Dr Aiken is Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine and the Director of the Mood Treatment Center in Winston-Salem, NC. He is Editor in Chief of The Carlat Psychiatry Report.
New Study Finds That Nitrate-Cured Meats May Play a Causative Role in Mania
Nitrate-cured meats may increase the risk of mania, according to a study published in Molecular Psychiatry.1 That includes meat sticks, beef jerky, and turkey jerky, but not prosciutto, which is dry-cured without nitrates.
The finding was striking, with a large odds ratio of 3.5. It surprised the research team, who set out to investigate the relationship between diet and psychiatric illness at the Sheppard Pratt Health System. Their cohort of 1101 subjects included patients with bipolar mania, bipolar depression, unipolar depression, schizophrenia, schizoaffective disorder, and normal controls. Midway through the 10-year study, they noticed a sharp spike of dry cured meats among the patients hospitalized for mania. Other psychiatric illnesses did not show this association, and the finding held up after controlling for age, gender, race, current cigarette smoking, body mass index, socioeconomic status, and multiple statistical comparisons.
To further test that association with a controlled design, they added a series of animal studies in collaboration with the Nutrition Department at Purdue University. Compared with a standard diet, beef jerky increased manic behavior in rats, as measured by increased locomotor and novelty-seeking behavior. Additional experiments suggested that nitrates were part of the problem. Adding nitrates to the standard diet also increased manic behavior, although to a lesser degree than the beef jerky. When fed dried beef that was free of nitrates, the rats showed no increase in mania.
How can dietary nitrates trigger mania? Nitric oxide is one possibility. This gas rises with nitrate consumption and is increased in patients with bipolar disorder. Post-mortem analysis of the rat brains found alterations in brain regions that interact with nitric oxide: serotonin receptor signaling, nuclear factor (NF)-κB signaling, bacterial pattern recognition, and sphingosine-1-phosphate signaling. With the exception of sphingosine, each of those pathways has been linked to mania in human studies.
Another hypothesis is that the nitrate-rich foods alter the gut flora in ways that elevate the risk of mania. That may sound far-fetched, but it’s supported by basic science—the mind-gut connection—as well as by a recent controlled study (from the same Sheppard Pratt group) that found significant preventative benefits with probiotics after a manic episode.2 Indeed, the nitrate-fed rats had higher counts of two bacterial species associated with behavioral and cognitive changes in animals: Lachnospiraceae and Erysipelotrichales.
Dr Aiken does not accept honoraria from pharmaceutical companies but receives honoraria from W.W. Norton & Co. for a book he co-authored with James Phelps, MD, Bipolar, Not So Much.
1. Khambadkone SG, Cordner ZA, Dickerson F, et al. Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats. Mol Psychiatry. July 2018 [epub ahead of print].
2. Dickerson F, Adamos M, Katsafanas E, et al. Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: A randomized controlled trial. Bipolar Disord. April 2018 [epub ahead of print].
3. Brkić D, Bošnir J, Bevardi M, et al. Nitrate in leafy green vegetables and estimated intake. Afr J Tradit Complement Altern Med. 2017;14:31-41.
4. Song P, Wu L, Guan W. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: a meta-analysis. Nutrients. 2015;7:9872-9895
5. Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial). BMC Med. 2017;15:23.
6. Parletta N, Zarnowiecki D, Cho J, et al. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci. 2017:1-14.
7. Beyer JL, Payne ME. Nutrition and Bipolar Depression. Psychiatr Clin North Am. 2016;39:75-86.
8. Cook’s Illustrated, July 2010. https://www.cooksillustrated.com/how_tos/5734-nitrate-free-bacon. Accessed September 14, 2018.