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Physiology & Behavior Apr 2008Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and... (Review)
Review
Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.
Topics: Adolescent; Adult; Affect; Aging; Anorexia; Appetite; Body Image; Brain; Brain Chemistry; Bulimia; Cognition; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Male; Nervous System; Neuropeptides; Neurotransmitter Agents; Puberty; Radiography; Sex Characteristics
PubMed: 18164737
DOI: 10.1016/j.physbeh.2007.11.037 -
Journal of Cachexia, Sarcopenia and... Jun 2020Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and... (Review)
Review
Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age-related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.
Topics: Anorexia; Asthenia; Cachexia; Humans; Quality of Life; Sarcopenia
PubMed: 32142217
DOI: 10.1002/jcsm.12528 -
Trends in Cancer May 2022The cachexia syndrome in cancer is characterized by weight loss resulting from the combination of anorexia and atrophy of adipose and skeletal muscle. For decades,... (Review)
Review
The cachexia syndrome in cancer is characterized by weight loss resulting from the combination of anorexia and atrophy of adipose and skeletal muscle. For decades, inflammatory circulatory factors have been identified to regulate wasting, but inhibitors of these factors have not yielded the same clinical benefit as in animal models. Therefore, additional mediators of cachexia likely regulate this syndrome, and such factors might be more suitable for targeted intervention. We highlight several anorexia-cachexia signaling mediators, including activin A, myostatin, GDF15, and lipocalin-2. We discuss current evidence that these factors associate with cachexia in cancer patients, and summarize translational efforts including essential early-phase clinical trials. We conclude with thoughts on targeted and personalized approaches for future anti-cachexia treatments.
Topics: Adipose Tissue; Animals; Anorexia; Cachexia; Humans; Neoplasms; Signal Transduction
PubMed: 35190301
DOI: 10.1016/j.trecan.2022.01.004 -
Age (Dordrecht, Netherlands) Aug 2015Many, 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... (Review)
Review
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.
Topics: Aging; Anorexia; Appetite; Eating; Gastrointestinal Absorption; Gastrointestinal Motility; Humans
PubMed: 26232135
DOI: 10.1007/s11357-015-9821-x -
Nutrients Jan 2016Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in... (Review)
Review
Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.
Topics: Aging; Anorexia; Appetite; Eating; Humans; Malnutrition; Nutritional Status; Sarcopenia
PubMed: 26828516
DOI: 10.3390/nu8020069 -
The Journal of Clinical Endocrinology... May 2022Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of... (Review)
Review
CONTEXT
Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of menopausal status. Investigators have examined their potential beneficial effects in normal women and those with DHEA-deficient states.
EVIDENCE ACQUISITION
A review of the literature from 1985 to 2021 on the potential benefits and risks of androgen prohormones in women.
EVIDENCE SYNTHESIS
Studies have examined the potential benefit of DHEA therapy for anti-aging, sexual dysfunction, infertility, metabolic bone health, cognition, and wellbeing in hormone-deficient states such as primary adrenal insufficiency, hypopituitarism, and anorexia as well as administration to normal women across the lifespan.
CONCLUSIONS
Data support small benefits in quality of life and mood but not for anxiety or sexual function in women with primary or secondary adrenal insufficiency or anorexia. No consistent beneficial effects of DHEA administration have been observed for menopausal symptoms, sexual function, cognition, or overall wellbeing in normal women. Local administration of DHEA shows benefit in vulvovaginal atrophy. Use of DHEA to improve induction of ovulation response in women with diminished ovarian reserve is not recommended. Risks of high physiologic or pharmacologic use of DHEA include androgenic and estrogenic side effects which are of concern for long-term administration.
CLINICAL CASE
A 49-year-old woman with Addison's disease who is on low dose estrogen with cyclic progesterone therapy for menopausal symptoms returns for follow-up. She is on a stable glucocorticoid replacement strategy of hydrocortisone 10 mg in the morning and 5 mg in the early afternoon and fludrocortisone 0.05 mg each morning. She has read on the internet that additional therapy with DHEA may help her overall quality of life and libido. She asks whether she should add this therapy to her regimen and at what dose.
Topics: Androgens; Anorexia; Dehydroepiandrosterone; Estrogens; Female; Hormone Replacement Therapy; Humans; Middle Aged; Quality of Life
PubMed: 35254428
DOI: 10.1210/clinem/dgac130 -
Medicina Clinica Jan 2024Anorexia nervosa and bulimia nervosa are eating disorders associated with life-threatening multisystemic medical complications. This narrative review aimed to present... (Review)
Review
Anorexia nervosa and bulimia nervosa are eating disorders associated with life-threatening multisystemic medical complications. This narrative review aimed to present the medical complications most related to these disorders. In anorexia nervosa, many of them are linked to malnutrition and underweight, usually reversible with renutrition and weight restoration, although refeeding can also be linked to some medical complications. Purging behaviors observed in the anorexia nervosa binge-purging subtype and bulimia nervosa have been mainly related to hydrolectrolyte and acid-base disturbances, in addition to local complications. Thus, an early identification and therapeutic intervention of these disorders is considered crucial. Integral medical monitoring should be ensured to prevent potential serious complications from the early stages, with the involvement of physicians, psychologists, nutritionists, and other specialists in a multidisciplinary approach according to the patient's needs.
Topics: Humans; Bulimia Nervosa; Anorexia; Anorexia Nervosa; Feeding and Eating Disorders; Malnutrition
PubMed: 37598049
DOI: 10.1016/j.medcli.2023.07.028 -
The Cochrane Database of Systematic... Mar 2013This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.
OBJECTIVES
To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
SEARCH METHODS
We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.
SELECTION CRITERIA
Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.
DATA COLLECTION AND ANALYSIS
Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.
MAIN RESULTS
We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.
AUTHORS' CONCLUSIONS
This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Topics: Acquired Immunodeficiency Syndrome; Anorexia; Appetite Stimulants; Cachexia; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome
PubMed: 23543530
DOI: 10.1002/14651858.CD004310.pub3 -
Nutrients Apr 2019Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample... (Review)
Review
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.
Topics: Anorexia; Depressive Disorder, Major; Fatty Acids, Omega-3; Humans; Neoplasms; Pain; Paraneoplastic Syndromes
PubMed: 31035457
DOI: 10.3390/nu11050945 -
Journal of Cachexia, Sarcopenia and... Apr 2023Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore,... (Review)
Review
Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, abstracts and full text of identified records against pre-defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full-text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject-reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.
Topics: Humans; Aged; Anorexia; Appetite; Malnutrition; Hospitals; Europe
PubMed: 36807868
DOI: 10.1002/jcsm.13186