Chasing Life, page 5
No one disputes the immense damage caused by free radicals. These unstable oxygen molecules produce what is called oxidative stress, which has now been linked to more than one hundred diseases. Search the medical literature on oxidative stress, and you will find more than 39,000 papers. What’s more, free radicals and the resulting oxidative stress have been linked to aging, which is why I am including them in this book.
Back in 1969, when McCord and Fridovich published their groundbreaking findings on superoxide dismutase in the Journal of Biological Chemistry, their paper was met largely with indifference, even in the field. McCord remembers presenting the findings for the first time to his peers at the Federation of American Societies for Experimental Biology in Atlantic City, New Jersey. He talked about this remarkable antioxidant enzyme that scavenges free radicals.
“Almost everyone’s response was, ‘What’s a free radical?’” recalls McCord, who is now a professor of medicine at the University of Colorado Health Sciences Center and works for a supplement maker.
There are different markers of oxidative stress in the body that increase more or less in a straight line as we age. Your level at forty is greater than your level at thirty. Your level at fifty is greater than your level at forty, and so on. Oxidative stress is like the wear and tear on a car, McCord says. In fact, one way to view aging is the slow oxidation of your body. This raises a question: What, if anything, can we do to stop free radicals in our bodies from oxidizing—or aging—us in order to extend our lives and improve our health? Before I look at that question, let’s consider what we mean when we talk about antioxidants.
FIGHTING FREE RADICALS
Many of the systems in our body exist simply to take in oxygen and get it to our cells. We breathe oxygen into our lungs, transfer it to our red blood cells, and then our heart pumps it around our bodies, where cells use it to burn sugars to create energy. Unfortunately, there is a downside to this process. A by-product of this energy production is an unstable form of the oxygen molecule. This is a free radical, and it can wreak havoc at the cellular level, damaging cells. That means oxygen, the same basic element that sustains us, may sew the seeds of cellular aging. Extending the car analogy, McCord likens these free radicals to incomplete combustion in a car’s engine. In a car, the result is the production of carbon monoxide.
Unlike a car, we have built-in ways to repair minor damage and neutralize free radicals: antioxidants. They are able to scavenge most of these free radicals. However, they do not get all of them, and as we age, the remaining free radicals cause damage. Our own “engine” becomes less efficient. The “tailpipe emissions” get dirtier. These dirty emissions, the free radicals, eventually cause too much damage to be repaired by the body’s own mechanisms. As a result, our bodies start breaking down.
Ground zero for oxidative damage is the mitochondria, the cells’ power plants. Mitochondria are microscopic, sausage-shaped structures inside the cells. Hundreds of mitochondria exist in every cell. The mitochondria convert sugars and oxygen into adenosine triphosphate (ATP), an energy-releasing molecule that powers most of what goes on in the cell.
Like most power plants, the process is not perfectly efficient. There is some “pollution.” In the case of the mitochondria, the potentially harmful by-products are the free radicals. The free-radical oxygen molecules are highly reactive because they are missing one electron, and electrons are most stable when they’re paired. To become more stable, free radicals steal electrons from other molecules. These molecules, in turn, become unstable and steal molecules from still other molecules. The chain reaction results in cellular damage, including damage to DNA and the mitochondria themselves. Damage to the DNA can cause tumors and cancer. Damage to the mitochondria causes them to become less efficient and, over time, generate less energy-producing ATP and more free radicals. Eventually, enough oxidative damage occurs to trigger the cell to self-destruct. As oxidative damage accumulates, it can damage connective and nerve tissues and blood vessels.
Energy production in our cells is not the only reason free radicals form in our bodies. Smoking, exposure to the sun, and other environmental factors also produce free radicals that can cause premature cellular aging.
It stands to reason that anything we can do to eliminate free radicals would greatly benefit us in our quest to live longer, healthier lives. So it shouldn’t come as a surprise that our bodies have developed ways to fight rampaging free radicals. Vitamins A, C, and E, SOD, and two other enzymes you probably haven’t heard of—catalase and glutathione peroxidase—prevent most but not all of the oxidative damage in cells. As I mentioned earlier, oxidative damage still takes place. Stopping that process could be one of the biggest keys to chasing life. How can we better arm our bodies’ own defenses to fight more successfully against these free radicals?
For years, researchers thought the solution might lie in antioxidant vitamins. Supplementing our diets with these vitamins, scientists reasoned, might reduce the number of free radicals and help prevent age-related diseases, such as cancer and heart disease. The government and others underwrote large-scale, long-term studies to see whether increased doses of vitamin E, vitamin A, and vitamin C would offer extra disease-fighting protection. The experiments did not produce the hoped-for results.
“I think we unfortunately went down the garden path,” McCord says. “We had the idea that more would be better, and there was very little evidence of that.”
The American Heart Association released a science advisory in 2004 that said research on vitamin C, vitamin E, and beta-carotene (a form of vitamin A) supplements failed to justify their use to prevent or treat cardiovascular disease. The American Cancer Society also does not advocate taking these vitamins as supplements, because the results of studies testing their results against cancer have been disappointing. In fact, in cancer patients, taking vitamin E might hurt the body’s natural ability to fight tumor cells by actually helping keep tumor cells alive.
Jeffrey Blumberg, director of the Antioxidants Research Laboratory at the USDA Human Nutrition Research Center on Aging, at Tufts University, was not surprised by the studies’ disappointing results and is critical of studies that look for a single nutrient, such as vitamin E, to prevent cancer or heart disease. The antioxidant defense network is complicated, he says, involving both what we eat and what our cells produce.
“It’s not a one nutrient, one disease sort of thing. It’s complex.” Studies of the disease-fighting power of different vitamins tend to be overly simplistic, he says, trying to cure one disease with one supplement at one dose. Antioxidants work in concert, he says, as part of a dynamic system in the body.
Like the American Heart Association and American Cancer Society, Blumberg advocates a balanced diet rich in whole grains and a variety of fruits and vegetables. As we’ve seen, eating fruits and vegetables, which are loaded with antioxidants, has been linked to a lower risk for many chronic and potentially life-shortening diseases.
“I do feel there is an enormous power to nutrition,” Blumberg says, adding that we need to eat in moderation and eat a wide array of fruits and vegetables to maximize the power of good nutrition. “You need that diversity, that variety of plant foods to provide the full complement of antioxidant nutrients.”
McCord, now in the Division of Pulmonary Sciences and Critical Care Medicine at the University of Colorado Health Sciences Center, is not ready to give up on using supplements as antioxidants just yet. The biochemist thinks the disappointments from vitamin studies do not show that antioxidant supplements do not work, just that the research has been misdirected.
“Antioxidant therapy is by no means a dead topic; we have simply been looking at the wrong ones,” McCord says. The focus, he says, should be on how we can supplement our diets to increase the levels of the two enzymes that do the heavy lifting when it comes to neutralizing free radicals: superoxide dismutase (SOD), the enzyme he codiscovered almost four decades ago, and catalase. These two enzymes, he says, are responsible for scavenging 99 percent of the free radicals in the body. If we can get the body to produce more of these enzymes, he reasons, then it would do a better job at fighting free radicals. Don’t bother popping pills containing SOD. This is useless, because it is digested and churned up by the stomach like any other protein.
McCord says there are about forty plants, most of them used in traditional medicine in India and China, that have been shown to induce the body to produce more SOD and catalase. McCord recently coauthored an article in the journal Free Radical Biology and Medicine that showed how a supplement containing five such plant extracts not only increased the body’s production of SOD and catalase but decreased the markers for oxidative stress associated with aging. Whether this translates into longer life remains to be seen. The supplement contained extracts of the following:
1. green tea
2. turmeric
3. milk thistle
4. ashwaganda and
5. bacopa.
Ashwaganda (also spelled ashwagandha) is a plant also known as winter cherry. Bacopa is an herb. This was a very small study, with only twenty-nine participants, but statistically very strong. Still a lot more research needs to be done.
“It may not be the final answer, but it may open a doorway that has a lot of answers behind it,” says McCord. He enjoys thinking that the enzyme he discovered almost forty years ago may be at the heart of antioxidant research in the years to come.
BUYERS BEWARE
Of course, supplements are not limited to antioxidants, and increasingly, Americans have been turning to them to cure what ails them, looking for help for everything from weight loss and sore joints to depression and diabetes. I suspect the rise in popularity of herbal medicine coincides to some degree with a growing dissatisfaction with modern medicine, which is too bad.
In any event, millions of Americans now take supplements; estimates range from 15 percent to 40 percent of the population. Even President Bush reportedly takes supplements. Annual supplement sales in the United States now top $20 billion, yet the industry is largely unregulated.
Unlike prescription drugs, supplements do not require approval from the Food and Drug Administration (FDA). Because supplements are derived from natural ingredients, many people assume they are inherently safe. Most of the 29,000 supplements on the market are, but there are no guarantees and little government supervision—at least in the United States. Also, there are no guarantees about the concentration and purity of supplements on the market. Some have been found to contain prescription medication to boost their efficacy. Others have contained toxic heavy metals.
Even when the supplements themselves are safe and reliable, they can cause medical problems if they are not used correctly or if they are taken in large doses. Supplements also have the potential for dangerous interactions with drugs, a real danger, considering the huge number of Americans who take prescription medicine. Certainly, you should consult your doctor before taking any supplements, especially if you are already taking any prescription medicine.
I was amazed to learn that even when a supplement is dangerous, the federal government has trouble banning it. Under the 1994 law governing supplements, federal regulators must prove supplements unsafe, not the other way around. In 2004, the FDA attempted to ban the diet supplement ephedra after it was linked to heart attack, stroke, high blood pressure, and at least 164 deaths. A federal judge overturned the ban, ruling that the federal government could not issue a blanket ban on the supplement, but needed to state which dosages were unsafe.
Supplement makers also do not have to report adverse reactions to their products, as drug companies do. The federal government estimates only about 1 percent of adverse reactions are reported, despite a hotline and Web site set up to record such reports. More than one in eight calls to the California Poison Control Center was prompted by a child’s adverse reaction to a dietary supplement, including vomiting, nausea, and increased heart rate, the Los Angeles Times reported.
Shining the light on one potentially harmful supplement does not prevent other potentially dangerous supplements from filling the void in the marketplace. For example, when the dangers of ephedra became known, a supplement made from bitter orange peel, Citrus aurantium, was advertised as an ephedra-free alternative for dieters and athletes. However, Citrus aurantium may pose many of the same risks as ephedra, according to a research review published in the journal Experimental Biology and Medicine.
Many companies that produce supplements suggest they are safe because they have been used for thousands of years or are derived from ancient medicine. Being natural or part of a traditional treatment does not make it safe. Aristolochic acid, derived from a Chinese herb, was sold for a variety of ailments, but turned out to be a carcinogen linked to kidney failure and death. The supplements chaparral, comfrey, germander, and kava have also been linked to liver damage and death. None of these cautionary tales has slowed the booming market for dietary supplements.
Echinacea and the Common Cold
The best selling of these is echinacea, an extract from the coneflower, which is a member of the sunflower family. An estimated 15 million Americans take echinacea to prevent and treat colds. There is little clinical evidence it does either. A 2005 study funded by the federal government and published in the New England Journal of Medicine found none of three different preparations of echinacea on the market were successful at preventing the cold. Supporters of echinacea said the dose tested was too low. Other government-funded studies found echinacea did not work as a treatment for the common cold in adults or for upper respiratory tract infections in children. Nonetheless, the National Center for Complementary and Alternative Medicine is continuing to fund the study of echinacea as a possible treatment for upper respiratory infections.
Supplement takers, including Laura Brown, reading the preceding paragraphs will no doubt conclude that I have been somehow coopted or brainwashed by some medical-pharmaceutical industrial complex. My response is that I believe in the scientific method, and if a well-run trial shows a treatment does not work any better than a placebo, we should first try to replicate the results and then think twice about continuing that course of treatment.
Still, I doubt anything I write here will dissuade anyone of the efficacy of echinacea or any other supplement. To be sure, belief alone is a powerful healing tool, which I will take up in detail in chapter 8.
Let’s consider some of the other popular dietary supplements, such as garlic. The lower rate of heart disease among southern Europeans, who eat the garlic-rich Mediterranean diet, has led to a lot of interest in the plant. An estimated 7 million Americans use garlic supplements. Three dozen clinical trials in adults have found that taking various garlic preparations resulted in a small but statistically significant reduction in total cholesterol over the short term. Studies show garlic also may protect against platelet aggregation, which can raise the risk of stroke. Few studies have looked at the efficacy of fresh garlic, although research suggests heating garlic right after it is crushed or chopped appears to diminish garlic’s beneficial properties. Some scientists recommend letting crushed or chopped garlic sit for ten minutes before cooking with it. Several population studies suggest garlic and other vegetables in its class, such as onions and leeks, may help protect against cancer.
Saint-John’s-wort, a long-lived plant with yellow flowers, has been used for centuries as an herbal treatment for depression. An estimated 1.5 million Americans take Saint-John’s-wort supplements. There is some evidence Saint-John’s-wort works to treat mild to moderate depression, but studies have concluded the supplement does not work to treat more severe depression.
Consuming the root of the Asian ginseng plant is said to improve overall health, increase mental and physical performance, lower blood sugar, and control blood sugar. It should come as no surprise, then, that drinks and other products add ginseng to attract health-conscious consumers. Does it work? Some studies have concluded ginseng may lower blood sugar and boost immune function. According to the National Center for Complementary and Alternative Medicine, the research has not been conclusive.
Gingko biloba is another supplement added to various beverages. It has long been touted as a memory-boosting supplement. However, research suggests it does not improve memory as advertised.
Soy products are also popular supplements, reputed to be heart healthy and protective against prostate and breast cancers. Proponents point to the Japanese and others in Asia who eat soy-rich diets and have far fewer cases of these cancers than their counterparts in much of the West. No clinical evidence currently supports the assertion that soy lowers the risk for these hormone-related cancers. Studies do suggest soy products offer moderate benefits in lowering LDL (“bad”) cholesterol and triglycerides.
Let’s consider the supplements President Bush is known to take. First, he takes a daily multivitamin. The president also takes a combination of glucosamine and chondroitin and a fish oil supplement. Glucosamine and chondroitin are taken for joint pain. President Bush suffers from knee pain from years of jogging, something he forgoes now in favor of riding a mountain bike or using an elliptical machine.
A government study found glucosamine and chondroitin together did not provide significant relief for most knee pain, compared to a placebo. The two widely used supplements also failed when tested separately. However, the supplements did bring relief for participants with moderate to severe pain, according to the large-scale study. President Bush had knee surgery in 1997 on his left knee, so it’s quite possible he fits in this moderate to severe group.
