Low-density lipoprotein (LDL) cholesterol is a lipoprotein particle responsible for transporting cholesterol throughout the bloodstream to supply the body’s cells. Often referred to as “bad” cholesterol, high levels are a well-known risk factor for heart disease due to the buildup of plaque in artery walls. This focus often overshadows the less frequent scenario where LDL levels drop significantly below the normal range. When the production or absorption of these lipid-carrying particles is disrupted, it can signal an underlying health condition. This article explores the causes of unusually low LDL cholesterol, examining both genetic and acquired factors.
Understanding What Constitutes Low LDL
Lower LDL cholesterol numbers are generally considered desirable, with an optimal level typically falling below 100 milligrams per deciliter (mg/dL) for healthy adults. When LDL levels fall to extremely low concentrations, such as below 40 mg/dL, a clinician may investigate the cause. This threshold suggests the low level may indicate a primary or secondary disorder rather than just a healthy lifestyle.
An extremely low level of LDL cholesterol is medically termed hypobetalipoproteinemia or hypocholesterolemia. This state suggests a problem in the synthesis, assembly, or transport of lipoproteins. While a naturally low LDL level is protective against heart disease, levels that are too low can sometimes be associated with deficiencies in fat-soluble vitamins, which rely on lipoproteins for transport.
Inherited Conditions Leading to Low LDL
The most definitive causes of low LDL cholesterol are inherited genetic conditions that disrupt the body’s normal lipid metabolism. One such condition is Familial Hypobetalipoproteinemia (FHBL), characterized by a lifelong reduction in LDL and apolipoprotein B (ApoB) levels, often caused by a mutation in the APOB gene.
The APOB gene provides instructions for making apolipoprotein B, a protein integral to very-low-density lipoprotein (VLDL) and LDL. A mutation typically results in a truncated ApoB protein, which impairs the liver’s ability to assemble and export VLDL—the precursor to LDL.
Individuals inheriting a single copy of the mutated gene (heterozygotes) usually have low LDL (20 to 50 mg/dL) and remain largely asymptomatic. Those inheriting two copies (homozygotes) may have nearly undetectable LDL levels and can develop serious health concerns, including fat-soluble vitamin deficiencies and neurological issues. A related, rarer condition, Abetalipoproteinemia (ABL), is a severe genetic disorder resulting in virtually no LDL or VLDL, leading to profound fat malabsorption from infancy.
Acquired Factors and Underlying Illnesses
Beyond genetics, several acquired factors and underlying medical conditions can cause LDL cholesterol to drop significantly. These secondary causes mean the low level is a consequence of another physiological process or disease state.
An overactive thyroid gland, known as hyperthyroidism, accelerates the body’s overall metabolism and lipid processing. Thyroid hormones increase the activity of LDL receptors on liver cells. This enhancement allows the liver to clear LDL particles from the bloodstream excessively fast, leading to lower circulating LDL levels.
Severe malnutrition or malabsorption disorders are another major cause, as the body lacks the necessary raw materials to synthesize lipoproteins. Conditions that impair the absorption of dietary fat, such as celiac disease, chronic pancreatitis, or post-surgical changes, limit the lipids needed for VLDL production. Without sufficient fat intake and absorption, the entire cascade of lipoprotein creation slows down, resulting in low LDL.
Serious systemic illnesses, including chronic infections like hepatitis C, certain blood cancers, and acute inflammation, can temporarily suppress lipid production. The body’s response to severe illness often involves a broad metabolic shift, which includes a marked decrease in lipid levels. Extremely restrictive, severely low-fat dietary patterns may also contribute to this reduction.