Sulforaphane

What Is It?

Sulforaphane is an organic compound within the group of phytochemicals called isothiocyanates$^{1}$. It is commonly found in cruciferous vegetables, with the highest concentrations found in broccoli sprouts$^{1,2}$. The precursor compound found in these vegetables called glucoraphanin is broken down by the plant enzyme myrosinase (which is usually involved in a plant’s defence response) to form sulforaphane during chewing or food processing$^{3,4}$. Consumption of cruciferous vegetables is commonly associated with a lower risk of developing cancer at various sites such as the prostate, breast, lung, and colon$^{2,5}$. The anticancer effects provided by these vegetables can be predominantly attributed to the phytochemical sulforaphane, which is why this compound is commonly studied for its cancer prevention and treatment abilities$^6$.

What Are Its Other Names?

Sulforaphane is also know as 1-Isothiocyanato-4-(methylsulfinyl)-butane, 4-methylsulfinylbutyl Isothiocyanate, (+-)-sulforaphane, DL-sulforaphane and sulforafan$^{7}$. Note: (R)-sulforaphane is more biologically active than the (S)-sulforaphane configuration$^{8}$.

What Foods Have It?

What Are Its Main Benefits?

Sulforaphane may be beneficial in cancer prevention and treatment due to its profound ability to protect against oxidative damage and carcinogens$^{14}$. Since cancer can initiate and progress through various mechanisms, sulforaphane appears to be particularly beneficial because it can target more than one cellular mechanism at a time$^{6}$. Additionally, sulforaphane used alongside other therapeutic drugs has been shown to have promising anti-cancer effects$^{15}$. Overall, although more human trials are needed to elucidate the effects of sulforaphane on cancer, many in vitro studies suggest that sulforaphane may be capable of modifying disease risk factors, therefore presenting promising health benefits$^{16}$.

What Are Its Main Drawbacks?

In human clinical trials utilizing dosages of sulforaphane ranging from 2.7 mg to 35.5 mg per day for 1 month, the results indicate that sulforaphane is well tolerated and relatively safe$^{1,17}$. Low doses of sulforaphane appear to be free of adverse effects while participants consuming higher doses (e.g. 35.5 mg) reported side effects including gastrointestinal discomfort, nausea, constipation and heartburn$^{17}$. One of the main drawbacks of this phytochemical is that the amount of sulforaphane formed from glucosinolates varies depending on food preparation$^{18}$. Sulforaphane is very sensitive to heat so it can be destroyed by boiling or microwaving vegetables$^{16}$. Another drawback is that sulforaphane is rapidly metabolized, so it may be difficult to achieve desired concentrations in all areas of the body$^{16}$. In terms of efficacious dosages, there seems to be a disconnect between effective doses used in animal/cell models and the tolerable doses in humans$^{17}$. Many studies report preventative effects using doses that would not be achievable in humans$^{17}$. Therefore, further research with a focus on translation of animal model data into plausible clinical trials is needed to provide necessary information about the anticancer effects of sulforaphane in humans$^{16,17}$.

How Does It Work?

Sulforaphane exerts preventative and therapeutic effects by targeting multiple mechanisms within the cell to control carcinogensis$^{6,19}$. These anticancer mechanisms include inhibiting cell proliferation, inducing cell death, promoting detoxification, suppressing inflammation and anti-tumour activity$^{6}$. Ultimately, these chemopreventive and treatment effects are produced via modulation of signaling pathways and genes$^{2,15}$.

What are its Mechanisms of Action?

Sulforaphane has a mechanistically diverse ability to protect and treat cells$^{17}$. Notably, many studies suggest that these mechanisms work synergistically to produce the beneficial effects$^{5,14}$. A more detailed look at each mechanism is provided below:

1. Inhibiting Cell Proliferation: Sulforaphane has been found to inhibit the activity of enzymes called histone deacetylases which leads to the accumulation of acetylated histones and subsequently the upregulation of genes involved in cell cycle arrest$^{16,21,22}$. Sulforaphane also downregulates genes (e.g. cyclin B1 and D1) related to cell cycle progression which causes G2/M phase cell cycle arrest and leads to the inhibition of tumour proliferation$^{15}$. Additionally, sulforaphane increases levels of a protein called p21 which also inhibits cell cycle progression$^{15}$. Lastly, this phytochemical inhibits the activity of signaling pathways involved in cell proliferation, such as the PI3K pathway, which is frequently dysregulated in cancer$^{20}$.
2. Inducing Cell Death (Apoptosis): Sulforaphane has been found to induce apoptosis (programmed cell death) in cancerous cells. Sulforaphane achieves this by activating the intrinsic apoptotic pathway through modulation of mitochondrial function$^{5}$. This causes an increase in reactive oxygen species and a decrease in levels of the antioxidant glutathione in cancer cells$^{17}$. Eventually, this leads to DNA damage resulting in the release of pro-apoptotic proteins (e.g. cytochrome C) which then activate caspase-9 and downstream caspases to induce cell death$^{17}$.
3. Promoting Detoxification: The most well-studied function of sulforaphane is its potent activation of a cellular defence mechanism called the Nrf2-antioxidant response element signalling pathway$^{6,16}$. Ultimately, activation of this pathway leads to the expression of genes (e.g. NQO1 and HO1) that help protect cells from DNA damage which can cause cancer development$^{6,15}$. Upregulation of these genes activates detoxification and antioxidant enzymes which help eliminate harmful compounds (e.g. reactive oxygen species and electrophiles) from the body, aiding in cancer prevention and treatment$^{2}$.

What Are Typical Doses and Durations?

It is important to note that the dietary form and dosing schedule of sulforaphane impacts its absorption and efficacy in humans$^{25}$. Since the most effective dose has yet to be determined, clinical trials have used a variety of dietary forms and doses to test the effects of sulforaphane in humans. Most human clinical trials use broccoli extract or sulforaphane supplements to achieve the desired anticancer effects. The dosages used in these clinical trials often exceed those that tend to be consumed in the average diet$^{26}$. Clinical trials that use sulforaphane supplements commonly use doses ranging from 60-90 mg/day$^{27,28}$. Clinical trials that study the effects of broccoli extract tend to use doses ranging from 8.9-35.5 mg/day$^{29,30,31}$. The duration of clinical trials varies significantly ranging from 2 weeks to 1 year$^{27-31}$.

Summary of Data

📄 Detailed Sulforaphane human clinical trial study notes analyzed by Anticancer.ca

References

1. Vanduchova, A., Anzenbacher, P. & Anzenbacherova, E. Isothiocyanate from Broccoli, Sulforaphane, and Its Properties. Journal of Medicinal Food 22, 121–126 (2019).
2. Clarke, J. D., Dashwood, R. H. & Ho, E. Multi-targeted prevention of cancer by sulforaphane. Cancer Letters 269, 291–304 (2008).
3. Guerrero-Beltrán, C. E., Calderón-Oliver, M., Pedraza-Chaverri, J. & Chirino, Y. I. Protective effect of sulforaphane against oxidative stress: Recent advances. Experimental and Toxicologic Pathology 64, 503–508 (2012).
4. Bhat, R. & Vyas, D. Myrosinase: insights on structural, catalytic, regulatory, and environmental interactions. Critical Reviews in Biotechnology 39, 508–523 (2019).
5. Juge, N., Mithen, R. F. & Traka, M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell. Mol. Life Sci. 64, 1105 (2007).
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9. Tříska, J. et al. Factors Influencing Sulforaphane Content in Broccoli Sprouts and Subsequent Sulforaphane Extraction. Foods 10, 1927 (2021).
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• Sulforaphane
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• How Does It Work?
• What are its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer