Unexplained Weight Loss

Unintentional weight loss is defined as a loss of more than 5% of body weight over six to twelve months without deliberate effort, and it is one of the highest-yield symptoms in clinical medicine. Roughly a quarter of cases turn out to be malignancy, another quarter non-malignant organic disease, and a substantial minority psychiatric or social — depression, bereavement, alcohol use, food insecurity and dental problems are all common and frequently overlooked. In perhaps a fifth of cases no cause is ever found, and those people generally do well. The mechanism falls into three groups: reduced intake, increased losses, or increased metabolic demand. Reduced intake covers depression, dementia, dysphagia, nausea, poor dentition and medication side effects. Increased losses covers malabsorption from coeliac disease, pancreatic insufficiency and inflammatory bowel disease, plus glycosuria in uncontrolled diabetes. Increased demand covers hyperthyroidism, chronic infection, heart failure and cancer cachexia, in which inflammatory cytokines drive muscle catabolism that extra calories alone cannot reverse. The critical point is sequencing. Oral nutritional supplements and protein drinks address the consequence, not the cause, and starting them before investigation risks masking a treatable diagnosis. Once a cause is identified and being treated, nutritional support with adequate protein and resistance exercise is genuinely valuable for preserving lean mass.

• •Clothes or rings becoming noticeably loose
• •Loss of appetite or early satiety
• •Visible loss of muscle bulk
• •Fatigue and reduced exercise tolerance
• •Night sweats or fever
• •Change in bowel habit or pale, floating stool

• •Malignancy, particularly gastrointestinal, lung and haematological
• •Hyperthyroidism
• •Uncontrolled or new type 1 diabetes
• •Coeliac disease and other malabsorption
• •Inflammatory bowel disease
• •Chronic infection including tuberculosis and HIV
• •Depression, dementia or bereavement
• •Alcohol use disorder
• •Medication side effects
• •Dental problems and swallowing difficulty

Three physiological routes: inadequate intake, impaired absorption, or elevated resting energy expenditure and catabolism. In cancer cachexia and chronic inflammatory disease, cytokine-driven proteolysis and lipolysis produce muscle loss disproportionate to calorie deficit, which is why simply eating more does not reverse it.