Why should you eat your greens? Sulforaphane, an active compound in broccoli and other Brassica vegetables, may help prevent prostate cancer from recurring. Read on to learn about this beneficial compound and where to get it in your diet.
What are Sulforaphane and Broccoli Sprouts?
Sulforaphane (SFN) is an isothiocyanate, a sulfur-containing organic compound [1, 2].
It is found in cruciferous vegetables such as broccoli, cabbage, cauliflower, Brussels sprouts, and kale [1, 2].
Sulforaphane is produced when glucoraphanin comes into contact with the enzyme myrosinase, contained within the same cells but in different compartments [1, 3].
For example, cutting, chewing, or otherwise disrupting the broccoli plant cells initiates the production of sulforaphane. Compared to the stable glucoraphanin, sulforaphane begins degrading soon after production [3].
Three-day-old sprouts of certain cruciferous vegetables contain 10 to 100 times higher concentrations of glucoraphanin than in mature plants [3].
Levels of glucoraphanin and sulforaphane are highest in broccoli sprouts [4].
Sulforaphane has antioxidant, antimicrobial, anticancer, anti-inflammatory, anti-aging, neuroprotective, and anti-diabetic properties [1].
Sulforaphane also protects against cardiovascular and neurodegenerative diseases [1].
Apart from sulforaphane, broccoli sprouts contain many other bioactive, health-promoting compounds, such as gallic, chlorogenic, ferulic, sinapinic, benzoic and salicylic acids, quercetin, kaempferol, and vitamin C [5].
To learn about the many potential benefits of sulforaphane and sulforaphane-rich vegetables, check out this post.
Cancer Research
Prostate Cancer
Sulforaphane (in the form of broccoli sprout extract) boasts some relatively strong clinical evidence for a role in the prevention of prostate cancer and management strategies for preventing recurrence of prostate cancer.
In multiple clinical studies, men with recurrent prostate cancer who took 60 mg of sulforaphane per day had less prostate specific antigen (PSA, a marker used to measure prostate cancer progression) than those who did not take sulforaphane [6, 7].
That being said, the FDA has not approved sulforaphane for the prevention of prostate cancer recurrence. Talk to your doctor before supplementing.
Research in Other Cancers
While studies have advanced the furthest for sulforaphane in prostate cancer, it is also under investigation for possible action against other types of cancer. Sulforaphane is considered a promising compound for a few reasons; not least of these is that people who eat sulforaphane-rich Brassica vegetables are significantly less likely to develop cancer [8, 9].
Three to five servings of Brassicas per week are associated with a 30% to 40% decline in the incidence of cancer compared to people who don’t eat these vegetables [8].
Subjects who consumed at least one portion of cruciferous vegetables per week were less likely to develop oral cavity, pharynx, esophageal, colorectal, breast, and kidney cancers [8].
Researchers are also investigating the potential of sulforaphane against glioblastoma, thyroid, prostate, mammary, tongue, and lung cancer in animals [10, 11, 12, 8, 13, 14].
Broccoli sprouts also significantly and dose-dependently inhibited bladder cancer development in rats, and UV-radiation-induced skin cancer development in mice [15, 16].
Possible Mechanisms
- SFN inhibits phase I enzymes that can activate pro-carcinogens [8]
- SFN induces phase II enzymes that are responsible for eliminating chemicals that damage DNA [8]
- SFN changes gene activation/deactivation, and causes demethylation, thereby restoring the activity of important tumor-suppressing and cell-cycle controlling genes [8]
- Sulforaphane induces cancer cell death [8]
- Sulforaphane inhibits the NF-κB pathway, thus reducing inflammation [8]
- Sulforaphane induces cell cycle arrest, and thereby inhibits cancer cell proliferation [8]
Apart from being effective in its own right, sulforaphane may also enhance the efficacy of anti-cancer drugs including cisplatin, gemcitabine, doxorubicin, and 5-fluorouracil, toward pancreatic and prostate cancer cells, while limiting their toxicity to normal cells [8].
However, although sulforaphane was found to be safe and effective in several studies, it was not effective in two clinical trials [7, 17].
Additional studies are still required before sulforaphane could be incorporated into conventional cancer therapies. Talk to your doctor before attempting to use sulforaphane and sulforaphane-rich foods for any medical purpose, let alone cancer prevention or treatment.
Sulforaphane Side Effects
Sulforaphane is considered safe when consumed in the amounts available in broccoli and other greens, and very few side effects have been observed in clinical trials of broccoli sprouts, their extracts, or purified sulforaphane. However, supplements are not standardized, and we do not have sufficient data to determine the safety of long-term sulforaphane use. Talk to your doctor to avoid adverse effects or unexpected interactions.
1) Genome Stability
Sulforaphane appears to increase the activation of many beneficial genes, including tumor suppressor genes. However, sulforaphane may also activate long terminal repeats (LTRs), DNA sequences found within our genome that impair genome stability and cause mutations [18].
Consumption of broccoli sprouts by human volunteers caused a 10-fold increase in LTR activation in white blood cells. These effects are transient, and it remains to be determined whether they are biologically meaningful [18].
Other studies on human volunteers recorded no abnormal events related to broccoli sprout consumption [19].
Genotoxic effects were observed in unpublished studies with pigs fed with 600 g of raw broccoli for 12 days. These pigs had an increase in DNA strand breaks by 21% in the colon [20].
Also, after feeding raw or steamed broccoli to mice and rats, an increase in DNA adducts (cancer-causing chemicals binding to DNA) was observed [20].
However, all these effects in animals were observed for mature broccoli plant consumption. An additional benefit of broccoli sprouts is that they contain negligible quantities of indole glucosinolates, which predominate in the mature vegetable, and may give rise to degradation products (e.g., indole-3-carbinol). This may enhance tumorigenesis [21].
2) Liver Toxicity
There is a single case report of liver toxicity after drinking large amounts of broccoli juice for 4 weeks (800 ml/day). Transaminases, aspartate aminotransferase, and c-glutamyltrans-peptidase were elevated but decreased to normal within 15 days [20].
This was also caused by consuming the mature plant; the contribution of sulforaphane is unknown. Until we know more, caution is advised.
Food Sources
The amount of sulforaphane (glucoraphanin) can vary widely in vegetables [3].
Broccoli is not the only cruciferous vegetable which has SFN, but it yields the highest amounts, with glucoraphanin content around 75% of total glucosinolates [3].
Furthermore, 3-day-old broccoli sprouts contain 10 to 100 times higher levels of glucoraphanin than does a mature broccoli [22, 23].
Do not confuse broccoli sprouts with Brussels sprouts (though Brussels sprouts also contain sulforaphane) [24].
Vegetables with high sulforaphane content include [24, 25]:
- Broccoli sprouts
- Brussels sprouts
- Kale
- Cabbage
- Cauliflower
Additional Information
Genetics And Sulforaphane Metabolism
GSTs are a large family of glutathione conjugating enzymes, which attach glutathione to the substance that needs to be detoxified out of the body. Three of them, GSTM1, GSTP1, and GSTT1 have been implicated in the metabolism of isothiocyanates, and sulforaphane in particular [26].
SNPs in the GSTM1 gene
Null mutations in GSTM1 result in the absence of a functional enzyme. The frequency of the GSTM1-null variant is estimated to be between 27 and 53% in human populations [26].
Individuals with GSTM1-null mutations may benefit more from SFN due to the decreased degradation of SFN, which therefore increases exposure [26].
However, several other studies suggest otherwise. In these studies, GSTM1-positive individuals benefited more from either broccoli or cruciferous vegetable consumption compared to GSTM1-null individuals. GSTM1-null carriers excrete more SFN and SFN-metabolites, and excretion is faster [26].
SNPs in the GSTT1 gene
Null mutations in the GSTT1 gene result in the absence of a functional enzyme. The frequency of the GSTT1-null variation has been estimated to be between 10 and 21% for Caucasian populations and as high as 64% for Asian populations [26].
Broccoli sprouts are more effective in detoxification when GSTT1-positive carriers are exposed to airborne pollution compared to the null carriers [27].
SNPs in the GSTP1 gene
Sulforaphane Mechanism of Action
As an Indirect Antioxidant:
- SFN activates Nrf2 by binding Keap1 [8, 28]
- SFN reacts with Keap1, thereby releasing Nrf2 from Keap1 binding [29]
- SFN promotes ARE-driven gene expression [8, 28]
- SFN increases other phase II enzymes: NQO1, GSTA1, and HO-1 [30, 31, 32, 33]
- SFN inhibits phase I enzymes CYP1A1, CYP1A2, CYP1B1, CYP2B2, and CYP3A4 [22, 8]
- SFN blocks SXR [8]
Inflammation:
- SFN inhibits NfkB [34, 8, 35]
- SFN decreases TNF-α, NLRP3, IL-1β, IL-18, IFN-gamma and IL6 [36, 37, 38, 39, 40, 41]
- SFN increases IL-10, IL-4, Arg1, and YM-1 [36, 41, 33, 42]
- SFN decreases NO, iNOS and COX-2 [37, 41, 43]
- SFN silences Th17/Th1 responses [44, 33]
- SFN decreases IL-17 [39, 44]
- SFN decreases TGF-β/Smad [45]
- SFN decreases IL-23 and IL-12 expression [44]
- SFN decreases MMP-9 [33, 43]
- SFN decreases LDH and PGE2 [43]
Gene Expression:
- DNA hypermethylation can inhibit tumor suppressor genes and genes involved in cell cycle regulation and apoptosis (cell death). DNA methyltransferases (DNMTs) methylate DNA, and an overexpression of DNMTs is observed in a number of cancers, including leukemia, gastric, lung, and prostate cancer [8, 46]
- Sulforaphane inhibits DNMT1 and DNMT3A [8]
- SFN is one of the most potent (histone deacetylase) HDAC inhibitors found to date [47]
- SFN inhibits HDAC1, HDAC2, HDAC3, and HDAC4 [47, 8]
- SFN decreases miR-21 and TERT [47]
Against Cancer:
- SFN activates caspase-3, caspase-7, caspase-8, caspase-9 [46, 8]
- SFN decreases anti-apoptotic Bcl-2 and Bcl-XL [46, 8]
- SFN increases pro-apoptotic Bax [8]
- SFN induces p21 (CDKN1A) and p53 [8]
- SFN inactivates PARP [8]
- SFN decreases HIF1A [8]
- SFN decreases β-catenin (CTNNB1) [8]
Weight Management:
- SFN‐induced browning of white adipocytes (fat cells) [48]
- SFN decreases PPARγ and C/EBPα [49]
- SFN increases AMPK [49]
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Takeaway
Sulforaphane is an organic compound abundant in cruciferous vegetables like kale, cabbage, and broccoli. The richest dietary source of sulforaphane is broccoli sprouts.
Sulforaphane is being investigated for its potential to prevent recurrent prostate cancer and in several other clinical oncological settings. While there is nowhere near enough evidence to recommend this compound in the prevention or treatment of cancer, this research does support the importance of a healthy, vegetable-rich diet for long-term health.
Some animal research suggests that sulforaphane has the potential to disrupt DNA or to be toxic to the liver. Some people may have genetic variants that alter the way their body processes and metabolizes it.
Further Reading
