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1.
Anorexia of Aging - An Updated Short Review.
Jadczak, AD, Visvanathan, R
The journal of nutrition, health & aging. 2019;(3):306-309
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Abstract
The anorexia of aging affects approximately a quarter of older people and is a major contributor to the development of under-nutrition and many other adverse health outcomes in older people. Despite the high prevalence, the anorexia of aging is frequently overlooked by clinicians and, of even more concern, it is commonly accepted as inevitable and a part of 'normal' aging. Early identification of risk coupled with efforts to mitigate these risks through appropriate interventions might stem the deleterious consequences of the anorexia of aging. This review aims to provide an update on the current knowledge base whilst making some practical suggestions that may be of use in clinical practice. Interventions such as exercise and good nutrition remain the preferred treatment while pharmacological options, whilst they continue to be trialed, are not currently recommended for routine clinical use.
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Cachexia Anorexia Syndrome and Associated Metabolic Dysfunction in Peritoneal Metastasis.
Archid, R, Solass, W, Tempfer, C, Königsrainer, A, Adolph, M, Reymond, MA, Wilson, RB
International journal of molecular sciences. 2019;(21)
Abstract
: Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1α (HIF-1α) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1α upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1α also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.
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Mechanisms of the anorexia of aging-a review.
Wysokiński, A, Sobów, T, Kłoszewska, I, Kostka, T
Age (Dordrecht, Netherlands). 2015;(4):9821
Abstract
Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the lack of hunger have been termed as the anorexia of aging. The etiology of the anorexia of aging is multi-factorial and includes a combination of physiological changes associated with aging (decline in smell and taste, reduced central and peripheral drive to eat, delayed gastric emptying), pathological conditions (depression, dementia, somatic diseases, medications and iatrogenic interventions, oral-health status), and social factors (poverty, loneliness). However, exact mechanisms of the anorexia of aging remain to be elucidated. Many neurobiological mechanisms may be secondary to age-related changes in body composition and not associated with anorexia per se. Therefore, further studies on pathophysiological mechanisms of the anorexia of aging should employ accurate measurement of body fat and lean mass. The anorexia of aging is associated with protein-energy malnutrition, sarcopenia, frailty, functional deterioration, morbidity, and mortality. Since this symptom can lead to dramatic consequences, early identification and effective interventions are needed. One of the most important goals in the geriatric care is to optimize nutritional status of the elderly.
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4.
Use of corticosteroids for anorexia in palliative medicine: a systematic review.
Miller, S, McNutt, L, McCann, MA, McCorry, N
Journal of palliative medicine. 2014;(4):482-5
Abstract
BACKGROUND Anorexia is a significant problem in patients approaching the end of life, for which corticosteroids are widely prescribed. It is not clear which regimen is the most safe and effective for this indication. OBJECTIVE The study objective was to identify the evidence for the use of corticosteroids, and the most safe and effective dosing regimen for management of anorexia in palliative care patients. METHODS A search of MEDLINE and CINAHL was carried out to identify original studies relevant to this question. These were reviewed against inclusion criteria and articles for inclusion were identified. Data was extracted and a narrative analysis was carried out. Subjects were adult patients with life-limiting diagnoses prescribed corticosteroids for anorexia in any care setting. Quality of studies was assessed using the system used by the Scottish Intercollegiate Guidelines Network for grading evidence. RESULTS Eight articles were identified that met the inclusion criteria. The corticosteroid drugs and dosing regimens used were wide ranging, and a variety of tools were used to assess appetite within these studies. All studies showed improvement in appetite with the corticosteroid used, although this did not always reach statistical significance. It was not possible to identify the most effective corticosteroid drug, dose, or duration of treatment from the identified studies: the best quality evidence was for an eight-week course of intravenous methylprednisolone; however the studies using this regimen had the highest attrition rates. CONCLUSIONS Corticosteroids are beneficial in treating anorexia in palliative care patients with malignancies; however there is no evidence for their use in anorexia due to end-stage nonmalignant disease. There is insufficient evidence to recommend any particular corticosteroid drug over another, or to recommend a dosing regimen.
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5.
Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target?
Schütz, P, Bally, M, Stanga, Z, Keller, U
Swiss medical weekly. 2014;:w13957
Abstract
Loss of appetite and ensuing weight loss is a key feature of severe illnesses. Protein-energy malnutrition (PEM) contributes significantly to the adverse outcome of these conditions. Pharmacological interventions to target appetite stimulation have little efficacy but considerable side effects. Therefore nutritional therapy appears to be the logical step to combat inadequate nutrition. However, clinical trial data demonstrating benefits are sparse and there is no current established standard algorithm for use of nutritional support in malnourished, acutely ill medical inpatients. Recent high-quality evidence from critical care demonstrating harmful effects when parenteral nutritional support is used indiscriminately has led to speculation that loss of appetite in the acute phase of illness is indeed an adaptive, protective response that improves cell recycling (autophagy) and detoxification. Outside critical care, there is an important gap in high quality clinical trial data shedding further light on these important issues. The selection, timing, and doses of nutrition should be evaluated as carefully as with any other therapeutic intervention, with the aim of maximising efficacy and minimising adverse effects and costs. In light of the current controversy, a reappraisal of how nutritional support should be used in acutely ill medical inpatients outside critical care is urgently required. The aim of this review is to discuss current pathophysiological concepts of PEM and to review the current evidence for the efficacy of nutritional support regarding patient outcomes when used in an acutely ill medical patient population outside critical care.
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6.
Pathophysiology of the anorexia of aging.
Morley, JE
Current opinion in clinical nutrition and metabolic care. 2013;(1):27-32
Abstract
PURPOSE OF REVIEW Anorexia represents a major problem for older persons leading to weight loss, sarcopenia, functional decline, and mortality. There is increasing information on the pathophysiological mechanisms that lead to anorexia. RECENT FINDINGS Increasing evidence has shown the importance of gastrointestinal hormones (ghrelin, cholecystokinin, and glucagon-like peptide) and adipokines in producing the anorexia of aging. Numerous neurotransmitters have been shown to be involved in this aging anorexia, but evidence in humans is lacking. SUMMARY The early recognition of anorexia of aging is important to allow intervention and prevent functional deterioration in older persons. Screening tests for anorexia have been developed. New approaches to managing anorexia are being tested.
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Gastrointestinal hormones: the regulation of appetite and the anorexia of ageing.
Moss, C, Dhillo, WS, Frost, G, Hickson, M
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2012;(1):3-15
Abstract
Loss of appetite is frequently observed during ageing, termed the 'anorexia of ageing'. Ageing is associated with the inability to appropriately increase food intake after under-eating in the short- and long-term. Older people also report lower feelings of hunger and increased feelings of satiety and fullness. Gastrointestinal peptide hormones are a major part of the appetite regulatory system and are released in response to nutritional stimuli. They can be classified as: anorexigenic (satiety) [e.g. peptide tyrosine tyrosine (PYY), glucagon-like peptide-1, pancreatic polypeptide, oxyntomodulin and cholecystokinin (CCK)] or orexigenic (hunger) (e.g. ghrelin). Although the control of appetite is not fully understood, it is clear that these hormones play an important role, and may influence the development and treatment of obesity and under-nutrition. The literature shows a consistent finding that there is a loss of appetite in those aged over 65 years, although how this loss is mediated is not yet clear. Some evidence suggests that with advancing age there is an increase in satiety hormones, such as CCK and PYY, and a decrease in the hunger hormone, ghrelin. However, not all studies agree, emphasising the need for more in-depth research to clarify age-related changes. This knowledge will enable us to develop therapies to help prevent under-nutrition during ageing. This review explores how age influences gastrointestinal appetite hormones in humans, as well as how this may contribute to the development of age-related malnutrition.
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Causes of poor appetite in patients on peritoneal dialysis.
Chung, SH, Carrero, JJ, Lindholm, B
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2011;(1):12-5
Abstract
Anorexia is common in patients with chronic kidney disease and is a main contributor to the high prevalence of protein-energy wasting in them. The peritoneal dialysis (PD) procedure may further impair appetite by causing abdominal discomfort and also through the absorption of the osmotic agent and other factors. An increased peritoneal solute transport rate has been linked to protein-energy wasting and also to the malnutrition, inflammation, and atherosclerosis syndrome, which has been associated to poor appetite and plays a role in most premature deaths in these patients. The pathogenesis of these associations is unclear. In this review, we discuss the effect of PD, in particular, PD solutions, inflammation, and increased peritoneal solute transport rate, on appetite. We also describe strategies to increase appetite in PD patients.
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9.
Appetite disorders in uremia.
Carrero, JJ, Aguilera, A, Stenvinkel, P, Gil, F, Selgas, R, Lindholm, B
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2008;(1):107-13
Abstract
Patients with chronic kidney disease frequently experience loss of appetite (anorexia), which increases in severity during the progression of the disease and may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents a multiple, complex, and multifactorial disorder that may have its origin in renal failure (contemplating not only retention of uremic toxins but also peptides and cytokines) but that later on also involves metabolic abnormalities not yet corrected by dialysis therapy. This paper reviews current knowledge about the clinical signs of uremic anorexia as well as mechanisms involved. Based on megestrol acetate interventions and the recent observation that sex may modulate uremic appetite behavior, the potential role of sex hormones in treating chronic kidney disease anorexia needs to be further explored.
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Emerging results of anticatabolic therapy with ghrelin.
Akamizu, T, Kangawa, K
Current opinion in clinical nutrition and metabolic care. 2007;(3):278-83
Abstract
PURPOSE OF REVIEW This review summarizes recent developments in research into anticatabolic therapies with ghrelin. Potential conditions in which ghrelin treatment may be useful include cachexia, anorexia and ageing. We highlight a number of intriguing basic topics related to the anticatabolic effects of ghrelin. RECENT FINDING Repeated administration of ghrelin to patients with congestive heart failure or chronic obstructive pulmonary disease improved appetite, body composition, muscle wasting and functional capacity in open-label pilot studies. An acute, randomized, placebo-controlled, crossover clinical trial of cancer patients with anorexia revealed marked increases in energy intake following treatment. The effects of ghrelin treatment in patients with anorexia nervosa are controversial. Basic research studies have extended our understanding of the upstream regulation of neuropeptide Y/agouti-related protein signalling and the central control of adipocyte metabolism. In addition, alterations in fat-free mass may play a role in ghrelin regulation. SUMMARY A number of studies are currently evaluating the anticatabolic effects of ghrelin in the treatment of various diseases, including cachexia, anorexia and age-related disorders. These studies will hopefully lead to the development of novel clinical applications for ghrelin treatment. These studies have also facilitated a better understanding of the molecular basis of the anticatabolic effects of ghrelin.