Rat study links high-fructose corn syrup to anxiety markers and autism-linked gene activity

A study of young female Sprague-Dawley rats found that those raised on water sweetened with 13% high-fructose corn syrup (HFCS) had increased adrenal gland mass, suggesting chronic stress. They also exhibited lengthened estrous cycles. Analysis of gene expression in the hypothalamus revealed alterations in genes involved in regulating the sleep–wake cycle and in the Engrailed-2 gene, which has been linked to autism spectrum disorder in humans. The findings were published in Nutritional Neuroscience.

High-fructose corn syrup is a sweetener derived from corn starch that has been enzymatically processed to convert some of its glucose into fructose, resulting in a mixture of both sugars. Developed in the 1960s, HFCS gained popularity due to its lower cost compared to cane sugar and its convenience in liquid form. It is now widely used in soft drinks, sweetened beverages, baked goods, condiments, and processed foods.

From a taste and caloric perspective, HFCS is similar to regular table sugar. However, its pervasive use in processed foods has led to much higher consumption levels. It is currently the leading source of added sugars in the American diet. Studies have associated excessive HFCS intake with weight gain, obesity, and various metabolic issues, partly because liquid calories are easier to consume in excess without promoting satiety. Other research suggests that high HFCS intake may contribute to insulin resistance, fatty liver disease, and elevated triglyceride levels, all of which increase the risk of cardiovascular disease.

Study author Sundus S. Lateef and colleagues sought to investigate the effects of consuming HFCS-, sucrose-, or fructose-sweetened water from the weaning stage through early adulthood in rats. They focused on physiological processes regulated by the hypothalamus, a brain region that controls hunger, thirst, temperature regulation, sleep, stress responses, and hormonal activity via the pituitary gland.

The experiment involved 28 weanling female Sprague-Dawley rats, a widely used laboratory strain known for its calm temperament and rapid growth. The rats were 21 days old at the study’s onset.

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After a 7-day acclimation period, the rats were randomly assigned to four groups, each given a different water solution. One group received plain water, while the other three were given carbohydrate-sweetened solutions containing 13% sugar by weight. One group drank a fructose solution (130 grams per liter), another drank a sucrose solution (130 grams per liter), and the third consumed HFCS-sweetened water (168.8 grams of syrup per liter).

The rats were housed individually in metabolic cages that allowed researchers to precisely monitor food and fluid intake. All groups had free access to standard chow. The sweetened water regimen continued for eight weeks. During this period, the researchers tracked body weight weekly and monitored the estrous cycles of the rats. The estrous cycle, lasting about 4–5 days in rats, reflects hormonal changes associated with reproductive readiness. At the end of the study, the rats were euthanized for tissue analysis.

The results showed that rats consuming HFCS and sucrose drank more liquid but ate less food. Rats in the HFCS group had the greatest absolute adrenal gland mass, indicating prolonged activation of the stress response.

Gene expression analyses of hypothalamic tissue revealed that rats in the HFCS group showed the most pronounced differences in genes related to circadian rhythm regulation, neuronal function, and Engrailed-2 (En2), a gene associated with autism spectrum disorder in humans.

“Among the different caloric-sweetened solutions, young female rats drinking HFCS solution showed food selectivity, elevated basal stress, and reproductive irregularity, which are characteristics associated with ASD [autism spectrum disorder, in humans]. RNA-Seq [RNA sequencing] revealed DEGs [differentially expressed genes] in rats drinking HFCS solution, including disrupted circadian sleep cycles, neurotoxicity, and ASD. The results of this preclinical study suggest that HFCS intake should be limited due to its potential for increasing the risk of neurodevelopmental disorders,” the study authors concluded.

The findings shed light on how chronic consumption of high-fructose corn syrup may affect stress responses, reproductive cycles, and neurodevelopmental pathways in young female rats. However, it is important to emphasize that this was an animal study. While rats share many physiological traits with humans, they are not identical, and results from rodent studies do not always translate directly to human outcomes.

The paper, “Hypothalamic regulated physiological function and gene expression changes suggest high fructose corn syrup intake affects neurodevelopment in adolescent female rats,” was authored by Sundus S. Lateef, Vanessa L. Mueller, Eloisa Vendematti, Vagner A. Benedito, Joseph C. Gigliotti, R. Chris Skinner, and Janet C. Tou.