Introduction
Atherosclerosis, often known as hardening of the arteries,
leads to cardiovascular disease and is the leading cause of death in men age
thirty-five years and older and of all people older than age forty-five years.
Most heart
attacks and strokes are caused by atherosclerosis. Although
the origin of this condition is not completely understood, it is known that
atherosclerosis is accelerated by factors such as hypertension
(high blood pressure), high cholesterol, diabetes and
milder forms of impaired glucose tolerance, smoking, physical inactivity, and
obesity. Chronic inflammation in the body (of various types)
is also hypothesized to play a role.
Theories suggest that atherosclerosis begins with injury to the lining of the arteries. High blood pressure physically stresses this lining, while circulating substances such as low-density lipoprotein (LDL) cholesterol, homocysteine, free radicals, and nicotine chemically damage it. White blood cells then attach to the damaged wall and take up residence. Then, for reasons that are not entirely clear, the artery lining begins to accumulate cholesterol and other fats. Platelets also latch on, releasing substances that cause the formation of fibrous tissue. The overall effect is a thickening of the artery wall called a fibrous plaque.
Over time, the thickening increases, narrowing the bore of the artery. When
blockage of the coronary arteries (the arteries supplying the heart) reaches 75 to
90 percent, symptoms of angina develop. In the lower legs,
blockage of the blood flow leads to leg pain with exercise, a condition called
intermittent claudication.
Blood clots can develop on the irregular surfaces of arteries and may become detached and block downstream blood flow. Fragments of plaque can also detach. Heart attacks are generally caused by such blood clots, whereas strokes are more often caused by plaque fragments or gradual obstruction. Furthermore, atherosclerotic blood vessels are weak and can burst.
With a disease as serious and progressive as atherosclerosis, the best
treatment is prevention. Conventional medical approaches focus on lifestyle
changes, such as increasing aerobic exercise, reducing the consumption of
saturated fats, and quitting smoking. The regular use of aspirin also
appears to be quite helpful by preventing platelet attachment and blood clot
formation. If necessary, drugs may be used to lower cholesterol levels or blood
pressure.
Principal Proposed Natural Treatments
This section presents some promising and not-so-promising natural approaches for preventing cardiovascular disease by fighting atherosclerosis. Two classes of treatments have been omitted from this discussion: those that reduce elevated cholesterol and blood pressure and those that reduce levels of homocysteine.
Omega-3 fatty acids. Omega-3 fatty acids are healthy fats, found
in certain foods such as cold-water fish. Some evidence suggests that fish or
fish
oil might help fight atherosclerosis. However, study results
on fish or fish oil for cardiovascular disease have yielded contradictory results.
A 2002 review (technically a meta-analysis) of many studies on the subject
concluded that when all the evidence is put together, it appears that fish or fish
oil can slightly reduce overall mortality, heart disease mortality, and sudden
cardiac death (heart stoppage caused by arrhythmia). However, a subsequent
comprehensive review published in 2004 included additional studies and came to a
more pessimistic conclusion. According to the authors, “It is not clear that
dietary or supplemental omega-3 fats alter total mortality, combined
cardiovascular events or cancers in people with, or at high risk of,
cardiovascular disease or in the general population.”
A large study (more than eighteen thousand participants) published in 2007 was widely described in the media as finally proving that fish oil helps prevent heart problems. This study, however, lacked a placebo group and therefore failed to provide reliable evidence.
If it does provide benefit for atherosclerosis, fish oil is thought to do so primarily by reducing serum triglycerides. Like cholesterol, triglycerides are a type of fat in the blood that tends to damage the arteries, leading to heart disease. According to most studies, fish oil can modestly reduce triglyceride levels. However, the standard drug, gemfibrozil, appears to be more effective than fish oil for this purpose. The most important omega-3 fatty acids found in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA may have different effects on triglycerides, but as is typical for studies involving marginally effective treatments, study results are not consistent; some found EPA more effective than DHA, while others did not find a difference. Similarly, some studies also suggest that fish, fish oil, or EPA or DHA separately can modestly raise levels of HDL (good) cholesterol.
Flaxseed oil (another source of omega-3 fatty acids) has been suggested as an alternative to fish oil. While fish oil is much better studied, there is some evidence, including two double-blind studies, that flaxseed oil or whole flaxseed may reduce LDL (bad) cholesterol, perhaps slightly reduce hypertension, and slow down atherosclerosis. Finally, while it is commonly stated that people require a certain optimum ratio of omega-3 to omega-6 fatty acids in the diet, there is no real evidence that this is true and some evidence that it is false.
Lifestyle approaches. There is no doubt that quitting smoking
will significantly reduce heart disease risk. Increasing exercise and losing
weight (if one is overweight) will most likely help too. Although for years there
has been an emphasis on reducing fat in the diet, the balance of evidence
indicates that it is more useful to substitute healthy fats (such as the
monounsaturated fats in olive oil) for saturated fats than to try to reduce total
fat intake. Evidence suggests that any low calorie diet, whether low-carbohydrate,
low-fat, or in between, will result in weight loss and reduced cardiac risk.
However, while it may not be important to cut down on total fat, accumulating
evidence hints that trans-fatty acids, a type of fatty acid found in margarine and
other hydrogenated oils, increase risk of cardiovascular disease. In July 2002,
the Institute of Medicine of the U.S. National Academy of Sciences concluded that
there is no safe intake level of trans-fatty acids and recommended that overall
consumption be kept as low as possible.
The moderate use of alcohol is thought to help reduce cardiovascular risk, but the evidence regarding this subject is both inherently unreliable (because it is based on observational studies) and self-contradictory. According to the best evidence available, it appears to be the alcohol in alcoholic drinks that provides benefits rather than, as previously thought, particular substances found in wine. The optimal intake appears to be about one drink per day for women and one to two drinks per day for men. However, all of these statements are subject to revision, because they are based on problematic evidence.
Other Proposed Natural Treatments
Several natural products have shown some promise for helping to prevent atherosclerosis.
Garlic. Garlic is generally said to produce several effects that together reduce atherosclerosis risk. Although garlic is no longer believed to strongly reduce cholesterol levels, it may improve cholesterol profiles to a modest extent; in addition, it may (mildly) lower blood pressure levels, protect against free radicals, and reduce the tendency of the blood to coagulate. However, the actual evidence for benefit is incomplete.
Garlic preparations have been shown to slow the development of atherosclerosis in rats and rabbits and in human blood vessels, reducing the size of plaque deposits by nearly 50 percent. Furthermore, in a double-blind, placebo-controlled study that followed 152 persons for four years, standardized garlic powder at a dosage of 900 milligrams (mg) per day significantly slowed the development of atherosclerosis as measured by ultrasound. This study, however, had some significant statistical problems.
An observational study of two hundred people suggests that garlic protects the
arteries in other ways too. The study measured the flexibility of the
aorta, the main artery exiting the heart. Participants who
took garlic showed less evidence of damage to their arteries. However,
observational studies are notoriously unreliable.
Finally, in another study, 432 people who had experienced a heart attack were given either garlic oil extract or no treatment over a period of three years. The results showed a significant reduction of second heart attacks and an approximately 50 percent reduction in the death rate among those taking garlic. The researcher’s failure to use a placebo in this trial greatly decreases the meaningfulness of the results.
Other potentially beneficial treatments. The substance red yeast rice has shown promise for reducing cholesterol levels. A double-blind study in China compared red yeast rice with placebo in almost five thousand people with heart disease. Over a four-year study period, the use of the supplement reportedly reduced the heart attack rate by about 45 percent compared with placebo and reduced total mortality by about 35 percent. However, these levels of reported benefit are so high that they raise questions about the study’s reliability.
Mesoglycan is a substance obtained from the intestines of pigs. In one study, 200 mg per day of mesoglycan significantly slowed the rate of thickening of arteries. After eighteen months of treatment, the additional layering of the inside vessel lining was 7.5 times less in the group receiving mesoglycan than in the group that did not receive any treatment. However, because this was not a double-blind, placebo-controlled trial, the results cannot be taken as truly reliable. Preliminary evidence suggests that this supplement may work in several ways: supplying material for repair of arteries, “thinning” the blood, and improving cholesterol levels.
Magnesium also appears to be helpful. In a six-month, double-blind, placebo-controlled study, 187 persons with angina were given either 365 mg of magnesium daily or placebo. The results showed that the use of magnesium significantly improved exercise capacity, lessened exercise-induced chest pain, and improved general quality of life. Additionally, magnesium may reduce the atherosclerosis risk caused by hydrogenated oils, the margarine-like fats found in many junk foods.
Mildly impaired responsiveness to insulin (excluding diabetes) is a fairly common condition that appears to increase the risk of heart disease. Chromium supplementation might restore normal insulin responsiveness, aid in weight loss, and possibly improve cholesterol levels. The net result might be decreased risk of heart disease. In support of this theory, an observational trial found associations between higher chromium intake and reduced risk of heart attack.
Some observational studies suggest that green tea might help prevent heart disease. Black tea has shown inconsistent promise. Chocolate contains some of the same active ingredients as tea, and on this basis, it is sometimes mentioned as a potentially heart-healthy food.
Many herbs and supplements, including bilberry, feverfew, ginger, ginkgo, policosanol, and hawthorn, appear to decrease platelet stickiness. Whether this translates into an actual benefit for preventing atherosclerosis remains unknown.
Indirect evidence suggests that dehydroepiandrosterone might help prevent heart disease, especially in men. Also, frequent consumption of nuts may reduce the risk of heart disease, probably because the monounsaturated fats in nuts reduce cholesterol levels.
Whole grain oats may help prevent heart disease, but the supporting evidence is almost entirely limited to studies conducted by manufacturers of whole grain oat products. There is little to no evidence of benefit for other whole grains because studies have not been performed.
Chelation
therapy, a technique that involves intravenous administration
of the substance EDTA, is widely promoted in some alternative medicine circles as
a treatment for atherosclerosis. However, there is no meaningful evidence that it
works, and there is growing evidence that it does not work.
Antioxidants
The body is in constant battle with damaging chemicals called free
radicals, or pro-oxidants. These highly reactive substances are
believed to play a major role in atherosclerosis, cancer, and aging in general. To
counter the harmful effects of free radicals, the body manufactures
antioxidants to chemically neutralize them. However, the
natural antioxidant system may not always be equal to the task. Sources of free
radicals, such as cigarette smoke and smoked meat, may overwhelm this defense
mechanism.
Certain dietary nutrients augment the body’s natural antioxidants and may be
able to help when the primary system is under stress. Vitamins E and C and
beta-carotene are the best known, but many other substances found in fruits and
vegetables are also strong antioxidants. For years it was believed that
antioxidant supplements might offer considerable protection against heart disease,
especially vitamin E. However, later evidence appears to counter this
theory.
Before presenting this information, it is necessary to explain the weaknesses of the observational studies that raised the hopes of the researchers looking into the effectiveness of antioxidants. Observational studies are relatively inexpensive and are often used to evaluate the potential health benefits of nutrients such as antioxidants. This type of study follows large groups of people for years and keeps track of a great deal of information about them, including diet. Researchers then examine the data closely and try to identify what dietary factors are associated with better health and longer life.
However, the results can be misleading. For example, if an observational study finds that people who take vitamin supplements live longer, it is not necessarily the vitamins that deserve the credit. Vitamin users also tend to exercise more and to eat more healthful foods, habits that may play a more important role than the vitamins. It is impossible to know for sure simply by evaluating the results of such a study.
Similarly, several observational studies have found that men who consume more foods that are rich in lycopene are less likely to develop prostate cancer. This does not necessarily mean, however, that taking lycopene supplements will reduce prostate cancer risk. Such foods contain many other nutrients, which may be more important than lycopene.
A more reliable kind of study is the intervention trial. In these studies, some people are given a specific substance, such as a vitamin, and are then compared with others who are given a placebo (or sometimes no treatment). The best intervention trials use a double-blind, placebo-controlled design. The results of intervention trials are far more conclusive than those of observational studies. In examinations of antioxidant therapy for preventing atherosclerosis, observational studies raised hopes, but intervention trials dashed them.
Vitamin E. Most observational studies have found associations between high intake of vitamin E and reduced risk of cardiovascular disease. Intervention trials, however, have failed to find vitamin E supplements effective.
The Heart Outcomes Prevention Evaluation (HOPE) trial found that natural vitamin E (d-alpha-tocopherol) at a dose of 400 international units (IU) daily did not reduce the number of heart attacks, strokes, or deaths from heart disease any more than placebo. The details of this well-designed double-blind trial were published in the January 20, 2000, issue of the New England Journal of Medicine. The trial followed more than nine thousand men and women who had existing heart disease or were at high risk for it.
In addition, a large open trial compared the effectiveness of aspirin and vitamin E for the prevention of heart attacks, strokes, and other diseases related to atherosclerosis. Although aspirin treatment proved somewhat helpful, vitamin E produced little to no benefit.
Negative results have been seen in other large trials. A few trials have even found weak indications that the use of vitamin E may worsen certain outcomes.
When the results of these studies began to come in, some antioxidant proponents suggested that the persons enrolled in these trials already had too advanced disease for vitamin E to help. However, a large trial found vitamin E ineffective for slowing the progression of heart disease in healthy people. Moreover, in an extremely large placebo-controlled trial involving more than fourteen thousand American male physicians at low risk for heart disease, 400 IU of vitamin E every other day failed to lower the risk of major cardiovascular events or mortality in a period of eight years. On the contrary, vitamin E was associated with a slightly increased risk of stroke.
On balance, the evidence strongly suggests that vitamin E in the form used in these studies (alpha-tocopherol) is not helpful for preventing heart disease. It has been suggested that another form of vitamin E, gamma-tocopherol, might be more helpful than alpha-tocopherol. Gamma-tocopherol is present in the diet much more abundantly than alpha-tocopherol, and it could be that the studies showing benefits with dietary vitamin E actually tracked the influence of gamma-tocopherol. However, an observational study specifically looking to see if gamma-tocopherol levels were associated with risk of heart attack found no relationship between the two.
Beta-carotene. Beta-carotene is one member of a large category of substances in foods known as carotenoids, which are found in high levels in yellow, orange, and dark green vegetables. Many studies suggest that eating foods high in carotenoids can prevent atherosclerosis. However, isolated beta-carotene in supplement form may not help and could actually increase risk, especially if one consumes too much alcohol.
A huge double-blind intervention trial involving Finnish male smokers found 11 percent more deaths from heart disease and 15 to 20 percent more strokes in those participants taking beta-carotene supplements.
Similar poor results with beta-carotene were seen in another large double-blind study of smokers. Furthermore, beta-carotene supplementation was also found to increase the incidence of angina in smokers.
Smoking presents a challenge to antioxidants. However, the question remains: Why should beta-carotene not only fail to help but actually worsen the situation? One possible explanation is that beta-carotene in the diet always appears with other naturally occurring carotenes. It is likely that other carotenoids in the diet are at least as important as beta-carotene alone. Taking beta-carotene supplements may actually promote deficiencies of other natural carotenes, and overall, this may hurt more than it helps.
Other antioxidants. A single double-blind study suggests that the antioxidant coenzyme Q10 may help prevent the progression of atherosclerosis after a heart attack. Many other antioxidant vitamins, supplements, and herbs (including selenium, oligomeric proanthocyanidins from grape seed or pine bark, lipoic acid, turmeric, and resveratrol from red wine and grape skins) have been suggested as preventive treatments for atherosclerosis. However, although a number of studies have suggested that these substances may be beneficial, the state of the evidence is too preliminary to draw any conclusions.
Like other berries, sea buckthorn contains high levels of natural antioxidants. It has been widely advertised as effective for preventing heart disease, but the studies upon which this claim is based are far too preliminary to prove anything. Also, one large double-blind study explored the potential benefit of vitamin C for preventing cardiovascular problems in women at high risk for them, but it failed to find benefit.
Combined antioxidants. It has been suggested that the best approach is to use a combination of antioxidants. This makes sense theoretically because, for example, vitamin E fights free radicals that dissolve in fats while vitamin C fights those that dissolve in water. However, evidence for benefit with such combinations comes only from observational studies.
A three-year, double-blind, placebo-controlled study of 160 persons found no benefit with combined antioxidant treatment providing vitamin E (800 IU), vitamin C (1,000 mg), beta-carotene (25 mg), and selenium (100 micrograms). Similarly, a three-year, double-blind, placebo-controlled study of 423 menopausal women with coronary artery disease found no benefit with combined vitamin E (800 IU daily) and vitamin C (1,000 mg daily). Furthermore, a seven-year, double-blind, placebo-controlled study of more than thirteen thousand French men and women failed to find any significant reduction of cardiovascular disease rates through the use of a daily supplement containing 120 mg of vitamin C, 30 mg of vitamin E, 6 mg of beta-carotene, 100 micrograms of selenium, and 20 mg of zinc.
Herbs and Supplements to Use Only with Caution
Various herbs and supplements may interact adversely with drugs used to treat atherosclerosis, so one should be cautious when considering the use of herbs and supplements.
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