Benecol - Healthcare Professionals

Absorption of Cholesterol with / without Plant Stanol Ester

Role of Sterols and Stanols in Reducing Cholesterol  

The use of foods containing plant sterols and stanols provide a novel approach to lowering plasma LDL by dietary means. Known since the early 1950s, they are structurally analogous to cholesterol. They lower serum levels of total cholesterol and low-density lipoprotein cholesterol by inhibiting the absorption of dietary cholesterol and the reabsorption of biliary cholesterol in the human intestine. The effective dose of 1-2 g/day decreases LDL-C by 6-15%. This effect is long-term and appears to be similar with a once-daily or divided dosage, and is independent of the fat content of the food vehicle. Together with cholesterol-lowering drugs and therapeutic lifestyle changes (TLC), sterols and stanols can lower cholesterol even further. Functional foods containing plant stanols have the potential of becoming the basis of cholesterol management for all individuals at risk.

Origin of Plant Sterols

Plant sterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. The natural dietary intake of plant sterols is about 150-350 mg/day, and that of plant stanols 15-50 mg/day. Plant sterols are plant equivalents of cholesterol and have a very similar molecular structure. According to their structure, they can be divided into sterols and stanols, stanols being a saturated subgroup of sterols. Sterols and stanols appear in everyday diets in concentrations too low to change blood cholesterol levels significantly. In the esterified form, the solubility of stanols in fat is increased, and while in that form, they can be added to several kinds of foods. In the digestive tract, stanol ester is cleft into stanols and fatty acids by pancreatic enzymes. Attempts to measure biological effects of sterols in feeding studies have been hampered by the limited solubility of free sterols in both water and fat. Esterification of plant sterols with long-chain fatty acids increases their solubility in fat by 10 and allows delivery of several grammes per day in different foods.

Absorption and Safety

Plant sterols have traditionally been considered non-absorbable. In humans consuming solid food diets, more than 90% of sitosterol is recovered in the stool. Plant sterol absorption is quite low, particularly for stanols, for which the absorption efficiency is over 10 times lower than for the equivalent sterols. Plasma levels of fat-soluble vitamins and other vegetable-derived compounds have been studied following plant sterol ingestion due to concerns about the possibility of reduced absorption. Alpha- and beta-carotene are slightly reduced, although results have been inconsistent. However, no reduction in beta-carotene level was seen when plant sterols or plant stanols were consumed as part of a healthy diet containing fruits and vegetables. It has been shown that dietary plant sterols safely reduce serum cholesterol in a broad range of patients, including children. Following evidence from toxicological studies and numerous clinical trials, stanols are characterised as safe by authorities in several EU countries as well as by the FDA (USA).

Mode of Action

The molecular mode of actions of stanols has been described in several preclinical and clinical trials and can be divided into two steps. Step 1: Cholesterol absorption occurs via the formation of micelles with bile acids. Stanols displace cholesterol from these micelles so that less cholesterol is absorbed. Stanols need to be taken as part of a meal in order to be incorporated in the micelles. Step 2: In vitro studies have shown that stanols activate LXR alpha, LXR beta and ABCA1 transporter proteins. It is thus hypothesised that stanols work in enterocytes by activating the excretion of cholesterol back into the intestinal lumen. Only stanols have been proven to retain their efficacy in long-term use, most likely due to the minimal absorption of stanols, and consequently their lack of effect on bile acid metabolism.

Combining Dietary Plant Stanols into Pharmaceutical Therapy

The cholesterol-lowering effect of plant stanols provides an additional effect in combination with statin therapy, and is well tolerated and safe. Statins lower cholesterol levels by inhibiting cholesterol synthesis, which leads to an increase in the number of LDL receptors on liver cells and to higher uptake of LDL-cholesterol. By comparison, plant stanols reduce intestinal absorption of cholesterol. Combining dietary plant stanols with statin therapy will deliver both these effects. The cholesterol-lowering effect is maintained even in combination with a diet low in saturated fat and cholesterol.