Anorexia Nervosa (AN) is a restrictive eating disorder characterized by self-imposed starvation, leading to profound malnutrition. Individuals struggling with AN present with numerous complex medical complications. One frequently observed and perplexing finding is hypercholesterolemia, or abnormally high levels of cholesterol in the blood. This phenomenon occurs in a significant percentage of acutely ill patients and appears to contradict the expectation that severe undernourishment would lead to depleted fat stores. The elevation of total cholesterol is predominantly driven by an increase in low-density lipoprotein (LDL) cholesterol, prompting investigation into the physiological adaptations causing this unexpected lipid profile.
The Counterintuitive Nature of High Cholesterol in Starvation
The presence of high cholesterol in patients with Anorexia Nervosa seems paradoxical, given the extreme restriction of dietary fat and calories these individuals maintain. For most people, high cholesterol is associated with a diet rich in saturated fats. In contrast, the body’s usual response to starvation is to break down stored lipids for energy, which generally leads to a reduction in circulating cholesterol levels.
The body of a person with AN is in a state of chronic energy deficit, yet research consistently shows total cholesterol and LDL cholesterol levels are elevated compared to healthy individuals. This highlights a fundamental difference in how the body processes lipids during AN versus other forms of malnutrition. The increase in cholesterol is not a result of dietary intake but rather a metabolic consequence of the body’s attempt to conserve energy and adapt to the prolonged nutritional crisis.
Primary Cause: Reduced Cholesterol Clearance
The main driver behind elevated cholesterol levels in Anorexia Nervosa is a significant reduction in the body’s ability to clear cholesterol from the bloodstream, largely mediated by changes in thyroid hormone function. Severe caloric restriction triggers a protective mechanism that drastically slows the overall metabolic rate to conserve energy stores. This adaptive response is often referred to as euthyroid sick syndrome, where the thyroid gland appears functionally normal but its peripheral hormone activity is severely dampened.
The body achieves this slowdown by altering the conversion of thyroxine (T4) into its biologically active form, triiodothyronine (T3). In AN, the conversion of T4 to T3 is reduced, resulting in lower circulating levels of active T3. This reduction in T3 is particularly impactful on the liver, which is responsible for managing cholesterol clearance.
Active T3 hormone normally plays a regulatory role in maintaining the expression of low-density lipoprotein (LDL) receptors on the surface of liver cells. These LDL receptors bind to and remove LDL cholesterol particles from the circulation for breakdown and disposal. With diminished T3 activity, the liver downregulates the number and function of these LDL receptors, making the entire clearance process sluggish. Consequently, LDL particles remain in the bloodstream longer, causing the observed hypercholesterolemia. The decreased removal rate of these lipoproteins is the most important physiological mechanism contributing to high cholesterol levels in this population.
Secondary Factors: Altered Lipid Synthesis and Transport
While reduced clearance is the primary mechanism, other factors related to the body’s altered lipid handling also contribute to elevated cholesterol. The body’s internal production of cholesterol, known as endogenous synthesis, continues despite the lack of dietary intake. In some cases of AN, the liver may adjust its internal metabolic machinery in response to chronic energy deprivation, affecting the balance of synthesis and breakdown.
Changes in specific lipid transport proteins also play a role. One such protein is Cholesterol Ester Transfer Protein (CETP), which facilitates the exchange of lipids between different lipoprotein particles. CETP has been found to be accelerated in AN patients. This increased activity contributes to the remodeling of lipoprotein particles, enriching LDL particles with more cholesterol and triacylglycerol. The net result is a shift towards a more cholesterol-rich LDL subclass.
Furthermore, the state of starvation leads to elevated levels of cortisol, a stress hormone, which influences metabolic pathways. Research suggests this cortisol increase may indirectly promote the synthesis of cholesterol precursors in the liver. These complex shifts in synthesis, combined with the primary defect in clearance, result in the characteristic buildup of LDL cholesterol in the malnourished state.
Implications for Diagnosis and Recovery
The presence of hypercholesterolemia is clinically relevant for the diagnosis and management of Anorexia Nervosa. Measuring cholesterol levels serves as an objective biomarker that often correlates with the severity of the patient’s malnutrition and weight loss. This finding is useful because it helps distinguish AN from other severe malabsorptive or wasting conditions, such as inflammatory bowel disease, where cholesterol levels are typically low or normal.
Crucially, elevated cholesterol levels are a direct consequence of the starved state, meaning the primary treatment is nutritional restoration, not lipid-lowering medication. As patients begin the refeeding process and achieve consistent weight gain, their metabolic and endocrine systems normalize. This restoration of normal thyroid hormone function reactivates the liver’s LDL receptors, allowing cholesterol clearance to resume. Consequently, total cholesterol and LDL levels typically fall and normalize as the patient recovers, underscoring the reversibility of this metabolic complication.