Non-invasive Human Oxidative Stress Profiling and its Biomedical Application
Richard G. Cutler
Kronos Science Laboratories, Inc., 2222 East Highland Avenue, Suite 220, Phoenix, AZ 85016, USA
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.
Key words:
Oxidative Stress Profiling, Antioxidant Status Profiling, Dietary Supplements, Trace Metal Profiling, Inflammatory Marker Profiling, Cardiovascular Disease Risk Factors
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