“It appears that the whole food, containing both the vitamins and polyphenols, is the best way to consume these antioxidants for health benefits.”

Heart disease is the number one cause of death in developed countries so it is widely investigated by scientists. The process of atherosclerosis is initiated by the oxidation of low density lipoprotein and very low density lipoprotein (LDL and VLDL). This eventually leads to foam cell formation and the deposition of atherosclerotic plaque. So heart disease and most forms of stroke are simply rusting of the arteries. The model in this paper is essentially heart disease in a test tube, i.e., the in vitro oxidation of lower-density lipoproteins and the effect of antioxidants on this process. The fast-growing antioxidant field is dependent upon models for comparison of antioxidants, which include the vitamins and polyphenols.

Our research group had been involved in the investigation of vitamins and minerals in animals and humans. Of course vitamins C, E, and beta carotene are the well-known antioxidants. We looked at a citrus extract containing polyphenols and ascorbic acid and found it provided more protection from lipid peroxidation in vivo than did the vitamin C alone. We thought it might be the polyphenols providing extra antioxidants in the citrus extract. After looking at the literature, I became concerned that antioxidant comparisons were made on pure compounds at one or two different concentrations and then statements were made as to which was the better antioxidant. Much of these in vitro comparisons were made at concentrations that were impossible in vivo. Also all antioxidant comparisons relevant to heart disease were made using LDL isolated by ultracentrifugation, which is an expensive, tedious, and slow process. There is evidence in the literature that centrifugation changes the physical properties of the lipoprotein and also changes the chemical composition by oxidation. We developed an affinity column method to quickly, simply, and cheaply isolate LDL and VLDL. We used a dose-response study of the antioxidants at physiologically relevant concentrations, pH, and temperature. We then determined the "quality" of the antioxidants as a single number, the concentration to inhibit the oxidation 50% compared to the control with no added antioxidants.

We have unequivocally demonstrated that many polyphenols (natural ingredients in plants including fruits and vegetables) are superior antioxidants compared to vitamins. The best antioxidant compound in our model was epigallocatechin gallate, a major polyphenol in green tea, which has been shown in epidemiological studies to be protective for heart disease. Polyphenols are antioxidants in our model at physiological levels, i.e., 1 micromolar. This corroborates epidemiological studies indicating that consumption of fruits and vegetables, which contain both vitamins and polyphenols, may be protective for chronic diseases such as heart disease and cancer due to the presence of the polyphenols as well as the vitamins. In other words, the active ingredients in fruits and vegetables are not simply the vitamins. As further evidence, taking single purified vitamins has not been proven to be very successful in clinical studies. It appears that the whole food, containing both the vitamins and polyphenols, is the best way to consume these antioxidants for health benefits.

Since the article, there have been publications demonstrating that beverages containing polyphenols, such as tea, wine, and beer, can inhibit atherosclerosis in animal models through multiple mechanisms, including antioxidants. Polyphenols have also been shown to beneficially influence cognitive function in the elderly by decreasing oxidative stress. What is becoming clear is that polyphenols have numerous biochemical mechanisms, including antioxidant functions.

Read the literature, always with a critical eye, and don’t always follow the crowd. Also realize that you don’t have to be at a large or high-level research university or institute to have an impact in science. On my office wall I have a quote from Albert Szent-Gyorgi, the discoverer of vitamin C, "Discovery consists in seeing what everybody else has seen and thinking what nobody else has thought."