Is This the Best Vegetable for Your Brain?

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Dr. Joseph Mercola, writing on his blog, Mercola.com, suggests that sulforaphane, well known for its cancer-fighting properties, may also be of great benefit to your brain. The best place to find sulforaphane is in broccoli. He writes:

Science has proven time after time that food is potent medicine. Broccoli, for example, has a solid scientific foundation showing it’s one of the most valuable health-promoting foods around. While it contains several health-promoting compounds, one of the most widely studied is sulforaphane.

The cancer-fighting properties of sulforaphane are perhaps the most well-known, but it has also been shown to benefit your heart and brain, boosting detoxification¹ and helping prevent and/or treat high blood pressure,² heart disease, Alzheimer’s³ and even autism.^4,5,6 Now, researchers report sulforaphane may also be helpful in the treatment of schizophrenia.^7,8,9

Sulforaphane May Improve Cognition

An initial study,¹⁰ published in Clinical Psychopharmacology and Neuroscience in 2015, involved just 10 outpatients with schizophrenia. Patients were given 30 milligrams (mg) of sulforaphane glucosinolate per day for eight weeks. As reported by the authors:

“Clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) and cognitive function using the Japanese version of CogState battery were evaluated at the beginning of the study and at week 8.

A total of 7 patients completed the trial. The mean score in the Accuracy component of the One Card Learning Task increased significantly after the trial … This result suggests that SFN [sulforaphane] has the potential to improve cognitive function in patients with schizophrenia.”

Schizophrenia Linked to Chemical Imbalances in the Brain

More recently, a series of three animal and human studies¹¹ by researchers at Johns Hopkins School of Medicine suggest sulforaphane may also benefit patients with schizophrenia by helping to rebalance the glutamate levels in their brain. As reported by Neuroscience News:¹²

“Schizophrenia is marked by hallucinations, delusions and disordered thinking, feeling, behavior, perception and speaking. Drugs used to treat schizophrenia don’t work completely for everyone, and they can cause a variety of undesirable side effects, including metabolic problems increasing cardiovascular risk, involuntary movements, restlessness, stiffness and ‘the shakes.'”

According to Dr. Akira Sawa, director of the Johns Hopkins The Schizophrenia Center, “It’s possible that future studies could show sulforaphane to be a safe supplement to give people at risk of developing schizophrenia as a way to prevent, delay or blunt the onset of symptoms.”¹³

One of the studies¹⁴ in this series, published January 9, 2019, in JAMA Psychiatry, assessed differences in brain metabolism between 81 schizophrenic patients and 91 healthy controls, finding schizophrenics had lower levels of key brain chemicals associated with the disease — glutamate, N-acetylaspartate,¹⁵ GABA and glutathione — in their anterior cingulate cortex, a brain region involved in executive function, emotional affect and cognition.¹⁶

According to the paper¹⁷ “Cognitive and Emotional Influences in Anterior Cingulate Cortex,” this brain region appears to be “the brain’s error detection and correction device,” and “is part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing.”

In the brain, glutamate — an excitatory neurotransmitter¹⁸ — plays an important role in brain cell communication, and lower levels have been linked to both schizophrenia and depression.

Schizophrenics also had lower levels of N-acetylaspartate in the orbitofrontal region, an area involved in cognitive processing and decision-making, as well as the thalamus, an area involved in the relaying of sensory signals and the regulation of consciousness.

They also had lower levels of glutathione in the thalamus. Glutathione, a master antioxidant produced by your body, is made up of glutamate, cysteine and glycine, and is a physiologic reservoir of neuronal glutamate.¹⁹

Modulating Glutamate Levels May Improve Schizophrenia

For the second study in the series, the researchers focused on the management of glutamate in the brain. As reported by Neuroscience News,²⁰ they wondered whether faulty glutamate management might be a key problem in the disease, and whether drugs could be used to “shift this balance to either release glutamate from storage when there isn’t enough, or send it into storage if there is too much.”

So, in this study,²¹ published February 12, 2019, in PNAS, they blocked an enzyme that turns glutamate into glutathione in the brain cells of rats, using a drug called L-Buthionine sulfoximine, thereby allowing glutamine to be used up.

“The researchers found that these nerves were more excited and fired faster, which means they were sending more messages to other brain cells. The researchers say shifting the balance this way is akin to shifting the brain cells to a pattern similar to one found in the brains of people with schizophrenia,” Neuroscience News ²² explains.

Next, to increase the level of glutamine stored as glutathione, they used sulforaphane, as it activates a gene that makes an enzyme required for the synthesis of glutathione from glutamate. As expected, this slowed the speed with which neurons fired.

In other words, it helped normalize the brain cells, allowing them to behave in a manner more like healthy controls. Dr. Thomas Sedlak, assistant professor of psychiatry and behavioral sciences told Neuroscience News:²³

“We are thinking of glutathione as glutamate stored in a gas tank. 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 Boosts Glutathione Levels in the Brain

In an earlier pilot study²⁴ (counted as the third in this series) by the same team, published in the May 2018 issue of Molecular Neuropsychiatry, they used mice and healthy human subjects to assess the effect of sulforaphane on glutathione levels in the brain. Here, patients with a history of psychiatric illness were specifically excluded. As explained by the authors:

“The participants completed two visits, scheduled 7 days (1 week) apart. The participants were given 100 µmol sulforaphane as standardized broccoli sprout extract in the form of 2 gel capsules, and instructed to ingest the extract each morning for 1 week …

Urine and blood specimens were collected prior to the first dose of broccoli sprout extract and within 4 h of the final dose. MRS [magnetic resonance spectroscopy] scans were performed prior to the first dose and within 4 h of ingesting the final dose …

Following 1-week administration of sulforaphane, the study participants demonstrated a significant augmentation of GSH in non-monocytes that include a mixture of T cells, B cells, and NK cells. The GSH level was 9.22 nmol/mL before sulforaphane administration and 12.2 nmol/mL following sulforaph­ane administration, a 32% increase …

We report that a short-term administration of sulfo­raphane was sufficient to significantly increase peripheral GSH levels in human subjects. We found an increase in GSH in the HP [hippocampus], but not elsewhere in the brain regions assessed. The peripheral GSH ratio had a strong and significantly positive correlation with brain GSH levels in the THAL [thalamus] upon sulforaphane treatment …

[I]n a submitted study, we will report that peripheral GSH levels may be correlated with cognitive functions. We thus posit the significance of exploring the possible correlations between peripheral GSH and clinical/neuropsychological measures and the influence of sulforaphane on such functional measures that are altered in neuropsychiatric disorders. The present study is a key first step toward such future studies.”

In summary, these findings suggest sulforaphane might be a safe alternative to help reduce psychosis and hallucinations in schizophrenic patients, although the researchers warn more studies are required to identify optimal dosing and assess long-term effects.