For cholesterols of over 200 mg/dl, cholesterol lowering medication is probably indicated.  The new guidelines from the National Cholesterol Education Program recommend lowering LDL cholesterol to below 70 mg/dL only for patients at very high risk for coronary heart disease and to below 100 mg/dL for those at moderately high risk.  

A growing body of studies shows that aggressively lowering the LDL cholesterol of heart attack victims to quite low levels decreases their future risk of illness and death.  How to best go about doing this is unclear, but the statin family of medicines in high doses can achieve this.  They have been heavily researched, in part since there are huge profits to be gained from these patent-protected medications.  Lipitor is the #1 best selling medication in the U.S., making its manufacturer billions of dollars every year.  While statins are valuable for heart attack victims, it is their very high cost does not justify their use in patients who have not suffered any ill effects from their elevated cholesterol.  Low cost alternatives are available and may be as good or better.

The least expensive way to lower cholesterol is to use policosanol ($3-7/month: see Policosanol), which costs one-twentieth as much as the statins and is available over-the-counter.  It also has virtually no side-effects, while the statins (Lipitor, Zocor, Provachol, Crestor, Leschol, Mevacor; $56-$252: see Statins) cause at least some uncomfortable side-effects (muscle aches, diarrhea, rash, constipation, gas, abdominal pain) with rare cases of serious kidney failure and death.  So far, research on policosanol looks very good, but it is all from Cuba and needs to be replicated outside of Cuba.  Fiber supplements BiosLife and psyllium may also help, although the research is more limited.

The best deal in statins appears to be the new Vytorin, which combines simvastatin (Zocor) and ezetimibe (Zetia) into one pill for $84/month regardless of the simvastatin dosage (myopathy is a problem primarily for simvastatin 80 mg/d, the highest dose).

If you have to pay for your own statin medication and don't want to use policosanol, the cheapest way to buy a statin is to buy red yeast.  This is a Chinese coloring which contains lovastatin (Mevacor).  Of course, it will have the same side-effects as lovastatin.  For patients with low levels of HDL good cholesterol despite policosanol and a healthy diet with exercise, adding niacin ($4-$15: see Niacin) to policosanol appears a likely helpful strategy, but this is best done under the care of an educated physician.  Niacin can also be used by itself.

Ezetimibe (Zetia; $79: see below) is a new cholesterol absorption inhibitor with few side-effects and lowers bad LDL cholesterol (Zetia can cause diarrhea).  Colesevelam (WelChol; $159: see below) forms nonabsorbable complexes with bile acids in the gastrointestinal tract, resulting in changes in plasma lipid levels, including decreases in total, and bad LDL cholesterol.  Neither is as well researched as policosanol, i.e. no long-term studies showing benefits, and neither has as strong an impact of LDL and HDL cholesterol.

I haven't figured out whether its cost-effective to be measuring cholesterol and lipid profiles ($55) repeatedly.  With policosanol just $36 per year at 5 mg/day (1/2 tab), testing can be a significant part of the expense.  Probably, testing every 3-5 years is more cost-effective for most people.

Following my Healthy Living recommendations is much more certain to increase life at a much lower cost than the very high cost of the statins for primary prevention.  However, for secondary prevention (e.g. after a heart attack), aggressive cholesterol lowering therapy is definitely beneficial and worth the expense, although policosanol may do just as well or better.  While the statins are currently being promoted for osteoporosis and Alzheimer's disease as well, the research evidence is not at all clear that there is any benefit and there are much less expensive and better proven ways of achieving those goals (vitamins D and K for both men and women and for women only added calcium). 

Lowering Bad LDL Cholesterol Further is Better; Four Studies: The 2-year DB PROVE IT study —  of 4,162 acute coronary syndrome patients with an LDL cholesterol average of 106 mg/dL found pravastatin ( Pravachol) 40 mg daily lowered LDL to 95 with 26% suffering more cardiovascular difficulty (death, myocardial infarction, unstable angina pectoris requiring hospitalization, revascularization and stroke) vs. atorvastatin ( Lipitor) 80 mg daily. with an LDL lowered further to 62 and 22% experiencing difficulty. CP Cannon et al, N Engl J Med 2004; 350:1495. Two other trials also compared atorvastatin 80 mg with pravastatin 40 mg daily. The REVERSAL study, a DB of 502 patients with obstructions in coronary arteries, found that after 18 months, mean LDL cholesterol concentrations were 79 mg/dL with atorvastatin and 110 mg/dL with pravastatin, and there was less progression of atherosclerosis with atorvastatin. SE Nissen et al, JAMA 2004; 291:1071. The ARBITER study used ultrasound to measure carotid intima-media thickness in patients who met criteria for lipid-lowering therapy; after 1 year, mean LDL cholesterol was 76 mg/dL with atorvastatin and 110 mg/dL with pravastatin. There was more regression of atherosclerosis with atorvastatin. AJ Taylor et al, Circulation 2002; 106:2055. In the large 5-year HPS study of patients at high risk for death from coronary heart disease including 3421 with a mean baseline LDL cholesterol below 100 mg/dL, in this sub-group, simvastatin (Zocor) 40 mg/d lowered mean LDL cholesterol to 65 mg/dL and reduced the incidence of a first major vascular event by 22% compared to placebo (Heart Protection Study Collaborative Group, Lancet 2002; 360:7). Ed: Atorvastatin (Lipitor) 80 mg/day is less expensive than the alternative simvastatin (Zocor) ($101 vs. $132). These are the two recommended for the most powerful decrease in LDL. Rosuvastatin (Crestor) is less expensive ($72), but newer with controversial side-effects.  However, policosanol may be as good or better.  Someday, research might be funded.

Very Low LDL Healthy: Patients with heterozygous familial hypobetalipoproteinemia, who have mean LDL cholesterol concentrations <50 mg/dL, have no symptoms and live on average 10 years longer than the general population, suggesting that intensive cholesterol-lowering therapy may not have adverse effects due to low LDL concentrations. 

Low Cholesterol Associated with Slower Visualmotor speed: In a study of 4110 adults ages 20-59 from the third National Health and Nutrition Examination Survey, after adjustment for sociodemographic variables, serum trace elements and vitamins, dietary energy intake, and risk factors for cardiovascular disease, low serum total cholesterol and non-HDL cholesterol were associated with slow visuomotor speed in young and middle-aged men. Zhang J, et al. University of South Carolina, Columbia, SC. Am J Clin Nutr. 2004 Aug;80(2):291-8.

Low Cholesterol Associated with Slightly Poorer Memory: In a study of 326 women in the Melbourne Women's Midlife Health Project ages 52-63, there was a small but significant association between current low density lipoprotein cholesterol (LDL-C) concentrations and memory. Better memory was associated with positive changes in TC and LDL-C based on lipid measurements three years, but not six years, earlier. Memory performance was lowest among women in the lowest quartile of current LDL-C values and among women whose LDL-C levels declined over the previous three years. High density lipoprotein cholesterol (HDL-C) and triglyceride concentrations were unassociated with memory. Lipid measures and self-rated mood were unrelated. Serum lipids and memory in a population based cohort of middle age women.  Henderson VW, Guthrie JR, Dennerstein L. University of Arkansas. J Neurol Neurosurg Psychiatry. 2003 Nov;74(11):1530-5. Similar findings from the Framingham study. There are cases of poorer memory linked to starting a statin cholesterol medication although these appear rare. Pharmacotherapy. 2003 Jul;23(7):871-80.

Increasing Good HDL Cholesterol Important, Too: For every 1-mg/dL increase in HDL, the risk of cardiovascular events decreases by 2% to 3%. HDL mediates reverse cholesterol transport and has antioxidant, antiinflammatory, and antithrombotic effects on the vasculature. HDL enhances nitric oxide production and improved endothelium-dependent relaxation. The National Cholesterol Education Program Adult Treatment Panel guidelines encourage more aggressive screening and treatment of lipid abnormalities. High-density lipoprotein cholesterol and coronary heart disease. Young CE, Karas RH, Kuvin JT.Tufts University. Cardiol Rev. 2004 Mar-Apr;12(2):107-19. Ed: This increase can be best accomplished by exercise, and policosanol. Niacin can also be of value, although there is no research combining policosanol and niacin. Up to one alcoholic drink per day, cautiously avoiding any addictive urge to increase beyond this, can also increase HDL and protect the heart.  Again, no research exists showing whether alcohol adds any additional benefit to policosanol, although alcohol has high risks of violence, abuse, and addition. 

Low Cholesterol Bad in the Very Old: In a 3-year follow-up of 2277 non-demented Medicare recipients, average age 76, living in northern Manhattan, patients in the lowest fourth of total cholesterol, non-high density lipoprotein cholesterol, and low density lipoprotein cholesterol were almost twice as likely to die as those in the highest fourth, after adjustment for other risk factors. In elderly people, low cholesterol levels are significantly associated with higher mortality. This association could reflect frailty, malnutrition, or subclinical disease. Schupf N, Costa R, et al. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc 2005;53: 219-26

Other Non-Prescription Approaches

Psyllium and Oat Bran Cookies Lower: A Mexican study of sedentary normal (cholesterol <200mg/dL) and hypercholesterolemic (>220) found in 8-weeks 4 ounces (100mg) of cookies with 1.3 or 2.6 g/day of psyllium or oat bran lower LDL cholesterol by 22% and 26%. J Am Coll Nutr 17:601-8, ’98. After psyllium supplementation, the percentage change in postprandial glucose in type 2 diabetes patients, ranged from -12.2 to -20.2%. In hypercholesterolemic children, the effect of psyllium in LDL-cholesterol serum concentrations ranged from 2.78 to -22.8%; the effect in HDL-cholesterol from -4.16 to 3.05%; and the effect on triglycerides from 8.49 to -19.54%. J Physiol Biochem. 2003 Sep;59(3):235-42. Ed: While oats lower cholesterol, it appears unlikely that they increase longevity.

Over-the-Counter BiosLife Fiber Worked for Cholesterol in Small Study: In a 90-day DB PC manufacturer study of 78 type 2 diabetics, participants received 10g to 15g of BiosLife 2, an over-the-counter fiber supplement manufactured by Unicity International. The drink contains both soluble and insoluble fiber from guar gum, gum arabic, locust bean gum, pectin and oat fiber dispersed in calcium carbonate. It was administered in 5-gram doses two to three times daily 5 to 10 minutes before eating. The manufacturer claims the fiber decreases reabsorption of cholesterol from a meal. Total cholesterol had dropped from 215 mg/dL to 184 mg/dL, 14.4%. Triglycerides decreased 14% from 299 mg/dL to 257 mg/dL. LDL decreased 28.7% from 129 mg/dL to 92 mg/dL. HDL rose 21.8% from 43 mg/dL to 55 mg/dL. Amer. Heart Assoc. Convention. Washington DC. 4/30/05.

Vegetarian Diet As Good As Lovastatin (Mevacor): University of Toronto David Jenkins in a JAMA 7/23/03 study of 46 high cholesterol patients randomly assigned that to 1 month of a regular low saturated fat diet with lovastatin or special diet combined nuts (almonds), soy proteins, viscous fiber (high-fiber) foods such as oats and barley and a special margarine with plant sterols (found in leafy green vegetables and vegetable oils) or control. Lovastatin 30% decrease LDL vs. 29% decrease with diet.

Red Yeast Lowers Cholesterol: Red yeast is used to color Peking duck, a favorite Chinese dish. The Chinese have long thought that red yeast helps heart. A study did find that 9.6 mg/day and 13.5 mg/day of the active compounds decreased cholesterol by 26% and 18% in a Chinese and in a U.S. multicenter study of patients with cholesterols of 225 and 242. The long-term effect of the red yeast not known. Sci News 4/17/99.  Red yeast contains lovastatin, so it would have the same side-effects. 

Other Lipid Lowering Meds:

Colesevelam (WelChol; $159/month) Reduces Bad Cholesterol: Colesevelam forms nonabsorbable complexes with bile acids in the gastrointestinal (GI) tract, resulting in changes in plasma lipid levels, including total, LDL, and high-density-lipoprotein cholesterol and triglycerides. It is four to six times as potent as traditional bile acid sequestrants (BASs), perhaps because of its greater binding affinity for glycocholic acid. Unlike cholestyramine and colestipol, colesevelam appears to reduce LDL cholesterol in a dose-dependent manner. Efficacy either alone or in combination with HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia. Combination therapy is more effective. Side-effects do not differ significantly from those occurring with placebo. The constipation that typically hinders compliance with traditional BASs is minimal. Compliance was 93%. No interactions. Three 625-mg tablets twice daily or six tablets once daily, with meals. Colesevelam hydrochloride. Steinmetz KL. U Pitt. Am J Health Syst Pharm 2002 May 15;59(10):932-; HDL increased 3% in 24 week 494 patient study with 20% decrease LDL and 10% decrease cholesterol on 4.5g/d. Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial. Insull W Jr, Toth P, Mullican W, Hunninghake D, Burke S, Donovan JM, Davidson MH. Mayo Clin Proc 2001 Oct;76(10):971-82

Colesevelam + Low Dose Atorvastatin = High Dose: 38% with 40 mg/d dose, 48% lower LDL with combo (3.8 g/d) and 53% with 80 mg/d dose. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Hunninghake D, Insull W Jr, Toth P, Davidson D, Donovan JM, Burke SK. Atherosclerosis 2001 Oct;158(2):407-16

Ezetimibe (Zetia; $79/month), a New Cholesterol Absorption Inhibitor, Helps Lower Bad Cholesterol: In a 887-patient 12-week DB PC study of simvastatin with or without ezetimibe 10 mg/day, the combination was considerably more effective than simvastatin alone is lowering LDL-cholesterol without any added side-effect frequency. Triglycerides and apolipoprotein B were also lower. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB; Ezetimibe Study Group. Washington University. Mayo Clin Proc. 2004 May;79(5):620-9

Ezetimibe (Zetia) Lowers LDL Cholesterol: In adults, ezetimibe 10 mg/day reduced intestinal cholesterol absorption by 54% in association with a compensatory increase in endogenous cholesterol synthesis. Within 2 weeks, ezetimibe produced a 17% to 20% reduction in low-density lipoprotein cholesterol (LDL-C); in combination with statins, ezetimibe produced a reduction in LDL-C of up to 40%. Ezetimibe appears to be well tolerated, with a safety profile similar to that of placebo. Trials have lasted no longer than 12 weeks; the long-term effect of ezetimibe on cardiovascular morbidity and mortality remains to be determined. Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Jeu L, Cheng JW. Veterans Affairs Medical Center, Bronx. Clin Ther. 2003 Sep;25(9):2352-87. Ed: Policosanol does better but much less money and has long-term studies showing clear benefit on disease.  

Lipid Lowering Effective in Clinical Setting: A VA study by Hanna Bloomfield Rubins of 16,470 patients with coronary heart disease treated between 1994 and 1996. During follow-up until the end of 2000, 43% were treated with niacin, bile acid binding resin, statins or gemfibrozil for at least 30 days. 51% of those not prescribed lipid-lowering medication had died, compared with 18% in those treated. Treated patients survived an average 15 months longer than their counterparts. Patients with the highest baseline cholesterol levels benefited the most from treatment. After adjusting for age, baseline cholesterol levels and other confounders, the hazard ratio associated with treatment was 0.76 (p < 0.0001). There was a a 39% reduction in mortality in patients 76 years old or older. Am J Cardiol 2003;92:1177-1182.

Measuring Cholesterol Every Visit with Rapid Test Increases Compliance: Normally, 50% of patients after one year drop off statins. Only 11% with standard care achieve goal of within 10% of the standard recommended LDL goal. However, with measurement program 93% maintained that level after one year. U Ill, Stephen Devries.

Squalene and Pravastatin Better than Pravastatin Alone: A small DB study of 105 Patients found pravastin better than squalene at lowering total cholesterol and LDL and TG and increasing HDL but that the combination was better than either alone. Taiwan. : J Clin Pharmacol 1996 May;36(5):422-7. Squalene is a precursor of cholesterol. Squalene blood levels can be measured. The presence of coronary artery disease (CAD) in postmenopausal women is independently associated with altered cholesterol metabolism, as reflected by low synthesis and inefficient elimination of cholesterol. Squalene levels were high as was squalene to cholesterol ratio in those with CAD. Squalene is an edible oil obtained primarily from fish but also found in amaranth (3-6%). Inhibition of squalene synthetase is being researched to decrease cholesterol.  Arterioscler Thromb Vasc Biol 2001 Oct;21(10):1650-5. Shark liver oil toxicity is similar to polar bear liver disease with hypervitaminosis A and headaches and desquamation of skin sometimes with fever and blistering and dizziness. It can also cause a lipoid pneumonia. 34 cases have been reported in two studies due to squalene aspiration from shark liver oil. Six had taken shark liver oil by nose. It has been used for 40 years to prevent cancer radiation toxicity and to treat leukemia via stimulation of macrophages. Ed: I am not impressed by squalene.

Fibrates

Fibrates: Used for hypertriglyceridemia, but worthless. No effect on total mortality (Ericsson, Lancet 347:849 ’96; Frick, Circ 96:2137 ’97). Indeed, clofibrate (Atromid-S) incr total mortality due to CA and GI disease (Heady, Lancet 340:1405 ’92). Fenofibrate (Tricor) $62/mo, Gemfibrozil generic $11/mo, Lopid $82/mo. All potentiate oral anticoagulants.

Fenofibrate: Micronized Tricor and similar to clofibrate (Atromid-S) and gembibrozil (Lopid) are approved for hypertriglyceridemia which increased the risk of coronary heart disease. It increased HDL, some decrease in LDL and a big decrease in triglycerides, but no data on the effect on CHD. Other fibrates slow atherosclerosis and decrease CHD but have no effect mortality due to increase in cancer and GI disease. Med Let 7/3/98

Fenofibrate Adds to Simvastatin: In a DB PC study of 20 patients crossed over for 12 weeks on each of simvastatin alone or  simvastatin 10/d + fenofibrate 200/d found major increases in HDL on the combination of 23% vs. 6% with simvastatin alone. Am J Cardiol 4/15/03

Fibrate Very Small Beneficial Effect on HDL: In an Israeli DB PC study of 3,000 patients for eight years with 400mg/day of benzafibrate, 15% of the placebo group died from heart disease vs. 13.9%. While this was statistically significant, it was extremely small. HDL levels among those treated with benzafibrate rose 17%, compared with just 3% in the placebo. 4/4/03