Say No To Cancer… with Diet
Cancer, one of the diseases associated with modern diet, is at least partially preventable
Every year, the American Cancer Society (ACS) compiles the most recent data on cancer incidence, mortality, and survival rates. Sources include the National Center for Health Statistics; the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Assn. of Central Cancer Registries. ACS uses this information to project the numbers of new cancer cases and deaths that will occur in the US in the current year.
Projections for this year still reflect the challenges cancers pose to the health care system. By 2018, we can expect around 1.7 million new cases of cancer, with a projected mortality rate of about 36% (600,920 deaths). The picture is worse for men than women, with a projected incidence rate of 20% higher for men and a cancer death rate 40% higher.
Naturally, consumers want to know what can be done on an individual basis to prevent cancer. Are there realistic lifestyle changes that can mitigate the odds of contracting cancer? Can damage be minimized and survival chances increased, if diagnosed? The answer to both is “Yes.”
Cancer is one of the diseases associated with modern diet and lifestyle, and has been deemed at least partially preventable. Some modifiable behaviors can skew the odds against getting cancer, and the odds of recovering from it, in our favor.
Topping any list of preventative strategies is diet. This is because of the potentially direct impact of individual nutrients—and because of the indirect impact on obesity, a definite risk factor in many cancers.
The big picture of cancer risk reduction hasn’t changed much in decades, and the dietary prescription remains, “increase the proportion of fruits and vegetables in the diet and maintain a healthy body weight.” However, attention increasingly is turning to more specific ingredients. The effects of fiber, antioxidants, meat, and sugar, as well as any nutrient that affects the immune system, are key. More recently, the gut microbiome (the system of healthy bacteria that populate the digestive system) is gaining attention for its role in immunity and cancer prevention.
The nature of cancer itself presents challenges regarding specific recommendations of its prevention. Cancer is not a single disease, but an overall term that describes cells of different origins that share the general mechanism of continuous cell division without normal regulation. That is, cell growth is out of control, and the cells themselves are abnormal.
These aberrant cells fail to differentiate normally, to grow up and mature into well-behaving cells as part of healthy tissue. Instead, endlessly-dividing cells at different stages of maturity invade tissues both locally and far from the origin of formation. That means the strategy of prevention has multiple and different potential targets. Thus, prevention may focus on cell transformation (the conversion to out-of-control cell division), proliferation, and invasion.
The development of cancer requires an accumulation of mutations that begins with the cells of origin and continues with descendants of those original cells. These descendants evolve over time through successive cycles of natural
selection in the local environment, in much the same way that evolution works on populations of plants and animals.
At each stage of progression, cancer cells are presented with new challenges. The local environment might be low in oxygen, scarce in nutrients, or rife with natural barriers to migration. When cancer cells divide, they form clones of the original aberrant cell. But, with successive mutations and natural selection, subclones are formed, resulting in new species that differ from the original cells.
Cancer cells metabolize fuel differently from normal (referred to as “somatic”) cells. Normal cells have two ways of utilizing blood glucose as fuel. One mechanism requires oxygen, and the other doesn’t. They are referred to as aerobic and anaerobic metabolism. The former produces more energy, while the latter produces energy at a faster rate.
In normal cells, the by-products of aerobic metabolism inhibit the anaerobic pathway from consuming more glucose. But in cancer cells, this feedback mechanism is held in check; it doesn’t halt the use of glucose through the anaerobic pathway, so the cells can still consume glucose without oxygen at a high rate.
The increased ability to consume glucose by some cancer cells has led to a major diagnostic procedure that looks at the rate of utilization of a glucose derivative. This, coupled with the fact that some cancers have insulin receptors that enhance the uptake of glucose, has led to the simplistic strategy of blaming cancer on carbohydrate intake.
The rapid and potentially invasive cell division that characterizes cancer cells requires more than just a source of energy. It also requires a source of nitrogen for amino acid synthesis. Nitrogen is the critical element that separates proteins from fats and carbohydrates.
For example, the non-essential amino acid glutamine is important for tumor growth, where it serves as a nitrogen donor. Researchers have made many recent advances in understanding the metabolism of cancer cells and have identified several other metabolic pathways. They are moving beyond the idea that cancer metabolism amounts to little more than increased capacity for glucose and glutamine metabolism as sources of energy production.
The story of cancer metabolism turns out to be far more complex, as the aberrant cells have to cope with insufficient nutrients resulting from insufficient circulation. This can require the cancer cells to rely on a number of metabolic fuels, depending upon the local environment, thwarting the strategy to selectively starve cancer cells.
Antioxidants and Cancer
Because diets associated with low risk of cancer contain many antioxidants, there is much interest in the potential for preventing cancer by using isolated forms of these compounds. Antioxidants are naturally occurring in foods, especially plant foods, such as fruits and vegetables, and have the potential to halt the damage done by free oxygen radicals.
Free radicals are highly reactive chemicals that can harm cells. They are formed naturally in the body as a byproduct of metabolism and play an important role in many normal cellular processes. The damaging compounds are created when an atom gains or loses an electron, a small negatively charged particle found at distinct distances from the nucleus or center of the atom. This loss or gain makes the atom (or molecule consisting of two or more atoms) highly reactive.
However, at high concentrations in certain locations, free radicals can damage the major components of cells, including DNA, proteins, and cell membranes. Free radical damage, especially damage to DNA, has been shown to play a role in the development and proliferation of cancer cells.
In response to the production of free radicals, the body makes its own antioxidants. However, the amount the body produces is not enough to cope with the additional generation of free radicals resulting from the disease process itself.
Many nutrients found in foods either double as antioxidants or participate in antioxidant activity. These nutrients include vitamin A and its plant precursor beta-carotene; vitamins C; and vitamin E in its tocopherol and especially its tocotrienol forms, along with minerals like selenium and iron that are used to create antioxidants. Numerous studies have investigated the anti-cancer potential of isolated antioxidants.
One antioxidant vitamin is showing impressive promise when it comes to battling cancer is the tocotrienol form of vitamin E. A study of cancer patients published in 2015 in EBioMedicine built on previous studies in which tocotrienol demonstrated abilities to prevent the abnormal growth of cells and the chemical activity of cancer cell development and growth in preclinical models of pancreatic cancer.
Results of the study, which was designed to determine the biologically effective dose of delta-tocotrienol, as well as its potential effectiveness against precancerous pancreatic cells, established that 800mg daily was able to “induce apoptosis [programmed cell death] in pre-malignant lesions but not in adjacent normal tissue,” and helped confirm findings by the study’s authors and researchers showing a “selective killing effect of tocotrienols against cancer cells over normal cells.”
Observational cases reported in patients with pancreatic, ovarian, breast, metastatic colorectal, and other cancers have shown good response to tocotrienol, especially in patients during the late-stage phase, affirms Alexander Schauss, PhD, senior director of research and CEO of AIBMR Life Sciences Inc. He points to a number of studies scheduled or in progress based on such observational cases, stressing that the principal investigators—considered some of Europe’s most respected—are different for each study.
“Should the results of these cancer studies show similar benefits to those observed in the NCI-funded study of late-stage pancreatic cancer patients, one could expect an explosion of interest to incorporate delta-tocotrienol into a wide range of foods,” Schauss states.
According to Schauss, the annatto seed of the Brazilian achiote tree (Bixa orellana) is a premier source of delta-tocotrienol. This form of vitamin E, he explains, “has demonstrated the most promising results to date of any of the four tocotrienols found in vitamin E, as reported in many in vitro and in vivo animal studies, and in several human studies.”
Achiote seed is well-known in the food industry, since the fruit is the source of red color owing to its carotenoid pigments (mainly bixin and norbixin) found in the seed’s waxy, reddish coating. The FDA classifies the colorant derived from this fruit as “exempt of certification,” meaning it is considered a natural color, often shown as “annatto color” or “colored with annatto” on labels.
“It would be wise for the food industry to target an interest in delta-tocotrienol, given it has shown the most promise as a potential potent anti-cancer agent among any of the tocotrienols of the eight isomers of vitamin E,” adds Schauss.
On the other hand, Schauss cautions, “Attention also should be paid by the food industry to emerging evidence suggesting that alpha-tocopherol, an effective antioxidant, might interfere with the anti-cancer benefits of gamma- and delta-tocotrienol.”
This is worth noting, because alpha-tocopherol is one of the most commonly used natural antioxidants in food processing.
“Food formulators should consider focusing on the use of polyphenol extracts to replace alpha-tocopherol as an antioxidant should further studies offer more compelling evidence of tocopherol inhibiting the beneficial properties of tocotrienols,” says Schauss. “Much more is still to be learned about the tocotrienols and their benefits, particularly regarding the ‘billion-dollar question’: Can they prevent common cancers from developing or progressing?”
In addition to nutrients, there is a vast number of antioxidants created by plants to protect themselves from free radicals that result from normal photosynthesis and exposure to ultraviolet light. Many of these received a great deal of attention in the past, and many more are yet to be discovered. Some that have shown a long history of potential are being investigated more carefully, with encouraging results.
An excellent example is that of broccoli and other vegetables in the Brassica genus, including cabbage, Brussels sprouts, kale, and mustard (also called cruciferous vegetables). In addition to being nutrient-dense and rich in several carotenoids
(beta-carotene, lutein, zeaxanthin), they also contain vitamins C, E, and K; folate; and minerals.
Cruciferous vegetables also contain phytochemical compounds called glucosinolates. These are converted to several other compounds during digestion including indoles, nitriles, thiocyanates, and isothiocyanates. All of these compounds have been studied for their anti-cancer properties, including an ability to inhibit the development of cancerous cells of the bladder, breast, colon, liver, lung, and stomach.
Suggested mechanisms of protection include protection from DNA damage; induction of cancer cell death (rather than endless cell division), and inhibition of tumor migration into healthy tissues. A although results of studies have been mixed, this holds great promise for humans, because said mixed results generally range from inconclusive or statistically insignificant protection to significant protection via consumption of the compound-containing plant itself.
Researchers at Oregon State University recently published findings of a more in-depth study of broccoli in the Journal of Nutritional Biochemistry. The researchers focused on the glucosinolate compound sulforaphane, previously recognized as contributing to the prevention of prostate cancer. The results of the study indicated that sulforaphane works at the genetic level, influencing a type of RNA called lncRNA, once believed to have no function.
The researchers determined that, instead, lncRNAs could “play a critical role in triggering cells to become malignant and spread” and serve a “major role in cell biology and development,” controlling which genes are switched on. It has been suggested that when such genes are “dysregulated” they can “contribute to multiple disease processes, including cancer.” The scientists further noted that lncRNAs are “highly cell- and tissue-specific.”
Emily Ho, PhD, a principal investigator with the Linus Pauling Institute, suggests that sulforaphane—which is especially concentrated in broccoli—“could open the door to a whole range of new dietary strategies.” Ho, who also is the endowed director of the Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health at Oregon State University, adds that “foods or drugs that might play a role in cancer suppression or therapeutic control.”
A Rainbow of Protection
In the class of colorful plants that can protect against cancer, purple, red, and blue fruits and vegetables also have a long history of study for anti-cancer properties. These foods include the dark and juicy berries rich in the phytochemical groups called flavonoids (including especially the anthocyanins that give them their color) and polyphenols.
Polyphenols are a well-studied group of antioxidants, and many of these compounds have the potential to prevent several diseases. Numerous polyphenols display potent antioxidant properties and may reduce the oxidative stress associated with some diseases. Regarding cancer, polyphenols have been shown in laboratory studies to inhibit carcinogenesis and induce tumor cell death. Two of the most interesting polyphenols are curcumin and resveratrol.
Curcumin and resveratrol have been the subject of thousands of studies in the past 10 years. Both have been described as promising anticancer compounds, but the exact mechanism of action remains unclear. Curcumin (diferuloylmethane) is an active ingredient found in the perennial herb Curcuma longa, or turmeric. It is responsible for the spice’s bright yellow color. It has long been employed as a traditional medicine component in China and India, and is considered both an anti-inflammatory and an antioxidant.
Resveratrol (trihydroxystilbene) is synthetized by a variety of plants, including peanuts, pistachios, grapes, blueberries, cranberries, and cocoa. Its antioxidant effect has been well established using several laboratory techniques. As a result, resveratrol has been closely investigated for its potential as a preventative, use as a treatment for several diseases, regulation of the immune system, and cancer prevention. However, results from clinical studies in humans remain mixed.
Many foods like nuts, seeds, vegetable oils, cereals, and legumes are rich sources of specific phytosterols, such as the subgroups sitosterol and campesterol. Diets rich in phytosterols could reduce cancer risk by up to 20%.
Some studies suggest that phytosterols might inhibit tumor growth and metastasis without interfering with normal cell death. Phytosterols could also enable antitumor responses by improving immune response.
An increased interest in the medicinal value of mushrooms includes
investigation of the science behind centuries of anecdotal evidence. Of value to food product developers, a number of medicinal mushrooms also have GRAS status for use in foods. These include maitake (Grifola frondosa), popularly called hen of the woods and considered one of the best-selling immune-boosting mushrooms used by people fighting cancer.
The common and well-employed shiitake mushroom (Lentinus edodes) is being studied for possible cancer-fighting attributes, as is the black fungus mushroom, also called the wood ear (Auricularia polytricha). The latter, while more exotic, is commonly used in Asian recipes. These are just a few of dozens of mushrooms pulling double duty as tasty, savory vegetarian sources of umami flavoring and as health-protection agents.
Vitamin D and Cancer
Vitamin D describes fat-soluble pro-hormones (substances that the body converts into hormones). Its primary function is to stabilize blood levels of calcium and phosphorus, enhancing absorption, and pulling reserves of these minerals from bones when necessary.
The effect is to maintain steady blood levels while strengthening bones and teeth. Vitamin D is a derivative of cholesterol. It concentrates in the skin and is activated in a series of reactions following sun exposure. Since few foods are naturally rich in vitamin D (the exception being fatty fish, dairy, eggs, and certain mushrooms), most people get vitamin D from sunlight exposure and from D-fortified products like milk, milk analogs, juices, and cereals.
The link between vitamin D and cancer stemmed from early epidemiologic research that showed lower incidence and death rates for certain cancers among individuals living in southern latitudes, where levels of exposure to sunlight were relatively high, compared with those living in northern latitudes. Animal and in vitro studies suggested an association between vitamin D and cancer risk, along with potential mechanisms.
Vitamin D might slow or prevent the development of cancer by promoting normal cellular differentiation. It also could decrease cancer cell growth, stimulate tumor cell death via apoptosis, or inhibit cancer’s invasive capability.
Several epidemiologic studies have investigated the potential link between higher vitamin D intakes or higher blood levels of vitamin D and lower risks of specific cancers. The results have been inconsistent, possibly due to the inherent difficulties in the studies. Some dietary studies failed to consider vitamin D made in the skin from sunlight exposure. For this reason, blood levels of vitamin D did not necessarily reflect true vitamin D status.
Some epidemiologic studies have shown a connection between higher intake or blood levels of vitamin D and reduced risk of colorectal cancer. Also, the Women’s Health Initiative’s randomized trial found no incidence of colorectal cancer in healthy women who took vitamin D and calcium supplements for an average of seven years. Research is ongoing, but with many Americans deficient in this powerful vitamin, processors still benefit from finding more ways to include it in formulations.
A recent review of soy foods suggested a weak but inverse association between higher consumption of dietary isoflavones from soy products, and legumes and endometrial cancer risk. In other words, more soy consumption apparently resulted in a slightly lower risk of this form of cancer. However, some research into the connection between soy intake and reduced risk of breast cancer yielded mixed results. Thus, some women at risk for estrogen-influenced breast cancer are warned to avoid soy due to its phytoestrogen content.
On the other hand, other studies indicate that early and continued intake of soy can reduce later risk of breast cancer in some women. The current recommendation, according to the nonprofit breast cancer information group Breastcancer.org, is “that women who take hormonal therapy or who have estrogen-receptor-positive breast cancer [should] avoid soy supplements, because they contain high concentrations of isoflavones. But in general, it’s fine to eat moderate amounts of soy foods as part of a balanced diet.”
The Sweet Ending
Good news in the area of eating to help ward off cancer is that compounds in chocolate appear to be helpful. Cocoa beans, and the chocolate made from them (especially dark chocolate) are rich in flavonols and procyanidins, as well as other compounds that have been shown to help inhibit growth and proliferation of cancers of the colon, with the latter compound even showing evidence of an ability to induce programmed cell death in some cancer cells.
While cocoa butter is a component in some skin creams, a 12-week, parallel, double-blind, randomized clinical trial published in 2014 in the Nutrition Journal did demonstrate a slight increase in protective effect of dietary cocoa on skin damage from UV rays. However, the effect was not deemed statistically significant enough to warrant recommending chocolate for skin health.
A recent study on ovarian cancer that used a procyanidin-rich extract of natural cocoa powder did confirm an ability to induce cancer cell death. Other studies have shown cocoa compounds to be especially effective in helping the body excrete harmful oxygen free-radicals and reduce inflammation.
Cancer cells seem to thrive on extremes—inflammation, pollutants, obesity, and dietary excesses, including alcohol. While the translation from promising chemicals in plants to cancer prevention is not without difficulties and complications, plants contain thousands of chemicals acting synergistically in ways that cannot be duplicated by isolated systems.
It is clear is that diet does play a general role in protection against cancer. This confirms that specific foods and ingredients can be reasonably included in food and beverage formulations with an eye toward thwarting or derailing this killer disease.
Originally appeared in the May, 2017 issue of Prepared Foods as Say No To Cancer… with Diet.
Quick Cancer Stats
Cancer cells are of varied origins. They can arise from different tissues by an accumulation of mutations, or mistakes in the genetic code during cell division that happen over time. (In the average lifespan there are more than 10 trillion cell divisions.) Or, cancer cells can arise due to outside damages to the genetic code. Such insults, as they are called, are caused by the sun; other forms of electromagnetic radiation; and pollutants in the air, water, and food. These, too, take time. The rise in cancers resulting from the nuclear explosions in Hiroshima and Nagasaki occurred about five years after the attacks. Similarly, cancers arising from industrial exposure to carcinogens may happen five, 10, or 20 years later.
Cancers grow at an unsteady pace marked by starts and stops as inherited changes resulting from successive mutations (some of which provide advantages over more normal cells). There is a large element of chance in this progression, which explains why there can be spontaneous remissions, and why most people die of causes other than cancer, even though cancer cells are present.
Over the past decade (2004-2013), the overall cancer incidence rate has been stable in women, but declined by approximately 2% annually in men. The cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. However, this reflects a cumulative drop of about 25% from the peak of the 1990s. Also, according to the American Cancer Society, “although the cancer death rate was 15% higher in African Americans than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of African Americans who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%).”
Meat and Cancer
In October of 2016, 22 scientists from 10 countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to review more than 800 studies on the link between meat consumption and cancer. These results have been published online in the medical journal The Lancet. The majority position “concluded that there is sufficient evidence in human beings for the carcinogenicity of the consumption of processed meat.”
The strongest link was between processed meats and colon and stomach cancer. In addition, red meat was classed as “probably carcinogenic to humans,” with the link extending to pancreatic and prostate cancer.
However, the scientists noted that there was “inadequate evidence in experimental animals” to definitively prove this link. Recommendations are to limit red meat consumption to 500g per week—less than 3oz per day. It should be noted that the findings were strongly contested by not only industry, but also by other nutrition researchers, and further study has been called for.