What are Cruciferous Vegetables?
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Arugula
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Bok Choy
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Broccoli
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Broccoli romanesco
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Brussels sprouts
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Cabbage
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Cauliflower
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Chinese cabbage
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Collard greens
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Daikon radish
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Horseradish
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Kale
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Kohlrabi
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Land cress
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Mustard greens
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Radish
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Rutabaga
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Sheperd's purse
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Turnip
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Watercress
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Image by Natural History Museum
What are isothiocyanates?
An isothiocyanate is the chemical group –N=C=S, formed by substituting the oxygen in the isocyanate group with a sulfur. Many natural isothiocyanates from plants are produced by enzymatic conversion of metabolites called glucosinolates.
What are Glucosinolates?
Glucosinolates are natural components of plants belonging to cruciferous vegetables. These natural chemicals most likely contribute to plant defense against pests and diseases, but are also consumed by humans and are believed to contribute to many health promoting properties.
What is sulfuraphane?
Sulforaphane is a compound within the isothiocyanate group of organic compounds that contain sulfur. It is obtained from cruciferous vegetables such as broccoli, Brussels sprouts or cabbage. It is produced when the enzyme myrosinase transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant (such as from chewing), which allows the two compounds to mix and react. Sulforaphane was identified in broccoli sprouts, which, of the cruciferous vegetables, have the highest concentration of sulforaphane.
What are cruciferous vegetables?
Cruciferous vegetables are vegetables that belong to the genus Brassica (also called Cruciferae) with many species being raised for food production such as cabbage, broccoli, Brussels sprouts and similar green leaf vegetables. The family takes its name (Cruciferae, New Latin for "cross-bearing") from the shape of their flowers, whose four petals resemble a cross. Cruciferous vegetables are high in a variety of nutrients that carry many health-promoting properties.
Why Consume Cruciferous Vegetables?
In our modern society, chronic disease is becoming a global epidemic. According to data provided by the CDC from 2014, more than 75% of the leading causes of death resulted from noncommunicable diseases, including but not limited to cardiovascular disease (CVD), cancer, stroke, neurodegenerative diseases, and diabetes. While the trend for overall mortality may be decreasing, morbidity and certain risk factors for mortality are increasing (U.S. Department of Health and Human Services, 2016). There exist a number of modifiable risk factors associated with chronic disease, which are ultimately responsible for a large portion of premature deaths (Danaei et al., 2011). Among the major modifiable risk factors identified, poor diet and nutrition remain largely accountable for the observed increase in disease throughout the world (Ezzati & Riboli, 2013). Researchers have well established that dietary patterns significantly impact morbidity and mortality from all causes (Heidemann et al., 2008). The nutrient requirements that humans established via natural selection over the course of human evolution emerged exclusively from uncultivated plants and wild animals. This diet consisted of whole, plant-based foods, and rich in a variety of nutrients, rather than a diet composed of processed, calorically dense foods with fewer nutrients. However, with the progressive advent of the modern western diet, rich in simple sugars and saturated fat, through industrial-scale food production and distribution, a growing portion of the population has inherently increased the risk of chronic disease (Sebastian, Frassetto, Sellmeyer, Merriam, & Morris, 2002). Increasing the consumption of vegetables is a widely accepted method to reduce the risk of chronic disease and increase life span through innate physiological mechanisms. Benefits from vegetable consumption vary by each vegetable group. Research suggests that cruciferous vegetables may be more beneficial than other groups of vegetables (Zhang et al., 2011). High in a sulfur-containing compound known as glucoraphanin (a glucosinolate), cruciferous vegetables are unique from other groups of vegetables (Zhang et al., 2011). Glucoraphanin is a relatively inert water-soluble precursor stored within the cytoplasm of cruciferous vegetables, separately but along with the enzyme myrosinase. As the mechanical separation of normal mastication destroys the cell walls, hydrolysis of glucoraphanin, via contact with myrosinase, results in the production of sulforaphane, an isothiocyanate (Houghton, Fassett & Coombes, 2016). Although less efficient, glucoraphanin can also be converted to sulforaphane via bacterial enzymes present in the gastrointestinal system (Tarozzi, Angeloni, Malaguti, Morroni, Hrelia & Hrelia, 2013).
Nonetheless, sulforaphane is a highly reactive and hydrophobic compound, present in cruciferous vegetables, that evidence suggests that may be a safe and effective therapeutic tool to reduce oxidative stress and inflammation by activating the Nrf2 transcription factor, among other mechanisms (Suppipat, Park, Shen, Zhu, & Lacorazza, 2012; Zhang et al., 2011; Zhang, Feng, & Narod, 2014). Other potential mechanisms present in cruciferous vegetables that may exert health-promoting properties include dietary fiber, vitamins, minerals, carotenoids, polyphenols, phenolic acids and indoles, such as diindolymethane (Navarro et al., 2014; Nishi et al., 2011; Zhang et al., 2014).
Nonetheless, sulforaphane is a highly reactive and hydrophobic compound, present in cruciferous vegetables, that evidence suggests that may be a safe and effective therapeutic tool to reduce oxidative stress and inflammation by activating the Nrf2 transcription factor, among other mechanisms (Suppipat, Park, Shen, Zhu, & Lacorazza, 2012; Zhang et al., 2011; Zhang, Feng, & Narod, 2014). Other potential mechanisms present in cruciferous vegetables that may exert health-promoting properties include dietary fiber, vitamins, minerals, carotenoids, polyphenols, phenolic acids and indoles, such as diindolymethane (Navarro et al., 2014; Nishi et al., 2011; Zhang et al., 2014).
In other words, cruciferous vegetables are phenomenal for your health.
How Much To Consume
If you enjoy cruciferous vegetables, be sure to include them as you eat on a regular basis in order to receive the fantastic health benefits provided by the cruciferous vegetable family. At a minimum, include cruciferous vegetables as part of your diet 2-3 times per week, and make the serving size at least 1 1/2 cups. Even better from a health standpoint, enjoy vegetables from the cruciferous family 4-5 times per week, and increase your serving size to 2 cups.
Possible Mechanisms
A unique feature of cruciferous vegetables is their high content of sulfur-containing compounds, known as glucosinolates (Zhang et al., 2011). When you chew cruciferous vegetables, glucoraphanin, one particular glucosinolate, is hydrolyzed (broken down with water) and is converted into an isothiocyanate, through an enzyme known as myrosinase (Cornblatt et al., 2007). Sulforaphane, one particular isothiocyanate, is a highly reactive compound that has been shown to reduce oxidative stress and inflammation by activating a transcription factor called (Nrf2) (Suppipat, Park, Shen, Zhu, & Lacorazza, 2012). In fact, sulforaphane is the most potent naturally occurring-inducer of the Nrf2 pathway (Calabrese et al., 2012). The Nrf2 pathway is a transcription factor that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Growing evidence suggests that sulforaphane may reduce the risk of various cancers (Li et al., 2010), cardiovascular disease, and total mortality. Aside from sulforaphane, there are several other health-promoting mechanisms found in cruciferous vegetables, such as vitamins, fiber and various phytochemicals (Zhang et al., 2011).
Fights Inflammation
A number of chronic degenerative diseases, such as cardiovascular disease (CVD) and cancer, all begin with inflammation (Navarro et al., 2014). There are various risk factors that may place individuals at a higher risk of disease-specific death (Danaei et al., 2011). It is well established that diet and nutrition influence the risk of disease (Ezzati, M., & Riboli, E., 2013). Vegetables are rich in antioxidant vitamins, detoxifying enzymes and various phytochemicals that may improve health through various methods. Benefits from vegetable consumption may vary between certain groups of vegetables (Zhang et al., 2011). Cruciferous vegetables are uniquely rich in sulforaphane, a molecule that has been observed to reduce reactive oxygen species (ROS) by 83%, thereby reducing levels of inflammation (Xue et al., 2008).
Over the course of three years, researchers evaluated over 1000 participants (between the ages of 48-67 y) from the Shanghai Women’s Health Study (SWHS). A baseline survey and questionnaire was conducted to obtain data on anthropometric measurements, demographics, diet intake, lifestyle habits, medical history and other characteristics. In addition, biospecimens were collected to measure levels of inflammation [tumor necrosis factor- α (TNF- α), interleukin (IL)-1β, and IL-6] and oxidative stress [F2-isoprostanes (F2-IsoP); 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M)], from blood and urine, respectively. Participants were separated into 5 groups based on cruciferous vegetable intake; data was obtained and validated using a food-frequency questionnaire. The researchers discovered that a higher intake of cruciferous vegetables was associated with significantly lower circulating concentrations of inflammation. A similar, but less evident, inverse association was observed with the intake of all vegetables combined. However, a inverse association was not observed with the intake of noncruciferous vegetables. No statistically significant association was observed between oxidative stress markers and intake of vegetables, a phenomenon seen in many epidemiological studies. Nonetheless, the evidence provided in this study supports that claim that the consumption of cruciferous vegetables may have antinflammatory effects (Jiang et al., 2014).
A separate group of researchers conducted a study over the course of 5 weeks on 63 participants (32 men, 31 women) between the ages of 20 and 40 years old. Participants were separated into 4 groups and were assigned to consume a specific diet for 2 week, with a 3 week washout period. The diet for the first group was fruit- and vegetable-free. The diet for the second group incorporated 7 grams of cruciferous vegetables (broccoli, cauliflower, cabbage, and radish sprouts) per kilogram of body weight. The third group was assigned double the dose of the second group, or 14 grams of the same cruciferous vegetables per kilogram of body weight. And the diet for the final group was the same as the second group (7 g/kg), however in addition, 4 grams of apiaceous vegetables (carrots, celery, dill weed, parsley, and parsnips) were assigned. After blood and urine samples were collected on days 0 and 14 of the diet, the researchers observed significantly reduced levels of IL-6, a marker of inflammation. Between these two studies, IL-6 was the only marker of inflammation in which a reduction was consistently observed. Researchers speculate that IL-6 is more responsive to environmental factors compared to other levels of inflammation (Navarro et al., 2014).
Over the course of three years, researchers evaluated over 1000 participants (between the ages of 48-67 y) from the Shanghai Women’s Health Study (SWHS). A baseline survey and questionnaire was conducted to obtain data on anthropometric measurements, demographics, diet intake, lifestyle habits, medical history and other characteristics. In addition, biospecimens were collected to measure levels of inflammation [tumor necrosis factor- α (TNF- α), interleukin (IL)-1β, and IL-6] and oxidative stress [F2-isoprostanes (F2-IsoP); 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M)], from blood and urine, respectively. Participants were separated into 5 groups based on cruciferous vegetable intake; data was obtained and validated using a food-frequency questionnaire. The researchers discovered that a higher intake of cruciferous vegetables was associated with significantly lower circulating concentrations of inflammation. A similar, but less evident, inverse association was observed with the intake of all vegetables combined. However, a inverse association was not observed with the intake of noncruciferous vegetables. No statistically significant association was observed between oxidative stress markers and intake of vegetables, a phenomenon seen in many epidemiological studies. Nonetheless, the evidence provided in this study supports that claim that the consumption of cruciferous vegetables may have antinflammatory effects (Jiang et al., 2014).
A separate group of researchers conducted a study over the course of 5 weeks on 63 participants (32 men, 31 women) between the ages of 20 and 40 years old. Participants were separated into 4 groups and were assigned to consume a specific diet for 2 week, with a 3 week washout period. The diet for the first group was fruit- and vegetable-free. The diet for the second group incorporated 7 grams of cruciferous vegetables (broccoli, cauliflower, cabbage, and radish sprouts) per kilogram of body weight. The third group was assigned double the dose of the second group, or 14 grams of the same cruciferous vegetables per kilogram of body weight. And the diet for the final group was the same as the second group (7 g/kg), however in addition, 4 grams of apiaceous vegetables (carrots, celery, dill weed, parsley, and parsnips) were assigned. After blood and urine samples were collected on days 0 and 14 of the diet, the researchers observed significantly reduced levels of IL-6, a marker of inflammation. Between these two studies, IL-6 was the only marker of inflammation in which a reduction was consistently observed. Researchers speculate that IL-6 is more responsive to environmental factors compared to other levels of inflammation (Navarro et al., 2014).
Influence on Oxidative Stress
Oxidative stress is the product of a disparity present between antioxidants and pro-oxidants, inducing the production of free radicals (Giacoppo et al., 2015). Evidence suggests that oxidative damage, via an increased concentration of reactive oxygen species (ROS), alters cellular renewal cycles resulting in cellular damage (Giacoppo et al., 2015; Sikdar, Papadopoulou & Dubois, 2015). The formation and accumulation of free radicals and ROS are speculated to react with cellular molecules, promoting pro-inflammatory pathways and triggering cellular apoptosis, DNA damage, and age-related degeneration, such as photoaging (Calabrese et al., 2012; Riso et al., 2010; Tarozzi et al., 2013). Advantageously, an intrinsic network of cellular protective proteins, regulated by the Keap1/Nrf2/ARE pathway, is present in all eukaryotic organisms (Calabrese et al., 2012). Sulforaphane, present in cruciferous vegetables, is among the most potent inducers of the Keap1/Nrf2/ARE pathway, and is suggested to reduce oxidative stress markers (Calabrese et al., 2012). Riso et al., (2012) administered steamed broccoli (250 g/day) for 10 days to healthy participants who engaged in smoking cigarettes, a practice that generates large amounts of ROS, and resulted in lowered oxidized DNA lesions and an increased resistance to H2O2-induced DNA strand breaks, markers of oxidative stress. The results of this study suggest that the consumption of cruciferous vegetables offers anti-oxidative properties (Riso et al., 2012).
Reduces Overall Mortality and Cardiovascular Disease
As mentioned, the production of inflammation is present in many diseases, including CVD (Calabrese et al., 2012). Researchers have evaluated the association between consumption of cruciferous vegetables and CVD. Data was analyzed from 2 studies conducted in China – the Shanghai Women’s Health Study (SWHS) and the Shanghai Men’s Health Study (SMHS). Participants, from 7 urban communities, included over 73,000 women between the ages of 40-70 years and over 61,000 men between the ages of 40-74 years. Over the course of 10.2 and 4.6 years, over 3000 deaths among females and nearly 2000 among males were identified, respectively. Deaths were determined by death certificates and dietary intake was validated using a food frequency questionnaire. In both men and women, individuals with a higher total fruit and vegetable consumption tended to be younger with higher education, occupational status, family income, frequency of exercise, and were less likely to smoke cigarettes. Of the identified deaths between the groups, the groups with a higher fruit and vegetable consumption, especially cruciferous vegetable consumption, displayed a reduced risk of total mortality. Compared to total mortality, a stronger inverse relationship was observed between the risk of CVD mortality, in both men and women, and the consumption of total vegetables, especially cruciferous vegetables. Once again, cruciferous vegetables are uniquely characterized by their high content of glucosinolates. Glucosinolates are sulfur-containing compounds that are suggested to reduce oxidative stress and inflammation within the cardiovascular system. These findings support the recommendation to increase consumption of fruits and vegetables, particularly cruciferous vegetables, to promote cardiovascular health and overall longevity (Zhang et al., 2011).
Defends Against Cancer
Becoming more prevalent among populations in developing nations, cancer is a convoluted disease characterized by various physiological alterations, namely genetic damage and mutation, due to the exposure of a wide variety of carcinogens (Lenzi, Fimognari & Hrelia, 2013). Lenzi, Fimognari & Hrelia, (2013) speculate that various chemicals induce oxidative stress, initiating the abnormal proliferation of cells in the form of a tumor over time. Later stages may progress to malignant characteristics, leading to the development of secondary cancers separate from the site of origin (Lenzi, Fimognari & Hrelia, 2013). According to Lenzi, Fimognari & Hrelia, (2013), due to the complex pathology of cancer, the ideal treatment should have the capacity to operate at different stages of cancer development.
Indeed, dietary interventions, such as an increased consumption of vegetables, including cruciferous vegetables, have been strongly associated with a decreased risk of cancer (Boggs et al., 2010; Wu et al., 2012). Boggs et al., (2010) observed that an increased consumption of fruits and vegetables, including cruciferous vegetables reduces the risk of breast cancer among African American women. One meta-analysis found that a high consumption of cruciferous vegetables is inversely related with the risk of colorectal cancer (Wu et al., 2012). Similarly, Tang et al., (2010) followed over 200 bladder cancer patients, for an average of 8 years, to evaluate the relationship between the consumption of cruciferous vegetables and survival of bladder cancer – in which a strong inverse associated was observed between broccoli consumption and bladder cancer mortality.
Among cancer treatments available, isothiocyanates, and consequently sulforaphane, show promise based on an array of experiments conducted. In a double-blind, randomized, placebo-controlled trial, 60 mg of sulforaphane was administered to patients with increasing prostate specific antigen (PSA) levels, a phenomenon that commonly occurs in prostate cancer patients after prostatectomy who have a high potential for relapse, for 6 months followed by 2 months without treatment (Cipolla et al., 2015). During the 6-month period, PSA levels among the patients in the sulforaphane group were significantly lower compared to the placebo group (Cipolla et al., 2015). In addition, the rate at which PSA levels double was 86% longer in the sulforaphane group compared to the placebo (Cipolla et al., 2015). Cipolla et al., (2015) suggests that sulforaphane may be a promising option to manage relapsing prostate cancer. In a similar experiment, administration of sulforaphane (50 mg/kg) to mice resulted in the down-regulation of Wnt/b-catenin pathway, a self-renewal mechanism of cancer stem cells (Li et al., 2010). In the same study, administration of sulforaphane resulted in significantly reduced breast cancer stem cell size in vivo (Li et al., 2010).
Researchers have observed that sulforaphane inhibits phase I enzymes – an essential step that prevents the activation, and conversion, of pro-carcinogens into carcinogens (Cipolla et al., 2015; Lenzi, Fimognari & Hrelia, 2013). In addition, sulforaphane has been demonstrated to induce phase II enzymes, both in vitro and in vivo – a process that promotes the detoxification of carcinogens, through the activation of a gene, regulated by transcription factor Nrf2, that contains a particular DNA sequence known as ARE (Bahadoran, Mirmiran & Azizi, 2013; Boggs et al., 2010; Cipolla et al., 2015; Lenzi, Fimognari & Hrelia, 2013; Riso et al., 2010; Sun et al., 2014; Tang et al., 2010). Researchers have identified that the Nrf2 pathway is associated with the ability of cells to defend against oxidative stress, an effective medicinal target in chronic diseases, such as cancer (Lenzi, Fimognari & Hrelia, 2013). Thus, sulforaphane is often viewed as an indirect antioxidant, able to provide defense against the production of free radicals, through the expression of phase II enzymes (Sikdar, Papadopoulou & Dubois, 2015; Wagner et al., 2012). Further, sulforaphane is able to neutralize the toxicity that carcinogens exhibit on DNA through a variety of mechanisms, although not fully understood (Lenzi, Fimognari & Hrelia, 2013). Sulforaphane can also inhibit the progression of abnormal cell division through cell cycle delay, cell cycle arrest and apoptosis (Lenzi, Fimognari & Hrelia, 2013; Li et al., 2010; Sun et al., 2014; Suppipat et al., 2012). Lastly, sulforaphane can inhibit the growth of blood vessels that supply abnormal benign cells, thus preventing the metastasis of cancer cells (Lenzi, Fimognari & Hrelia, 2013; Sun et al., 2014).
Sulforaphane has also exhibited a dose-dependent inhibition of the NF-kB pathway, a transcription factor that plays a prime role in inflammation, cell proliferation and apoptosis (Wagner et al., 2012). Researchers have also observed that other isothiocyanates, such as phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC), terminate lung cancer cell metastasis, via inhibition of the NF-kB pathway (Wu et al., 2010).
This body of evidence suggests that sulforaphane, an environmental detoxicant present in cruciferous vegetables, may be a safe and effective molecule for treating and preventing cancer (Lenzi, Fimognari & Hrelia, 2013; Singh et al., 2014).
Indeed, dietary interventions, such as an increased consumption of vegetables, including cruciferous vegetables, have been strongly associated with a decreased risk of cancer (Boggs et al., 2010; Wu et al., 2012). Boggs et al., (2010) observed that an increased consumption of fruits and vegetables, including cruciferous vegetables reduces the risk of breast cancer among African American women. One meta-analysis found that a high consumption of cruciferous vegetables is inversely related with the risk of colorectal cancer (Wu et al., 2012). Similarly, Tang et al., (2010) followed over 200 bladder cancer patients, for an average of 8 years, to evaluate the relationship between the consumption of cruciferous vegetables and survival of bladder cancer – in which a strong inverse associated was observed between broccoli consumption and bladder cancer mortality.
Among cancer treatments available, isothiocyanates, and consequently sulforaphane, show promise based on an array of experiments conducted. In a double-blind, randomized, placebo-controlled trial, 60 mg of sulforaphane was administered to patients with increasing prostate specific antigen (PSA) levels, a phenomenon that commonly occurs in prostate cancer patients after prostatectomy who have a high potential for relapse, for 6 months followed by 2 months without treatment (Cipolla et al., 2015). During the 6-month period, PSA levels among the patients in the sulforaphane group were significantly lower compared to the placebo group (Cipolla et al., 2015). In addition, the rate at which PSA levels double was 86% longer in the sulforaphane group compared to the placebo (Cipolla et al., 2015). Cipolla et al., (2015) suggests that sulforaphane may be a promising option to manage relapsing prostate cancer. In a similar experiment, administration of sulforaphane (50 mg/kg) to mice resulted in the down-regulation of Wnt/b-catenin pathway, a self-renewal mechanism of cancer stem cells (Li et al., 2010). In the same study, administration of sulforaphane resulted in significantly reduced breast cancer stem cell size in vivo (Li et al., 2010).
Researchers have observed that sulforaphane inhibits phase I enzymes – an essential step that prevents the activation, and conversion, of pro-carcinogens into carcinogens (Cipolla et al., 2015; Lenzi, Fimognari & Hrelia, 2013). In addition, sulforaphane has been demonstrated to induce phase II enzymes, both in vitro and in vivo – a process that promotes the detoxification of carcinogens, through the activation of a gene, regulated by transcription factor Nrf2, that contains a particular DNA sequence known as ARE (Bahadoran, Mirmiran & Azizi, 2013; Boggs et al., 2010; Cipolla et al., 2015; Lenzi, Fimognari & Hrelia, 2013; Riso et al., 2010; Sun et al., 2014; Tang et al., 2010). Researchers have identified that the Nrf2 pathway is associated with the ability of cells to defend against oxidative stress, an effective medicinal target in chronic diseases, such as cancer (Lenzi, Fimognari & Hrelia, 2013). Thus, sulforaphane is often viewed as an indirect antioxidant, able to provide defense against the production of free radicals, through the expression of phase II enzymes (Sikdar, Papadopoulou & Dubois, 2015; Wagner et al., 2012). Further, sulforaphane is able to neutralize the toxicity that carcinogens exhibit on DNA through a variety of mechanisms, although not fully understood (Lenzi, Fimognari & Hrelia, 2013). Sulforaphane can also inhibit the progression of abnormal cell division through cell cycle delay, cell cycle arrest and apoptosis (Lenzi, Fimognari & Hrelia, 2013; Li et al., 2010; Sun et al., 2014; Suppipat et al., 2012). Lastly, sulforaphane can inhibit the growth of blood vessels that supply abnormal benign cells, thus preventing the metastasis of cancer cells (Lenzi, Fimognari & Hrelia, 2013; Sun et al., 2014).
Sulforaphane has also exhibited a dose-dependent inhibition of the NF-kB pathway, a transcription factor that plays a prime role in inflammation, cell proliferation and apoptosis (Wagner et al., 2012). Researchers have also observed that other isothiocyanates, such as phenethyl isothiocyanate (PEITC) and benzyl isothiocyanate (BITC), terminate lung cancer cell metastasis, via inhibition of the NF-kB pathway (Wu et al., 2010).
This body of evidence suggests that sulforaphane, an environmental detoxicant present in cruciferous vegetables, may be a safe and effective molecule for treating and preventing cancer (Lenzi, Fimognari & Hrelia, 2013; Singh et al., 2014).
Stroke
Stroke is the fifth leading cause of mortality in the United States (U.S. Department of Health and Human Services, 2016). Diet is an important modifiable risk factor impacting the development of chronic disease, including stroke (Danaei et al., 2011). More specifically, fruit and vegetable consumption is inversely related with the risk of stroke (Hu, Huang, Wang, Zhang, & Qu, 2014). Kuo et al., (2017) observed that 3H-1,2-dithiole-3-thione (D3T), a sulfur-containing compound found in cruciferous vegetables, induces antioxidant and anti-inflammatory effects through activation of the Nrf2 pathway. In this experiment, mice that were subjected to an equivalent of a stroke were also administered D3T, in which the researchers observed that D3T reduced the size of dead tissue produced from the occlusion, decreased brain swelling, lessened blood-brain barrier disruption, and improved neurological deficits (Kuo et al., 2017). These results suggests that D3T, and thus cruciferous vegetables, may offer protection against ischemic stroke.
Manages Type-2 Diabetes
Diabetes mellitus, a complicated endocrine and metabolic disorder, is prevalent throughout the United States (Bahadoran, Mirmiran, & Azizi, 2013; U.S. Department of Health and Human Services, 2016). Many factors have been related to development of diabetes, including insulin resistance (IR), b cell impairment, oxidative stress and inflammation (Bahadoran, Mirmiran, & Azizi, 2013). Given the anti-inflammatory effects of cruciferous vegetables, researchers evaluated the consumption of cruciferous vegetables as a treatment to manage diabetes. Based on in vitro studies, in animal models and clinical trials, the consumption of broccoli sprouts has been proposed to be an effective and safe treatment for managing diabetes, via the activation of Nrf2 pathway, induction of phase II enzymes, reduction of oxidative stress, and inactivation of NF-kB – key factors in the development and pathogenesis of diabetes (Bahadoran, Mirmiran, & Azizi, 2013). In addition, sulforaphane, via activation of Nrf2, has been observed to significantly reduce the formation of ROS by mitochondria – a hallmark of an increased risk of vascular disease among diabetic patients with hyperglycemia (Xue, Qian, Adaikalakoteswari, Rabbani, Babaei-Jadidi, & Thornalley, 2008). This evidence suggests that the consumption of cruciferous vegetables, and consequently sulforaphane, has a favorable role in the treatment and management of type 2 diabetes and other complications associated with diabetes.
Protects the Brain from Neurodegeneration
The nervous system is an extremely intricate network of nerve cells, each characterized by different functions, which collectively support homeostasis. While innate defense mechanisms are present, the nervous system can become vulnerable to damage and disease. Neurodegenerative disorders are a group of diseases that are all characterized by the progressive loss of neurons within the central nervous system. Examples of neurodegereative diseases include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. While the cause of neurodegeneration is unknown, researchers speculate that oxidative stress plays a primary role (Giacoppo et al., 2015; Tarozzi et al., 2013). While there are no known cures for neurodegenerative diseases, the anti-oxidative and anti-inflammatory properties of glucosinolates and isothiocyanates, via the activation of Nrf2/ARE pathway, are becoming a potentially promising alternative treatment (Giacoppo et al., 2015; Kim et al., 2012; Tarozzi et al., 2013). The neuroprotective effects of sulforaphane stem from their ability to cross the blood brain barrier and accumulate in the central nervous system (Giacoppo et al., 2015; Tarozzi et al., 2013). Kim et al., (2012) observed that injection of sulforaphane in vivo, improved spatial working memory and short-term memory in mouse models that were injected with amyloid-beta aggregates, in order to cause a disease similar to Alzheimer's disease. Thus, sulforaphane, present in cruciferous vegetables, may be a useful dietary intervention to protect the brain from neurodegeneration (Kim et al., 2012).
Treats Autism
Autism spectrum disorder (ASD), a prevalent neurodevelopmental abnormality characterized by difficulty in communicating and forming relationships, and affects about 1 in 68 children, predominantly males, in the United States (Singh et al., 2014). ASD has become an enormous medical and economic problem, with no mechanism-based treatment (Singh et al., 2014). Since sulforaphane has been demonstrated to protect cells against oxidative stress, inflammation, and DNA-damage, researchers have evaluated the use of sulforaphane as a possible treatment of ASD (Calabrese et al., 2012; Singh et al., 2014). In a double-blind, placebo-controlled, randomized experiment, Singh et al., (2014) administered a daily dose of sulforaphane (50 mmol/100 pounds of body weight), obtained from broccoli sprout extract, for 18 weeks and observed a consistent and significant improvement in deviant behavior, social interaction, and verbal communication among the participants. The mechanisms for which sulforaphane may exert the aforementioned effects may lie in its ability to activate several cytoprotective cell-signaling pathways. Not only does sulforaphane shed light on the pathophysiology of ASD, the potential benefits of sulforaphane as a safe and effective treatment of ASD may play a role in the prevention in ASD (Singh et al., 2014).
Defends Against Pathogens and Pollutants
Nishi et al., (2011) invested the effects of kale, a cruciferous vegetable, on the immune system in vitro and in vivo, by measuring the activity of factors that produce and stimulate immunoglobulin, also known as antibodies. The researchers observed that an extract of kale stimulated the production of hybridoma cells and lymphocytes, suggesting that kale offers protection against pathogens, such as bacteria and viruses (Nishi et al., 2011). Similar results were seen by Johansson, Pavia & Chiao, (2008), after evaluating the effects of concentrations sulforaphane, varying between 1 - 4 μg/mL, on 28 different bacterial and fungal pathogens – in which, sulforaphane inhibited the growth of 23 different species. These results suggest that administration of sulforaphane may help prevent certain types of infections and support the immune system (Johansson, Pavia & Chiao, 2008; Nishi et al., 2011).
Influence on Obesity
Obesity, a condition characterized by the accumulation of lipids in adipose tissue, has been associated with the increased risk of developing insulin-resistance, diabetes, hypertension, cardiovascular disease, and various cancers (Lee et al., 2012). Lee et al., (2012) evaluated and observed that dose-dependent administration of sulforaphane increases the breakdown and mobilization of lipids via hormone sensitive lipase stored in adipose tissue. Shawky et al., (2016) administered sulforaphane (0.5 mg/kg/day) in a western diet-fed obese mouse model for 3 weeks and observed significantly decreased weight gain, plasma leptin, insulin resistance, glucose tolerance, and plasma lipid concentrations. Similarly, sulforaphane has been demonstrated to decrease visceral adipose tissue in mice (Shawky et al., 2016). These results suggest that sulforaphane may be a favorable therapeutic intervention for obesity (Lee et al., 2012; Shawky et al., 2016).
Maximizing Sulforaphane Bioavailability
Glucosinolate content varies widely by each cruciferous vegetable (broccoli compared to cauliflower) (Houghton, C., Fassett, R., & Coombes, J. (2016). Oxidative Medicine And Cellular Longevity, 2016, 1-17.). Freezing cruciferous vegetables destroys myrosinase, thus results in significantly less sulforaphane bioavailability, compared to fresh cruciferous vegetables (Fahey, Zhang & Talalay, 1997), (Saha et al., 2012). Blanching cruciferous vegetables at 66◦C for about 3-4 minutes yields significantly more sulforaphane formation (as seen in broccoli), compared to raw or blanching at higher temperatures and/or for longer durations (Dosz & Jeffery, 2013). Among CV, broccoli sprouts have the highest content of glucoraphanin, precursor to sulforaphane (Bahadoran, Mirmiran & Azizi, 2013), (Fahey, Zhang, & Talalay, 1997), (Li et al., 2010). Serving recommendations vary by modifiable disease, e.g. 3-5 servings per week may be sufficient to decrease risk of prostate cancer by ∼30%–40% (Tortorella, Royce, Licciardi, & Karagiannis, 2015).
Cooking Cruciferous Vegetables
The optimal way to consume cruciferous vegetables, such as broccoli, cauliflower, kale, Brussels sprouts, and cabbage, depends on various factors, and both raw and cooked forms offer different nutritional benefits. Here's a breakdown of the advantages of each:
1. Raw Cruciferous Vegetables:
1. Raw Cruciferous Vegetables:
- Enzyme Activity: Raw cruciferous vegetables contain myrosinase, an enzyme that facilitates the conversion of glucosinolates into biologically active compounds, such as sulforaphane. Sulforaphane is associated with various health benefits, including anti-cancer properties.
- Vitamin C Content: Raw vegetables generally retain more vitamin C compared to cooked ones. Vitamin C is an antioxidant that supports the immune system and helps with collagen formation.
- Digestive Enzymes: Consuming cruciferous vegetables in their raw form provides digestive enzymes that may aid in digestion.
- Improved Digestibility: Cooking cruciferous vegetables can make them easier to digest for some individuals. It can break down tough fibers and make nutrients more bioavailable.
- Reduced Goitrogen Content: Cooking can help reduce the goitrogenic compounds found in cruciferous vegetables, which may interfere with thyroid function. While the effect is generally mild, individuals with thyroid concerns may prefer cooked forms.
- Enhanced Nutrient Absorption: Certain nutrients, like lutein and zeaxanthin, are more easily absorbed from cooked cruciferous vegetables.
- Neutralized Anti-Nutrients: Cooking can neutralize or reduce the levels of anti-nutrients like oxalates and tannins, making the vegetables gentler on the digestive system.
- Balanced Approach: Including both raw and cooked cruciferous vegetables in your diet provides a balanced approach, offering a variety of nutrients and bioactive compounds.
- Individual Tolerance: Some individuals may find raw cruciferous vegetables harder to digest, leading to gas or bloating. Cooking can help alleviate these symptoms.
- Preference: Personal taste preferences also play a role. Some people enjoy the crispness of raw cruciferous vegetables in salads, while others prefer the milder flavor of cooked vegetables.
Promising areas of research
Research on the consumption of cruciferous vegetables, such as broccoli, has yielded promising findings across various health domains. The studies highlighted suggest potential benefits associated with the intake of cruciferous vegetables, particularly focusing on compounds like sulforaphane and other bioactive components. Here's a summary of the key areas of research:
- Heterocyclic Aromatic Amine Metabolism:
- The study by Murray et al. (2001) explores the effect of cruciferous vegetable consumption on the metabolism of heterocyclic aromatic amines. These compounds, formed during the cooking of meat, are associated with cancer risk. Cruciferous vegetables may play a role in modulating their metabolism.
- Breast Cancer Stem Cells Inhibition:
- Li et al. (2010) investigated sulforaphane, a component of broccoli and broccoli sprouts, and its inhibitory effects on breast cancer stem cells. This suggests a potential role for cruciferous vegetables in breast cancer prevention and treatment.
- Sulforaphane for Breast Cancer Chemoprevention:
- Cornblatt et al. (2007) conducted preclinical and clinical evaluations of sulforaphane for breast cancer chemoprevention. The study suggests that sulforaphane may have chemopreventive properties in the context of breast cancer.
- Non-Hodgkin Lymphoma Survival:
- The research by Han et al. (2010) explores the association between vegetable and fruit intake and survival in non-Hodgkin lymphoma among women. Higher intake is linked to potential benefits in non-Hodgkin lymphoma survival.
- Total Antioxidant Capacity and Non-Hodgkin Lymphoma Risk:
- Holtan et al. (2011) used food-frequency questionnaires to estimate total antioxidant capacity from diet and its association with the risk of non-Hodgkin lymphoma. Cruciferous vegetables, rich in antioxidants, may contribute to a reduced risk.
- Protection Against Oxidative Stress and Cataract Prevention:
- Liu et al. (2013) investigated the protective effects of sulforaphane against oxidative stress on lens cells, suggesting potential implications for cataract prevention. This highlights a novel area of research on the ocular health benefits of cruciferous vegetables.
- Inhibition of Aryl Hydrocarbon Receptor Transformation:
- The study by Ashida et al. (2000) focuses on flavones and flavonols found in cruciferous vegetables, demonstrating their inhibitory effects on the transformation of the aryl hydrocarbon receptor induced by dioxin. This suggests a potential role in protecting against the harmful effects of environmental pollutants.
References
Ashida, H., Fukuda, I., Yamashita, T., & Kanazawa, K. (2000). Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin. FEBS Letters, 476(3), 213–217. doi:10.1016/s0014-5793(00)01730-0
Bahadoran, Z., Mirmiran, P., & Azizi, F. (2013). Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications. Journal of Medicinal Food, 16(5), 375–382. doi:10.1089/jmf.2012.2559
Boggs, D. A., Palmer, J. R., Wise, L. A., Spiegelman, D., Stampfer, M. J., Adams-Campbell, L. L., & Rosenberg, L. (2010). Fruit and vegetable intake in relation to risk of breast cancer in the black women’s health study. American Journal of Epidemiology, 172(11), 1268–1279. doi:10.1093/aje/kwq293
Calabrese, V., Cornelius, C., Dinkova-Kostova, A., Iavicoli, I., Di Paola, R., & Koverech, A. et al. (2012). Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease, 1822(5), 753-783. http://dx.doi.org/10.1016/j.bbadis.2011.11.002
Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M., Fahey, J. W., Singh, N. K., … Visvanathan, K. (2007). Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis, 28(7), 1485–1490. doi:10.1093/carcin/bgm049
Danaei, G., Ding, E., Mozaffarian, D., Taylor, B., Rehm, J., Murray, C., & Ezzati, M. (2011). Correction: The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors. Plos Medicine, 8(1). http://dx.doi.org/10.1371/annotation/0ef47acd-9dcc-4296-a897-872d182cde57
Dosz, E. , & Jeffery, E. (2013). Modifying the processing and handling of frozen broccoli for increased sulforaphane formation. Journal of Food Science, 78(9), H1459-H1463.
Ezzati, M., & Riboli, E. (2013). Behavioral and Dietary Risk Factors for Noncommunicable Diseases. New England Journal Of Medicine, 369(10), 954-964. http://dx.doi.org/10.1056/nejmra1203528
Fahey, J. W., Zhang, Y., & Talalay, P. (1997). Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. , 94(19), . Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23369/pdf/pq010367.pdf
Fimognari, C., & Hrelia, P. (2007). Sulforaphane as a promising molecule for fighting cancer. Mutation Research/Reviews in Mutation Research, 635(s 2–3), 90–104. doi:10.1016/j.mrrev.2006.10.004
Han, X., Zheng, T., Foss, F., Holford, T. R., MA, S., Zhao, P., … Bai, Y. (2010). Vegetable and fruit intake and non-hodgkin lymphoma survival in Connecticut women. Leukemia & Lymphoma, 51(6), 1047–1054. doi:10.3109/10428191003690364
Holtan, S. G., O’Connor, H. M., Fredericksen, Z. S., Liebow, M., Thompson, C. A., Macon, W. R., … Cerhan, J. R. (2011). Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-hodgkin lymphoma. International Journal of Cancer, 131(5), 1158–1168. doi:10.1002/ijc.26491
Jiang, Y., Wu, S.-H., Shu, X.-O., Xiang, Y.-B., Ji, B.-T., Milne, G. L., … Yang, G. (2014). Cruciferous vegetable intake is inversely correlated with circulating levels of Proinflammatory markers in women. Journal of the Academy of Nutrition and Dietetics, 114(5), 700–708.e2. doi:10.1016/j.jand.2013.12.019
Li, Y., Zhang, T., Korkaya, H., Liu, S., Lee, H. F., Newman, B., … Sun, D. (2010). Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clinical Cancer Research, 16(9), 2580–2590. doi:10.1158/1078-0432.ccr-09-2937
Liu, H., Smith, A. J. O., Lott, M. C., Bao, Y., Bowater, R. P., Reddan, J. R., & Wormstone, I. M. (2013). Sulforaphane can protect lens cells against Oxidative stress: Implications for cataract prevention. Investigative Opthalmology & Visual Science, 54(8), 5236. doi:10.1167/iovs.13-11664
Murray, S. , Lake, B. , Gray, S. , Edwards, A. , Springall, C. , et al. (2001). Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man. Carcinogenesis, 22(9), 1413-1420.
Navarro, S., Schwarz, Y., Song, X., Wang, C., Chen, C., & Trudo, S. et al. (2014). Cruciferous Vegetables Have Variable Effects on Biomarkers of Systemic Inflammation in a Randomized Controlled Trial in Healthy Young Adults. Journal Of Nutrition, 144(11), 1850-1857. http://dx.doi.org/10.3945/jn.114.197434
Nishi, K., Kondo, A., Okakmoto, T., Nakano, H., Daifuku, M., Nishimoto, S., … Sugahara, T. (2011). Immunostimulatoryin Vitroandin VivoEffects of a water-soluble extract from kale. Bioscience, Biotechnology, and Biochemistry, 75(1), 40–46. doi:10.1271/bbb.100490
Riso, P., Martini, D., Moller, P., Loft, S., Bonacina, G., Moro, M., & Porrini, M. (2010). DNA damage and repair activity after broccoli intake in young healthy smokers. Mutagenesis, 25(6), 595–602. doi:10.1093/mutage/geq045
Saha, S., Hollands, W., Teucher, B., Needs, P., Narbad, A., & Ortori, C. et al. (2012). Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli. Molecular Nutrition & Food Research, 56(12), 1906-1916. http://dx.doi.org/10.1002/mnfr.201200225
Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences, 111(43), 15550–15555. doi:10.1073/pnas.1416940111
Suppipat, K., Park, C. S., Shen, Y., Zhu, X., & Lacorazza, H. D. (2012). Sulforaphane induces cell cycle arrest and Apoptosis in acute Lymphoblastic leukemia cells. PLoS ONE, 7(12), e51251. doi:10.1371/journal.pone.0051251
Tarozzi, A., Angeloni, C., Malaguti, M., Morroni, F., Hrelia, S., & Hrelia, P. (2013). Sulforaphane as a potential protective Phytochemical against Neurodegenerative diseases. Oxidative Medicine and Cellular Longevity, 2013, 1–10. doi:10.1155/2013/415078
Tortorella, S., Royce, S., Licciardi, P., & Karagiannis, T. (2015). Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition. Antioxidants & Redox Signaling, 22(16), 1382-1424. http://dx.doi.org/10.1089/ars.2014.6097
Wagner, A., Ernst, I., Iori, R., Desel, C., & Rimbach, G. (2010). Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. Experimental Dermatology, 19(2), 137-144. http://dx.doi.org/10.1111/j.1600-0625.2009.00928.x
Wu, X., Zhu, Y., Yan, H., Liu, B., Li, Y., Zhou, Q., & Xu, K. (2010). Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells. BMC Cancer, 10(1), . doi:10.1186/1471-2407-10-269
Xue, M., Qian, Q., Adaikalakoteswari, A., Rabbani, N., Babaei-Jadidi, R., & Thornalley, P. (2008). Activation of NF-E2-Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease. Diabetes, 57(10), 2809-2817. http://dx.doi.org/10.2337/db06-1003
Zhang, X., Shu, X.-O., Xiang, Y.-B., Yang, G., Li, H., Gao, J., … Zheng, W. (2011). Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. The American Journal of Clinical Nutrition, 94(1), 240–246. http://doi.org/10.3945/ajcn.110.009340
Bahadoran, Z., Mirmiran, P., & Azizi, F. (2013). Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications. Journal of Medicinal Food, 16(5), 375–382. doi:10.1089/jmf.2012.2559
Boggs, D. A., Palmer, J. R., Wise, L. A., Spiegelman, D., Stampfer, M. J., Adams-Campbell, L. L., & Rosenberg, L. (2010). Fruit and vegetable intake in relation to risk of breast cancer in the black women’s health study. American Journal of Epidemiology, 172(11), 1268–1279. doi:10.1093/aje/kwq293
Calabrese, V., Cornelius, C., Dinkova-Kostova, A., Iavicoli, I., Di Paola, R., & Koverech, A. et al. (2012). Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease, 1822(5), 753-783. http://dx.doi.org/10.1016/j.bbadis.2011.11.002
Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M., Fahey, J. W., Singh, N. K., … Visvanathan, K. (2007). Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis, 28(7), 1485–1490. doi:10.1093/carcin/bgm049
Danaei, G., Ding, E., Mozaffarian, D., Taylor, B., Rehm, J., Murray, C., & Ezzati, M. (2011). Correction: The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors. Plos Medicine, 8(1). http://dx.doi.org/10.1371/annotation/0ef47acd-9dcc-4296-a897-872d182cde57
Dosz, E. , & Jeffery, E. (2013). Modifying the processing and handling of frozen broccoli for increased sulforaphane formation. Journal of Food Science, 78(9), H1459-H1463.
Ezzati, M., & Riboli, E. (2013). Behavioral and Dietary Risk Factors for Noncommunicable Diseases. New England Journal Of Medicine, 369(10), 954-964. http://dx.doi.org/10.1056/nejmra1203528
Fahey, J. W., Zhang, Y., & Talalay, P. (1997). Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. , 94(19), . Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23369/pdf/pq010367.pdf
Fimognari, C., & Hrelia, P. (2007). Sulforaphane as a promising molecule for fighting cancer. Mutation Research/Reviews in Mutation Research, 635(s 2–3), 90–104. doi:10.1016/j.mrrev.2006.10.004
Han, X., Zheng, T., Foss, F., Holford, T. R., MA, S., Zhao, P., … Bai, Y. (2010). Vegetable and fruit intake and non-hodgkin lymphoma survival in Connecticut women. Leukemia & Lymphoma, 51(6), 1047–1054. doi:10.3109/10428191003690364
Holtan, S. G., O’Connor, H. M., Fredericksen, Z. S., Liebow, M., Thompson, C. A., Macon, W. R., … Cerhan, J. R. (2011). Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-hodgkin lymphoma. International Journal of Cancer, 131(5), 1158–1168. doi:10.1002/ijc.26491
Jiang, Y., Wu, S.-H., Shu, X.-O., Xiang, Y.-B., Ji, B.-T., Milne, G. L., … Yang, G. (2014). Cruciferous vegetable intake is inversely correlated with circulating levels of Proinflammatory markers in women. Journal of the Academy of Nutrition and Dietetics, 114(5), 700–708.e2. doi:10.1016/j.jand.2013.12.019
Li, Y., Zhang, T., Korkaya, H., Liu, S., Lee, H. F., Newman, B., … Sun, D. (2010). Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clinical Cancer Research, 16(9), 2580–2590. doi:10.1158/1078-0432.ccr-09-2937
Liu, H., Smith, A. J. O., Lott, M. C., Bao, Y., Bowater, R. P., Reddan, J. R., & Wormstone, I. M. (2013). Sulforaphane can protect lens cells against Oxidative stress: Implications for cataract prevention. Investigative Opthalmology & Visual Science, 54(8), 5236. doi:10.1167/iovs.13-11664
Murray, S. , Lake, B. , Gray, S. , Edwards, A. , Springall, C. , et al. (2001). Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man. Carcinogenesis, 22(9), 1413-1420.
Navarro, S., Schwarz, Y., Song, X., Wang, C., Chen, C., & Trudo, S. et al. (2014). Cruciferous Vegetables Have Variable Effects on Biomarkers of Systemic Inflammation in a Randomized Controlled Trial in Healthy Young Adults. Journal Of Nutrition, 144(11), 1850-1857. http://dx.doi.org/10.3945/jn.114.197434
Nishi, K., Kondo, A., Okakmoto, T., Nakano, H., Daifuku, M., Nishimoto, S., … Sugahara, T. (2011). Immunostimulatoryin Vitroandin VivoEffects of a water-soluble extract from kale. Bioscience, Biotechnology, and Biochemistry, 75(1), 40–46. doi:10.1271/bbb.100490
Riso, P., Martini, D., Moller, P., Loft, S., Bonacina, G., Moro, M., & Porrini, M. (2010). DNA damage and repair activity after broccoli intake in young healthy smokers. Mutagenesis, 25(6), 595–602. doi:10.1093/mutage/geq045
Saha, S., Hollands, W., Teucher, B., Needs, P., Narbad, A., & Ortori, C. et al. (2012). Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli. Molecular Nutrition & Food Research, 56(12), 1906-1916. http://dx.doi.org/10.1002/mnfr.201200225
Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences, 111(43), 15550–15555. doi:10.1073/pnas.1416940111
Suppipat, K., Park, C. S., Shen, Y., Zhu, X., & Lacorazza, H. D. (2012). Sulforaphane induces cell cycle arrest and Apoptosis in acute Lymphoblastic leukemia cells. PLoS ONE, 7(12), e51251. doi:10.1371/journal.pone.0051251
Tarozzi, A., Angeloni, C., Malaguti, M., Morroni, F., Hrelia, S., & Hrelia, P. (2013). Sulforaphane as a potential protective Phytochemical against Neurodegenerative diseases. Oxidative Medicine and Cellular Longevity, 2013, 1–10. doi:10.1155/2013/415078
Tortorella, S., Royce, S., Licciardi, P., & Karagiannis, T. (2015). Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition. Antioxidants & Redox Signaling, 22(16), 1382-1424. http://dx.doi.org/10.1089/ars.2014.6097
Wagner, A., Ernst, I., Iori, R., Desel, C., & Rimbach, G. (2010). Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. Experimental Dermatology, 19(2), 137-144. http://dx.doi.org/10.1111/j.1600-0625.2009.00928.x
Wu, X., Zhu, Y., Yan, H., Liu, B., Li, Y., Zhou, Q., & Xu, K. (2010). Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells. BMC Cancer, 10(1), . doi:10.1186/1471-2407-10-269
Xue, M., Qian, Q., Adaikalakoteswari, A., Rabbani, N., Babaei-Jadidi, R., & Thornalley, P. (2008). Activation of NF-E2-Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease. Diabetes, 57(10), 2809-2817. http://dx.doi.org/10.2337/db06-1003
Zhang, X., Shu, X.-O., Xiang, Y.-B., Yang, G., Li, H., Gao, J., … Zheng, W. (2011). Cruciferous vegetable consumption is associated with a reduced risk of total and cardiovascular disease mortality. The American Journal of Clinical Nutrition, 94(1), 240–246. http://doi.org/10.3945/ajcn.110.009340
