Atherosclerosis, one of the major causative factors of cardiovascular diseases (CVD), is thought to be initiated by oxidative stress. Particular attention has been paid to the atherogenic effects of oxidative damage on low density lipoproteins (LDL). Current research shows that dietary antioxidant supplementation protects against oxidative stress, and therefore may present preventative measures and treatments for patients with diseases influenced by oxidative stress. Isoflavones found in soy, such as genistein and daidzein are reported to have potent antioxidant properties and have been shown to inhibit LDL oxidation in vitro. Although there is a strong base of data that supports the correlation between soy consumption, cholesterol reduction and cardiovascular protection, it remains to be elucidated whether it is the soy protein, the isoflavone, or a combination of both that confers benefits. This study investigated the effect of isoflavone supplementation on the following parameters: plasma genestein levels, oxidized LDL levels, plasma cholesterol, vitamin E, and C-reactive protein. Elevated serum cholesterol and C-reactive protein (CRP) have been identified as risk factors for cardiovascular disease. In a randomized, double-blind, placebo-controlled study, 150 mg/d isoflavone was supplemented for four weeks by 30 healthy, yet sedentary male subjects who underwent 30 minute exercise sessions at 80% VO2pk before and after a 28 day period of supplementation. The purpose of the exercise was to induce oxidative stress. The average plasma genistein and daidzein concentrations increased significantly after isoflavone supplementation from 0 ng/ml to 561.6 ± 39.3 and 466.3 ± 35.5 ng/ ml (SE) respectively (P < 0.0001), compared to 0 ng/ml in the placebo group throughout the study. There was no significant beneficial effect of isoflavone supplementation on oxidized LDL, plasma vitamin E concentrations, total cholesterol, LDL, HDL, or triglycerides. Isoflavone supplementation resulted in an average increase in CRP levels by 44% (P = 0.014), which was opposite from expectations. This study supports the theory that it may not be soy isoflavones alone that benefit lipid profiles, or offer protection from oxidative stress.