Antioxidants: bridging the gap between biochemistry and clinical practice.

When my friends ask me “What dose of vitamin E should I take?” or “What vitamin should I take to prevent this problem?” I am hesitant to reply “I do not know. There is not enough clinical evidence to give a good answer for that question.” Unfortunately with the topic of antioxidants, however, this generally has been my response. Additionally, I am often frustrated, wondering, “What antioxidant supplements should I be taking?” Because of the widespread interest in these agents among the public, it behooves the practitioner to stay abreast of the validity and viability of antioxidants as potential therapeutic or protective agents. Despite conflicting results of clinical trials, practitioners and the lay public want to find the ideal agent, the ideal dose, or the ideal “cocktail” to provide antioxidant benefits. Dr Susan Clark provides an excellent, intensive review of the biochemistry of antioxidant agents and their extensive interrelationships, and she suggests basic tenets for the practitioner’s consideration before prescribing these agents. I believe that Dr Clark provides information that not only reminds practitioners of the theory behind the use of these agents, but also may aid researchers in designing clinical trials that will investigate the use of these agents in concert with each other. It seems for every clinical trial suggesting a protective role for a particular antioxidant, there are an equal number of trials suggesting no benefit or even harmful effects. For example, the Cambridge Heart Antioxidant Study (CHAOS) provided promising hope for a cardioprotective effect with vitamin E supplementation. Disappointing results, however, were reported by the Heart Outcomes Prevention Evaluation (HOPE) and GISSI Prevenzione Trials for this protective role. Before the -Tocopherol, -Carotene Study (ATBC) and -Carotene and Retinol Efficacy Trial (CARET) reports, most considered antioxidants as potentially beneficial only, but we now know that in certain patient populations, these agents can have harmful effects. Explanations for these discrepancies and conflicting results have been proposed. Perhaps antioxidants should not be used to “treat” an existing disease; instead, the protective/preventive role must be in effect before a disease develops. Perhaps there are lifestyle differences that have an unmeasured impact on the development or progression of disease. Perhaps the length of therapy or dose of the agent used was suboptimal. Perhaps another component of the diet, such as a phytochemical, had been overlooked as offering the protective benefit. As suggested by Dr Clark, we should consider the interrelationships of the antioxidant vitamins and use the synergistic relationship when designing a clinical investigation. I like the five lessons that Dr Clark provides to aid the practitioner in making clinical applications. I always knew that both of my grandmothers were very intelligent and intuitive. This belief was further confirmed by Dr Clark’s conclusion that “grandmother’s advice rules: eat your fruits and vegetables.” As suggested by the American Dietetic Association, the best way to acquire antioxidant vitamins is through the consumption of a variety of fruits and vegetables. From my own personal experience, my grandmothers always served a colorful array of fruits and vegetables at most meals. Many unanswered questions regarding antioxidants remain. I continue to be reluctant to recommend specific vitamins or specific doses of vitamins for general prevention of disease; however, in states of deficiency I believe there are occasions when supplementation could be beneficial. Finding the balance between antioxidant and pro-oxidant benefits proves to be a challenging task; however, Dr Clark’s review will aid the practitioner in making rational, informed decisions when prescribing these agents. Her review can also be viewed as an appeal to researchers to continue refining study designs to capitalize on the synergistic effects of these vitamins. After reviewing Dr Clark’s article, I telephoned my mother and made the request, “Will you prepare a dinner like Grandmother used to serve?” Correspondence: Jeffrey F. Binkley, PharmD, BCNSP, Vanderbilt Center for Human Nutrition, Medical Arts Building, Suite 514, Nashville, Tennessee 37212. Electronic mail may be sent to jeff.binkley@mcmail.vanderbilt.edu.