Broccoli Gummies White Paper
What is Sulforaphane?
Sulforaphane is a naturally occurring isothiocyanate compound found in cruciferous
vegetables, particularly broccoli, Brussels sprouts, cabbage, and kale. It is produced when the
enzyme myrosinase transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage
to the plant, such as from chewing or chopping during food preparation. Sulforaphane has two
possible stereoisomers due to the presence of a stereogenic sulfur atom. The R-sulforaphane
enantiomer occurs naturally, while the S-sulforaphane can be synthesized
Sulforaphane is a naturally occurring compound found in cruciferous vegetables such as
broccoli, Brussels sprouts, cabbage, cauliflower, and kale. It is part of the isothiocyanate group
of organosulfur compounds and is produced when the enzyme myrosinase transforms
glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant, which can occur
through chopping, chewing, or other forms of processing.
Sulforaphane has garnered significant attention due to its potential health benefits. It is
known for its antioxidant, antimicrobial, and anti-inflammatory properties. Research has
indicated that sulforaphane may offer a variety of health benefits, including the potential to
prevent cancer, improve heart health, aid in the management of diabetes, protect against brain
damage, and possibly improve symptoms of autism. It has been studied for its chemoprotective
properties, meaning it may help stop carcinogens from impacting the body.
The compound is also being explored for its role in cancer prevention and therapy, as it
has been found to promote programmed cell death (apoptosis), induce cell cycle arrest, inhibit
angiogenesis, reduce inflammation, and alter susceptibility to carcinogens. Sulforaphane is
available through dietary sources, and it can also be taken as a supplement, although the
efficacy and safety of supplements are still under investigation.
To activate sulforaphane and gain its health benefits, cruciferous vegetables must be
damaged (cut, chopped, or chewed) to allow glucoraphanin to come into contact with
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
myrosinase. This enzyme is sensitive to heat, and excessive cooking can destroy it, preventing
the formation of sulforaphane. However, certain cooking methods, such as steaming for short
periods, can preserve the myrosinase activity and thus the potential health benefits of
sulforaphane.
Mechanism of Action
Sulforaphane exerts its biological effects through several key mechanisms. One major
pathway is the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription
factor that upregulates antioxidant and phase II detoxification enzymes like NAD(P)H:quinone
oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutathione S-transferases (GSTs).
SFN also modulates histone deacetylase (HDAC) activity, leading to altered gene expression
and cell cycle arrest. Additionally, SFN can reduce inflammation by inhibiting the nuclear
factor-κB (NF-κB) pathway and scavenge reactive oxygen species like superoxide and
hydrogen peroxide (H2O2). Other potential mechanisms include induction of autophagy via
extracellular signal-regulated kinase (ERK) activation and inhibition of the antiapoptotic proteins
Bcl-2 and p38 mitogen-activated protein kinase (MAPK) isoforms.
What are the Health Benefits of Sulforaphane?
Sulforaphane has demonstrated potential health benefits in various conditions, including
cancer, diabetes, cardiovascular disease, and neurodegenerative disorders. In vitro and animal
studies suggest SFN may reduce cancer risk by inducing apoptosis, inhibiting angiogenesis,
and modulating epigenetic mechanisms. SFN improved glycemic control and insulin sensitivity
in a 12-week study of type 2 diabetics. Cardiovascular benefits may stem from SFN's
anti-inflammatory and antioxidant effects, with animal studies showing reduced blood pressure
and atherosclerosis. Neuroprotective properties are evidenced by improved cognitive function in
mouse models of Alzheimer's and Parkinson's diseases. However, high-dose SFN supplements
can cause adverse effects like gastrointestinal discomfort, and may interact with certain
medications metabolized by cytochrome P450 enzymes. While dietary consumption appears
safe, caution is warranted with supplements, especially in pregnant women, children, and those
with liver disease or seizure disorders due to limited safety data.
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
Sulforaphane, a compound found in cruciferous vegetables like broccoli, kale, and cauliflower,
has been studied for its numerous potential health benefits:
1. Antioxidant and anti-inflammatory effects: Sulforaphane is a potent activator of Nrf2, a
transcription factor that regulates cellular antioxidant and anti-inflammatory responses. It
can help reduce oxidative stress and inflammation, which are linked to various chronic
diseases.
2. Cancer prevention: Studies suggest that sulforaphane may have chemoprotective
properties, helping to prevent or slow the progression of various types of cancer,
including prostate, breast, and colon cancer. It can inhibit carcinogen activation, induce
apoptosis in cancer cells, and block tumor growth and metastasis.
3. Cardiovascular health: Sulforaphane may help improve heart health by reducing
inflammation, lowering blood pressure, and improving cholesterol levels. These effects
can potentially lower the risk of heart disease and stroke.
4. Diabetes management: Sulforaphane has been shown to improve glucose tolerance,
reduce fasting blood sugar levels, and enhance long-term blood sugar control in people
with type 2 diabetes.
5. Neuroprotection: Sulforaphane's antioxidant and anti-inflammatory properties may offer
protection against neurodegenerative diseases like Alzheimer's, Parkinson's, and
Huntington's disease. It may also help improve symptoms of autism and aid in recovery
from brain injury.
6. Skin health: Sulforaphane may protect the skin from UV damage and photoaging,
potentially reducing the risk of skin cancer and premature aging.
7. Liver detoxification: Sulforaphane can induce phase II detoxification enzymes in the liver,
supporting the body's natural detoxification processes and protecting against toxins and
pollutants.
Sources and Dietary Intake
Cruciferous vegetables, such as broccoli, kale, Brussels sprouts, and cabbage, are rich
sources of sulforaphane. Broccoli and broccoli sprouts contain particularly high levels, with
young sprouts having 10-100 times more sulforaphane than mature broccoli. Other good
sources include cauliflower, bok choy, watercress, collard greens, and turnips. Myrosinase is
essential for sulforaphane formation, so raw or lightly steamed vegetables provide the highest
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
levels, as cooking above 140°C inactivates the enzyme. Dietary supplements are also available,
typically containing broccoli seed or sprout extracts. While no official intake recommendations
exist, most supplements provide around 400 μg of sulforaphane per day. However, their safety
and efficacy in humans are still under investigation.
Glucoraphanin: Sulforaphane's Crucial Precursor
Glucoraphanin is a glucosinolate compound found in high concentrations in cruciferous
vegetables like broccoli, Brussels sprouts, cabbage, and kale. It is the precursor to
sulforaphane, a potent isothiocyanate with numerous potential health benefits. Glucoraphanin is
converted to sulforaphane by the plant enzyme myrosinase when the vegetable is damaged,
such as by chewing, chopping, or light cooking.
Broccoli seeds and young broccoli sprouts contain the highest levels of glucoraphanin,
with concentrations 10-100 times higher than in mature broccoli. However, the glucoraphanin
content can vary significantly between different broccoli cultivars and growing conditions.
Glucoraphanin has a potassium salt form and is derived from the amino acid dihomomethionine
through a chain elongation process. The sulfinyl group in glucoraphanin is chiral and has an R
absolute configuration, which is set by the action of a flavin monooxygenase enzyme on
4-methylthiobutylglucosinolate.
In plants, glucoraphanin and its hydrolysis product sulforaphane serve as natural
defense compounds, deterring insect predators and acting as selective antibiotics. When
consumed by humans, glucoraphanin is hydrolyzed by gut microbiota-derived myrosinase into
bioactive sulforaphane. This conversion process varies between individuals due to differences in
gut microbiome composition.
Glucoraphanin and sulforaphane have been studied extensively for their potential
biological effects, particularly in cancer prevention, detoxification, and anti-inflammatory
pathways. However, more clinical evidence is needed to fully understand the efficacy and safety
of glucoraphanin supplementation in humans. Consuming cruciferous vegetables rich in
glucoraphanin remains the most reliable way to obtain its potential health benefits.
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
Myrosinase: The Glucosinolate-Activating Enzyme
Myrosinase (EC 3.2.1.147) is an enzyme found in plants, particularly in cruciferous
vegetables like broccoli, cabbage, and mustard. It plays a crucial role in the plant's defense
system against herbivores and is responsible for the conversion of glucosinolates, such as
glucoraphanin, into biologically active compounds like isothiocyanates, including sulforaphane.
Myrosinase and glucosinolates are stored separately in plant cells. When the plant tissue is
damaged, such as by chewing or chopping, myrosinase comes into contact with glucosinolates
and catalyzes their hydrolysis. This reaction releases glucose and an unstable aglycone, which
then undergoes a spontaneous rearrangement to form isothiocyanates, nitriles, or other
products, depending on the specific glucosinolate and reaction conditions.
Myrosinase is the only known enzyme capable of cleaving the unique thio-linked glucose
in glucosinolates. It requires no cofactors for its activity but can be enhanced by the presence of
ascorbate, a natural cofactor found in plants. Myrosinase activity is also influenced by pH and
the presence of certain ions, with nitrile formation favored under acidic conditions and in the
presence of Fe2+.
The enzyme is a glycoprotein consisting of two subunits, each with a molecular weight of
60-70 kDa, and is stabilized by salt bridges, disulfide bonds, and glycosylation. Myrosinase is
most stable at temperatures up to 50°C and can retain some activity even after cooking.
However, prolonged exposure to high temperatures, such as during boiling or microwaving, can
significantly reduce myrosinase activity
The thermal stability of myrosinase varies among different plant species and cultivars.
Broccoli, mustard seeds, and daikon radish are known to have high myrosinase activity and
relatively heat-stable forms of the enzyme. Adding a small amount of raw cruciferous vegetables
or mustard powder to cooked vegetables can help restore myrosinase activity and boost
sulforaphane production
Glucoraphanin and Myrosinase Interaction
Glucoraphanin and myrosinase are two key components found in cruciferous vegetables
that work together to produce sulforaphane, a potent bioactive compound. Glucoraphanin is a
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
glucosinolate that serves as the precursor to sulforaphane, while myrosinase is the enzyme
responsible for catalyzing the conversion reaction.
In intact plant cells, glucoraphanin and myrosinase are stored separately in different
compartments. Glucoraphanin is located in the vacuoles of specific cells called S-cells, while
myrosinase is found in distinct myrosin cells. This spatial separation prevents the premature
hydrolysis of glucoraphanin and allows the plant to control the production of sulforaphane as a
defense mechanism against herbivores and pathogens.
When the plant tissue is damaged, such as by chewing, chopping, or light cooking, the
cell walls and membranes are disrupted, allowing glucoraphanin and myrosinase to come into
contact. Myrosinase then catalyzes the hydrolysis of glucoraphanin, cleaving off the glucose
moiety and releasing an unstable aglycone intermediate, which spontaneously rearranges to
form sulforaphane.
The hydrolysis reaction is influenced by various factors, including pH, temperature, and
the presence of certain cofactors like ascorbate and iron ions. Under optimal conditions,
myrosinase can rapidly convert glucoraphanin into sulforaphane, which can then be absorbed
by the human body and exert its potential health benefits.
However, the efficiency of this conversion process can be affected by cooking methods
and the individual's gut microbiome composition. Boiling or microwaving cruciferous vegetables
can significantly reduce myrosinase activity, limiting sulforaphane production. In the absence of
active plant myrosinase, certain gut bacteria capable of producing myrosinase-like enzymes can
still convert glucoraphanin into sulforaphane, although with lower efficiency.
To maximize sulforaphane production and bioavailability, it is recommended to consume
cruciferous vegetables raw or lightly cooked, or to add a small amount of raw vegetables or
mustard powder (a rich source of myrosinase) to cooked vegetables. This ensures that active
myrosinase is present to efficiently catalyze the conversion of glucoraphanin into sulforaphane,
allowing the body to fully benefit from this potent phytochemical.
The information presented in this paper is based on publicly available data regarding ingredients
and is intended for informational purposes only. It is not intended for marketing health claims or
as a substitute for professional medical advice.
Bioavailability: Sulforaphane vs Glucoraphanin
The bioavailability of sulforaphane varies significantly depending on whether it is
consumed directly as sulforaphane or as its precursor glucoraphanin, and whether active
myrosinase enzymes are present. When glucoraphanin is consumed without active myrosinase,
such as in cooked broccoli, the bioavailability of sulforaphane is only around 5%, as it relies on
gut bacteria for conversion. In contrast, when active myrosinase is present, either in raw broccoli
or as a supplement, the bioavailability of sulforaphane increases to 35-40%.
Glucoraphanin itself is water-soluble and relatively inert. It requires myrosinase to be
converted into the bioactive sulforaphane. Myrosinase is heat-sensitive, so cooking methods
like boiling or microwaving can significantly reduce its activity and limit sulforaphane production.
However, the gut microbiome is also capable of converting some glucoraphanin to
sulforaphane, even in the absence of active plant myrosinase.
Supplements containing glucoraphanin plus active myrosinase show a median
bioavailability of 20%, with less inter-individual variability compared to other formulations.
Clinical trials using doses of 1-10 μmol/kg/day of glucoraphanin plus myrosinase or 1-3
μmol/kg/day of sulforaphane have demonstrated efficacy.
The whole-body half-life of sulforaphane is approximately 2.4 hours when consumed
directly, compared to 7.3 hours for glucoraphanin, leading to more rapid elimination.
Bioavailability studies suggest that a blend of sulforaphane and glucoraphanin plus
myrosinase may be optimal, providing both peak concentrations for target activation and
prolonged inhibition of other pathways. Careful dosing based on excreted sulforaphane
metabolites, rather than administered dose, is crucial due to the significant differences in
bioavailability between formulations.
In summary, glucoraphanin, myrosinase, and the gut microbiome work together to
optimize sulforaphane production and bioavailability. Myrosinase is essential for efficiently
converting glucoraphanin to sulforaphane, while the gut microbiome can provide some
additional conversion capacity. Combining sulforaphane with glucoraphanin plus myrosinase may offer the best balance of rapid peak concentrations and sustained release for maximizing
the potential health benefits of this potent phytochemical.
Safety and Side Effects
Sulforaphane, glucoraphanin, and myrosinase are generally considered safe when
consumed in amounts typically found in cruciferous vegetables. However, there are some
potential side effects and safety considerations to be aware of, especially when taking
concentrated supplements:
Sulforaphane:
● Sulforaphane is likely safe when consumed in food amounts. Sulforaphane supplements
have been used safely in clinical trials for up to 6 months.
● Common side effects of sulforaphane supplements may include increased gas,
constipation, and stomach upset.
● In rare cases, seizures have been reported in people with a history of seizures after
taking sulforaphane. Use caution if you have a seizure disorder.
● Sulforaphane may interact with certain medications metabolized by the liver, potentially
altering their effects and side effects. Consult a healthcare provider if taking medications.
Glucoraphanin:
● Glucoraphanin is safe when consumed in food amounts, such as from broccoli and
radish. It is unlikely to cause side effects as part of a varied, healthy diet.
● Glucoraphanin supplements are generally considered safe at recommended doses,
typically 1-2 pills per day. However, more research is needed to fully establish their
long-term safety and effectiveness.
Myrosinase:
● Myrosinase is an enzyme naturally found in cruciferous vegetables and is not known to
cause adverse effects when consumed in food amounts.
● Some glucoraphanin supplements also contain active myrosinase to enhance
sulforaphane production. These supplements appear to be well-tolerated, but their
long-term safety is not yet fully established.
Pregnancy and Breastfeeding:
● Sulforaphane, glucoraphanin, and myrosinase are likely safe during pregnancy and
breastfeeding when consumed in food amounts. However, there is insufficient reliable
information on the safety of taking supplements in larger doses. It is best to consult a
healthcare provider and stick to obtaining these compounds from food sources.
While sulforaphane, glucoraphanin, and myrosinase are generally considered safe,
especially when obtained from whole foods, it is always advisable to consult a healthcare
professional before starting any new supplement regimen. They can help you weigh the
potential benefits and risks based on your individual health status and medical history.
Conclusion
In conclusion, sulforaphane is a potent phytochemical found in cruciferous vegetables
that has been studied for its numerous potential health benefits, including antioxidant,
anti-inflammatory, chemoprotective, and neuroprotective effects. Sulforaphane is produced
when glucoraphanin, a glucosinolate precursor, is converted by the plant enzyme myrosinase
upon damage to the vegetable. The bioavailability of sulforaphane varies significantly depending
on whether it is consumed directly or as glucoraphanin, and whether active myrosinase is
present.
Cooking methods like steaming can help preserve glucosinolates while stir-frying retains
the most myrosinase activity. Adding raw cruciferous vegetables or mustard powder to cooked
vegetables can restore myrosinase activity and boost sulforaphane production. The gut
microbiome also plays a crucial role in converting glucoraphanin to sulforaphane, with certain
bacterial species being more efficient than others.
Supplements containing glucoraphanin plus myrosinase show better bioavailability than
sulforaphane alone. A blend of sulforaphane and glucoraphanin with myrosinase may provide
the optimal balance of rapid peak concentrations and sustained release. While generally
considered safe, especially in food amounts, sulforaphane supplements can cause side effects
like digestive issues and may interact with certain medications.
Overall, consuming a variety of cruciferous vegetables prepared in ways that optimize
sulforaphane production appears to be the safest and most effective way to obtain the potential
health benefits of this promising dietary compound. More clinical research is needed to fully
elucidate the therapeutic applications and long-term effects of sulforaphane supplementation.
References
1. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers
of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U S A.
1997;94(19):10367-10372. doi:10.1073/pnas.94.19.10367
2. Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective
enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A.
1992;89(6):2399-2403. doi:10.1073/pnas.89.6.2399
3. Fahey JW, Wehage SL, Holtzclaw WD, et al. Protection of humans by plant
glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the
gastrointestinal microflora. Cancer Prev Res (Phila). 2012;5(4):603-611.
doi:10.1158/1940-6207.CAPR-11-0538
4. Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Human metabolism and
excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous
vegetables. Cancer Epidemiol Biomarkers Prev. 1998;7(12):1091-1100.
5. Fahey JW, Holtzclaw WD, Wehage SL, Wade KL, Stephenson KK, Talalay P.
Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active
Endogenous Myrosinase. PLoS One. 2015;10(11):e0140963. Published 2015 Nov 2.
doi:10.1371/journal.pone.0140963
6. Dinkova-Kostova AT, Fahey JW, Wade KL, et al. Induction of the phase 2 response in
mouse and human skin by sulforaphane-containing broccoli sprout extracts. Cancer
Epidemiol Biomarkers Prev. 2007;16(4):847-851. doi:10.1158/1055-9965.EPI-06-0934
7. Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant
enzymes in the human upper airway. Clin Immunol. 2009;130(3):244-251.
doi:10.1016/j.clim.2008.10.007
8. Yanaka A, Fahey JW, Fukumoto A, et al. Dietary sulforaphane-rich broccoli sprouts
reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and
humans. Cancer Prev Res (Phila). 2009;2(4):353-360.
doi:10.1158/1940-6207.CAPR-08-0192
9. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the
growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol
Med (Maywood). 2007;232(2):227-234.
10. Alumkal JJ, Slottke R, Schwartzman J, et al. A phase II study of sulforaphane-rich
broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs.
2015;33(2):480-489. doi:10.1007/s10637-014-0189-z
11. Cipolla BG, Mandron E, Lefort JM, et al. Effect of Sulforaphane in Men with Biochemical
Recurrence after Radical Prostatectomy. Cancer Prev Res (Phila). 2015;8(8):712-719.
doi:10.1158/1940-6207.CAPR-14-0459
12. Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose
production and improves glucose control in patients with type 2 diabetes. Sci Transl
Med. 2017;9(394):eaah4477. doi:10.1126/scitranslmed.aah4477
13. Kikuchi M, Ushida Y, Shiozawa H, et al. Sulforaphane-rich broccoli sprout extract
improves hepatic abnormalities in male subjects. World J Gastroenterol.
2015;21(43):12457-12467. doi:10.3748/wjg.v21.i43.12457
14. Bahadoran Z, Mirmiran P, Hosseinpanah F, Hedayati M, Hosseinpour-Niazi S, Azizi F.
Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind
clinical trial. Eur J Clin Nutr. 2011;65(8):972-977. doi:10.1038/ejcn.2011.59
15. Bahadoran Z, Tohidi M, Nazeri P, Mehran M, Azizi F, Mirmiran P. Effect of broccoli
sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind
clinical trial. Int J Food Sci Nutr. 2012;63(7):767-771.
doi:10.3109/09637486.2012.665043
16. Armah CN, Derdemezis C, Traka MH, et al. Diet rich in high glucoraphanin broccoli
reduces plasma LDL cholesterol: Evidence from randomised controlled trials. Mol Nutr
Food Res. 2015;59(5):918-926. doi:10.1002/mnfr.201400863
17. Mirmiran P, Bahadoran Z, Hosseinpanah F, Keyzad A, Azizi F. Effects of broccoli sprout
with high sulforaphane concentration on inflammatory markers in type 2 diabetic
patients: A randomized double-blind placebo-controlled clinical trial. J Funct Foods.
2012;4(4):837-841. doi:10.1016/j.jff.2012.05.012
18. Healy ZR, Liu H, Holtzclaw WD, Talalay P. Inactivation of tautomerase activity of
macrophage migration inhibitory factor by sulforaphane: a potential biomarker for
anti-inflammatory intervention. Cancer Epidemiol Biomarkers Prev.
2011;20(7):1516-1523. doi:10.1158/1055-9965.EPI-11-0279
19. Dinkova-Kostova AT, Fahey JW, Benedict AL, et al. Dietary glucoraphanin-rich broccoli
sprout extracts protect against UV radiation-induced skin carcinogenesis in SKH-1
hairless mice. Photochem Photobiol Sci. 2010;9(4):597-600. doi:10.1039/b9pp00130a
20. Talalay P, Fahey JW, Healy ZR, et al. Sulforaphane mobilizes cellular defenses that
protect skin against damage by UV radiation. Proc Natl Acad Sci U S A.
2007;104(44):17500-17505. doi:10.1073/pnas.0708710104
21. Knatko EV, Ibbotson SH, Zhang Y, et al. Nrf2 Activation Protects against Solar-Simulated
Ultraviolet Radiation in Mice and Humans. Cancer Prev Res (Phila). 2015;8(6):475-486.
doi:10.1158/1940-6207.CAPR-14-0362
22. Dinkova-Kostova AT, Jenkins SN, Fahey JW, et al. Protection against UV-light-induced
skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout
extracts. Cancer Lett. 2006;240(2):243-252. doi:10.1016/j.canlet.2005.09.012
23. Kensler TW, Chen JG, Egner PA, et al. Effects of glucosinolate-rich broccoli sprouts on
urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized
clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol
Biomarkers Prev. 2005;14(11 Pt 1):2605-2613. doi:10.1158/1055-9965.EPI-05-0368
24. Egner PA, Chen JG, Wang JB, et al. Bioavailability of Sulforaphane from two broccoli
sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China.
Cancer Prev Res (Phila). 2011;4(3):384-395. doi:10.1158/1940-6207.CAPR-10-0296
25. Kensler TW, Ng D, Carmella SG, et al. Modulation of the metabolism of airborne
pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in
Qidong, China. Carcinogenesis. 2012;33(1):101-107. doi:10.1093/carcin/bgr229
26. Egner PA, Chen JG, Zarth AT, et al. Rapid and sustainable detoxication of airborne
pollutants by broccoli sprout beverage: results of a randomized clinical trial in China.
Cancer Prev Res (Phila). 2014;7(8):813-823. doi:10.1158/1940-6207.CAPR-14-0103
27. Heber D, Li Z, Garcia-Lloret M, et al. Sulforaphane-rich broccoli sprout extract attenuates
nasal allergic response to diesel exhaust particles. Food Funct. 2014;5(1):35-41.
doi:10.1039/c3fo60277j
28. Brown RH, Reynolds C, Brooker A, Talalay P, Fahey JW. Sulforaphane improves the
bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir
Res. 2015;16(1):106. Published 2015 Sep 15. doi:10.1186/s12931-015-0253-z
29. Sudini K, Diette GB, Breysse PN, et al. A Randomized Controlled Trial of the Effect of
Broccoli Sprout Extract on Antioxidant Gene Expression and Airway Inflammation in
Asthmatics. J Allergy Clin Immunol Pract. 2016;4(5):932-940.
doi:10.1016/j.jaip.2016.03.012
30. Duran CG, Burbank AJ, Mills KH, et al. A proof-of-concept clinical study examining the
NRF2 activator sulforaphane against neutrophilic airway inflammation. Respir Res.
2016;17(1):89. Published 2016 Aug 11. doi:10.1186/s12931-016-0406-8
31. Wise RA, Holbrook JT, Criner G, et al. Lack of Effect of Oral Sulforaphane Administration
on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.
PLoS One. 2016;11(11):e0163716. Published 2016 Nov 4.
doi:10.1371/journal.pone.0163716
32. Fahey JW, Talalay P, Kensler TW. Notes from the field: "green" chemoprevention as
frugal medicine. Cancer Prev Res (Phila). 2012;5(2):179-188.
doi:10.1158/1940-6207.CAPR-11-0572
33. Fahey JW, Haristoy X, Dolan PM, et al. Sulforaphane inhibits extracellular, intracellular,
and antibiotic-resistant strains of Helicobacter pylori and prevents
benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci U S A.
2002;99(11):7610-7615. doi:10.1073/pnas.112203099
34. Fahey JW, Stephenson KK, Wade KL, Talalay P. Urease from Helicobacter pylori is
inactivated by sulforaphane and other isothiocyanates. Biochem Biophys Res Commun.
2013;435(1):1-7. doi:10.1016/j.bbrc.2013.03.126
35. Haristoy X, Angioi-Duprez K, Duprez A, Lozniewski A. Efficacy of sulforaphane in
eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice.
Antimicrob Agents Chemother. 2003;47(12):3982-3984.
doi:10.1128/aac.47.12.3982-3984.2003
36. Fahey JW, Stephenson KK, Dinkova-Kostova AT, Egner PA, Kensler TW, Talalay P.
Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian
phase 2 cytoprotective genes. Carcinogenesis. 2005;26(7):1247-1255.
doi:10.1093/carcin/bgi068
37. Kensler TW, Egner PA, Agyeman AS, et al. Keap1-nrf2 signaling: a target for cancer
prevention by sulforaphane. Top Curr Chem. 2013;329:163-177.
doi:10.1007/128_2012_339
38. Dinkova-Kostova AT, Holtzclaw WD, Cole RN, et al. Direct evidence that sulfhydryl
groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect
against carcinogens and oxidants. Proc Natl Acad Sci U S A. 2002;99(18):11908-11913.
doi:10.1073/pnas.172398899
39. Dinkova-Kostova AT, Talalay P. Direct and indirect antioxidant properties of inducers of
cytoprotective proteins. Mol Nutr Food Res. 2008;52 Suppl 1:S128-S138.
doi:10.1002/mnfr.200700195
40. Dinkova-Kostova AT, Fahey JW, Kostov RV, Kensler TW. KEAP1 and Done? Targeting
the NRF2 Pathway with Sulforaphane. Trends Food Sci Technol. 2017;69(Pt B):257-269.
doi:10.1016/j.tifs.2017.02.002
41. Fahey JW, Holtzclaw WD, Wehage SL, Wade KL, Stephenson KK, Talalay P.
Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active
Endogenous Myrosinase. PLoS One. 2015;10(11):e0140963. Published 2015 Nov 2.
doi:10.1371/journal.pone.0140963
42. Dinkova-Kostova AT, Fahey JW, Wade KL, et al. Induction of the phase 2 response in
mouse and human skin by sulforaphane-containing broccoli sprout extracts. Cancer
Epidemiol Biomarkers Prev. 2007;16(4):847-851. doi:10.1158/1055-9965.EPI-06-0934
43. Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant
enzymes in the human upper airway. Clin Immunol. 2009;130(3):244-251.
doi:10.1016/j.clim.2008.10.007
44. Yanaka A, Fahey JW, Fukumoto A, et al. Dietary sulforaphane-rich broccoli sprouts
reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and
humans. Cancer Prev Res (Phila). 2009;2(4):353-360.
doi:10.1158/1940-6207.CAPR-08-0192
45. Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the
growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol
Med (Maywood). 2007;232(2):227-234.
46. Alumkal JJ, Slottke R, Schwartzman J, et al. A phase II study of sulforaphane-rich
broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs.
2015;33(2):480-489. doi:10.1007/s10637-014-0189-z
47. Cipolla BG, Mandron E, Lefort JM, et al. Effect of Sulforaphane in Men with Biochemical
Recurrence after Radical Prostatectomy. Cancer Prev Res (Phila). 2015;8(8):712-719.
doi:10.1158/1940-6207.CAPR-14-0459
48. Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose
production and improves glucose control in patients with type 2 diabetes. Sci Transl
Med. 2017;9(394):eaah4477. doi:10.1126/scitranslmed.aah4477
49. Kikuchi M, Ushida Y, Shiozawa H, et al. Sulforaphane-rich broccoli sprout extract
improves hepatic abnormalities in male subjects. World J Gastroenterol.
2015;21(43):12457-12467. doi:10.3748/wjg.v21.i43.12457
50. Bahadoran Z, Mirmiran P, Hosseinpanah F, Hedayati M, Hosseinpour-Niazi S, Azizi F.
Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind
clinical trial. Eur J Clin Nutr. 2011;65(8):972-977. doi:10.1038/ejcn.2011.59
51. Bahadoran Z, Tohidi M, Nazeri P, Mehran M, Azizi F, Mirmiran P. Effect of broccoli
sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind
clinical trial. Int J Food Sci Nutr. 2012;63(7):767-771.
doi:10.3109/09637486.2012.665043
52. Armah CN, Derdemezis C, Traka MH, et al. Diet rich in high glucoraphanin broccoli
reduces plasma LDL cholesterol: Evidence from randomised controlled trials. Mol Nutr
Food Res. 2015;59(5):918-926. doi:10.1002/mnfr.201400863
53. Mirmiran P, Bahadoran Z, Hosseinpanah F, Keyzad A, Azizi F. Effects of broccoli sprout
with high sulforaphane concentration on inflammatory markers in type 2 diabetic
patients: A randomized double-blind placebo-controlled clinical trial. J Funct Foods.
2012;4(4):837-841. doi:10.1016/j.jff.2012.05.012
54. Healy ZR, Liu H, Holtzclaw WD, Talalay P. Inactivation of tautomerase activity of
macrophage migration inhibitory factor by sulforaphane: a potential biomarker for
anti-inflammatory intervention. Cancer Epidemiol Biomarkers Prev.
2011;20(7):1516-1523. doi:10.1158/1055-9965.EPI-11-0279
55. Dinkova-Kostova AT, Fahey JW, Benedict AL, et al. Dietary glucoraphanin-rich broccoli
sprout extracts protect against UV radiation-induced skin carcinogenesis in SKH-1
hairless mice. Photochem Photobiol Sci. 2010;9(4):597-600. doi:10.1039/b9pp00130a
56. Talalay P, Fahey JW, Healy ZR, et al. Sulforaphane mobilizes cellular defenses that
protect skin against damage by UV radiation. Proc Natl Acad Sci U S A.
2007;104(44):17500-17505. doi:10.1073/pnas.0708710104
57. Knatko EV, Ibbotson SH, Zhang Y, et al. Nrf2 Activation Protects against Solar-Simulated
Ultraviolet Radiation in Mice and Humans. Cancer Prev Res (Phila). 2015;8(6):475-486.
doi:10.1158/1940-6207.CAPR-14-0362
58. Dinkova-Kostova AT, Jenkins SN, Fahey JW, et al. Protection against UV-light-induced
skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout
extracts. Cancer Lett. 2006;240(2):243-252. doi:10.1016/j.canlet.2005.09.012
59. Kensler TW, Chen JG, Egner PA, et al. Effects of glucosinolate-rich broccoli sprouts on
urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized
clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol
Biomarkers Prev. 2005;14(11 Pt 1):2605-2613. doi:10.1158/1055-9965.EPI-05-0368
60. Egner PA, Chen JG, Wang JB, et al. Bioavailability of Sulforaphane from two broccoli
sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China.
Cancer Prev Res (Phila). 2011;4(3):384-395. doi:10.1158/1940-6207.CAPR-10-0296