Increased intake of selenium (Se) may reduce the risk of degenerative diseases including cancer but excessive intake may be toxic. Wheat is a major source of dietary Se in humans. However, the effect of Se from wheat that is agronomically biofortified with Se on biomarkers of human health status is unknown. This study aimed to investigate whether improving Se status, by increased dietary intake of Se-biofortified wheat, affects biomarkers of cancer risk, cardiovascular disease risk, oxidative stress, and immune function in healthy South Australian men. A 24-week placebo-controlled double-blind intervention was performed in healthy older men (n = 62), with increased dose of Se intake every 8 weeks. Wheat was provided as 1, 2, and 3 puffed wheat biscuits, during weeks 1-8, 9-16, and 17-24, respectively. Blood was collected to measure a wide range of disease risk biomarkers. Consumption of Se-biofortified wheat was found to increase plasma Se concentration from a baseline level of 122 to 192 microg/L following intake of three biscuits/day, which provided 267 microg Se. Platelet glutathione peroxidase, chromosome aberrations, and DNA damage in lymphocytes measured using the cytokinesis-block micronucleus cytome assay and with the Comet assay, plasma F2-isoprostanes, protein carbonyls, plasma C-reactive protein, and leukocyte number were unaffected by the improved Se status. Improvement of Se status by consumption of Se-biofortified wheat did not substantially modify the selected biomarkers of degenerative disease risk and health status in this apparently selenium-replete cohort of healthy older men in South Australia. ; Jing Wu, Carolyn Salisbury, Robin Graham, Graham Lyons and Michael Fenech