Other methods for treating cholesterol problems

Scientists are looking into other methods to treat cholesterol problems. Cholesterol ester transfer protein inhibitors may be able to stop or even “reverse” cholesterol transport for HDL to VLDL or IDL, thus improving the HDL/LDL ratio. Microsomal triglyceride transfer proteins (MTP) inhibitors would, like statins, affect cholesterol production in the liver. Early concerns are that side effects could include liver disease (cirrhosis). Acyl cholesterol acyl transferase inhibitors (ACAT) would prevent conversion of the cholesterol molecule to the form that is stored along the arterial walls. Unfortunately, this also means the cholesterol isn't stored in the places it should be stored in – the adrenals and gonads. Scientists are searching for an ACAT inhibitor that stops only cholesterol storage in the arteries.

Fibrates

Fibrates, aka fibric acid derivatives, work by stimulating expression of a bunch of proteins involved in metabolism of lipids. This is the results in the accelerated breakdown of triglycerides, and it is for people with high triglycerides that fibrates have been most used. They can also increase HDL levels in the blood by 20%. The major effects of the fibrates are to lower plasma triglyceride and raise HDL-C levels. Fibrates are effective for treatment of combined hyperlipidemia, hypoalphalipoproteinemia and hypertriglyceridemia. The risk of muscle toxicity may increase when patients take both statins and fibrates. Two fibrates are approved for cholesterol problems in the US: Gemfibrozil and Fenofibrate.

Niacin inhibits hormone sensitive lipase in fatty tissue, thus lowering fatty acid levels in the blood, and thereby lowering the body’s production of cholesterol and triglycerides. Niacin also results in higher HDL levels. Scientists speculate this is due to a decrease in the rate of elimination of apolipoprotein apoA1, which is the apolipoprotein most associated wit HDL.

Nicotinic acid

Patients diagnosed with hypercholesterolemia, hypoalphalipoproteinemia and hyperlipidemia cab be treated effectively with nicotinic acid. Nicotinc acid produces positive results based on dosage (a range of 1-3 g per day) in lowering VLDL and LDL-C levels. Patient intolerability creates nicotinic acid limitations. More on niacin for cholesterol problems

Ezetimibe

Patients utilizing low dose statin therapy that fail to meet cholesterol goals may use ezetimibe in lieu of high statin doses avoiding risk of potential muscle injury. The clinical benefit of ezetimibe and statin therapy or ezetimibe monotherapy is unproven.

Bile acid sequestrants

Patients with mild to moderate LDL-C elevations are effectively treated with bile acid sequestrants. Cholestramine or colestiol dosages lower LDL-C from 10 to 24 percent. Colesevelam may also produce similar results. These medications work in the digestive system by binding with bile and thereby preventing the reabsorption to the bloodstream. With less bile in the liver, less cholesterol is synthesized.

Typical doses are 24 to 30 g/day for cholestramine and colestiol and only 2 to 4 g/day for colesevelam. These are much higher quantities than you typically see in drugs that enter the bloodstream (like statins) because the medicines physically bond to the bile in the intestines.

Patients with elevated LDL-C can also benefit from the addition of bile acid sequestrants in combination with nicotinic acid and a statin. Side effects hamper bile acid sequestrant usage. These effects are mostly in the digestive system and can include bloating and cramping.

Blocking absorption in the digestive system

There is an over-the-counter margarine that stops the body from absorbing cholesterol in the digestive system. Margarine is defined as a butter substitute made from vegetable oils. The plant equivalent of cholesterol is sitosterol. A chemical modification (partial hydrogenation) of sitosterol is used for cooking and when eaten, inhibits the “sterol pumps” in the digestive system. Cholesterol is not absorbed.

One interesting method of lowering cholesterol isn’t a drug; it involved swallowing a resin that binds with bile acid. In the intestines the resin participates in an ion exchange reaction and effectively pulls bile from the body. Less bile is recycled and the liver compensates by using cholesterol to produce more bile. Regular use of these resins, cholestryamine and colestipol, can result in a steady-state reduction of LDL levels by 10-25%. Because the resins are swallowed but not digested (they pass through) they can produce abdominal discomfort and interfere with absorption of drugs and nutrients.

Summary