Functional Magnetic Resonance Imaging has been used for over a decade to measure the effects of sugar on the hypothalamus, the appetite-regulating center of the brain. Hypothalamic activity decreases in a dose-dependent manner in response to glucose solution consumption. Fructose elicits an increase in hypothalamic activity. This study aimed to understand the effects of high fructose corn syrup, a combination of glucose and fructose on hypothalamic activity. Fasting blood samples were collected from 8 (4M /4F) healthy adult volunteers who were then fed a standard breakfast and transported to the Maryland Neuroimaging Center. Participants underwent two successive scans. Prior to the first scan participants drank 12 oz. of either cola or water. After the first scan participants received 6 oz. of either cola or water immediately prior to the beginning of the second scan. Treatments were assigned in a Latin square crossover design. Each scan included ~17mins of T2 weighted functional scanning of the hypothalamus (12 mm mid-sagittal slice; echo time: 5ms; repetition time 40ms; flip angle: 40°; FOV: 210 mm; in-plane resolution: 1.6mm X 1.6mm). MANOVA revealed a statistically significant three-way interaction between time, volume and treatment when the model was weighted with either fasting insulin (p<0.0001) or fasting triglycerides (p=0.023). Gender also significantly interacted with time, volume and treatment (p=0.008). Further, age was negatively correlated with overall average hypothalamic signal intensity with volume as well with treatments. Both demographics and metabolites strongly influence hypothalamic response, making it difficult to determine the specific effects of high fructose corn syrup sweetened cola on appetite signals in the hypothalamus.