What are the potential causes of loss of appetite?

Causes of Loss of Appetite

Loss of appetite (anorexia) results from a complex interplay of disease-related systemic inflammation, metabolic derangements, physical barriers to eating, medications, and psychosocial factors—with cancer, chronic respiratory disease, neurological conditions, and acute illness being the most common underlying pathological causes.

Disease-Related Causes

Cancer and Systemic Inflammation

• Cancer-related cachexia is the most extensively documented cause of appetite loss, driven by systemic inflammatory cytokines (TNF-α, IL-1, IL-6) that directly suppress appetite centers in the brain while simultaneously causing metabolic derangements including insulin resistance, increased lipolysis, and accelerated protein breakdown 1.
• The inflammatory response causes anorexia and tissue breakdown that results in significant weight loss, alterations in body composition, and declining physical function 1.
• Tumor-derived factors such as lipid mobilizing factor (LMF) and proteolysis inducing factor (PIF) add additional catabolic signals that further stimulate cytokine production and the acute phase response 1.
• Physical barriers to eating occur with gastrointestinal, head and neck, and esophageal cancers that directly interfere with swallowing or cause severe local mucositis 1.

Chronic Respiratory Disease (COPD)

• Pronounced loss of appetite is central to weight loss in COPD, particularly marked during acute exacerbations 1.
• Multiple mechanisms contribute: tissue hypoxia, chronic inflammatory processes, increased resting metabolic rate, and difficulties in chewing/swallowing secondary to altered breathing mechanics 1.
• Hypoxia may be directly responsible for appetite loss via neurohumoral actions of leptin and cytokines 1.
• Between 25-40% of patients with advanced COPD (FEV1 <50%) experience clinically relevant weight loss 1.

Neurological and Neurodegenerative Conditions

• Stroke, dementia (including Alzheimer's disease), Parkinson's disease, and amyotrophic lateral sclerosis are the most common neurological causes of oropharyngeal dysphagia leading to appetite loss 1.
• In persons with Alzheimer's disease and mild cognitive impairment, depression and difficulty maintaining attention while eating are significantly associated with poor appetite 2.
• Lower vitality, more comorbidities, non-use of antidementia drugs, and use of psychotropic drugs are also significantly associated with poor appetite in AD patients 2.

Physiological and Age-Related Causes

Normal Aging Changes

• Aging naturally causes alterations in olfaction and gustatory sensation that reduce appetite and dietary intake 1.
• Sarcopenia affects swallowing muscles, with decreased oral tongue force generation capacity leading to reduced pressure during the oral phase and poor bolus clearance 1.
• Changes in muscles of mastication result in slower and inefficient chewing, increasing aspiration risk 1.
• Lower salivary flow rates combined with medication effects lead to xerostomia, further impairing appetite 1.

Medication-Induced Appetite Loss

Common Culprit Medications

• Anticholinergics directly impair swallowing function and reduce appetite 1.
• Many medications consumed by older adults contribute to decreased appetite, incoordination, and esophagitis 1.
• Cholinesterase inhibitors used in dementia treatment can suppress appetite 3.
• Chemotherapeutic agents, particularly cisplatin, cause anorexia as a known adverse effect 1.

Acute Illness and Adaptive Response

Physiological Adaptation vs. Pathology

• Loss of appetite in acutely ill medical inpatients may represent an adaptive, protective physiological response that improves cellular recycling (autophagy) and detoxification rather than a therapeutic target requiring aggressive intervention 4.
• Protein-energy malnutrition contributes significantly to adverse outcomes, but indiscriminate nutritional support—particularly parenteral nutrition—can cause harm when used in the acute phase of illness 4.

Psychiatric and Behavioral Causes

Depression and Eating Disorders

• Depression is a critical cause of appetite loss across all age groups, with appetite disturbance (either decreased or increased) being a core diagnostic criterion for major depressive disorder 5.
• Anorexia nervosa involves restriction of food intake leading to lower than expected body weight, intense fear of weight gain, and body image distortion 1.
• Avoidant/restrictive food intake disorder results in significant weight loss or nutritional deficiency without body image distortion 1.

Metabolic and Endocrine Causes

Diabetes and Weight Loss Physiology

• During weight loss, increased appetite plays a primordial role in weight regain, driven by strong physiological adaptations including changes in mitochondrial efficiency and energy expenditure 1.
• Better understanding of molecular, behavioral, and social drivers of appetite could increase compliance with dietary interventions and prevent weight cycling 1.

Critical Clinical Pitfalls

• Do not assume appetite loss in elderly patients with dementia requires pharmacological appetite stimulation—evidence shows no consistent benefit and potential harms outweigh uncertain benefits 3.
• Avoid restrictive diets (such as "diabetic diets" or "no concentrated sweets") in elderly patients, as these lack evidence and may worsen malnutrition 6.
• Distinguish between true dysphagia and other factors affecting eating (olfactory/gustatory changes, medication effects, environmental factors) before attributing appetite loss solely to swallowing problems 1.
• In cancer patients, recognize that cytokine-induced metabolic alterations prevent cachectic patients from regaining body cell mass during nutritional support alone—pharmacological modulation of inflammation should be integrated into management 1.