The body requires cholesterol to function properly. This waxy, fat-like substance is produced primarily by the liver and is a necessary component of every cell membrane. Hypocholesterolemia describes a condition where the total amount of cholesterol in the bloodstream falls to an abnormally low level. While moderate cholesterol reduction is desirable for heart health, a deficit can signal an underlying medical problem that interferes with metabolic processes. Understanding the root cause of low cholesterol is important because it is generally a symptom, not a diagnosis.
Defining Low Cholesterol Levels
Cholesterol is transported through the blood by lipoproteins, primarily low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Hypocholesterolemia is often defined by total cholesterol levels below 120 to 150 milligrams per deciliter (mg/dL) or LDL cholesterol falling below 40 mg/dL. Some definitions classify it as levels within the bottom five percent of the general population. Cholesterol gives structure to cell membranes, maintains their permeability, and serves as the precursor for synthesizing steroid hormones, such as cortisol and sex hormones. It is also converted by the liver into bile acids, which are necessary for the digestion and absorption of fats and fat-soluble vitamins. An insufficient supply of cholesterol can disrupt these essential functions.
Underlying Acquired Health Conditions
A variety of conditions acquired during life can interfere with cholesterol production, absorption, or clearance. Severe liver disease, such as advanced cirrhosis or chronic hepatitis, is a frequent cause because the liver is the main organ for cholesterol synthesis. When the liver’s function is significantly impaired, its ability to manufacture apolipoproteins like Apo A and Apo B, necessary to form lipoprotein particles, is diminished. The severity of the hypocholesterolemia often correlates directly with the extent of the liver damage.
Hyperthyroidism, or an overactive thyroid gland, leads to low cholesterol through an accelerated metabolic rate. Thyroid hormones enhance the expression of LDL receptors on the surface of liver cells. This increase in receptor availability causes the liver to rapidly clear low-density lipoprotein particles from the bloodstream, decreasing circulating cholesterol levels.
Certain types of cancer, particularly hematological malignancies like leukemia, can cause a significant drop in cholesterol. Rapidly dividing cancer cells have a high demand for cholesterol to construct new cell membranes for proliferation. These malignant cells often over-express LDL receptors, effectively stripping cholesterol from the blood supply to fuel their growth. This accelerated consumption of circulating lipids leads to measurable hypocholesterolemia.
Conditions that impair nutrient uptake, such as malabsorption syndromes, contribute to low cholesterol levels. Inflammatory bowel diseases or Celiac disease can damage the lining of the small intestine, reducing the body’s ability to absorb dietary fats and fat-soluble vitamins, including cholesterol. Severe systemic infections, like sepsis, trigger an acute inflammatory response that alters lipid metabolism, resulting in a temporary but sometimes profound drop in total and LDL cholesterol.
Inherited Metabolic Disorders
Some causes of low cholesterol are genetic, arising from inherited mutations that interfere with the body’s lipid transport system. Familial Hypobetalipoproteinemia (FHBL) is a common genetic cause, resulting from a mutation in the APOB gene. This gene provides instructions for making apolipoprotein B, an essential structural component of very-low-density lipoprotein (VLDL) and LDL particles. The mutation leads to a truncated, non-functional version of apolipoprotein B, impairing the body’s ability to assemble and secrete lipoproteins into the bloodstream.
A more severe, though rarer, inherited condition is Abetalipoproteinemia (ABL), also known as Bassen-Kornzweig syndrome. This disorder is caused by a defect in the MTP gene, which codes for the microsomal triglyceride transfer protein. MTP is necessary for loading triglycerides and cholesterol onto apolipoprotein B to form VLDL and chylomicrons. A defective MTP protein means these lipoproteins cannot be correctly formed or secreted, leading to virtually absent levels of LDL and VLDL cholesterol in the blood.
These inherited defects lead to profound malabsorption of fats and fat-soluble vitamins from the diet. The consequences are often apparent in infancy, with symptoms stemming from the inability to transport and utilize these essential nutrients. Other rare genetic disorders, such as Smith-Lemli-Opitz syndrome, interfere with the synthesis of cholesterol itself, leading to very low levels and developmental consequences.
Medications and Extreme Dietary Factors
Certain medications designed to lower high cholesterol can occasionally be too effective, causing levels to drop below the normal range. Potent cholesterol-lowering drugs, such as statins, PCSK9 inhibitors, and ezetimibe, directly target cholesterol synthesis or increase its clearance from the blood. PCSK9 inhibitors block a protein that normally degrades LDL receptors on the liver, allowing more receptors to remain active and remove LDL cholesterol from circulation.
Ezetimibe works by blocking the Niemann-Pick C1-Like 1 (NPC1L1) protein in the small intestine, which reduces the absorption of dietary and biliary cholesterol. While these drugs are usually well-tolerated, their action can occasionally push cholesterol levels into the hypocholesterolemia range, requiring dosage adjustment.
Extreme dietary choices or severe malnutrition can also lead to low cholesterol. Severely restricted, very-low-fat diets can limit the raw materials the body needs to synthesize lipoproteins. Though the body can produce most of the cholesterol it needs, a prolonged deficit of dietary fat can exacerbate underlying metabolic issues. Restricting fat intake can specifically decrease levels of HDL cholesterol, the particle responsible for carrying cholesterol away from the arteries.