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

[Source ⁷]

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

[Source ²]

Cruciferous vegetables are part of a healthy diet. The federal government’s Dietary Guidelines for Americans ⁸ 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 ⁹. 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 ¹⁰.

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 ¹¹.

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 ¹². 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 ¹³. Studies in animals and experiments with cells grown in the laboratory have identified several potential ways in which these compounds may help prevent cancer ¹⁴:

• 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 ¹⁵ 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 ¹⁵, 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 ¹⁶. Glutathione-S-transferases (GSTs) are involved in the metabolism of isothiocyanates (ITCs) and may modulate the effect of cruciferous vegetables on cancer risk ¹⁷. Other study results by the International Agency for Research on Cancer working group ⁹ 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 ¹⁸). Breast cancer has also been reported to be inversely related to cruciferous vegetables ¹⁹. 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 ²⁰; these cancers, however, have been consistently related to low vegetables consumption ²¹. Data are even scantier for kidney cancer ²². 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 ¹⁷.

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 ²³. 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 ²⁴. In cultured human cancer cells, ITCs can induce apoptosis and arrest of cell cycle that are critical processes in the prevention of tumor growth ²⁵. 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 ¹⁶. ITCs can also affect xenobiotic-metabolizing enzymes that are able to modulate the access of chemical carcinogens to DNA in target tissues ²⁶. 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 ²⁷. Indoles can also decrease estrogen receptor-α expression ²⁸. 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 ²⁸.

Cruciferous vegetables list

Table 2. List of common cruciferous vegetables

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 ²⁹. 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 ³⁰. 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 ³¹. 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 ³². 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 ³³, ³⁴. 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 ³⁵. 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) ³⁶, whereas the rate in Asian nations can be up to tenfold lower ³⁷. 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 ³⁸. With regard to cruciferous vegetable intake, Asian nations tend to consume much higher amounts per person than Western nations ³⁹, 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 ⁴⁰. 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 ⁴¹, United States ⁴², and Europe ⁴³ 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 ⁴⁴.

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) ⁴⁵. Walters et al. ⁴⁵ 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 ⁴⁶, ⁴⁷, most prospective cohort studies have not found significant inverse associations between cruciferous vegetable intake and the risk of developing colorectal cancer over time ⁴⁸, ⁴⁹, ⁵⁰. Cohort studies in the United States and the Netherlands have generally found no association between cruciferous vegetable intake and colorectal cancer risk ⁵¹. 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) ⁵². Surprisingly, higher intakes of cruciferous vegetables were associated with increased risk of rectal cancer in women in that study ⁵². 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 ⁵³.

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 ⁵⁴. 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 ⁵⁵, the findings of more recent prospective cohort studies have been mixed. Prospective studies of Dutch men and women ⁵⁶, 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 ⁵⁷ and Finnish men ⁵⁸ 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 ⁵⁹ 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 ⁶⁰, ⁶¹.

Breast cancer

One case-control study found that women who ate greater amounts of cruciferous vegetables had a lower risk of breast cancer ⁶².

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 ⁶³. 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 ⁶⁴. 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 ⁶⁵, ⁶⁶, ⁶⁷, but larger case-control and prospective cohort studies did not find significant associations between urinary 2OHE1:16αOHE1 ratios and breast cancer risk ⁶⁸, ⁶⁹, ⁷⁰. 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 ⁷¹, ⁷², ⁷³, 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 ⁷⁴. An additional cohort study of women in the United States similarly showed only a weak association with breast cancer risk ⁷⁵.

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 ⁷⁶.

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 ⁷⁷.

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 ⁷⁸, ⁷⁹. 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) ⁸⁰, stomach ⁸¹, colon ⁸², lung ⁸³ and liver ⁸⁴. 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 ⁸⁵. However, I3C also has been found to promote or enhance cancer of the liver ⁸⁶, thyroid ⁸⁷, colon ⁸⁸ and uterus ⁸⁹ 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 ⁹⁰, ⁹¹.

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