Poison Paradise

That Girl is Poison(ed)

There are many reasons why Carlota of Mexico would have been paranoid that someone was poisoning her. Her husband was unfaithful, she was stripped of her influence in the government, and her throne and very life were in imminent danger. That particular combination would probably put most people on edge. When you consider she was also exhibiting insomnia and disordered, constant speech, bipolar disorder or schizophrenia also seems like a likely explanation. But like any good detective from a true crime documentary, I have to wonder if the simplest explanation could be the correct one: what if Carlota thought she was being poisoned because she actually was?

The Green Monster

I’m far from the first person to suggest that Carlota’s fears were not completely unwarranted. I’ve come across some claims that someone was slipping small amounts of bromide, a toxic ionic form of the element bromine, into her morning coffee. But given that the neurological effects of bromide poisoning are more common when it is inhaled in a gaseous form, I’m not sure how likely this is. There are also theories that she was being given small amounts of psychotropic drugs while living in South America. This doesn’t quite add up since Carlota first claimed that she was poisoned when she fell ill in Yucatan, but then became absolutely fixated on it a year later in Europe. Besides, I’m not quite sure what anyone would have gained from poisoning Carlota. The empire in Mexico was poised to fall with or without her, and it’s not like her presence was holding Max back from pursuing other women. 

But in the 19th century, you didn’t need a mortal enemy to end up being poisoned; you only needed expensive taste. In our Ivan the Terrible series, we talked about how the ubiquity of mercury in beauty products and medications in the 1500s might have contributed to his dramatic change in personality. It wasn’t until 1865, the year Carlota first claimed she was being poisoned, that the first report of lethal mercury poisoning was published. But there was another toxin hiding in plain sight: arsenic.

Beauty was literally pain in Carlota’s era. The trendiest shade of green meant risking arsenic poisoning. Esquire

It was not news by Carlota’s lifetime that arsenic, one of the metalloid elements from the periodic table, was dangerous; it was described as a toxin as early as the first century (!) and because of the prevalence of intentional arsenic poisonings, a test had been developed in the 1830s to detect it. The problem was that arsenic was cheap and useful. Arsenic was a byproduct of common manufacturing processes during the industrial revolution and was sold in the white powdered form of arsenic trioxide. This “white arsenic” was then given a second life in food, drink, candles, home furnishings, and more. And green dyes made from arsenic and copper found their way into wallpapers, clothing, and accessories when the color reached peak popularity in the 1860s and 1870s. The widespread use of arsenic is typically associated with England, the industrial revolution powerhouse, but also found its way across Europe and America. It wasn’t until 1903 that Britain set limits on arsenic levels in food and drinks, but they never passed legislation regulating arsenic in other consumer products. Moreover, it seems pretty clear that limiting arsenic levels isn’t enough; any amount can have grave effects. 

In Plain Sight

Lest we look at history with judgmental eyes, I want to point out that our modern society is not above including dangerous chemicals in consumer products. My high school science fair project (and I’m not that old) was about an emerging chemical of concern called bisphenol a (BPA). BPA belongs to a class of chemicals known as endocrine disruptors, a major concern in modern manufacturing. As you might have guessed based on the name, endocrine disruptors are chemicals that interfere with the endocrine (hormone) system by mimicking endogenous hormones, altering their levels, or interfering with their production. If you read our series on Alexandra Romanov, you know that messing with the endocrine system is a big no-no, seeing as hormones play an important role in, well, everything that your body does. 

The three main mechanisms of actions of endocrine disruptors. NIH

BPA is in polycarbonate plastics and resins that were pervasive components of food and beverage packaging and storage. Because BPA can leach out of these materials into food and drinks, and are stable in the environment for a long time, it’s not surprising that a 2008 study found that out of 2500 participants, 96% had measurable levels of BPA. Once in the body, BPA can interfere with components of the estrogen, thyroid hormone, androgen, and glucocorticoid pathways. BPA also produces epigenetic changes in mice exposed to the chemicals. This widespread disruption is reflected by studies exploring the links between BPA and diabetes, infertility, impaired sexual and neural development, and neuronal plasticity. 

However, the Food and Drug Administration (FDA) had conducted independent studies and reviewed others demonstrating that BPA is rapidly inactivated or eliminated when ingested orally. They are continuing to research the effects of BPA since there is a lot of conflicting data, and therefore, the FDA currently only restricts BPA in baby bottles, sippy cups, and packaging for infant formula, given that infants are the most vulnerable to the developmental dangers presented by endocrine disruptors. Individual states may have additional regulations on products made for pregnant women and young children. Luckily, many companies, much like wallpaper manufacturers of the Victorian age, have eliminated BPA from their packaging due to customer concerns. 

The chemical structures of BPA, the synthetic estrogen DES, and the natural hormone estradiol. Rubin, 2011

The truth is, we are not all that different from the average shopper in the 1860s. We like what we like and we don’t tend to think about how our benign purchases might affect our health in the long run. I’m guilty of it too. A study finding high levels of another endocrine disruptor, per- and polyfluoroalkyls (PFAS), in some brands of carbonated waters hasn’t done much to curb my seltzer habit. It takes longer for us to learn how chemicals affect our bodies than it does for them to become staples in manufacturing. So be curious about what you’re putting into and onto your body. If my suspicions are true, such a curiosity could have saved Carlota from a tragic psychological demise.

Forget Me Not

Other than the massive coincidence that arsenic-containing products were at the peak of fashion at exactly the same time that Carlota began exhibiting symptoms of mental illness, what evidence supports that her condition might have been caused by arsenic poisoning? Sadly, arsenic from rocks continues to contaminate drinking water in some parts of the world, especially China, India, and the western United States. We know from studies of people in the US that acute arsenic poisoning is associated with the “development of a psychosis associated with paranoid delusions, hallucinations, and delirium” (Saha et al, 1999). Sounds an awful lot like Carlota’s manic episode at the Vatican and constant fears of being poisoned by her inner circle. 

However, if Carlota experienced acute arsenic poisoning, there’s no way that she would have lived to be 88. Depending on how much arsenic you are exposed to and how frequently, it could take anywhere from a matter of months up to a decade for symptoms to emerge. Symptoms of chronic arsenic poisoning begin with changes to the skin and then progress to the eyes, gut, and lungs. I wish that I knew what Carlota’s physical symptoms were when she first complained that she was poisoned. If she had none of these symptoms, it’s unlikely that she was suffering from arsenic poisoning. But what is consistent between Carlota’s experience and modern studies of chronic arsenic poisoning is that there is an increased level of insomnia, depression, and anxiety, and other mood disorders in people exposed to arsenic. 

For all the overachievers looking to learn about LTP in more detail.

If arsenic was the cause of Carlota’s mental illness, we need to understand how it affects the brain. Observations that learning and memory were impaired in people exposed to arsenic was the first clue. Memory formation occurs in a region of the brain called the hippocampus. While the molecular basis of memory formation is not fully understood, the leading hypothesis is a process called long-term potentiation (LTP). LTP goes a little something like this: neurons in the hippocampus release a neurotransmitter called glutamate. This glutamate binds to receptors on other neurons. If the signal is strong enough, the neuron on the receiving end will have an electrical response that opens up a different kind of glutamate receptor called NMDAR. This NMDAR triggers a cascade in signaling events, resulting in the neuron being more receptive to future neurotransmitter signals. The strengthened connection between the two cells is the physical correlate of the memory. But in multiple studies, rodents exposed to arsenic have impaired performance on memory and learning tasks, and their hippocampuses do not exhibit normal LTP. This was driven by decreased expression of NMDAR genes and other proteins that signal downstream of glutamate. Arsenic also interferes with other neurotransmitter signaling pathways, like cortisol, serotonin, and dopamine, explaining how it is able to destabilize mood.

Additionally concerning is the observation that arsenic exposure decreases generation of new neurons in adults. So-called adult neurogenesis is already a limited and delicate process, and may be disrupted by alterations to neurotransmitter signaling. Neural stem cells treated with arsenic in culture dishes had lower levels of protein needed for them to mature into neurons. In rodents exposed to arsenic, neural stem cells showed increased levels of cell death. The link between decreased adult neurogenesis and mental illness is still tenuous, but it’s notable that many antidepressants and some antipsychotic medications promote neurogenesis. Thus, arsenic’s interference with neurogenesis may contribute to neuropsychiatric manifestations of its poisoning.

Cold Case

In my research, I came across a case study from 1989 of two men in their late 20s who were exposed to arsenic at work. They experienced psychiatric symptoms like anxiety, suicidal ideation, confusion, memory impairments, difficulty focusing, and cognitive deficits. In some ways, they reminded me of Carlota. But while she lived another half century grappling with her mental illness, these men recovered within a year and a half of being removed from the source of exposure.

So either Carlota had a constant source of arsenic throughout the rest of her life, or something else was to blame for her mental collapse. Given that there is no evidence that she experienced the tell-tale somatic signs of arsenic poisoning, I think the latter is most likely the case. Her insomnia, fits of rage, disordered speech, and paranoia are consistent with schizophrenia, a developmental disease that affects neural communication. But that doesn’t necessarily mean she was never poisoned. What I hope you take away from this post is that chronic poisoning can have profound effects on neurological functioning. And based on modern evidence, it can also increase the likelihood that a person develops a mental illness. Maybe Carlota never was exposed to arsenic. But maybe she wasn’t that crazy after all; maybe there was something slipped into her teacup that triggered a cascade of biological consequences. And in the wake of her psychiatric crisis, the Mexican empire crumbled. All that, next week when we wrap up our series on Carlota.


Aimee, A. (2020, September 24). Some sparkling water brands have PFAS chemicals, study finds. Retrieved from https://www.cbsnews.com/news/pfas-chemicals-in-sparkling-water-polar-topo-chico-study/

Barrett, J. R. (2010). An Uneven Path Forward: The History of Methylmercury Toxicity Research. Environmental Health Perspectives,118(8). doi:10.1289/ehp.118-a352bEndocrine Disruptors. (n.d.). Retrieved from https://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm

Meyer, M. (2019, July 10). An Everyday Poison. Retrieved from https://www.sciencehistory.org/distillations/an-everyday-poison

Mo, C. (2020, December 09). Bisphenol A (BPA) Regulations in the United States: An Overview. Retrieved from https://www.compliancegate.com/bisphenol-a-regulations-united-states/#Which_products_and_materials_may_contain_Bisphenol_A

Morton, W. E., & Caron, G. A. (1989). Encephalopathy: An uncommon manifestation of workplace arsenic poisoning? American Journal of Industrial Medicine,15(1), 1-5. doi:10.1002/ajim.4700150102

Rae, H. (2016, October 11). When Poison Was Everywhere. Retrieved from https://www.theatlantic.com/health/archive/2016/10/the-era-when-poison-was-everywhere/503654/

Rubin, B. S. (2011). Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects. The Journal of Steroid Biochemistry and Molecular Biology,127(1-2), 27-34. doi:10.1016/j.jsbmb.2011.05.002

Saha, J. C., Dikshit, A. K., Bandyopadhyay, M., & Saha, K. C. (1999). A Review of Arsenic Poisoning and its Effects on Human Health. Critical Reviews in Environmental Science and Technology,29(3), 281-313. doi:10.1080/10643389991259227

Schoenfeld, T. J., & Cameron, H. A. (2014). Adult Neurogenesis and Mental Illness. Neuropsychopharmacology,40(1), 113-128. doi:10.1038/npp.2014.230

Smith, R. (n.d.). Arsenic: A Murderous History. Retrieved from https://sites.dartmouth.edu/toxmetal/arsenic/arsenic-a-murderous-history/

Tyler, C. R., & Allan, A. M. (2014). The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review. Current Environmental Health Reports,1(2), 132-147. doi:10.1007/s40572-014-0012-1

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