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Clinical and molecular evidence of the consumption of broccoli, glucoraphanin and sulforaphane in humans


Abstract and Figures

Introduction: Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin (GRA), which is found in great amounts especially in broccoli. Its consumption has been reported to be associated with a lower risk of myocardial infarction and cancer development. Additionally, its effects have been studied in neurodegenerative diseases, diabetes, and atherosclerosis, most of the times using animal models and cell cultures. Objectives: Given the promising results of SFN, this review aimed to investigate evidence documented in human intervention studies with broccoli, GRA and SFN. Methods: A search was performed on PubMed and Virtual Health Library databases by two independent researchers using the descriptors "broccoli" or "glucoraphanin" or "sulforaphane", which should appear on the study's title or abstract. This review included randomized clinical trials performed in humans that were published in English and Portuguese from 2003 to 2013 and that considered clinical and molecular parameters of cell damage as outcomes of interest. Results: Seventeen studies were selected, and the predominant type of intervention was broccoli sprouts. More consistent results were obtained for the clinical parameters blood glucose and lipid profile and for molecular parameters of oxidative stress, indicating that there was an improvement in these parameters after intervention. Less solid evidence was found with regard to decreased inflammation, Helicobacter pylori colonization, and protection against cancer. Conclusion: Although being relevant, the evidence for the use of broccoli, GRA and SFN in humans are limited; thus, further intervention studies are needed to evaluate outcomes more consistently and reach better grounded conclusions. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
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Nutr Hosp. 2015;31(2):559-569
S.V.R. 318
Clinical and molecular evidence of the consumption of broccoli,
glucoraphanin and sulforaphane in humans
Adriana Conzatti1, Fernanda Carolina Telles da Silva Fróes2, Ingrid Dalira Schweigert Perry3,4
and Carolina Guerini de Souza4,5
1Departamento de Fisiologia, Universidade Federal do Rio Grande do Sul (UFRGS). 2Departamento de Bioquímica, Universidade
Federal do Rio Grande do Sul (UFRGS). 3Unidade Acadêmica da Saúde (UNASAU), Universidade do Extremo Sul Catarinense
(UNESC). 4Centro de Estudos em Alimentação e Nutrição (CESAN)- Hospital de Clínicas de Porto Alegre (HCPA) – UFRGS.
5Faculdade de Medicina, Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul (UFRGS). Brazil.
Introduction: Sulforaphane (SFN) is an isothiocyanate
derived from glucoraphanin (GRA), which is found in
great amounts especially in broccoli. Its consumption has
been reported to be associated with a lower risk of myo-
cardial infarction and cancer development. Additionally,
its effects have been studied in neurodegenerative disea-
ses, diabetes, and atherosclerosis, most of the times using
animal models and cell cultures.
Objectives: Given the promising results of SFN, this re-
view aimed to investigate evidence documented in human
intervention studies with broccoli, GRA and SFN.
Methods: A search was performed on PubMed and
Virtual Health Library databases by two independent
researchers using the descriptors “broccoli” or “glucora-
phanin” or “sulforaphane”, which should appear on the
study’s title or abstract. This review included randomi-
zed clinical trials performed in humans that were publi-
shed in English and Portuguese from 2003 to 2013 and
that considered clinical and molecular parameters of cell
damage as outcomes of interest.
Results: Seventeen studies were selected, and the pre-
dominant type of intervention was broccoli sprouts. More
consistent results were obtained for the clinical parame-
ters blood glucose and lipid profile and for molecular
parameters of oxidative stress, indicating that there was
an improvement in these parameters after intervention.
Less solid evidence was found with regard to decreased
inflammation, Helicobacter pylori colonization, and pro-
tection against cancer.
Conclusion: Although being relevant, the evidence for
the use of broccoli, GRA and SFN in humans are limited;
Introducción: El sulforafano (SFN) es un isotiocianato
derivado de la glucorafanina (GRA), encontrada en gran
cantidad especialmente en el brócolis. Su consumo está
asociado a un menor riesgo de infarto del miocardio y
de cáncer. Además, sus efectos están siendo estudiados en
enfermedades neurodegenerativas, diabetes y ateroscle-
rosis, casi siempre utilizando modelos animales y cultivos
Objetivos: Debido a los resultados prometedores del
compuesto SFN, esta revisión buscó investigar evidencias
ya documentadas en intervenciones con brócoli, GRA y
SFN en humanos.
Métodos: Se realizó una búsqueda en las bases de datos
PubMed y Biblioteca Virtual en Salud, por dos investiga-
dores independientes, utilizando los descriptores “broc-
coli” o “glucoraphanin” o “sulforaphane”, que debían
constar en el título o resumen del trabajo. Se incluyeron
ensayos clínicos randomizados realizados en humanos,
publicados en inglés y portugués entre 2003 y 2013, y que
consideraron como desenlaces de interés parámetros clí-
nicos y moleculares de daño celular.
Resultados: Se seleccionaron 17 estudios y el tipo de
intervención predominante fueron brotes de brócoli.
Los resultados más consistentes fueron obtenidos con
los parámetros clínicos glicemia y perfil lipídico y los pa-
rámetros moleculares de estrés oxidativo, que presenta-
ron mejora después de la intervención. Se encontraron
evidencias menos sólidas respeto a la disminución de la
inflamación, de la colonización por Helicobacter pylori y
protección contra cáncer.
Conclusión: Aunque relevantes, las evidencias del uso
de brócoli, GRA y SFN en humanos son limitadas, siendo
Correspondence: Carolina Guerini de Souza.
Faculdade de Medicina. Departamento de Medicina Interna.
Universidade Federal do Rio Grande do Sul,
Rua Ramiro Barcelos 2400 - 4º andar, Santa Cecília.
CEP: 90035-003. Porto Alegre - Rio Grande do Sul.
Recibido: 14-VI-2014.
Aceptado: 1-IX-2014.
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560 Nutr Hosp. 2015;31(2):559-569 Adriana Conzatti et al.
GSL = Glucosinolate.
GRA = Glucoraphanin.
SFN = Sulforaphane.
Nrf2 = Nuclear factor erythroid 2–related factor 2.
Keap1 = Kelch-like ECH-associated protein 1.
ARE = Antioxidant response element.
DNA = Deoxyribonucleic acid.
NQO1 = NADPH quinone oxidoreductase 1.
HO-1 = Heme oxygenase-1.
GST = Glutathione S-transferase.
PRISMA = Preferred Reporting Items for Systema-
tic Reviews and Meta-Analyses.
RCT = Randomized clinical trial.
VHL = Virtual Health Library.
H. Pylori = Helicobacter pylori.
DM2 = Diabetes mellitus type 2.
HOMA IR = Homeostatic Model Assessment for
Insulin Resistance.
TC = Total cholesterol.
LDL = Low-density lipoprotein.
HDL = High-density lipoprotein.
TG = Triglycerides.
IL-6 = Interleukin-6.
CRP = C-reactive protein.
TNF-a = Tumor necrosis factor a.
CVD = Cardiovascular disease.
GSTM1 = Glutathione S-transferase M1.
GSTP1 = Glutathione S-transferase P1.
PSA = Prostate-specific antigen.
IGF-1 = Insulin-like growth factor-1.
HpSA = H. pylori stool antigen.
UBT = Urea breath test.
PGI = Pepsinogen I.
PGII = Pepsinogen II.
NF-kB = Nuclear factor kappa-B.
Epidemiological evidence suggests that the con-
sumption of cruciferous vegetables is related to bene-
ficial health effects, such as lower risk for myocardial
infarction and for the development of cancers1-5. Addi-
tionally, compounds extracted from these vegetables
have been studied for the treatment of neurodegene-
rative diseases, diabetes, and atherosclerosis, showing
promising results6-8.
thus, further intervention studies are needed to evaluate
outcomes more consistently and reach better grounded
(Nutr Hosp. 2015;31:559-569)
Key words: Broccoli. Sulforaphane. Glucoraphanin. Iso-
necesarios más estudios de intervención para avaluar los
desenlaces de forma más consistente y producir conclu-
siones mejor fundamentadas.
(Nutr Hosp. 2015;31:559-569)
Palabras clave: Brócoli. Sulforafano. Glucorafanina. Iso-
Cruciferous species belong to the genus Brassica
(families Brassicaceae and Cruciferae) and include
vegetables such as broccoli, cauliflower, kale, brusse-
ls sprout, cress, radish, cabbage, and mustard9. These
vegetables represent a good source of phytochemicals,
including phenolic compounds, sulphur glycosides,
and carotenoids10. However, their anticarcinogenic
and antioxidant potential has been attributed mainly to
their high glucosinolate (GSL) content11,12.
GSLs are thioglucosides that have one cyano group
and one sulfate group, encompassing nearly 120 che-
mically stable compounds13. When the tissues of these
plants are processed by cutting, cooking, freezing, or
mastication, GSLs are exposed to an enzyme named
mirosinase, present in the very vegetable, which hi-
drolizes them to isothiocyanates, substances that are
bioactive compounds14. Human intestinal microflora
also has a mirosinase isoform15 and, although there are
different types of GSLs and isothiocyanates in nature,
glucoraphanin (GRA) and sulforaphane (SFN) are the
most studied compound and the one that currently has
the strongest evidence for beneficial effects, respecti-
Broccoli, more especially its sprouts, is recognized
as the best source of SFN, and GRA corresponds to
90% of the GSL content in some of its species17. SFN
is considered a very promising compound because it
was found to have properties that prevent, delay or
reverse the development of preneoplastic lesions and
to improve survival rates, acting on cancer cells as a
therapeutic agent18-19.
SFN may interact with many molecular targets, but
its well described mechanism of action is through nu-
clear factor (erythroid-derived 2)-like 2 (Nrf2). Nrf2
is a transcription factor essential to the regulation of
the cellular redox state that, in non-stimulated cells,
remains bound to kelch-like ECH-associated protein
1 (Keap1), forming an inactive complex20. When
entering the cell, SFN may interact with Keap1 and
disrupt the binding between Nrf2 and Keap1, which
allows for Nrf2 activation and nuclear translocation21.
In the nucleus, Nrf2 binds to the antioxidant response
element (ARE), a DNA promoter region of genes co-
difying antioxidant enzymes, such as NADPH quinone
oxidoreductase (NQO1), heme-oxygenase-1 (HO-1),
thioredoxin, and superoxide dismutase8,22. Increased
transcription of Nrf2 target genes leads to a strong
cytoprotective response, which increases resistance to
carcinogenesis and to other diseases whose pathophy-
005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 560 07/01/15 21:24
Nutr Hosp. 2015;31(2):559-569Clinical and molecular evidence of the
consumption of broccoli, glucoraphanin
and sulforaphane in humans
siology involves oxidative stress6,20. Additionally, with
Nrf2 activation, SFN increases the activity of phase
II enzymes involved in the elimination of xenobiotic
compounds, such as glutathione S-transferase (GST)
and quinone reductase23.
Several studies have shown the protective effect of
SFN against insults and diseases, most of the times
using animal models and cell cultures. In view of the
above, the present review aimed to investigate eviden-
ce already documented in human intervention studies
with broccoli, GRA and SFN.
This systematic review was performed using a pre-
determined protocol established according to the re-
commendations of the Cochrane Manual24, and results
were presented according to the criteria defined in the
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement25.
The review included clinical trials, controlled cli-
nical trials, and randomized clinical trials (RCTs) on
the possible effects of the consumption of broccoli,
GRA or SFN on humans that were published in Engli-
sh after 2003. Research was conducted on the PubMed
and Virtual Health Library (VHL) electronic databa-
ses from September to November 2013 and consis-
ted of searching on article titles and abstracts for the
following descriptors: “broccoli” or “glucoraphanin”
or “sulforaphane”. In addition, one study was inde-
pendently included due to its relevance. Outcomes
of interest were clinical and molecular parameters of
cell damage in study participants. The content, absorp-
tion, metabolism, and excretion of SFN metabolites
were not considered outcomes of interest. Similarly,
this review did not include studies conducted but not
published, abstracts from scientific events (whether
published or not), theses, and dissertations. It was es-
tablished that the intervention should exclusively use
broccoli, GRA or SFN in at least one group, in order
to assess their isolated effects. The articles identified
underwent a blinded independent evaluation by two
authors of the present manuscript (AC and FF). Disa-
greements with regard to inclusion in the study were
resolved by a third investigator (CGS).
Seventeen articles were selected, based on the com-
bination of the abovementioned descriptors and filters.
The degree of agreement between reviewers was rated
at κ= 1.0. The flow chart of study selection is shown
in figure 1. The impact factor of the selected journals
ranged from 1.257 to 6.504, with most of them (65%)
showing values above 3.0. The year of publication
ranged from 2004 to 2013, with most articles being
published in 2012.
Mean sample size was 48±44 individuals, and mean
intervention time was 41±86 days. The predominant
intervention included broccoli sprouts, used in their
powdered (29% of the studies), fresh (18%), and ho-
mogenized (0.6%) forms or in the form of infusions
or beverage (12%), totaling 11 studies. The other six
studies used broccoli commercially cultivated or te-
chnologically developed to have high levels of GSL
when cooked, raw, or prepared in soups. Study sam-
ples comprised healthy individuals, smokers or nons-
mokers, individuals at risk for the development of
cardiovascular diseases or cancer, and patients under
oncologic follow-up, with type 2 diabetes, or infected
with Helicobacter pylori (H. Pylori).
The results of the search are shown in table I. For a
better understanding of the results, they were grouped
into the three categories below, according to the main
outcomes of the studies.
Type 2 diabetes and cardiovascular diseases -
clinical parameters
Four studies analyzed the effects of broccoli intake
on diabetes parameters in patients with type 2 diabetes
mellitus (DM2)26-29. All studies performed the same in-
tervention: consumption of 5 or 10 g of broccoli sprout
Fig. 1.—Flow chart of study selection.
Articles found in a
search on PubMed and
VHL databases sources
(n = 8112)
Additional articles
identified through other
Articles after the application of filters:
Randomized Clinical Trial, Clinical Trial,
or Controlled Clinical Trial (n = 184)
(n = 7929)
Studies included for
qualitative synthesis
(n = 65)
Articles excluded:
Not conducted in humans
included Published before
2003 (n=76)
Written in languages other
than English (n=5)
Duplicates (n = 27)
according to
outcomes of
(n = 65)
Articles excluded after
of the reading of their
(n = 48)
005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 561 07/01/15 21:24
562 Nutr Hosp. 2015;31(2):559-569 Adriana Conzatti et al.
Table I
Studies that assessed the effect of the intake of broccoli, GRA and SFN on clinical and molecular parameters
in humans
and year Type of study
and sample Intervention Parameters
evaluated Results
Bahadoran et
al.(2012)26 Double-blind RCT
with type 2 diabetes
patients (n=63)
5 or 10 g/day broc-
coli sprout powder
containing nearly
22.5 μmol/g SFN vs.
placebo (corn starch
stained with chloro-
phyll) for 4 weeks
Fasting blood glu-
cose, plasma insulin
concentration, insulin
sensitivity (fasting blood
glucose/insulin), insulin
resistance (HOMA-IR
Decreased fasting blood glucose in both
intervention groups compared with base-
line values. Decreased insulin concen-
tration and HOMA-IR index only in the
group that received 10 g in comparison
with the placebo group. There was no
difference in the index of insulin sensiti-
vity in both intervention groups.
Mirmiran et
al. (2012)27 Double-blind RCT
with type 2 diabetes
patients (n=63)
5 or 10 g/day broc-
coli sprout powder
containing nearly
22.5 μmol/g SFN vs.
placebo (corn starch
stained with chloro-
phyll) for 4 weeks
Fasting blood glucose,
serum C-reactive protein
concentration, IL-6,
Decreased fasting blood glucose and
C-reactive protein in both intervention
groups compared with baseline values.
Non-significant decrease in IL-6 and
TNF-α levels in both intervention
groups compared with baseline.
Decreased C-reactive protein and IL-6
levels in the group that received 10 g/
day in comparison with the placebo
Bahadoran et
al. (2012)28 Double-blind RCT
with type 2 diabetes
patients (n=72)
5 or 10 g/day broc-
coli sprout powder
containing nearly
22.5 μmol/g SFN vs.
placebo (corn starch
stained with chloro-
phyll) for 4 weeks
Fasting blood glucose,
TC, TG, LDL, HDL, and
oxidized LDL, oxidi-
zed LDL/LDL ratio,
atherogenic index of
plasma (log TG/HDL),
TC/HDL ratio, and LDL/
HDL ratio
Decreased fasting blood glucose, TC,
and LDL levels in both intervention
groups compared with baseline values.
Decreased TG levels, oxidized LDL/
LDL ratio and atherogenic index of
plasma with the consumption of 10 g of
broccoli sprouts compared with baseli
ne values. Decreased HDL levels in
comparison with baseline only in place-
bo group and in the intervention group
that received 5 g of broccoli sprouts; in
the group that consumed 10 g of sprouts,
the HDL concentration remained the
same; no changes in the remaining
Bahadoran et
al. (2011)29 Double-blind RCT
with type 2 diabetes
patients (n=63)
5 or 10 g/day broc-
coli sprout powder
containing nearly
22.5 μmol/g SFN vs.
placebo (corn starch
stained with chloro-
phyll) for 4 weeks
Oxidative stress pa-
rameters (serum total
antioxidant capacity,
total oxidant status,
oxidative stress index,
serum malondialdehyde
concentration, and oxidi-
zed LDL)
Decreased malondialdehyde concentra-
tion and increased total antioxidant ca-
pacity with both interventions compared
with placebo. Decreased oxidized LDL
and oxidative stress index with both
interventions compared with baseline
values. No effect was found on total
oxidant status.
Armah et al.
(2013)30 RCT with indivi-
duals with moderate
risk for the develo-
pment of cardio-
vascular diseases
400 g high-GSL
broccoli (21.6
μmol/g GRA) vs.
400 g standard
broccoli (6.9 μmol/g
GRA) vs. 400 g
steamed peas/week
for 12 weeks
Systolic and diastolic
blood pressure, TC,
HDL, LDL, oxidized
C-reactive protein,
pulse wave velocity, and
arterial pulse stiffness
assessed by the augmen-
tation index
No changes in any of the parameters
sen et al.
RCT with hyperten-
sive patients
10 g/day brocco-
li sprout powder
containing nearly
30.3 μmol/g GRA
vs. usual diet for 4
Blood pressure, endo-
thelial function (flow
mediated dilation), TC,
No significant changes were observed in
the parameters assessed.
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Nutr Hosp. 2015;31(2):559-569Clinical and molecular evidence of the
consumption of broccoli, glucoraphanin
and sulforaphane in humans
Table I (cont.)
Studies that assessed the effect of the intake of broccoli, GRA and SFN on clinical and molecular parameters
in humans
and year Type of study
and sample Intervention Parameters
evaluated Results
ma et al.
Pilot study with
healthy individuals
100 g/day fresh
broccoli sprouts for
7 days
uric acid , urea, aspartate
aminotransferase, ala-
nine aminotranferease,
ferase, natural killer
cell activity, plasma
amino acid concentra-
tion (total, essential,
branched-chain, glycine,
cystine, and glutamate)
and oxidative stress
markers (plasma
PCOOH concentration,
CoQ10H2/CoQ10 ratio,
urinary 8-isoprostane,
urinary 8-OHdG)
Decreased TC and LDL levels in men
and increased HDL levels in women
compared with baseline levels.
Increased plasma concentration of the
amino acid cystine and no changes in
the remaining amino acids.
Decreased plasma PCOOH concentra-
tion, increased CoQ10H2/CoQ10 ratio,
decreased urinary 8-isoprostane and uri-
nary 8-OHdG compared with baseline.
No changes in the remaining parameters
Kensler et al.
(2012)33 Crossover RCT
with individuals
from a community
with a high inciden-
ce of hepatocellular
carcinoma (n=50)
Beverages made
with lyophilized
broccoli sprouts
diluted with mango
juice and containing
800 μmol GRA or
150 μmol SFN/day juice for
7 days
Urinary excretion of me-
tabolites from airborne
pollutants (mercaptu-
ric acids of acrolein,
crotonaldehyde, ethylene
oxide and benzene)
Increased levels of excretion of gluta-
thione-derived conjugates of acrolein,
crotonaldehyde and benzene compared
with pre-treatment values in individuals
who received beverages containing SFN
or GRA. No differences were observed
between the effects of SFR and GRA.
Riso et al.
(2010)34 Crossover RCT
with adult smokers
250 g/day steamed
broccoli vs.usual
diet without crucife-
rous vegetables for
10 days
DNA damage and repair
biomarkers Decreased DNA oxidation in blood
mononuclear cells compared with
pre-treatment values. Increased resistan-
ce to H(2)O(2)-induced DNA
strand breaks compared with pre-treat-
ment. No changes either in the activity
of the repair enzyme OGG1 or in the
expression levels of the enzymes OGG1,
nucleoside diphosphate linked moiety
X-type motif 1, and heme-oxygenase 1
Riso et al.
(2009)35 Crossover RCT of
adult smokers and
nonsmokers (n=20)
200 g/day steamed
broccoli vs. usual
diet without crucife-
rous vegetables for
10 days
Biomarkers of endo-
genous oxidative DNA
damage, biomarkers of
cancer risk (HDAC acti-
vity) in lymphocytes,
serum IGF-1 levels.
Decreased oxidized DNA bases in
smokers compared with baseline values.
Increased resistance to H(2)O(2)-indu-
ced DNA strand breaks compared with
pre-treatment in smokers and nons-
mokers. No changes in HDAC activity
or in serum IGF-1 levels.
Riedl et al.
(2009)36 Dose escalation cli-
nical trial of healthy
individuals (n=57)
25, 100, 125, 150,
175 or 200 g of ho-
mogenized broccoli
sprouts containing
nearly 0.283 μmol/
ml SFN vs. 200 g
alfafa sprouts for 3
Expression of phase II
antioxidant enzymes
ferase M1, glutathio-
ne-S-transferase P1,
NADPH quinone
oxidoreductase, and
HO-1) in nasal lavage
Dose-dependent increase in enzyme
expression, with maximal enzyme
induction observed with the intake of
200 g of broccoli sprouts compared with
baseline. Increased enzyme expression
with the intake of 200 g of broccoli
sprouts compared with control.
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564 Nutr Hosp. 2015;31(2):559-569 Adriana Conzatti et al.
Table I (cont.)
Studies that assessed the effect of the intake of broccoli, GRA and SFN on clinical and molecular parameters
in humans
and year Type of study
and sample Intervention Parameters
evaluated Results
Traka et al.
(2008)37 RCT with adult and
elderly men under
urologic follow-up
400 g of cooked
broccoli vs. 400 g of
cooked peas/ week
following usual diet
for 12 months
Markers of prostate
growth (PSA) and sig-
naling pathways of cell
proliferation for prostate
No difference in PSA levels between the
groups before and after treatment. Mo-
dulation of cell proliferation pathways
reduced the chance of tumorigenesis
Gasper et al.
(2007)38 Crossover RCT
with healthy indivi-
duals (n=16)
A single 150-ml dose
of soup made with
standard broccoli
or with high-GSL
broccoli containing
retrospectively 682.6
μmol/L and 2295.9
μmol/L of SFN, vs.
Expression of genes
related to xenobiotic me-
tabolism and cell cycle
control in gastric mucosa
Up-regulation of xenobiotic metaboli-
zing genes, including thioredoxin reduc-
tase, aldoketoreductases, and glutamate
cysteine ligase modifier subunit in the
group that consumed high-GSL broccoli
compared with baseline.
Suppressed expression in four genes
(nuclear receptor subfamily 1 group D
member 2, MAX 1 dimerization protein,
thyrotroph embryonic factor, and basic
helix-loop-helix domain class B2) in
both groups who consumed broccoli
Hakooz and
Pilot study with
healthy individuals
500 g of raw broc-
coli vs. 500 g of
cooked broccoli for
6 days
Activity of cytochrome
P450 enzymes (CYP2A6
and CYP1A2) related to
xenobiotic metabolism
Increased CYP2A6 and CYP1A2 activi-
ty compared with baseline.
Kensler et al.
(2005)40 RCT with indi-
viduals from a
community with a
high incidence of
hepatocellular carci-
noma (n=200)
125 ml of an
infusion of broccoli
sprouts containing
400 μmol of GRA
vs. placebo for 2
Excretion of carcinogen
biomarkers (urinary afla-
toxin and metabolites of
trans, anti-phenanthrene
tetraol polycystic aroma-
tic hydrocarbons [trans,
Although urinary levels did not differ
between the groups at the end of
the treatment, there was an inverse
correlation between dithiocarbama-
te concentrations (marker of SFN
excretion) and aflatoxin-N7-guanine
and trans, anti-PheT in the intervention
Galan et al.
(2004)41 Pilot study with
adults infected with
H. pylori (n=9)
Broccoli sprouts (14,
28 or 56 g)
twice daily for 7
Biomarkers of H. pylori
colonization (HpSA and
Seven of the nine patients were negative
for HpSA after 7 days (the tree patients
from the 14 g group, two from the 28 g
group, and two 56 g group)
and six remained negative after 35 days
(the tree patients from the 14 g group,
one from the 28 g group, and two from
the 56 g group). UBT was performed
in six patients, with negative results in
two of them. H. pylori eradication was
observed in one patient from each of the
three groups (14, 28 and 56 g broccoli
Yanaka et al.
(2009)42 Pilot study with
adults infected with
H. pylori (n=48)
70 g/day of broccoli
sprouts containing
nearly 6 μmol/g of
GRA (420 μmol
GRA/portion) vs. al-
fafa sprouts (control)
for 8 weeks
Biomarkers of H. pylori
colonization (HpSA,
UBT) and biomarkers
of gastric inflammation
(serum PGI e PGII
concentrations, PGI/
PGII ratio)
Reduced serum PGI and PGII con-
centrations, increased PGI/PGII ratio,
decreased HpSA and UBT values in
comparison with baseline values. No
differences compared with the control
group. The levels returned to baseline
values after 2 months.
RCT: randomized clinical trial; SFN: sulforaphane; GRA: glucoraphanin; GLS: glucosinolate; TC: total cholesterol; TG: triglycerides;
LDL: low-density lipoprotein; HDL: high-density lipoprotein; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; HOMA-IR:
Homeostatic Model Assessment for Insulin Resistance; OGG1: HO-1:heme-oxygenase 1; HpSA: H. pylori stool antigen; UBT: urea breath
test; PGI: pepsinogen I; PGII: pepsinogen II; HDAC: histone deacetylase; IGF-1: insulin-like growth factor-1; PSA: prostate-specific
antigen; PCOOH: phosphatidylcholine hydroperoxide; CoQ10H2: reduced form of coenzyme Q10; CoQ10: coenzyme Q10; 8-OHdG:
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Nutr Hosp. 2015;31(2):559-569Clinical and molecular evidence of the
consumption of broccoli, glucoraphanin
and sulforaphane in humans
powder vs. corn starch stained with chlorophyll (pla-
cebo) for 4 weeks. The number of participants ranged
from 63 to 72 (mean age 51.8±6.5 years).
In three of the studies that measured fasting blood
glucose, there was a significant mean decrease of
30.34±11.94 mg/dl in this parameter after interven-
tions as compared with baseline values26-28, and one
of the studies29 found a significant decrease of 62 mg/
dl only in the group that consumed 10 g of broccoli
sprout powder per day. Only one study measured insu-
lin concentration and the Homeostatic Model Assess-
ment for Insulin Resistance (HOMA IR) index, which
decreased respectively from 5.2±4.11 to 4.35±3.11
mU/l and from 2.21±2.04 to 1.55±1.32 in comparison
with baseline values (p<0.05) with the intake of 10 g
of broccoli sprouts26.
One study evaluated patients’ complete lipid profile
(total cholesterol [TC], low-density lipoprotein [LDL],
high-density lipoprotein [HDL], and triglycerides [TG])
and found a decrease in TC and LDL levels after both
interventions as compared with baseline. However, the-
re was an increase in HDL and a decrease in TG only in
the group that consumed 10 g of broccoli sprouts28.
Only one of the studies evaluated the inflammation
parameters interleukin-6 (IL-6), C-reactive protein
(CRP), and tumor necrosis factor a (TNF-a). Although
there was a decrease in these parameters in both inter-
vention groups compared with baseline (2.81 vs. 2.74
pg/ml; 3.33 vs. 2.38 ng/ml; 13.53 vs. 11.8 pg/ml in the
group that received 10 g of broccoli sprouts, and 3.99
vs. 3.59 pg/ml; 4.37 vs. 3.24 ng/ml; 13.08 vs. 10.38 pg/
ml in the group that received 5 g of broccoli sprouts,
respectively), only CRP reached statistical significan-
ce (p<0.05), which occurred also when the group that
received 10 g was compared with the placebo group27.
Similarly, only one study evaluated oxidative stress
parameters, finding a decrease of 18% in lipid peroxida-
tion and an increase of 14% in total antioxidant capacity
in both intervention groups as compared with the place-
bo group (p<0.01). There was also a decrease of 14% in
the oxidative stress index with the consumption of 10 g
of broccoli sprouts and of 8% with the consumption of 5
g in comparison with baseline values (p<0.01)29.
Five studies analyzed cardiovascular disease (CVD)
parameters28-32. Two of them were conducted with dia-
betic patients28,29, one with individuals with moderate
risk for CVD30, one with hypertensive individuals31,
and one with healthy individuals32. The interventions
used were 400g of high-GSL broccoli vs. 400g of stan-
dard broccoli vs. 400g of peas (control)30, 5 or 10 g
broccoli sprout powder vs. corn starch stained with
chlorophyll (placebo)28,29, 10 g of broccoli sprout pow-
der + usual diet vs. usual diet31, or 100g of fresh broc-
coli sprouts/day32. The follow-up time ranged from 7
days to 12 weeks, and the number of participants ran-
ged from 12 to 72.
As for the studies with diabetic patients, one of them
evaluated patients’ complete lipid profile, as previous-
ly described, in addition to oxidized LDL, oxidized
LDL/LDL ratio, atherogenic index of plasma, TC/
HDL ratio, and LDL/HDL ratio28, while the other one
evaluated only oxidized LDL29, which decreased only
in the group that received 10 g of broccoli sprouts as
compared with baseline (5%) (p<0.05). Similarly, only
this intervention was able to decrease oxidized LDL/
LDL ratio (from 3.16 to 2.63) and the atherogenic in-
dex of plasma (0.049 to 0.041) in comparison with ini-
tial values (p<0.05)28.
The studies with individuals with moderate risk for
CVD and with hypertensive individuals30,31 measured
blood pressure and lipid profile and did not find any
change in these parameters after interventions. One of
these studies also measured oxidized LDL, CRP, pul-
se wave velocity, and arterial pulse stiffness assessed
by the augmentation index30, while the other also me-
asured flow mediated dilation31, and no changes were
observed in these variables as well.
The study with healthy individuals evaluated their
complete lipid profile and found a decrease in TC and
LDL levels (from 178±25 to 160±28 mg/dl and from
94±22 to 75±40 mg/dl respectively) in males and an
increase in HDL levels (7%) in females as compared
with baseline values (p<0.05)32.
Most results in this category point out to an im-
provement in the parameters assessed in intervention
groups from baseline to the end of intervention, but
few differences were found between these groups and
control or placebo groups.
Toxicity, oxidant/antioxidant response, and cancer
This review found nine studies analyzing broccoli
intake with regard to parameters related to toxicity,
oxidant/antioxidant response, and cancer develop-
ment32-40. Participants selected for these studies in-
cluded communities with a high incidence of hepa-
tocellular carcinoma33,40, smokers34,35, nonsmokers35,
patients under urologic follow-up37, and healthy in-
dividuals36,38,39. The interventions used were the fo-
llowing: beverage containing lyophilized broccoli
sprouts + mango juice vs. mango juice (placebo)33,
steamed broccoli (250 or 200g) vs. usual diet without
cruciferous vegetables34,35, homogenized broccoli
sprouts vs. alfafa sprouts (control)36, cooked broccoli
(400g) vs. cooked peas (control)37, standard broccoli
soup vs. high-GSL broccoli soup vs. water38, raw broc-
coli vs. steamed broccoli39, infusion containing broc-
coli sprouts vs. placebo infusion40. The follow-up time
ranged from 6 hours to 12 months, sample size ranged
from 10 to 200 individuals, participants’ age ranged
from 18 to 70 years, and the majority of subjects were
female (55%).
One of the studies measured urinary excretion of
metabolites of airborne pollutants derived from acro-
lein, crotonaldehyde and benzene, and observed an in-
crease of respectively 36%, 17% and 62% in urinary
excretion of these metabolites compared with their
005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 565 07/01/15 21:24
566 Nutr Hosp. 2015;31(2):559-569 Adriana Conzatti et al.
pre-treatment values in groups receiving GRA or SFN,
with no differences in the potential for increased ex-
cretion between GRA and SFN33.
Two studies evaluated biomarkers of cancer risk and
of DNA damage and repair; both of them found a de-
crease in DNA oxidation (mean of 42%) and an increa-
se in the resistance to DNA breaks (22%) compared
with baseline, although no changes were observed in
the activity of damage or repair enzymes34,35.
Two studies investigated cellular redox state through
the expression or activity of antioxidant enzymes36 and
through oxidative stress markers32. The first study found
an increase in antioxidant defense due to a dose-depen-
dent increase in the expression of the enzymes gluta-
thione S-transferase M1 (GSTM1), glutathione S-trans-
ferase P1 (GSTP1), NQO1, and HO-1, with maximal
enzyme induction observed at the dose of 200g of
broccoli sprouts (increase of 119%, 101%, 199% and
121% compared with baseline values respectively).
An increase was also observed in comparison with the
control group (p<0.05)36. The other study evaluated the
oxidative stress markers phosphatidylcholine hydrope-
roxide, 8-isoprostane, and 8-hydroxydeoxyguanosine,
and found a decrease of 17%, 39% 25% respectively in
their levels and an increase of 50% in reduced/oxidized
coenzyme Q ratio compared with pre-intervention va-
lues (p<0.05). This study also evaluated the toxicity of
bioactive compounds from broccoli by assessing liver
function tests (transaminases), uric acid levels, urea le-
vels, and natural killer cell activity, and did not find any
difference in their values after treatment32.
One of the studies evaluated gene expression in
the gastric mucosa 6 hours after the intake of broc-
coli soup and found an increase in the expression of
genes involved in the metabolism of xenobiotics and
in antioxidant activity, such as thioredoxin reducta-
se38. Another study found an increase in the activity
of phase II enzymes (cytochrome P450) after the con-
sumption of 500g of broccoli, with CYP2A6 enzyme
activity increasing 48% in women and 216% in men,
and CYP1A2 enzyme activity increasing 32% in wo-
men and 148% in men compared with baseline values
Two other studies measured variables of cell growth
(prostate specific antigen [PSA] and insulin-like grow-
th factor-I [IGF-1]) and the pathways of cell prolife-
ration. These studies did not find any change in PSA
and IGF-1 levels but observed a modulation in proli-
feration pathways that reduced the chance of tumori-
Finally, one study evaluated urinary excretion of
carcinogen biomarkers present in foods and in the air.
Although these biomarkers did not differ between in-
tervention and placebo groups at the end of the treat-
ment, there was an inverse correlation between the
marker of SFN excretion and the carcinogen biomar-
kers aflatoxin-N(7)-guanine (R=0.31 and P=0.002)
and trans, anti- phenanthrene tetraol (PheT) (R= 0.39
and P=0.001) in the intervention group40.
In this category, only one study found differences
between the results from intervention and control
groups in only one of the parameters evaluated36. The
other studies observed an improvement in the results
from intervention groups only in comparison with
their own pre-treatment values.
Helicobacter pylori
The present review identified two studies that used
broccoli sprouts in the treatment of adults infected with
H. pylori, according to the following intervention plans:
14, 28 or 56g twice daily41 or 70g/day vs. alfafa sprouts
(control)42 for 7 days or 8 weeks, including 9 and 48
participants, respectively. Both studies evaluated the
following markers of H. pylori colonization: H. pylori
stool antigen (HpSA) and urea breath test (UBT).
One of the studies42 found a decrease in these pa-
rameters from baseline to 8 weeks after intervention
(p<0.05), but no difference was observed with regard
to the control group. This study also evaluated the
pepsinogen I (PGI)/pepsinogen II (PGII) ratio, which
increased during intervention, indicating reduced in-
flammation. None of the subjects showed negative
UBT results in any of the study periods; however, 32%
of intervention group subjects had HpSA levels below
the cutoff point at the end of the 8-week treatment. No-
netheless, 8 weeks after stopping the consumption of
broccoli sprouts, these values increased again in 75%
of the subjects.
Conversely, the other study41 found negative HpSA
results in seven of the nine patients (78%) after the
seven days of intervention and six remained negative
at day 35. Of these six patients, two showed negati-
ve UBT results at day 35. One of the patients with an
indeterminate UBT underwent gastric biopsy, which
showed negative results for H. pylori. The consump-
tion of broccoli sprouts was associated with the era-
dication of H. pylori in 33% of the patients, i.e., one
patient for each dosage group.
Data obtained in this review allowed to analyze
the consumption of broccoli in different forms and
amounts, indicating that the most consistent results
in humans are those related to the clinical parameters
blood glucose and lipid profile26-28,29,32 and to molecu-
lar parameters of oxidative stress29,32,34-36,38, either by
increasing antioxidant defenses or by decreasing insult
markers. The findings from the present study also in-
dicated that there was a decrease in low-grade chronic
inflammation27 and in H. pylori colonization41,42, as
well as a higher protection against cancer due to the
inhibition of tumorigenesis pathways37 or to the excre-
tion of potentially carcinogen metabolites33,40. Additio-
nally, two studies found that their treatment protocols
005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 566 07/01/15 21:24
Nutr Hosp. 2015;31(2):559-569Clinical and molecular evidence of the
consumption of broccoli, glucoraphanin
and sulforaphane in humans
did not have any effect on the parameters assessed30,31,
and the only study that evaluated toxicity parameters
after the consumption of broccoli did not observe any
change in this regard32.
The decrease in fasting blood glucose among
DM2 patients, which was found in four of the studies
analyzed here26-29, is one of the most relevant results
of this investigation. The only study to measure in-
sulin concentration and HOMA-IR index observed a
decrease in these parameters26. DM2 is a progressive
disease that requires a growing number of oral hypo-
glycemiant agents, which leads 50% of diabetic indi-
viduals to need exogenous insulin within a 10-year
period after disease onset43. The investigation of the
compounds that may help in the control of diabetes is
relevant, and the data obtained here suggest that SFN
should be considered a possible complementary treat-
ment to control diabetes and prevent its complications
in the long term and reinforce the recommendation to
consume cruciferous vegetables in our regular diet.
These results corroborate findings from animal mo-
dels, which observed higher glucose tolerance and
lower insulin resistance after the treatment with SFN44.
With regard to lipid profile, the studies analyzed in
this investigation found somewhat controversial results.
Three studies showed a decrease in TC, LDL, oxidi-
zed LDL, and TG levels and in the atherogenic index
of plasma and/or an increase in HDL levels28,29,32, while
two other studies did not observe any change in these
parameters after intervention30,31. However, due to the
methodological differences between the studies and to
the fact that the number of positive results was grea-
ter than that of negative results, the findings on lipid
profile may be considered relevant. Recent data from
our research group also showed a significant improve-
ment in lipid profile among diabetic rats treated with
SFN for 21 days (Souza et al., data not published). It
is known that changes in plasmatic lipids through SFN
result from its capacity to induce genes through Nrf2
and that this induction vary from individual to indivi-
dual and according to the time when it was measured
after SFN intake45. Nevertheless, the effects observed
in the present study are of potential interest and require
further investigation, since changes in lipid metabolism
are common in the general population, especially in dia-
betic patients, contributing to increased risk of CVDs,
which account for 60% of deaths in these patients and
are the main cause of mortality worldwide46.
Although clinical parameters are more palpable
health outcomes in terms of improvement in indivi-
duals’ prognosis, molecular parameters are also very
important, since they work by modulating aspects that
will present as clinical in the long term. In this sense,
nine of the studies found in this review focused on mo-
lecular parameters32,-40, both on increasing antioxidant
response29,32,36 and minimizing oxidative damage29,34,35,
although oxidative damage as measured in these stu-
dies had included different parameters (lipid peroxi-
dation, DNA damage, and quantification of reactive
species and urine metabolites of reactive species). It is
important to highlight that the improvement in antioxi-
dant response was limited to the increase in phase II
enzymes36,38 with no effect on DNA repair enzymes34,35.
The antioxidant action of SFN is very relevant in hu-
mans, since nearly 200 diseases have been associated
with oxidative stress, especially chronic non-com-
municable diseases47, which evidences the undenia-
ble role of reactive species in the pathophysiology of
these diseases. An association between molecular and
clinical parameters obtained in this study pointed out
that individuals with hyperglycemia showed increased
production of reactive species, which favors atheroge-
nesis by stimulating LDL oxidation, a response similar
to that of euglycemic individuals exposed to oxidative
stress48,49. Therefore, it is possible to believe that in-
dividuals who had their clinical parameters measured
could show an improvement in molecular parameters
as well, and vice versa.
It is also important to comment on the following fin-
dings: the anti-inflammatory effect of SFN resulting
from the decrease in IL-6, PCR e TNF-a levels, which
were evaluated in only one study27; the modulation
of the pathways of cell proliferation, which leads to a
lower stimulation of tumorigenesis and was evalua-
ted by one study37; the increased excretion of airbor-
ne pollutants and toxic metabolites coming from the
diet33,40; and the decrease in H. pylori colonization41,42.
With regard to anti-inflammatory mechanisms and de-
creased tumorigenesis, SFN is believed to inhibit cell
signaling pathways, e.g., nuclear factor kappa-B (NF-
kB) inflammatory pathway, through Nrf2 or through
the increase in phase II enzymes, which have been
classically described as participating in the stimulation
of tumorigenesis. However, although Nrf2 is the best
described mechanism of action of SFN, its effects can-
not be attributed only to this pathway. Agyeman et al.50
compared gene expression modulated by SFN in Keap1
knockdown cells and found that only 14% of the genes
modulated by SFN were similarly modulated by Keap1
knockdown, which indicates that most SFN-regulated
genes appear not to be regulated through the Keap1/
Nrf2 pathway. Conversely, the increased excretion of
carcinogenic metabolites in urine is possibly related to
the high detoxification capacity of SFN, due to the hi-
gher elimination of mercapturic acids through urine, a
pathway through which SFN is also eliminated51.
Although consistent epidemiological evidence as-
sociates the consumption of cruciferous vegetables
with a lower risk of cancer development, there were
few intervention studies on this topic in humans, with
the most convincing evidence about intervention co-
ming from two studies that evaluated H. pylori in-
fection41,42. H. pylori infections are common and may
cause gastroduodenal inflammation and peptic ulcer,
in addition to increasing the risk of gastric neoplasm.
Conventional treatment consists of triple therapy with
two antibiotics and proton-pump inhibitor. However,
eradication rates are far from ideal, possibly due to the
005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 567 07/01/15 21:24
568 Nutr Hosp. 2015;31(2):559-569 Adriana Conzatti et al.
increase in the number of antibiotic-resistant H. pylori
strains and to the several treatment side effects, such as
nausea, diarrhea, dyspepsia, headache, and changes in
gastrointestinal microflora. These problems point out
to the need of new strategies for H. pylori prevention
and eradication52, and the two studies found in this re-
view reinforce the bactericidal potential of SFN, sug-
gesting that it can be used in a possible diet therapy53.
The mechanism of SFN antibacterial activity is re-
lated to urease inactivation. The ability of H. pylori
to thrive in the unfavorable acid environment of the
stomach depends on the generation of great amounts
of the enzyme urease. Through the production of am-
monia from urea provided by the host, urease neutrali-
zes gastric acidity, promotes inflammation, and favors
H. pylori proliferation. Due to its ability to inactivate
urease, SFN could reduce gastric colonization and as-
sociated inflammation54. However, studies with longer
intervention times, a control group, and a larger sample
size may obtain better results and solidify them, since
one of the studies evaluated in this review showed a
great limitation in this regard41.
An important limitation for achieving result con-
sistency is the scarcity of studies on the same topics
or evaluating similar outcomes, in addition to the
variability in the parameters measured in each study
and to the heterogeneity in interventions, follow-up
times, and sample sizes. Not all studies determined
the amount of GRA or SFN present in the intervention
performed, which makes it difficult to draw a conclu-
sion about which dosage or concentration should be
recommended. Furthermore, the non-quantification of
cruciferous vegetable intake in the usual diet of study
subjects is also a limitation, since the frequent intake
of these vegetables may be an influencing factor in
the response to intervention, especially for those who
were already adapted to a greater intake of these foods.
There are potential benefits from broccoli consump-
tion with regard to clinical and molecular parameters
in humans, especially fasting blood glucose, lipid pro-
file, and oxidative stress, permeated by the intake of
GRA and SFN. However, evidence for these benefits
is still limited.
It is necessary to conduct more interventions studies
that are well controlled, less heterogenous, and that
analyze the dosage of these compounds of interest,
in order to evaluate outcomes more consistently and
reach better grounded conclusions.
The authors would like to thank Fundo de Incentivo
a Pesquisa e Eventos (FIPE) of Hospital de Clínicas de
Porto Alegre (HCPA) for its financial support.
Conflict of interest statement
The authors report no conflict of interest to disclo-
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005_7685 Clinical and Molecular Evidence of the Consumption of Broccoli Glucoraphanin.indd 569 07/01/15 21:24
... The vacuoles in the tissues of broccoli sprouts bear the glucosinolates which are spatially segregated from myrosinase enzyme present in myrosin cells, and on exposure to common processing practices such freezing, cooking, and cutting or human digestion, the inherent glucosinolates are exposed to myrosinase with a subsequent hydrolyses into other bioactives such as oxazolidines, epithionitriles, nitriles, thiocynates, and isothiocyanates; though this process could also be naturally initiated by the plant as a defense mechanism against abiotic and biotic stresses (Bohinc et al., 2012;Yang et al., 2016). The bioactive: 1-isothiocyanato-4-(methyl-sulfinyl) commonly referred to as Sulforaphane is a potential agent in prohibiting, retarding, or reversing the development of tumor precursors termed as prenoplastic lesions and also as therapeutic agents against cancer (Conzatti et al., 2015). It naturally induces the potentiality of phase II detoxification enzymes including quinone reductase and S-transferase in its mechanism for anticancer (Kwak et al., 2004). ...
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The employment of proteases directly from enzymes or indirectly from microorganisms during fermentation for the purpose of proteolysis of food proteins has been the conventional trend for the derivation of bioactive peptides from food matrices. However, recent studies have shown that inherent protease enzymes can be activated for this activity for vegetable foods using the sprouting process. The benefits of ease of operation, and reduced processing costs are formidable advantages for the optimal consideration of this technique. On another note, the demand for functional foods with therapeutic health effects has increased in recent years. Globally, plant foods are perceived as dietetic choices bearing sufficient quantities of concomitant nutraceuticals. In this manuscript, the sprouting route for the isolation of peptides and glucosinolates, and for the enhancement of total phenolic contents, polyunsaturated fatty acid profiles, and other bioactive constituents was explored. Advances regarding the phytochemical transformations in the course of sprouting, the therapeutic functionalities, and microbiological safety concerns of vegetable sprouts are delineated. In addition, consumption of vegetable sprouts has been shown to be more efficient in supplying nutraceutical components relative to their unsprouted counterparts. Biochemical mechanisms involving the inhibition of digestive enzymes such as α‐amylase, β‐glucosidase, and dipeptidyl peptidase IV (DPP‐IV), single electron transfer, and metal chelation, for impartation of health benefits, have been reported to occur from bioactive components isolated from vegetable sprouts. Practical applications Sprouting initiates proteolysis of vegetable proteins for the release of bioactive peptides. Abiotic stresses can be used as elicitors during the sprouting process to achieve enhanced phytochemical profiles of sprouts. Sprouting is a relatively more convenient approach to the improvement of the health benefits of vegetable foods. Vegetable sprouts are potential for the management of metabolic syndrome disorders.
... There is a growing body of literature on the therapeutic effects of cruciferous plants like broccoli largely attributed to their high content of glucosinolates. Broccoli is well known worldwide for its anti-cancer effects (10) and its antioxidant properties, which make it the finest natural active substance for scavenging free radicals (11,12), as an antigenotoxic agent (13), a reducer of fasting blood glucose in type 2 diabetes patients (14), a protection agent of the cardiovascular (15) and central nervous systems, against diabetic nephropathy and neuropathy (16), beneficial in the restoration of skin integrity (17), against Helicobacter pylori infection (18), and for the improvement of social interaction in patients with autism (19). ...
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Introduction: Broccoli (Brassica oleracea) is well known for its properties as an anticancer, antioxidant, and scavenger of free radicals. However, its benefits in enhancing spermatogenesis have not been well established. Objective: To study broccoli aqueous extract effects on sperm factors and the expression of genes Catsper1, Catsper2, Arl4a, Sox5, and Sox9 in sperm factors in mice. Material and methods: Male mice were divided randomly into six groups: (1) Control; (2) cadmium (3 mg/kg of mouse body weight); (3) orally treated with 200 μl broccoli aqueous extract (1 g ml-1); (4) orally treated with 400 μl of broccoli aqueous extract; (5) orally treated with 200 broccoli aqueous extract plus cadmium, and (6) orally treated with 400 μl of broccoli aqueous extract plus cadmium. We analyzed the sperms factors and Catsper1, Catsper2, Arl4a, Sox5, and Sox9 gene expression. Results: An obvious improvement in sperm count and a slight enhancement in sperm motility were observed in mice treated with broccoli extract alone or with cadmium. Sperm viability was reduced by broccoli extract except for the 200 μl dose with cadmium, which significantly increased it. Interestingly, Arl4a gene expression increased in the 400 μl broccoli-treated group. Likewise, the Arl4a mRNA level in mice treated with cadmium and 200 μl of broccoli extract was higher than in the cadmium-treated mice. Furthermore, broccoli extract enhanced the mRNA level of Catsper2 and Sox5 genes in mice treated with 200 μl and 400 μl broccoli extract plus cadmium compared with the group treated solely with cadmium. Conclusion: The higher sperm count in broccoli-treated mice opens the way for the development of pharmaceutical products for infertile men.
... SFN, along with several other phytochemicals, is known to induce Nrf2 thereby increasing the resistance to radicals and other reactive chemicals. It may interact with other molecular targets, and the mechanism of actions through Nrf2 are well described [23] . Chemical modification of the sensor cysteines of Kelch-like ECH-associated protein 1 (Keap1) by inducers such as SFN blocks the cycle of Keap1-dependent Nrf2 degradation [24] . ...
Visible impairments in skin appearance, as well as a subtle decline in its functionality at the molecular level, are hallmarks of skin aging. Activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-pathway, which is important in controlling inflammation and oxidative stress that occur during aging, can be triggered by sulforaphane (SFN), an isothiocyanate found in plants from the Brassicaceae family. This study aimed to assess the effects of SFN intake on age-related skin alterations. Male C57BL6 young (2 months) and old (21 months) mice were treated for 3 months with SFN diet (442.5 mg per kg) or control diet. The antioxidant capacities of the skin were increased in old SFN-treated animals as measured by mRNA levels of Nrf2 (p<0.001) and its target genes NQO1 (p<0.001) and HO1 (p<0.001). Protein expression for Nrf2 was also increased in old SFN fed animals (p<0.01), but not the protein expression of NQO1 or HO1. Additionally, ROS and MMP9 protein levels were significantly decreased (p<0.05) in old SFN fed animals. Histopathological analysis confirmed that there was no difference in epidermal thickness in old, when compared to young, SFN treated animals, while the dermal layer thickness was lower in old vs. young, treated animals (p<0.05). Moreover, collagen deposition was improved with SFN treatment in young (p<0.05) and structurally significantly improved in the old mice (p<0.001). SFN dietary supplementation therefore ameliorates skin aging through activation of the Nrf2-pathway.
... In HUVECs, allicin abrogated cell death against H 2 O 2 -mediated oxidative stress through PARP cleavage, reduced pro-caspase-3 levels, Bax expression, MDA, and incr eased SOD, NO release, and eNOS mRNA ( Table 1,2) (119). and iNOS (122,(128)(129)(130). Additionally, sulforaphane has been shown in HCD-fed rabbits to attenuate atherosclerotic lesion development due to its antioxidant and anti-inflammatory effects, together with a reduction in TC, LDL-C, LDH, CRP, and MDA. ...
Cardiovascular diseases are the leading cause of death in the world. Atherosclerosis is characterized by oxidized lipid deposition, and inflammation in the arterial wall and represents a significant problem in public health and medicine. Some dietary spices have been widely used in many countries; however, the mechanism of their action as it relates to the prevention and treatment of atherosclerosis is still poorly understood. In this review, we focus on the properties of various spice-derived active ingredients used in the prevention and treatment of atherosclerosis, as well as associated atherosclerotic risk factors. We provide a summary of the mechanisms of action, epidemiological analyses, and studies of various components of spice used in the clinic, animal models, and cell lines related to atherosclerosis. Most notably, we focused on mechanisms of action by which these spice-derived compounds elicit their lipid-lowering, anti-inflammatory, antioxidant, and immunomodulatory properties, as well as their involvement in selected biochemical and signal transduction pathways. It is suggested that future research should aim to design well-controlled clinical trials and more thoroughly investigate the role of spices and their active components in the prevention/treatment of atherosclerosis. Based on this literature review, it appears that spices and their active components are well tolerated and have few adverse side effects and, therefore, provide a promising adjunctive treatment strategy for patients with atherosclerosis.
Background 1-isothiocyanato-4-methyl-sulfonyl (SFN) butane is a naturally occurring compound from broccoli. Cisplatin (CP) reported has a standard chemotherapeutics agent. This study focused on the impact of SFN on cisplatin-induced testicular dysfunctions. Method Ninety adult-male Sprague-Dawley rats were randomly divided into nine groups of ten (n=10) rats each. Group A (control) received normal saline, group B received a single dose of 10 mg/kg CP (i.p.), group C received 50 mg/kg bwt of SFN, group D received 100 mg/kg bwt of SFN, group E received 10 mg/kg bwt CP and 50 mg/kg bwt of SFN, group F received 10 mg/kg bwt CP and 100 mg/kg bwt of SFN, group G received 10 mg/kg bwt CP and 50 mg/kg bwt vitamin C, group H received 50 mg/kg bwt of SFN and 10 mg/kg bwt CP, group I received 100 mg/kg bwt of SFN and 10 mg/kg bwt CP. The procedure lasted for 56 days. Testicular histology, and other parameters such as sperm, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (TT), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), inflammatory markers, Caspase 3, adrenal and steroidogenic enzymes and corticosterone were investigated. Results Cisplatin depleted the germ cells and arrest spermatogenesis; reduced the sperm quality, LH, FSH, TT, SOD, CAT, GPx, GSH, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenases and Jonhsen score (JS) and increased lipid peroxidation, IL-1β, TNF-α, IL-6, NF-ĸB, NO and iNOS, caspase-3, adrenal 3-HSD and corticosterone and damage score (DS). Treatment with SFN increased hormonal, antioxidant, and JS, and reduced lipid peroxidation, inflammatory makers, caspase-3, adrenal 3-HSD, and corticosterone and DS. Conclusion SFN thus provides protective effects against CP-induced testicular dysfunctions in rats.
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Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.
The immunity and system functions to fight against infections square measure considerably wedged by inappropriate food and nutrition. Long run deficiency disease is universally thought-about because the leading explanation for system deficiency. A considerable proportion of the worldwide population doesn't meet the counselled daily intake of nutrient. The COVID-19 pandemic has targeted attention on the role of the system, with health scientists and nutritionists urging folks to require supplements and/or eat specific foods (nutrients) to super-charge their immune systems. The system is that the most complicated system of physical structure. For this we have a tendency to needed the supplements like food for maintenance of this article here could be a discussion of foods like Citrus fruits like lemon, orange, lime etc., broccoli, spinach, turmeric, yoghurt, kiwi, garlic, papaya, almonds, ginger, tulsi, etc things helps in boosting our immunity to fight against infections. In this report, foods that helps in maintain system or immunity boosting material is mentioned.
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Sulforaphane (SFN), a naturally-occurring isothiocyanate enriched in cabbage and broccoli, has been provided as food supplements to improve weight management and reduce lipid levels. However, its effects on serum lipid profiles are contradictory. In this review, a meta-analysis and systematic review of SFN on lipid reduction and weight control is assessed with mice and rats fed on high-fat diet. The effects of SFN supplementation were evaluated by weighted mean difference (WMD) in body weight (BW), liver weight (LW) and also by its effect on serum lipids. A random-effects model was applied to estimate the overall summary effect. SFN reduced BW (WMD: − 2.76 g, 95% CI: − 4.19, − 1.34) and LW (WMD: − 0.93 g, 95% CI: − 1.63, − 0.23) significantly in our ten trials. Its effects on serum total cholesterol (TC) (WMD: − 15.62 mg/dL, 95% CI: − 24.07, − 7.18), low-density lipoprotein cholesterol (LDL-C) (WMD: − 8.35 mg/dL, 95% CI: − 15.47, − 1.24) and triglyceride (TG) (WMD: − 40.85 mg/dL, 95% CI: − 67.46, − 14.24) were significant except for high-density lipoprotein cholesterol (HDL-C) component (WMD: 1.05 mg/dL, 95% CI: − 3.44, 5.54). However, species, disease model, duration, SFN dosage as well as route of administration did not explain the heterogeneity among studies. In summary, these findings provide new insights concerning preclinical strategies for treating diseases including obesity, diabetes, hypertension, non-alcoholic fatty liver disease as well as cardiovascular disease with SFN supplements.
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Beside oil, oilseed rape (Brassica napus) seeds contains nutritional bioactives such as polyphenols and glucosinolates. However, to date their nutritional properties have been overlooked in the new “double zero” breeds. Seed alcoholic extracts from two B.napus cultivars most contrasting in their phytochemical contents as measured by mass-spectrometry were given to ob-mice. Biological outcomes including clinical metrics, gut and plasma metabolomes, liver transcriptome and metabolome were compared to ob-mice given a similar broccoli extract (Brassica oleracea). One B.napus extract induced a reduction of the oxidative stress indicated by the decrease of plasma isoprostanoids. This was associated to the regulation of the antioxidant stress defense Nrf2 pathway, to ‘omic’ oxidative stress functions, metabolic and cell process regulations, and the metabolomics microbiota profile. Extracts of B.napus seeds demonstrated health effects that may be improved by selecting appropriate agronomical traits, highlighting the potential benefits of better utilizing agronomy for improved human and animal nutrition.
Objectives: Sulforaphane, a major ingredient isolated from Brassica oleracea var. italica (broccoli), is known to exhibit anti-inflammatory, anti-cancer, and anti-diabetic effects. In this study, we employed an in vitro model of phorbol 12-myristate 13-acetate and a23187 (PMACI)-stimulated human mast cells (HMC-1 cells) to investigate the anti-allergic inflammatory effects and mechanisms of sulforaphane and Brassica oleracea var. italica extracts. Methods: Cytokine levels were measured by ELISA and quantitative real-time-PCR methods. Caspase-1 activity was determined by caspase-1 assay. Binding mode of sulforaphane within caspase-1 was determined by molecular docking simulation. Protein expression was determined by Western blotting. Results: Water extract of Brassica oleracea var. italica (WE) significantly reduced thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity on activated HMC-1 cells. In the molecular docking simulation and in vitro caspase-1 assays, sulforaphane regulated caspase-1 activity by docking with the identical binding site of caspase-1. Sulforaphane significantly inhibited the levels of inflammatory mediators including TSLP, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in a dose-dependent manner. Immunoblotting experiments revealed that sulforaphane and WE reduced translocation of NF-κBp65 into the nucleus and phosphorylation of IκBα in the cytosol. Furthermore, phosphorylation of mitogen-activated protein kinases (MAPK) was down-regulated by treatment with sulforaphane or WE. Conclusion: Our findings suggest that sulforaphane and WE have anti-allergic inflammatory effects by intercepting caspase-1/NF-κB/MAPKs signaling pathways.
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A wide variety of acute and chronic neurodegenerative diseases, including ischemic/traumatic brain injury, Alzheimer's disease, and Parkinson's disease, share common characteristics such as oxidative stress, misfolded proteins, excitotoxicity, inflammation, and neuronal loss. As no drugs are available to prevent the progression of these neurological disorders, intervention strategies using phytochemicals have been proposed as an alternative form of treatment. Among phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, has demonstrated neuroprotective effects in several in vitro and in vivo studies. In particular, evidence suggests that sulforaphane beneficial effects could be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway. Therefore, sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing neurodegeneration.
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Observational and experimental studies suggest that diets rich in cruciferous vegetables and glucosinolates may reduce the risk of cancer and cardiovascular disease (CVD). We tested the hypothesis that a 12-wk dietary intervention with high-glucoraphanin (HG) broccoli would modify biomarkers of CVD risk and plasma metabolite profiles to a greater extent than interventions with standard broccoli or peas. Subjects were randomly assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk and 347 plasma metabolites were quantified before and after the intervention. No significant differences in the effects of the diets on biomarkers of CVD risk were found. Multivariate analyses of plasma metabolites identified 2 discrete phenotypic responses to diet in individuals within the HG broccoli arm, differentiated by single nucleotide polymorphisms associated with the PAPOLG gene. Univariate analysis showed effects of sex (P < 0.001), PAPOLG genotype (P < 0.001), and PAPOLG genotype × diet (P < 0.001) on the plasma metabolic profile. In the HG broccoli arm, the consequence of the intervention was to reduce variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines between the 2 PAPOLG genotypes. The metabolic changes observed with the HG broccoli diet are consistent with a rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of fatty acid β-oxidation with TCA cycle activity. These modifications may contribute to the reduction in cancer risk associated with diets that are rich in cruciferous vegetables. This trial was registered at as NCT01114399.
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To do a systematic review and meta-analysis of studies comparing sequential therapy for eradication of Helicobacter pylori with pre-existing and new therapies, thus providing a glimpse of eradication success worldwide. Systematic review and meta-analysis. Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2013; abstract books of major European, American, and Asian gastroenterological meetings. Randomised controlled trials in previously untreated adults, in which sequential therapy was compared with a pre-existing or new therapy. 46 randomised controlled trials were reviewed and analysed. 5666 patients were randomised to sequential therapy and 7866 to other (established and new) treatments. The overall eradication rate of sequential therapy was 84.3% (95% confidence interval 82.1% to 86.4%). Sequential therapy was superior to seven day triple therapy (relative risk 1.21, 95% confidence interval 1.17 to 1.25; I(2)=29.3%; number needed to treat 6 , 95% confidence interval 5% to 7%), marginally superior to 10 day triple therapy (1.11, 1.04 to 1.19; I(2)= 67.2%; NNT 10, 7 to 15), but not superior to 14 day triple therapy (1.00, 0.94 to 1.06; I(2)=54.3%), bismuth based therapy (1.01, 0.95 to 1.06; I(2)=21.1%), and non-bismuth based therapy (0.99, 0.94 to 1.05; I(2)=52.3%). Data on eradication according to pre-treatment antimicrobial susceptibility testing were available in eight studies, and sequential therapy was able to eradicate 72.8% (61.6% to 82.8%) of the strains resistant to clarithromycin. Eradication rates with pre-existing and new therapies for H pylori are suboptimal. Regional monitoring of resistance rates should help to guide treatment, and new agents for treatment need to be developed.
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The lower incidences of many chronic diseases such as cancer and cardiovascular related ailments are associated with consumption of vegetables rich dietary regimes and this has been substantiated through numerous in vitro, pre-clinical and clinical investigations. Members of cruciferous family are cultivated and widely consumed universally as a part of daily diet. The major vegetables includes broccoli, cauliflower, radish, kale, brussels sprouts, watercress and cabbage that are used either fresh (salads), steamed or cooked. Besides nutritional components, these vegetables are also rich in health beneficial secondary metabolites, which include sulfur containing glucosinolates and S-methylcysteine sulfoxide, flavonoids, anthocyanins, coumarins, carotenoids, antioxidant enzymes, terpenes and other minor compounds. Based on the worldwide popularity and health benefits of these vegetables, this review provides collective information on nutritional and health benefits. In addition, information on evidence based therapeutic and prophylactic benefits of commonly used cruciferous vegetables are discussed with emphasis on cancer and cardiovascular disease. Some of the unique mechanisms of cancer inhibition such as effect on Nrf2, polymorphism, anti-inflammatory, inhibition of histone deacetylase activity and influence on estrogen metabolism are also included.
Little is known about the direct effect of broccoli sprouts on human health. So we investigated the effect of broccoli sprouts on the induction of various biochemical oxidative stress markers. Twelve healthy subjects (6 males and 6 females) consumed fresh broccoli sprouts (100 g/day) for 1 week for a phase 1 study. Before and after the treatment, biochemical examination was conducted and natural killer cell activity, plasma amino acids, plasma PCOOH (phosphatidylcholine hydroperoxide), the serum coenzyme Q10, 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 10H2/CoQ10 ratio. Only one week intake of broccoli sprouts improved cholesterol metabolism and decreased oxidative stress markers.
Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided.
Glucosinolates were evaluated in 5 groups and 65 accessions of Brassica oleracea (50 broccoli, 4 Brussels sprouts, 6 cabbage, 3 cauliflower, and 2 kale) grown under uniform cultural conditions. Glucosinolates and their concentrations varied among the different groups and within each group. The predominant glucosinolates in broccoli were 4-methylsulfinylbutyl glucosinolate (glucoraphanin), 3-butenyl glucosinolate (gluconapin), and 3-indolylmethyl glucosinoate (glucobrassicin). Glucoraphanin concentration in broccoli ranged from 0.8 mu mol g(-1) DW in EV6-1 to 21.7 mu mol g(-1) DW in Brigadier. Concentrations of the other glucosinolates in broccoli varied similarly over a wide range. In Brussels sprouts, cabbage, cauliflower, and kale, the predominant glucosinolates were sinigrin (8.9, 7.8, 9.3, and 10.4 mu mol g(-1) DW, respectively) and glucobrassicin (3.2, 0.9, 1.3, and 1.2 mu mol g(-1) DW, respectively). Brussels sprouts also had significant amounts of gluconapin (6.9 mu mol g(-1) DW). Wide variations in glucosinolate content among genotypes suggest differences in their health-promoting properties and the opportunity for enhancement of their levels through genetic manipulation.