A study of the dietary habits of more than 1,000 people with and without psychiatric disorders has found a link between eating nitrated cured meats such as beef jerky and meat sticks, and episodes of mania, a serious neuropsychological disorder that is one of the defining characteristics of bipolar disorder (BPD). Results from the study, which was led by Robert H. Yolken, M.D., Theodore and Vada Stanley distinguished professor of neurovirology in pediatrics at the Johns Hopkins University School of Medicine, showed that people who were hospitalized for an episode of mania were more than three times more likely to have ever eaten nitrate-cured meats than those without a history of a serious psychiatric disorder. “We looked at a number of different dietary exposures and cured meat really stood out,” says Dr. Yolken. “It wasn't just that people with mania have an abnormal diet.”
Further experiments showed that healthy rats fed a diet containing nitrate-cured meats or added nitrates triggered mania-like hyperactivity within just a few weeks. The researchers suggest their results add weight to evidence associating dietary factors with the risk for neuropsychiatric disorders such as BPD. Reporting in their published paper in Molecular Psychiatry, they suggest the findings may also “lead to new methods for preventing mania and for developing novel therapeutic interventions.”
“Future work on this association could lead to dietary interventions to help reduce the risk of manic episodes in those who have bipolar disorder or who are otherwise vulnerable to mania,” says Dr. Yolken. The team’s published paper is titled, “Nitrated meat products are associated with mania in humans and altered behaviour and brain gene expression in rats.”
Prior studies have identified a number of genetic risk factors for BPD and other neuropsychiatric disorders, but these aren't the complete answer, the authors point out. The resulting “heritability gap” points to “the role of the environment in mediating and propagating neuropsychiatric disease.” Diet has been highlighted as a potentially key environmental factor that may contribute to the risk of BPD and other neuropsychiatric disorder risks, through a variety of mechanisms that may range from neurotoxicity from trace heavy metals, to changes to the gut microbiome and gut-brain axis.
To investigate the potential link between environmental exposures and psychiatric conditions, Dr. Yolken’s team undertook a study through which they collected demographic, health, and dietary data for 1,101 individuals with and without psychiatric disorders. The study was part of ongoing research, initiated back in 2001, and including dietary data collected since 2007. Participants with a range of psychiatric disorders were recruited from patients who were undergoing psychiatric treatment at the Sheppard Pratt Health System in Baltimore.
The main inclusion criterion for participants with mania was current admission to hospital for symptoms of mania or hypomania. Patients with mania had been diagnosed with different forms of bipolar disorder or schizoaffective disorder. Data on food exposure was assessed through a questionnaire developed by the researchers, which asked participants whether they or not they had eaten certain types of food, but did not go into details such as the amount or over what period of time.
The resulting analyses “unexpectedly” found that a history of eating nitrate-cured meats such as beef jerky and meat sticks – but not dry-cured meats such as salami or prosciutto – was independently associated with being hospitalized with acute mania, even after adjusting for confounding factors. No other foods were linked with mania, and nitrate-cured meats were not directly associated with a diagnosis of any other neuropsychiatric disorder, including schizophrenia or schizoaffective disorder, BPD, bipolar depression, or major depressive disorder.
The human study wasn’t powered to investigate cause-and-effect, so the team next investigated the potential effects of nitrate-cured meats on the behaviors of healthy rats. Working with Johns Hopkins colleagues Seva Khambadkone, and Kellie Tamashiro, Ph.D., associate professor of psychiatry and behavioral sciences, the researchers carried out three sets of experiments in which animals were fed on either normal rat chow, or on diets supplemented with nitrate-cured meat preparations, cured meats prepared without added nitrates, or non-nitrate cured meat to which nitrate was added separately. Importantly, the amount of nitrate being consumed by the rats was equivalent to the amount a human might ingest in a daily snack, such as a hotdog or beef jerky stick. “We tried to make sure the amount of nitrate used in the experiment was in the range of what people might reasonably be eating,” Dr. Yolken comments.”
Within just a couple of weeks, the rats consuming nitrate-cured meat or added nitrates developed locomotor hyperactivity that mimicked symptoms of human mania. These animals also demonstrated changes to hippocampal pathways in the brain that have been implicated in human bipolar disorder, as well as alterations to their intestinal microbiota. In contrast, a diet high in meats prepared without nitrates didn’t induce behavior changes or hyperactivity.
Dietary exposure to nitrate-cured meat has previously been implicated in disorders including different types of cancer, asthma, and chronic obstructive pulmonary disease, but the underlying mechanisms aren’t understood, the researchers point out. “To our knowledge, this is the first study associating exposure to cured meat with a neuropsychiatric disorder,” they point out, acknowledging that further studies will be needed. Nevertheless, they write, “individuals at risk for mania may consider limiting ingestion of added dietary nitrates.”
“It's clear that mania is a complex neuropsychiatric state, and that both genetic vulnerabilities and environmental factors are likely involved in the emergence and severity of bipolar disorder and associated manic episodes,” comments Khambadkone. “Our results suggest that nitrated cured meat could be one environmental player in mediating mania.”
Dr. Yolken's group has previously reported results demonstrating that bipolar disorder patients treated using probiotics after a manic episode are less likely to be hospitalized within the next six months. “There's growing evidence that germs in the intestines can influence the brain,” says Dr. Yolken. “And this work on nitrates opens the door for future studies on how that may be happening.”