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.

Too Much Iron and Manganese Lead to Higher Risk for Parkinson’s

Too much iron and manganese in the diet may put people at increased risk for Parkinson’s disease, find researchers publishing in the June 2003 issue of Neurology.

Investigators from the University of Washington in Seattle believe the two minerals, common in foods such as spinach, beans, nuts, and whole grains, may impact Parkinson’s risk through their effect on the brain. Both iron and manganese are known to cause oxidative stress, which releases toxic substances known as free radicals and can cause degeneration of brain cells that produce dopamine. The loss of these brain cells plays a crucial role in the development of the disease.

The study involved 250 people with recently diagnosed Parkinson’s and 388 people without the disease. All were questioned extensively about their diets during their adult lives. Participants were then placed into categories depending on how much iron and manganese they consumed and also whether they were regular users of multivitamin or iron supplements.

Researchers found those in the top 25 percent of iron consumption were 1.7-times more likely to have Parkinson’s than those in the bottom 25 percent. Those with higher than average consumption of both minerals were 1.9 times more likely to have the disease. Participants with higher iron intake and a history of daily supplement use were 2.1-times more likely to have Parkinson’s. Those with higher manganese consumption and daily supplement use were 1.9-times more likely to have the disease.

However, the investigators do not suggest people limit their intake of foods rich in iron and manganese, noting the health benefits of eating these nutrient-rich foods probably outweigh the increased risk of Parkinson’s.

Harvey Checkoway, Ph.D., from the University of Washington in Seattle, says, “Our findings may improve understanding of how Parkinson’s disease develops. But there are most likely numerous environmental, lifestyle, and genetic factors that determine who will develop the disease. It’s too early to make any recommendations about potential dietary changes.”

SOURCE: Neurology, 2003;60:1761-1766

Trace Minerals – Selenium and More

Selenium Functions

Selenium is a trace mineral that works with vitamins C and E as an antioxidant to protect cells from damage caused by harmful free radicals. It also supports immune and thyroid function. Selenium can play a role in reducing the risk or growth of some cancers.

Selenium is found in a variety of foods, such as seafood, organ meats, nuts, and grains, though nothing tops the notable Brazil nut for selenium content. So much so, you should not eat more than two Brazil nuts per day.

Although rare, selenium deficiency can occur in those who have Crohn’s disease or other severe digestive disorders or conditions or who rely on total parenteral nutrition (TPN), a method of feeding intravenously. Symptoms of a deficiency can include heart problems, hypothyroidism, and a weakened immune system. Low levels of selenium can predispose children to a rare form of heart disease and is also associated with a higher risk of cancer.

Too much selenium in the blood from foods or supplements can cause selenosis. Symptoms include gastrointestinal problems, hair loss, brittle nails, fatigue, irritability, and mild nerve damage.


Copper is a trace mineral with many important functions in the body. It’s part of an enzyme involved in iron metabolism and helps make red blood cells. It is also a part of enzymes that act as antioxidants to remove free radicals. Copper also helps keep the immune system, nerves, and blood vessels healthy. It also helps for the pigments in the skin, hair, and eyes.

Copper deficiency is rare but can occur in preterm infants and those with malabsorption conditions such as Celiac Sprue. Symptoms include anemia and bone problems.

Getting too much copper from foods or supplements can cause nausea, vomiting or diarrhea. Too much copper can also decrease iron and zinc absorption. In rare cases, excess copper intake can cause anemia and in some cases, death.


Manganese is a trace mineral that has many essential functions in the body. It is a key component of many enzymes that help form cartilage, the foundation of bones and skin, and support the metabolism of amino acids (which form proteins), cholesterol, and carbohydrates.

Various plant foods and tea contain manganese. Drinking water can also supply manganese to the diet.

It’s uncommon to be deficient in manganese, but people with epilepsy, phenylketonuria (PKU), multiple sclerosis, and some other conditions can be deficient. Symptoms include impaired growth and bone problems.

Too much manganese from foods, water, supplements, or the environment (from dust) can be toxic. High levels can lead to irritability, hallucinations, and extreme coordination problems. People with liver problems can be especially vulnerable to the negative effects of too much manganese.


Iodine is a trace mineral that is a key component of two thyroid hormones that regulate body temperature, basal metabolic rate (BMR), reproduction, and growth.

Iodine is found in foods in the form of iodide and iodates. Although there is limited information about specific amounts of iodine in foods, the richest sources include iodized salt and processed foods made with it, seafood, milk and dairy products, and some grains.

Deficiencies of iodine in America are uncommon because salt is iodized and we consume so much salt and salty foods. Iodine deficiency is still a risk, however, for many people around the world. People who consume a lot of raw vegetables such as cabbage, turnips, rutabagas, and cassava can be at risk because these foods contain goitrogens – compounds that prevent iodine from being absorbed and used properly. A deficiency of iodine overstimulates the thyroid gland and can cause goiter (enlarged thyroid gland) and symptoms such as intolerance to cold, weight gain, lower body temperature, and sluggishness. A severe deficiency of iodine in early pregnancy causes cretinism, characterized by stunted growth, deafness, and mental retardation.

Too much iodine especially from supplements can also cause goiter.


Fluoride is a trace mineral that is essential for maintaining strong bones and teeth (especially tooth enamel) and preventing dental caries.

Few foods naturally contain fluoride; however, some is found in tea, fish (with and without bones), and canned meats and poultry. Fluoride-fortified foods and supplements (available by prescription only) and toothpaste also provide fluoride. The American Dental Association (ADA) recommends fluoride supplements for children whose drinking water supplies less than 0.6 milligrams per liter.

Too little fluoride from the diet or drinking water increases the risk of tooth decay and dental caries.

Too much fluoride in the diet or from toothpaste, fortified foods, and supplements can cause fluorisis (discolored teeth with specs in them). Fluoride toxicity, which can develop in those who receive hemodialysis treatments for kidney disease, can cause headaches, nausea, and abnormal heart rhythms.


Chromium is a trace mineral that helps the hormone insulin function properly to maintain normal blood glucose levels. It also helps release energy from carbohydrates and fats. Chromium can also support immune function.

There is limited information about the content of chromium in specific foods, but very small amounts are found in a variety of foods and beverages including meats and poultry, whole grains, fruits and vegetables, spices, and beer.

Too little chromium in the diet can cause high blood sugar and insulin levels. Those on TPN who have low levels can experience brain and nerve disorders.

Excessive chromium might not be a problem for most people because it’s so poorly absorbed. However, animal studies suggest that chromium picolinate supplements can damage DNA – important genetic material.


Molybdenum is a trace mineral needed by many enzymes in the body to help them function properly. It can support a healthy nervous system, create energy in cells, and process wastes in the kidneys.

Although little is known about how much molybdenum is found in foods, legumes (beans and peas), grains (including ready-to-eat cereals), and nuts appear to be good dietary sources.

A molybdenum deficiency does not occur in people who consume a normal diet. Those on parenteral nutrition (intravenous feedings) can develop a molybdenum deficiency and experience symptoms such as weakness, mental confusion, and night blindness.

Too much molybdenum from food or supplements can lower the body’s absorption of copper, another trace mineral.

Microcytic hypochromic anemia is a type of anemia in which the red blood cells are smaller than normal and do not contain as much hemoglobin (a protein that carries oxygen) as normal; this can be caused by an iron deficiency or impaired production of hemoglobin.

Selenosis is a condition that can occur from excess dietary selenium intake; symptoms include hair loss, brittle nails, garlicky breath, intestinal problems, and mental changes

Basal metabolic rate (BMR) is the amount of energy the body expends at rest; it makes up the largest portion of total calories the body expends or burns each day.

Caries is another name for cavities or tooth decay.

Insulin is a hormone naturally made by the pancreas; it helps body cells use glucose (the key fuel for the brain and nervous system) for energy by regulating blood glucose or blood sugar levels in the body.

Dietary reference intakes (DRIs) are established for all minerals and include the following:

• Estimated average requirements (EARs)
• Recommended dietary allowances (RDAs)
• Adequate intakes (AIs)
• Tolerable upper intake levels (UL)

Multivitamins and Minerals


Manganese has received a lot of attention for its role in bone and joint health. Most multivitamins provide only a few milligrams of manganese – enough to satisfy the minimum requirements – but you may want to look for one that provides more than the minimum or consider taking a separate trace mineral supplement.

Benefits of Manganese

  • Promotes normal growth and development
  • Assists enzymes in generating energy
  • Promotes normal cellular function


Chromium is important in sugar and lipid metabolism and should be included in any multivitamin formula. However, some manufacturers include far less than the recommended 50 to 200 microgram sin their product’s daily dose. Organically bound chromium is much better absorbed than inorganic chromium chloride.

Benefits of Chromium

  • Assists in the regulation of blood sugar
  • Improves glucose tolerance in people with type 2 diabetes
  • Promotes healthy glucose metabolism


Selenium is an important antioxidant cofactor and may be important in cancer prevention. A new RDI has been established at 70 micrograms, but many formulas contain as much as 200 micrograms, which some authorities consider to be in the upper range of recommended intakes.

Benefits of Selenium

  • Acts as a powerful antioxidant
  • Teams up with vitamin E for additional antioxidant properties
  • Promotes normal growth and development

Other Nutrients

Multivitamins vary widely in their nutritional composition. Many include trace minerals such as boron, molybdenum and vanadium. While there are no established recommendations for these nutrients, experts agree that they’re necessary for good health. If your multivitamin doesn’t contain trace minerals, consider taking an occasional trace mineral supplement.

The Bottom Line

If you were to take only one dietary supplement, a good multivitamin would be your best bet. Many of us aren’t getting optimal levels of all the essential nutrients, but a multivitamin can ensure that our nutritional needs are met. The multivitamin / mineral supplement could now replace the apple in a new adage, “A multi a day keeps the doctor away”.

Multivitamin / Mineral Fast Facts

Product forms: Tablets, capsules, liquid, powder and chewables.

Uses and Benefits: Multivitamin supplements prevent nutrient deficiencies and help maintain basic body functions and processes. Multivitamin supplements may also help prevent health conditions such as heart disease, diabetes, cancer and arthritis.

Special Considerations: Always consult with a qualified health care provider before taking a dietary supplement to help treat a specific disease or condition.