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Nutrition

Antioxidants Overview

Diabetes  |  HIV  |  Hypertension

Introduction

Within the last 20 years, the putative health benefits of antioxidants on the risk for heart disease and cancer and the aging process suggested by research studies have increased their popularity as dietary supplements.  According to the latest NHANES data (1999-2000), over half of U.S. adults take dietary supplements; most commonly reported were multivitamins (35%), followed by single-nutrient supplements of the antioxidant vitamins C (12%) and E (13%). [1]

Dietary antioxidants are substances in foods that significantly decrease the adverse effects of reactive species, such as reactive oxygen and nitrogen species, on normal physiological function in humans.  An imbalance between antioxidant defenses and the production of reactive species (also called free radicals) is defined as oxidative stress.  Oxidative stress has been  implicated in the pathogenesis of many degenerative diseases, including cardiovascular disease, cancer, diabetes, cataracts, rheumatoid arthritis, and neurodegenerative diseases. [2]

Antioxidant Defense Mechanisms

Free radicals are formed endogenously from normal metabolism as well as during inflammatory processes.  Environmental sources of free radicals include cigarette smoke, ultraviolet radiation, and air pollution.  Most but not all reactive species contain one or more unpaired electrons, thus making them highly reactive molecules.  Free radicals can oxidize adjacent cellular constituents, including lipids, proteins and nucleic acids, oftentimes causing irreversible damage and impairment of cell function.  Antioxidants like vitamins C and E can quench free radicals by donating electrons while remaining relatively stable themselves in an oxidized state until they are recycled (reduced) to their bioactive form or metabolized.  Dietary antioxidants are commonly found in plant foods like fruits, vegetables, whole grains, nuts, wine, and tea.  Common dietary antioxidants include tocopherols (vitamin E), ascorbic acid (vitamin C), carotenoids, polyphenolics like flavonoids, and other phytochemicals.  

The antioxidant defense network also includes endogenous compounds such as the enzymes catalase, glutathione peroxidase, and superoxide dismutase, as well as uric acid, a-lipoic acid, coenzyme Q10, and the transition metal binding proteins, e.g., transferrin and ceruloplasmin.[3]  Levels of endogenous antioxidants are determined by their rate of synthesis and, therefore, not as readily manipulated via the diet as antioxidant nutrients and phytochemicals in foods and supplements.[4]

Research

Most dietary antioxidants potently quench free radicals in biological systems such as plasma, lipoproteins, and cultured cells though their relative efficacy in vivo varies substantially due, in part, to their bioavailability, metabolism, distribution, and elimination.[5]  Observational studies consistently show that diets rich in antioxidant-containing fruits and vegetables are associated with reduced risk for chronic diseases such as cancer [6] and heart disease. [7]  Large cohorts such as the WHO/MONICA Project [8], Basel Study [9], Health Professionals Follow-up Study [10], and Iowa Women’s Health Study [11], have show an inverse association between dietary intake or plasma levels of antioxidants and decreased risk of, or mortality from, cardiovascular diseases and many types of cancer. 

In contrast, randomized clinical trials of antioxidant micronutrient supplementation have been mostly equivocal with respect to primary or secondary prevention.  For example, the Alpha-Tocopherol Beta-Carotene (ATBC) [12] and the Beta-Carotene and Retinol Efficacy Trial (CARET) [13] concluded that supplemental β -carotene provided no protection against lung cancer among heavy smokers and asbestos workers.  Unexpectedly, these trials found a higher risk for lung cancer for those subjects given β -carotene compared with those receiving a placebo.  However, in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study [14] of middle-aged adults from the general French population, a low-dose combination of antioxidant micronutrients lowered total cancer incidence and all cause mortality in men, but not women.  Similarly, supplementation with a combination of antioxidant micronutrients in a poorly nourished Chinese population [15] lowered total mortality, mostly due to reduced rates of stomach and esophageal cancers.

Critical Thinking Questions:

  1. Could high dietary and plasma antioxidant levels simply be markers of fruit and vegetable intake?

  2. How might a clinical trial of antioxidant supplements be designed to address primary disease prevention among apparently healthy people? 

  3. Does oxidative stress play a causal role in chronic diseases, or is it a consequence of disease?

  4. How is oxidative stress measured in the body?

  5. Does the efficacy of antioxidant supplementation depend on the patient’s initial level of oxidative stress?

  6. How might appropriate dosages and combinations of micronutrient antioxidant supplements be determined?

  7. Can trials employing combinations of antioxidant supplements adequately assess their synergistic effects?

  8. When might the effects of antioxidant supplements be mitigated by standard therapies?

  9. What other bioactivities have been demonstrated for dietary antioxidants other than quenching free radicals and diminishing oxidative stress?

Links:

From the Institute of Medicine:

Professional Societies, Agencies, and Government Organizations:

Nutrient Databases:

Quality of Dietary Supplements:

TUFTS UNIVERSITY PROGRAM IN EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
A joint Tufts University Medical School and New England School of Acupuncture program
Acknowledgements and disclaimer | Date last modified: Friday, October 31, 2008

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