HDL - Kresser Institute Membership Site

Marker Name: HDL

REFERENCE RANGES FOR HDL CHOLESTEROL:

Laboratory reference range: 39+ mg/dL

Functional reference range: 50–85 mg/dL

DESCRIPTION:

HDL, or high-density lipoprotein, is one of the five major lipoproteins in plasma. Unlike other lipoproteins, HDL primarily shuttles fatty acids from adipocytes and other fat-containing cells to the liver for eventual excretion in the feces.^1,2 HDL also transfers cholesterol to steroidogenic tissues such as the ovaries, testes, and adrenal glands to serve as precursors for steroid-containing hormones.³ HDL also appears to play a role in removing cholesterol from lipid-laden macrophages (i.e., foam cells) in atherosclerotic plaques.⁴

HDL primarily participates in the reverse cholesterol transport pathway.⁵ The liver synthesizes HDL, which is secreted as flattened spherical particles of apolipoproteins and phospholipids.^4,6 As a lipoprotein with both fatty and proteinaceous components, HDL can associate itself in a micelle structure, with hydrophobic ends on its interior and hydrophilic ends on its exterior.⁷ With this structure, HDL serves as a carrier of water-insoluble lipids such as cholesterol and triglycerides within plasma.

Nascent HDL particles attract free cholesterol and cholesterol from cell membranes into the growing HDL particle.⁵ During this maturation process, known as the HDL cycle, maturing HDL particles attract free cholesterol by interacting with the ATP-binding cassette transporter A1.^8,9 Free cholesterol is enzymatically converted into cholesterol esters that migrate to the core of the growing lipoprotein particle. HDL particles deposit cholesterol in target tissues by interacting with specific HDL receptors, such as scavenger receptor BI.³ HDL degradation and catabolism take place largely in the liver.⁴

While laboratory reports list the test by the name “HDL,” what is actually reported and what is actually of clinical interest is HDL-C, or HDL cholesterol. HDL-C reflects HDL particles that contain cholesterol. Strictly speaking, HDL refers only to the lipoprotein. Modern laboratories are currently transitioning from older to newer methods for measuring HDL and other cholesterol levels in blood samples.¹⁰ Some inherent limitations to these methods remain, including heterogeneity of LDL and HDL particle size and composition.¹¹

Abnormally high levels of HDL are uncommonly referred to in the literature as hyperalphalipoproteinemia. This term can be confusing since there are heritable causes of elevated HDL that are commonly called hyperalphalipoproteinemia.¹² Other, secondary causes of elevated HDL are virtually never called hyperalphalipoproteinemia (though they could be, strictly speaking). HDL-C levels can be increased by regular physical activity, weight loss, and certain drugs.^13,14 On the other hand, very high levels of HDL may increase the risk of cardiovascular events, such as heart attack.¹⁵ This may be because excess HDL at the levels described becomes dysfunctional.¹⁶

As with elevated HDL, the term hypoalphalipoproteinemia is usually reserved for familial cases of low HDL. Several rare genetic disorders cause decreased circulating HDL.¹⁷ Other metabolic abnormalities can lower HDL levels (e.g., elevated cholesteryl ester transfer protein activity, lipoprotein lipase deficiency, elevated hepatic triglyceride lipase activity).¹⁸ Obesity and lifestyle issues such as smoking and physical inactivity are associated with low HDL-C levels. Acute infection, inflammation, and certain chronic diseases can lower HDL as well.⁶

HDL cholesterol is measured as part of the standard serum lipid profile. The serum lipid profile includes total cholesterol, LDL cholesterol, and triglycerides. This report may also provide calculated estimates of VLDL cholesterol, non-HDL cholesterol, and the cholesterol/HDL ratio.¹⁹

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS: High in:^3,13,15,18

Cholesteryl ester transfer protein deficiency
Familial hyperalphalipoproteinemia
Drugs
- Bile acid sequestrants
- Fibrates
- Nicotinic acid (niacin)
- Omega-3 fatty acids
- PCSK9 inhibitors
- Statins

Low in:^17,18

Insulin resistance
Uncontrolled diabetes mellitus
Malnutrition
Cigarette smoking
Acute infection
Inflammation
Hepatocellular disease
Cholestasis
Chronic renal failure
Primary causes
- Familial primary hypoalphalipoproteinemia
- Non-familial hypoalphalipoproteinemia
- Familial hypoalphalipoproteinemia with hypertriglyceridemia
Elevated cholesteryl ester transfer protein activity
Lipoprotein lipase deficiency
Elevated hepatic triglyceride lipase activity
Gammopathy (artifact)
Drugs
- Beta blockers
- Benzodiazepines
- Anabolic steroids

FUNCTIONAL RANGE INDICATIONS:

High in:

Inflammation

Low in:

Insulin resistance and metabolic dysfunction
Inflammation
Impaired liver function
Numerous chronic disease states

References: