News broke this week about a study that followed up on men who took high doses of vitamin E for about five years. The study found that these men had a slightly increased risk of prostate cancer, even after they stopped taking the supplement.
First, this study chose to use a synthetic form of vitamin E (dl-alpha-tocopherol-acetate). The form of vitamin E that has been associated with decreased risk of prostate cancer in prior studies was d-alpha-tocopherol succinate. These can be metabolized differently by the body. Additionally, the study that suggested lower prostate cancer risk associated with vitamin E used 50 mg doses - much smaller doses.
But my major beef with this type of study is that they are applying a system of randomized clinical trials that was designed to evaluate drug effects to evaluate nutrients. Nutrients are not drugs and don't act like drugs - they act together in complex networks.
For someone eating an average diet of processed foods, which is antioxidant-poor, taking a large dose of an antioxidant like vitamin E means dumping a large dose into what is very likely an inadequate antioxidant network.
What does this mean? Once vitamin E quenches a free radical, it becomes a free radical itself, until quenched by another antioxidant within its network. Polyphenol antioxidants, such as resveratrol or quercetin etc., because of their ring structure, can donate an electron without becoming a free radical themselves; this property is called electron resonance. When vitamin E, vitamin C or vitamin A become free radicals, they must be reduced (get an electron) from another member of the antioxidant network to be restored to being an active antioxidant.
Large doses of single antioxidants that don't have electron resonance capability, like vitamin E, have the potential to become longer-lived free radicals, which can contribute to, rather than alleviate, oxidative stress.
I believe this to be an explanation for the findings: If one is under high oxidative stress, consuming an antioxidant-poor diet and taking high doses of antioxidants, these antioxidants have the capacity of becoming longer-lived damaging free radicals. That's why when consuming few antioxidants, taking smaller doses of antioxidants will be safer.
From a biological perspective, it would make sense to use dozens of antioxidant compounds together. Often scientific studies want to know what the sole active ingredient is, which is like asking, "What part of the car engine makes it work?" All parts of the engine have to work together. Thus, a series of antioxidant compounds have to work together, too. Studying nutrients with drug models is always going to lead to flawed conclusions, and we need to develop more appropriate research models for studying nutrients clinically.
Some might find it strange that the statistically significant increase in prostate cancer cases occurred years after the study participants had stopped taking vitamin E. However, this makes perfect sense in the context of cancer biology. An increase in oxidative stress means DNA damage. After a period of DNA damage, an increase in tumors is never seen before 5 years.
The good news is that there are also many DNA repair mechanisms in normal cells. These can be supported by a variety of naturally occurring compounds in plants, particularly the ones used in botanical medicine, but also in normal diet, such as the polyphenolic antioxidant ellagic acid found in many berries and pomegranate. This is just one of hundreds of possible examples of natural compounds that stabilize DNA and support its repair.