Where is dietary cholesterol absorbed

This is consistent with the need to treat individual patients with different therapeutic modalities. In patients heterozygous for familial hypercholesteraemia, higher plasma mevalonic acid a surrogate for cholesterol synthesis 24 predicted a good response to statin therapy and those with a good response showed greater reduction in plasma mevalonic acid concentrations on treatment.

Furthermore, the E4 genotype, which has been associated with relatively greater absorption of cholesterol, was more common in poor responders than good responders to statin therapy in heterozygous familial hypercholesteraemia patients. The severity of the underlying mutation in the LDL receptor had no predictive value. The higher prevalence of metabolic syndrome and cardiovascular disease observed in South Asians, African-Americans and Hispanics highlights the need to research cholesterol metabolism in different ethnic groups.

This increasing prevalence of cardiovascular disease in these populations is partially related to urban living and the adoption of Western lifestyles and diet. Several overdue statin trials in these populations, such as the Investigation of Rosuvastatin in South-Asian subjects IRIS , will provide valuable information on cholesterol metabolism in these populations.

An understanding of shifting cholesterol metabolism is also important when we give dietary advice to our patients. It is now recognised that reducing cholesterol in the diet is not as important as reducing saturated fat and weight loss. The importance of recognising that genetic and environmental factors lead to differences in cholesterol metabolism is of clinical importance for the treatment of hyperlipidaemia.

Even though statins will remain the gold standard for treating hypercholesteraemia for many years to come, many high-risk patients fail to reach LDL targets or do not tolerate statins. As we have the therapeutic options to inhibit cholesterol absorption as well as cholesterol synthesis, we are able to individually tailor LDL therapy. As we aim for lower LDL cholesterol targets, we will need to use combination drugs more often.

Karam M Kostner ,. Open access: The copyright in this work belongs to Radcliffe Medical Media. Implications and Conclusion The importance of recognising that genetic and environmental factors lead to differences in cholesterol metabolism is of clinical importance for the treatment of hyperlipidaemia.

Miettinen TA, Kesaniemi YA, Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels, Am J Clin Nutr, ;49 4 — Response to changes in dietary fat quality and cholesterol quantity, J Clin Invest, ;79 6 — Kern F Jr, Normal plasma cholesterol in an year-old man who eats 25 eggs a day.

Mechanisms of adaptation, N Engl J Med, ;—9. So when bile salt sequestrants increase cholesterol loss as bile salts, the liver compensates with more synthesis, depleting its store of cholesterol and adding to the total amount of cholesterol excreted in the feces.

Cholesterol is synthesized in the body at a rate of up to 1. Statins inhibit cellular synthesis of cholesterol from acetate by inhibiting hydroxymethyl glutaryl coenzyme A reductase, the rate-limiting enzyme in the synthesis. Cells need cholesterol for membrane synthesis, so if they do not get enough cholesterol from synthesis, they upregulate their LDL receptors, take LDL from the plasma, and thereby lower plasma LDL.

Another class of molecules to control serum cholesterol is inhibitors of intestinal absorption. While they inhibit absorption of dietary cholesterol, "the real target in cholesterol balance is inhibiting reabsorption of biliary cholesterol," thereby inhibiting LDL formation, according to Dr Cohen. Available agents include plant sterols, stanols in the form of dietary supplements, and the new drug, ezetimibe, the only approved drug in the class. Ezetimibe appears to be a specific inhibitor of the NPC1LI channel in the enterocyte, slowing the rate of cholesterol uptake.

It blocks the channel to about the same degree as if the NPC1L1 gene were deleted, as shown in knockout mice Figure 2. Lower intestinal absorption means less cholesterol input into chylomicrons. Cholesterol-poor circulating chylomicrons return to the liver and are cleared with whatever cholesterol they contained. They are essentially a shunt for moving cholesterol from the intestine to the liver. Lowering the rate of this shunting by inhibiting absorption in the first place is important "because a good proportion of that cholesterol is packaged right back up and made into VLDL particles, which downstream turn into LDL," Dr Cohen explained.

Dual inhibition by blocking cholesterol absorption with ezetimibe and synthesis with statins is a highly effective strategy for reducing serum LDL levels, he continued. Blocking absorption reduces the amount of cholesterol in chylomicrons, which eventually return to the liver with their cholesterol loads and contribute to VLDL production.

In response to this decrease in cholesterol absorption, the liver upregulates cholesterol synthesis, and this tends to negate the effectiveness of reducing absorption. Statins reduce the compensatory upregulation that occurs in the liver and restore the effectiveness of inhibiting cholesterol absorption in reducing VLDL output by the liver.

Therefore, in addition to promoting clearance of LDL particles from plasma, in the setting of dual therapy, statins help to reduce the formation. Cholesterol balance is regulated by both synthesis and absorption. Each pathway may compensate for changes in the other, partially negating any beneficial therapeutic effect. The human intestine is responsible for absorbing a significant amount of cholesterol each day.

In addition to approximately 0. Approximately 0. However, the human body seems to allow only cholesterol to enter and remain in the body, with almost negligible amounts of plant sterols being retained.