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Functional Blood Chemistry Manual

Cholesterol, Total

Marker Name: Cholesterol, Total


Laboratory reference range:
Male and female: 100–199 mg/dL

Functional reference ranges:
Male: 150–220 mg/dL
Female: 150–230 mg/dL


Cholesterol is the major lipid in the circulation and is a prominent component of cell membranes throughout the body. Cholesterol provides structural integrity to the phospholipid bilayer within cell membranes and increases cell membrane permeability.1 Cholesterol is also the structural precursor to various steroid molecules including bile acids, vitamin D, cortisol, corticosteroid, aldosterone, and sex steroids.2

As a lipid, cholesterol is insoluble in water, and, by extension, insoluble in plasma.3 Instead, cholesterol can circulate in the bloodstream by attaching to lipoproteins. The five major lipoproteins in plasma are chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), intermediate-density lipoproteins, and high-density lipoproteins (HDL).3 LDL is the major carrier of cholesterol, and VLDL is the major carrier of triglycerides.3 HDL also carries cholesterol.

Cholesterol may be generated and transported through three major pathways: the exogenous pathway, the endogenous pathway, and the reverse cholesterol transport pathway.4 In the exogenous pathway of lipid metabolism, dietary cholesterol and fatty acids are absorbed from the gastrointestinal tract and cholesterol is esterified.5 Triglycerides and cholesterol combine to form chylomicrons, which enter the circulation and travel throughout the body. Remnants of these chylomicrons form HDL.

In the endogenous pathway, VLDL is created in the liver from triglycerides and cholesterol esters. VLDL undergoes several changes, ultimately being incorporated into LDL. LDL, which primarily contains cholesterol esters, is internalized in the liver and other tissues. LDL in the liver is converted into bile acids and secreted into the intestines. LDL in other tissues may be used as a steroid precursor molecule, used in cell membrane synthesis, or stored for future use.5

The reverse cholesterol transport pathway removes cholesterol from the tissues and returns it to the liver.4 HDL is the primary lipoprotein in this pathway. Mature HDL is formed from nascent HDL particles that have been secreted by the liver and intestine.4 During this maturation process, known as the HDL cycle, maturing HDL particles attract free cholesterol and cholesterol from cell membranes into the growing HDL particle.6

Total cholesterol is measured directly from serum samples, as are HDL and triglycerides.3 LDL cholesterol is determined by mathematical calculation of measured cholesterol. While many clinicians still insist on fasting determination of total cholesterol, studies indicate that differences between fasting and non-fasting total cholesterol values are negligible.7

An abnormally high total cholesterol level in the blood is called hypercholesterolemia.8 Since total cholesterol includes HDL cholesterol, LDL cholesterol, and other lipids, abnormally high levels of total cholesterol may also be called hyperlipidemia. Strictly speaking, however, hypercholesterolemia is not precisely synonymous with hyperlipidemia, since hyperlipidemia also describes abnormally elevated triglyceride levels, and triglycerides are not a form of cholesterol. Hypercholesterolemia may be the result of a primary or secondary disorder. Primary hypercholesterolemia is due to a heritable condition such as familial hypercholesterolemia or polygenic hypercholesterolemia.9 While von Gierke disease is heritable, it is considered a secondary cause of hypercholesterolemia. Secondary causes of hypercholesterolemia may be due to endocrine disturbances, such as diabetes or hypothyroidism; diseases of the kidney or liver; the effect of various stressors, such as cigarette smoking; or the effect of various drugs.10

Hypocholesterolemia is the name given to abnormally low circulating levels of total cholesterol.11 As with hyperlipidemia, hypolipidemia and hypocholesterolemia are used interchangeably, although this is imprecise.12 The causes of hypocholesterolemia can also be categorized as primary and secondary. Abetalipoproteinemia and hypobetalipoproteinemia are the most common primary causes of hypocholesterolemia.13 Malnutrition and malabsorption are unfortunately common causes of hypocholesterolemia, although abnormally low levels of cholesterol may occur in chronic inflammatory diseases and chronic liver diseases, which are also common. Blood disorders such as anemia, sickle cell disease, and hematologic malignancy may also reduce circulating levels of cholesterol. Supratherapeutic doses of statins may lead to abnormally low levels of circulating cholesterol.

Total cholesterol is measured as part of the standard serum lipid profile. The serum lipid profile includes total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. This report may also provide calculated estimates of VLDL cholesterol, non-HDL cholesterol, and the cholesterol/HDL ratio.14


  • Primary disorders of cholesterol metabolism
    • Familial hypercholesterolemia
    • Familial combined hypercholesterolemia
    • Familial hyperapobetalipoproteinemia
    • Polygenic hypercholesterolemia
  • Diabetes mellitus
  • Hypothyroidism
  • Obesity
  • Cigarette smoking
  • Excessive alcohol consumption
  • Anorexia nervosa
  • Nephrotic syndrome
  • Renal failure
  • Obstructive liver disease
  • Hepatitis
  • Acute intermittent porphyria
  • Systemic lupus erythematosus
  • Von Gierke disease
  • Drugs
    • Adrenal steroids
    • Beta-blockers
    • Isotretinoin
    • Thiazides
    • Anticonvulsants
    • Protease inhibitors
    • Oral estrogens

Low in:11,12,17

  • Primary disorders of cholesterol metabolism
    • Abetalipoproteinemia
    • Hypobetalipoproteinemia
    • Chylomicron retention disease
  • Anemia
  • Chronic inflammation
  • Infection (acute or chronic)
  • Hyperthyroidism
  • Chronic liver disease
  • Sickle cell disease
  • Malabsorption and undernutrition (e.g., critical illness)
  • Gaucher type I disease
  • Malignancy
  • Drugs
    • Statins


High in:

  • Same as conventional indications
  • Poor thyroid function
  • Intestinal permeability
  • Chronic infections
  • Heavy metal toxicity (and possibly presence of other toxins such as mold)

Low in:

  • Same as conventional indications


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