The primary objective of this pilot clinical trial was to evaluate the effects of UP165 (derived from Zea mays L., commonly known as corn) over time. The secondary objective was the comparison for outcomes versusS-adenosyl-methionine (SAM-e). Subjects with mild depression or anxiety were given the Beck Depression Inventory second edition (BDI-II), the Beck Anxiety Inventory (BAI), and the Schwartz Outcome Scale (SOS-10). Forty-two subjects (21-65 years old) were randomized to eight-weeks of supplementation with UP165 or SAM-e with questionnaires being administered at randomization, week four and eight. Those receiving UP165 achieved significant reduction from baseline at weeks four and eight, respectively for the BDI-II, as well as a trend for reduction in BAI at week four and significance at week eight. There was a trend for improvement on the SOS at week four and significance at week eight. SAM-e demonstrated a trend for improvement on the BDI-II by week eight over the UP165 with no differences between the two for the BAI or the SOS. Overall, this study indicates that there may be benefit to UP165 for mood enhancement in those with mild depression or anxiety. Randomized placebo comparator trials appear warranted.