From the Journals

Artificial sweeteners in processed foods tied to increased depression risk



A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.


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