Higher consumption of cruciferous vegetables preventing blood vessel disease

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New research has shown some of our least favorite vegetables could be the most beneficial when it comes to preventing advanced blood vessel disease.

Published in the British Journal of Nutrition the research has found higher consumption of cruciferous vegetables, such as broccoli, Brussels sprouts and cabbage, is associated with less extensive blood vessel disease in older women.

Using data from a cohort of 684 older Western Australian women recruited in 1998, researchers from ECU’s School of Medical and Health Sciences and The University of Western Australia found those with a diet comprising more cruciferous vegetables had a lower chance of having extensive build-up of calcium on their aorta, a key marker for structural blood vessel disease.

Blood vessel disease is a condition that affects our blood vessels (arteries and veins) and can reduce the flow of blood circulating around the body.

This reduction in blood flow can be due to the build-up of fatty, calcium deposits on the inner walls of our blood vessels, such as the aorta.

This build-up of fatty, calcium deposits is the leading cause of having a heart attack or stroke.

Broccoli and Brussels sprouts a cut above

Lead researcher Dr. Lauren Blekkenhorst said there was something intriguing about cruciferous vegetables which this study has shed more light on.

“In our previous studies, we identified those with a higher intake of these vegetables had a reduced risk of having a clinical cardiovascular disease event, such as a heart attack or stroke, but we weren’t sure why,” she said.

“Our findings from this new study provides insight into the potential mechanisms involved.”

“We have now found that older women consuming higher amounts of cruciferous vegetables every day have lower odds of having extensive calcification on their aorta,” she said.

“One particular constituent found abundantly in cruciferous vegetables is vitamin K which may be involved in inhibiting the calcification process that occurs in our blood vessels.”

Eat an extra serve of greens every day

Dr. Blekkenhorst said women in this study who consumed more than 45g of cruciferous vegetables every day (e.g. ¼ cup of steamed broccoli or ½ cup of raw cabbage) were 46 percent less likely to have extensive build-up of calcium on their aorta in comparison to those consuming little to no cruciferous vegetables every day.

“That’s not to say the only vegetables we should be eating are broccoli, cabbage and Brussels sprouts. We should be eating a wide variety of vegetables every day for overall good health and wellbeing.”

Dr. Blekkenhorst said it was important to note the study team were very grateful to these Western Australian women, without whom these important findings would not be available for others. While observational in nature this study design is central to progressing human health.

Research welcomed by the Heart Foundation

Heart Foundation Manager, Food and Nutrition, Beth Meertens said the findings were promising and the Heart Foundation would like to see more research in this area.

“This study provides valuable insights into how this group of vegetables might contribute to the health of our arteries and ultimately our heart,” Ms Meertens said.

“Heart disease is the single leading cause of death in Australia and poor diet is responsible for the largest proportion of the burden of heart disease, accounting for 65.5 percent of the total burden of heart disease.

“The Heart Foundation recommends that Australians try to include at least five serves of vegetables in their daily diets, along with fruit, seafood, lean meats, dairy and healthy oils found in nuts and seeds.

Unfortunately, over 90 percent of Australian adults don’t eat this recommended daily intake of vegetables.”


History and Epidemiology of Cruciferous Vegetables Intake and Disease Risk

In the 21st century, reduced consumption of fruits and vegetables is related with increased risk of chronic diseases [1].

Consuming cruciferous or Brassica vegetables (brussel sprouts, cabbage, broccoli, etc.) is inversely associated with the risk of developing chronic diseases [2], including various malignancies, such as prostate [3], lung [4], colon [5], and breast cancer [6].

The non-nutritive bioactive compounds in cruciferous vegetables are also known as phytochemicals or phytonutrients. They are also referred to as guardians of our health, for having multiple potentially protective effects.

Since the period of the Roman Empire, Brassicas have been considered very valuable vegetables, and in the mid-18th century in England, broccoli was first introduced as “Italian asparagus”, and in the 1920s, it first became popular in USA [7,8].

Early research was conducted in to the dose–response relationship between decreasing consumption of cruciferous vegetables and increasing risks of colon cancer, reported by Graham et al. [9].

Various studies have been conducted regarding the medicinal benefits of consuming cruciferous vegetables. Many of them have reported the constituents or bioactive compounds present in these vegetables to be cancer preventive.

Furthermore, an extensive review on epidemiological cohort or case-control studies conducted previously has also reported inverse associations between cancer risk and the consumption of cabbage, broccoli, cauliflower, and brussel sprouts [10].

Although a few studies showed no or positive association, the majority of studies supported the potential anticancer effects of cruciferous vegetables. In a population-based prospective cohort study, it was reported that increased intake of cruciferous vegetables promotes cardiovascular health and reduces related mortality [11].

However, no direct effects were found on reducing the risk of type-2 diabetes by consuming cruciferous vegetables [12]. Another prevailing low-grade inflammatory disease is obesity, which leads to various other chronic diseases.

Daily servings of cruciferous vegetables may have a significant effect on reducing body weight [13]. Despite the cumulative supporting evidence on health impacts of cruciferous vegetable consumption, this review will briefly discuss the one potential nutraceutical present in cruciferous vegetables, sulforaphane (SFN), and introduce the protective health benefits of SFN against oxidative stress and inflammation alongside the purported mechanisms of action. Furthermore, we discuss the potential role of SFN in the field of exercise, alongside potential limitations and future directions.

Biologically Active Constituents of Cruciferous Vegetables: SFN

Glucosinolates (GCS) are the most studied biologically active compound within cruciferous vegetables, and they are also a major secondary metabolite. GCS are the precursors of isothiocyanates (ITCs), produced by enzymatic degradation (myrosinase enzyme) during chopping, harvesting, and mastication of these vegetables [14].

In cooked cruciferous vegetables (i.e., mustard leaves, watercress) the typical hot, pungent flavor of ITCs are very familiar due to presence of volatile ITCs. SFN is one of the most extensively studied naturally occurring ITCs, and holds some unique attributes that may not be offered by other phytochemicals [15].

In the mid-1990s, it was isolated from red cabbage or hoary cress as an antibiotic [16]. Later, another group of scientists isolated it from broccoli and reported it as possessing cancer chemopreventive properties [17].

SFN is a temperature-sensitive small molecule, and degrades in many aqueous solutions, including water [18,19]. It is lipophilic in nature and has a low molecular weight, (M.W. 177.29 and log P = 0.23), and has higher bioavailability than other widely used phytochemical-based supplements, i.e., curcumin, silymarin, and resveratrol [15].

Although it possesses a wide spectrum of biological activities, the fate of this molecule in food or dietary supplements is yet to be discovered.

The edible portion of mature broccoli contains 507–684 µg/g SFN dry matter [20], while broccoli sprouts contain 10 times greater SFN concentration (1153 mg/100g dry weight) and are therefore considered to be rich sources of SFN.

From 1980 to 2015, the production of broccoli increased by around 400%, due to its potential health-promoting effects [21]. Cooking or blanching broccoli at less than 100 °C makes it more effective through releasing the enzyme myrosinase.

However, if the enzyme is destroyed during processing or preparing a meal, the intestinal microflora may contribute to the microbial degradation of GSC to ITCs [22]. In a recently published research article, the metabolic pathway of activating GSC by gut bacterium has been reported [23].

In the past several years, the protective effects of SFN have been well studied in a myriad of in vivo model and in vitro studies. Furthermore, it was established that administering SFN to humans is nontoxic and well tolerated [24].

Bioavailability and Pharmacokinetics of SFN

Examining a phytochemical’s bioavailability is a key step in establishing its effectiveness. The magnitude and bioavailability of SFN depends to some extent on the cutting style or preserving process; before considering intra- or interindividual differences in biochemistry, SFN’s mode of delivery and gut microbiota composition should be considered [25].

Several human or animal studies have been conducted to identify the efficacy of SFN using three routes of administration; oral, intraperitoneal, and topical. Inside the mammalian cell, SFN is metabolized rapidly via a conjugation reaction with glutathione.

This conjugate undergoes a series of reactions catalyzed by two enzymes to produce the final product, N-acetylcysteine derivatives (mercapturic acids). These are collectively known as conjugates of SFN, or dithiocarbamates (DTC). F

ollowing SFN administration to animals or humans, the conjugates (DTC) of SFN or individual metabolites can be identified in blood, plasma, urine, and tissues by cyclocondensation reactions, or even more refined methods, e.g., liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [22,26,27].

It was reported that around 70% to 90% of DTC metabolites are identified in the urine (within 2 h), followed by an oral dose of 200 µmol of SFN (extracted from broccoli seeds or sprouts) [28].

To determine the absolute bioavailability of SFN following oral and intravenous administration, a pharmacokinetics study was conducted using an animal model.

It was identified that the lowest oral dose of SFN (2.8 µmol/kg or 0.5 mg/kg) has an absolute bioavailability of more than 80%, whilst with the highest dose (28 µmol/kg or 5 mg/kg) had only 20% bioavailability [29].

The bioavailability of SFN further depends on the preparation process of broccoli and broccoli sprouts [30].

For example, quickly steaming broccoli sprouts, followed by myrosinase treatment, contains the highest amount SFN, which is approximately 11 and 5 times higher than freeze dried and untreated steamed broccoli sprouts, respectively [31].

The peak concentration of SFN metabolites (1.91 ± 0.24 µM) was identified in urine after 1 h of oral dose (200 µmol) of broccoli sprout ITCs to four healthy human volunteers [25].

Similarly, in another study with 20 participants, providing 200 µmol of SFN in capsule form revealed a peak of SFN equivalence (0.7 ± 0.2 µM) at 3 h [32]. A dietary study conducted with broccoli soups comparing standard broccoli against super broccoli (high GCS) reported that blood concentrations of SFN and its metabolites were three-fold greater in the super-broccoli-fed group compared to standard broccoli [27].

Furthermore, it was suggested that higher SFN concentration in broccoli leads to longer exposure within the body after consumption [27].

Effects of SFN on Reducing Inflammation

SFN Reduces Inflammatory Responses by Suppressing NF-κB Activation

SFN is renowned for its promising anti-inflammatory effects. After cellular stimulation related to stress, bacteria, viruses, and proinflammatory cytokines, the IκB kinase is phosphorylated, followed by degradation of kinases, which leaves the dimer of NF-κB free to translocate into the nucleus and induce transcription of proinflammatory cytokines (IL-6, IL-10, TNF-α) [63].

SFN inhibits the activation of I-κB and translocation of NF-κB, thereby reducing inflammation [64,65]. It has been reported that SFN can also attenuate inflammation by inhibiting NF-κB binding to DNA [65].

Several in vitro studies have been conducted with various cell lines; using different stimuli such as lipopolysaccharide (LPS) and TNF-α to mimic inflammatory states and test various concentrations of SFN to identify the most effective dose to minimize inflammatory responses [65,66,67,68,69,70,71].

A few in vivo studies have also been carried out, and reported that selective doses of SFN were inversely related to inflammatory responses [72,73,74]. Tumor-cell proliferation, apoptosis, or cancer-cell mutations can be stimulated with the activation of NF-κB and production of cascade of inflammatory cytokines or chemokines [75].

Therefore, inhibiting the activation of NF-κB is an important approach to prevent deleterious effects. Previously cited studies showed that SFN can significantly attenuate various inflammatory mediators, e.g., IL-6, IL-1β, TNF-α, nitric oxide (NO), and prostaglandin E2 (PGE2), and inflammatory enzymes, e.g., inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), by suppressing activation of the NF-κB signaling pathway.

Effects of SFN on Exercise-induced Organ Damage

Exercise is a purposeful activity to maintain both physical and mental health. Routine exercise boosts our immune system, improves general health, and protects against different metabolic and chronic diseases [76].

Moreover, the activities of proteolytic enzymes significantly increases due to the adaptive response of moderate routine exercise [77]. Whilst regular physical exercise has many health benefits, these beneficial effects can be reversed with intense/exhaustive exercise.

As such, depending on the intensity and duration of exercise, it may cause muscle and/or organ damage [78]. During acute and/or exhaustive exercise, inflammatory cells such as neutrophils and macrophages infiltrate into injured tissues and can, therefore, reduce exercise performance and increase fatigue and soreness.

Exercise enhances free radical production and oxygen supply via the mitochondrial electron transport chain (ETC), which is a prime source of ROS production. Exercise increases blood supply in muscle tissue, but excessive production of ROS causes hypoperfusion of other internal organs, and results in organ damage.

Production of cytokines, chemokines, and damage-associated molecular patterns (DAMPs) are increased in the damaged cells, which enhances migration of leukocytes to the damaged tissues and causes further damage [78].

In this regard, SFN is an active antioxidant to prevent muscle and internal organ damage (Figure 2). Although NF-κB is activated in response to inflammatory responses, modulation of Nrf2 is also considered as an important step in reducing inflammation [73].

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Figure 2
The organ protective effect of SFN after exercise. Acute exhaustive exercise increases the production of reactive oxygen species (ROS), cytokines, and chemokines in liver and muscles. SFN treatment activates Nrf2, which translocates into the nucleus to induce production of cellular defense enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase (HO) 1, NADPH quinone oxidoreductase (NQO) 1, etc. Therefore, SFN reduces ROS, cytokines, and chemokines expression.

Administering SFN has been shown to increase muscle strength, improve muscle function and exercise capacity, and protect muscle from oxidative damage and inflammation [79]. SFN treatment induces expression of phase 2 enzymes via activation of Nrf2.

Moreover, expression of inflammatory and proinflammatory cytokines was also mitigated by decreasing the expression of NF-κB [73].

To ensure the interaction between SFN and Nrf2 activation, an animal experiment was conducted using wild-type mice (Nrf2+/+) and Nrf2-null mice (Nrf2−/−). It was reported that SFN induces Nrf2 activation and reduces exercise-induced muscle fatigue due to antioxidative properties via the upregulation of cellular defensive antioxidants and phase 2 enzymes [80].

Furthermore, creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) (two enzymatic markers to assess muscle damage) were significantly lower after SFN treatment compared to a placebo [81].

SFN treatment also protects exercise-induced liver damage, evidenced by reducing blood levels of enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), via inducing antioxidant defense response through the transcriptional activation of the Nrf2/HO-1 signal transduction pathway [82,83].

Although exercise increases production of proinflammatory cytokines in the liver, kidney, and intestine [82,84,85,86], SFN induces phase 2 enzymes through Nrf2 activation in renal tissue to reduce renal oxidative insults [87].

SFN treatment has been shown to reduce p38 and NF-κB phosphorylation to protect kidney tissue from injury [88]. Moreover, SFN pretreatment for seven days confers protection from inflammation of the inner lining of the colon by, once again, increasing mRNA expression of Nrf2-dependent genes and reducing expression of inflammatory genes [89].

reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346151/


More information: Lauren C. Blekkenhorst et al, Cruciferous vegetable intake is inversely associated with extensive abdominal aortic calcification in elderly women: a cross-sectional study, British Journal of Nutrition (2020). DOI: 10.1017/S0007114520002706

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