Volume 2, Number 3: Fall Equinox, 2000

Cholesterol PART III - BC Endocrine Research Foundation

Dr. Eric G. Norman PhD

Staff Member with the Division of Endocrinology University of British Columbia, Vancouver, B.C.

Lowering Plasma Lipid Levels Using Medications

In Part II of this series we discussed improving your diet and exercise regimen and giving up smoking as ways to improve your plasma lipid profile (cholesterol). Unfortunately, not everyone responds to, or is capable of, these lifestyle modifications and as a result lipid lowering medications are often recommended by physicians. Here in Part III of this series we will consider a number of the cholesterol lowering medications currently available. These include HMG-CoA reductase inhibitors (statins), bile acid sequestrants (resins), nicotinic acid (niacin), fibric acid derivatives (fibrates) and Probucol (anti-oxidants). You can think of each one of these as a family, each family working in its own particular way to alter the plasma lipid profile, and each family having several members who vary in their relative tolerance and efficacy.

HMG-CoA Reductase Inhibitors (statins)

The enzyme HMG-CoA reductase is a key enzyme in the synthesis of cholesterol. There are a number of compounds that have been developed to block this point in the pathway thereby reducing plasma cholesterol. These include lovastatin, simvastatin, fluvastatin (Lescol), cerivastatin (Baycol), atorvastatin (Lipitor). Collectively these are referred to as “statins” (a term used in the media) and they are capable of reducing total cholesterol by as much as 30% and low-density lipoprotein (LDL) cholesterol levels by as much as 40%. They often reduce triglycerides (TG) by as much as 20% and increase high density lipoproteins (HDL) by 5-10%. These medications are most effective when taken at night as this is when maximal cholesterol biosynthesis occurs. These medications are well tolerated and the main significant side effect is myopathy (muscle aches). This risk is increased when these medications are taken in combination with niacin, gemfibrozil, erythromycin or cyclosporine. Liver enzyme function should be monitored if taking combinations of medications. Long term side effects of these inhibitors are not known although lovastatin, which has been in use for over ten years has no observed long term toxicities.

Bile Acid Sequestrants (resins)

These are anion-exchange resins that exchange chloride for negatively charged bile acids. The bile acids, bound to the resin, are then excreted with the feces. This results in stimulated oxidation of cholesterol to replace the bile acids, an increase in LDL receptors in the liver and eventually a lowering of plasma LDL concentrations. This is very similar to the principal of dietary fibre and its mode of action in reducing cholesterol discussed in Part II of this series. Most of the side effects of resins are localized in the gastrointestinal tract and include bloating, gas and constipation. They can potentially lower plasma cholesterol by 15-25%. Two main points of caution. They are not recommended for people with high triglycerides since they have been known to increase plasma triglyceride levels. Secondly, these resins can also bind certain medications such as levothyroxin, digoxin, warfarin, and thiazide diuretics. For this reason the resins should be taken 4 hours before or 1 hour after other medications.

Nicotinic Acid (niacin)

Niacin is a B vitamin and one of the cheapest drugs used to treat hyperlipidemia. Taken at therapeutic doses (2.0-4.5 grams per day) niacin can lower total and LDL cholesterol by 15-30%, lower triglycerides by 30-40%, and raise HDL by 15-25%. Two points worth clarifying here. We are referring to niacin, not niacinamide, which has no efficacy. Secondly the doses of niacin used are very high, 20-50 times higher than the usual nutritional supplement amounts. As a therapy niacin is well tolerated. The main side effect is a flushing of the skin (redness) that occurs shortly after taking the niacin. This can be reduced by starting therapy at a low dose (eg. 100 mg) and gradually increasing the daily dose over a period of weeks to months, as a tolerance is built up. Taking an aspirin I hour before the niacin can also reduce the flushing. A more serious side effect of niacin therapy can be liver toxicity and therapy should be accompanied by liver function tests. A slow-release form of niacin is available that reduces the flushing side-effect but unfortunately liver toxicity is more common with this form and therefore the immediate-releaseform is preferred.

Niacin can worsen glucose intolerance and therefore its use by diabetics is questionable. In addition it is not recommended for people with a history of gout or an active peptic ulcer.

Fibric Acid Derivatives (fibrates)

This class of medications which includes clofibrate, fenofibrate and gemfibrozil have been shown to lower plasma triglycerides by as much as 40% and to increase HDL levels by about 10%. Typically they are well tolerated. Minor side-effects include gastrointestinal discomfort and a possible increase in the incidence of gallstones. One note of caution is the use of fibrates in the case of renal insufficiency due to increased myopathy in this setting.

Antioxidants

Commonly used antioxidant food supplements such as vitamin E and C are believed to have benefits with regards to prevention of heart disease but there is a lack of scientific evidence to back this up. Most of the large well-designed trials have shown in fact that these supplements have no effect on plasma lipids and the progression of heart disease or rates of death. It doesn’t mean that they don’t benefit some other aspect of your health, simply that the available evidence suggests that lower plasma lipids and heart disease prevention is not one of their benefits.

Fish Oil Supplementation

Fish are an excellent source of the omega-3 polyunsaturated fatty acids and high dosages of fish oil (4 or more grams per day) can dramatically reduce plasma triglycerides. This benefit appears to be sustainable as long as the dosages are continued. Keep in mind this is very different from simply eating fish. Comparable to what we discussed about niacin therapy vs niacin in our regular diet, in terms of doses fish oil supplementation should be considered a medical therapy and should only be done under physician guidance. It is typically used only for patients with very high triglycerides and is not generally recommended. When it is used it has been shown to reduce triglycerides by 39% and increase HDL by 6% although benefits with regards to coronary heart disease have not been established.

Summary

The use of any of these medications is not a trivial matter. They should only be used under a physician’s supervision and absolutely should not be used to compensate for an unhealthy lifestyle. Even when using these medications you should always be optimizing your diet and exercise habits.

Eric Norman is a research scientist investigating heart disease in post-menopausal women and in individuals with type II diabetes.

References

  1. Manual of Lipid Disorders. Reducing the risk for coronary heart disease. Antonio M. Gotta Jr.; Henry J. Pownall. Second Edition. Publisher: Williams and Wilkins. 1999.
  2. Disorders of Lipid Metabolism. Chapter 23. Mahley, R.W.; Weisgraber, K.H.; Farese, R.V. in Williams Textbook of Endocrinology, Ninth Edition. Editors: Wilson,J.D.; Foster, D.W.; Kronenberg,H.M.; Larsen,P.R.. Publisher: W.B. Saunders Company. 1998.
  3. Advanced Nutritional Therapy. Cooper, K.H.(M.D., M.P.H.). Thomas Nelson Publishers. 1996.
  4. 8 Steps To A Healthy Heart. Kowalski, R.E. Warner Books Inc. 1992.

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