Glucosinolates

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Glucosinolates are a group of phytochemicals found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, cauliflower, radishes, collard greens, maca, and others. They confer the pungent odor and bitter taste associated with these foods.

Notably, glucosinolates must be transformed into bioactive compounds. When cruciferous vegetables are damaged, such as by chopping or crushing, it allows myrosinase, a plant enzyme, to come into contact with glucosinolates, transforming them into different bioactive compounds. The gut microbiota can also transform glucosinolates into bioactive compounds.

Common glucosinolates include:

  • Glucoraphanin
  • Sinigrin
  • Progoitrin
  • Glucobrassicin

Bioactive products of glucosinolates include:

  • Isothiocyanates
  • Nitriles
  • Epithionitriles
  • Thiocyanates
  • Sulforaphane and sulforaphene
  • Diindolylmethane (DIM)
  • Indole-3-carbinol (I3C)
  • Phenethyl isothiocyanate (PEITC)

Figure 1. Glucosinolate metabolization. Image credit: Costa-Pérez, A.; Núñez-Gómez, V.; Baenas, N.; et al. Systematic Review on the Metabolic Interest of Glucosinolates and Their Bioactive Derivatives for Human Health. Nutrients 202315, 1424. https://doi.org/10.3390/nu15061424. https://creativecommons.org/licenses/by/4.0/

Because glucosinolates have little biological activity when intact, the compounds created from them during hydrolysis are responsible for the many health benefits associated with eating cruciferous vegetables. For example, sulforaphane activates several genes via induction of nuclear factor erythroid-2-related factor 2 (Nrf2), and such genes may have antioxidant, anti-inflammatory, and antiapoptotic effects, among others.

Figure 2. Enzymatic conversion of glucoraphanin (GRP) to sulforaphane (SFN). Image credit: van Steenwijk HP, Winter E, Knaven E, et al. The beneficial effect of sulforaphane on platelet responsiveness during caloric load: a single-intake, double-blind, placebo-controlled, crossover trial in healthy participants. Front Nutr. 2023;10:1204561. Published 2023 Jul 6. doi:10.3389/fnut.2023.1204561. https://creativecommons.org/licenses/by/4.0/

Health Benefits of Glucosinolates

Cancer. Research has shown an inverse relationship between cruciferous vegetable consumption and various cancers including breast, colon, lung, prostate, and bladder. Most recently, a 2024 systemic review and meta-analysis concluded that a lower risk of ovarian cancer may be linked to cruciferous vegetable consumption.

Cruciferous vegetables can protect against cancers in a variety of ways. For example, glucosinolate metabolites like isothiocyanates are shown to inhibit the activation of some carcinogens by inhibiting cytochrome P-450 (CYP) enzymes in phase 1 of detoxification. On the other hand, isothiocyanates also induce phase 2 detoxification enzymes that help rid the body of carcinogens. Sulforaphane also protects against cancer by inducing apoptosis and cell cycle arrest, as well as inhibiting cancerous growth.

Additionally, numerous studies have explored the benefits of sulforaphane for prostate cancer. A 2019 study looked at the effect of glucoraphanin-rich broccoli soup consumed for one year by 49 men with localized prostate cancer. The participants received one of three soups to consume weekly: standard broccoli soup, broccoli soup with three times the amount of glucoraphanin compared to control, and broccoli soup with seven times the amount of glucoraphanin compared to control. By comparing biopsies taken before and after the study, researchers saw that the control group exhibited changes in gene expression associated with cancer pathways. However, these changes were attenuated in those consuming the glucoraphanin-rich broccoli soup. Further, those consuming the soup with the highest amount of glucoraphanin completely suppressed changes in gene expression that occurred in the control group. Another study found that sulforaphane accumulates in prostate tissue after supplementation in men diagnosed with or suspected prostate cancer. Authors speculate that this accumulation could inhibit cancer growth.

One recent study involving human triple-negative breast cancer cell lines found that sulforaphane inhibited metastasis by inhibiting actin stress fiber formation, which promotes the migration and invasion of cancer cells.

Despite evidence for the protective effects of cruciferous vegetables against cancer, confusion exists concerning the prooxidant effects of high amounts of antioxidants from cruciferous vegetables. Indeed, high or pharmacological amounts of antioxidants can promote production of free radicals and trigger oxidative stress. However, this process is also essential to activate cell death pathways, and inducing oxidative stress may be a strategy used during cancer treatment. Further, sulforaphane can have prooxidant activity when combined with chemotherapy drugs, and it may sensitize cancer cells to treatment and help reverse chemoresistance in tumor cells.

Nonetheless, using antioxidants during cancer treatment is complex and could depend on a variety of factors, including cancer severity and treatment plan. Individuals undergoing cancer treatment should consult with their physician before using supplemental antioxidants.

Cardiometabolic Health. Several animal studies support the consumption of cruciferous vegetables for cardiometabolic health. A recent animal study implies that sulforaphane improved the lipid profile of male apoE−/− mice fed a high-fat diet. The study additionally suggests that sulforaphane reduces foam cell formation, which contributes to the development of atherosclerosis. Furthermore, in a 2022 study involving mice fed a high-fat diet, sulforaphane ameliorated insulin resistance, improved liver function, and reduced body weight and hyperlipidemia.

Glucosinolates, and the metabolite sulforaphane in particular, may support cardiometabolic health by reducing platelet aggregation, which is observed in conditions such as myocardial infarction, atherosclerosis, and type 2 diabetes. A 2023 study explored the effect of sulforaphane from broccoli sprouts on 11-dehydro-thromboxane B2, a thromboxane metabolite measured via urine that is used to assess platelet reactivity in response to heart disease prevention therapies like aspirin. In the study, healthy participants (ages 18-50 years) consumed 16 g of broccoli sprouts (or pea sprouts as a placebo, as these do not contain sulforaphane) followed by a high-calorie drink. Urine samples were taken before the intervention, between the intervention and high-calorie drink, and after the high-calorie drink. Results showed reduced urinary 11-dehydro-thromboxane B2, which indicates reduced platelet aggregation.

Sulforaphane may also regulate glucose metabolism and reduce oxidative stress associated with excess glucose. A 2021 study involving men with type 2 diabetes found that broccoli supplementation combined with an aerobic and resistance exercise training program improved glycemic control, insulin resistance, and lipid profiles compared to baseline. Authors concluded that this combination had additive effects compared to, for example, training or broccoli supplementation alone.

Interestingly enough, a 2018 prospective cohort study using data from the Nurses’ Health Study found that consumption of glucosinolates was associated with an increased risk of type 2 diabetes in a dose-response manner. This study included men and women without cardiovascular disease, diabetes, and cancer at the start of the study. Using food frequency questionnaires every 2-4 years, researchers estimated consumption of individual and total glucosinolates. Those with a higher intake of glucosinolates tended to have a better diet quality, lower intake of trans fats, and more physical activity. Nonetheless, there was a statistically significant association between higher glucosinolate intake and type 2 diabetes risk, even after adjusting for demographic and lifestyle factors like smoking and alcohol consumption. It’s unclear whether antioxidants help prevent diabetes as they may attenuate glucose-stimulated insulin secretion, in which reactive oxygen species from glucose metabolism act as a signal to mediate this process in pancreatic β-cells. Indeed, the interplay between antioxidants and blood sugar regulation is complicated. However, authors of the prospective study also speculate that genetics, along with the storage and preparation of cruciferous vegetables, may partially explain their unexpected findings.

Gut Microbiome. Cruciferous vegetable consumption has been shown to alter the composition of the gut microbiome. Results from various human and animal studies have exhibited changes in specific bacteria with cruciferous vegetable consumption, including an increase in Akkermansia and a decrease in Clostridium. On the other hand, there also appears to be inter-individual variation in the metabolism of glucosinolates into bioactive compounds, which may be due to differences in gut microbiome composition.

Research indicates that there may be a relationship between the gut microbiome and autism spectrum disorder (ASD). Further, sulforaphane has been investigated for its effect on symptoms of ASD. A 2023 study involving both children with ASD (ages 4-7 years) and rats with ASD-like behaviors found that sulforaphane could improve symptoms of autism by modulating the gut microbiome. In the clinical trial portion of the study, participants were given tablets with glucoraphanin (a glucosinolate) and myrosinase to produce sulforaphane, and stool samples were taken before and after the 12-week treatment. Though it was a small sample size, half of the children with ASD experienced an improvement in symptoms after sulforaphane treatment, and the authors speculate that these results could be associated with changes to the gut microbiome.

Hormone Health. Cruciferous vegetables may support hormone health. A 2023 clinical trial explored the effect of a supplement containing glucosinolates, citrus flavonoids, and phytosterols on menopausal symptoms in 54 women. The study participants were split into three groups: two groups consumed the herbal supplement at different doses (1500 mg and 3000 mg per day), and one group used estrogen plus progestogen therapy (EPT). Compared to EPT, the herbal supplement was more helpful in reducing physical, global, and psychosocial menopausal symptoms, though the EPT was more effective at reducing vasomotor symptoms.

Diindolylmethane (DIM) exhibits both estrogenic and anti-estrogenic effects, and it may regulate signaling pathways that protect against estrogen receptor-positive breast cancer. During detoxification, DIM, and its precursor indole-3-carbinol (I3C), induces CYP1A1 and promotes the metabolism of estrogen into 2-hydroxyestrone (2OHE1), an “anti-cancer” metabolite with anti-proliferative, pro-apoptotic, and anti-angiogenic properties. This same mechanism may be why I3C is shown to inhibit the development of lesions in endometriosis.

Maca root, a cruciferous vegetable, is rich in glucosinolates. Although the health benefits of maca haven’t been attributed to a single constituent, maca is shown to modulate the endocrine system and is used for improving reproductive health, symptoms of menopause, and fertility.  Notably, despite being a cruciferous vegetable, maca does not have significant amounts of I3C or DIM.

Incorporating Glucosinolates into the Diet

There is no shortage of options when it comes to cruciferous vegetables and the glucosinolates they contain. They can be easily incorporated into salads, soups, stir-fries, and curries. Cruciferous vegetables, like cauliflower and kale, can even be added to smoothies. To improve their texture in smoothies, these vegetables can be frozen first.

Cruciferous vegetables to incorporate into the diet include:

  • Arugula
  • Bok choy
  • Broccoli and broccoli microgreens
  • Brussels sprouts
  • Cabbage
  • Cauliflower
  • Collard greens
  • Daikon radish
  • Kale
  • Radish
  • Rutabaga
  • Tatsoi
  • Turnip
  • Watercress

Cruciferous vegetables should be cut or chopped, and preferably allowed to sit for at least 40 minutes, to improve the bioavailability of glucosinolates. When possible, buying the whole vegetable rather than a pre-chopped version may maximize the bioavailability of glucosinolates. Importantly, the bioavailability of glucosinolates is influenced by heat exposure and cooking time, so lightly cooking cruciferous vegetables may be preferable to increase the bioavailability of bioactive compounds. In the absence of myrosinase due to cooking, bacterial myrosinase can transform glucosinolates into bioactive derivatives. Adding mustard seed powder to cooked cruciferous vegetables can improve myrosinase activity and the release of isothiocyanates. Finally, long storage times can reduce the glucosinolate contents of cruciferous vegetables.

Safety Concerns

Glucosinolates may have anti-thyroid effects, and excessive intake of glucosinolates could have undesired consequences, such as an enlargement of the thyroid gland (goiter) or reduced thyroid hormone levels. However, toxicity often requires the consumption of an unnaturally large amount of cruciferous vegetables, and goiter may be more likely when such foods are accompanied by an iodine deficiency. Therefore, it’s important to eat a varied and well-balanced diet containing iodine, which can be found in foods like fish, shellfish, seaweed, eggs, yogurt, and iodized table salt.

Cruciferous vegetables contain some oxalates, which may promote kidney stone formation in susceptible individuals. However, the amount is often small. For example, spinach can contain upwards of 1,200 mg total oxalates per 100 g fresh weight, whereas broccoli contains only 50 mg per 100 g fresh weight. Nonetheless, cooking methods like boiling and steaming can decrease oxalate content as oxalates are soluble in water.

Final Remarks

Cruciferous vegetables contain glucosinolates, which are transformed into bioactive compounds that are responsible for their numerous health benefits. These pungent vegetables are a nutritious addition to the diet, and the long list of choices, from broccoli and bok choy to radishes and rutabaga, ensures there is an option to suit most taste preferences. If you have questions about glucosinolate-containing vegetables and whether they are appropriate for you, talk to your doctor, nutritionist, dietician, or another healthcare team member for personal options based on your circumstances.

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