High Cholesterol

Cholesterol is a soft waxy substance that is a natural component of the fats in the bloodstream and in all the cells of the body. While cholesterol is an essential part of a healthy body, high levels of cholesterol in the blood (known as hypercholesterolemia) increase a person's risk for cardiovascular disease, which can lead to stroke or heart attack. When there is too much cholesterol circulating in the blood, it can create sticky deposits (called plaque) along the artery walls. Plaque can eventually obstruct or even block the flow of blood to the brain, heart, and other organs. A recent report indicates that more and more Americans have high cholesterol—the condition is most common among those living in Western cultures. While heredity may be a factor for some people, increasingly sedentary lifestyles combined with diets high in saturated fats appear to be the main culprits.

The normal range for total blood cholesterol is between 140 and 200 mg per decilitre (mg/dL) of blood. Levels between 200 and 240 mg/dL indicate moderate risk, and levels surpassing 240 mg/dL indicate high risk. While total cholesterol level is important, it does not tell the whole story. There are two main types of cholesterol: low density lipoproteins (LDL) and high density lipoproteins (HDL). HDL is generally considered to be "good" cholesterol, while LDL is considered "bad." Triglycerides are a third type of fatty material found in the blood. While their role in heart disease is not entirely clear, it appears that as triglyceride levels rise, levels of "good" cholesterol fall. It is the complex interaction of these three types of lipids that is thrown off when a person has hypercholesterolemia. High cholesterol is characterized by elevated levels of LDL cholesterol, normal or low levels of HDL cholesterol, and normal or elevated levels of triglycerides.

Signs and Symptoms

In its preliminary stages, high cholesterol generally occurs without any symptoms. For this reason, screening through routine blood tests is crucial for early detection. In its advanced state, however, high cholesterol may result in any of the following:

Causes

In some cases, abnormally high cholesterol may be related to an inherited disorder. Certain genetic causes of abnormal cholesterol and triglycerides, known as hereditary hyperlipidemias, are often very difficult to treat. High cholesterol or triglycerides can also be associated with other diseases a person may have, such as diabetes. In most cases, however, elevated cholesterol levels are associated with an overly fatty diet coupled with an inactive lifestyle. It is also more common in those who are obese, a condition that has now reached epidemic proportions in the United States, affecting as much as half of the adult population.

Causes of high total and LDL cholesterol levels include: Causes of low HDL cholesterol include: Causes of high triglyceride levels include:

Risk Factors

There are certain factors that put a person at increased risk of having high cholesterol. While some factors cannot be altered by changes in lifestyle, many can be changed. The most important risk factors for high cholesterol are:

Diagnosis

Since most people have few if any symptoms of hypercholesterolemia (another term for high cholesterol), blood screening is very important. An initial blood test is done to check a "random" measurement of total and HDL cholesterols, meaning that the test is performed at any time during the day, regardless of what has been eaten. Those with abnormal levels (total cholesterol more than 200 mg/dL or HDL less than 40 mg/dL), will go on to have a test called fasting lipid profile (in which the person being tested refrains from eating for 8 to 12 hours, usually overnight, prior to the test). The fasting test will indicate whether or not total cholesterol levels fall within the normal range (between 140 and 200 mg/dL), are moderately high (between 200 and 240 mg/dL), or if they are in the very high range (240 mg/dL or greater). This blood test also reveals the levels of LDL, HDL, and triglycerides. According to guidelines released by the National Cholesterol Education Program (NCEP), the optimal level for LDL cholesterol depends on whether you have heart disease or not and whether there are other risk factors present for heart disease (such as diabetes and high blood pressure). The optimal level for HDL for all people (healthy or otherwise) is a measurement higher than 60 mg/dL; low levels are 40 mg/dL and below.

Adults with normal total and HDL cholesterol levels should have their cholesterol checked every 5 years. Those being treated for hypercholesterolemia should have their cholesterol levels measured every 2 to 6 months and have liver function tests as well if they are on cholesterol-lowering medication.

Preventive Care

Changing eating habits is key in preventing high cholesterol. Other lifestyle changes that can reduce the risk of developing high cholesterol and cardiovascular disease include maintaining a normal weight and increasing physical activity. Diet
The best ways to lower cholesterol through diet include the following: There are a number of diets designed to keep cholesterol levels in check including the American Heart Association (AHA) diet, the Mediterranean diet, and the Ornish diet. While these three diets vary in some ways, they all emphasize whole grains and include fiber, fresh fruits and vegetables, lean protein, particularly soy and fish, and avoidance of saturated fats and trans fatty acids. These diets are outlined below.

The AHA Step I Diet is considered appropriate for the general population, including those who have normal cholesterol levels and want to prevent the development of high cholesterol. This diet calls for up to 55% of daily calories from carbohydrates, 15% from protein, and no more than 30% from fat. The diet also outlines quite specific of types of fat and the proportions to include: This diet also specifies the level of calories that helps people achieve and maintain a healthy weight, and it is ideal for those who currently include a lot of fat in their diets and have not previously attempted to lower their cholesterol levels through dietary changes.

The AHA Step II Diet is designed for patients who require greater LDL lowering, and includes the Step I guidelines (above) with two modifications: The Mediterranean Diet is comprised of whole grains, fresh fruits and vegetables, fish, olive oil, garlic, and moderate, daily consumption of red wine. Although this diet is not low in fat, it is high in monounsaturated fatty acids and has been shown to increase HDL cholesterol levels and to inhibit the process whereby LDL cholesterol adheres to artery walls. One large, well-designed study found that people who had had at least one heart attack were between 50% and 70% less likely to suffer a another heart attack if they followed the Mediterranean diet. This diet puts a great emphasis on bread, root and green vegetables, and the daily consumption of fruit, fish, and poultry. Only olive and rapeseed (canola) oils are used in this eating plan and margarine (with alpha-linolenic acid) is used instead of butter. Eating beef and lamb is discouraged. This diet is naturally rich in fiber, antioxidants, and omega-3 fatty acids. It contains the same amount of protein as the AHA diet, but the source of protein is primarily fish. The Mediterranean diet has less carbohydrates than the AHA or Ornish diets, but places the same emphasis on consuming fruits, vegetables, nuts, legumes, and beans.

The Ornish Diet is a completely vegetarian diet that has been shown to dramatically reduce cholesterol levels and to actually reverse the risk of heart disease. No oils or animal products are allowed in the Ornish diet, except nonfat dairy products and egg whites. In this diet, total fat is limited to 10% of daily calories, saturated fats are significantly limited, and carbohydrates generally make up 75% of calories. Complex carbohydrates from whole grains and other high-fiber foods and from fresh fruits and vegetables are emphasized.

Weight Reduction
Being overweight increases risk of high cholesterol and heart disease. Even small degrees of weight loss can make nutritional changes more effective in lowering LDL—a 5 to 10 pound weight loss can double the LDL reduction achieved by dietary adjustment alone. Weight loss is often accompanied by lowered triglycerides and increased HDL levels as well. The goal for weight loss should be a realistic one, rather than a rapid or dramatic loss. Very low calorie diets (500 to 800 calories) can be dangerous and are not recommended. A reasonable caloric restriction is considered a reduction of 250 to 500 calories per day in the usual diet aimed at achieving a gradual, weekly weight loss of one-half to one pound.

Physical Activity
Regular physical activity by itself both reduces the risk of death from heart disease and enhances the effects of diet on LDL cholesterol levels. In a study of 377 people who were divided into four groups (aerobic exercise, the AHA Step II diet, the Step II diet plus exercise, or no intervention), those who only made dietary changes did not show reduced LDL while the group on the Step II diet plus exercise had a significant reduction in LDL cholesterol. Moderate exercise three to five times per week (the equivalent of walking 7 to 14 miles per week) can help promote weight loss in overweight individuals, reduce LDL and triglyceride levels, and produce favorable levels of HDL. Exercise may also lower blood pressure. For these reasons, everyone with risk factors for heart disease should consider starting a program of regular, aerobic physical activity, individualized to suit physical fitness level, heart health, and exercise preferences.

Treatment Approach

The main goal of treatment is to reduce the risk of cardiovascular diseases, such as heart disease and stroke, by lowering blood cholesterol levels. Studies have shown that for every 1% reduction in cholesterol levels there is a 2% reduction in the rate of heart disease. People who benefit most from lowering their cholesterol are those who already have heart disease or who have multiple risk factors for the disease. In addition to lifestyle changes, specific cholesterol-lowering medications are often prescribed.

Changes in lifestyle are the most effective means of both preventing and, in less severe cases, treating elevated LDL cholesterol levels. The cornerstone of this treatment strategy is dietary modification and exercise. In addition to little fat and cholesterol, lean protein (such as soy and fish), and lots of fruits and vegetables, diets should include: In addition, herbs and supplements may help lower cholesterol levels. The most promising include:

Lifestyle

The following changes in life habits have been shown to both prevent high cholesterol and to lower high levels of cholesterol and triglyceride:

Medications

According to the National Cholesterol Education Program (NCEP) guidelines, healthcare practitioners should prescribe cholesterol-lowering medication when: The following are commonly prescribed medications for high cholesterol:

Nutrition and Dietary Supplements

There is considerable evidence that dietary antioxidants, particularly vitamin E, as well as folic acid, fiber, and soy can help to prevent the development of heart disease. Substances that have shown promise in lowering cholesterol specifically or that have demonstrated benefit in preventing heart disease in people with high cholesterol are discussed below.

Fiber and Fiber Sources
The American Heart Association (AHA) recommends increased intake of dietary fiber in the form of whole grains, vegetables, fruits, legumes, and nuts because they have been shown to do the following: Soluble fibers such as those in psyllium husk, guar gum, and oat bran have a cholesterol-lowering effect when added to a low-fat, cholesterol-lowering diet. Studies have shown psyllium, in particular, to be quite effective in lowering total as well as LDL cholesterol levels. Oat bran (3 g per day) has also been shown to lower total cholesterol. Soy
Many studies have shown that replacing some animal protein with soy protein in the diet results in lower blood cholesterol levels, especially when soy is consumed as part of a general low-fat diet. One study has shown that as little as 20 g of soy protein per day is effective in reducing total cholesterol, but that 40 to 50 g shows faster effects (in 3 weeks instead of 6). This evidence suggests that soy protein should be included in a healthy diet. In fact, since October of 1999, the FDA has allowed the labels of foods containing 6.25 g or more of soy protein to carry the claim that these foods reduce the risk of heart disease. Moreover, the AHA recommends that people with elevated total and LDL cholesterol add soy to their daily diet. Ethanol-washed soy preparations should be avoided because this procedure causes the soy to lose its isoflavones (the substances likely responsible for its cholesterol-lowering effects) in the process.

Omega-3 fatty Acids

EPA and DHA

Numerous studies have reported the benefits of consuming fish oils, rich in the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), at doses ranging from 850 mg to 4 g per day for those with heart disease. Supplementation with DHA, for example, has been shown to reduce triglycerides and LDL levels and raise HDL levels.

Alpha-Linolenic Acid
Walnuts are one of the best sources of the omega-3 fatty acid alpha-linolenic acid. Replacing a major portion (35%) of the monounsaturated fat in the Mediterranean diet with walnuts appears to significantly improve cholesterol and triglyceride levels in people with high cholesterol. Almonds, although not as well studied as walnuts, appear to have similar effects when used as a substitute for a portion of monounsaturated fats in low-fat diets.

Vitamin E
A number of studies conducted over the last 10 years have reported beneficial results from the use of vitamin E supplements for the treatment and prevention of heart disease including for those with elevated cholesterol levels.

Vitamin C
Preliminary evidence suggests that vitamin C (3 glasses of orange juice per day or up to 3 g per day as a supplement) may help decrease total and LDL cholesterol and triglycerides, and increase HDL levels.

Coenzyme Q10 (CoQ10)
Coenzyme Q10 (CoQ10), also known as ubiquinone, is an antioxidant that is essential for energy production. Levels of CoQ10 have been found to be lower in people with high cholesterol when they were compared to healthy individuals of the same age. Furthermore, when person with high cholesterol take statin drugs, CoQ10 levels appear to decline in direct proportion to the level of decrease in cholesterol. This is particularly important to bear this in mind when statin drugs are used for long periods of time. Taking CoQ10 supplements, however, can correct the deficiency caused by statin medications without affecting the medication's positive effects on cholesterol levels.

Folic Acid (Vitamin B9)
High blood levels of homocysteine (an amino acid produced by the body) have been shown to increase the risk of heart attacks. Evidence suggests that high homocysteine levels are also related to low folate levels. This means that an adequate supply of folate and other B vitamins may be important, particularly for those with heart disease.

Plant Sterols
Plant sterols (fats present in fruits, vegetables, seeds, and nuts) appear to interfere with the absorption of cholesterol, thereby lowering the level of cholesterol in the blood. A daily intake of 1.6 g of margarine containing plant sterols has been shown to reduce total and LDL cholesterol, with larger intakes not necessarily providing any additional benefit. Questions have been raised, however, regarding the possibility that plant sterols interfere with the absorption of certain antioxidants such as alpha- and beta-carotenes, alpha-tocopherol, and lycopene. While the significance of this is still unclear, it warrants further investigation, and these micronutrients must be carefully monitored in the blood of those using plant sterols.

L-Carnitine
L-carnitine is produced in the liver and kidneys from the amino acids lysine and methionine. It is stored in skeletal muscles and the heart and may be beneficial in treating conditions such as chest pain, heart attack, heart failure, diabetes, and abnormal cholesterol. In several human studies, supplementation with 2 to 3 g per day of L-carnitine led to a significant reduction in total cholesterol and triglycerides, and to increases in HDL cholesterol levels.

Red wine
Red wine contains flavonoids, which inhibit LDL oxidation (the process whereby LDL cholesterol adheres to artery walls). Studies have demonstrated a relationship between flavonoid consumption (from food) and reduced risk of death from coronary heart disease.

Although nonalcoholic grape products contain flavonoids, red wine contains much higher concentrations of flavonoids. However, the use of alcohol is not advocated by the AHA and other organizations because of the potential for addiction and the other serious repercussions such as motor vehicle accidents and the development of hypertension, liver disease, breast cancer, weight gain. If red wine is consumed, it is recommended that men have no more than 2 glasses (20 g ethanol) per day and women, no more than 1 glass (15 g ethanol).

Red Yeast Rice
Red yeast rice, the fermented product of rice and red yeast, has been used in China since at least 800 AD to make wine and preserve food, and for its medicinal properties, which are believed to include, among other things, improvement in blood circulation. Recent well-designed studies have shown that red yeast rice significantly reduces total cholesterol, LDL cholesterol, and triglyceride concentrations.

Chromium
Brewer's yeast is an important source of chromium. Ninety percent of Americans are deficient in this important mineral. Chromium has demonstrated the ability to lower LDL levels in the blood and raise HDL levels.

Calcium
Preliminary studies in animals and people suggest that calcium supplements, in the range of 1,500 to 2,000 mg per day, may help to lower cholesterol. The information available thus far suggests that keeping cholesterol levels normal or even low by using calcium supplements (along with many other measures such as changing your diet and exercising) is likely to be more beneficial than trying to treat it by adding calcium once you already have elevated cholesterol. More research in this area is needed.

Vitamin B5 (Pantothenic Acid)
Research has shown that vitamin B5 lowers cholesterol. Studies are currently underway to determine if this vitamin helps prevent heart disease.

Herbs

Hawthorn (Crataegus oxyacantha and monogyna)
The flowers and berries of the hawthorn plant have been used in traditional herbal and homeopathic remedies to protect against stroke and to treat chest pain, irregular heartbeat, and heart failure. In addition, studies using rats suggest that the tincture of Crataegus (made from the berries) may be a powerful agent for the removal of LDL from the blood stream. The tincture of hawthorn berries also reduced the production of cholesterol in the liver of rats who were being fed a high-cholesterol diet. Studies to determine if hawthorn will confer the same effects in humans are needed.

Green Tea (Camellia sinensis)
Green tea has been observed to have a variety of beneficial effects, including anticancer and antioxidant effects. The tea has also demonstrated an ability to lower total cholesterol and raise HDL cholesterol in both animals and people. Although an animal study conducted to determine how green tea effects these changes was not conclusive, results from the study suggest that the catechins in green tea may block intestinal absorption of cholesterol and promote its excretion from the body.

Garlic (Allium sativum)
Long hailed for its beneficial effects, a number of studies have found that garlic reduces elevated total cholesterol levels more effectively than placebo. However, the size of the effect in these studies was small, and study limitations make it difficult to draw any firm conclusions. More research with better-designed studies is warranted in order to assess the safety and effectiveness of garlic and to determine the most appropriate dose and form (fresh garlic vs. supplements).

Red clover (Trifolium pratense)
Preliminary studies suggest that chemicals in red clover known as isoflavones may raise HDL levels, especially in menopausal women. Not all studies, however, have shown such positive effects. Further studies are needed before a definitive conclusion can be made.

Bilberry (Vaccinium myrtillus)
Animal studies suggest that bilberry may prevent the oxidation of LDL cholesterol, thereby lessening the risk of this bad form of cholesterol contributing to the development of atherosclerotic plaque in the arteries. Research in people is needed.

Massage and Physical Therapy

While no studies have examined the effect of massage on cholesterol levels, massage has been shown to reduce cortisol (stress-related hormone) levels and to induce relaxation. Massage may therefore have an indirect effect on risk factors that result from or are worsened by stress, such as poor eating habits and obesity, cigarette smoking, or lack of exercise. Lowering cortisol levels may also have a positive effect on cholesterol levels.

Mind/Body Medicine

Stress Reduction
Emotional and social stress increases the risk for heart disease. Stress is thought to promote hardening of the arteries and effective stress reduction techniques can help to reduce high cholesterol levels and other risk factors. In several studies of Transcendental Meditation (TM), significant reductions in total cholesterol levels as well as reductions in blood pressure, obesity, and cigarette smoking were seen after 3 to 11 months of practice. Although TM appears to be one of the more effective methods for relaxation, other methods that may be considered include:

Other Considerations

Pregnancy
Cholesterol-lowering medications should be avoided during pregnancy.

Prognosis and Complications

A number of complications may occur if high cholesterol is left untreated. These include: It is also important to note that lowering cholesterol too rapidly may contribute to the development of depression, which may be related to low levels of omega-3 fatty acids.

Maintaining an appropriate weight, eating a low-fat diet, and exercising can have a significant impact on cholesterol levels and improve long-term prognosis.

References

Ackermann RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L, Lawrence VA. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med. 2001;161:813-824.

Al-Habori M, Raman A. Antidiabetic and hypocholesterolemic effects of fenugreek. Phyto Res. 1998;12:233-242.

Anderson JW, Davidson MH, Blonde L, et al. Long-term cholesterol-lowering effects on Psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia. Am J Clin Nutr. 2000a;71:1433-1438.

Anderson JW, Allgood LD, Lawrence A, et al. Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials. Am J Clin Nutr. 2000b;71:472-479.

Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. New Engl J Med. 1995; 333:5:276-282.

Arsenian, MA. Carnitine and its derivatives in cardiovascular disease. Progr in Cardiovasc Dis. 1997;40:3:265-286.

Atorvastatin. NMIHI. Accessed at http://www.nmihi.com/a/atorvastatin.html on June 8, 2018.

Baber R, Bligh PC, Fulcher G, Lieberman D, Nery L, Moreton T. The effect of an Isoflavone dietary supplement (P-081) on serum lipids, forearm bone density & endometrial thickness in post menopausal women [abstract]. Menopause. 1999;6:326.

Binaghi P, Cellina G, Lo Cicero G, et al. Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age [in Italian]. Minerva Med. 1990;81:475-479.

Birketvedt GS, Aaseth J, Florholmen JR, Ryttig K. Long-term effect of fibre supplement and reduced energy intake on body weight and blood lipids in overweight subjects. Acta Medica. 2000;43(4):129-132.

Bonovich K, Colfer H, Davidson M, et al. A multi-center, self-controlled study of cholestin in subjects with elevated cholesterol. Paper presented at: American Heart Association 39th Annual Conference on Cardiovascular Disease Epidemiology and Prevention; March 1999; Orlando, Fla:Abstract.

Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinal) and fenugreek (Trigonella foenumgraecum) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins, Leukotrienes and Essential Fatty Acids. 1997;56(5):379-384.

Bostick RM, Fosdick L, Grandits GA, Grambsch P, Gross M, Louis TA. Effect of calcium supplementation on serum cholesterol and blood pressure. Arch Fam Med. 2000;9:31-39.

Calderon Jr. R, Schneider RH, Alexander CN, Myers HF, Nidich SI, Haney C. Stress, stress reduction and hypercholesterolemia in African Americans: a review. Ethn Dis. 1999;9:451-462.

Castillo-Richmond A, Schneider RH, Alexander CN, et al. Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans. Stroke. 2000;31:568-573.

Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ. 1997;314:112-117.

Clarkson P, Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest. 1996;97:8:1989-1994.

Cholesterol-reducing drugs. NMIHI. Accessed at http://drugs.nmihi.com/cholesterol-lowering-drugs.htm on November 9, 2018.

Cholesterol-lowering Medicines. American Academy of Family Physicians Accessed at https://familydoctor.org/ on November 9, 2018.

Davidson MH, Maki KC, Kalkowski J, Schaefer EJ, Torri SA, Drennan KB. Effects of docosahexeaenoic acid on serum lipoproteins in patients with combined hyperlipidemia. A randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 1997;16:3:236-243.

de Logeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999;99(6):779-785.

Frei B. On the role of vitamin C and other antioxidants in atherogenesis and vascular dysfunction. Proc Soc Exp Biol Med. 1999;222(3):196-204.

Ginsberg HN, Goldberg IJ. Disorders of Lipoprotein Metabolism. IN: Fauci A, et al. eds. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill; 2000: 2138-2149.

Hallikainen MA, Sarkkinen ES, Uusitupa MIJ. Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutr. 2000a;130:767-776.

Hallikainen MA, Sarkkinen ES, Gylling H, Erkkila AT, Uusitupa MIJ. Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations of hypercholesterolemic subjects on a low-fat diet. Euro J Clin Nutr. 2000b;54:715-725.

HarrisWS. Omega-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65:1645S-1654S.

Havel R. Dietary supplement or drug? The case of cholestin. Am J Clin Nutr. 1999;69(2)175-176.

Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VLW. Cholesterol-lowering effects of a proprietary Chinese red-yeast rice dietary supplement. Am J Clin Nutr. 1999;69:231-236.

High cholesterol . NMIHI. Accessed at http://www.nmihi.com/c/cholesterol.htm on June 8, 2018.

High cholesterol. NHS. Accessed at https://www.nhs.uk/ on June 7, 2018.

Hosobuchi C, Rutanassee L, Bassin SL, Wong ND. Efficacy of acacia, pectin, and guar gum-based fiber supplementation in the control of hypercholesterolemia. Nutr Res. 1999;19(5):643-649.

Howes JB, Sullivan D, Lai N. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of postmenopausal women with mild to moderate hypercholesterolemia. Atherosclerosis. 2000;152(1):143-147.

Human JA, Ubbink JB, Jerling JJ, et al. The effect of simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolemia. Clin Chim Acta. 1997;263(1):67-77.

Jenkins D, Kendall C, Vidgen E, Agarwal S, Rao AV, Rosenberg RS et al. health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999;69:395-402.

Keenan JM, Wenz JB, Myers S, Ribsin C, Huang ZQ. Randomized, controlled, crossover trial of oat bran in hypercholesterolemic subjects. J Fam Pract. 1991;33(6):600-608.

Knopp RH, Superko R, Davidson M, et al. Long-term blood cholesterol-lowering effects of a dietary fiber supplement. Am J Prev Med. 1999;17(1):18-23.

Kokkinos PF, Fernhall B. Physical activity and high density lipoprotein cholesterol levels. Sports Med. 1999;28(5):307-314.

Kontush A, Schippling S, Spranger T, Beisiegel U. Plasma ubiquinol-10 as a marker for disease: is the assay worthwhile? Biofactors. 1999;9(2-4):225-229.

Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Scientific Statement: AHA Dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation. 2000;102(18):2284-2299.

Kris-Etherton P, Eckel RH, Howard BV, St. Jeor S, Bazzare TL. AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Circulation. 2001;103:1823.

Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr. 2000;72(5):1095-1100.

Laplaud PM, Lelubre A, Chapman MJ. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol. 1997;11(1):35-40.

Lopez-Miranda J, Gomez P, Castro P, et al. Mediterranean diet improves low density lipoproteins' susceptibility to oxidative modifications. Med Clin (Barc) [in Spanish]. 2000;115(10):361-365.

Marz W, Wieland H. HMG-CoA reducatse inhibition: anti-inflammatory effects beyond lipid lowering. Herz. 2000;25(6):117-25.

Mensink RR, Katan MB. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 1992;12:8:911-919.

Miller AL. Botanical influences on cardiovascular disease. Altern Med Review. 1998;3(6):422-431.

Miyake Y, Shouza A, Nishikawa M, Yonemoto T, Shimizu H, Omoto S, Hayakawa T, Inada M. Effect of treatment with 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung. 1999;49(4):324-329.

Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18Suppl:S137-S144.

National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.

National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Circulation. 1994; 89:3:1333-1445.

Nestel PJ, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab. 1999;84(3):895-898.

Nutrition Committee of the American Heart Association. AHA Dietary Guidelines. Revision 2000: A Statement for Healthcare Professionals. Circulation. 2000; 102:2284-2299.

Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merrit KL, et al. Intensive lifestyle change for reversal of coronary heart disease. JAMA. 1998;280(23):2001-2007.

Plat J, van Onselen ENM, van Heugten MMA, Mensink RP. Effects on serum lipids, lipoproteins, and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters. Euro J Clin Nutr. 2000;54:671-677.

Qin S, Zhang W, Qi P, et al. Elderly patients with primary hyperlipidemia benefited from treatment with a Monacus purpureus rice preparation: a placebo-controlled, double-blind clinical trial. Paper presented at: American Heart Association 39th Annual conference on Cardiovascular Disease Epidemiology and Prevention; March 1999; Orlando, Fla. Abstract.

Orlistat. NMIHI. Accessed at http://www.nmihi.com/n/orlistat.html on June 8, 2018.

Raitakari OT, McCredie RJ, Witting P, Griffiths KA, Letter J, Sullivan D, Stocker R, Celermajer DS. Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults. Free Radic Biol Med. 2000;28(7):1100-1105.

Rajendran S, Deepalakshmi PD, Parasakthy K, Devaraj H., Devaraj SN. Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed an atherogenic diet. Atherosclerosis. 1996;123:235-241.

Redlich CA, Chung JS, Cullen MR, Blaner WS, Van Benneken AM, Berglund L. Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET). Atherosclerosis. 1999;143: 427-434.

Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328(20):1450-1456.

Ripsin CM, Keenan JM, Jacobs Jr. DR, et al. Oat products and lipid lowering: a meta-analysis. JAMA. 1992;267:24:3317-3325.

Shintani TT, Beckham S, Brown AC, O'Connor HK. The Hawaii diet: ad libitum high carbohydrate, low fat multi-cultural diet for the reduction of chronic disease risk factors: obesity, hypertension, hypercholesterolemia, and hyperglycemia. Hawaii Med J. 2991;60(3):69-73.

Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs and Therapy. 1994;8:659-664.

Sirtori CR, Pazzucconi F, Colombo L, Battistin P, Bondioli A, Descheemaeker K. Double-blind study of high-protein soya milk v. cow's milk to the diet of patients with severe hypercholesterolaemia and resistance to or intolerance of statins. Brit J Nutr. 1999;82:91-96.

Spiller GA, Jenkins DAJ, Boselloo Gates JE, Cragen LN, Bruce B. Nuts and plasma lipids: an almond-based diet lowers LDL-c while Preserving HDL-c. J Am Coll Nutr. 1998;17(3):285-290.

Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328(20):1444-1449.

Statins. NMIHI. Accessed at http://drugs.nmihi.com/statins.htm on November 9, 2018.

Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Effectsof diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. New Engl J Med. 1998;339(1):12-20.

Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996; 347(9004):781-786.

Stevinson C, Pittler MH, Ernst E. Garlic for treating hypercholesterolemia. Ann Intern Med. 2000;133(6):420-429.

Sum CF, Winocour PH, Agius L, et al. Does oral L-carnitine alter plasma triglyceride levels in hypertriglyceridemic subjects with or without non-insulin dependent diabetes mellitus. Diabetes Nutr Metab Clin Exp. 1992;5:175-181.

Teixeira SR, Potter SM, Weigel R,Hannam S, Erdman Jr. JW, Hasler CM. Effects of feeding 4 levels of soy Protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. Am J Clin Nutr. 2000;71:1077-1084.

Tofler GH, Stec JJ, Stubbe I, Beadle J, Feng D, Lipinska I, Taylor A. The effect of vitamin C supplementation on coagulability and lipid levels in healthy male subjects. Thromb Res. 2000;100(1):35-41.

Van Golde PH, Sloots LM, Vermeulen WP, et al. The role of alcohol in the anti low density lipoprotein oxidation activity of red wine. Atherosclerosis. 1999;147(2):365-370.

Verhaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. Circulation. 1999;100(4):335-338.

Villalobos MA, De La Cruz JP, Martin-Romero M, Carmona JA, Smith-Agreda JM, Sanchez de la Cueta F. Effect of dietary supplementation with evening primrose oil on vascular thrombogenesis in hyperlipidemic rabbits. Thromb Haemost. 1998;80:696-701.

Williams JC, Forster LA, Tull SP, Wong M, Bevan RJ, Ferns GAA. Dietary vitamin E supplementation inhibits thrombin-induced platelet aggregation, but not monocyte adhesiveness, in patients with hypercholesterolaemia. M J Exp Path. 1997;78:259-266.

Wang J, Lu Z, Chi J, et al. Multicenter clinical trial of serum lipid-lowering effects of a Monascus purpureus (red yeast) rice preparation from traditional Chinese medicine. Curr Ther Res. 1997;58(12):964-978.

Wong WW, Smith EO, Stuff JE, Hachey DL, Heird WC, Pownell HJ. Cholesterol-lowering effect of soy protein in normocholesterolemic and hypercholesterolemic men. Am J Clin Nutr. 1998;68(suppl):1385S-1389S.

What is cholesterol?. MedlinePlus. Accessed at https://medlineplus.gov/ on June 8, 2018.

Yang TTC, Koo MWI. Chinese green tea lowers cholesterol level through an increase in fecal lipid excreiton. Life Sciences. 1999:66:5:411-423.

Yu-Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris-Etherton PM. Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr. 1999;69:632-646.

Zambón D, Sabate J, Munoz S, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. Ann Intern Med. 2000;132:538-546.