocaine-amphetamine-regulated transcript; CCK, cholecystokinin; CSF, cerebrospinal fluid; GLP-1, glucagon like peptide-1; NPY, neuropeptide Y; PYY, peptide tyrosine tyrosine. 646 S. Soenen, I.M. Chapman / JAMDA 14 (2013) 642e648 explanation for some of the decline in appetite and body weight that occurs in many older people. Increased cortisol and catecholamines stimulate the release of IL-6 and TNF-a, and decreased sex hormones inhibit IL-6 and growth hormone.69 Once undernutrition is established in older people, this may promote further worsening of undernutrition. For example, undernourished older women report being less hungry and more full than their well-nourished young and older counterparts.34 The senses of smell and taste deteriorate with age,70 leading to a reduced capacity to enjoy food and develop sensory-specific satiety,71 the normal decline in pleasantness of the taste of a particular food after it has been consumed, leading to a decrease in its consumption and a tendency to shift consumption to other food choices during a meal. Age-related reduction in sensory-specific satiety favors a less varied, more monotonous diet, and the development of micronutrient deficiencies. Diagnosis and Treatment of Weight Loss and Undernutrition in Older People To reduce the risk of harmful weight loss, weight loss diets should be recommended to “overweight” older people with caution, and probably only if the excess weight is clearly causing functional impairment, rather than because of body weight alone. Weight loss from dieting leads to loss of lean (muscle) as well as fat tissue, and this is particularly so and harmful in older people. Such diets should therefore contain sufficient amount of protein to build up muscle tissue in older people, as has been observed in young people,72,73 and should be combined with a muscle-preserving exercise program if possible, preferably with a component of resistance exercise.17,74 Numerous screening tools and methods to diagnose undernutrition in older people have been developed and proposed,75 and a detailed discussion of them is beyond the scope of this article. Nevertheless, weight loss and undernutrition in older people, and their association with adverse outcomes, are still often not recognized. Important clues are loss of weight, particularly if more than 5% and unintentional, and low body weight (BMI <22 kg/m2). Once identified, causes or exacerbating factors, such as depression, lack of availability of food, and excessive medications, should be addressed if possible. A multidisciplinary approach, including the timely involvement of a nutritionist/dietician, is often useful. A logical and common strategy for undernourished older people is to try to increase their energy intake. Intake of “usual” food can be increased by encouragement to eat more and eat with others (for example, by residents of nursing homes eating in a communal dining area and having a staff member sit with them and encourage them to eat76 or by providing meals at home through programs such as “Meals on Wheels”). Liberalizing diets as opposed to restrictive diets have been shown to enhance quality of life and food intake, and the addition of flavor enhancers, such as sauce, to food may be of benefit.77 Energy-rich, often protein-rich, nutritional supplements are being increasingly recommended to older, undernourished people.78e81 There is evidence that they help. A Cochrane review of 62 trials (10,187 hospitalized and community-dwelling participants randomized to a protein-energy supplements or a control) concluded that “energy and protein” supplementation resulted in a small, but consistent, weight gain and reduced mortality, particularly when participants were undernourished, 75 years or older, and when supplementation was 400 kcal or more or sustained for more than 35 days.78 A systemic review and meta-analysis of effects of high protein oral nutritional supplements (36 trials among 3790 older people aged >65 years) concluded that protein supplements produce clinical benefits (eg, reduced complications, reduced readmissions to hospital, improved grip strength, and increased intake of protein and energy) with little reduction in normal food intake and improvements in body weight.82 Another recent systemic review of 17 trials, including measurements of body composition, between 1991 and 2012 (1287 patients aged between 65 and 85 years) concluded that protein supplementation has a protective and beneficial effect on muscle mass and strength, which is furthermore increased when combined with physical exercise.17 The optimum composition for nutritional supplements is not known. They appear to be least satiating, and therefore increase overall energy intake (total of supplement and other food) the most, if given in liquid form between meals.83 Daily protein intakes of 1.25 to 1.5 g/kg (higher than the Recommended Dietary Allowance for adults of 0.8 g/kg) are often recommended. However, protein has higher satiating effects than fat or carbohydrate in younger adults.84 If it has similar effects in older people, this may limit the increase in overall energy intake resulting from the use of high-protein supplements and possibly also contribute to the relatively poor long-term adherence to such supplements.17 The effects of nutritional supplements of different macronutrient compositions on appetite and energy intake in both well-nourished and malnourished older people, as well as further study of the mechanisms underlying the physiological anorexia of aging, warrant more examination. References 1. Decaria JE, Sharp C, Petrella RJ. 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