Antioxidants have long been known to have protective effects against a host of chronic diseases, cancer included. Their ability to neutralize compounds called free radicals—the unstable molecular entities responsible for disease development—has secured their recommendation in any healthy diet and led to their widespread availability on stores’ supplement aisles.
In this article, we take a deeper look into the role of free radicals in disease development and explain just how antioxidants function to prevent radical-mediated damage. Finally, we tackle an often-ignored question: do antioxidant supplements (usually available as multivitamin formulations) actually work? Do they work better/as well as antioxidant-heavy diets? Importantly, can they reverse the damage done by irresponsible dieting?
How Are Free Radicals Created?
Oxygen is often referred to as one of biology’s biggest paradoxes. It is necessary for all human life and is the basis of cellular metabolism, the process by which cells convert the calories from food to the energy needed to complete basic functions required for normal health. The flip side--oxygen is also a highly reactive molecule. An inevitable consequence of cellular metabolism involves the formation of radicals called Reactive Oxygen Species (ROS), chemically unstable compounds that have the ability to “attack” and damage cellular DNA, protein, and lipids. In addition to metabolism, free radicals may also come from environmental sources (such as food or air) or form from exposure to the sun’s UV radiation.
Although ROS are thought to be the most common free radicals in the body, reactive species may also be derived from nitrogen and sulfur containing compounds (RNS and RSS, respectively).
Health Effects of Free Radicals
While free radicals exist in a variety of chemical configurations, they all share one defining feature: the ability to “steal” electrons from any and all molecules that will yield them (in chemical jargon, this process is called oxidation). Because chemical structure is based on electron-sharing (how chemicals bonds exist), “stealing” electrons has the ability to drastically alter a molecules structure and, thereby, its behavior.
Unpaired electrons create an energetically unfavorable chemical structure, a condition that makes the molecule unstable and prompts it to try to restore proper electron balance. The problem lies in the molecules urgency to restore its missing electron–that is, it becomes a volatile and reactive species ready to take any electron available for the taking.
As the radical restores its electron balance, the molecule from which that electron was taken (the “donor”) becomes oxidized and, itself, becomes a radical. This single process has the potential to become a cycle, as one reactive species creates another reactive species. If not quelled, this cycle can wreak havoc on cellular systems and lay the foundation of disease.
Are All Free Radicals Bad?
Common knowledge suggests that all oxidants are bad for our health–the sole reason for the popularity of antioxidant-rich supplements and the advertised benefits of antioxidant-heavy diets.
Oxidants (electron-stealing molecular entities like radicals) are actually essential for some biological processes, playing roles in cell signaling and homeostasis. In fact, exposure to small amounts of toxins or other cellular stressors may actually improve health. The theory is that the body learns how to prevent major damage (should it be exposed to larger quantities of the same stressor) once it learns how to deal with small amounts. The effect is called hormesis.
Animal testing has previously shown that endogenous free radical production actually extends life. Physical activity, which has the ability to increase oxygen consumption by more than 10x and boost metabolism, will subsequently and necessarily leads to increased oxidative stress. Is this a bad thing? Oxidants are suggested to remove any damaged tissue following physical activity and contribute to other health benefits, such as increase insulin sensitivity. Excessive intake of antioxidants after exercise may actually reverse some of these effects and prevent or delay recovery/adaptation following exercise and reduce possible cardiovascular and metabolic benefits.
Oxidants become detrimental to health when their number begins to exceed our body’s capacity to neutralize them; this cumulative effect is often described as oxidative stress. A correction to commonly held beliefs: antioxidants should not completely eradicate oxidant threat. Instead, they simply need to keep oxidant levels in check and maintain optimal levels.
The Dangers of Oxidative Stress Left Untreated
Prolonged and untreated oxidative stress can lead to a number of health complications. It is known, for example, to have the ability to access and damage DNA, changing cellular instruction. It is also known increase the oxidation of LDL cholesterol (“bad” cholesterol), making it more prone to stick to artery walls and cause plaque buildup. Its connection to cardiovascular disease and cancer are among the best understood, although it is also suggested to contribute heavily to chronic diseases such as diabetes and rheumatoid arthritis. Because the brain is especially susceptible to oxidative damage (due to its high metabolic rate and large amounts of unsaturated fats, the typical targets of lipid peroxidation), oxidative stress is also suggested to hasten cognitive decline and the development of neurological disease such Alzheimer’s and Parkinson’s disease.
What Are Antioxidants & How Do They Work?
The name “antioxidant” doesn’t belong to any one substance, but instead refers to a general chemical property. Antioxidants are molecules that have the ability to neutralize free radicals by donating electrons, effectively eliminating the unpaired condition of the radical. In effect, they “stabilize” a radical’s instability. We mentioned before that any electron “donor” (that molecule that gives up an electron to the oxidant) itself becomes a radical. How are antioxidants different?
Oxidized compounds vary in their stability, depending on their chemical structure. That is, some compounds are better able to handle a missing electron (due to a process called electron delocalization). That is, they are more stable radicals than the molecules to which they gave up an electron–and will not propagate the oxidative cycle. The antioxidants we’ve all become used to hearing about–vitamin A, C, and E, for example–are all “less active, longer-lived and less dangerous than those radicals they have neutralized,” according to published study. Additionally, vitamin C has been noted to not only neutralize the radical form of other antioxidants (such as the glutathione radical and the vitamin E radical) but also regenerate them.
Antioxidant Effects: a Clinical Perspective
Do the health claims about antioxidants intake stack up? The Harvard School of Public Health notes that while the nutrients found in fruits, vegetables, and whole grains (antioxidants, vitamins, minerals, and fibers) help prevent or slow the development of chronic disease, high doses of antioxidants (such as those supplied in supplement form) are unlikely to have the same effects.
The results of large, randomized, double-blind studies–which should, theoretically, provide the most convincing scientific evidence–have mostly suggested that high-dose antioxidant supplementation had no effect on longevity or prevention of chronic disease, and in some cases even increased mortality.
The Women’s Health Study, which followed nearly 40,000 initially healthy women for 10 years, indicated that vitamin E had no effect on the rates of cardiovascular events but did reduce overall cardiovascular mortality by 24%. The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) trial, which studied the effects of vitamin E (taken for 3 years) on 11,000 heart attach survivors, showed mixed results but generally noted no preventative cardiovascular effects. A separate vitamin E trial in Israel, however, showed some cardiovascular protective effects in those with type-2 diabetes, who are predisposed to greater oxidative stress than healthy adults. Similarly, beta-carotene supplementation did not show any cardiovascular protection, courtesy of the Physicians’ Health Study.
When it comes to cancer prevention, clinical results are fairly similar. The Physicans’ Health Study showed no difference in the incidence of cancer among those taking beta-carotene and those taking placebo. A study on the effects of selenium on cancer, however, showed promising results. Subjects taking selenium saw a reduced risk of developing skin, colon, lung, and prostate cancer. These effects were strongest in those who started with the lowest baseline selenium levels.
In the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study, a combination of vitamin C, vitamin E, beta-carotene, selenium, and zinc had no effects on cardiovascular disease prevention after seven and half years of supplementation. It did, however, show a marked reduction in the risk of developing cancer as well as all-cause mortality in men, but not women. The Women’s Antioxidant Cardiovascular Study similarly suggested that combinations of vitamin C, vitamin E, and/or beta-carotene had the same effects as placebo on incidence of cardiovascular events (heart attack, stroke, cardiovascular revascularization, and death by cardiovascular dysfunction).
- Header Image: Clemens v. Vogelsang (Flickr)
- Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems - Journal of Cellular and Molecular Medicine
- Antioxidants: Beyond the Hype - Harvard School of Public Health