Cruciferous Vegetables

What are cruciferous vegetables

Cruciferous vegetables also called Brassica vegetables, is a member of the family of vegetables known to botanists as Cruciferae or alternatively Brassicaceae, that includes broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, kohlrabi, mustard, rutabaga, kale, garden cress, bok choy and turnips 1). Plants in the Cruciferae family have flowers with four equal-sized petals in the shape of a ‘crucifer’ cross. “Brassica” is the latin term for cabbage 2). These vegetables contain substances that may protect against cancer 3).

Like other vegetables, cruciferous vegetables contain a number of nutrients and phytochemicals with cancer chemopreventive properties, including several carotenoids (beta-carotene, lutein, zeaxanthin); vitamins C, E, and K; folate; chlorophyll and minerals. They also are a good fiber source.

In addition, cruciferous vegetables are unique in that they are rich sources of substances known as glucosinolates, which are sulfur-containing chemicals 4). These chemicals are responsible for the pungent aroma and bitter flavor of cruciferous vegetables. The hydrolysis of glucosinolates by the plant enzyme myrosinase results in the formation of biologically active compounds, including indoles and isothiocyanates (Figure 1) 5). More than 100 glucosinolates with unique hydrolysis products have been identified in plants. For example, broccoli is a good source of glucoraphanin, the glucosinolate precursor of sulforaphane and glucobrassicin, the precursor of indole-3-carbinol (I3C) 6). In contrast, watercress is a rich source of gluconasturtiin, the precursor of phenethyl isothiocyanate (PEITC). Table 1 lists some of the isothiocyanates and indoles that are currently under investigation for their cancer chemopreventive properties, along with their glucosinolate precursors.

Figure 1. Breakdown of glucosinolates

Breakdown of glucosinolates
[Source 7)]

Table 1. Some food sources of selected isothiocyanates and their glucosinolate precursors

food sources of selected isothiocyanates and their glucosinolate precursors
[Source 8)]

Cruciferous vegetables are part of a healthy diet. The federal government’s Dietary Guidelines for Americans 9) recommend consuming a variety of vegetables each day. Different vegetables are rich in different nutrients. The intake of cruciferous vegetables is highly variable in different populations 10). Asian and Middle Eastern populations have relatively high intakes (40–80 g/day) as compared with European ones (5.7–32.7 g/day) with an estimate in the Italian population of ∼11.5 g/day 11).

Vegetables are categorized into five subgroups: dark-green, red and orange, beans and peas (legumes), starchy, and other vegetables. Cruciferous vegetables fall into the “dark-green vegetables” category and the “other vegetables” category. More information about vegetables and diet, including how much of these foods should be eaten daily or weekly, is available from the U.S. Department of Agriculture website Choose My Plate 12).

During food preparation, chewing, and digestion, the glucosinolates in cruciferous vegetables are broken down to form biologically active compounds such as indoles, nitriles, thiocyanates, and isothiocyanates 13). Indole-3-carbinol (an indole) and sulforaphane (an isothiocyanate) have been most frequently examined for their anticancer effects.

Indoles and isothiocyanates have been found to inhibit the development of cancer in several organs in rats and mice, including the bladder, breast, colon, liver, lung, and stomach 14). Studies in animals and experiments with cells grown in the laboratory have identified several potential ways in which these compounds may help prevent cancer 15):

  • They help protect cells from DNA damage.
  • They help inactivate carcinogens.
  • They have antiviral and antibacterial effects.
  • They have anti-inflammatory effects.
  • They induce cell death (apoptosis).
  • They inhibit tumor blood vessel formation (angiogenesis) and tumor cell migration (needed for metastasis).

Studies in humans, however, have shown mixed results.

This study 16) confirms that cruciferous vegetables have a beneficial role on the risk of various common cancers, in particular, those of the upper digestive tract, colorectum, breast, and kidney. In that study 17), the inverse association with cruciferous vegetables was stronger in smokers than in nonsmokers in the absence, however, of significant heterogeneity. In a recent intervention study, smokers had a reduction in both endogenous and ex vivo-induced DNA damage following the regular intake of 250 g of steamed broccoli for 10 days, and this effect was particularly evident in subjects with glutathione-S-transferase (GST) M1-null genotype 18). Glutathione-S-transferases (GSTs) are involved in the metabolism of isothiocyanates (ITCs) and may modulate the effect of cruciferous vegetables on cancer risk 19). Other study results by the International Agency for Research on Cancer working group 20) and the results from a few subsequent publications showing that the intestine is among the cancer sites for which the evidence of a beneficial effect of cruciferous vegetables is more convincing 21)). Breast cancer has also been reported to be inversely related to cruciferous vegetables 22). Inverse relations for cancers of the oral cavity and esophagus have been reported in a few other (case–control) studies, although data for these neoplasms are limited 23); these cancers, however, have been consistently related to low vegetables consumption 24). Data are even scantier for kidney cancer 25). The absence of an inverse relation with gastric cancer in our data is somewhat in contrast with the results of previous studies suggesting a beneficial effect of cruciferous vegetables, although the issue remains open to discussion 26).

The beneficial effect of cruciferous vegetables on various common cancers may be due to their high content of several antioxidants and vitamins, including carotenoids, polyphenols, vitamin C, and folate 27). Moreover, they contain high levels of glucosinolates, whose major breakdown products (indoles and ITCs) have been shown—in in vitro and animal studies—to have high anticarcinogenic properties, particularly on cancers of the digestive tract, liver, lung, and breast 28). In cultured human cancer cells, ITCs can induce apoptosis and arrest of cell cycle that are critical processes in the prevention of tumor growth 29). Moreover, ITCs seem to inhibit histone deacetylase activity, which removes acetyl groups from histones, thus enabling transcription of tumor suppressor proteins that promote differentiation and apoptosis in precancerous cells 30). ITCs can also affect xenobiotic-metabolizing enzymes that are able to modulate the access of chemical carcinogens to DNA in target tissues 31). In particular, ITCs can modulate expression of phase II enzymes, while indoles act as bifunctional inducers of both phase I and phase II enzymes. This mechanism of action can explain the protection against numerous xenobiotics and carcinogens (e.g. those produced through tobacco smoke or cooked food mutagens), and it was demonstrated also in human colon cancer cell lines following the supplementation with ITCs and indoles where the induction of phase I and phase II enzymes was able to protect cells against benzo[a]pyrene-induced DNA damage 32). Indoles can also decrease estrogen receptor-α expression 33). Through this mechanism, estrogen-dependent signal transduction that results in breast cancer cell proliferation would be decreased, thus providing a molecular basis for the chemopreventive activity against breast cancer.

In summary, this large integrated series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancer sites. Promoting the intake of cruciferous vegetables in populations where consumption is comparably low should be considered 34).

Cruciferous vegetables list

Table 2. List of common cruciferous vegetables

Common name
Horseradish
Land cress
Ethiopian mustard
Kale
Collard greens
Chinese broccoli (gai-lan)
Cabbage
Savoy cabbage
Brussels sprouts
Kohlrabi
Broccoli
Broccoflower
Broccoli romanesco
Cauliflower
Wild broccoli
Bok choy
Komatsuna
Mizuna
Rapini (broccoli rabe)
Choy sum (Flowering cabbage)
Chinese cabbage, napa cabbage
Turnip root; greens
Rutabaga (swede)
Siberian kale
Canola/rapeseed
Wrapped heart mustard cabbage
Mustard seeds, brown; greens
White mustard seeds
Black mustard seeds
Tatsoi
Wild arugula
Arugula (rocket)
Field pepperweed
Maca
Garden cress
Watercress
Radish
Daikon
Wasabi

Cruciferous vegetables benefits

Like most other vegetables, cruciferous vegetables are good sources of a variety of nutrients and phytochemicals that may work synergistically to help prevent cancer 35). One challenge in studying the relationships between cruciferous vegetable intake and cancer risk in humans is separating the benefits of diets that are generally rich in vegetables from those that are specifically rich in cruciferous vegetables 36). An extensive review of epidemiologic studies published prior to 1996 reported that the majority (67%) of 87 case-control studies found an inverse association between some type of cruciferous vegetable intake and cancer risk 37). At that time, the inverse association appeared to be most consistent for cancers of the lung and digestive tract. The results of retrospective case-control studies are more likely to be distorted by bias in the selection of participants (cases and controls) and dietary recall than prospective cohort studies, which collect dietary information from participants before they are diagnosed with cancer 38). In the past decade, results of large prospective cohort studies and studies taking into account individual genetic variation suggest that the relationship between cruciferous vegetable intake and the risk of several types of cancer is more complex than previously thought.

Higher consumption of vegetables in general may protect against some diseases, including some types of cancer. However, when researchers try to distinguish cruciferous vegetables from other foods in the diet, it can be challenging to get clear results because study participants may have trouble remembering precisely what they ate. Also, people who eat cruciferous vegetables may be more likely than people who don’t to have other healthy behaviors that reduce disease risk. It is also possible that some people, because of their genetic background, metabolize dietary isothiocyanates differently. However, research has not yet revealed a specific group of people who, because of their genetics, benefit more than other people from eating cruciferous vegetables.

Researchers have investigated possible associations between intake of cruciferous vegetables and the risk of cancer. The evidence has been reviewed by various experts. Findings for lung, colorectal, breast and prostate cancer, which are the four major causes of cancer-related death in the US, are summarized next,

Prostate cancer

A growing number of epidemiological studies have drawn an association between cruciferous vegetable intake and decreased prostate cancer risk 39), 40). Further epidemiological analysis stratifying specifically on glucosinolate intake (a class of natural compounds produced by crucifers) identified a significant inverse trend with prostate cancer risk 41). Controlled experimentation with glucosinolate derivatives, such as sulforaphane and indole-3-carbinol (I3C), has characterized inhibitory and cytotoxic activity in prostate cancer cells and animal model systems and has provided a mechanistic explanation for how crucifers are causative in lowering cancer risk.

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Clinical prostate cancer incidence by nation however shows considerable variability. In general, Western nations tend to have a high incidence of prostate cancer, while Asian nations are characterized by a low incidence. In the USA, prostate cancer is predicted to account for 28.5% of all male cancer diagnoses in 2012, affecting over 240,000 men (154 per 100,000) 42), whereas the rate in Asian nations can be up to tenfold lower 43). Diet and lifestyle are thought to be primary contributors to the difference in prostate cancer rates between Western and Asian nations. The proposed influence of diet on prostate cancer rate is supported by studies showing convergence with Western prostate cancer rates in Asian immigrant communities in the USA 44). With regard to cruciferous vegetable intake, Asian nations tend to consume much higher amounts per person than Western nations 45), suggesting that crucifer intake may be an important diet and lifestyle factor contributing to differences in prostate cancer risk.

The cruciferous vegetable family (Brassicaceae) includes many vegetables that are found in the diet—from broccoli, Brussels sprouts, and cauliflower, that are common in the Western diet, to daikon, watercress, and bok choy that are more common in Asian cuisine. Cruciferous vegetables contain a number of glucosinolates whose presence and relative abundance are specific to each species and even to specific cultivars 46). Glucosinolates are the natural plant chemicals (phytochemicals) that give rise to bioactive species. They are cleaved by the endogenous plant enzyme myrosinase to yield active phytochemicals that possess varying degrees of anti-cancer activity. Two phytochemicals that have drawn a significant amount of attention are sulforaphane and I3C. In this review, we will highlight the ability of these phytochemicals to inhibit prostate cancer, focusing on their post-initiation suppressive activity.

Cohort studies in the Netherlands 47), United States 48), and Europe 49) have examined a wide range of daily cruciferous vegetable intakes and found little or no association with prostate cancer risk. However, some case-control studies have found that people who ate greater amounts of cruciferous vegetables had a lower risk of prostate cancer 50).

Colorectal cancer

A small clinical trial found that the consumption of 250 g/d (9 oz/d) of broccoli and 250 g/d of Brussels sprouts significantly increased the urinary excretion of a potential carcinogen found in well-done meat, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) 51). Walters et al. 52) concluded that high cruciferous vegetable intake might decrease colorectal cancer risk by enhancing the elimination of PhIP and related dietary heterocyclic amine carcinogens. Although a number of case-control studies conducted prior to 1990 found that people diagnosed with colorectal cancer were more likely to have lower intakes of various cruciferous vegetables than people without colorectal cancer 53), 54), most prospective cohort studies have not found significant inverse associations between cruciferous vegetable intake and the risk of developing colorectal cancer over time 55), 56), 57). Cohort studies in the United States and the Netherlands have generally found no association between cruciferous vegetable intake and colorectal cancer risk 58). One exception was a prospective study of Dutch adults, which found that men and women with the highest intakes of cruciferous vegetables (averaging 58 g/d) were significantly less likely to develop colon cancer than those with the lowest intakes (averaging 11 g/d) 59). Surprisingly, higher intakes of cruciferous vegetables were associated with increased risk of rectal cancer in women in that study 60). As with lung cancer, the relationship between cruciferous vegetable consumption and colorectal cancer risk may be complicated by genetic polymorphisms. The results of several recent epidemiological studies suggest that the protective effects of cruciferous vegetable consumption may be influenced by inherited differences in the capacity of individuals to metabolize and eliminate glucosinolate hydrolysis products 61).

Lung cancer

When evaluating the effect of cruciferous vegetable consumption on lung cancer risk, it is important to remember that the benefit of increasing cruciferous vegetable intake is likely to be small compared to the benefit of smoking cessation 62). Although a number of case-control studies found that people diagnosed with lung cancer had significantly lower intakes of cruciferous vegetables than people in cancer-free control groups 63), the findings of more recent prospective cohort studies have been mixed. Prospective studies of Dutch men and women 64), U.S. analysis—using data from the Nurses’ Health Study and the Health Professionals’ Follow-up Study—showed that women who ate more than 5 servings of cruciferous vegetables per week had a lower risk of lung cancer 65) and Finnish men 66) found that higher intakes of cruciferous vegetables (more than three weekly servings) were associated with significant reductions in lung cancer risk, but prospective studies of U.S. men 67) and European men and women Miller AB, Altenburg HP, Bueno-de-Mesquita B, Boshuizen HC, Agudo A, Berrino F, et al. Fruits and vegetables and lung cancer: findings from the european prospective investigation into cancer and nutrition. Int J Cancer. 2004;108:269–76. found no inverse association. The results of several studies suggest that genetic variation affecting the metabolism of glucosinolate hydrolysis products may influence the effects of cruciferous vegetable consumption on lung cancer risk 68), 69).

Breast cancer

One case-control study found that women who ate greater amounts of cruciferous vegetables had a lower risk of breast cancer 70).

The endogenous estrogen 17β-estradiol can be metabolized to 16α-hydroxyestrone (16αOHE1) or 2-hydroxyestrone (2OHE1). In contrast to 2OHE1, 16αOHE1 is highly estrogenic and has been found to enhance the proliferation of estrogen-sensitive breast cancer cells in culture 71). It has been hypothesized that shifting the metabolism of 17β-estradiol toward 2OHE1 and away from 16αOHE1 could decrease the risk of estrogen-sensitive cancers, such as breast cancer 72). In a small clinical trial, increasing cruciferous vegetable intake of healthy postmenopausal women for four weeks increased urinary 2OHE1:16αOHE1 ratios, suggesting that high intakes of cruciferous vegetables can shift estrogen metabolism. However, the relationship between urinary 2OHE1:16OHE1 ratios and breast cancer risk is not clear. Several small case-control studies found that women with breast cancer had lower urinary ratios of 2OHE1:16αOHE1 73), 74), 75), but larger case-control and prospective cohort studies did not find significant associations between urinary 2OHE1:16αOHE1 ratios and breast cancer risk 76), 77), 78). The results of epidemiological studies of cruciferous vegetable intake and breast cancer risk are also inconsistent. Several recent case-control studies in the US, Sweden and China found that measures of cruciferous vegetable intake were significantly lower in women diagnosed with breast cancer than in cancer-free control groups 79), 80), 81), but cruciferous vegetable intake was not associated with breast cancer risk in a pooled analysis of seven large prospective cohort studies conducted in the United States, Canada, Sweden, and the Netherlands 82). An additional cohort study of women in the United States similarly showed only a weak association with breast cancer risk 83).

A few studies have shown that the bioactive components of cruciferous vegetables can have beneficial effects on biomarkers of cancer-related processes in people. For example, one study found that indole-3-carbinol was more effective than placebo in reducing the growth of abnormal cells on the surface of the cervix 84).

In addition, several case-control studies have shown that specific forms of the gene that encodes glutathione S-transferase, which is the enzyme that metabolizes and helps eliminate isothiocyanates from the body, may influence the association between cruciferous vegetable intake and human lung and colorectal cancer risk 85).

Cruciferous vegetables Adverse effects

In vivo, naturally occurring isothiocyanates and their metabolites have been found to inhibit the development of chemically-induced cancers of the lung, liver, esophagus, stomach, small intestine, colon and mammary gland (breast) in a variety of animal models 86), 87). When administered before or at the same time as the carcinogen, oral indole-3-carbinol (I3C) has been found to inhibit the development of cancer in a variety of animal models and tissues, including cancers of the mammary gland (breast) 88), stomach 89), colon 90), lung 91) and liver 92). However, a number of studies found that I3C actually promoted or enhanced the development of cancer when administered chronically after the carcinogen (post initiation). The cancer promoting effects of I3C were first reported in a trout model of liver cancer 93). However, I3C also has been found to promote or enhance cancer of the liver 94), thyroid 95), colon 96) and uterus 97) in rats. The long-term effects of I3C supplementation on cancer risk in humans are not known, but the contradictory results of animal studies have led some to caution against the widespread use of indole-3-carbinol (I3C) and dimer 3,3′-diindolylmethane (DIM) supplements in humans until the potential risks versus benefits are better understood 98), 99).

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