testosterone but not placebo. Chapman et al.65 showed a reduced rate of hospitalization over one year in older men and women either undernourished or at risk of undernutrition given a combination of oral testosterone and a nutritional supplement compared with an untreated group. Srinivas‐Shankar et al.66 treated older, frail men with low circulating testosterone concentrations with transdermal testosterone or placebo for six months and found improvements in muscle strength and physical function, the latter effects confined to older (≥75 years) and more frail men. These results are not conclusive but justify further studies of testosterone treatment in frail older people.
In women, serum concentrations of testosterone and the adrenal androgens gradually and progressively decline from the decade preceding menopause. Even if testosterone therapy does not increase food intake in older, undernourished people, it may provide functional benefits by treating the associated sarcopenia.
Cytokines
Age‐associated increases in the production and/or effect of satiating cytokines may contribute to the anorexia of ageing67. Cytokines are secreted in response to significant stress, often because of malignancy or infection. Circulating concentrations of the cytokines interleukin 1 (IL‐1), interleukin 6 (IL‐6), and TNF‐α are increased in cachectic patients with cancer or AIDS. They act to decrease food intake and reduce body weight via a number of central and peripheral pathways. Blockade of these cytokines – for example, of TNF‐α in mice with TNF‐producing sarcomas – significantly attenuates weight loss in high‐stress conditions associated with cachexia. Ageing itself may be a form of stress. It is associated with stress‐like changes in circulating hormonal patterns, increased cortisol and catecholamines, and decreased sex hormones and growth hormone. Increased cortisol and catecholamine levels, in turn, stimulate the release of IL‐6 and TNF‐α, whereas sex hormones inhibit IL‐6. Interleukin 1 and IL‐6 levels are elevated in older people with cachexia, whereas plasma IL‐6 concentrations apparently increase as a function of normal ageing and correlate inversely with levels of functional ability in elderly people. Higher circulating levels of CRP and cytokine receptors also appear to be associated independently with physical dysfunction and disability.68 Increased cytokine levels due to the stress of ageing per se or the amplified stressful effects of other pathologies may explain some of the declines in appetite and body weight that occur in many older people.30
Chronic disease and anorexia in older adults
Common medical conditions in the elderly, such as gastrointestinal disease, malabsorption syndromes, acute and chronic infection, and hyper‐metabolism (i.e. hyperthyroidism), often cause anorexia, micronutrient deficiencies, and increased energy requirements. Cancer and rheumatoid arthritis, which produce anorectic effects by releasing cytokines, are also common in older adults. Protein‐energy malnutrition is particularly likely to develop in the presence of other ‘pathological’ factors, many of which become more common with increased age. The majority are at least partly responsive to treatment, so recognition is important.
Depression, often associated with bereavement and the deterioration of social networks, is a common psychological problem in older people, present in 2–10% of community‐dwelling older people and a much greater proportion of those in institutions. Depression is more likely to manifest as reduced appetite and weight loss in the elderly than in younger adults and is an important cause of weight loss and undernutrition in this group. Undernutrition per se, particularly if it produces folate deficiency, may further worsen depression, thus setting up a vicious cycle. Treatment of depression is effective in producing weight gain and improving other nutritional indices.
Dementia may also contribute to reduced food intake in the elderly, with a nearly twofold increased risk of anorexia compared with non‐demented subjects,69 because individuals simply forget to eat. Up to 50% of institutionalized dementia patients have been reported to suffer from protein‐energy malnutrition.27 Behavioral and psychological symptoms of dementia (BPSD) include eating problems. Apraxia of swallowing, including pocketing and spitting, delayed swallowing, and recurrent aspiration are associated with disease progression. Reduction of taste and smell may play a significant role. Weight loss is present very early, and even precedes dementia, and may be a significant preclinical marker.70
Chronic diseases including chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and chronic kidney disease (CKD) are associated with reduced appetite. Older adults with COPD are in a catabolic state due to increased whole‐body energy expenditure, and caloric intake was found to be inadequate for measured energy expenditure, which widens during severe acute exacerbations. Anorexia in COPD is also associated with nicotine use, opioid use for pain leading to early satiety, and gastrointestinal motility disorders.71
Loss of appetite occurs in over 40% of adults with end‐stage CHF.72 Generalized loss of lean, fat, and bone tissue occur. Cachetic CHF patients have raised plasma levels of norepinephrine, epinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone levels. Hypoxia may be the stimulus for increased TNF‐a production in CHF patients.73 TNF has a variety of effects, including induction of apoptosis, rearrangement of the cytoskeleton leading to increased permeability to albumin and water, leading to impairment of the endothelial function.73 Increased TNF leads to increased plasma concentrations of the hormone leptin, effects noted previously.74
Anorexia affects 30–40% of adult patients on maintenance hemodialysis; it is associated with greater hospitalization rates, decreased quality of life, and a fourfold increase in mortality.75 Uremic toxins including leptin, ghrelin, and neuropeptide Y, as well as altered amino acid pattern and inflammation, are involved.76 Studies have shown that injections of uremic ultrafiltrate lead to reduced ingestion of sucrose and mixed nutritional solution in normal rats, although the effect was not specific for one type of nutrient.77 Increased frequency of hemodialysis can improve appetite and food intake.76
Environment and social determinants of health
One of the social factors contributing to decreased food intake in the elderly is poverty, which is associated with an increased rate of hunger and food insecurity. Many older individuals have limited financial means, which makes it difficult to afford food of good nutritional quality. Community‐dwelling older women with lower neighbourhood socioeconomic status have been found to have a lower serum carotenoid concentration, correlated with higher mortality.8
Older people are more likely to live alone than young adults, with approximately 29.3% of non‐institutionalized older adults living alone.8 Social isolation and loneliness have been associated with decreased appetite and energy intake in the elderly. Elderly people tend to consume substantially more food (up to 50%) during a meal when eating in the company of friends than when eating alone. The simple measure of having older people eat in company rather than alone may be effective in increasing their energy intake. For institutionalized older adults, facilities fail to cater to ethnic food preferences, negatively affecting the desire for food.78 Assisted living facilities have less regulated food and nutrition services compared to long‐term care. The nature and quality of food are mostly unknown, and assisted living facilities do not seem to provide the preventative health and nutrition services needed by older adults.8
Iatrogenic impact
Older adults often utilize multiple prescription medications, a number of which can cause malabsorption of nutrients, dysguesia (related to the inhibition of the cytochrome P450 metabolism system), gastrointestinal symptoms (such as dry mouth and constipation), and loss of appetite.30,79 For example, digoxin and some forms of chemotherapy can cause nausea, vomiting, and loss of appetite. Other medications can deplete
