Anorexia, cachexia and fatigue

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Weight loss in advanced illness has several components. Reduced intake causes starvation; inflammation drives cachexia; fluid accumulation can hide tissue loss; and inactivity accelerates muscle wasting. Measure trend using prior weights, clothing, mid-arm or functional change and oedema context. Ask about appetite separately from ability to chew, swallow, digest, shop and prepare food.

A reversible-cause screen should remain proportionate. Examine mouth, teeth, tongue, swallowing, abdomen, oedema, muscle and neurological function. Review nausea, bowel, pain, breathlessness, fever, sleep, depression, medicines and food access. Target blood tests for anaemia, infection, renal, hepatic, thyroid, glucose, calcium and electrolytes when results could lead to a wanted treatment.

Food carries emotional and cultural meaning. Families may fear that the person is starving or believe encouragement proves care. Explain that inflammatory cachexia alters appetite and metabolism and that forcing food can cause distress. Offer choices, small portions and permission to stop. Continue social presence at meals and mouth care even when calories are no longer the priority.

Dietary intervention is goal specific. Fortify familiar foods, use oral supplements between meals and adapt texture after swallowing assessment. Dietitians can balance energy, protein, renal or hepatic restrictions and treatment needs; overly restrictive chronic-disease diets may no longer add benefit. If enteral or parenteral nutrition is considered, define the expected functional or treatment outcome and review date before insertion.

Artificial nutrition is a medical treatment, not basic care automatically. It may support a reversible swallowing problem, recovery from treatment or prolonged obstruction in a selected patient. It may also cause aspiration, diarrhoea, line infection, thrombosis, fluid overload and repeated hospital care. In the last days, clinically assisted nutrition rarely changes trajectory and may add burden; mouth care, sips and shared presence continue.

Fatigue management combines activity and rest. Identify the most important task, plan it for the best time, sit for personal care, use equipment and schedule short rests before exhaustion. Gentle resistance and walking can preserve function when safe. Treat sleep disruption and reduce sedating or non-beneficial medicines. Transfusion may help selected symptomatic anaemia, but discuss chance and duration of benefit, travel and fluid burden.

Appetite medicines offer limited windows. Dexamethasone can improve appetite rapidly but causes insomnia, mood change, hyperglycaemia, infection and muscle weakness. Megestrol can increase appetite and weight, much of it fluid or fat, without reliable functional benefit and raises thrombosis and adrenal risk. Use only a goal-defined time-limited trial with informed review.

Key points

Anorexia is reduced desire to eat; cachexia is a multifactorial loss of muscle with or without fat that nutrition alone does not fully reverse; fatigue is subjective exhaustion.
First-line assessment asks what prevents eating or activity, examines mouth and swallow, reviews weight trajectory and fluid, and checks symptoms, medicines, mood and social access.
Treat contributors that can improve a valued outcome: pain, nausea, constipation, thrush, dysphagia, infection, anaemia, endocrine disturbance, sleep and depression.
Explain cachexia physiology early: smaller intake is part of illness and pressure to eat can increase nausea, conflict and guilt.
Offer small preferred energy-dense portions, flexible timing, taste adaptation and drinks between rather than with meals when early satiety dominates.
Dietitian review is first-line when nutrition can improve treatment tolerance, function or recovery; artificial nutrition requires a functional route, sufficient prognosis and explicit goal.
Use light resistance or functional exercise and energy conservation when feasible to preserve muscle and independence; bed rest worsens deconditioning.
A short dexamethasone trial may improve appetite and wellbeing for days to weeks, but benefit wanes and toxicity rises; stop if no rapid meaningful response.
The gold-standard plan states whether the goal is comfort, strength, treatment support or survival and matches food, supplements, feeding route and medicine time to that goal.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Inflammatory cancer cachexia

Tumour and host cytokines drive anorexia, insulin resistance, proteolysis and lipolysis that ordinary calorie replacement cannot fully reverse.

Reduced intake and mechanical barriers

Nausea, mouth pain, dysphagia, obstruction, early satiety, altered taste, breathlessness and dependence make eating difficult or unpleasant.

Systemic and treatment contributors

Anaemia, infection, organ failure, endocrine disease, chemotherapy, radiotherapy, sedatives and deconditioning cause overlapping fatigue and appetite loss.

Psychological and social factors

Depression, anxiety, food insecurity, isolation, conflict and loss of cultural food practices reduce intake and amplify exhaustion.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Hypothalamic appetite change
Inflammatory and tumour signals alter central hunger and satiety pathways, producing early fullness and reduced desire despite energy deficit.
2
Skeletal-muscle catabolism
Proteolytic signalling, inactivity and endocrine resistance reduce muscle protein faster than nutrition alone can replace it.
3
Altered energy metabolism
Insulin resistance, futile substrate cycling and tumour metabolism increase energy inefficiency while fat and lean reserves fall.
4
Fatigue network
Inflammation, anaemia, sleep disruption, pain, low mood and physical deconditioning interact to reduce both physical and cognitive endurance.
5
Refeeding electrolyte shift
Insulin release after renewed carbohydrate drives phosphate, potassium and magnesium intracellularly, causing cardiac, respiratory and neurological failure in high-risk malnutrition.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Anorexia

Reduced hunger, early satiety and smaller desired portions occur without necessarily indicating a mechanical inability to eat.

Cachexia

Ongoing muscle and weight loss, reduced strength and inflammatory advanced disease persists despite ordinary nutrition support.

Sarcopenic obesity

Muscle depletion and weakness can be severe despite a normal or high body weight and may be hidden by adiposity.

Fluid-masked wasting

Ascites and oedema can maintain scale weight while muscle, subcutaneous tissue and function continue to decline.

Potentially reversible fatigue

New pallor, fever, endocrine symptoms, bleeding, sleep loss or medicine sedation should prompt cause-focused assessment.

Refeeding riskRed flag

Very low BMI, major recent weight loss, little intake, alcohol use or low phosphate, potassium or magnesium requires controlled nutrition initiation.

Red flags requiring action

New focal weakness, dysarthria, choking or wet voice suggests neurological or swallowing emergency and requires aspiration-safe assessment.
Fever, hypotension, confusion or abrupt functional collapse suggests infection, metabolic disturbance or adrenal insufficiency rather than cachexia alone.
Melaena, haematemesis, heavy bleeding, angina or breathlessness with anaemia may require urgent haemoglobin and source assessment.
BMI and weight loss can conceal oedema or ascites; rapid scale change does not always represent tissue gain or loss.
Starting nutrition after prolonged minimal intake can cause refeeding syndrome and requires phosphate, potassium, magnesium, thiamine and fluid planning.
Corticosteroids can worsen infection, delirium, hyperglycaemia and proximal weakness, making prolonged appetite treatment self-defeating.
Megestrol increases venous thrombosis, oedema and adrenal suppression and should not be used as an unreviewed routine appetite stimulant.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line intake and barrier assessmentFirst stepFirst line
Why
Separate appetite, taste, chewing, swallowing, nausea, early satiety, bowel, access, preparation and family pressure.
Interpretation and limitations
Treat the limiting barrier rather than assuming additional calories are the only intervention.
02
Weight, fluid and functional trend
Why
Review prior dry weights, percentage loss, oedema, ascites, muscle bulk, grip or transfers and performance over time.
Interpretation and limitations
Fluid can conceal tissue loss; functional decline may be more clinically useful than one current weight or BMI.
03
Mouth and swallowing assessment
Why
Identify thrush, mucositis, dentition, xerostomia, aspiration, obstruction and need for texture or route adjustment.
Interpretation and limitations
Unsafe swallowing requires speech and language assessment and goal-based feeding decisions rather than simple appetite stimulation.
04
Targeted laboratory screen
Why
Assess full blood count, inflammation, renal and liver function, glucose, calcium, thyroid and electrolytes when treatment is plausible.
Interpretation and limitations
Results guide transfusion, infection, endocrine, renal and refeeding management but do not provide a single diagnostic marker for cachexia.
05
Refeeding-risk assessment
Why
Use BMI, percentage weight loss, duration of minimal intake, alcohol, medicines and baseline phosphate, potassium and magnesium.
Interpretation and limitations
High risk requires thiamine, controlled calorie introduction, electrolyte replacement and close clinical and biochemical monitoring under NICE CG32.
06
Nutrition-treatment benefit review
Why
Define whether supplements, tube feeding or parenteral nutrition improves intake, strength, treatment access, quality of life or another agreed outcome.
Interpretation and limitations
This repeated goal review is the practical gold standard; stop when burdens exceed benefit or the outcome is no longer achievable.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Simple starvation

Energy deficit without major inflammation produces adaptive metabolic slowing and is more responsive to nutrition than established cachexia.

Depression

Persistent low mood, anhedonia, guilt and suicidal thought can cause poor appetite and fatigue and merits direct assessment.

Endocrine or metabolic illness

Hypothyroidism, adrenal insufficiency, diabetes, calcium disturbance, renal failure and hepatic disease produce potentially treatable weakness and anorexia.

Anaemia and infection

Breathlessness, palpitations, fever, night sweats and acute decline supports blood loss, marrow failure or infection rather than cachexia alone.

Dysphagia or obstruction

Hunger with inability to swallow or vomiting differs from loss of appetite and requires mechanical and aspiration assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Initial assessmentFind barriers and define the nutrition goalFirst stepThe person reports poor appetite, weight loss or fatigue or family raises concern about intake.

1Clarify appetite versus ability, examine mouth, swallow, abdomen, fluid and muscle and review symptoms, medicines, mood, access and disease trajectory.
2Treat reversible contributors and agree whether the priority is enjoyment, strength, treatment tolerance, recovery or survival, including the person's information preference.
3Use dietitian, therapy, psychological and palliative support to create small practical actions and a review measure, explaining cachexia to family.

02Oral supportIncrease value without increasing pressureSwallowing is safe and the person wants help to improve or maintain oral intake.

1PreferredOffer preferred high-energy and protein foods in small portions, flexible timing and adapted texture, with mouth and nausea care before meals.
2Use fortification or supplements between meals and relax low-value dietary restrictions after renal, diabetic or cardiac review.
3PreferredMonitor enjoyment, intake, symptoms, weight-fluid context and function and stop products that replace preferred food or cause fullness, diarrhoea or burden.

03Artificial nutritionMatch route and prognosis to benefitOral intake is inadequate and enteral or parenteral nutrition is being considered.

1Assess gastrointestinal function, aspiration, obstruction, refeeding risk, performance, expected survival, disease treatment and decision-specific capacity.
2Explain route-specific chance of achieving the stated outcome plus infection, thrombosis, aspiration, fluid, monitoring and lifestyle burdens and consider a time-limited trial.
3Start under nutrition-team protocol with thiamine and controlled refeeding when indicated and review the goal, complications and stopping conditions at agreed intervals.

04Short appetite trialUse medicine only for a time-matched goalAppetite distress persists after reversible causes and nutrition conversation and rapid temporary improvement would matter.

1AlternativeChoose dexamethasone or an exceptional specialist alternative after infection, diabetes, thrombosis, fluid, mood and muscle-risk review.
2State the target such as meal enjoyment or energy for an event, use the lowest effective morning dose and set a review within days.
3Stop if no meaningful benefit and taper after sustained exposure; avoid continuing as appetite fades while myopathy, delirium or oedema increases.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Can transiently improve appetite, energy and wellbeing when rapid benefit over days matters more than long-term toxicity.

Dexamethasone short appetite trial

Use 2 to 4 mg orally once each morning for a short palliative trial, reviewing within 5 to 7 days and stopping for no meaningful benefit; taper according to duration, dose and adrenal-risk guidance.

Hyperglycaemia, infection, insomnia, mood or psychotic change, gastrointestinal harm and proximal myopathy rise with dose and duration and hepatic metabolism interactions matter.

May improve appetite and produce weight gain in selected cancer cachexia, though functional and survival benefit is uncertain.

Megestrol acetate under specialist review

When selected after informed risk discussion, use a protocol dose commonly beginning at 160 mg orally daily and review within weeks; higher dosing should follow oncology or palliative specialist guidance and product information.

Venous thrombosis, oedema, hypertension, hyperglycaemia, adrenal suppression and hypogonadism occur; avoid routine use in high thrombotic or fluid-overload risk.

Prevents thiamine-deficiency neurological and cardiac complications when carbohydrate delivery resumes after prolonged depletion.

Thiamine for high refeeding risk

Give oral thiamine 200 to 300 mg daily immediately before and during the first 10 days of feeding, together with the multivitamin and electrolyte plan specified by NICE CG32 and the local nutrition protocol.

Thiamine does not replace controlled calorie initiation or phosphate, potassium, magnesium, fluid and cardiac monitoring; intravenous therapy may be required when oral absorption is unreliable.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Functional dependence

Muscle loss impairs transfers, cough, swallowing and mobility, causing falls, pressure damage, infection and increasing care needs.

Treatment intolerance

Malnutrition and poor performance increase chemotherapy toxicity, surgical complications, delayed healing and inability to attend or complete treatment.

Refeeding syndrome

Rapid feeding after severe depletion can cause arrhythmia, heart failure, respiratory weakness, delirium, seizures and death.

Food-related conflict

Relatives may equate feeding with love and perceive reduced intake as neglect, creating coercion, guilt and distress at meals.

Medicine adverse effects

Appetite stimulants can cause thrombosis, oedema, infection, diabetes, delirium and myopathy without meaningful function or survival gain.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track what the person can and wants to eat, meal-related symptoms and family distress rather than calories alone.
Interpret weight with oedema and ascites and monitor transfers, walking, cough and a patient-selected energy task.
During refeeding monitor pulse, fluid, oedema, glucose, phosphate, potassium and magnesium at protocol-defined frequency.
During dexamethasone review appetite target, sleep, mood, glucose, infection and proximal strength within days.
During megestrol ask about leg swelling, chest symptoms, oedema, glucose and adrenal symptoms and stop when no goal benefit appears.
Review artificial nutrition for line or tube infection, thrombosis, aspiration, diarrhoea, fluid overload and the original functional outcome.
Revisit the food conversation as disease changes and reassure family that comfort care continues when intake naturally falls.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Calories cannot cancel inflammation

Cachexia includes metabolic and inflammatory muscle loss, so nutritional failure is not evidence that patient or family did something wrong.

Weight can rise while muscle falls

Ascites, oedema, corticosteroid and megestrol can add fluid or fat while strength and lean tissue continue to decline.

Food is relational

Preserving choice, taste and shared mealtime presence may matter more than achieving a prescribed portion.

Restriction can outlive benefit

Low-fat, diabetic or renal rules may reduce enjoyment when their long-term prevention purpose no longer matches prognosis.

Steroid benefit is brief

Rapid appetite improvement often fades after weeks while infection, myopathy and metabolic harm continue to accumulate.

Artificial feeding needs a stop rule

A trial is clinically honest only when the team states what outcome, timeframe and complication would prompt discontinuation.

11Common pitfallsFrequent interpretation and management errors.

01
Using scale weight without accounting for oedema and ascites.
02
Calling all weakness cachexia and missing infection, anaemia or endocrine disease.
03
Pressuring food as proof of care despite nausea and loss of appetite.
04
Starting supplements before treating mouth pain, constipation or dysphagia.
05
Assuming tube or parenteral feeding reverses inflammatory cachexia.
06
Starting full calories rapidly in a patient at high refeeding risk.
07
Continuing dexamethasone after appetite benefit fades.
08
Using megestrol without thrombosis, fluid and adrenal review.
09
Prescribing bed rest for fatigue and accelerating deconditioning.
10
Continuing burdensome artificial nutrition after the original goal is no longer achievable.