*Article* **Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood**

**Kristi A. Clark 1, Jasmin M. Alves 2,3, Sabrina Jones 2,3, Alexandra G. Yunker 2,3, Shan Luo 2,3,4, Ryan P. Cabeen 5, Brendan Angelo 2,3, Anny H. Xiang <sup>6</sup> and Kathleen A. Page 2,3,\***


Received: 13 February 2020; Accepted: 24 March 2020; Published: 26 March 2020

**Abstract:** In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7–11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of added sugars and the monosaccharide, glucose, on the same brain measures. We found that increased dietary intake of fructose, measured as a percentage of total calories, was associated with both an increase in the volume of the CA2/3 subfield of the right hippocampus and increased axial, radial, and mean diffusivity in the prefrontal connections of the right cingulum. These findings are consistent with the idea that increased fructose consumption during childhood may be associated with an inflammatory process, and/or decreases or delays in myelination and/or pruning. Increased habitual consumption of glucose or added sugar in general were associated with an increased volume of right CA2/3, but not with any changes in the connectivity of the hippocampus. These findings support animal data suggesting that higher dietary intake of added sugars, particularly fructose, are associated with alterations in hippocampal structure and connectivity during childhood.

**Keywords:** children; cingulum; development; dietary sugar; fructose; hippocampus
