In the last article, we discussed some of the major ways in which cruciferous vegetables and garlic can work as anticancer vegetables to stress our system to fight cancer. Much like the drill sergeant in Full Metal Jacket, chemicals in these vegetables act to potentially stress our cells to prepare for battle. In this latest installment, we discuss how these same vegetables support our detoxification system to disarm carcinogens before they start.
Anticancer Vegetables and Vegetable-Fueled Detoxification
Dozens of informative diet and cancer studies performed in the first half of the 20th century further support this sensible strategy to avoid cancer. With rudimentary laboratories, one could argue that more was accomplished with regards to the effect of diet on cancer in the former half of the century, as revolutionary researchers like Tannenbaum, Rous, and their colleagues provided us with dozens of animal studies linking diet and cancer by exposing mice to free radical-laden vegetable oils.32,33 Several decades later, two other researchers, Dayton and Pearce, provided one of the few studies revealing what happens when we give humans vegetable oils and their accompanying free radicals when they randomized men to a corn oil solution and a similar rise in cancer followed.34 It is no surprise that corn oil is often used in animal studies to cause cancer, as the ingestion of damaging free radicals predictably hastens cancer development.35 Furthermore, these scientists were the first to show that fasting, restricting calories, and cutting carbohydrates could lower the chance of cancer in animals exposed to dangerous chemicals and carcinogens.
While we can avoid Tannenbaum and Rous’ oxidative damage by avoiding vegetable oils, countless other chemicals within the environment have an uncanny ability to provide us with similar unwanted injury. Many are impossible to avoid and others are self-inflicted (I am drinking a glass of red wine as I write this). Sulfur-rich vegetables provide some mechanisms to lessen the potential injury, or perhaps more advantageous, to rid the body of these harmful compounds before any damage is done.
For example, the pungent chemicals in garlic can offset some of the cancerous damage from the oxidizing free radicals in vegetable oils that bombard our DNA.36 Other animal studies reveal that even garlic powder, as opposed to the actual vegetable, can offset the damage of some cancer-causing chemicals.37 Perhaps most intriguing, are the several steps of complex mechanisms by which these pungent vegetables help rid us of harmful chemicals.
Vegetable-Fueled Detoxification: Step One
The body has several ingrained mechanisms in dealing with harmful chemicals and substances that bombard our cells on the regular. Phase I detoxification is the first step of our body’s enzymatic system to counterbalance harm from toxic chemicals, including pharmaceutical drugs and xenobiotics, and hormones within our foods, like steroids and estrogens. CYP450, the notorious enzyme that helps our liver detoxify many common medications, is a large part of this pathway, and individuals prescribed these medications are cautioned about combining other drugs and foods that interact with this mechanism. This is one reason why many patients are advised to avoid grapefruit.
Within phase I detoxification, multiple subsets of enzymes are called to action to disarm toxins. During this process, enzymes like CYP1 metabolize carcinogens, hormones, and pharmaceutical medications, readying them to be shipped out of the body. One slip up in this process is that it also activates potentially cancerous chemicals, including those formed during high heat cooking and charring of food, known as heterocyclic aromatic amines and polycyclic aromatic hydrocarbons (PAH), along with harmful environmental chemicals, like polychlorinated biphenyls (PCB).
These substances are initially detoxified to potentially more reactive and dangerous chemicals, a scary proposition. However, the detoxification system quickly hands them over to other enzymes that prepare them for entry into phase II detoxification, which can rapidly lessen their harm. This is, however, assuming we have adequate support from a healthy and active phase II detoxification system – introducing another major benefit of eating those green leafy and cruciferous vegetables. Broccoli, for instance, supports phase II detoxification in conjunction with the CYP1 pathway of phase I detoxification, providing complete cellular detoxification of cancerous chemicals in both phases.38
Curcumin, the bright yellow chemical found in turmeric, on the other hand, significantly supports CYP1 detoxification but can inhibit it at much higher doses – at least in petri dish and animal studies.39,40 As is usually the case with our physiology, it is far from straightforward, as some healthy sources of fruits and vegetables can actually inhibit CYP1, but generally these foods support detoxification by interacting with multiple CYP enzymes. Overall, there is a fine interplay of chemicals from cruciferous vegetables, red wine, spices, teas, and other foods that impact multiple points throughout the phase I detoxification system. Some studies even suggest that cruciferous vegetables upregulate phase II detoxification, while downregulating phase I, which would leave less cancerous chemicals present.
Phase II Detoxification – The Big Guns Against Cancer
When it comes to fighting cancer and chronic disease, supporting phase II detoxification seems to take the lion’s share of responsibility. The reasons are plenty, but the two most important include its ability to disarm the reactive leftovers from phase I detoxification and its association with Nrf2. The former turns a potentially dangerous compound into one that dissolves in water and is evacuated during a short trip to the bathroom. This fine interplay of chemical reactions uses various substances to bind the reactive intermediate and allow the body to excrete it in the feces through the bile system or in urine through the kidneys. The later process with Nrf2 intimately links our antioxidant defense system to the chemicals in our environment and food. The following foods upregulate Phase II detoxification:
For instance, phytochemicals from cruciferous vegetables, blueberries, and even coffee act to upregulate Nrf2, linking phase II detoxification of harmful chemicals and the production of antioxidants that subsequently disarm free radicals. When mice are genetically modified to lose Nrf2 function, they also lose many of the anti-inflammatory and antioxidant benefits of isocyothianate exposure, further linking cruciferous vegetables and Nrf2.41 Studies even suggest that Nrf2 is required to gain the beneficial effects of isocyothianates, connecting the benefits of exercise, fasting, periodic ketogenesis, and healthy cellular stresses with vegetable and spice consumption, as they all can stress our cells and engage Nrf2.42
Several processes are at play during phase II detoxification, but conjugation – the process of making harmful chemicals dissolve in water – may be most important to rid our bodies of carcinogens. The detoxification steps also overlap with mechanisms to disarm free radicals before they can damage our cells and mutate our DNA, leading to cancer. Glutathione may be one of the most important – if not the most popular – of these antioxidants, as it sacrifices itself to bind the reactive portion of the intermediate in the process known as conjugation. With its selfless tendency to “jump on the grenade,” it is the most abundant antioxidant within our cells.
These detoxification pathways overlap with several of the other dedicated antioxidant defense mechanisms like NAD(P)H: quinone oxidoreductase 1 (NQO1). Supporting them is vital to combat damage, and sulfur from garlic and onions, for example, has been shown to increase the activity of NQO1, hastening phase II detoxification.43
However, the importance of glutathione goes far beyond detoxifying harmful chemicals and metabolites. Its ability to bind and offset reactive metabolites allows it to defuse free radicals before they bind to our DNA, damage it, and encourage the development of cancer. Other plant chemicals like cinnamates (from cinnamon) and curcuminoids (from turmeric) also activate phase II enzymes to enhance detoxification and have a seemingly large stimulus effect on NQO1.44 Even plants exhibit similar internal pathways to increase antioxidant production upon encountering toxins.45
The nuances of phase I and II detoxification and the exact interaction with our food becomes complicated, if not impossible, to predict. For instance, too much activation of phase I can lead to the accumulation of toxic biproducts, stressing the importance of an active phase II to disarm them. Some studies suggest that cruciferous vegetables may slow phase I and accelerate phase II, decreasing the harmful intermediates and removing potential carcinogens.46 Healthy diets should include an array of foods that support both mechanisms, and foods that increase detoxification are listed below. For individuals on medications, some of these may need to be avoided as they can increase breakdown of certain medications, making them less effective.
|Apiaceous vegetables (celery, etc.)||Turmeric|
|Raspberry and Blueberry||Rosemary|
|Green, black, and other teas||Medium chain triglycerides|
|Purple sweet potato||Fish oil|
|Allium vegetables||Citrus fruits|
Removing toxins from our environment
Benzenes, parabens, heavy metals, hormones, irradiation, petrols, and exhaust; the laundry list of carcinogenic chemicals that we encounter seems to expand daily. The barrage of exposure is unavoidable, but recent studies provide some clues that indicate we are not powerless in the fight against chemical damage. We have mechanisms in place to prevent chemical damage either by disarming the toxins before they inflict any damage, or if all else fails, fixing the damage before it turns more serious, like cancer. Supporting these damage control mechanisms mirrors the ways in which we support the human body: a healthy diet and exercise. The defensive chemicals from the vegetables listed above “exercise” these pathways by calling them to action, though they pose little tangible danger. These same foods contain many of the building blocks to support these mechanisms, providing a two-for-one when it comes to detoxification and damage repair.
On the other hand, our lungs are constantly barraged with harmful chemicals, thanks to airborne pollutants, while a handful of dangerous substances accompany our food and water supply, exposing our digestive tract to their own damaging effects. While the concern here is obvious, these two major pathways of damage provide several methods for study.
For instance, we can give smokers different concoctions containing cruciferous vegetables and measure changes in their rate of excretion of toxins from cigarette smoke (as opposed to the harmful metabolism of them within the body). There are, unfortunately, enough present smokers subjecting themselves to this barrage of cancerous chemicals to perform these studies. As predicted, when smokers consume a solution containing watercress extract (watercress is a member of the Brassicaceae vegetable family), it blocks the breakdown and absorption of several of these cancerous chemicals, and instead discards them in the urine.47 When these smokers stop consuming the watercress, their urinary levels of the chemicals drop, suggesting the carcinogens are no longer being discarded and instead metabolized within the body.
Other studies confirm these findings – cruciferous-based compounds can reduce the amount of free radical damage within the lungs along with the cancerous lesions that accompany this damage.48 The esophagus, running along the center of the lungs, also appears to derive protection from cancer with cruciferous vegetables.49 Much like the multiple studies from the former half of the 20th century showing that certain diets can offset the cancer-causing damage of chemicals and oxidizing vegetables oils, dozens of animal studies illustrate the ability of isothiocyanates to offset cancerous damage in the esophagus, lung, breasts, and liver.29
Moving further down the gastrointestinal tract to the bowels, two potentially DNA-damaging chemicals give meat a bad name: heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are formed during high heat cooking like grilling and open flame cooking, smoking, or pan frying of the muscle meat. As the protein in lean meat encounters the scorching flame, the high temperature provokes a chemical reaction forming these elements that are felt to be largely to blame for any negative impact of meat in the diet. While HCAs are found mostly in overcooked meats, PAHs can be found in car exhaust and cigarette smoke.
Studying the effects of these chemicals in humans is difficult, but scientists have a much easier time exposing animals to high doses and then measuring the damage within their bowels. Ethical issues aside, this model has imperfections, as it often utilizes doses that are larger than in normal encounters, like in a hamburger at the ballpark, but it can at least provide some information on how effective some foods are at stopping the damage.
For instance, when animals are exposed to high doses of these chemicals in burnt meat, aberrant crypts start forming throughout the bowels.50 These aberrant crypts are a fancy way of describing abnormal changes occurring within the lining of the bowel. These same changes generally occur before polyps – the mushroom-like lesions often snipped off during a colonoscopy – but can often be a precursor to colon cancer.
Scientists have tested these hypotheses, and their studies reveal that, alongside the same aberrant crypt-causing chemicals, Brussels sprout extract and red cabbage extract helped to detoxify the dangerous substances and protect the lining of the bowels, reducing the formation of cancerous lesions.51 As a side note, Brussel sprouts seem to be better than their cabbage counterparts. Additional studies reveal that other Brassica vegetables, like garden cress, enhance detoxification of these chemicals,52 which could in theory reduce the risk of colon cancer. In an interesting twist of fate, conjugated linoleic acid – the cancer-fighter found in the fatty portions of meat and dairy from grass-fed cows – appears to provide similar benefits when consumed with these carcinogens,53 nudging us to consider the likely difference between that ballpark burger and one that was made of well-sourced beef from a grass-fed cow and higher in fat.
Finally, important bacterial species camping within our bowels, like lactobacillus, appear to chip in and play an additional role in binding and metabolizing HCAs.55 Feeding these bowel bacteria will help to increase their presence in our gut, further potentiating the breakdown of harmful chemicals like HCAs, all the while converting organosulfurs to their cancer-fighting byproducts.
It’s not just vegetables
The ability of onions, cruciferous vegetables, and leafy greens to support and promote our antioxidant and chemical defense systems is not limited to these vegetables. Tea, spices, red wine, and generally most foods that taste bitter or tannic provide similar benefits through their ability to train and rouse our cellular defenses. Coffee, thyme, broccoli, rosemary, turmeric, and red onions all enhance Nrf2 activation in animal studies.56 Detoxification mechanisms are boosted by these substances as well. For instance, when animals are provided a simple concoction made of garlic oil, liver detoxification enzymes increase.57
Furthermore, much like the tannins in red wine and even terpenes that we are exposed to when out in the forest, the sulfur in these vegetables inhibits many inflammatory pathways like NF-KB and MAPK with uncanny similarities between these plant-based weapons of chemical warfare.58 Several physiologic consequences accompany the reduction in these pathways, but perhaps most important is the decrease in inflammation.59 Counter to this, these and several additional pathways may be enhanced via sulfur exposure in cancer cells, potentially leading to dysregulated cell turnover, reproduction errors, and programmed suicide.29 In other words, isocyothianates rewire cancer cells to self-implode, while arming our cells with the skills to stop cancer before it starts.
The science behind the benefits of eating pungent vegetables is compelling, and while an ounce of daily pungent vegetables may provide a pound of cure, there are methods to maximize the benefit. Increasing the time that myrosinase interacts with the glucosinolates maximizes production of sulphoraphane. Unfortunately, myrosinase is heat sensitive and degraded during the cooking process. An easy way to combat this is to cut the vegetables ahead of time, facilitating the contact between myrosinase and the glucosinolates to produce more sulforaphane. While chewing the vegetables can help release myrosinase, it will be inactivated only a short distance away in the acidic environment of the stomach.60
Additionally, maximizing the benefit of organosulfur compounds may not be as simple as eating raw cruciferous vegetables, though this will provide at least some sulfur and many other health benefits. For the raw sources, the young sprouts seem to have more beneficial sulforaphane. Steaming the vegetables is the safest way to preserve and maximize sulfur levels, and may even increase the amount present.
As you notice from the graphs above, while the amount of sulforaphane looks similar between the three, the degradation of sulforaphane occurs over seconds with microwaving as opposed to minutes with boiling or steaming. Furthermore, the amount of sulforaphane actually rises with short amounts of cooking, and then sharply falls off.61 As with most foods, it seems prudent to avoid the microwave when cooking sprouts and most vegetables. Also, some heat is good, as it denatures a myrosinase-like chemical that can convert glucosinolates to a sulforaphane-like chemical that does not provide the anti-cancer benefits of sulforaphane.
Heating is not the only destructive force that myrosinase faces – freezing broccoli causes its myrosinase to experience an icy death.62 Fresh vegetables are best to maximize the health benefit.
However, for those of us that love the taste of Brussels sprouts cooked in butter on the cast iron pan with some sea salt and pepper, we are not out of luck. There are several hacks to increase the amount of myrosinase, and subsequently produce more sulforaphane. For instance, adding powder from mustard seeds, which contain a more durable form of myrosinase, can help offset some of the issues with cooking.63 Adding lemon juice can double the amount of available sulforaphane.64 Further issues surface, however, as the final sulfur products share myrosinase’s kryptonite; they are also heat sensitive. Adding mustard seed powder after cooking may help to maximize production of sulforaphane by breaking down the residual glucosinolates.
Garlic’s benefit shares a similar fate: as little as 60 seconds in the microwave or 45 minutes in the oven (both are amounts that can offset the breath-crushing aroma of garlic) can minimize its anticancer benefits. In some cruel twist of fate, we must ironically pay for the benefits of garlic with an offensive breath, a garlicy body odor, and annoyed coworkers and loved ones, as much of the benefit of chopped garlic is maximized when the pungency is present. However, much like broccoli and Brussels sprouts, crushing the garlic for ten minutes beforehand helps to salvage some of its anticancer benefits that may be lost with cooking.65 We may be able to maximize cancer-fighting sulfur production by steaming, cutting, and chewing, but what happens when the myrosinase is simply broken down by heat?
Forming sulforaphane from within
Even though heating destroys myrosinase, glucosinolates can resist the damage from cooking and are more stable in their native form. By the time they reach our bowels, the critters that live there take over for myrosinase to produce sulforaphane from the more heat-stable glucosinolates. Bacteria species like Bacteroides, lactic acid bacteria, Enterobacteriaceae, and Bifidobaicterium contain enzymes like myrosinase that break down glucosinolates to sulforaphane. While these levels remain unfortunately low, animal studies provide us with some clues as to how to increase the sulforaphane yield of these bacteria – feed them more.66 In just four days of a high broccoli diet, those bacteria that thrive on cruciferous vegetables grow in number, leading to a change in composition of the microbial community and an increase in opportunistic bacteria that turn our broccoli into cancer-fighting sulforaphane. A key point, however, is that in several studies, the increase in free-radical and cancer fighting NQO1 is upregulated only locally within the bowels as opposed to throughout the body.67 Yet, even this is being questioned as recent studies show it may be absorbed more systemically, albeit at lower amounts.68
For instance, studies reveal that isothiocyanate metabolites can be detected in the blood and urine after cooked glucosinolate-containing foods are eaten, although to a lesser extent than their raw glucosinolate-containing counterparts.69 In far messier studies, scientists have taken cooked watercress and simply mixed it with human feces, which converted the glucosinolates to isothiocyanates through their intrinsic myrosinase activity. This method of acquiring organosulfurs is much less efficient, but at least provides some rationale for continuing to eat deliciously-cooked Brussels sprouts.
Furthermore, the same goes when consuming them freshly after cutting and chopping, and not allowing adequate time for myrosinase to jump into action. The bowel bacteria will break down some of the residual glucosinolates to isothiocyanates.70
This is good news for those of us that can only engage in limited amounts of self-torture by eating steamed broccoli and Brussels sprouts. It seems that if we cut our crucifers ahead of time and eat them frequently, benefits are plentiful regardless of the preparation technique. Those of us willing to go the extra mile by steaming them 100% of the time deserve some credit, but for the rest of us mere mortals, it is encouraging to know that we can enjoy them with butter, salt, and pepper in a cast-iron pan and still derive some benefits.
Like Humans, Stressed Plants are Healthier
Finally, vegetables contain varying amounts of organosulfurs based on their growing conditions.29 Since these sulfur-based chemicals are part of the plant defense system, plants that encounter insects often contain higher amounts of these substances. Furthermore, soil quality is important, as nitrogen and sulfur-rich soil nurtures a growing environment that enhances a plant’s amount of glucosinolates. Plant stress parallels human stress – plants that undergo reasonable stresses create more organosulfurs. For example, stress from lack of water and higher temperature increase plant levels of glucosinolates.29
The environmental factors that impact sulfur concentration in plants are remarkably similar to the factors that increase healthy tannins in grapes and wine.
In other words, plants that are doused with pesticides and grown in soils depleted of minerals and nutrients are likely to contain less healthy organosulfurs. Much like the human body, plants need to struggle for optimal health (and to pass that health onto us). Even the transportation of the vegetables is important; when Brussels sprouts are transported under cold storage they can lose a majority of their glucosinolate content.
While cooking broccoli for even several minutes meaningfully reduces isocyothianate content,71 an optimal dose is unknown, nor is it known with certainty that the “more is better” approach applies. However, when worst comes to worst, a cooked allium or cruciferous vegetable is better than none as it provides vitamins, minerals, food for bowel bacteria, and some residual beneficial chemicals. I aim to eat cruciferous and allium vegetables daily. I cut them ahead of time and avoid high heat. Like my other vegetables, I often try to undercook them or eat them raw with olive oil and salt, but always try to make sure they maintain some pungent flavor. I also put them in marinades for flavor and to reduce cooking damage.
Raw garlic, onions, and other vegetables that leave an offensive breath should be consumed at the start of the meal – that is, if you are trying to spare those around you. This personally seems to cause less bad breath afterwards, and several scientific studies actually confirm the strategy.72 Specifically eating foods high in water and fat after garlic seems to have the largest deodorizing effect.73 Unfortunately, in a cruel twist of fate, the strong and offensive smell of garlic often parallels the level of beneficial sulfur.74 Finally, if all else fails, a little swish and swallow of baking soda seems to adequately lessen the intensity of garlic and onion breath.
Scientists are only beginning to discover the plethora of anticancer benefits of allium and cruciferous vegetables, but we still have much to learn. Defensive chemicals in other plants and spices may have similar benefits. While growing conditions, storage, preparation, and cooking methods are important, the array of benefits that accompany these vegetables certainly provide us with a “more is better” strategy. The daily support of our detoxification system to help us eliminate dangerous and cancerous chemicals, and the deployment of the antioxidant defense system to disarm free radicals before they strike, are both ample reasons to make these ingredients part of our strategy to maximize our health.
While plants’ only defense mechanism may be to wage chemical warfare on their predators, our cells have evolved over millions of years to capitalize on the situation, turning potential poisons into anticancer potions. Make sure to consume a healthy spread of cruciferous vegetables to help provide cells with a full metal jacket against cancer.
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