Hypercholesterolemia in Underweight Individuals: Mechanisms, Clinical Significance and Practical Recommendations

Abstract

Introduction. Hypercholesterolemia is typically associated with obesity and metabolic syndrome, yet elevated total and LDL cholesterol are also frequently observed in underweight individuals, including patients with anorexia nervosa (AN). This paradox can cause diagnostic uncertainty when lipid results are interpreted based on concepts derived from obesity-related dyslipidemia. Aim. To summarize current evidence on mechanisms underlying hypercholesterolemia in underweight individuals, with emphasis on AN, and to outline its clinical significance and management. Materials and Methods. A narrative review of PubMed and Google Scholar literature published up to July 2026, prioritizing systematic reviews, meta-analyses, and observational studies on lipid abnormalities in underweight populations. Results. Hypercholesterolemia in starvation states arises from reduced hepatic LDL-receptor activity, a low-T3 endocrine state, altered cortisol, insulin and leptin signalling, impaired bile acid synthesis, and altered lipoprotein transport, rather than dietary cholesterol intake. These adaptations differ from obesity-driven dyslipidemia and generally improve with nutritional rehabilitation. Conclusions. Hypercholesterolemia associated with underweight is usually a reversible metabolic adaptation to prolonged energy deficiency. Nutritional rehabilitation should be the primary treatment strategy, whereas persistent lipid abnormalities after weight restoration require further diagnostic evaluation.