By Benjamin V. Treadwell, Ph.D.

It's likely that anyone who pays even passing attention to his or her health is aware that antioxidants are generally good for us. But what are they, really? How do antioxidants work? Are some better than others?

What Are Antioxidants?

Before we get to the "anti" part of the story, let's begin with the oxidants that the "antis" fight. The sun is a source of oxidants familiar to all. Its effects on manufactured products are well known. Colors fade in clothing, plastics, and on painted surfaces. The rubber tires on your car harden and then crack. The sun essentially takes the life out of the products exposed to its rays.

This happens because sun's ultraviolet rays disrupt the chemical bonds that hold together materials such as rubber and plastics. Electrons in pairs characterize these bonds. The sun's energy agitates the electrons and splits off some of them, leaving disrupted or broken bonds with, figuratively speaking, jagged ends characterized by a single unpaired electron. The unglued or broken bond with its single unpaired electron is an oxidant. And it doesn't like the single life. It aggressively pursues a mate, another electron to pair-up with. The result is an attack on a chemical bond in the vicinity of the ruptured bond. The single electron ends up with a mate, but only by breaking up an existing pair, and thereby propagating another oxidant, or free radical. This series of events unfolds in chain-reaction fashion until the attacked material is completely oxidized (bleached and weakened fabric, or cracked rubber tire).

In the case of paint, rubber and fabrics, chemists have figured out ways to prevent, or at least inhibit oxidation by adding specific antioxidant compounds to the materials during their manufacture. These compounds safeguard the material through their greater susceptibility to oxidation than that of the materials they are protecting. When they are oxidized, their chemical structure stabilizes the unpaired electron. Thus they prevent and/or terminate the oxidant-induced chain of reactions and protect the material in which they are imbedded.

What About Human Cells?

Living tissue requires protection from environmental oxidants (the sun, smoke, pesticides, drugs etc.), as well as oxidants produced as by-products of normal metabolism. However, oxidants, including free radicals, are necessary for numerous reactions involved in cellular energy production and survival. Since the oxidation reactions necessary for normal cell health are tightly confined to specific cellular machinery known as enzymes, the antioxidants normally present in the cell cannot breach their domain. For this reason it is difficult (but not impossible) to overdose on most essential antioxidants.

Approximately 1-2% of the oxygen taken in through the lungs and used by the body to produce energy is released from the enzyme confines as nasty free radicals. This amounts to a whopping 20 billion molecules of free radicals produced by each cell per day. These molecules are the targets for the antioxidants that our bodies need to maintain cellular health.

Fighting the Oxidants

To disarm the oxidants, our bodies use antioxidants that are either produced by our tissues or absorbed from the foods we eat. They divert the attack of free radicals from vital cellular components to the more oxidant-prone antioxidant. They, too, form free radicals when oxidized, but the odd reactive electron is dispersed over the specialized structure of the antioxidant, thus stabilizing it.

Scientists previously thought the organism excreted usurped (oxidized) antioxidants. Researchers have shown, however, that biological antioxidants are recyclable, unlike those added to synthetic materials such as paints and plastics. Work performed in the laboratories of Dr. Lester Packer (a member of Juvenon's Scientific Advisory Board) and others has demonstrated the existence of a rechargeable antioxidant system utilized by our cells.

Which Antioxidants Are Best?

Two general types of antioxidants work together to protect the cells and tissues of our bodies. One type protects the aqueous (watery) portion of the tissues and the other the hydrophobic, or lipid (fatty) component. The aqueous environment is protected by vitamin C, and at least two additional antioxidants produced by tissues, glutathione and thioredoxin. Cell membranes are protected by the lipid-soluble antioxidants, including vitamin E, and the ubiquinols (CoQ10). Another antioxidant, alpha lipoic acid, is unique in that it can enter and protect both lipid and water environments.

When vitamins C and E react with and neutralize a free radical, the oxidized or spent vitamins are converted back to the reduced or recharged, active form. Vitamin C can donate electrons to oxidized vitamin E and convert the E back to its active state, leaving vitamin C oxidized. Vitamin C, in turn, can be recharged after reacting with glutathione or the more potent antioxidant, alpha lipoic acid.

The most versatile antioxidant in the cell is alpha lipoic acid. It is one of the more potent antioxidants, owing to its property of being the most easily oxidized. Alpha lipoic acid is the foundation of an antioxidant network involved in the conversion of the spent or oxidized forms of four different cellular antioxidants back to their active protective forms. The obvious questions, then, are how lipoic acid is regenerated and whether this process ever ends.



The answer lies in the unique property of lipoic acid, its solubility in both water and lipid. Lipoic acid can be converted from its oxidized state to its reduced state with the aid of a mitochondrial enzyme (the organelle within the cell where energy is produced). Unlike vitamins C and E, the cell has machinery specifically designed for the regeneration of reduced lipoic acid. Therefore, lipoic acid can itself react with and neutralize free radicals in addition to recycling vitamins C and E (as well as CoQ10, glutathione and thioredoxin). This is critical, since each antioxidant has a unique function. The conclusion, then, is that all of these antioxidants are required for optimal cellular health.

Without vitamin E, we essentially turn rancid. Vitamin E is fat-soluble, that is, able to penetrate the fatty areas of our tissues. As it does so, it neutralizes toxic oxidants and protects oxidant-sensitive membranes. Thus vitamin E is justifiably known as an antioxidant, and for helping to prevent age-associated increases in oxidative insults to our bodies.

The Eight Forms of Vitamin E

In reality, vitamin E comes in eight different forms, all of which are derived from plants. The eight E's are divided into two classes:

• The tocopherols consist of 4 types of vitamin E, alpha, beta, gamma, and delta. The features distinguishing each are slight chemical differences (location and number of methyl groups) on its core structure.
• The tocotrienols are virtually identical to the tocopherols in structure, except for the presence of 3 unsaturated bonds (hence trienol). Alpha, beta, gamma and delta tocotrienols are more permeable to cell membranes because of their unsaturated bonds. This chemical difference imparts certain advantages over the less permeable tocopherols.

The most potent antioxidant of the group is alpha tocopherol. For reasons still unknown, this form of E represents the bulk of vitamin E present in our serum. This is puzzling, since the plants we normally consume contain much more gamma tocopherol. Scientists originally speculated that our bodies require high serum levels of alpha tocopherol and have developed mechanisms to retain it. Thus, multi-vitamins almost always contain alpha tocopherol.

It is becoming more evident, however, that all forms of E are important and that they serve very different functions. Laboratory experiments have indicated that gamma and alpha tocopherol may complement one another with respect to antioxidant protection. Alpha tocopherol is most effective at neutralizing oxygen-based free radicals, whereas gamma tocopherol does best with nitrogen-based free radicals. Both types of radicals are destructive to our bodies.

The vitamin E offered on the market is either man-made or isolated from plants. Man-made (or synthetic) vitamin E is designated on the bottle's label as DL alpha tocopherol. The D and L are isomers or mirror images of each other. Only the D form is representative of the natural vitamin E alpha tocopherol. There is considerable controversy as to whether the L form interferes with the natural D form in the body. Some researchers believe it may be toxic.

Natural vitamin E is usually labeled D alpha tocopherol but almost always contains all 4 tocopherols. Typically, the bottle's label mentions only D alpha tocopherol because of the expense the manufacturer would incur to assay for the presence and quantity of the other three. The 4 tocopherols are derived from soybean oil or, less commonly, wheat germ. The 4 tocotrienols are usually prepared from extracts of palm oil or rice bran.

Vitamin E deficiency is not common, but it can occur with poor nutrition and/or a problem with absorption of fats. The RDA for vitamin E is 30 International Units (IU) per day for DL and 22 IU/day for D alpha tocopherol. A diet totally devoid of fats can result in a deficiency of E, since some fat is required for absorption from the intestines.

Fragile red blood cells are a common characteristic of E deficiency. Blood cell membranes, normally protected by E, tend to oxidize and rupture easily. Recent studies indicate vitamin E may help in slowing cognitive decline in Alzheimer's patients, and it may even lower blood pressure and cholesterol levels. Significant evidence also supports the vitamin as important for protecting tissues from the destructive action of oxidants and consequent disease, including heart disease, cataracts, cancer, neurological disorders and disorders of the muscular system. The incidence of these diseases increases with age. Thus it is important to obtain enough E to attenuate the age-associated destructive process.

Vitamin E is more than an antioxidant. Growing evidence supports specific roles for the different forms of vitamin E. For example, recent research demonstrates gamma tocopherol to be capable of blocking the activity of an enzyme involved in producing cellular mediators of inflammation (prostaglandins), which can lead to disease. Other tocopherols, including the more popular alpha, are largely ineffective in this context.

Alpha tocotrienol has now been shown in cell culture experiments to protect cells of the nervous system from the degenerative action created by the overproduction of the neurotransmitter, glutamate. This chemical, better known as monosodium glutamate, is used as a food enhancer and is infamous for its reputation as the agent responsible for the Chinese restaurant syndrome (bad headaches, etc.) in those who consume too much of it. Normally, an excess of this neurotransmitter activates a neurotoxic enzyme (12-LOX). Tocotrienol, in very small amounts, stops this toxic enzyme in its tracks, thus potentially protecting the nervous tissue.

The unique behavior of the different forms of vitamin E helps explain the advice of nutritionists to consume a variety of fruits, vegetables, legumes and grains. All are good sources of the various forms of vitamin E. Grains should preferably be non-refined. The tocotrienols, as well as other micronutrients, are present in the rice bran, which is lost in processing. People on low-fat diets, such as vegans, are often deficient in vitamin E and should consider taking supplements.

How much E should one take, if any? The upper safe limit for D alpha tocopherol is 1,500 IU/day, according to The Institute of Medicine. The major danger in taking high levels of E is its capacity to inhibit the adherence of platelets to the walls of blood vessels. This is positive for cardiovascular health in those with over-active clotting, but too much E can cause bleeding, especially for people taking other anticoagulants, such as aspirin or coumadin. If you are inclined to take vitamin E, 400 IU/day of natural vitamin E is a reasonable target. However, it is advisable to consult with your physician before taking this supplement.

Finally, the E vitamins function as antioxidants only in their reduced, non-oxidized state. In a subsequent newsletter we will describe how the cells of the body maintain these antioxidants in their reduced or active state. We will also describe how the versatile antioxidant, alpha lipoic acid, functions to recycle these and other antioxidants to maintain cellular health as we age.

Substantial progress has been made in understanding the bio- chemistry of the mitochondria - the organelles that power our cells. Similarly, mitochondrial decay is broadly recognized as playing a central role in the aging process. However, much less is known about effective nutritional approaches to maintain and promote mitochondrial health.

A recent literature review in Canada has evaluated the effects of a wide variety of substances that are reported to produce positive effects on the mitochondria. These include coenzyme Q₁₀; other antioxidants, such as ascorbic acid, vitamin E, and lipoic acid; niacin; creatine; carnitine, and some others. For further information, click here.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.