Antioxidants, Statins and Lowering Cholesterol

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The future looks bright for companies that make cholesterol-lowering drugs. According to new guidelines from the National Cholesterol Education Program (NCEP), a subsidiary of the National Institutes of Health, an estimated 36 million Americans–about 18 percent of the adult population–are considered to be at very high risk for having a heart attack or stroke. The guidelines indicate that these individuals are beyond the point where lifestyle and dietary changes alone are sufficient to reduce their risk. In other words, they need to be taking medication to lower their cholesterol.

The antioxidant connection

Not long after these recommendations made national news, a somewhat disturbing headline appeared that read, “Substudy Shows No Heart Benefits from Antioxidants.” These conclusions were based on a five-year British study of 20,539 people, all of whom had a history of heart disease, stroke, or diabetes and were therefore at a high risk for further problems. Half of them were given a daily supplement of antioxidants consisting of vitamin C, vitamin E, and beta-carotene, while the other half were given a placebo pill. At the end of the study, the researchers were unable to find any discernible benefits (or side effects) from the antioxidants. This was in direct contrast to results from another group of these same patients who were given simvastatin, a member of the “statin” family of cholesterol-lowering drugs. After five years, it was found that people who took simvastatin experienced a 33 percent reduction in their risk of having an additional heart attack or stroke.

Another disturbing study from the University of Washington in Seattle that was published in August 2001 found that adding both an antioxidant supplement and niacin to simvastatin could actually counteract the effectiveness of the therapy. In test subjects, simvastatin lowered the “bad” LDL cholesterol while the niacin kept the levels of HDL, the “good” cholesterol, in a healthy range. But when the antioxidants were added to the mix, the HDL levels remained low, thus blunting the favorable response achieved by the drug-niacin mixture.

Some cardiology experts can barely conceal their excitement about all of this. When the results of the British study were presented to the American Heart Association, they were called “spectacular” and “stunning.” At the same time, other pundits were commenting that the last nails had been placed in the coffin of antioxidants as a preventive medicine for heart disease. Some have gone so far as to propose that we stop worrying about cholesterol, diet, and lifestyle and simply proceed to put most everyone older than forty on statins. The only obvious problem–at least as far as the public is concerned–appears to be the cost. Depending on the dose and the brand, a typical course of statins ranges from $60 to $120 per month.

Using caution

Perhaps I’m just a gadfly, but this trend toward embracing statins and downplaying the value of diet and lifestyle makes me nervous. It’s easy to forget that the history of medicine is full of so-called magic bullets against disease that end up backfiring and exploding in the barrel. Consider what happened with antibiotics, which were embraced in a similar fashion not long after they were introduced. It took years of careless overprescribing before the downside of antibiotics became obvious–lethal bacteria that have evolved into drug-resistant superstrains.

Statins clearly have a downside. Cerivastatin, marketed under the brand name Baycol, was permanently taken off pharmacy shelves in 2001, after numerous reports of toxicity and thirty-one fatalities. Side effects of statins include inflammation of the muscles, liver problems, rashes, upset stomach, abdominal pain, constipation, diarrhea, and flatulence. Statins work by blocking the enzyme that makes cholesterol in the liver. This same enzyme also makes Coenzyme Q10, an antioxidant critical to normal functioning of the heart and brain. Studies have shown that long-term use of statins can decrease CoQ10 levels. The long-term consequences of this persistently lowered production of CoQ10 are unknown but could potentially include chronic fatigue and weakness, congestive heart failure, and neurodegenerative disorders.

Antioxidant benefits

How could it be that these studies were not only unable to show any benefits but appeared to show that antioxidants could cancel out the effects of conventional therapy? First, some clarification is in order. The supplements that these researchers referred to as antioxidants were only a small group of compounds with antioxidant activity. Even so, the researchers’ conclusions were generalized into an attention-grabbing headline that implied that all antioxidants are worthless. Anyone with a background in nutritional biochemistry knows that beta-carotene, vitamin C, vitamin E, and selenium are just a few members of a very large family of phytochemicals with antioxidant activity. In fact, all plants contain antioxidants of one form or another–otherwise, they could not exist in Earth’s high-oxygen environment.

It’s important to realize that the initial interest in antioxidants as a potential preventive for coronary heart disease came from examining the diet of large population groups. These studies found that a greater intake of fruits and vegetables was associated with a lower mortality rate from heart disease. Further studies found even more potent effects from red wine, purple grape juice, apples, onions, and tea. Research dating as far back as 1979 showed a strong association between wine consumption in France and a lowered risk of heart attacks. This effect has been called the “French Paradox” because the French diet, rich in fatty foods, would seem to be a guarantee for clogged arteries.

When these foods were first analyzed, they were all found to be rich in the now well-known basic antioxidants mentioned earlier, such as vitamin C, vitamin E, and carotenoids (e.g., beta-carotene and lycopene). Given the abundance of data showing that heart disease is an inflammatory process fueled by toxic free radicals, it seemed logical that neutralizing this process with antioxidants could put a stop to it. This time, it was antioxidants that were held out to be the mythical magic bullets. The concept launched a decade of research into their potential benefits. Unfortunately, all the research and enthusiasm met with disappointing results.

Perhaps the problem came from placing too much attention on a few isolated nutrients and neglecting the thousands of other beneficial compounds found in foods and herbs. For example, flavonoids, a group of purple, blue, yellow, and orange pigments, have many properties that make them potential candidates for preventing cardiovascular disease. In addition to being antioxidants, they have anti-inflammatory effects and an ability to make platelets less sticky, which can help prevent abnormal blood clotting. In fact, it appears to be the flavonoids in red wine and green tea that help ward off heart attacks.

Research lessons

What lessons are to be gleaned from all of this? Regarding the statin drugs, it’s hard to deny the evidence of their efficacy, especially for people at high risk for heart disease. However, I do have a nagging concern that we are using statins as the easy way out so we can avoid much more difficult issues, like trying to get people to eat a healthy diet and exercise regularly. I’m also concerned that statins could have hidden toxic effects, effects that only reveal themselves after we’ve experimented on 36 million people. In my opinion, everyone who takes statins should also take 100 mg daily of CoQ10.

If you must take a statin, there’s no evidence that antioxidants in supplements or foods will interfere. If you take high-dose niacin to lower your cholesterol, instead of worrying about whether to stay on your multivitamin, simply keep close track of your HDL level. If it’s too low, you might need to stop the supplement. As for whether to take vitamin E, vitamin C, or beta-carotene to prevent heart disease, at this point the evidence for them is relatively weak. You are much more likely to benefit from a glass of purple grape juice, pinot noir, orange juice, or a couple of cups of green tea every day. And don’t forget the garlic.

Robert Rountree, M.D., is a physician in private practice in Boulder, Colorado, where he practices integrative medicine. He is co-author of Smart Medicine for a Healthier Child (Avery, 1994) and Immunotics (Putnam, 2000), and is an Herb Research Foundation advisory board member.

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