Evidence from biochemical and animal models suggests that nutritional antio
xidants should inhibit the development of diseases such as CHD and certain
cancers. This evidence is not clearly corroborated by intervention studies
in human subjects, due, in part, to inadequacies in current analytical meth
odologies. Although in vitro assays can give useful information on the attr
ibutes required by a compound to act as an antioxidant, results may have li
ttle nutritional relevance due to limited bioavailability. The determinatio
n of antioxidants in blood is often used as a measure of antioxidant status
in vivo, but may not necessarily reflect concentrations in target tissues
where oxidative stress is greatest. In addition, the accumulation of antiox
idants in selective tissues may not be apparent from plasma measurements. P
articipation in quality-control schemes for antioxidant determination by HP
LC allows inter-laboratory comparison of results. Moderation of indices of
oxidative damage to lipids, proteins and DNA can provide information on the
effectiveness of compounds as nutritional antioxidants. However, most curr
ent methods of assessing oxidative stress are subject to confounding factor
s of non-oxidative origin. Assays for total antioxidant capacity in plasma
differ in their type of oxidation source, target and measurement used to de
tect the oxidized product. They give different results, should never be use
d in isolation, and results should be interpreted with caution. Until more
is known about the activity and metabolic fate of antioxidants, caution sho
uld be exercised in the consumption of large amounts of commercially-availa
ble antioxidant preparations.