This begins with the mevalonate or HMG-CoA reductase pathway, the target of statin drugs, which encompasses the first 18 steps.

The intake of naturally occurring phytosterols, which encompass plant sterols and stanols, ranges between ≈200–300 mg/day depending on eating habits.

[citation needed] Cholesterol is also implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane, which brings receptor proteins in close proximity with high concentrations of second messenger molecules.

For many neuron fibers, a myelin sheath, rich in cholesterol since it is derived from compacted layers of Schwann cell or oligodendrocyte membranes, provides insulation for more efficient conduction of impulses.

[32] Inhibition of ERRα signaling by reduction of cholesterol production has been identified as a key mediator of the effects of statins and bisphosphonates on bone, muscle, and macrophages.

"[34][35] Together with ceramides and free fatty acids, cholesterol forms the lipid mortar, a water-impermeable barrier that prevents evaporative water loss.

Steroid sulfate sulfatase then decreases its concentration in the stratum corneum, the outermost layer of the epidermis.

[36] The relative abundance of cholesterol sulfate in the epidermis varies across different body sites with the heel of the foot having the lowest concentration.

About 80% of total daily cholesterol production occurs in the liver and the intestines;[37] other sites of higher synthesis rates include the brain, the adrenal glands, and the reproductive organs.

Synthesis within the body starts with the mevalonate pathway where two molecules of acetyl CoA condense to form acetoacetyl-CoA.

Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins (a class of cholesterol-lowering drugs).

Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning some of the mechanisms and methods of regulation of cholesterol and fatty acid metabolism.

Their subsequent work shows how the SREBP pathway regulates the expression of many genes that control lipid formation and metabolism and body fuel allocation.

Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteasome.

These surface receptors serve as unique molecular signatures, which then help determine fat distribution delivery throughout the body.

Additional roles for oxysterols in human physiology include their participation in bile acid biosynthesis, function as transport forms of cholesterol, and regulation of gene transcription.

[58] The excretion and reabsorption of bile acids forms the basis of the enterohepatic circulation, which is essential for the digestion and absorption of dietary fats.

This cholesterol originates from the diet, bile, and desquamated intestinal cells, and it can be metabolized by the colonic bacteria.

[citation needed] Although cholesterol is a steroid generally associated with mammals, the human pathogen Mycobacterium tuberculosis is able to completely degrade this molecule and contains a large number of genes that are regulated by its presence.

[67] A typical diet contributes on the order of 0.2 gram of phytosterols, which is not enough to have a significant impact on blocking cholesterol absorption.

[71] Some supplemental guidelines have recommended doses of phytosterols in the 1.6–3.0 grams per day range (Health Canada, EFSA, ATP III, FDA).

[73] According to the lipid hypothesis, elevated levels of cholesterol in the blood lead to atherosclerosis which may increase the risk of heart attack, stroke, and peripheral artery disease.

Because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is larger in older people.

A post hoc analysis of the IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein A-I and apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on the cardioprotective role of "good cholesterol".

[81] Elevated cholesterol levels are treatable by a diet that reduces or eliminates saturated fat, and trans fats,[82][83] often followed by one of various hypolipidemic agents, such as statins, fibrates, cholesterol absorption inhibitors, monoclonal antibody therapy (PCSK9 inhibitors), nicotinic acid derivatives or bile acid sequestrants.

[85] Human trials using HMG-CoA reductase inhibitors, known as statins, have repeatedly confirmed that changing lipoprotein transport patterns from unhealthy to healthier patterns significantly lowers cardiovascular disease event rates, even for people with cholesterol values currently considered low for adults.

The researchers attributed this phenomenon to a different correlation, whereby the disease itself increases risk of death, as well as changes a myriad of factors, such as weight loss and the inability to eat, which lower serum cholesterol.

Research into the causes of this state is relatively limited, but some studies suggest a link with depression, cancer, and cerebral hemorrhage.

[103] A separate set of American Heart Association guidelines issued in 2013 indicates that people taking statin medications should have their cholesterol tested 4–12 weeks after their first dose and then every 3–12 months thereafter.

[104][3] Blood cholesterol in people with lifestyle, aging, or cardiovascular risk factors, such as diabetes mellitus, hypertension, family history of coronary artery disease, or angina, are evaluated at different levels.