Antioxidants Studies

As everyone knows, eating and drinking are necessary for life. Less well known, however, is the fact that the body generates what are called free radicals in the process of turning food into energy. Free radicals are chemicals that are capable of damaging cells and genetic material. But eating is not the only way free radicals spring into being. The food we eat and the sunlight we feel also generate free radicals.

To be sure, free radicals come in many shapes, sizes, and chemical configurations. The characteristic feature of this chemical is that it soaks up electrons from bodily substances that yield them, which can leave the “loser’s” structure or function radically altered. Free radical damage can change the instructions coded in a strand of DNA; it can also make a circulating low-density lipoprotein (LDL, sometimes called bad cholesterol) molecule more likely to get trapped in an artery wall. Free radicals also have the potential to alter a cell’s membrane, changing the flow of what enters the cell and what leaves it.

Fortunately, we aren’t defenseless against free radicals. The body puts up natural defenses against free radicals by making molecules that smothers the errant chemicals. We also extract free-radical fighters from food. Often called “antioxidants”, certain kinds of food give electrons to free-radicals without themselves turning into electron-scavenging substances. There are many different substances that can act as antioxidants. The most familiar ones are vitamin C, vitamin E, beta-carotene, and other related carotenoids, along with the minerals selenium and manganese. They’re joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, and many more.

However, the term “antioxidant” can be misleading. These substances do not emit chemical properties that fight so much as they emit properties that facilitate. Indeed, some substances that act as antioxidants in one situation may be prooxidants—electron grabbers—in a different chemical milieu. Another big misconception is that antioxidants are interchangeable. This is not true. Each anti-oxidant has unique chemical behaviors and biological properties. It is believed, and has been strongly corroborated through scientific study, that anti-oxidants evolved as parts of elaborate networks, each substance having a different role to play. It follows that no single substance can fulfill the function of every other substance.

Health Benefits of Antioxidants: What’s the Buzz?

Antioxidants came to public attention in the 1990s. It was then that scientists began to understand that free radical damage was involved in the early stages of artery-clogging atherosclerosis, and that the chemicals may contribute to cancer, vision loss, and a host of other chronic conditions. A number of studies stated that people with low intakes of antioxidant-rich fruits and vegetables were at greater risk for developing these chronic conditions than were people who ate sufficient amounts fruits and vegetables. Clinical trials tested the impact of single substances, especially beta-carotene and vitamin E, on cancer, heart disease, and similar maladies. But even before the results of these trials were in, the media, and the dietary supplement and food industries began promoting the benefits of “antioxidants.” Foods such as frozen berries and green tea were hyped as being rich in antioxidants. The consequences of this publicity were predictable: certain foods were labeled as rich in antioxidants and were marketed as such in stores; the makers of dietary supplements began touting the disease-fighting properties of all sorts of antioxidants.

In the meantime, the results of the actual trials were mixed. Most have not found the hoped-for benefits. And research teams reported that vitamin E and other antioxidant supplements didn’t protect against heart disease or cancer. One study even showed that taking beta-carotene may actually increase the chances of developing lung cancer in smokers. However, some of the trials reported benefits. One such study found that taking beta-carotene is associated with a modest reduction in the rate of cognitive decline.

The rather most, if not downright disappointing, results of the antioxidant trials have not stopped the commercial interests from misrepresenting the benefits of antioxidants in order to make money. Antioxidant supplements are a $500 million dollar industry that continues to grow. Antioxidants are still added to breakfast cereals, sports bars, energy drinks, and other processed foods, and they are promoted as additives that can prevent heart disease, cancer, cataracts, memory loss, and a host of other conditions. The claims made by the food and dietary supplement industries often distort the data. It is true that the package of antioxidants, minerals, fiber, and other substances found naturally in fruits, vegetables, and whole grains help prevent a variety of chronic diseases; but there is no solid evidence that high doses of antioxidants can accomplish the same feat. The conclusion is clear: randomized, placebo-controlled trials—which, when performed well, provide the strongest evidence—offer little support that taking vitamin C, vitamin E, beta-carotene, or other single antioxidants provides substantial protection against heart disease, cancer, or other chronic conditions. The results of the largest such trials have been mostly negative.

Heart Disease and Antioxidants

Vitamin E, beta-carotene, and other so-called antioxidants are not a panacea for heart disease and should not be promoted as such. In the Women’s Health Study, 39,876 initially healthy women took 600 IU of natural source vitamin E or a placebo every other day for 10 years. The results of the study showed that the rates of major cardiovascular events and cancer were no lower among those taking vitamin E than they were among those taking the placebo; however, a 24 percent reduction in total cardiovascular mortality was observed, which can be considered a quite significant result.

Earlier large vitamin E trials, conducted among individuals with previously diagnosed coronary disease or at high risk for it, generally showed no benefit. In the Heart Outcomes Prevention Evaluation (HOPE) trial, the rates of major cardiovascular events were essentially the same in the vitamin E (21.5 percent) and placebo (20.6 percent) groups, although participants taking vitamin E had higher risks of heart failure and hospitalization for heart failure. (3) Another trial, the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI), showed mixed results; there were no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors. Nevertheless, some studies suggest potential benefits among certain subgroups. A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress. In any case, Beta-carotene, as was shown in the Physicians’s Health Study, does not provide any protection against heart disease or stroke.

There have been combinations, but the findings are complicated and unclear. In the Supplementation en Vitamins et Mineraux Antioxydants (SU.VI.MAX) study, 13,017 French men and women took a single daily capsule that contained 120 milligrams of vitamin C, 30 milligrams of vitamin E, 6 milligrams of beta-carotene, 100 micrograms of selenium, and 20 milligrams of zinc, or a placebo, for seven and a half years. The vitamins had no effect on overall rates of cardiovascular disease. In the Women’s Antioxidant Cardiovascular Study, vitamin E, vitamin C, and/or beta-carotene had much the same effect as a placebo on myocardial infarction, stroke, coronary revascularization, or cardiovascular death, although there was a modest and significant benefit for vitamin E among women with existing cardiovascular disease.

Cancer and Antioxidants

There is also no conclusive proof that antioxidants help prevent cancer. Scientists need more time to determine the impact of antioxidants on the risk of getting cancer. In the long-term Physicians’ Health Study, cancer rates were similar among men taking beta-carotene and among those taking a placebo. Other trials have also largely showed no effect, including HOPE. The SU.VI.MAX trial showed a reduction in cancer risk and all-cause mortality among men taking an antioxidant cocktail but no apparent effect in women; it is possible that this is a result of the men in the study having low blood levels of beta-carotene at its beginning. A randomized trial of selenium in people with skin cancer demonstrated significant reductions in cancer and cancer mortality at various sites, including colon, lung, and prostate. The effects were strongest among those with low selenium levels at baseline.

Age-Related Eye Disease and Antioxidants

The effects of antioxidants on age-related eye disease may be one of the most hopeful leads scientists have. A six-year trial, the Age-Related Eye Disease Study (AREDS), found that a combination of vitamin C, vitamin E, beta-carotene, and zinc provided some protection against the development of advanced age-related macular degeneration in people who were at high risk of the disease. Lutein, a naturally occurring carotenoid found in green, leafy vegetables such as spinach and kale, may also protect vision. It is too early to tell what the impact of lutein supplements may be. The trials of such substances have been relatively short, and their ability to slow or prevent age-related macular degeneration has not been ascertained. A new trial of the AREDS supplement regimen plus lutein, zeaxanthin, and fish oil is underway, and it could yield better information.

Potential Hazards of Antioxidants

There have been a few studies which showed that the consumption of antioxidants, as opposed to being beneficial in all instances or at least harmless in fact can interfere with the health of the consumer. The first trial which showed this possible negative effect was undertaken in Finland where heavy smokers were fed beta-carotene. Because of their smoking habits there was a already a lung cancer risk but it was noticed that a significant increase in the incidence of lung cancer amongst the trial group as opposed to the placebo. The trial was stopped so conclusive results are hard to deduce.

A different test which was conducted with heavy smokers exposed to asbestos being fed beta-carotene and vitamin A. This too shows an increase in the incidence of Lung cancer. It must be emphasized that not all trials of Beta-carotene have been negative. A physicians health study which only had a few smokers did not show any significant differences even when followed up after 18 years.

In a separate study showing possible negative effects of a variety of health supplements showed a higher incidence of skin cancer in women being fed supplements of Vitamins C & E, Beta-carotene, selenium and zinc.

Conclusions to be drawn from the above studies, amongst others, is that it is known that although free radicals have been shown to contribute to the incidence of heart disease, cancer, Alzheimer’s and even vision loss, there is no automatic conclusion that can be drawn that antioxidants will fix the problem. And certainly not when consumed away from their normal context.

Studies to date do not show conclusive evidence one way or another but there is certainly no strong evidence to suggest that antioxidants are effective against disease. A rider must be mentioned and that is that the trials conducted till now have been short in duration, conducted with people some of whom had an existing disease.

There has been a noticeable benefit to the consumption of beta-carotene on cognitive ability after 18 years. This is exceptional as it is the only study to have continued so long. (Physicians health follow up study) Nevertheless there is abundant evidence suggests that eating whole fruits, vegetables, and whole grains—all rich in networks of antioxidants and their helper molecules—provides protection against many of these scourges of aging.

Clarification with regard to supplemental studies

There are any number of studies conducted on any number of vitamins and other dietary supplements that are often contradictory. The picture presented to the consumer is confusing and will often seem frustrating in that instead of clarifying things these studies muddy the waters.

Examining exactly what the vitamins trial study did will often go some way to explaining the varying results. Here are a few items to check when looking at apparently conflicting vitamins studies.

  • What was the precise dosage taken by the participants and how long was the study’s duration. This is significant as few studies will have identical dosages and identical time spans. A study in Vitamin D showed that a dosage of 700 plus IU per day had a significant protection against fractures whereas a study of people taking only 400 IU per day showed no such effect. The same applies to the duration as the build up of the protective mechanisms is not a short process.
  • The age, health and life styles of the participants. Studies drawn from young, active gym going participants is likely to differ significantly from heavy drink and smoking office workers. Exercise and other lifestyle choices such as diet affect out health and how the body responds to vitamins.
  • At what stage is was the supplement fed to a study participant. If studying the effect of a supplement on someone already suffering from a disease it may be found that something taken at the onset has a differing effect from something taken when a disease is far advanced. An example being that Folate supplements are only effective against neural tube defects in the early stages of pregnancy.
  • How were the results tabulated and calculated. This is a significant problem as measurement as to benefit may and probably will vary widely. Heart disease is a wide subject and a measurement of coronary thrombosis may miss out on the incidence of strokes.

Vitamin Regrows Lungs

Two million Americans live with emphysema, a disease that literally eats holes in the lungs. It’s often caused by years of smoking, but some doctors believe it’s possible to reverse the damage by simply popping a pill.

There’s nothing unusual about getting out of breath exercising, but Sharon Hanna often loses her breath before she even starts. She says, “Two years ago I was waking up in the middle of the night, just couldn’t breathe in my sleep, without any exertion, without doing anything. That was really frightening.”

A 30-year, three-pack-a-day, smoking habit has literally eaten holes in Hanna’s lungs. She knows her emphysema will only get worse. Doctors say there is no cure, but now there is hope. Inside these tiny pills is a form of vitamin a that could save her life.

Doctors know vitamin A signals lung tissue to grow in a developing fetus. Why then couldn’t it regrow lung tissue destroyed by emphysema?

“Experimental studies would show if you take away that Vitamin A the lungs fail to develop, and if you put back extra Vitamin A you can repair injury to the lung,” says pulmonologist Michael Roth, M.D. of the UCLA School of Medicine.

For the study, Hanna takes the pills for six months. Nevertheless, doctors believe it may take a year to see results. If the pill works, it won’t be available for at least five years. Until then, Hanna’s only option is to keep the rest of her body in tiptop shape.

Hanna says, “You can live a long time with it, but I’m in this study because I don’t want to just do that. I want to get better.”

Dr. Roth stresses that this is a derivative of vitamin A. He says the vitamin A on the market today would not have the same effect.

This article was reported by, who offers Medical Alerts by e-mail every day of the week. To subscribe, go to:

Too Much Vitamin A and Higher Risk of Fracture

Vitamins are considered a healthy part of a person’s diet, but a new study finds too much of a good thing may be harmful. Researchers from Brigham and Women’s Hospital in Boston say too much vitamin A may increase a woman’s risk of hip fracture.

Diane Feskanich, Sc.D., and colleagues, studied more than 72,000 women between ages 34 and 77. The reviewed records of the food the women ate, the supplements they took, and their risk of postmenopausal hip fractures. The women were part of the Nurses’ Health Study, which lasted 18 years.

Vitamin A, for the purpose of this study, encompasses a number of compounds that are required for vision, growth, reproduction, and the well being of the immune system among other functions. Animal studies have suggested too much vitamin A can have a negative effect on the skeleton.

In this study, researchers found women who took 3,000 micrograms or more of vitamin A either through food or supplements had a significantly higher risk of hip fracture. Retinol is considered the most potent source of vitamin A and appeared to have the greatest impact on the rate of fracture.

Researchers say these findings offer a reason for officials to reassess the increased fortification of foods with vitamin A, particularly from retinol. Currently, it’s recommended that men consumer 800 micrograms of vitamin A and women 700 micrograms. The recommendations say 3,000 micrograms is considered a safe level.

SOURCE: Journal of the American Medical Association, 2002;287:47-54

Vitamin A Supplements Help Growth Rate in Sick Kids

The Harvard University study involved about 690 children from Tanzania between 6 months and 60 months old who had been admitted to the hospital with pneumonia. Twenty-four percent of the children were also suffering from malaria and 9 percent tested positive for HIV infection. Some children in the study received either an oral dose of vitamin A on their first day of admission, a second dose on the second day, and third and fourth doses four and eight months after they were discharged. A second group of children received placebo doses at the same times. Children were assessed for length, weight, and other measures of growth at the beginning of the study and again during monthly visits to the clinic.

After one year, results showed HIV-positive children under 18 months old who received vitamin A supplements improved in terms of length, while those who had malaria and were less than a year old improved in terms of weight. Children who lived in areas with poor water supplies also showed an improvement in length, and the supplements virtually eliminated the risk of growth stunting associated with persistent diarrhea.

Researchers conclude providing vitamin A supplements every four months to children under the age of 5 who live in areas with a high rate of infectious diseases such as HIV, malaria, and diarrhea could be an effective and inexpensive way to help these children reach their full growth potential.

SOURCE: Pediatrics, 2002;109;E6

Heart Disease Q&A

What is the prevalence of heart diseases in Americans?

Heart disease is the biggest killer of all of the chronic diseases. Cancer comes second. They say if you don’t die of heart disease you’re likely going to die of cancer, but heart disease is the one that gets us first. I think probably over 20 percent of deaths are heart related as this point in time.

How big of an impact does diet have on the heart?

Well, diet plays a big role. We know genetics is a big factor, too. That’s the thing with heart disease, there are just so many factors that come into play, including your level of physical activity, your genetics, and how you’ve managed your blood pressure and blood cholesterol levels. Now, we’re looking at homocystine levels and then the C-reactive protein that’s associated with inflammatory activity in the body. All of these things come into play. So, diet fits in with that whole scheme of things as a real important factor. The way I look at it a lot of times is that if you’ve got a family history of heart disease then its even more important for you to focus on a heart-healthy diet.

You just touched on C-reactive protein. What is CRP?

Essentially, it’s associated with increased inflammatory activity in the body. We know increased inflammatory action in the body puts stress on the heart. It also is related with a lot of other diseases like arthritis, for example. It is a known risk factor for heart disease, and so we are looking at it as a risk factor similar to things like blood cholesterol, low-density lipoprotein, high-density lipoprotein levels, homocystine and things like that.

How much would a healthy diet impact somebody’s health? Could it prevent heart disease?

The size of a role that diet plays in preventing heart disease probably depends on somebody’s genetics. However, studies like those done by Dr. Dean Arnish in San Francisco where he looked at the role of diet, he also incorporated exercise, stress reduction, and also enjoyable social situations. All of these things seemed to play a role, and any one alone was not really the whole piece of pie. Diet probably plays a pretty big factor, but I don’t think heart disease can be prevented by diet.

So a healthy diet is just one piece of the puzzle?

Right. You could be very physically active, in great shape from a lot of exercise and doing your yoga, reduce your stress, but if you have a junk diet then that’s another brick in that wall so to speak that’s missing and it’s going to fall down. A healthy diet is one of many bricks that help hold up the wall.

Specifically, how do fruits and vegetables affect the heart?

Fruits and vegetables impact the heart in a lot of ways actually. One of the basic things is that they are a good source of dietary fiber, and dietary fiber is associated with helping reduce the amount of cholesterol that gets absorbed or reabsorbed into the body. Dietary fiber is also good for overall intestinal health. The other things that are in all of these fruits and vegetables is a lot of important minerals. For example, a banana is very high in potassium, which is a real heart-healthy mineral. There are a lot of vitamins, of course. There is vitamin C in things like mangos, papayas and of course oranges. You can find vitamin A in colorful vegetables, including the green vegetables. So, carrots, red bell peppers, spinach and broccoli are all good sources of vitamin A.

How is vitamin A helpful?

Vitamin A is in the form of what’s called beta carotene and other carotenoids, and it functions as an antioxidant. Certain amounts of heart damage and blood vessel damage is thought to be related to oxidative stress, and so components such as beta carotene help reduce that oxidative stress on the body. There are also other chemicals in a lot of these fruits and vegetables that we call phytochemicals — phyto meaning plant and plant chemicals. A lot of them are very powerful antioxidants. They don’t function as nutrients so it’s not like we actually need them like we need vitamin C and vitamin A, which are required nutrients. These things aren’t really required but they enhance health if they are consumed.

Say someone hates fruit but he has got to work fruit into his diet, what are the most powerful players?

If you have a fruit-phobic person, usually I just encourage him to eat the ones he likes the most because they all have different strengths and weaknesses from a nutrient and phytochemical perspective. Variety really is the spice of life in terms of health. I guess if I was to pick just a few I would probably go with something like the colorful grapes for the nice phytochemicals that we know that those have. Wine is famous for that as well. Then I would want to have something that was a good source of vitamin C, and so that could be something like an orange or even pineapple. Then if you have your vitamin A and your vegetables, you want to think about the type of minerals that are important in these foods too and maybe throw in the banana for the potassium.

What about for vegetables? If you could only have one vegetable, what are the most powerful players?

Well, would it be better to have broccoli than a potato if you were real picky? Certainly, a potato is considered a vegetable, and potatoes have some strengths that often aren’t recognized. For example, they’re a real good source of vitamin B6, which we know is a heart protective nutrient. But I think if I was only going to go with say three vegetables, I would want to have probably three different colored vegetables — maybe an orange or yellow vegetable would be one, certainly a green vegetable would be another, and the other one could be like the red bell pepper, potato or a sweet potato. It’s really the variety that confers the most protection.

What is fiber’s role as it protects the heart?

We’re probably still just beginning to understand it, but fiber, on one hand, tends to bind up certain lipid-type of compounds, especially cholesterol and some of the bio acids that are released from our liver into the intestinal tract. What happens with these bio acids is they get reabsorbed into the body and reutilized. But if the fiber holds onto them and pulls them on through the body, and what happens is in order to make more of those bio acids, we need to use some of our body’s cholesterol to produce them. So it reflects a drain on our body’s cholesterol.

What are some of the foods that pack the most fiber?

Probably near the top of the list are beans and legumes, which often times don’t get recognized for their high levels of dietary fiber. Next would have to be fruits and vegetables. The grains, if they’re whole grains, are equivalent pretty much to fruits and vegetables. If you pick some of the cereals too, even some of the ready-to-eat cereals, are extremely high in fiber.

How much fiber should the average person get in a day?

The recommended intake of fiber is around 14 grams of fiber for every 1,000 calories in your diet. That’s sort of the standard recommendation. So for most people, that comes out to about around 25 to 30 grams per day.

What would be an example of what you would need to eat in a day to get that?

Generally, you could get that by eating according to the old food guide pyramid way. Most people kind of zone out when you mention the food guide pyramid because they’ve seen it too much. But the reality is if you get those number of servings from the grain group in terms of the whole grain products, the fruits, and you include beans as part of your high-protein food group, then you’re going to get that easily.

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Combining food with medication

The food you eat can affect the medication you are taking. You should be aware, for example, that grapefruit can increase the risk of side effects from a wide variety of drugs. The side effects described below can occur from eating grapefruit while on the specified medications.

• Grapefruit can cause flushing, headaches, and increased heart rate if eaten while taking calcium-channel blockers (such as nifedipine, amlodipine, verapamil, and felodipine), which help decrease blood pressure.
• Grapefruit increase quinidine levels.
• Grapefruit can cause irregular heart rhythms if eaten while taking the antihistamine terfenadine.
• Grapefruit can increase levels of benzodiazepines (sedatives that include alprazolam, diazepam, midazolam, and triazolam).
• Grapefruit can cause kidney and lvier toxicity if eaten while taking cyclosporine.
• Grapefruit increases caffeine levels and can cause nervousness and insomnia.
• Grapefruit can decrease the absorption of macrolide antibiotics such as clarithromycin.
• Grapefruit can decrease the absorption of the antihistamine fexofenadine (such as Allegra).
• Grapefruit can increase the medication level of HMG-CoA reductase inhibitors (statin drugs).
• Grapefruit can delay the absorption of Viagra, a male impotence medication.
• Grapefruit can cause hives if taken with the pain reliever naprosyn.
• Grapefruit can increase certain levels, which may lead to nausea, tremors, drowsiness, dizziness, or agitation, if eaten while taking carbamazepine (such as Tegretol).
• Grapefruit may elevate blood levels and cause nausea, drowsiness, tremors, or agitation if eaten while taking amiodarone.
• Grapefruit can increase estrogen levels in both men and women. No interaction with medication is necessary for this to occur.

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Combining Vitamins and Minerals

Vitamins and minerals can interact with each other, as well as with other nutrients. These relationships and interrelationships can have various effects. The following examples show how certain vitamins and minerals interact.

• A certain amount of vitamin C is necessary for your body to use selenium effectively.
• Vitamin C can enhance the availability of vitamin A.
• Too much zinc can decrease calcium absorption.
• Vitamin D increases the absorption of calcium and magnesium.
• Vitamin D helps your body use zinc effectively.
• Too much copper can decrease the uptake of manganese in your system.
• A vitamin A deficiency can decrease iron utilization.
• Too much iron can lower your manganese and copper levels.
• Too much vitamin B2 (riboflavin) can cause a magnesium deficiency.
• Vitamin B6 can cause a decrease in copper absorption.
• A vitamin E deficiency can decrease absorption of vitamin A.
• A vitamin B6 (pyridoxine) deficiency can lead to a decreased use of selenium.
• Adequate phosphorus intake is needed to maintain vitamin D.