How intervening on gastrointestinal reabsorption can reduce serum cholesterol
Activated Charcoal and Cholestyramine
Activated Charcoal (from now a.c.) is a form of carbon processed to be riddled with small pores in order to increase the surface area giving it a great surface/volume ratio. Due to its high degree of microporosity, just one gram of a.c. has a surface area in excess of 500 m. This particular propriety makes it perfect for absorption. It is in fact most used in the Emergency Departments in association with gastric lavage as primary health care for poisoning and overdose following oral ingestion.
From XIX Century a.c. was used to treat flatulence and other gastric disorders.
Its ability to restrain molecules in the gastrointestinal tract can used to treat patients with hypercholesterolemia. A.c. is neither absorbed in the gastrointestinal tract nor metabolized, and it is excreted in feces, so that everything has been captured in its structure is expelled by feces
Cholestyramine is a bile acid sequestrant which binds bile in the gastrointestinal tract to prevent its re-absorption. When bile acids are excreted, plasma cholesterol is converted to bile acid to normalize bile acid levels. This conversion of cholesterol into bile acids lowers plasma cholesterol concentrations.
Concerning Cholesterol Influx It is very important consider that roughly 2/3 of intestinal cholesterol is from bile while just 1/3 comes from diet. Serum Cholesterol is in fact determined by the balance of its synthesis and its catabolism and intestinal absorption. While the most common Statins based therapy acts inhibiting the HMG-CoA Reductase, therefore its synthesis, activated charcoal and cholestyramine ("Resins" in figure) can be useful reducing the intestinal absorption.
Daily intake of cholesterol is about 250/400 mg within daily synthesis is about 750/1000 mg (in a healthy man). The enterohepatic circulation of bile acids and cholesterol makes that only a small quantity is expelled by feces(just about 3%). Blocking intestinal absorption is therefore a key point of hypercholesterolemia therapy .
A study conducted by the University of Helsinki showed the clinical result of the therapy based on a.c. for patients affected by hypercholesterolemia (The mechanism of the hypocholesterolaemic effect of activated charcoal, 1989 ). Activated charcoal, 8 g t.i.d. for 4 weeks, reduced serum concentration of total cholesterol by 27% (P less than 0.01) . This trial showed that the interference with the enterohepatic circulation of bile acids caused an increased cholesterol synthesis.
A second study conducted by the same research team showed the effects of different a.c. doses and the combination with cholestyramine in reducing serum Cholesterol (Activated charcoal in the treatment of hypercholesterolaemia: dose-response relationships and comparison with cholestyramine, 1989.)
The dose-response relationship of activated charcoal in reducing serum cholesterol was determined and the effects of charcoal and cholestyramine were compared in patients with hypercholesterolaemia. In a cross-over study 7 patients ingested charcoal 4, 8, 16 or 32 g/day, and finally bran, each phase lasting for 3 weeks. Serum total and LDL-cholesterol were decreased (maximum 29% and 41%, respectively) and the ratio of HDL/LDL-cholesterol was increased (maximum 121%) by charcoal in a dose dependent manner. Ten further patients with severe hypercholesterolaemia ingested daily for 3 weeks, in random order, activated charcoal 16 g, cholestyramine 16 g, activated charcoal 8 g + cholestyramine 8 g, or bran. The concentrations of total and LDL-cholesterol were reduced by charcoal (23% and 29%, respectively), cholestyramine (31% and 39%) and their combination (30% and 38%). The ratio of HDL/LDL-cholesterol was increased from 0.13 to 0.23 by charcoal, to 0.29 by cholestyramine, and to 0.25 by their combination. Serum triglycerides were increased by cholestyramine but not by charcoal. Other parameters, including the serum concentrations of vitamin A, E and 25(OH)D3 remained unaffected. The changes in lipids only partly subsided during the 3-week bran phase. In general, the acceptability by the patients and the efficacy of activated charcoal, cholestyramine and their combination were about equal, but there were individual preferences for particular treatments.
The most frequent adverse effect of cholestyramine resin is constipation, which occurs in about 20% of patients receiving the drug; cholestyramine resin may also increase the severity of preexisting constipation (American Hospital Formulary Service- Drug Information, 2004). Fecal impaction and/or hemorrhoids with or without bleeding have been reported rarely in association with constipation, most often when high dose of cholestyramine have been used in children and in the elderly. This kind of adverse effect could be avoided by the association of bran or cathartics such as Sorbitol. Other less common gastrointestinal adverse effects such as nausea, vomiting, flatuolence and bloating are reported in the American Hospital Formulary Service- Drug Information; however, a direct relationship of these effects to drug therapy has not been established.
Concerning a.c. there no relevant adverse gastrointestinal effects. Charcoal bezoars are a rare complication of activated charcoal administration (Bezoar causing small bowel obstruction after repeated activated charcoal administration, 2005). They have been associated with treatment for intoxication (wich provides larger doses) with carbamazepine, amitriptyline, theophylline, benzodiazepines and barbiturates. The parasympatholytic effects of the drugs can precipitate or contribute to paralytic ileus, allowing charcoal to accumulate (potentially with remnants of undigested tablets) and form bezoars.
These evidences makes believe that a.c. combined with cholestyramina could be a useful treatment for hypercholesterolemia. The high availability and the very low price of activated charcoal makes it a solution for those people risking hypercholesterolemia and have to keep their cholesterol serum level under control. It could may be a solution even for those who don't tolerate a Statin based Therapy.
It is dutiful remember that an healthy lifestyle and an adequate diet are pillars of hypercholesterolemia prevention