Antioxidants act as cell protectors. They are substances that are capable of counteracting the damaging, but normal, effects of the physiological process of oxidation in animal tissues. Oxygen, an essential element for life, can create damaging by-products during normal cellular metabolism. Antioxidants counteract these cellular by-products, called free radicals, and bind with them before they can cause damage.

Oxidative stress occurs when the production of free radicals exceeds the protective capability of our natural antioxidant defenses. Free radicals are chemically active atoms or molecular fragments that have a charge due to an excess or deficient number of electrons in the outer shell. Examples of free radicals are the superoxide anion, hydroxyl radical, transition metals such as iron and copper, nitric oxide, and ozone.

Because free radicals have one or more unpaired electrons, they are highly unstable. Generally free radicals attack the nearest stable molecule, “stealing” its electron. When the “attacked” molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. Once the process is started, it can cascade, finally resulting in the disruption of the living cell.

Anti-oxidants neutralize free radicals by donating one of their electrons, ending the electron-stealing reaction. The antioxidant nutrients don’t themselves become free radicals by donating an electron because they are stable in either form. They act as scavengers, helping to prevent cell and tissue damage that could lead to cellular damage and disease.

Fruits and vegetables can provide an abundant supply of different types of antioxidants, along with other, less well-understood, components that could be important factors in achieving optimum health benefits. A great variety of the antioxidants found in foods are also available in nutritional supplement form. It is a matter of some debate whether the higher amounts of antioxidants that can be taken in supplement form, offset the theoretical advantage of the combined benefit of all components of the food source. Much research still needs to be done on this question, and on the role and mechanism of action of specific antioxidants in different disease states.


Bioavailability is understood to mean the rate and extent to which the active substance is absorbed from a pharmaceutical formulation and becomes available in the general circulation. It is further defined as the extent to which the active moiety enters systemic circulation, thereby gaining access to the site of action.

Differences in bioavailability among formulations of a given drug or supplement can have clinical significance. When a drug or supplement rapidly dissolves and readily crosses membranes, absorption tends to be complete, but absorption of orally administered drugs is not always complete. Before reaching the vena cava, a drug must move down the GI tract and pass through the gut wall and liver, common sites of drug metabolism. Many drugs have low oral bioavailability because of extensive first pass metabolism.

Low bioavailability is most common with oral dosage forms of poorly water-soluble, slowly absorbed drugs. More factors can affect bioavailability when absorption is slow or incomplete than when it is rapid and complete, so slow or incomplete absorption leads to variable therapeutic responses.

Assessment of bioavailability from plasma concentration-time data usually involves determining the maximum (peak) plasma drug concentration, the time at which maximum plasma drug concentration occurs, and the area under the plasma concentration-time curve (AUC). AUC is the most reliable measure of bioavailability, and is directly proportional to the amount of unchanged drug that reaches the systemic circulation.


A large percentage of drugs and dietary supplements are poorly water-soluble or water-insoluble. More than one-third of the drugs listed in the United States Pharmacopoeia fall into the poorly water soluble or water insoluble categories. To improve the absorption and bioavailability of oral dosage forms of these compounds, a wide variety of techniques have been developed to “solubilize” poorly-soluble active ingredients. These techniques include solid dispersions, lipid-based self-emulsifying systems, liposomes, complexation, and polymeric micelles.

Solubilized drugs generally improve the pharmacokinetic properties of the drugs, increasing their absorption and bioavailability. Solubilized formulations are generally more complex and more expensive to produce, and are thus usually employed for formulating high-cost active ingredients. The added cost of solubilized formulations is more than offset by the increased absorption, allowing use of lower dosages, and the more uniform delivery of the drug to the circulation.