An editorial in a December 2013 Annals of Internal Medicine journal declared vitamins are useless. Over the past decade an increasing number of articles have appeared in well-known medical journals cautioning people not to take certain vitamins such as vitamins A and E or other antioxidants, except to treat a diagnosed vitamin deficiency. “The literature is providing growing evidence that these supplements – in particular, at high doses – do not necessarily have the beneficial effects they have thought to,” stated Demetrius Albanes, a senior investigator at the Nutritional Epidemiology Branch of the National Cancer Institute. Some articles were alarming, indicating there might be an increased risk of heart disease or cancer by taking vitamins. Part of the problem in evaluating these negative articles is it is unknown whether synthetic vitamins and inorganic minerals were used as opposed to natural vitamins and naturally chelated minerals. The vitamin E studied in this science review, for example, was synthetic, isolated vitamin E which already has a long history of being toxic for human consumption. These researchers never looked at full-spectrum vitamin E, including the tocopherols, nor did they bother to study a food concentrate form of vitamin E.
Just a few weeks after the Annals of Internal Medicine article came out, a study sponsored by the Department of Veterans Affairs was published in the JAMA (Journal of the American Medical Association) where over 600 elderly veterans were given high doses of vitamin E and this vitamin delayed the decline in daily living skills, such as making meals, getting dressed and holding a conversation. This is the first time any treatment has been shown to slow the course of dementia in mild-to-moderate Alzheimer’s disease.
Because multiple other studies presented at medical conferences I have attended showed a benefit of taking vitamins in terms of reduction in cancer and cardiovascular risk, I initially ignored the negative journal articles. Most of the studies quoted, but not all, were what are called meta-analyses. A meta-analysis refers to methods focused on contrasting and combining results from different studies, in the hope of identifying patterns among study results, sources of disagreement among those results, or other interesting relationships that may come to light in the context of multiple studies. This is a retrospective type of study and is not the same thing as a prospective study where one group of patients would be given a drug or vitamin, and a similar group would receive a placebo, and the outcomes determined at the conclusion of the study.
As we gain more and more medical knowledge the evidence is now suggesting aging is a far more complex process than exposure to free radicals and that there might be validity to a downside from taking too many antioxidants.
Is The Free Radical Theory of Aging A Myth?
Rebeca Gerscham and her colleagues first introduced the notion that free radicals are toxic agents in Science in 1954. Roughly sixty years ago a physician and researcher by the name of Denham Harman hypothesized free radicals might be the cause of the aging process. He knew ionizing radiation, pollution and even normal metabolism by breathing oxygen sparked the production of free radicals. Because both cellular damage and free radical levels increased with age, Harman thought free radicals caused the damage and antioxidants probably slowed it.
Dr. Harman tested his hypothesis by feeding mice antioxidants, and showed they lived longer. In 1969 researchers at Duke University discovered SOD (superoxide dismutase), an antioxidant enzyme produced inside the body. They hypothesized that SOD evolved to counter the effects of free radical accumulation. Over time, scientists had difficulty replicating some of Harman’s experimental results on a consistent basis.
By the 1990s genetic advances allowed researchers to test the effects of antioxidants by directly manipulating genomes to change the amount of antioxidant enzymes an animal was capable of producing. Arlan Richardson, director of the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center genetically engineered 18 different strains of mice. Some of the mice produced more than average antioxidants and some produced less than average. The life span curves between the two groups showed no significant difference, indicating the amount of oxidative damage the mice endured had no bearing on how long they lived. Researchers at the University of Washington have demonstrated that mice live longer when they are genetically engineered to produce high levels of an antioxidant known as catalase. So the results in the Washington study are completely the opposite of the Texas study. Of course, what applies to mice may not apply to humans.
Oxidation and the Formation of Free Radicals
What is oxidation? Oxidation is defined as the addition of oxygen to an atom or molecule. It is defined more technically as the loss of electrons from an atom or molecule. Reduction is the addition or gain in electrons. “Redox” refers to reduction/oxidation agents or reactions and changes in oxidative states (usually with electron transfer). There cannot be an oxidation reaction without a simultaneous reduction reaction. The term “reactive oxygen species” is defined by the U.S. Library of Medicine as “Molecules or ions formed by the incomplete one-electron reduction of oxygen.” These reactive oxygen species were thought to cause oxidative damage to nucleic acids, proteins and lipids.
Within mitrochondria a stream of electronically modified oxygen derivatives are continuously being formed and may not be as harmful as previously thought. In fact, after donating an electron, an antioxidant becomes a free radical, by definition, and some are capable of initiating chain reactions. Many vitamins and supplements classified as antioxidants are actually redox agents, meaning they act as antioxidants in some instances and pro-oxidants in others. Vitamin E and Vitamin C fit this category. So what we are finding is that antioxidants don’t “destroy” free radicals, they simple are involved in electron exchange.
Are Free Radicals Helpful or Harmful?
Assuming free radicals accumulate as we age but do not necessarily cause aging itself, some researchers have speculated that free radicals, in some cases, might be produced in response to cellular damage as a way to turn up the expression of genes that help repair the body’s tissues. A 2010 study out of the University of California showed some free radicals turn on a gene called HIF-1 that is itself responsible for activating a number of genes involved in cellular repair, including a gene that helps repair mutated DNA. This study was done in worms.
In January 2013, researchers at the University of Manchester (Colorado State) found that oxygen free radicals aid rather than harm cell regeneration in tadpoles. Hydrogen peroxide is not only harmless to cells, but is actually the catalyst that makes it possible for tadpoles’ tails to completely regenerate in less than a week. This regeneration process was inhibited by antioxidants.
Exercise can increase oxygen consumption up to 15-20 fold over resting levels, which, in turn, generates vastly more free radicals. Exercise has been proven very beneficial to one’s overall health and longevity. Basically, a bout of exercise gives us a “dose” of free radicals.
High dose intravenous vitamin C works as a pro-oxidant and causes the generation of hydrogen peroxide by white blood cells. Dr. Levine at NIH (National Institutes of Health) determined in his research with vitamin C that this was the mechanism intravenous high dose vitamin C killed certain types of human cancer cells – through the production of hydrogen peroxide. This finding was published in recent medical journals. Going back to the 1960s and 1970s, a group at Baylor University Medical Center found that intra-arterial and intravenous administration of hydrogen peroxide would aid in killing cancer and pathogens, and aid in the regression of atherosclerotic plaque. Humans do not produce vitamin C, but many animals can. According to H.M. Howes, M.D., Ph.D, animals that produce 1 molecule of vitamin C also produce 1 molecule of hydrogen peroxide.
So as counter-intuitive as it may seem, there is growing evidence that taking antioxidants in excessive amounts may have a negative effect by countering the positive effects of pro-oxidants and free radical stress. What constitutes an “excessive amount” remains to be seen. In my opinion, what may be excessive for one person may be therapeutic for another. I do not subscribe to a “one size fits all” concept for medication dosing or supplement dosing.
We know large amounts of oxidative damage have indisputably been shown to cause cancer and organ damage, and plenty of evidence indicates that oxidative damage plays a role in some chronic conditions e.g. heart disease. We also know B vitamins and antioxidants are prescribed by ophthalmologists to treat certain types of macular degeneration. But what current evidence now shows is that free radicals may be beneficial in some contexts and dangerous in others. In my opinion, aging is a complex, multifactoral process that doesn’t have a single cause or a single cure. Taking mega-doses of antioxidants on a daily basis may not be wise and we need to remember a diet high in vegetables and fruits is not the same thing as taking a pill. Having said that, a significant number of Americans have poor dietary habits (e.g. a donut and coffee for breakfast) and taking a daily multivitamin is just insurance. At the Center we target nutritional therapies to correct deficiencies, using traditional labs, Spectracell intracellular nutritional testing, and hair analysis of minerals to help us determine deficiency states.