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Sulforaphane as a potential therapeutic agent: a comprehensive analysis of clinical trials and mechanistic insights

Published online by Cambridge University Press:  16 September 2025

Atsushi Saito Open the ORCID record for Atsushi Saito [Opens in a new window] ,
Shoichi Ishikawa ,
Kun Yang ,
Akira Sawa  and
Koko Ishizuka
Atsushi Saito*
Affiliation:
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Shoichi Ishikawa
Affiliation:
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Kun Yang
Affiliation:
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Akira Sawa
Affiliation:
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Koko Ishizuka*
Affiliation:
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
*
Corresponding authors: Atsushi Saito; Email: asaito3@jhmi.edu, Koko Ishizuka; Email: kishizu2@jhmi.edu
Corresponding authors: Atsushi Saito; Email: asaito3@jhmi.edu, Koko Ishizuka; Email: kishizu2@jhmi.edu

Abstract

Sulforaphane (SFN), a bioactive compound derived from glucoraphanin in cruciferous vegetables such as broccoli, has been extensively studied for its therapeutic potential across diverse disease categories. SFN exerts its effects through well-characterised pathways, including the Keap1/Nrf2 axis, which regulates phase II detoxification enzymes, and epigenetic mechanisms such as histone deacetylase inhibition. This review evaluates clinical trials registered on ClinicalTrials.gov, focusing on those using SFN or broccoli-derived extracts.

As a result, we identified 84 trials, of which 39 have been published. Results suggest SFN’s potential in regulating redox and inflammatory pathways, improving metabolic and cardiovascular outcomes, and exerting anti-cancer and neuroprotective effects. For healthy subjects, SFN enhanced detoxification and reduced inflammation. In cancer patients, SFN showed promise in early-stage prostate and breast cancer, particularly in GSTM1-positive individuals, but had limited effects in advanced cases. For brain disorders, SFN demonstrated symptomatic improvements in autism spectrum disorder and cognitive benefits in schizophrenia but lacked robust biomarker integration. SFN had minimal impact on respiratory diseases but showed supportive roles in allergic rhinitis therapy. Metabolic disease studies revealed glycaemic control improvements in type 2 diabetes but no benefits for hypertension. Approximately 50% of completed trials remain unpublished, raising concerns about publication bias. While published results highlight SFN’s therapeutic potential, limited sample sizes and inconsistent outcomes underscore the need for more extensive, stratified trials. This review emphasises the importance of integrating mechanistic insights and precision medicine approaches to maximise SFN’s clinical utility.

Keywords

Clinical trialsInterventionMechanismsSulforaphane

Information

Type
Review
Information
Journal of Nutritional Science , Volume 14 , 2025 , e65
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

Introduction

In the past decade, many epidemiological and clinical research publications have suggested that daily food intake plays a role in the prevention of common diseases such as cancers, cardiovascular conditions, metabolic diseases, and brain disorders(Reference Sporn, Dunlop and Newton1–Reference Evert, Boucher and Cypress4). Such beneficial effects are likely to come from specific nutrients and chemicals included in daily food(Reference Carneiro and Pellerin5). One of these promising chemicals may be sulforaphane (SFN), which was first isolated from hoary cress and other plants in the mid-20th century. Importantly, glucoraphanin is consumed in daily meals as it is a component of cruciferous vegetables (cauliflower, cabbage, kale, and broccoli). SFN is the product as a result of the hydrolysis of glucoraphanin by myrosinase(Reference Zhang, Talalay and Cho6).

SFN is an active phytochemical found within the isothiocyanate group(Reference Zhang, Tropsha and McPhail7) and is a product of its precursor glucoraphanin (alias sulforaphane glucosinolate), which is hydrolysed by a thioglucosidase enzyme, myrosinase(Reference Yang, Palliyaguru and Kensler8). Although SFN was identified initially many years ago, its biological implication became known in 1992(Reference Zhang, Talalay and Cho6) when SFN was isolated from broccoli (Brassica oleracea italica). SFN is a significant inducer of phase II detoxification enzymes via the Kelch-like ECH-associated protein-1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway. SFN interacts with Keap1, which releases Nrf2 from the Keap1/Nrf2 complex, allowing Nrf2 to be a functional transcription factor for phase II detoxification enzymes(Reference Kim and Keum9). Major genes transcriptionally regulated by Nrf2 include NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1), quinone reductase, and glutathione S-transferases (GST), as well as inducible nitric oxide synthase(Reference Yagishita, Gatbonton-Schwager and McCallum10).

SFN can also interfere with signalling pathways involved in inflammation, such as nuclear factor-kappa B(Reference Heiss, Herhaus and Klimo11). SFN also reportedly inhibits the activity of histone deacetylases (HDACs)(Reference Myzak, Karplus and Chung12) and DNA methyltransferases(Reference Myzak, Hardin and Wang13,Reference Ho, Beaver and Williams14) , respectively, influencing the epigenetic mechanisms and suppression of tumour growth.

As briefly described above, SFN acts through well-defined mechanisms underlying many (or most) cells and organs in the body. Accordingly, clinical trials have taken place to evaluate the effect of SFN on a wide range of disorders, from cancers to brain disorders. Furthermore, since SFN and its precursor, glucoraphanin, can be easily consumed from vegetables, a substantial number of clinical trials using SFN or broccoli sprout on healthy subjects are also available. Nevertheless, to our knowledge, there has been no investigation considering both unpublished and published clinical trials together. To address this knowledge gap, we aimed to examine clinical trials registered in ClinicalTrial.gov (https://clinicaltrials.gov/ct2/home) and compare the clinical trial status of each disease category.

Selection of clinical trials

SFN is an organosulfur compound that contains isothiocyanate(Reference Zhang, Tropsha and McPhail7). SFN becomes available when its precursor, glucoraphanin, is hydrolysed by the enzyme myrosinase under neutral pH in cruciferous vegetables; broccoli is known as a common dietary source for SFN (Figure 1).

Fig. 1. Biosynthesis of sulforaphane (SFN). Glucoraphanin, a type of glucosinolate found in cruciferous vegetables such as broccoli sprouts, is hydrolysed when the plant is damaged. The enzyme myrosinase interacts with glucoraphanin, resulting in the formation of SFN, a beneficial isothiocyanate.

The database/literature search process is shown in Figure 2. To narrow the study records, we first filtered the ClinicalTrials.gov database (https://clinicaltrials.gov/ ) by using ‘broccoli’ or ‘sulforaphane’ as a keyword. Consequently, we found 182 and 91 trials for ‘broccoli’ and ‘sulforaphane’ respectively. By comparing these two lists, we found that 71 trials were duplicated, resulting in 202 unique clinical trials. We then carefully examined the content of these 202 trials and chose the target studies based on the following criteria. Inclusion criteria were (1) interventional studies with food or supplement and (2) studies to examine clinical effects, including symptoms and biomarkers. Exclusion criteria were (1) non-interventional study or (2) studies to examine only bioavailability or distribution of the metabolites. As a result, we identified 84 clinical trials that met these criteria. Thus, to explicitly address the effects of SFN, we decided to focus on these 84 trials.

Fig. 2. Scheme for clinical trial inclusion. Based on the search result on ClinicalTrials.gov as of June 2024.

To find which of these 84 trials had been published, we used the clinical trial number (NCT number) from each of these trials as a keyword on Google search (https://www.google.com/webhp). Notably, 39 trials have been successfully published in peer-reviewed journals (Table 1).

Table 1. Target conditions of clinical trials

Trials on healthy conditions

Of the 29 trials on healthy conditions, 15 were published (Table 2). Four trials assessed redox signalling outcomes under the Keap1/Nrf2 pathway, showing that SFN regulated redox markers such as NQO1 and HO-1. For example, broccoli sprout consumption reduced intracellular pro-inflammatory signalling (e.g. P38 MAP kinase) and reactive oxygen species in leukocytes(Reference Nguyen, Fiorentino, Reeves, Kwak, Pyo, Angelini, Anderson, Frost, Haskard and Evans15). Another trial showed broccoli sprout extract increased NQO1 mRNA in buccal cells, suggesting a chemopreventive role against oral cancer(Reference Bauman, Zang and Sen16). However, a proof-of-concept study revealed that SFN intake failed to mitigate neutrophilic airway inflammation or improve redox markers in peripheral blood mononuclear cells (PBMCs) or nasal epithelial cells after ozone exposure, despite SFN upregulation(Reference Duran, Burbank and Mills17).

Table 2. Trials for healthy conditions

R, redox; I, inflammation; E, epigenetics; and ‘✓’ indicate that the mechanism addressed in the paper. 200g of broccoli sprout homogenate, containing about 100g of fresh broccoli sprout, is estimated to contain approximately 100µmol of SFN(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . Mature broccoli is estimated to contain approximately one-tenth the amount of SFN compared to broccoli sprout(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . 150µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

Nrf2-independent pathways were also examined. Six trials explored inflammatory outcomes. SFN reduced allergic responses to diesel exhaust, decreasing nasal lavage fluid cells(Reference Heber, Li and Garcia-Lloret18). However, it failed to protect against ozone-induced airway neutrophilic inflammation(Reference Duran, Burbank and Mills17). SFN’s anti-inflammatory effects were also evident in virus-exposed individuals, where it enhanced natural killer cell granzyme B production, suggesting improved antiviral defenses(Reference Noah, Zhang and Zhou19,Reference Muller, Meyer and Bauer20) . Interestingly, SFN reduced virus-induced inflammatory markers and viral load in smokers(Reference Noah, Zhang and Zhou19). Another trial showed a decrease in body fat mass as well as interleukin 6 and C-reactive protein in the high body mass index group (BMI = 24.9–29.9)(Reference Lopez-Chillon, Carazo-Diaz and Prieto-Merino21). Three interrelated publications demonstrated that SFN mitigated caloric load-induced inflammation, improved platelet function, and enhanced heart rate variability in crossover trials(Reference van Steenwijk, Vinken and van Osch22–Reference van Steenwijk, Troost, Bast, de Boer and Semen24).

Epigenetic modulation was studied in one trial, where cruciferous vegetable intake decreased HDAC3 activity and increased the tumour suppressor gene p16 in PBMCs and colon biopsy samples(Reference Rajendran, Dashwood and Li25). Another trial demonstrated that topical application of broccoli extract protected the skin and may help manage keratin-based disorders(Reference Kerns, Guss and Fahey26). Several trials showed that broccoli sprout consumption increased urinary excretion of toxic carcinogens, supporting detoxification benefits(Reference Kensler, Ng and Carmella27–Reference Egner, Chen and Zarth30). Two cardiovascular disease-related trials found that high-glucoraphanin broccoli significantly lowered low-density lipoprotein cholesterol and improved mitochondrial function. Genetic factors, such as the poly(A) polymerase genotype, influenced these effects(Reference Armah, Traka and Dainty31,Reference Armah, Derdemezis and Traka32) .

Trials on cancers

Seven of 20 cancer-related trials were published (Table 3). Prostate cancer studies revealed SFN altered oncogenic gene expression in prostate tissue but did not reduce plasma prostate-specific antigen levels(Reference Traka, Gasper and Melchini33–Reference Zhang, Garzotto and Davis36). Interestingly, SFN’s effects were more pronounced in glutathione S-transferase mu 1 (GSTM1)-positive patients, suggesting genetic variability impacts therapeutic outcomes. The GSTM1 null genotype, which is prevalent globally, could diminish SFN’s effects(Reference Palma-Cano, Cordova and Orozco37).

Table 3. Trials for cancers

R, redox; I, inflammation; E, epigenetics; and ‘✓’ indicate that the mechanism addressed in the paper. 200g of broccoli sprout homogenate, containing about 100g of fresh broccoli sprout, is estimated to contain approximately 100µmol of SFN(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . Mature broccoli is estimated to contain approximately one-tenth the amount of SFN compared to broccoli sprout(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . 150µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

In breast cancer, two of six registered trials were published. Early-stage patients (ductal carcinoma in situ) showed decreased HDAC activity and reduced cell proliferation, but no benefits were observed in progressive cases(Reference Atwell, Zhang and Mori38–Reference Wang, Tu and Pratt40). SFN increased caspase-3 activity and reduced Ki-67 expression, suggesting anti-cancer activity. A trial on advanced pancreatic cancer showed no impact on patients’ overall function(Reference Lozanovski, Polychronidis and Gross41), potentially due to Nrf2’s dual role in cancer progression depending on genetic mutations(Reference Sporn and Liby42). These findings underscore the need for subgroup-specific studies considering tumour type, stage, and genetic context.

Trials on brain disorders

Seven of 19 trials on brain disorders were published (Table 4), including autism spectrum disorder (ASD), fragile-X-associated tremor/ataxia syndrome (FXTAS), and schizophrenia (SZ). ASD trials had relatively high publication rates, with four out of six trials published. The first study (2014) demonstrated clinical improvements with SFN treatment, but subsequent studies reported inconsistent results, including caregiver-rated improvement without significant changes in clinical scores(Reference Singh, Connors and Macklin43–Reference Ou, Smith and Tobe49). One study linked SFN treatment to redox and inflammatory marker changes in PBMCs, though clinical benefits were modest(Reference Liu, Zimmerman and Singh46). Another trial observed social and behavioural improvements on clinician-rated scales(Reference Yang, He and Dai48,Reference Ou, Smith and Tobe49) .

Table 4. Trials for brain disorders

R, redox; I, inflammation; E, epigenetics; and ‘✓’ indicate that the mechanism addressed in the paper. 150 µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

One FXTAS trial did not show improvement in behavioural scores or molecular markers with SFN treatment(Reference Santos, Clark and Biag50).

Two SZ studies reported no improvements in core symptoms but identified cognitive benefits, particularly in smaller cohorts(Reference Shiina, Kanahara and Sasaki51,Reference Dickerson, Origoni and Katsafanas52) . Although redox imbalance and inflammation are implicated in ASD and SZ(Reference Pangrazzi, Balasco and Bozzi53,Reference Upthegrove and Khandaker54) , most trials lacked biomarker analyses. Future studies should correlate molecular markers with clinical outcomes.

Trials on respiratory diseases

Four of five respiratory trials were published (Table 5). SFN had minimal effects on pulmonary function or inflammation in chronic obstructive pulmonary disease(Reference Wise, Holbrook and Criner55) or asthma(Reference Brown, Reynolds and Brooker56,Reference Sudini, Diette and Breysse57) . For example, two trials reported no significant redox or anti-inflammatory changes after SFN supplementation(Reference Wise, Holbrook and Criner55,Reference Sudini, Diette and Breysse57) . However, in allergic rhinitis, broccoli sprout extract combined with nasal steroids enhanced therapeutic effects, improving peak nasal inspiratory flow and reducing symptom scores(Reference Yusin, Wang and Henning58). These findings suggest SFN may support existing respiratory therapies rather than act as a standalone treatment.

Table 5. Trials for respiratory diseases

R, redox; I, inflammation; E, epigenetics; and ‘✓’ indicate that the mechanism addressed in the paper. 200g of broccoli sprout homogenate, containing about 100g of fresh broccoli sprout, is estimated to contain approximately 100µmol of SFN(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . Mature broccoli is estimated to contain approximately one-tenth the amount of SFN compared to broccoli sprout(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . 150µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

Trials on metabolic and cardiovascular diseases

Two of three metabolic and cardiovascular trials were published (Table 6). SFN supplementation did not improve hypertensive patients’ blood pressure or vascular function(Reference Christiansen, Bellostas Muguerza and Petersen59). However, it significantly reduced fasting blood sugar and haemoglobin A1C levels in overweight type 2 diabetes patients, with serum SFN levels correlating with glycaemic improvements(Reference Axelsson, Tubbs and Mecham60). Mechanistic insights, such as Nrf2 activation, were demonstrated in rodent studies but remain unexplored in human trials. Future research should investigate SFN’s effects on human metabolism and lipid regulation.

Table 6. Trials for metabolic and cardiovascular diseases

R, redox; I, inflammation; E, epigenetics. 200g of broccoli sprout homogenate, containing about 100g of fresh broccoli sprout, is estimated to contain approximately 100µmol of SFN(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . Mature broccoli is estimated to contain approximately one-tenth the amount of SFN compared to broccoli sprout(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . 150µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

Trials on infectious diseases

One trial evaluated SFN as an adjuvant therapy for Helicobacter pylori infection(Reference Chang, Park and Oh61) (Table 7). Adding SFN to standard triple therapy did not improve eradication rates or reduce antibiotic-associated adverse events.

Table 7. Trials for infectious diseases

R, redox; I, inflammation; E, epigenetics.

Trials on miscellaneous diseases

Among six miscellaneous disease trials, three were published (Table 8). Chronic kidney disease studies revealed that SFN upregulated Nrf2 and NQO1 in non-dialysis patients but did not impact oxidative or inflammatory markers in haemodialysis patients(Reference Ribeiro, Alvarenga and Coutinho-Wolino62,Reference Ribeiro, Cardozo and Paiva63) . Another study found no antimicrobial activity against E. coli despite high SFN levels(Reference Abukhabta, Khalil Ghawi and Karatzas64). SFN’s effects were also observed in sickle cell disease, where it increased HO-1 and foetal haemoglobin gene expression dose-dependently(Reference Doss, Jonassaint and Garrett65). These findings highlight SFN’s potential benefits in peripheral blood disorders.

Table 8. Trials for miscellaneous diseases

R, redox; I, inflammation; E, epigenetics, and ‘✓’ indicate that the mechanism addressed in the paper. 200g of broccoli sprout homogenate, containing about 100g of fresh broccoli sprout, is estimated to contain approximately 100µmol of SFN(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . Mature broccoli is estimated to contain approximately one-tenth the amount of SFN compared to broccoli sprout(Reference Nakagawa, Umeda and Higuchi71,Reference Asif Ali, Khan and Kaleem72) . 150µmol of SFN daily is generally not physiologically relevant through diet alone, implying that supplementation is needed to reach these concentrations(Reference Sivapalan, Melchini and Saha73).

The major mechanisms underlying SFN’s effects observed in all these studies are summarised in Figure 3.

Fig. 3. Venn diagram showing sulforaphane mechanisms suggested by the published clinical trials. COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease.

Additionally, we wish to introduce one study that is not in the database that may help achieve the overall goal of our review. That study examined the effect of SFN on the brain with magnetic resonance spectroscopy(Reference Sedlak, Nucifora and Koga66). It was reported that SFN administration can upregulate glutathione levels in specific brain regions. Ultimately, we may be able to assess the effect of SFN at the mechanistic level in brain disorders in future studies.

Conclusion and future directions

Numerous clinical trials have investigated the effects of SFN, showing significant benefits across various conditions (100–150 µmol of SFN was mainly used). Although the trials with a single dose (NCT01357070, NCT05146804) showed changes in biomarkers, longer intervention may be required for SFN to have significant clinical effects. However, most of these studies have involved a limited number of participants, and only a few have successfully achieved their primary outcomes. More extensive studies with increased sample sizes are essential to validate these findings. Stratifying participants by specific factors, such as GST genotypes or the severity of clinical stages, has proven effective in identifying populations that are more responsive to SFN. This approach, rooted in the principles of precision medicine, is expected to guide the design of future clinical trials.

We evaluated the number of published studies that show significant changes in outcome measures. Excluding infectious diseases (no publications with substantial changes in outcome measures out of 1 publication [0/1]), the success rate in other groups is 50% or more (Table 9). Given the limited number of publications, making definitive recommendations regarding SFN usage in treating various pathologies is challenging. Notably, about 50% of the completed trials have not been published, and no statistical results are available on ClinicalTrials.gov. This percentage is consistent with the broader issue that only 46% of registered clinical trials are eventually published(Reference Ross, Mulvey and Hines67). This low publication rate may suggest that many failed trials remain unreported. Consequently, we focused on unpublished trials with results deposited in the clinical trial database (‘ClinicalTrials.gov’). As no statistical data were deposited for these results, we tested significance using the Mann-Whitney U test. We categorised the trials into two groups: those with and without significant results (P < 0.05) (Table 9). The Fisher’s exact test, used to compare the groups (published or unpublished) and the categories (with significance or without significance), did not indicate significant publication bias in the SFN trials (Table 9). However, it is essential to note that data from approximately 40% of completed trials are still unavailable. Continued monitoring of these trials is necessary.

Table 9. Publication status and bias

A limitation of this review is that the number of studies listed in this review is relatively smaller than other comprehensive reviews about SFN(Reference Yagishita, Fahey and Dinkova-Kostova68,Reference Marino, Martini and Venturi69) . Although we have examined the most authentic and widely used database of clinical trials (‘ClinicalTrials.gov’), some studies may not be included in the database. We acknowledge that there are other databases, such as the International Standard Randomised Controlled Trial Number (ISRCTN) registry, EU Clinical Trials Register, and Pan African Clinical Trial Registry (PACTR). However, they are much smaller in size compared with the ClinicalTrials.gov database. Although another database, the International Clinical Trials Registry Platform (ICTRP), organised by the WHO, is relatively larger, as claimed by the WHO itself, this platform is not endorsed by the WHO. The WHO also stated that the agency is not responsible for the accuracy, completeness, and/or use of the content displayed for any trial record. Furthermore, two-thirds of the studies in this WHO platform are also available in the ClinicalTrials.gov database, addressing the specific topic covered in this review. Altogether, we have decided not to include the information from the ICTRP in our study. Nonetheless, we wish to note that several studies hoping to address the disease-related mechanism of SFN have not been covered in the present search. For instance, the first type 2 diabetes trial from an Iranian group is not included in the ClinicalTrials.gov database(Reference Bahadoran, Tohidi and Nazeri70).

We have reviewed over 80 clinical trials for this study; however, due to the comparison of each disease category, the number of studies in each category is relatively small. Therefore, our statement remains a qualitative comment, which is far from a quantitative statistical analysis. On the other hand, by taking advantage of the fact that the present study encompasses a wide range of disease conditions, spanning from cancers to neuropsychiatric disorders, we propose that SFN may be a useful tool for examining the body-brain connection and that clinical trials with SFN may provide more insight into its biology. This possibility is particularly timely, as the significance of the body-brain connection has been recently highlighted, such as through the concept of the gut-brain axis.

Data availability statement

All relevant data are available upon request to the corresponding authors.

Acknowledgements

We thank Dr Melissa Landek-Sargado, Ms Tranh Hai Tran, Mr James Harrison Ladd, Ms Antonia Mendrinos, Ms Lauren Guttman, Dr Ryosuke Yusa, and Dr Tomohide Sato for critical reading. We also thank Ms Yukiko Y. Lema for her figure organisation.

Authorship

Conceptualisation: AtS, AkS

Data curation and analysis: AtS, SI, KY, KI

Writing: AtS, SI, KY, AkS, KI

All authors approved the final version of the manuscript.

Financial support

This study was in part supported by NIMH [P50MH136297 (AkS), P50MH094268 (AkS), and R01MH107730 (AkS)], Murakami-Johns Hopkins fellowship (SI), and Tokushukai fellowship (SI).

Competing interests

The authors have declared that no competing interests exist.

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Figure 0

Fig. 1. Biosynthesis of sulforaphane (SFN). Glucoraphanin, a type of glucosinolate found in cruciferous vegetables such as broccoli sprouts, is hydrolysed when the plant is damaged. The enzyme myrosinase interacts with glucoraphanin, resulting in the formation of SFN, a beneficial isothiocyanate.

Figure 1

Fig. 2. Scheme for clinical trial inclusion. Based on the search result on ClinicalTrials.gov as of June 2024.

Figure 2

Table 1. Target conditions of clinical trials

Figure 3

Table 2. Trials for healthy conditions

Figure 4

Table 3. Trials for cancers

Figure 5

Table 4. Trials for brain disorders

Figure 6

Table 5. Trials for respiratory diseases

Figure 7

Table 6. Trials for metabolic and cardiovascular diseases

Figure 8

Table 7. Trials for infectious diseases

Figure 9

Table 8. Trials for miscellaneous diseases

Figure 10

Fig. 3. Venn diagram showing sulforaphane mechanisms suggested by the published clinical trials. COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease.

Figure 11

Table 9. Publication status and bias