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Diets high in nitrates were associated with higher risk for experiencing a manic episode, according to a prospective cohort study.

Among those with a history of psychiatric disorders, people who reported eating a history of dried meats cured with nitrates had increased odds of currently experiencing mania, a principal feature of bipolar disorder (adjusted odds ratio 3.49, 95% CI 2.24 to 5.45, P<8.97 × 10^-8), found Robert Yolken, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues, as reported in .

Eating nitrated cured meats was also significantly associated with increased odds of being hospitalized for acute mania, a finding that Yolken's group called "unexpected."

However, a diet comprising cured meats was not significantly associated with other psychiatric diagnoses or symptoms, such as schizophrenia, schizoaffective disorder, bipolar disorder, bipolar depression, or major depressive disorder.

The total analysis included 1,101 individuals with or without a history of psychiatric illness, recruited from the Baltimore area. Mania was defined as a diagnosis of bipolar I disorder with the most recent episode being mixed, bipolar II disorder with the most recent episode being hypomanic, or schizoaffective disorder with a bipolar type of manic, hypomanic, or mixed state. Information on food intake was assessed via a questionnaire.

"We looked at a number of different dietary exposures, and cured meat really stood out," explained Yolken in a statement, adding: "It wasn't just that people with mania have an abnormal diet."

Specifically, the group found that jerky was a major contributor to the association. In a subanalysis of the 42 individuals with mania who had more detailed information on meat consumption available, the three meats significantly tied to an increased odds of having a manic episode included dry cured meat such as meat sticks and jerky:

• Meat sticks: adjusted OR (aOR): 5.15 (95% CI 1.71 to 15.2, P=0.003)
• Beef jerky: aOR: 4.81 (95% CI 1.48 to 14.3, P=0.006)
• Turkey jerky: aOR: 3.54 (95% CI 1.11 to 11.3, P=0.032)

Consumption of other types of cured meats prepared through dehydration, such as prosciutto and salami, were not tied to mania, the researchers found. Additionally, other types of proteins such as raw or undercooked meat or fish were also not tied to an increase in mania.

Related Analysis in Rat Brains

In another analysis conducted by Yolken's group in the same paper, the team examined behavior and gene expression changes in the brains of rats exposed to nitrate-cured meats. Rats fed beef jerky cured with nitrates exhibited more hyperactive behaviors, which the authors called "reminiscent of human mania."

These rats also showed changes in their intestinal microbiota, as well as changes in their brain pathways, similar to what is seen in humans with bipolar disorder. Specifically, there was significant dysregulation in serotonin receptor signaling, bacterial pattern recognition, NF kappa beta signaling, and sphingosine-1-phosphate signaling. These changes were not seen in the group of rats whose food did not contain any nitrates.

The rats who were fed the beef jerky daily were given an amount scaled down to the equivalent of what a typical person would eat as a snack: "We tried to make sure the amount of nitrate used in the experiment was in the range of what people might reasonably be eating," noted Yolken.

Because of the retrospective data on participants' diets, additional research is needed, the researchers emphasized. In the meantime, however, they recommended that people who are already at risk for mania should consider limiting their intake of nitrates.

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