R.G. Cutler

Scientific evidence is steadily accumulating, supporting the general importance of oxidative damage of tissue and cellular components as a primary or secondary causative factor in many different human diseases and aging processes. However, critical evaluation of the role oxidative damage plays in the general health status of an individual and how this damage might be reduced requires better means to measure in vivo by non-evasive means in human patients, their particular status of oxidative damage and related defensive and repair processes. Our goal has been to develop high sensitive and reliable means to measure the oxidative damage and defense/repair status of an individual that could be easily used by a physician to determine if there is an immediate or long term increase health risk of their patients as related to oxidative damage, how this risk can best be reduced and finally if the prescribed therapy is working and how it might be best adjusted to optimize benefits. We have found that by combining both an oxidative damage profile with a defense/repair processes have the best potential to meet these objectives. This technique and its use have been called Oxidative Stress Profiling and its analysis. One of the many challenges in creating this technique has been in the selection of the oxidative damage and defense/repair assays that are most sensitive and reliable when using only non-evasive collected samples from the patient such as urine and blood samples. Our strategy to solve these problems is to build in a high degree of redundancy in the profiling process. This is done by including many different assays that measure similar types of oxidative damage as in different types of oxidative DNA, lipids and protein and the same type of damage but using different assays methods such measuring the same type of lipid peroxidation several ways. At this time, our defense/repair profile includes most antioxidants that are present in the serum sample. The profile also includes parameters that indirectly correlate to oxidative stress status such as trace metal profile, hormone profile, inflammation marker profile and risk factor profile to cardiovascular disease. Finally, we have used those markers of oxidative stress and antioxidant status that have shown value as markers in human disease and aging processes and those that correlated with the different aging rates of primate species. In addition to the calculation of the absolute values, these data are presented on a reference range percentile bases which then allows the data to be combined to create an estimated net oxidative stress status and net antioxidant status of the individual. Preliminary data will be presented showing typical data using a total of about 75 different assays. Success is indicated by demonstrating the expected inverse correlation of Oxidative Stress vs. Antioxidant Status of population of several hundred individuals. In addition, we find support that oxidative stress status appears to be under tight regulatory control for most individuals over a wide range of life styles as diet and various types of oxidative stress including exercise. Indeed only about 10% of the population we have analyzed appear to have unusually high oxidative stress levels and it is only these individuals that are the best responders to various therapy measures we have tried to lower their oxidative stress status levels. In most cases the problems appear to be too high iron intake, presence of a low grade chronic infection, or low absorption efficiency of food derived antioxidants such as alpha tocopherol. In these cases therapy measures were only able to bring the patient to and not significantly below the normal range of oxidative stress levels. Implications of these results as to human application and how current clinical studies are carried out in evaluation of the benefits of antioxidant supplements in reducing incidence of specific disease will be discussed.

Keywords (Optional): 
Oxidative Stress Profiling
Antioxidant Status Profiling
Dietary Supplements
Trace Metal Profiling
Inflammatory Marker Profiling