What are the causes of low appetite?

Causes of Low Appetite

Low appetite results from a complex interplay of disease-related metabolic alterations, psychological factors, physical barriers to eating, and medication effects, with the specific cause varying by clinical context.

Cancer-Related Causes

Primary Mechanisms

• Systemic inflammation drives anorexia through proinflammatory cytokines that alter central nervous system appetite signals in the arcuate nucleus of the hypothalamus and nucleus tractus solitarius, creating an imbalance favoring pro-opiomelanocortin over neuropeptide-Y 1, 2
• Metabolic derangements including elevated resting metabolic rate, insulin resistance, and catabolic factors produce anorexia independent of nutritional intake 1
• Cachexia and precachexia are characterized by involuntary weight loss with ongoing skeletal muscle mass loss, where anorexia is worsened by catabolic drivers that reduce nutrient intake while increasing metabolic needs 1

Secondary Physical Barriers

• Oral and gastrointestinal obstruction: mouth ulcers, xerostomia, poor dentition, intestinal obstruction, malabsorption 1
• Treatment-related symptoms: nausea, vomiting, diarrhea, constipation, chemosensory alterations, reduced intestinal motility 1
• Pain: uncontrolled pain directly suppresses appetite 3

Cancer Type Specificity

• Gastrointestinal malignancies show anorexia prevalence of 6-74%, with higher rates in advanced disease (25-45% in palliative care) 1
• Head and neck, liver, and lung cancers carry particularly high risk for malnutrition and associated anorexia 1

Psychological and Psychiatric Causes

Depression

• Major depressive disorder affects 10-25% of cancer patients and 6-32% of those receiving palliative care, with anorexia as a cardinal symptom 1
• Community-dwelling older adults with depressive symptoms show 8.38 times higher odds of appetite loss (OR = 8.38; 95% CI = 2.31-30.47) 4
• Functional gastrointestinal disorders demonstrate that decreased appetite is strongly associated with depressive symptoms, which predict the majority of FGIDs in patients with reduced appetite 5

Anxiety and Stress

• Physical and psychological stressors impact appetite regulation through neurohormonal pathways 6

Medication-Induced Causes

Antidepressants (SSRIs)

• Fluoxetine (Prozac) causes anorexia in 11% of major depressive disorder patients versus 2% on placebo, 17% of OCD patients versus 10% on placebo, and 8% of bulimia patients versus 4% on placebo 7
• Escitalopram produces appetite reduction, making it inappropriate for patients with pre-existing anorexia or cachexia 8

Other Medications

• Acetylcholinesterase inhibitors used in Alzheimer's disease cause cholinergic overstimulation affecting appetite 6
• Chemotherapy and radiotherapy directly cause anorexia through multiple mechanisms 1

Chronic Disease-Related Causes

Respiratory Disease

• COPD patients experience pronounced appetite loss (anorexia) particularly during acute exacerbations, triggered by difficulties in chewing and swallowing secondary to altered breathing mechanics, with hypoxia potentially responsible via neurohormonal actions of leptin and cytokines 1
• 25-40% of advanced COPD patients are malnourished, with muscle wasting found in 25% of GOLD stages 2-3 and up to 35% in severe disease 1

Cardiac Disease

• Congestive heart failure affects nutritional state through multiple mechanisms including metabolic alterations and physical limitations 1

Gastrointestinal Disorders

• Functional gastrointestinal disorders show appetite changes in 49% of patients, with 33% reporting decreased appetite associated with esophageal, gastroduodenal, bowel, and anorectal symptoms 5, 9
• Eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder) present with both primary appetite dysregulation and secondary GI symptoms that perpetuate poor intake 9

Age-Related and Sociodemographic Factors

Aging

• Each year of age increases odds of appetite loss by 11% (OR = 1.11; 95% CI = 1.03-1.20) in community-dwelling older adults 4
• Frailty correlates with appetite loss, though the relationship is complex and mediated by multiple factors 4

Socioeconomic Factors

• Non-White ethnicity shows 6.47 times higher odds of appetite loss (OR = 6.47; 95% CI = 1.63-25.58) in community settings 4
• Lower educational attainment may correlate with appetite loss through socioeconomic pathways 4

Acute Illness and Critical Care

Physiological Response

• Acute illness produces appetite loss as a potentially adaptive response that may improve cell recycling (autophagy) and detoxification, though this remains controversial 10
• Protein-energy malnutrition in acutely ill medical inpatients contributes to adverse outcomes, yet indiscriminate nutritional support may cause harm 10

Clinical Pitfalls and Caveats

Common diagnostic errors include:

• Attributing appetite loss solely to depression when underlying cancer cachexia or metabolic derangements are present 1
• Overlooking medication-induced anorexia, particularly with SSRIs in patients already at nutritional risk 8, 7
• Failing to distinguish between true anorexia and physical barriers to eating (obstruction, pain, nausea) that are potentially reversible 1, 3
• Missing sarcopenic obesity where muscle loss is masked by excess fat, leading to underestimation of nutritional compromise 1
• Interpreting appetite loss in acute illness as purely pathological when it may represent adaptive physiology 10

Assessment priorities:

• Screen for reversible causes first: pain, constipation, nausea, depression, medication effects 3
• Evaluate for systemic inflammation markers in cancer patients, as cytokine-driven anorexia will not respond to nutritional support alone 1
• Assess body composition (muscle mass, not just BMI) to detect sarcopenia or sarcopenic obesity 1
• Consider cultural and socioeconomic factors that may influence both appetite and reporting of symptoms 4