Loss of appetite and anorexia

Loss of appetite (anorexia) is a reduced desire to eat. Here it means the symptom, not anorexia nervosa. It is common in acute illness, usually transient, but persistent loss of appetite leads to weight loss, undernutrition, sarcopenia, frailty and worse outcomes, and may be the first symptom of cancer, depression, kidney disease or chronic infection.

Clinical relevance. Acute loss of appetite accompanies almost any infection or inflammatory illness. Persistent loss over 2 weeks needs a cause. In older adults it is called anorexia of ageing and is multifactorial, with reduced hunger, early satiety, loss of taste and smell, polypharmacy, dental problems and social factors.

Separate it from related symptoms. Early satiety is feeling full after a few mouthfuls. Food aversion is dislike of specific foods. Dysphagia and odynophagia limit eating because swallowing is difficult or painful. Nausea suppresses intake. Fear of eating (sitophobia) follows pain after meals in mesenteric ischaemia.

Physiology. Hunger and satiety are regulated by hypothalamic neurones (neuropeptide Y and agouti related peptide stimulate feeding; pro-opiomelanocortin and cocaine and amphetamine regulated transcript suppress it), peripheral hormones (ghrelin raises appetite; leptin, cholecystokinin, peptide YY and glucagon like peptide 1 reduce it), vagal signals, taste and smell, and cortical and emotional input.

Mechanisms of anorexia. Cytokines (interleukin 1, interleukin 6, tumour necrosis factor) in infection, inflammation and cancer act on the hypothalamus. Gastrointestinal causes act through delayed emptying, distension, pain and obstruction. Metabolic toxins (uraemia, hypercalcaemia, hepatic failure) cause nausea and aversion. Drugs and depression alter central drive.

Classification.

• Acute (under 2 weeks) and chronic (over 2 weeks).
• With or without weight loss.
• Primary (anorexia of ageing, hypothalamic) and secondary to disease, drugs or psychological causes.
• Cancer related anorexia and cachexia.

History.

• Onset, duration, course, whether hunger is lost or eating is limited by early satiety, nausea, pain or swallowing difficulty. Weight change, usual intake, food avoidance, specific aversions (meat in cancer).
• Gastrointestinal: nausea, vomiting, abdominal pain, bowel habit, bloating, heartburn, dysphagia, jaundice, dark urine, rectal bleeding.
• Constitutional: fever, night sweats, fatigue, lumps, cough, urinary symptoms, menstrual history, pregnancy.
• Taste and smell changes (after viral illness, zinc deficiency, drugs), dry mouth, mouth ulcers, dentition and dentures.
• Mood: low mood, anxiety, bereavement, grief, loss of interest, psychotic beliefs about food, body image, fear of weight gain, restrictive intake, purging or excessive exercise.
• Cognition, function, ability to shop and cook, social isolation, poverty, alcohol, substance use.
• Drugs: SSRIs and venlafaxine, digoxin, metformin, GLP-1 receptor agonists, opioids, antibiotics (metronidazole, macrolides), chemotherapy, antiretrovirals, levodopa, antiepileptics (topiramate, zonisamide), stimulants, iron and zinc supplements, NSAIDs, ACE inhibitors (taste).
• Use of appetite questionnaires (Simplified Nutritional Appetite Questionnaire; a score under 14 indicates risk of weight loss over 5% in 6 months).

Examination.

• Weight, body mass index, hydration, vital signs, temperature.
• Oral cavity: candidiasis, ulcers, glossitis, dry mucosa, dentition and dentures, gum disease.
• Pallor, jaundice, lymph nodes, thyroid, signs of heart failure.
• Abdomen: tenderness, masses, hepatomegaly, ascites, bladder, rectal examination.
• Chest, breast, skin. Neurological and cognitive assessment. Mental state and depression screen.
• Features of an eating disorder: lanugo, low pulse and temperature, parotid enlargement, Russell sign, dental erosion.

Red flags.

• Weight loss over 5% in 6 months, persistent vomiting, dysphagia, haematemesis, melaena.
• Jaundice, progressive abdominal pain, epigastric mass, palpable nodes.
• Fever, night sweats, haemoptysis.
• Confusion, severe dehydration, polyuria with ketones, hypotension.
• Pregnancy, suicidal thoughts, intense fear of weight gain with restriction.
• Age over 50 with new persistent symptoms.

Acute illness. Viral and bacterial infections of any system, acute hepatitis (A, B, E), gastroenteritis, malaria, typhoid, urinary tract infection, pneumonia, postoperative state, pain.

Gastrointestinal and hepatobiliary. Peptic ulcer disease, gastritis, Helicobacter pylori infection, gastro-oesophageal reflux disease, oesophageal disease, gastroparesis, gastric outlet obstruction, gastric, pancreatic, colorectal and hepatobiliary cancer, chronic pancreatitis, cholecystitis, hepatitis, cirrhosis, inflammatory bowel disease, coeliac disease, constipation and faecal impaction, mesenteric ischaemia, dental disease.

Malignancy. Gastrointestinal, lung, ovarian, renal and other cancers, lymphoma, leukaemia, cancer treatment (chemotherapy, radiotherapy), cancer cachexia.

Infective and chronic. HIV infection, tuberculosis, infective endocarditis, brucellosis, visceral leishmaniasis, helminth infestation.

Endocrine and metabolic. Hypothyroidism, adrenal insufficiency, hypercalcaemia (hyperparathyroidism), uraemia and chronic kidney disease, diabetic ketoacidosis, hyponatraemia, hypopituitarism, hepatic failure.

Cardiorespiratory. Heart failure (gut congestion and cachexia), chronic obstructive pulmonary disease, interstitial lung disease, hypoxia.

Neurological. Dementia, Parkinson disease, stroke, bulbar disease, anosmia and ageusia (post viral, head injury, neurodegeneration), delirium.

Psychiatric. Depression, anxiety disorders, grief, psychotic disorders, anorexia nervosa, avoidant restrictive food intake disorder, bulimia nervosa, substance and alcohol use disorder, post traumatic stress.

Drugs and nutritional. Those listed in the history; zinc, thiamine and vitamin B12 deficiency; chronic alcohol use; excessive vitamin A.

Physiological and social. Pregnancy (first trimester), ageing, hot weather, poverty, food insecurity, isolation, poor dentition, difficulty with self feeding, institutional care, elder neglect.

1. Acute loss of appetite with a clear cause (viral illness, gastroenteritis) needs no tests. Reassess in 1 to 2 weeks.
2. Persistent loss of appetite: weigh the patient, calculate body mass index, apply a validated tool (Malnutrition Universal Screening Tool, Mini Nutritional Assessment short form or Simplified Nutritional Appetite Questionnaire), and screen for depression and cognitive impairment.
3. Baseline tests: full blood count with film, ESR and C reactive protein, urea, creatinine and electrolytes, calcium, liver function tests with albumin, glucose or HbA1c, thyroid stimulating hormone, ferritin, vitamin B12 and folate, urinalysis (glucose, ketones, protein), pregnancy test, and HIV test with consent.
4. Directed tests: Helicobacter pylori stool antigen or urea breath test (stop proton pump inhibitor 2 weeks before), lipase, 08:00 cortisol, tissue transglutaminase IgA with total IgA, chest radiograph, abdominal ultrasound, tuberculosis tests, hepatitis serology, zinc level where taste loss is prominent.
5. Upper endoscopy for age over 55 with new persistent symptoms, dysphagia, vomiting, weight loss, anaemia or epigastric mass; colonoscopy for bowel changes or iron deficiency. CT of chest, abdomen and pelvis for red flags or unexplained weight loss.
6. Eating disorders: weight and body mass index trends, pulse, blood pressure, orthostatic changes, electrolytes (potassium, phosphate, magnesium), ECG for QT interval, glucose, bone density when chronic.
7. Observation with repeated weights and review of intake over 4 to 6 weeks when the first tests are normal and no red flags exist.

Limits. Appetite questionnaires are subjective. Normal tests do not exclude early cancer. Albumin reflects inflammation, not intake. Helicobacter pylori tests are unreliable after antibiotics and proton pump inhibitors.

Treat the cause. Treat infection, gastro-oesophageal reflux, constipation, pain, depression, hypercalcaemia, uraemia and endocrine disease. Stop or replace drugs that suppress appetite where possible. Treat oral candidiasis (nystatin 100,000 units/mL 1 mL four times daily for 7 days, or fluconazole 50 to 100 mg orally once daily for 7 to 14 days) and dental disease.

Nutritional approach.

• Food first: small frequent energy dense meals and snacks, fortified foods, enhanced flavour and presentation, eating with company, avoiding diet restrictions, and giving the largest meal at the time of greatest appetite.
• Oral nutritional supplements providing 300 to 600 kcal and 12 to 24 g protein daily when intake is inadequate.
• Dietitian review. Estimated needs: energy 25 to 30 kcal/kg daily, protein 1.2 to 1.5 g/kg daily.
• Zinc supplementation (zinc sulphate 220 mg, 50 mg elemental zinc, orally once daily for up to 8 weeks) only when deficiency is shown or taste is disturbed with low zinc.
• Assisted feeding, texture modification and speech and language assessment where swallowing is impaired.
• Enteral tube feeding when intake remains inadequate beyond 5 to 10 days or earlier with severe malnutrition.
• Refeeding risk when intake is minimal for over 10 days, body mass index is under 16, or electrolytes are low: correct potassium, phosphate and magnesium, start at 10 kcal/kg daily, and give thiamine 200 to 300 mg orally daily (or 100 mg intravenously two to three times daily) before and for the first 10 days of feeding.

Appetite stimulants (limited evidence; selective use).

• Mirtazapine 15 mg orally at night, increased to 30 mg, for depression with anorexia and insomnia. Monitor sodium and blood count.
• Megestrol acetate 160 mg orally daily, increased to 400 to 800 mg, for cancer or HIV cachexia; risk of venous thromboembolism, adrenal suppression and oedema; avoid with thrombosis history.
• Dexamethasone 2 to 4 mg orally each morning for 1 to 3 weeks in palliative care; limited duration due to steroid effects.
• Olanzapine 2.5 to 5 mg orally at night for anorexia and nausea related to chemotherapy or cancer.
• Metoclopramide 10 mg orally 30 minutes before meals three times daily for early satiety or gastroparesis (halve the dose when eGFR is under 60 mL/min; limit the course because of tardive dyskinesia).
• Cannabinoids and cyproheptadine are not advised in adults.

Specific conditions. Anorexia nervosa and other eating disorders need specialist eating disorder care and structured refeeding. Depression needs psychological therapy and an antidepressant such as sertraline 50 mg orally daily. Hypercalcaemia (corrected calcium 3.0 mmol/L or more) needs hydration with 0.9% sodium chloride and a bisphosphonate such as zoledronic acid 4 mg intravenously over 15 minutes, with renal adjustment.

Monitoring. Weigh weekly at first and monthly after. Review appetite and intake at 2 to 4 weeks. Repeat electrolytes after starting refeeding or when vomiting is present.

Referral and escalation. Urgent investigation or 2 week cancer referral for red flags. Dietetic, speech and language, dental, geriatric, palliative or psychiatric services as indicated. Eating disorder services for suspected anorexia nervosa.

Admission. Severe dehydration, electrolyte disorder, body mass index under 15, refeeding risk, unstable vital signs, inability to take fluids, eating disorder with heart rate under 40 beats/minute, systolic pressure under 90 mmHg, potassium under 3.0 mmol/L or prolonged QTc, suicidal risk, or need for urgent investigation.

Safety netting. Return for vomiting, black stool, jaundice, persistent fever, weight loss, severe abdominal pain, confusion, or inability to drink.

Special groups. Older adults: review polypharmacy, oral health, depression, cognition and social support; avoid dietary restriction; and treat anorexia of ageing with food fortification. Pregnancy: appetite loss with hyperemesis needs thiamine and electrolyte replacement. Children: persistent appetite loss and poor weight gain need paediatric assessment of feeding, infection and growth.

HIV and endemic regions: tuberculosis, HIV, helminths, malaria and food insecurity; treat helminths with albendazole 400 mg orally once and provide supplementary food where indicated. Palliative care: focus on comfort, small preferred meals and carer support rather than forced feeding.