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Complementary and Alternative Medicine Series

Hyperlipidemia: Nutritional, Botanical, and Life-style Influences

Tori Hudson, ND

Heart disease is the leading cause of death in US adults, accounting for approximately 1 million deaths annually. The public often thinks of heart disease as affecting men more than women, but for the past 18 years, cardiovascular death rates have been higher in women than in men.^{1, 2} Women do experience a 7- to 10-year delay in cardiovascular symptom onset, and a first myocardial infarction (MI) 20 years later than men do.³ The tragedy of heart disease is that preventive measures go a long way in reducing premature deaths—ie, eating a low-fat diet, exercising regularly, not smoking, and maintaining optimal body weight.

LIFE-STYLE MODIFICATIONS

Cigarette smoking is the most important preventable independent risk factor for cardiovascular disease (CVD) in both women and men. Two or more packs of cigarettes per day can increase the risk of CVD by as much as 3-fold.⁴ However, even light smokers (one to four cigarettes daily) are at increased risk. After not smoking for just 1 year, the risk decreases by 50%, and it almost disappears after 3 years.⁵

Alcohol consumption confers both health benefits and risks. For women, one glass of wine per day seems to be cardioprotective because it increases high-density lipoprotein (HDL) cholesterol levels.⁶ However, drinking two or more glasses per day can increase the risk factor for CVD by raising blood pressure.⁷

Increased physical activity and weight loss are fundamental steps in the improvement of abnormal cholesterol levels. Obesity—especially abdominal fat—may lower HDL and raise triglyceride (TG) levels, increasing the risk for hypertension and diabetes.^{8, 9} Individuals who are even moderately overweight have almost double the risk of coronary heart disease (CHD).¹⁰ A sedentary life-style is an independent risk factor for heart disease,¹¹ and the majority of adult Americans do not have even a minimum amount of physical activity.⁹ Having a regular aerobic exercise program, either walking or more vigorous exercise, will lead to substantial reductions in cardiovascular events in postmenopausal women (ie, those at greatest risk).¹² Current federal exercise guidelines endorse moderate-intensity exercise for at least 30 minutes, five times weekly.

A healthy diet should be considered one of the primary life-style modifications for any patient with abnormal cholesterol levels. The diet should emphasize fruits and vegetables; low-fat intake; whole grains, legumes, nuts, and seeds; and fish, poultry, and lean meats. Diets high in fruit and vegetable intake reduce the risk for developing CVD, stroke, and hypertension.^{13, 14} Diets high in grains and fiber have been shown to decrease the risk of CVD, and soluble fibers such as pectin, oat, and psyllium lower low-density lipoprotein (LDL) cholesterol and total cholesterol levels.

Saturated fat intake should be limited to not more than 75 kcal/d. In addition, the consumption of trans-fatty acids must be restricted; these are found in baked goods, fried foods, fast foods, margarine, and other products made with hydrogenated fat. Trans-fatty acids in the diet increase LDL and TG levels. Instead, trans-fatty acids should be replaced by monounsaturated and polyunsaturated fats, which reduce LDL levels. Olive oil is perhaps the best known monounsaturated fat. Fish is a source of beneficial fatty acids called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids have multiple beneficial effects on the cardiovascular system, including lowering TG and total cholesterol levels, and reducing strokes and MI.

Soy foods are rich in isoflavones, provide fiber, and are low in saturated fat and cholesterol, and they are very healthy for the heart. An analysis of 38 clinical trials with soy determined that soy protein significantly lowers total cholesterol (9.3%), LDL (12.9%), and TG (10.5%) levels. The soy intake averaged 47 g/d. No significant change was seen in HDL values.¹⁵ The US Food and Drug Administration (FDA) has confirmed that the consumption of 25 g/d of soy protein can reduce the risk of heart disease.

Since the 1950s, plant sterols have been known to reduce serum cholesterol levels.¹⁶ Phytosterols are to plants as cholesterol is to mammals; they are both sterols, but differ slightly in chemical structure. Although these substances are not as effective as drugs, they are helpful in maintaining healthy cholesterol levels, and are now added to foods such as margarine and salad dressings. Phytosterols impair the intestinal absorption of cholesterol, resulting in a 10% to 15% decrease in LDL levels from consuming 2 to 3 g/d.¹⁷ Phytosterols primarily lower LDL levels and have less of an effect on TG and HDL values. Phytosterol-rich margarines and spreads are termed "functional foods" in the food industry due to their medicinal effects. However, ingestion of these plant sterols may decrease absorption of b-carotene, a-tocopherol, and lycopene, so supplementation may be necessary.¹⁸

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DIETARY SUPPLEMENTS

Niacin

Niacin (nicotinic acid) has been shown to favorably affect all lipids and lipoproteins, and can be used either alone or in combination with other lipid-lowering agents.¹⁹ Even though it is widely used, the exact mechanism is not completely understood; it likely inhibits mobilization of free fatty acids from peripheral fat tissue to the liver. As a result, niacin reduces hepatic synthesis of very low-density lipoprotein (VLDL) and TG levels. Because there is less VLDL available, LDL levels decrease.²⁰

The Coronary Drug Project²¹ was the first trial to study the effect of niacin on cardiovascular endpoints. This study evaluated niacin therapy in men with prior MI. Niacin reduced the 5-year incidence of nonfatal reinfarction by 27%. In addition, after a mean follow-up of 15 years (nearly 9 years after the trial was completed), all-cause mortality was 11% lower in niacin-treated men compared with placebo-treated patients (P < .001).²²

Niacin—specifically nicotinic acid—may be used to reduce total cholesterol, TG, and LDL levels, and to raise HDL values. It is currently the best treatment to raise HDL levels,20 and can reduce the risk of nonfatal MI.²³ Niacin lowers LDL levels by about 5% to 25%, TG by 20% to 50%, lipoprotein(a) by 34%,²⁴ and the total cholesterol/HDL ratio by 27%,¹⁹ while increasing HDL levels by 15% to 35%.²⁵ The major problem with the therapeutic dosage (1.5 to 3 g/d) has to do with side effects. Flushing responses are common. More seriously, liver function findings can become abnormal, and niacin should not be taken by individuals with liver disease. Immediate-release niacin is recommended, as sustained-release niacin has been associated with severe liver toxicity in doses of more than 2 g/d. Niacin can also exacerbate elevated serum glucose levels in diabetic patients, and can worsen gout. Niacin in doses of more than 1 g/d are best taken under the guidance of a physician, with monitoring of liver-function tests.


Policosanols

Policosanols are extracted from sugar-cane wax or beeswax, and are a mixture of alcohols. A dose of 20 mg/d of policosanols has been shown to lower total cholesterol and LDL levels by about 20% while raising HDL values by as much as 15%, but seems to have little effect on serum TGs.²⁶


Fish Oils

Low rates of CVD in populations with a high intake of fish, such as Alaskan and Greenland native peoples^27-30 and Japanese people who reside in fishing villages,^{31, 32} suggest that fish consumption may protect against atherosclerosis. These observational studies have led to more rigorous prospective studies to determine cause and effect or other confounding variables. Several (but not all) prospective cohort studies have found an inverse association between higher fish intake and risk of CHD.^33-35 In addition, two secondary prevention trials demonstrated that increasing fish consumption or fish-oil supplementation reduced CHD mortality among patients with preexisting CHD.^{36, 37} However, virtually all of the studies on fish consumption and CHD were conducted in men. A more recent study on women found that higher consumption of fish (more than once per month) was associated with both a lower risk of CHD and CHD-related deaths. Consuming fish five or more times per week had the strongest inverse association and was better than two to four times per week, which in turn was better than one to three times per month.³⁸ A small clinical trial in 31 women compared fish-oil supplementation alone with fish oil plus two different doses of g-linolenic acid (GLA) and a control group. They found that a mixture of 4 g of omega-3 fatty acids from fish oil, EPA, and DHA plus 2 g of GLA favorably altered blood lipid profiles in healthy women.³⁹ A recent systematic scientific review found that fish-oil supplementation reduced TG levels in patients with type 2 diabetes, but it also raised LDL values.⁴⁰

Multiple mechanisms have been proposed whereby the omega-3 fatty acids in fish and fish oils reduce CHD incidence and mortality. These include reduction of serum TG levels,⁴¹ platelet aggregability,⁴² and antiarrhythmic effects.⁴³

Fish oils can be used in supplement form at doses of 0.21 g/d for EPA and 0.12 g/d for DHA. Buyers are encouraged to purchase products from companies that have independent assays to test for safety regarding mercury and other heavy metals, hormones, and pesticides. New federal laws governing good manufacturing practices will soon take effect, ensuring quality control for all supplements in the retail marketplace.

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BOTANICAL THERAPIES

Red Yeast Rice

Red yeast rice is made from cooked white rice fermented by the yeast Monascus purpureus, which is then sterilized and dried. Red yeast rice has been used as a dietary staple to make rice wine, and as a food preservative. The main active ingredient in red yeast rice is monacolin K (lovastatin),⁴⁴ which inhibits the enzyme that initiates the synthesis of cholesterol biosynthesis. Monacolin K is probably not the only cholesterol-lowering agent in red yeast rice; there are also omega-3 fatty acids, isoflavones, and plant sterols. Given that red yeast rice contains only 0.2% lovastatin, it is likely that these other agents are also responsible for its beneficial effects on lipids. However, there is significant variability in quality and potency of commercial red yeast rice products. In addition, the lovastatin content in dietary supplements of red yeast rice was lowered due to challenges by the FDA and others. The conflict involved a proprietary product used in clinical trials (Cholestin), which contained the patented lipid-lowering drug lovastatin. Cholestin is no longer available because of these legal issues, although there are other red yeast rice products. One of the early studies on red yeast rice used Cholestin, 2.4 g/d. Cholesterol levels were lowered in men and women by 17% after 8 weeks, LDL by 22%, and TG by 12%, and HDL values remained unchanged.⁴⁵


Garlic

Garlic has long been popular as a lipid-lowering agent, but its effect is slight at best. Numerous collected analyses have demonstrated a reduction in total cholesterol levels of 5% to 12%, but recent reports have suggested that these may have been too brief to draw conclusions.^46-48 Most garlic supplements have a standardized allicin content as a measure of its potency, and are generally enteric-coated to prevent gastric acid inactivation of the allicin-producing enzyme alliinase. The great variation in the amount of allicin in garlic products may account for some of the variability in research results. Even the studies showing a positive effect are plagued by lack of long-term follow-up, standardized laboratory measurements, and adequate dietary controls. While evidence supports at least a short-term benefit, the effect is typically a small but statistically significant decrease in lipid levels. Some controlled trials have yielded a different picture.^49-51 The possible short-term beneficial effect of garlic on lipids is not its only cardioprotective effect; it also has been shown to lower blood pressure slightly,⁵² inhibit clotting,⁵³ and regulate heart rhythms.^{54, 55} Overall, garlic should be viewed as having only limited effects on lipids.


Guggul

This medicinal herb comes from the guggul tree, which grows in India, Pakistan, and Afghanistan. Guggul appears to prevent the oxidation of LDL and may regulate the level of bile acids, helping the body to excrete cholesterol. Guggulsterones are thought to be one of the main active constituents responsible for these effects. Studies have shown that guggul can decrease total cholesterol levels by 11.7%, LDL by 12.5%, and TG by 12.0%, with no change in HDL values.⁵⁶ Most commercial extracts are standardized to 5% guggulsterone content, and the typical treatment dose is 500 mg three times per day (which provides 25 mg of guggulsterones three times daily).⁵⁷ This product is a standardized extract, and is available in the US retail marketplace.


Globe Artichoke

The leaf extract of the artichoke has been found to have some lipid-lowering activity. One clinical trial used 1,800 mg of artichoke extract versus placebo for 6 weeks for the treatment of high cholesterol.⁵⁸ The decrease in total cholesterol values was 18.5% in the artichoke group versus 8.6% in the placebo group. Also, LDL values fell by a significant 22.9%. For patients with gallstones or other bile-duct obstructions, globe artichoke supplementation should be avoided due to the choleretic activity of the extract.⁵⁷ This product is currently available as a nutritional supplement in the United States.

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