Why doctors don't like to talk about antioxidants.

Health and medicine explained.
Aug. 3 2011 10:04 AM

The Doctor and the Pomegranate

Antioxidants don't work, but no one wants to hear it.

Pomegranate. Click image to expand.
Are pomegranates good for you or not?

Few medical remedies have a more sterling reputation than that assortment of foods, pills, and general life maneuvers known collectively as "antioxidants." At last, here's something that promises better heart health, improved immunity, a pellucid complexion as well as relief against cancer, arthritis, and the blahs—and it's all-natural! What's not to like?

Well, there is a wee small problem in our ongoing anti-oxidize-athon: As it turns out, we have no evidence that antioxidants are beneficial in humans. (Though if you're a Sprague-Dawley rat, there's hope.) In fact, as Emily Anthes wrote last year in Slate, the best available data demonstrate that antioxidants are bad for you—so long as you count an increased risk of death as "bad."

But, hey, who ever let a little evidence stand in the way of a good time? Especially in this case, when the charge toward lifestyle legitimacy has been led by willowy celebrities with karmic equipoise, ably supported by the Four Horsemen of the Alternative: Drs. Weil, Oz, Null, and Chopra. The seduction of this confederacy (sex! doctors! pills!) is immense; to appreciate its power, one need only consider the pomegranate. Once a rare fruit requiring a complicated eating strategy, its derivatives are now stationed on every grocery shelf based on their promise of an antioxidant punch.

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The field of antioxidants is further buffeted by the fact that no one really understands much about them, so winning an argument is greatly simplified. (And never mind that the main commercial use of antioxidants is to act as food preservatives, placing them squarely on the axis of toxicity). Their story began in the 1940s when a physician-chemist named Denham Harman set out to determine the biochemical explanation for aging. As a young man, he had worked in the lubricating department of Shell—a place where the problems of a chemical spoilage caused by "free radicals" were well-known. By the mid-50s Harman hit upon the theory that the same free radicals that were cutting into petroleum industry profits could also simply and completely explain the phenomenon of aging. Better yet, he said, their effects could be ameliorated by something called antioxidants.

But first, what exactly is a free radical? Not a fiery Berkeley politico but rather a lonely unpaired electron lost and spinning around an atomic nucleus. Electrons are compelled to travel in pairs; an unpaired electron therefore will greedily grab the next electron it meets, regardless of pedigree or station. DNA, RNA, mitochondria—it's open season. Sometimes the miscegenation does serious damage to the cell, resulting (the theory goes) in a gradual and irreversible deterioration. For us this means wrinkles and sagging and creaking joints.

The role of antioxidants in this schema is simple: They are brought onboard to hook up with the vagrant electrons and prevent damage. Harman's observation was supported by then-novel insights into management of radiation exposure, a large concern in the 1950s. One known effect of radiation was tissue damage that looked to us like aging. Among the treatments that seemed to blunt this effect were antioxidants such as melatonin, Acetylcysteine, and pentoxiphylline. Presto: A star was born. Never mind how meager the slings and arrows of everyday life are compared with radiation from an atom bomb. If it (might) work for gamma rays, imagine what it can do for my tennis elbow.

If only reality would play along. As noted by Anthes, and Michael Specter in his book Denialism, the first clear crack in the façade was the 2007 revelation in JAMA that antioxidant vitamins were not merely useless but harmful. Building on this clinical observation, a German group has developed a plausible scientific explanation of the increased risk. The title of the group's most recent publication, " Extending life span by increasing oxidative stress," pretty much sums up their view: The human cell should toughen up. It can benefit from enduring something harsh like the insult caused by free radicals. This way, the organism is more prepared to fend off the inevitable Big One, be it cancer or a toxic fume or perhaps a bout of cholera. Practice makes perfect.

Whether this line of inquiry turns out to be hokum or the first step toward elucidation of antioxidants' role may take years to sort out. What is evident immediately however is the wishy-washiness of your local doctor throughout the antioxidant debate: We were slow to jump onto the antioxidant bandwagon and are slower still to jump off.

This brand of muddle is standard operating procedure for clinicians; we are eternally trying to appear modern and open to the new, while remaining anchored in a reality-based mindset that demands facts and data. Many patients are put off by such caution and come to view us as fuddy-duddies, self-promoting sticks in the mud, flapping bags of hot air (not to mention greedy bastards who may be invested, literally, in maintenance of the status quo). Or else we are seen as being handcuffed and controlled by the rigid iron of Big Pharma.

With something as popular as antioxidants, which comprise a substantial piece of the $23 billion U.S. vitamin and supplement market, the problem is particularly acute. If we swim against the riptide of popular delusion and warn our patients against them, it's like we're denying the benefits of sunshine and fresh air. Any appeal to "evidence" in support of that view would have little traction with the consumer; double-blinded medical studies are counterbalanced, in America, by a parallel system of peer review in the form of a nonstop confab of health-themed talk shows, print magazines, and blogs.

So when a patient comes in to ask (or tell) me about the curative powers of antioxidants, I am stuck. I can give him a boring recitation of the latest findings, or mention that the National Center for Complementary and Alternative Medicine has declared that "there is limited scientific evidence to support the use of antioxidant supplements to prevent disease." And he'll tell me that the pills worked wonders for his sister-in-law out in Queens. We both sigh and look away. If he goes ahead and starts guzzling pomegranate juice, he doesn't tell me.

This momentary awkwardness exposes a larger and potentially troubling problem: the fragility of that most complicated of all partnerships, the one between doctor and patient. Many are in an ongoing tug-of-war because of a simple difference of opinion: The patient wants to live forever (natch!) and may embrace any harebrained scheme available (cf.: antioxidants); in response, the doctor assumes the chilly pose of the threatened medical ruling class.

Usually, the tug-of-war doesn't amount to much. Most doctor visits turn out to be a big nothing: a bump that isn't; a pain that fades; a rash that will go away. But once in a while, and especially as people descend the hill from middle age, that routine visit finds its way to a miserable, frightening place. Bad news is disclosed; plans must be made. And that's when antioxidants do their real harm. The arguing through the years regarding pomegranate juice and vitamin E and whether to buy a juicer has slowly corroded the mutual confidence that underlies the doctor-patient relationship. And this is a damage that has no quick remedy, real or imagined.

Kent Sepkowitz is a physician in New York City who writes about medicine.

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