It never ceases to amaze me. When I evaluate a new patient and recommend, for example, a beta-blocker to control their blood pressure and a "statin" to lower their LDL (bad) cholesterol, an occasional response is, "But Doctor, I don't want to take any more pills!" When asked to elaborate, they say they already are taking a large number of vitamins, herbs and dietary supplements. The list usually includes something like: "Beta-carotene, vitamin E, vitamin C, multivitamins, garlic, ginkgo biloba, lethacin, and CoQ-10." What amazes me is that none of these vitamins, herbs and dietary supplements has been shown to decrease heart attacks and strokes or to improve survival, whereas both of the medications I had just recommended have - and in multiple studies.

Fortunately, scientists interested in finding out if vitamins, herbs and dietary supplements have health benefits are conducting appropriately designed studies; two of the most recent studies have looked at vitamin E.

We all had high hopes for the mega-dose vitamins, especially the antioxidant vitamins beta-carotene, vitamin E and vitamin C. One reason for our high hopes was the oxidative hypothesis of atherosclerosis. This hypothesis states that LDL, or "bad," cholesterol is not dangerous (that is it won't start the process of atherosclerosis) unless it is oxidized. Therefore, we hoped that studies would show that the antioxidant vitamins would help prevent cardiovascular disease.

We (the medical profession) learned about high-dose beta-carotene a few years ago when the results were reported from two large randomized placebo-controlled trials designed to find out if high dose beta-carotene would decrease the incidence of lung cancer. In the first study, the Beta-Carotene Retinol Efficacy Trial (CARET), 18,314 men and women - of whom 14,254 were current or former smokers and 4,060 men who were exposed to asbestos - were studied. They were treated with either 30 milligrams of beta-carotene or placebo. It was a surprise when the group who took high-dose beta-carotene had a 28 percent increase in lung cancer and a 17 percent increase in death rate (New England Journal of Medicine 1996; 334:1105). These results were hard to believe, and we thought something must have been wrong with the study design. Yet the results were confirmed in the second study, the Alpha-Tocopherol-Beta-Carotene (ATBC) trial. In this trial, 29,133 Finnish male smokers were treated with beta-carotene, vitamin E or placebo. Beta-carotene resulted in an 18 percent increase in lung cancer and an 8 percent increase in the death rate! (New England Journal of Medicine 1994; 330: 1029) At least in smokers, mega-dose beta-carotene increases cancer and mortality! How can this be when previous studies have shown that subjects with higher blood levels of beta-carotene are healthier? Beta-carotene is only one of hundreds of carotenoids. It is probable that diets high in fruits and vegetables have benefits far beyond their beta-carotene content.

Beta-carotene also was studied in 22,071 male physicians in the Physicians Health Study, in a two-by-two format, a method of determining the effects of two different drugs in the same study. Aspirin was used in one arm of the study. This arm was stopped after a little more than four years, as physicians over age 50 who were taking 325 milligrams every other day had a 44 percent decrease in the incidence of heart attacks. The beta-carotene arm, in which 50 milligrams of beta-carotene was given every other day, was continued for 12 years and finally discontinued when no benefit was found.

Thus, beta-carotene vitamin supplement was of no benefit in a group of predominantly nonsmoking physicians and was related to increased mortality in smokers. Based on these findings, the Women's Health Initiative - an ongoing National Institutes of Health-funded study to look at the effect of several oral medications, vitamins and activity in women - stopped the beta-carotene arm.

The effect of vitamin E also was reported in the ATBC trial and had "no significant effect on mortality or on the incidence of new angina pectoris" (chest pain). More concerning has been the report of two recent studies.

The GISSI-Prevention trial (Lancet 1999; 354: 447) also used a two-by-two format. Vitamin E (300 IU) and polyunsaturated fatty acids (PUFA), or fish oils, were studied in patients after a heart attack. The fish oil was found to decrease the death rate and recurrent heart attacks in these patients, but vitamin E had no effect whatsoever. The other large trial was the HOPE trial (New England Journal of Medicine 2000; 342: 154). In this trial, the patients were at increased risk for adverse cardiovascular events because of known cardiovascular disease or diabetes mellitus and at least one other risk factor. Vitamin E and an angiotensin converting enzyme inhibitor (ACE-inhibitor) were compared with placebo. Again, while the ACE-Inhibitor showed a marked beneficial effect, there was no benefit from vitamin E (Figure 1).

The combination of vitamin E and vitamin C supplements also failed to prevent strokes. An eight-year follow-up of 43,738 men without evidence of cardiovascular disease or diabetes reported two years ago found that neither the dose nor the duration of vitamin E or C supplements reduced the incidence of stroke (Annals of Internal Medicine 1999; 130: 963). In addition, a recent abstract raises concerns about vitamin C supplements, as the authors reported that as doses of vitamin C increased, so did thickening of the carotid artery wall (evidence of early atherosclerosis). (Circulation 2000; 101: 82).

These findings with the antioxidant vitamins (beta-carotene, vitamin E, and vitamin C) are disappointing as it is easier to take a few vitamin pills each day than to eat a healthy diet that includes several servings of fruits and vegetables. It is recommended that we eat five to seven servings of fruits and vegetables per day. It is said that the average American eats about two vegetables a day, but only in you count french fries as a vegetable!

To paraphrase Dr. R.D. Klausner of the National Cancer Institute: The antioxidant vitamins neither substitute for a good diet nor compensate for a bad one.