Cholesterol: Absorption and entero-hepatic circulation
The absorption of dietary cholesterol occurs at the level of the small intestine, especially in the duodenum and in the jejunum, proximal and intermediate sections of this segment of the digestive tract.
Of the 300 mg of cholesterol that we introduce approximately every day with food, only 50% is absorbed. This percentage varies significantly in relation to cholesterol reserves; for homeostatic laws, in fact, enteric absorption is as inferior the more abundant the body's cholesterol reserves, and vice versa.
Almost all of the triglycerides / circulating fatty acids derive from food absorption; the cholesterol introduced with food represents only 20-30% of blood cholesterol, while the remaining percentage comes from the endogenous production by the liver. Also in this case the extent of hepatic synthesis depends on the food intake: the more this is consistent, the lower the endogenous production, and vice versa.
In principle, it is estimated that intestinal absorption of cholesterol cannot exceed one gram per day.
Although the percentages just mentioned can vary significantly from individual to individual, it is clear that dietary cholesterol affects cholesterol levels to a modest extent. In fact, in addition to the aforementioned physiological limit of absorption, the increase in blood cholesterol, consequent to high dietary intake, determines an inhibition of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) necessary for its endogenous synthesis; consequently, there is a homeostatic system capable of adapting the endogenous synthesis to intestinal absorption. Simplifying everything:
in conditions of cholesterol deficiency, the body responds by increasing its absorption and endogenous synthesis, and vice versa.
In food, cholesterol is present both in free form and in esterified form, ie linked to a fatty acid. At the intestinal level, this bond is separated from an esterase present in the pancreatic juice, since the only free cholesterol can be effectively absorbed by the intestinal mucosa.
Thanks to the intervention of bile, free cholesterol is emulsified in micelles, lipoprotein droplets rich in phospholipids, fatty acids, bile salts and monoglycerides. The micellar cholesterol can then passively pass through the aqueous phase in contact with the cell membranes of the enterocytes, inside which it is partly re-esterified by the enzyme acyl-cholesterol-acyl-transferase (ACAT2) and incorporated into chylomicrons. These lipoprotein aggregates are then conveyed into the lymphatic circulation and from there to the bloodstream, which transports them to the liver where they are processed and distributed to the various tissues. A part of the cholesterol absorbed by the enteric mucosa is not incorporated into the chylomicrons (a rather slow process), but excreted by the enterocyte in the intestinal lumen, then removed with the faeces. This percentage is clearly high in the case of phytosterols (see below)
Decrease cholesterol absorption
The vegetable counterpart of cholesterol, which we remember being concentrated in animal foods and absent in fruit and vegetables, is represented by plant sterols or phytosterols. However, these substances, present in the diet in concentrations similar to cholesterol, are absorbed in significantly lower percentages, in the order of 2% (an excessive absorption is the basis of a disease known as Beta-sitosterolemia).
At the level of the intestinal mucosa, cholesterol competes with phytosterols for uptake by enterocytes; consequently, the higher the percentage of phytosterols in the diet, the lower the intestinal cholesterol absorption. This strategy, embodied in the use of supplements based on plant sterols, is used to decrease blood cholesterol levels in the presence of hypercholesterolemia, with all the limits linked on the one hand to the risk of excessive absorption of phytosterols in predisposed subjects, and on the other hand, the low impact of dietary cholesterol on plasma levels.
Even dietary fiber, especially soluble fiber, helps to reduce intestinal cholesterol absorption, through the formation of a gel that incorporates various nutrients, decreasing and slowing the absorption of bile salts and cholesterol. A drug called ezetimibe acts to hinder the absorption of cholesterol, while the active ingredient cholestyramine slightly inhibits the ability to absorb cholesterol, preventing that of bile acids.
Very important is the dietary limitation of sugars and saturated fats, which have an equivalent impact, if not even higher than cholesterol, on the blood concentrations of this lipid. In fact, saturated fatty acids and sugars increase the availability of acetyl-coA (a common intermediate in carbohydrate and lipid oxidation) necessary for the synthesis of cholesterol at the level of liver cells. Consequently, in the presence of hypercholesterolemia it is advisable to limit the intake of saturated fatty acids to percentages lower than 7% of the energy introduced, reducing as much as possible the intake of trans fatty acids and limiting that of cholesterol to no more than 300 mg per day. This result is obtained by preferring lean meats and vegetable protein sources, preferring skim milk and limiting the consumption of its more fat derivatives, but also minimizing the intake of partially hydrogenated lipids present in many margarines and packaged products (sweet and savory snacks, and baked goods in general). At the same time it is important to minimize the intake of drinks and food products with added sugar.
