ANTIOXIDANTS ARE MAGICAL. At least when it comes to marketing. Just slap the word on the label of a food or beverage and watch sales zoom. That’s because even people who have no idea what antioxidants are want more of these substances in their life than less. And they could be right. Or not. It seems the “free radical theory” of disease and aging may not be on as firm a ground as we have been led to believe. And if that is the case, antioxidants may not live up to their exalted status as the key to good health and longevity.

Back in the 1950s, Dr. Denham Harman proposed a theory that at the time seemed rather radical. Many ailments, including cancer and heart disease, as well as the aging process itself, he suggested, were the result of cumulative damage caused by reactive molecular species called free radicals. Since these were byproducts of metabolic reactions involved in energy production, their formation in the body was inevitable. Why? Because nutrients derived from food are slowly combusted in mitochondria— the small, membrane-enclosed regions of cells. And, as in any combustion process, oxygen is required. Unfortunately, as oxygen reacts with nutrients to produce energy, it also unleashes some “friendly fire” in the form of the notorious free radicals.

Different types of free radicals can appear, but they all descend from a highly reactive species of oxygen known as superoxide. Radicals are hungry for electrons and try to satisfy their appetites by feeding on innocent molecular bystanders. Since electrons are the glue that binds atoms in a molecule together, molecules that become the targets of free radical attack tend to fragment. Such damage in turn translates to disease, particularly when the victims of free radical onslaught are proteins, fats or molecules of DNA. Harman hypothesized that our bodies deal with free radicals by mounting “antioxidant defences.” Vitamins E and C, along with enzymes such as superoxide dismutase, catalase and glutathione peroxidase, were quickly labelled as antioxidants, acknowledging their ability to neutralize free radicals in the test tube. Harman then buttressed his theory by feeding antioxidants to mice, claiming that the animals lived longer. The free radical theory was off and running.

Over the next couple of decades, researchers tested more and more substances in the laboratory for free radical–neutralizing effects, discovering a plethora of antioxidants. The likes of polyphenols, carotenoids and lipoic acid, all found in fruits and vegetables, obliterated free radicals in laboratory experiments. Since populations consuming more fruits and vegetables were known to be healthier, a seemingly obvious explanation now emerged: antioxidants in food prevent disease! A corollary was that dietary antioxidant supplements should also prevent illness, an idea that gave rise to a new market trend. Touting their antioxidant potential, vitamins, minerals, various seed and bark extracts, teas and exotic fruit juices began to vie for the public’s attention. And they did so successfully. Sales of antioxidant supplements skyrocketed. Even skin creams joined in the game, hyping the efficacy of their antioxidant ingredients in the battle against the ravages of age.

But now the wheels on the antioxidant bandwagon are developing some squeaks. Since the 1990s, numerous randomized, placebo-controlled trials have investigated the effects of vitamin C, vitamin E, selenium and beta carotene, the classic antioxidants, on cancer and heart disease. While some studies offered hope, the majority failed to show any benefit associated with antioxidant supplements. Some, particularly those using beta carotene, actually suggested potential harm, for smokers at least. Recent studies have not brightened the outlook. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomly assigned more than thirtyfive thousand men to take either selenium, vitamin E, both or a placebo on a daily basis. The trial was stopped after five and a half years because no differences were observed between the groups in relation to prostate cancer risk. Similar results were noted in the Physicians’ Health Study II. About fifteen thousand male physicians were enrolled and asked to take either vitamin C, vitamin E or a placebo for eight years. Neither vitamin had an effect on prostate cancer or total cancer. And now a major study on heart disease has thrown more cold water on the antioxidant theory. This time, the subjects were diabetics, who are, in general, predisposed to heart disease. In the Prevention of Progression of Arterial Disease and Diabetes Trial, more than a thousand adults aged forty or older were assigned, on a random basis, to take either a daily capsule containing a mix of antioxidants or a placebo for eight years. The antioxidants offered no protection against cardiovascular disease.

Could the free radical theory of disease and aging be totally wrong? Not likely. But neither is it the complete answer to the complexity of aging and disease. This is now underlined by a fascinating study on nematode worms at University College in London and Ghent University in Belgium. Granted, people aren’t worms (in most cases anyways), but these tiny creatures do serve as an excellent model for the study of aging. Their normal life expectancy is only a few days, so any change is readily noted. The researchers managed to inactivate the worms’ genes that code for superoxide dismutase, one of the prime antioxidant enzymes.

They expected to see a reduction in life expectancy in response to increased oxidative stress; while there was evidence of increased free radical activity, the worms did not die any sooner. Aging apparently was unaffected by reducing antioxidant activity.

What does all of this mean? That when it comes to health, disease and aging, nothing is as simple as it seems. And so it is with the free radical theory. Evidence is mounting against antioxidants being as important as we thought. But at the same time, we have more and more evidence for the benefits of increased fruit and vegetable intake. A conundrum? Not necessarily. Fruits and vegetables contain hundreds of compounds that may have positive effects that are not yet fully understood, and perhaps we have been overzealous in attributing magical effects to antioxidants.

THE CHEEZ WHIZ EFFECT
NEWS FLASH! The Food and Drug Administration in the U.S. has approved the addition of trans fats to dairy products, meal-replacement bars, soy milk and fruit juice. Now, I know what you’re thinking: the agency has gone mad. Either that or it has capitulated to big business. After all, aren’t trans fats a nutritional pariah? Are these not the nasty, artery-clogging substances that food producers and restaurants are being urged to purge from their repertoires? Well, the fact is that not all trans fats are fiends. The ones producers are considering adding to foods are not the same as the ones that are terrifying people with their artery-clogging potential. In fact, these trans fats may be good for us. It all comes down to some subtle differences in molecular structure.

Fats are composed of long chains of carbon atoms, joined to each other either by single or double bonds. It is the latter that give rise to the trans conundrum. Depending on the particular arrangement of atoms around the double bond, the chain of carbon atoms will be straight (trans arrangement) or bent (cis arrangement) at the position of the double bond. This may not seem to be very important, but the way a fat engages in biochemical reactions depends on its molecular shape. As a further subtlety, fat molecules can have more than one double bond, each with the cis or trans configuration. Furthermore, the double bonds may be located at different positions along the chain of carbon atoms. The trans double bonds that we worry about are the ones that are separated from each other by more than one single bond. These arise as a result of the hydrogenation process used to harden liquid vegetable oils to improve their keeping properties and to make them more suitable for frying. Unfortunately, these fats don’t have excellent properties for keeping our health. They’re the trans fats that have been linked with heart disease.

However, trans fats also occur in nature, particularly in meat and dairy products. But in these, the double bonds are separated from each other by just one single bond. Such fats are referred to as “conjugated” and have a completely different health profile from the ones that result from hydrogenation. Conjugated linoleic acid (CLA) contains two double bonds, either of which can assume the cis or trans configuration. The molecules of interest in terms of health benefits are those that have one cis and one trans double bond. Although technically these are trans fats, there is a world of difference between their biological activity and those of the trans fats that may lurk in your doughnut or order of french fries.

The story of the “good” trans fats started with an investigation of the “bad” properties of hamburgers. In the late 1970s, Dr. Michael Pariza at the University of Wisconsin became interested in the chemical reactions that take place when meat is cooked. Suspicion had been raised that carcinogens may form at high temperatures, and indeed these fears were realized. But much to Pariza’s surprise, he also found that cooked hamburger contained some compounds with decided anti-cancer effects. These turned out to be the CLAs, which then understandably excited a number of researchers.

Before long, CLAs were also found to be present in dairy products, originating from chemical reactions in the stomachs of ruminating animals. That’s where enzymes convert naturally occurring cis fats in the animals’ diet to CLAs. When different dairy products were analyzed for CLA content, researchers were in for a surprise: that curious American concoction known as Cheez Whiz had a higher CLA content than any other food. This finding provided plenty of whimsical fodder for reporters who, with tongues planted firmly in cheeks, began to label Cheez Whiz as the new health food. Of course, the spread is no such thing— its CLA content is easily trumped by unhealthy doses of saturated fat and salt. The Cheez Whiz effect was actually not a boon for CLA research, as critics smirked at the prospect of an ingredient in this odd gustatory creation being touted as potentially “healthy.” But they are not smirking at the mention of CLAs now.

A stunning amount of research has been carried out since the initial Cheez Whiz caper brought CLAs into the public spotlight. While no anti-cancer effect has yet been demonstrated in humans, animal models and cell cultures have repeatedly confirmed the initial finding. The greatest excitement, though, has been over CLAs’ ability to reduce body fat while enhancing lean body mass. Although supplementing the diet with CLA does not result in a reduction of body weight, it is effective in reducing fat mass and increasing muscle mass. The most significant effects have been seen in people who have lost weight through a lowcalorie diet and then put the weight back again, as commonly happens. But subjects who were supplemented with about three grams of CLA a day were more likely to regain the weight as muscle rather than fat. Other experiments have suggested that CLAs can enhance immune function and reduce atherosclerosis, high blood pressure and inflammation. Quite a grab bag of positive findings! Pretty alluring, especially given that no significant side effects have been noted.

As one might expect, producers have been itching to add these compounds to regular foods so that they can then be promoted as having health properties beyond simple nutrition. While dietary supplements of CLAs made by chemically treating sunflower or safflower oils have been available for a couple of decades, their status as food additives has been in a regulatory limbo. Until now. With the FDA giving the go-ahead, producers are set to crank out cookies, eggs, yogourt, milk— and who knows what else— enriched with these “good” trans fats. Whether the promise of CLA enrichment is fulfilled remains to be seen. While the right dose may offer certain benefits, the Holy Grail has not been found. And if you want some CLA enrichment before fortified foods come our way, well, yak cheese and kangaroo meat are the way to go. Or you can take a supplement. Michael Pariza does— three grams a day. As for me, I’d like more evidence. But I just might dip my broccoli in Cheez Whiz. Geez . . . I can’t believe I said that.