broccoli

What is broccoli

Broccoli is an edible green plant in the cabbage family whose large flowering head is eaten as a vegetable. The word broccoli comes from the Italian plural of broccolo, which means “the flowering crest of a cabbage”, and is the diminutive form of brocco, meaning “small nail” or “sprout” 1). Broccoli is often boiled or steamed but may be eaten raw.

Broccoli is classified in the Italica cultivar group of the species Brassica oleracea. Broccoli has large flower heads, usually green in color, arranged in a tree-like structure branching out from a thick, edible stalk. The mass of flower heads is surrounded by leaves. Broccoli resembles cauliflower, which is a different cultivar group of the same species.

The promotion of health by a diet that is rich in Brassica vegetables like broccoli, including its association with a decreased risk of cardiovascular disease:

  • Lower risk of heart attack 2)
  • Reduce risk of stroke 3)
  • Cardiovascular disease risk reduction 4)
  • Lowers LDL “bad” cholesterol 5) and
  • a lower incidence in a wide variety of cancer types 6), including breast, lung 7), 8), prostate 9), and colorectal cancer 10), has been extensively reported in the literature. A diet of three to five servings per week is sufficient to decrease the risk of cancer development by ∼30%–40% 11).

Broccoli nutrition facts

As shown on the table 1, a 100 gram serving of raw broccoli provides 34 kcal and is an excellent source (20% or higher of the Daily Value, DV) of vitamin C and vitamin K. Raw broccoli also contains moderate amounts (10–19% DV) of several B vitamins and the dietary mineral manganese, whereas other essential nutrients are in low content. Broccoli has low content of carbohydrates, protein, fat, and dietary fiber.

Boiling broccoli reduces the levels of sulforaphane, with losses of 20–30% after five minutes, 40–50% after ten minutes, and 77% after thirty minutes. However, other preparation methods such as steaming, microwaving, and stir frying had no significant effect on the compounds 12).

Sulforaphane is a natural isothiocyanate derived from a glucosinolate found in cruciferous vegetables, especially broccoli 13). Sulforaphane has received a great deal of attention because of its ability to simultaneously modulate multiple cellular targets involved in cancer development, including 14):

  1. DNA protection by modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;
  2. Inhibition of cell proliferation and induction of apoptosis, thereby retarding or eliminating clonal expansion of initiated, transformed, and/or neoplastic cells;
  3. Inhibition of neoangiogenesis, progression of benign tumors to malignant tumors, and metastasis formation.

Sulforaphane is therefore able to prevent, delay, or reverse preneoplastic lesions, as well as to act on cancer cells as a therapeutic agent. Taking into account this evidence and its favorable toxicological profile, sulforaphane can be viewed as a conceptually promising agent in cancer prevention and/or therapy. Sulforaphane is the hydrolysis product of glucoraphanin, particularly high in the young sprouts of broccoli and cauliflower. Sulforaphane can also be obtained by eating cruciferous vegetables such as brussel sprouts, broccoli, cauliflower, bok choy, kale, collards, arugula, broccoli sprouts, chinese broccoli, broccoli raab, kohlrabi, mustard, turnip, radish, watercress and cabbage 15).

Broccoli also contains the carotenoid compounds lutein and zeaxanthin in amounts about 6 times lower than in kale.

Table 1. Broccoli nutrition facts

[Source: United States Department of Agriculture Agricultural Research Service 16)]

How to cook broccoli

Broccoli can be eaten raw, but blanching it quickly in boiling water helps give it a more crisp-tender texture and bring out its flavor. Broccoli can also be steamed, sautéed, and roasted. You could even throw long spears on the grill. To maintain the sulforaphane content of broccoli, it’s best broccoli are steamed for 4 to 5 minutes, until tender.

Benefits of broccoli

Epidemiological studies have revealed a particular inverse correlation between the intake of cruciferous vegetables and colorectal cancer risk; one stronger than that between the latter and the intake of other vegetables 17). Cruciferous vegetables refer to those of the Brassicaceae family and include broccoli, cabbage, and Brussel sprouts. Particular to this plant family are glucosinolates—a group of compounds endogenously synthesised and derived from glucose and amino acid residues. Upon the rupture of plant cells—such as occurs from the consumption of the vegetables or from parasitic attack—the glucosinolates are able to be hydrolysed by endogenous myrosinase enzymes. Intact plant tissue separates glucosinolates from myrosinase enzymes by compartmentalising the former in S-cells and the latter in myrosin cells. Only upon cell rupture are the myrosinase enzymes able to hydrolyse the glucosinolates. Several types of compound are potentially formed, including isothiocyanates, thiocyanates, and nitriles 18).

Isothiocyanates are to date the most-studied and best-characterised of known glucosinolate-hydrolysis-derived products in terms of their bioactivity. They are believed to play a defensive role in the plants via their cytotoxic effects on microorganisms and small parasitic animals, but to be directly beneficial to human health via broad anti-inflammatory and antioxidant effects, and thus are able to help inhibit the development of cancers 19), cardiovascular diseases 20), and osteoarthritis 21). Broccoli is particularly high in a particular glucosinolate called glucoraphanin, whose myrosinase-mediated hydrolysis generates an isothiocyanate called sulforaphane (1-isothiocyanato-4-(methylsulfinyl)butane), the structure of which is depicted in Figure 1.

A multitude of experiments in test tubes and in laboratory animals reportedly demonstrate the ability of sulforaphane to both defend healthy cells against chemical and/or radiation-induced carcinogenesis 22), 23), 24) and to inhibit the proliferation, migration, invasive potential and survival of tumour cells 25), 26), 27).

There are other glucosinolates and metabolites found in cruciferous vegetables which possess similar chemistry, metabolism, and anticancer effects as sulforaphane (eg. glucobrassicin- I3C, gluconasturtiin- phenethylisothiocyanate, glucoerucin-erucin (sulfide analog of sulforaphane), glucoiberin-iberin) 28). Also, there is a large body of research that has examined sulforaphane effects on many other cancers such as breast, hepatic, bladder, osteosarcoma, glioblastoma, leukemia, pancreatic, and melanoma. Although larger scale clinical trials are necessary, dietary sulforaphane shows promise as a safe and effective anti-cancer strategy that includes incorporating easily accessible foods into an individual’s regular diet.

Figure 1. Sulforaphane chemical structure

sulforaphane
[Source 29)]

To date very few human clinical trials have evaluated the effects of sulforaphane on cancer outcome, however, several pilot and phase 1 human sulforaphane trials have been conducted utilizing different sources of sulforaphane. The first study was a randomized, placebo-controlled, double-blind phase 1 clinical trial of healthy volunteers that used glucoraphanin or isothiocyanate as the sulforaphane source 30). The phase 1 trial consisted of three study groups; 25 µmol of glucosinolate, 100 µmol of glucosinolate, or 25 µmol isothiocyanate for 7 days and examined parameters of safety, tolerance, and pharmacokinetics. Importantly, there were no significant toxicities associated with taking the extracts at the doses employed. A second study was a randomized placebo-controlled chemoprevention trial performed in Qidong, People’s Republic of China which used a hot drinking water infused with 3-day old broccoli sprouts 31). Residents of Qidong are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of the airborne toxin phenanthrene. There was an inverse association for the excretion of dithiocarbamates and urinary aflatoxin-DNA adducts and trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene in the intervention arm. Thus, an inverse correlation between sulforaphane treatment and excretion of carcinogens was detected, suggesting induction of one or more phase 2 enzymes. Interestingly, in the Qidong trial, although there was consistency within an individual between doses, there was significant inter-individual variability in bioavailability of the dithiocarbamates. A third small preliminary human study interested in determining if the HDAC inhibition effects observed in cell culture and mice could be translated into humans was performed. After ingestion of 68g of broccoli sprouts, a significant decrease in histone deacetylase activity was evident in peripheral blood mononuclear cells with a concomitant increase in acetylated histones H3 and H4 32). The most recent pilot human study was performed in 8 healthy women who were undergoing elective reduction mammoplasty. Here the women were given an oral dose of broccoli sprout preparation containing 200 µmol sulforaphane 1 h prior to breast surgery. Mean epithelial-/stromal-enriched breast tissue dithiocarbamate concentration was 1.45±1.12 and 2.00±1.95 pmol/mg tissue for the right and left breast, respectively. NQO1 and HO-1 transcript levels were measured in both breasts of all subjects 33). These clinical trials provide the important link to human relevance for sulforaphane as a promising anticancer agent.

Although commercially available as a supplement, sulforaphane has yet to be FDA approved for the treatment of human disease, including cancer 34). However, the chemopreventive properties of sulforaphane, and its capacity to be selectively toxic to malignant cells and impart these effects through a number of mechanisms, provide rationale to completely elucidate and evaluate its potential as an anti-cancer compound alone, and in combination with clinically relevant therapeutic and management strategies.

Table 2. Summary of Human Clinical Trials on Sulforaphane in Progress or Recently Completed

Sulforaphane preparationSubject informationPhaseCurrent statusInformation/ResultsReference
BSE given 200 μmol orally once daily for 1 weekMale (<18 years) with recurrent prostate adenocarcinomaPhase IIActive, not recruitingTo determine: (1) therapeutic benefit, (2) safety profile, (3) pharmacokinetics, (4) pharmacodinamics)NCT01228084; clinicaltrials.gov
Four-week treatment with sulforaphane glucosinolate capsules (250 mg broccoli seed extract daily)Healthy male (21 years and older)Prostate cancer preventionRecruitingTo identify distribution of sulforaphane and HDAC inhibition in subjects at risk for prostate cancer (DNA methylation status and proliferation markers in -biopsy)NCT01265953; clinicaltrials.gov
14 day intervention of BSE consisting of a consistent dose of sulforaphane dissolved in mango juiceWoman (<18 years) with ductal carcinoma in situ (DCIS–breast)Phase IIRecruitingTo determine the therapeutic benefit (measure proliferative rate) of sulforaphane and evaluate the ability of sulforaphane to modulate specific cytoprotective enzymesNCT00982319; clinicaltrials.gov
BSE administered orally at 50, 100, or 200 μmol sulforaphane dailySubjects (<18 years) must have at least two atypical nevi before diagnosis of melanoma.Phase 0RecruitingTo determine (1) adverse effects (2) visual and cellular changes in atypical nevi, (3) biodistribution, and (4) effect of sulforaphane on STAT-1 and -3 expressionNCT01568996; clinicaltrials.gov
High sulforaphane BSE (100 μmol sulforaphane) every other day for 5 weeksMan (40–75 years) with low or intermediate grade prostate cancerPhase I and IIEnrolling by invitationTo identify biological effects of sulforaphane on normal prostate tissue, and determine whether the consumption of BSE will inhibit growth of prostate cancerNCT00946309; clinicaltrials.gov
Sulforaphane-containing BSE (topical application; 280 nmol daily)Woman (<18 years) with pathlogically confirmed invasive adenocarcinoma or ductal carcinoma in situ of the breastPhase IINot recruitingTo investigate the protective effects of topical sulforaphane on radiation-induced dermatitisNCT00894712; clinicaltrials.gov
BSE beverage:
600 μmol glucoraphanin, 40 μmol sulforaphane dissolved in 100 ml pinapple and lime juice daily for 84 days
Healthy subjects (21–65 years)Phase IICompletedTo assess the effect of sulforaphane treatment on level of air toxin mercapturic acid in urine.
BSE: 1.700 (1.235–2.386)
Placebo: 1.065 (0.686–1.826)
NOTE: no statistical analysis provided
No serious adverse effects reported
NCT01437501; clinicaltrials.gov
Consumption of two portions per week of standard broccoli, glucoraphanin-enriched broccoli, or a high glucoraphanin-enriched broccoli soup for 1 yearMan (18–80 years) with low or intermediate prostate cancerEnrolling by invitationTo assess the ability of sulforaphane to alter metabolism and gene expression within prostate tissue, and reduce the progression to aggressive cancerNCT01950143; clinicaltrials.gov
Glucoraphanin-rich BSE (800 mmol) or sulforaphane-rich BSE (150 mmol) daily for 7 days dissolved in 100 ml mango juiceHealthy subjects (25–65 years)Phase ICompletedStatistically significant increase of 20%–50% in the levels of excretion of glutathione-derived conjugates of carcinogens, including acrolein, crotonaldehyde, and benzene in individuals compared with preintervention baseline valuesNCT01008826; clinicaltrials.gov
(139)
Broccoli sprout grain capsule (90 mg sulforaphane) per day over 1 yearSubjects (<18 years) with advanced, surgically nontreatable pancreatic ductal adenocarcinomaNot yet open for recruitmentTo determine disease status and compound bioavailabilityNCT01879878; clinicaltrials.gov
BSE oral supplementation thrice daily for 2–8 weeksWoman (<21 years) who has undergone a diagnostic mammogramPhase IIActiveTo determine (1) bioavailability, (2) effect of supplement on biomarkers of prognosis, and (3) effect on HDAC inhibitionNCT00843167; clinicaltrials.gov
Stabilized synthetic sulforaphane compoundHealthy man (18–45 years)Phase ICompletedTo assess safety, tolerance, pharmacokinetics, and pharmacodynamics (NOTE: no data, has progressed further in human trials)NCT01948362; clinicaltrials.gov
Raw or cooked broccoli (200 g)Healthy subjects (22–50 years)Phase 0CompletedTo determine bioavailability after consumption through analysis of urinary biomarkers, and to assess the affect of preparation on metabolic fate (NOTE: no data, however extensive research has been published)NCT01743924; clinicaltrials.gov

BSE, broccoli sprout extract.

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