Dear Dr. Phaneuf,
You describe very clearly how antioxidants protect our cells, and in your book you also describe which plants have interesting antioxidants and how they work, but when it comes to people taking antioxidant pills, you become suddenly skeptical to the idea. How do you reconcile these points of view? -Lucas
Hi Lucas,
The bottom line is this: I still am excited about antioxidants, don't get me wrong. But antioxidants in pill or supplement form don't do anything dramatic according to the best clinical studies. Not only are some very expensive, but large doses of them turn them into free radicals and oxidizing agents, the very thing you are trying to avoid, by taking them.
If you don't understand how an antioxidant can turn into an oxidant, it is very simple, and I explain it in how antioxidants turn into oxidizing agents (click here).
First, you need to know that oxidizing agents and free radicals (which are often the same), generally known as ROS (reactive oxygen species) are an unavoidable consequence of cellular respiration--and these ROS do damage to our cells. It There is good evidence that these ROS may initiate many of our common diseases and general aging. Antioxidants (which chemists call reducing agents) neutralize ROS by a variety of mechanisms.
People who eat a lot of fruits and vegetables are less prone to diseases--the very diseases that we think may be caused by oxidizing agents. Now, people have formed a logical theory that since plants contain many antioxidants, these antioxidants are combating ROS and their associated ill effects. But hold on to your hats--this is just a theory and it may be all wrong!
We actually don't really know why people who eat a lot of fruits and vegetables live healthier lives. Perhaps the many studies are "confounded"--that is, what else do people who eat lots of fruits and vegetables do? Probably exercise, buckle their seat belts, avoid smoking, and all that. We try our best to statistically weed out confounding factors in these observational studies, but if you are a good scientist, you have to be honest and admit that some confounding might be going on.
Just because you can imagine a great mechanism, and see it take place in a test tube with isolated cells, does not mean that same mechanism will work in a person.
Well, here we were with this lovely theoretical mechanism for how antioxidants from plants could be helping us live longer lives. So based on this theory, isolated antioxidants in pill form ought to be great, right?
Wrong! We all held our breath for years as study after study came out, testing everything from classic antioxidants like vitamins E and C, to more obscure polyphenols and glutathione and so on. Nothing that dramatic appeared. For the most part, the only time you saw a noticeable effect is when the lab animals or people started out with a deficiency in the item tested to begin with. In some cases large doses of antioxidants proved harmful--one of the most dramatic cases was with beta carotene significantly increasing cancer among smokers, to the point that the investigators had to pull the plug on the study to save the participants. Large doses of tannins may cause cancer. Large doses of quercetin make you dizzy and make you throw up, and can cause tingly nerves in the extremities.
As someone who has synthesized and tested antioxidants in the lab, and been in on some of this research, I can't tell you how disappointing this has been for me.
But nature is always trying to tell us the truth through the data, I believe, and you always have to look especially hard at data that you don't like, because it might be telling you something even more wonderful than your previous conceptions allowed. Nobody likes to toss out their pet theories. But science forces us to do this repeatedly. I really trust that the truth is in good data, even data we don't personally like.
So for now it seems like a good idea to just eat your fruits and vegetables,drink tea and/or coffee (with or without caffeine) and put your favorite cooking spices and herbs on your food to flavor it. I would definitely skip the supplements.
Now, why might antioxidant pills be so ho hum in clinical studies? There are lots of good theories:
1) Targeting to mitochondria
One of the most intriguing theories, to me, is that antioxidants don't work unless they get to the very place where they are most useful--the mitochondrion. This is the cellular structure where respiration takes place. It is where about 90 percent of our oxygen gets used. This is the place where most of the harmful ROS are generated. Even cells in culture with antioxidants dumped on them may absorb the antioxidants, but the antioxidant still doesn't get inside the mitochondria in the cells.
Recently, chemists have synthesized antioxidants that are targeted to mitochondria. That is, they have given them chemical mailing addresses, so to speak, that help deliver them to the mitochondrion. (Actually, this is just a consequence of electrostatic forces--the inside of a mitochondrion is mostly negatively charged, and they put permanent positive charges on these antioxidants, and since negative attracts positive, the force of the charge pulls the drug into the mitochondrion.) So far no people, to my knowledge, have taken these mitochondrially targeted antioxidants, but they are getting positive results in studies with cells and rats.
2) Absorption into the bloodstream
Antioxidants in the polyphenol class in particular, including flavonoids, are notoriously bad at making a one way trip through your digestive tract, down to the bitter end. Many are physically large, and bind to proteins in your gut in some cases, literally "tanning your hide" in your gut in the case of tannins. Resveratrol in grapes is SO exciting--in test tubes. But just try to get that sucker into your bloodstream. OK, some trace amounts can get through, but those then are swiftly metabolized into other things. It may still be that their action in the gut alone is not to be dismissed and is helpful. Some scientists have proposed that in plant foods, the fiber of the food slows the release of such polyphenols so they are absorbed more efficiently, as opposed to in pill form. That is a good theory, but remains to be tested.
3) We actually need oxidizing agents and free radicals.
I have had to laugh out loud at some supplement sellers, who paint all free radicals as bad, if not actually "evil"! One described free radicals as "having only one purpose, to destroy you"! (Just a note--chemicals are not alive and have no purpose, and can't really be regarded as good or evil).
It would have indeed raised the eyebrows of the writer of this alarming passage to learn that many free radical scavengers work by becoming stable free radicals. So, these stable free radicals are actually helpful. Also, we need free radicals in the right places--we need a smattering of nitric oxide in our blood vessels, which is a free radical and a simple gas, as a very important hormone like molecule that lowers our blood pressure and performs so many other important functions.
So it is not that free radicals and ROS are "bad" and antioxidants are "good", but we need both, in the right places, and in balance with each other.
4) Plants also contain ROS. Maybe these are helpful.
Plants make all sorts of toxic things, often functioning as insecticides and antimicrobials (since they can't run away from insects and pests, they tend to synthesize some nasty chemical weapons). That is one reason why, as a chemist, I find plants so fascinating--they are much better synthetic chemists than I could ever hope to be. Not only does coffee and and tea--my own favorite plant derived products--contain a lot of antioxidants, but they also contain ROS like hydrogen peroxide! One theory is that these ROS kick-start our defensive processes like the induction of the synthesis of new antioxidant enzymes.
The bottom line is that the story is never as simple as the supplement sellers would have you believe--but it is far more interesting!
