The movie Full Metal Jacket opens with an infamous barrage of brutal insults and heckling by Senior Drill Instructor Gunnery Sergeant Hartman. Comedic at times, difficult to the ears at others, his job is wholly to train the troops, prepare them for war, and send them off as a coordinated squadron to work together to beat the enemy. The second half of the movie diverges from this plot as it focuses solely on the Vietnam war, but the message is clear: for success on the battle field, troops must be pushed to their limits during training. Otherwise, the movie has absolutely nothing to do with anticancer vegetables.
Strangely enough, nothing reminds me more of the role of vegetables, and especially anticancer vegetables, in our lives than the first half of the movie. These soft and cuddly sources of nutrition are often viewed as a harmless and innocuous retreat from the violent minefield known as the dietary world. On a cellular level, their bitter presence may be closer to Sergeant Hartman than their innocent reputation. Yet, much like the offensive drill instructor, they may be serving to stress our cells into becoming better troops in the fight against cancer, without actually harming them.
The 10,000-foot view
When it comes to analyzing diet and the effect of certain foods on our health, we often have nowhere to turn but large population studies, known affectionately in the medical world as epidemiologic studies. These studies – the art of following a large group of people and trying to connect the dots between their behaviors and health – receive their fair share of criticism due to serious reliability flaws (we have already given them their well-deserved whipping). Issues aside, when it comes to assessing the benefits of fruits and vegetables, we often have no choice but to rely on them, regardless of their shortcomings. There is limited to no funding from “big fruit” and “big vegetable” to support massive multi-million dollar studies that are a mere rounding error for “big pharma.”
The Achilles’ heel of these population-based epidemiologic studies is the population that they study; they have no choice but to follow a large group of individuals that have already been advised to eat fruits and vegetables, don’t smoke, exercise, avoid fat, and do a bunch of other doctor-prescribed healthy activities (some wrong, some right). Often, we end up simply selecting for people that are good at following directions. In other words, people that eat sufficient fruits and vegetables also exercise, avoid smoking, and engage in many other generally healthy activities. If anything, this leaves us in a chicken or the egg situation.
Supporting this notion, studies confirm that individuals who do not exercise, smoke, and drink heavily – all factors that can greatly increase cancer risk and bias these studies – eat less vegetables and fruit than their healthier counterparts.1 While the holes in epidemiology studies accumulate almost as fast as these studies are produced, saturating our daily news sources with “this just in, coffee will kill you” alerts, they are the best we have to work with and many demonstrate health benefits from consuming fruits and vegetables. For instance, a large (ahem) epidemiologic study of the diets of over 120,000 men and women reveals that individuals that eat more fruits and vegetables experience more weight loss.2 An even larger analysis of several studies found that heavy fruit and vegetable eaters have a lower risk of all-cause mortality (i.e. the risk of dying from anything, our most important scientific end point). They also have a lower risk of dying from any heart-based issues.3 The studies go on and on.
Though, the closer we look, the more the benefits of fruits begin to disappear, as opposed to the more persistent benefits of vegetables. As is always the case in the nutritional world, studies are mixed. For instance, when comparing different dietary food groups with our risk of stroke, a benefit of fruit and vegetables surfaces. However, when zooming in on that benefit, the advantage is much greater from green and cruciferous vegetables.4 When looking at all types of chronic diseases, the benefits point even more specifically to vegetables, but especially green, leafy vegetables.5
While most studies emphasize the interaction of fruits and vegetables with non-cancer-related endpoints like cardiovascular disease, obesity, and risk of stroke, the benefits of vegetables, and especially fruits, continue to drop when we focus on cancer. And even other studies suggest that the ability of vegetables to reduce our risk of cancer is miniscule, and the benefit may be most pronounced in those heavy smokers and drinkers, who are already at an increased risk of cancer.6 In other words, these vegetables may be working hard to offset the massive damage from these individuals’ unhealthy behaviors, but the benefits just aren’t there for the rest of us who follow a reasonably healthy lifestyle.
Supporting (but not proving) this stance is a massive analysis of 26 published studies from 1982-1997, confirming no benefit of fruit consumption in reducing the risk of breast cancer, while vegetables were associated with a 25% lower risk.7 When premenopausal, i.e. younger, women were specifically analyzed, scientists again saw a small benefit of dietary vegetables for breast cancer prevention, but no benefit for their sweeter fruit counterparts.8 In men, cruciferous vegetable consumption is associated with a decreased risk of prostate cancer.9 When we gravitate to newer studies, no benefit of fruits or vegetables was seen when scientists looked at over 350,000 women and their risk of breast cancer.10 Multiple other studies echoed these findings, revealing no reduction in breast cancer10,11 or any cancer5 with fruit or vegetable consumption. Other data may point to a benefit when eaten earlier in life as protective against breast cancer,12 but I think you are getting the point; the data are an inconsistent mess, and most studies are negative.
Zooming in on the benefits
At the end of the day, these studies are uniformly plagued by limitations, biases, and inescapable confines that can only nudge us to suggest that vegetables, and to a lesser extent fruits, may better our health and reduce our risk of cancer. The proof lies in the pudding, but we need to figure out the recipe before we can make firm recommendations, and this is a major flaw of these massive studies. For instance, on the surface it is easy to suggest that vegetables, fibrous fruits, and berries are healthier, because they have less sugar than many other foods. My colleagues in the medical field have no problem strongly making these recommendations to every patient.
Yet, when focusing on fruits, we find that many studies included fruit juice as a fruit, which biases results as it is more a heavily sugar-processed liquid as opposed to actual fruit. One of many issues with countless studies is the fact that the design greatly affects the outcome – one slip up, and we are left with massively different results. It is said that a journey of a thousand miles often begins with one misstep, and that misstep in these studies could lead to massive consequences decades later (think standard American diet…).
While newer studies account for the fruit juice issue and still generally find no benefit of fruits to fight cancer, vegetables may avoid this bias as they contain minimal amounts of sugar and instead larger amounts of fiber, minerals, and vitamins. This anatomic makeup of vegetables leaves their endorsement as a failsafe recommendation for physicians and dieticians, which is why most dietary recommendations begin and end with vegetables. Fat, dairy, meat, alcohol, coffee, and dozens of other foods are controversial, so are generally ignored by our health leaders for the easy targets. The ease of recommending these “safe” foods has left patients confused as they leave their doctor’s office, not knowing whether they should eat any nonvegetable foods, and how to optimize these foods. The dirty little secret, of course, is that both patients and doctors are eating them behind closed doors.
Like all foods, some vegetables are healthier than others. But when considering recommending vegetables, there are what I refer to as the easy benefits, i.e. those vague terms, that while true, may be present in many different foods, not just vegetables. For instance, vegetables contain many vitamins, nutrients, and minerals, and all three are found in an array of foods. They are also often comprised of fiber, the substance that has been praised for its ability to regulate our bowels habits, when in actuality, its largest benefit may be its ability to feed our bowel bacteria.13 The hundreds of trillions of critters that reside within our gastrointestinal tract help to support our immune system and fight inflammation,14 ensure the integrity of our bowel lining,15 and help to detoxify and metabolize potentially cancerous chemicals.16 We are just beginning to delve into the benefits and intricacies of bowel bacteria, but progress has been slowed due to the massive amount of bacterial species to study along with the hefty number of variables that complicates research, including their interaction with our diet, physiology, and each other. Regardless, they certainly need nourished and nurtured, but recommendations of dietary fiber rarely delve into this rationale.
Yet, more and more studies are suggesting that these “superficial” benefits of vegetables may pale in comparison to the impact of the chemistry lab of compounds within these plants. For instance, while sulfur has taken its fair share of shots in the past several decades, studies on the health benefits of anticancer vegetables may be providing it well-deserved vindication. As the paramount agent in mustard gas chemical warfare in World War II, to the unmistakable smell of rotten eggs, we have read about the malicious use of sulfur and experienced it firsthand as it has pestered our nostrils at some point. Yet, plants have capitalized on these volatile elements of sulfur as a defense mechanism to offset their lack of claws and teeth, inability to run away, and ease with which they are plucked from the ground and eaten.
We rarely contemplate the often-unrealized defense mechanisms of plant warfare that has been waged on us over the centuries. While instead considered harmless, they are often, like Sergeant Hartman, far from it. From hemlock, Shakespeare’s favorite deadly poison, to large doses of amygdalin from apple seeds, plants contain many hazardous and lethal chemicals. Dog owners know of these dangers better than the rest of us, since their furry little friends are often exquisitely sensitive to the chemicals in plants. In fact, as I was writing this and contemplating my next words, I watched as my French bulldog ate a grape. I thought nothing of it, yet, moments later she seemed listless, snapping me out of my daze and quickly prompting a Google search for dogs and grapes. To my horror, grapes are toxic to dogs – even in small doses – causing everything from nausea to kidney failure due to several of their chemicals.
Apparently (and luckily) one grape is not fatal to dogs, but several have the potential and I learned my lesson – plants are not the innocent objects that they are made out to be. While there is an array of plant-based toxins poisonous to humans and dogs alike, sulfur may be the one we encounter most frequently and can easily recognize when eating some typical foods. Many foods are loaded with sulfur, with some of the most common including pungent cruciferous vegetables, such as:
- Bok choy
- Mustard leaves
Other sources of sulfur include nuts, garlic, onions, and animal sources like meats, fish, eggs, and dairy. Meat versus plant sources of sulfur nudge our cells in slightly different directions when it comes to our health. For instance, proteins contain sulfur, often in the form of the amino acids cysteine and methionine. This “structural” form of sulfur plays a role in several important processes, including detoxification of potentially cancerous and harmful chemicals, supporting the mitochondria (our cellular energy powerhouse), supporting metabolism, and acting as the brick and mortar for the synthesis of important enzymes like glutathione. Brick and mortar amino acids that contain sulfur aid in protein synthesis and function, and help with protein structure. Sulfur is also required by many enzymes to function properly, and it also aids in folic acid integration. Major sources of this structural sulfur include:
- Beef and lamb
- Soy Products
- Nuts and seeds (lesser amounts)
While the structural benefits of proteins and sulfur-containing proteins are well-established, the major anticancer benefit of plant-derived chemical weapons is only recently becoming recognized. The organosulfur compounds in many of these vegetables – the chemical that gives them their often-pungent taste – supports health in ways that are exclusive of the brick and mortar benefits of methionine and cysteine-based sulfur from other foods. Several different organosulfur chemicals provide the potent and often volatile smell and taste of some common plant foods. For example, the following are the two main sulfurous vegetable groups:
Brassicaceae or Cruciferae:
Known to most as the cruciferous vegetable food group, these herbaceous plants give rise to crucifers, cabbages, and mustards. Broccoli, cabbage, turnips, and the exotic wasabi are all crucifers known for their pungent taste and smell. Glucosinolates are the strong-smelling sulfur chemicals found in these plants. Glucoraphanin is the glucosinolate chemical found in some of the most common vegetable sources of sulfur, including broccoli, mustard greens, and cauliflower. Sprouts, the younger forms of these vegetables, contain larger amounts than the adults. Upon cutting, chewing, or crushing these plants, the chemical myrosinase is released and mixes with glucoraphanin, transforming it into sulforaphane. While the word soup can get confusing, this organosulfur is an isothiocyanate, and provides the bulk of health benefits, much like anthocyanin in red wine.
Wasabi, for example, contains thioglucosides, the chemical compounds containing sulfur (thiol means “replaced by sulfur”). They are stored in the stems of the wasabi plant and broken down into isothiocyanates upon contact with myrosinase. The release of isothiocyanate is the key player in defending against predators, as unlike many animals, plants are not armed with teeth or claws.
Much like a futuristic bomb in a James Bond movie containing two cartridges of chemicals, which if combined will cause a massive explosion, plants store myrosinase and glucosinolates in separate areas, awaiting detonation. Myrosinase is released when we grate wasabi, but also when its stem is damaged by a hungry animal or insect. Its release potentiates the breakdown of the thioglucosides, ushering in the release of the volatile and pungent allyl isothiocyanate along with several other chemicals (the allyl is important, as some feel that more allyls means more cancer-fighting potential), leading to that burning sensation in our nostrils after dipping our sushi into wasabi.17 That burn is unattractive to insects and animals searching for a meal, and this same chemical provides the plant with antibacterial defense, further supporting its role in chemical warfare. Wasabi’s caustic chemicals are not oil based, allowing it to fill the air, further explaining why it hits our nostrils so intensely, but dissipates rapidly (unlike oil-based irritants found in chili peppers).
Another infamous anticancer vegetable containing pungent organosulfur compounds is the allium vegetable, garlic. Allium vegetables include those garlic-like vegetables whose aroma can fill a room, like chives, leeks, onions, and scallions. My grandfather used to eat multiple cloves of raw garlic per day. Some said this was why he lived just shy of 97, but what we can say with certainty is that it made him, his house, his clothes, and our house smell like freshly-chopped garlic year-round. When garlic is sliced, disruption of its membrane causes the release of a chemical, much like myrosinase, which transforms a sulfur-based chemical into allicin. Allicin, which is packed with sulfur, is what made my grandfather smell for days, but potentially live so long. These chemicals are further converted to sulfur-containing biproducts present in the urine and breath, thus explaining the phenomenon of garlic breath.
The sulfur-based chemicals in garlic, wasabi, and many similar plants provide more than a foul smell; they can kill harmful fungi on contact. Some even refer to it as “man’s oldest fungicide.”18 Insects seems to share a similar fate as fungi, as contact with sulfur often sends them to an early grave, especially after consuming it. Too much sulfur contact causes its fair share of problems in humans as well, including skin and eye irritation, gastrointestinal upset, and lung irritation and cough. However, significant toxicity from sulfur exposure is rare.
Fighting Cancer with Chemical Warfare?
These potent plant poisons may kill fungi and repel insects, but in humans, a different picture is painted on the cellular level – one that resembles the drill sergeant in Full Metal Jacket. When plants wage chemical warfare on potential predators, the effect on our cells leads to a beneficial process called chemoprevention. By definition, chemoprevention is the “use of natural, synthetic, or biologic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer.”19 In other words, chemoprevention trains and arms our cells to defend against cancer formation or defeat already present cancer cells.
As Benjamin Franklin once said, “an ounce of prevention is worth a pound of cure.” This may be in its truest form when it comes to cancer, as treatment is at times difficult, if not impossible. It comes as no surprise that researchers are always searching for better methods of prevention, and chemoprevention has been an attractive area of research for the past several decades.
Chemopreventative sources that are naturally occurring in our food have immense potential to safely and effectively help in the fight against cancer. Sulforaphane, the isothiocyanate in cruciferous vegetables, activates a cellular process called nuclear factor erythroid 2-related factor 2 (Nrf2 for short).20 Nrf2 then creates a domino effect as it triggers a plethora of cancer-fighting genes and pathways, including regulating the body’s response to free radical damage, or the more scientific terms, oxidative stress and oxidative damage. The specifics are less important, but we can think of Nrf2 as the alarm sounded to wake the troops for battle – in this case against free radical damage and oxidative stress – by activating what is known as the human antioxidant response system. This turns on several antioxidant genes to block oxidative damage and instead activate cellular responses to detoxify potentially damaging chemicals within our cells.21 For instance, Nrf2 is switched on to protect our pancreas from oxidative damage, effectively blocking its destruction and subsequent diabetes (the pancreas makes insulin and a lack of functioning insulin is in essence diabetes).22
Sulforaphane signals to Nrf2 that danger may be coming. As a result, Nrf2 supports detoxification of chemicals and activates the antioxidant defense system via GST, NQO1, and HO-1 to disarm free radicals before causing any damage.
Furthermore, sulfur-based activation of Nrf2 also aids in the detoxification and removal of potential harmful and cancerous chemicals by increasing their ability to mix with water and be discarded. In other words, Nrf2 is activated by oxidative stress and chemicals (harmful or not) to disarm them and alleviate any potential damage. Normally, Nrf2 floats around in the fluid-like cytoplasm within our cells, but upon sensing danger, it jumps to action and travels to the nucleus to activate several defense genes. While, unlike in insects, sulfur may pose little threat to our cells, it appears to directly trigger Nrf2 activation.
The key point with cruciferous and other sulfur-containing anticancer vegetables, is the “false-alarm” signal that our cells receive from organosulfur chemicals. The signal, like Sergeant Hartman, alarms our cellular machinery to produce and train more troops for antioxidant defense and the disarmament of potentially toxic chemicals, the proverbial battle with cancer that awaits us all. The difference of this “false-alarm” from a real threat is that the sulfur merely acts to train the cells – realistically posing minimal threat – to allow them to be better equipped to fight material threats like cancerous chemicals, heavy metals, and DNA-damaging free radicals.
Some fascinating research points to the impact of these vegetables as slightly toxic and stressful to our cells, which results in a form of hormesis to upregulate pathways which can eventually fight cancer. Hormesis is basically our cellular equivalent of the phrase “what doesn’t kill us only makes us stronger.” Sulforaphane is one of these chemicals that doesn’t kill us, but makes our cells stronger. It acts as an oxidant, which provides the stimulus and activation of Nrf2 and several antioxidant pathways within our cells. Other similar stresses include exercise, fasting, and general food restriction; both are activities that stress our body to make it “stronger” in the long run. These stresses can upregulate the mitochondria, an organelle within our cells that is famous for its ability to provide us with energy, but has recently been lauded for its vital role in the fight against cancer.26 Isocyothianates and similar chemicals appear to push the mitochondria into action, initiating an array of lethal defense mechanisms that may prevent or even help treat cancer by blocking the growth, proliferation, and survival of cancer cells.27
Similar to the physical and cellular burn of exercise that creates some oxidizing free radicals, the “stress” from cruciferous vegetables stimulates our mitochondria to produce homemade antioxidants to counterbalance the oxidation and protect our vital DNA.28 Even cancer cells have caught on to this central role of our mitochondria – the bastards can amplify their levels of some of these same pathways – further stressing their importance for survival.25 However, our cells still seem to have the upper hand, as multiple studies show that the organosulfur chemicals in many of these anticancer vegetables can severely stress cancer cells, leading to oxidative damage, and ultimately, death.29
The potential chemopreventative properties of plant derivatives exemplifies the power of food, and in this case, cruciferous vegetables. Studies even suggest that sprouts from cruciferous vegetables provide greater chemoprevention than mature vegetables.30 While vegetables and their defensive chemicals may stimulate our cancer-fighting machinery through cellular stress, their ability to disarm carcinogens before they strike may be just as important.
In the next article, we will discuss the other major benefit of sulfur-containing anticancer vegetables.
The Bitter Benefits of Anticancer Vegetables References:
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