Differences in intake of high-fat high-sugar diet are related to variations in central dopamine in humans.

Obesity is associated with alterations in dopaminergic transmission and cognitive function. Recent findings from rodent studies suggest that diets rich in saturated fat and refined sugars (HFS) induce changes in the dopamine system independent of excessive body weight. However, so far the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine dependent cognitive tasks between two groups that differ in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject crossover design to compare the effect of acute phenylalanine/tyrosine depletion (APTD) on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs. high intake: LFS vs. HFS group). We tested 31 healthy young women, who were matched for BMI (mostly normal weight to overweight) and IQ. Depletion of central dopamine reduced the working memory specific performance on the operation span task (OSPAN) in the LFS, but not in the HFS group (p = 0.023, r = 0.210). Learning from positive and negative reinforcement (probabilistic selection task: PST) was increased in both diet groups after dopamine depletion (p = 0.048, r = 0.144). As secondary exploratory research question we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (p = .048, r = -0.355). Our data provides first evidence that the intake of HFS is associated with changes in indirect measures of central dopamine levels in humans. The observed associations are independent of body weight status, suggesting that consumption of HFS might be associated with maladaptive behaviors contributing to the development of obesity.