Sulforaphane/Sulforaphane glucosinolate - Thorne Research

Clinical Research: Sulforaphane/Sulforaphane glucosinolate
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.
Kensler TW, Chen JG, Egner PA, et al. Cancer Epidemiol Biomarkers Prev 2005;14:2605-2613.
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular
carcinoma due to consumption of aflatoxin-contaminated foods and high environmental exposure to
phenanthrene, a toxic hydrocarbon. In a randomized, placebo-controlled chemoprevention trial 200
healthy adults drank hot water infusions of 3-day old broccoli sprouts containing glucoraphanin or
placebo nightly for two weeks. An inverse association was observed for excretion of glucoraphanin
metabolites and aflatoxin-DNA adducts in individuals receiving broccoli sprout glucosinolates. A robust
inverse association between a urinary phenanthrene metabolite and glucoraphanin metabolites was
also observed. This study represents the first direct observation of sulforaphane’s inhibitory effect on
cancer in humans.
Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway.
Riedl MA, Saxon A, Diaz-Sanchez D. Clin Immunol 2009;130:244-251.
Cellular oxidative stress is thought to be the principle mechanism by which oxidant pollutants such as
ozone and airborne particulates mediate their pro-inflammatory effects in the human upper airway. A
placebo-controlled dose escalation trial investigated the effects of sulforaphane, a naturally occurring
potent inducer of Phase II enzymes, in 57 healthy adults (average age = 34 years) receiving broccoli
sprout homogenates over three days. Oral sulforaphane safely and effectively induces mucosal Phase II
enzyme expression in the upper airway of human subjects, indicating its role in protection against upper
airway inflammation caused by airborne pollutants.
Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human
subjects.
Myzak MC, Tong P, Dashwood WM, et al. Exp Biol Med 2007;232:227-234.
Sulforaphane was first identified as a potent inducer of Phase 2 enzymes, but evidence indicates it also
affords chemoprotection in human colon and prostate cancer cells line via inhibition of histone
deacetylase. Histone deacetylase inhibition correlates with induction of G2M cell cycle arrest and
apoptosis. In human subjects, a single dose of 68 g 3-day old broccoli sprouts, a rich source of
sulforaphane, inhibited HDAC activity significantly in peripheral blood mononuclear cells three and six
hours following consumption, providing evidence that sulforaphane induces apoptosis and may be
effective as a tumor-suppressing agent.
Preclinical and clinical evaluation of sulforaphane for chemoprevention in the
breast.
Cornblatt BS, Ye L, Dinkova-Kostova AT, et al. Carcinogenesis 2007;28:1485-1490.
Sulforaphane has been shown to inhibit mammary carcinogenesis in animal models. Research in humans
also indicates sulforaphane exerts a direct chemopreventive effect on mammary tissue. In a pilot study,
eight healthy women undergoing reduction mammoplasty were given a single dose of a broccoli sprout
preparation containing 200 µmol of sulforaphane. Following oral dosing, sulforaphane metabolites were

eadily measurable in human breast tissue. Both detoxification enzyme gene transcripts NADH quinone
reductase (NQ01) and heme oxygenase-1(HO-1) were measureable in the excised breast tissue,
indicating cancer blocking activity after sulforaphane consumption. These findings provide a strong
rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women
at risk for breast cancer.
Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter
pylori-infected mice and humans.
Yanaka A, Fahey JW, Fukumoto A, et al. Cancer Prev Res 2009;2:353-360.
The isothiocyanate sulforaphane is powerfully bactericidal against Helicobacter pylori infections, which
are strongly associated with the worldwide pandemic of gastric cancer. Forty-eight H. pylori-infected
patients were randomly assigned to feeding of broccoli sprouts (70 grams daily; containing 420
micromol of sulforaphane precursor) for eight weeks or to consumption of an equal weight of alfalfa
sprouts (not containing sulforaphane) as placebo. Intervention with broccoli sprouts, but not with
placebo, decreased the levels of breath test urease as well as H. pylori stool antigen and serum
pepsinogens I and II (biomarkers of gastric inflammation). Daily intake of sulforaphane-rich broccoli
sprouts for two months reduces H. pylori colonization and improves the sequelae of infection in
humans.
Cruciferae interact with the UGT1A1*28 polymorphism to determine serum bilirubin levels in humans.
Peterson S, Bigler J, Horner NK, et al. J Nutr 2005;135:1051-1055.
Gilbert’s syndrome is characterized by genetic polymorphisms in the UDP-glucuronosyltransferase (UGT)
enzymes, the primary one being UGT1A1*28, which is involved in bilirubin glucuronidation. UGT
polymorphisms can manifest as benign unconjugated hyperbilirubinemia associated with reduced
hepatic conjugation, and may increase cancer risk in this population. In an observational study of 191
nonsmoking volunteers (ages 19-40), consuming 0-4 servings of cruciferous vegetables daily, there was a
statistically significant inverse association between the UGT1A1 gene/Cruciferae interaction and total,
direct, and indirect bilirubin measurements. Sulforaphane from Cruciferae has been shown to induce
UGT1A1 activity, resulting in greater bilirubin conjugation and clearance and possibly mitigating the
increased cancer risk.
Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of
broccoli sprouts.
Murashima M, Watanabe S, Zhuo XG, et al. Biofactors 2004;22:271-275.
In a Phase I study of 12 healthy subjects (6 males and 6 females) consuming fresh broccoli sprouts (100
grams daily) for one week, researchers investigated the effect of broccoli sprouts on the induction of
various biochemical oxidative stress markers. Pre- and post-treatment lipid panels, natural killer cell
activity, plasma amino acids, serum coenzyme Q(10), plasma PCOOH (phosphatidylcholine
hydroperoxide), urinary 8-isoprostane, and urinary 8-OHdG (8-hydroxydeoxyguanosine) were measured.
With treatment, total cholesterol and LDL cholesterol decreased, and HDL cholesterol increased
significantly. Plasma cystine decreased significantly. All subjects showed reduced PCOOH, 8-isoprostane
and 8-OHdG, and increased CoQ(10)H(2)/CoQ(10) ratio. Only one week intake of broccoli sprouts
improved cholesterol metabolism and decreased oxidative stress markers in humans.

Animal Research: Sulforaphane/Sulforaphane glucosinolate
Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by
sulforaphane, a naturally occurring isothiocyanate.
Kong JS, Yoo SA, Kim HS, et al. Arthritis Rheum 2010;62:159-170.
Rheumatoid arthritis involves a tumor-like expansion of the synovium characterized by
hyperproliferation of synoviocytes, infiltration of T and B cells and increases in interleukins-6, -8, and -
17. The in vivo effects of sulforaphane on synoviocyte hyperplasia and T cell activation were examined in
mice with experimentally induced rheumatoid arthritis. Sulforaphane induced synoviocyte apoptosis,
inhibited T cell proliferation, and production of interleukin-17 (IL-17) and tumor necrosis factor alpha
(TNFalpha). Intraperitoneal administration of sulforaphane to mice also suppressed the clinical severity
of arthritis. The antiarthritic and immune regulatory effects of sulforaphane suggest it may offer a
possible treatment option for RA.
Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association
with increased cytotoxicity of natural killer cells.
Singh SV, Warin R, Xiao D, et al. Cancer Res 2009;69:2117-2125.
An animal model of prostate cancer shows that oral gavage of sulforaphane thrice per week beginning
at six weeks of age, significantly inhibits prostate carcinogenesis and pulmonary metastasis in mice,
without causing any side effects. The incidence of prostatic intraepithelial neoplasia and welldifferentiated
carcinoma were approximately 23-28-percent lower in the dorsolateral prostate of
sulforaphane-treated mice when compared with controls. Strikingly, the sulforaphane-treated mice
exhibited approximately 50% and 63% decrease, respectively, in pulmonary metastasis incidence and
multiplicity compared with control mice. The dorsolateral prostate from treated mice showed decreased
cellular proliferation and increased apoptosis when compared with that from control mice. These results
indicate that sulforaphane administration inhibits prostate cancer progression and pulmonary
metastasis in mice by reducing cell proliferation and augmenting NK cell lytic activity.
Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells.
Li Y, Zhang T, Korkaya H, et al. Clin Cancer Res 2010;16:2580-2590.
A nonobese diabetic/severe combined immunodeficient xenograft mouse model was used to determine
whether sulforaphane could target breast cancer stem cells in vivo, as assessed by Aldefluor assay, and
tumor growth upon cell reimplantation in secondary mice. Sulforaphane (1-5 micromol/L) decreased the
aldehyde dehydrogenase-positive cell population by 65% to 80% in human breast cancer cells and
reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75%, respectively.
Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells
by >50% in nonobese diabetic/severe combined immunodeficient xenograft tumors and eliminated
breast cancer stem cells in vivo, thereby abrogating tumor growth after the reimplantation of primary
tumor cells into the secondary mice. These findings support the use of sulforaphane for the
chemoprevention of breast cancer and warrant further clinical evaluation.
Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal
light damage in mice.
Tanito M, Masutani H, Kim YC, et al. Invest Ophthalmol Vis Sci 2005;46:979-987.

PURPOSE: Thioredoxin is a multifunctional endogenous redox regulator that protects against various
types of cellular or tissue stresses. In a mouse model of retinal light damage, researchers determined
intraperitoneal and oral sulforaphane induced thioreduxin protein in the neural retina and retinal
pigment epithelium and effectively reduced retinal light damage. Evidence suggests that antioxidant
response element is involved in the mechanism of thioreduxin induction by sulforaphane in retinal
pigment epithelial cells.