Integrative Psychiatry Supplement Spotlight: Sulforaphane

Sulforaphane is finding its way into the psychiatric treatment world. This main phytochemical found in cruciferous vegetables such as broccoli and kale has studies showing effectiveness for mental health conditions largely because of its ability to reduce oxidative stress in the body and brain.

This is even more evidence that many of our mental health conditions, especially schizophrenia, autism, and bipolar disorder, have inflammatory etiologies. It is well-established that oxidative stress is connected to inflammation by causing an increase in pro-inflammatory proteins of the immune system, or cytokines.

Uses in Psychiatry

Possibly Mediating Side Effects of Antipsychotic Medication

One of my primary approaches in working with individuals taking the antipsychotic class of medications is not necessarily to stop the medication but asking the question: How do we reduce the side effects of antipsychotics and mood stabilizers? These classes of medications are known to cause metabolic side effects such as weight gain, and increase inflammation and oxidative stress.

While we are deeply in need of new medications for conditions such as bipolar disorder and schizophrenia, they can also be incredibly important medications that work - but often at a cost. Often because of the side effects of these medications, adherence is pretty low, as 74% of patients with schizophrenia stop their medications within 1.5 years (Lieberman, 2005).

Most of the antipsychotics work primarily by inhibiting or blocking dopamine receptors in the brain. Sulforaphane may be a helpful addition to antipsychotics because as an antioxidant, it protects against dopamine cell death. In a study from 2012 (Mas et al.) that looked at the impact of sulforaphane on cells that also were administered one of three commonly prescribed antipsychotics (haldol, risperidone, or pallperidone). All three antipsychotics increased oxidative stress in the cells. Sulforaphane was found to increase glutathione levels (a major antioxidant) and reduced the amount of neurotoxic free radical species.

Schizophrenia

Individuals with schizophrenia typically have both positive and negative symptoms. Positive symptoms include hallucinations, delusions, and paranoia, for example. Negative symptoms include isolation, lack of motivation, cognitive issues, and decreased speech output. In a study (Zeng) from 2023, researchers found that sulforaphane (90 mg daily) significantly decreased the negative symptoms of the study participants who had schizophrenia. Most antipsychotics do not help with the negative symptoms of schizophrenia so it is a valuable addition to consider. In this study, the usage of sulfurophane also reduced hsCRP levels in subjects, which is a non specific marker of inflammation.

Autism Spectrum Disorder

Sulforaphane has some evidence to support its effectiveness for helping reduce behaviors in individuals with autism; however, the three studies that were double blinded and randomized were small in sample size. The studies showed significant improvement in social interaction, behavior, and cognition measures. Another study found that when taken with the antipsychotic risperidone, sulforophane decreased irritability and hyperactivity symptoms in children with autism (Momtazmanesh, 2020).

Depression

There are a couple of studies exploring the use of sulforaphane for depression but most of the studies have been mice studies and these studies cannot be generalized to humans. Again - because of sulforaphane's antioxidant and anti-inflammatory properties, it makes intuitive sense that it may be a helpful treatment option for at least a certain subset of individuals with depression that is inflammatory in nature. There was a small randomized double blinded study from 2021 (Ghazizadeh-Hashemi) showing improvements in cardiac event-related depression when sulfuraphane was taken for 6 weeks at a dose of 30 mg daily.

HAM-D scores, the depression measurement used, decreased significantly in the sulforaphane group compared to the placebo group.

Practicalities of Sulforaphane

Supplement vs Food

The question arises if food or supplement is the better route. A food as medicine approach is always the best place to start, if at all possible. Plant foods are the ultimate delivery vehicle for active ingredients and have better bioavailibity (the amount your body absorbs and uses), rather than isolating the active ingredient. However, it is difficult if not impossible to standardize dose in food, such as broccoli so almost all clinical studies completed involve a sulforaphane supplement such as broccoli sprout powder or broccoli extract that can be standardized.

If taking supplement form, the direct form of sulforaphane is best. You might find supplements containing glucoraphanin (the precursor to sulforaphane) but studies show more benefit with the sulforaphane form.

If taking the food form, broccoli spouts contain the highest amount of sulforaphane compared to other cruciferous vegetables. Raw forms of cruciferous vegetables have the highest concentration of sulforaphane, compared to cooked forms.

Safety and Tolerability

The optimal dose of sulforaphane is unknown. Mild side effects have been reported, such as constipation, an increase in gas, and diarrhea.

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Interested in an integrative approach to schizophrenia, autism, or depression? Learn more about becoming a patient at Driftless Integrative Psychiatry here.

A kind reminder: This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.

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Sources:

Ghazizadeh-Hashemi, F., Bagheri, S., Ashraf-Ganjouei, A., Moradi, K., Shahmansouri, N., Mehrpooya, M., Noorbala, A.-A. and Akhondzadeh, S. (2021), Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial. Psychiatry Clin. Neurosci., 75: 250-255. https://doi.org/10.1111/pcn.13276

Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New Engl J Med. (2005) 353:1209–23. doi: 10.1056/NEJMoa051688

Mas S, Gassó P, Trias G, Bernardo M, Lafuente A. Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress. Fundam Clin Pharmacol. 2012 Dec;26(6):712-21. doi: 10.1111/j.1472-8206.2011.00988.x. Epub 2011 Sep 19. PMID: 21923690.

McGuinness G, Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI J. 2020 Jun 26;19:892-903. doi: 10.17179/excli2020-2487. PMID: 33013262; PMCID: PMC7527484.

Momtazmanesh S, Amirimoghaddam-Yazdi Z, Moghaddam HS, Mohammadi MR, Akhondzadeh S. Sulforaphane as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled clinical trial. Psychiatry Clin. Neurosci. 2020; 74: 398–405.

Zeng, J., Zhang, W., Lu, X. et al. The association of SOD and HsCRP with the efficacy of sulforaphane in schizophrenia patients with residual negative symptoms. Eur Arch Psychiatry Clin Neurosci (2023). https://doi.org/10.1007/s00406-023-01679-7