A 10-year study of over a thousand patients finds that nitrate-cured meats may play a causative role in mania. Hot dogs and bacon may be next.
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)-ÎºB 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.
Another side of nitrates
It’s unlikely that nitrates are the sole cause of this association. In the typical diet, 80% of nitrates come from vegetables like spinach, beets, and celery, foods that confer both physical and mental benefits. Only 5% to 10% is derived from nitrate-cured meats.3 Nitrates act differently in cured meats, where they combine with amines to form nitrosamines. Nitrosamines are thought to be responsible for other health risks that are associated with nitrate-cured meats, such as cancer, asthma, and chronic obstructive pulmonary disease.4
The bottom line
Although the human data in this study is associational, the animal data adds controlled confirmation and a plausible biological mechanism. What’s missing is replication, an important step with novel findings. Pending that, there is little harm in recommending that bipolar patients limit their consumption of processed meats, particularly beef sticks and jerky. Last year, two controlled studies found that a Mediterranean-style diet low in processed foods improved unipolar depression, and basic science suggests that following this type of diet is beneficial in bipolar disorder as well.5-7
What about hot dogs, bacon, sausage, pepperoni, and nitrate-cured fish? The study casts doubt on the safety of these nitrate-cured meats, although it did not examine them specifically. It did look at salami, which is often nitrate-cured, and found no risk there or with prosciutto, which is not made with nitrates. One word of caution for those wishing to avoid nitrates. The classification of nitrates as a probable carcinogen has led to some deceptive labeling such as “uncured” and “nitrate-free.” Look carefully for evidence of vegetable powder on those labels, such as celery or beets. Brining meats with these nitrate-rich vegetables causes the same risky chemicals to form as curing with nitrate salts, and often in greater amounts.8
Erratum: This article incorrectly used the name of Johns Hopkins’ Sheppard Pratt hospital. The correct name is Sheppard Pratt Health System.
This article was originally published 7/31/18 and has since been updated.
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. BrkiÄ D, BoÅ¡nir 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.