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19.05.2019

Sulforaphane, an antipsychotic from broccoli?

Sulforaphane is found in broccoli, Brussels sprouts, cauliflower and other cruciferous vegetables. This phytochemical activates the cellular manufacture of detoxifying proteins such as glutathione. In this way, sulforaphane may help prevent or combat psychosis, hope molecular psychiatrists from Johns Hopkins University in the US. But isn't the dose required for that too high?

Glutathione, glutamate & psychoses
In January 2019, the researchers published a study in which they examined the brains of 81 people admitted to hospital after receiving a psychosis and 91 healthy subjects using magnetic resonance spectroscopy. [JAMA Psychiatry. 2019;76(3):314-23.] Among other things, the study found that there was less glutamate and less glutathione among psychotic patients in critical parts of their brains.

In cells, the peptide glutathione functions, among other things, as a storage tank for glutamate. The figure below shows what that connection looks like.

In another study, the researchers blocked the conversion of glutamate to glutathione in brain cells with a pharmacological agent. [Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2701-6.] The drug increased the cellular concentration of glutamate and reduced the concentration of glutathione.

This shift made the brain cells hyperactive, en made them transmit more and stronger electrical stimuli to each other. This effect was somewhat similar to what happens in the brain during psychosis.

In the same in vitro tube study, the researchers stimulated the conversion of glutamate to glutathione by exposing brain cells to sulforaphane [figure below]. Sulforaphane is a bioactive substance in cabbage vegetables that activates the enzyme glutamate cysteine ​​ligase [GLCL]. GLCL glues glutamate into the glutathione molecule. As a result, the brain cells became quieter.

"We are thinking of glutathione as glutamate stored in a gas tank", explains psychiatrist and lead author Thomas Sedlak in a press release. [sciencedaily.com May 8, 2019] "If you have a bigger gas tank, you have more leeway on how far you can drive, but as soon as you take the gas out of the tank it's burned up quickly. We can think of those with schizophrenia as having a smaller gas tank."

Sulforaphane as an antipsychotic?
Nice of course. But can you change the activity of brain cells by giving sulforaphane to people? The researchers give the beginning of an answer to that question in a study that appeared in Molecular Neuropsychiatry. [Mol Neuropsychiatry. 2018 May;3(4):214-22.]

In that study, Sedlak and his co-workers gave 9 healthy test subjects 2 capsules a day each with 100 micromoles of sulforaphane for a week. As a result, the concentration of glutathione in blood cells did indeed increase significantly.

According to magnetic resonance spectroscopy, the concentration of glutathione increased in the brain as well, but this trend was not significant. The figure above relates to the glutathione concentration in the thalamus.

The researchers are nevertheless hopeful. If they had used more than 9 subjects, the effects on the glutathione concentration would probably have been significant, they write.

Conclusion
"It's possible that future studies could show sulforaphane to be a safe supplement to give people at risk or develop schizophrenia as a way to prevent, delay or blunt the onset of symptoms," says research director Akira Sawa in a press release. [sciencedaily.com May 8, 2019]

"For people predisposed to heart disease, we know that changes in diet and exercise can help stave off the disease, but there is nothing like that for severe mental disorders yet," adds author Sedlak. "We are hoping that we will one day make some mental illness preventable to a certain extent."

Just whining
The researchers are not sure whether sulforaphane actually counteracts psychosis. They haven't investigated that yet. But that is not the reason why we feel compelled to make a whining comment.

The daily dose of 200 micromoles of sulforaphane that the researchers gave to their test subjects amounted to 35.5 milligrams per day. That is a lot. A capsule of any heavy-dose supplement with sulforaphane usually contains several hundred micrograms of the substance. The supplementation scheme of the researchers amounts to a more than a jar of such a supplement per day.

Source:
Mol Neuropsychiatry. 2018 May;3(4):214-22.

More:
Sulforaphane supplement mitigates autism traits 08.02.2015
Sulforaphane - a natural anticatabolic 15.01.2013

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