Mediterranean Diet, Hunger and Cancer

Evolutionary, our ancestors were able to survive on one daily meal, but sometimes went hungry for days.  Today, however, most Americans consume three meals a day with additional snacks. The notion that many small meals a day is healthy is being popularized; however, epidemiological studies have reported that a lesser number of eating episodes is associated with a reduced risk of colon cancer and other types of cancer.  Consistent with these results, rodent studies, controlled for caloric intake, have revealed that longer intervals between meals increase resistance to cancer.

Periods of strictly vegetarian diet and fasting are incorporated in many religious traditions.  For example, throughout the year, the Eastern Orthodox calendar includes 180 days of fasting, during which vegetarian days alternate with periods of complete abstinence from food. Thus, a strict Orthodox Christian observes the following weekly fasting rules: only one vegetarian meal on Wednesdays and no food on Fridays. In addition, there are prolonged periods of fasting during the year: the three main ones being the forty days before Christmas, Lent (40-48 days) and the Assumption (15 days).   According to the rules of these fasts, any meat and meat products, eggs, dairy products, fish, oil, and wine are excluded from the diet, although fish, wine, and oil are allowed on certain days of the week.  Interspersed within the long fasting periods are days or even weeks of complete abstinence from food (e.g., the week before Easter, Holy Week).  

Interestingly, this Orthodox Christian fasting regimen has been proposed as an alternative explanation for the health benefits of the Greek Mediterranean diet. Thus, the Mediterranean diet is not only rich in fiber (grains, vegetables and fruit) and olive oil, but it is accompanied by periods of fasting that might be beneficial by slowing down tumor cell growth and preventing cancer.  

The slowing of abnormal cell growth by fasting could be mediated by the changes in metabolism. What are these changes? Fasting forces the body to switch from one source of energy (carbohydrates, such as glucose), to another – fats.  According to metabolite studies, the glucose from the blood and its storage (glycogen, which is simply a chain of many glucose molecules) is utilized within the first 12 hours of complete fast. On day 2 of the fast, the body already relies on processing of fats (from the adipose tissues) to ketones as a source of energy. Does this major shift in metabolism explain the protective effect of fasting against cancer? Likely, yes. It has been long known that some cancer cells are addicted to sugar (glucose) as a source of energy; now we know that many human cancers exhibit this behavior.  

Such abnormal cells have an excess of glucose receptors on their surface, and therefore, “devour” more glucose from the blood than normal cells. Additional mechanisms also force cancer cells to rely mostly on glucose as their source of energy. Because of this dependence on glucose, the depletion of glucose (as in fasting) can result in the death of the tumor cells. Furthermore, in all cancer cells the depletion of glucose is likely to suppress all signaling pathways that support survival.

In 1921, Dr. Wilder proposed that the effects of fasting on the body could be mimicked by a diet, in which fat was the main component, the ketogenic diet. This diet consists mostly of fat; thus, the ratio of fat : protein : carbohydrate in this diet is close to 90 : 8 : 2. With this diet, the organism uses fat as its main source of energy and forms ketones the same way these compounds are produced during fasting. However, whereas in fasting the body uses its own fat storage to cope with the lack of other energy sources, during the ketogenic diet, exogenous (external) fat from the food is being processed. This difference between fasting and ketogenic diet results in very different levels of LDL cholesterol: fasting individuals compared to controls present with 12.5% lower end-total cholesterol (p < 0.001) and 15.9% lower end-LDL cholesterol (p< 0.001). Therefore, be aware that during ketogenic diet the levels of cholesterol skyrocket, and this is obviously not good for the long-term health outcomes.

Despite the ability of the fasting regimen and ketogenic diet to suppress tumor growth, the cancer therapeutic application of these approaches is limited in the U.S. These modalities are mostly applied as adjuvant (complimentary) modalities to mainstream cancer treatments. One reason to shy away from these approaches is that our medical doctors are not taught about them, and therefore, nor aware of them.

Here I did not discuss the benefits of fasting in reducing obesity and the obesity-related metabolic syndrome with its downstream consequences (e.g., cardiovascular diseases, type 2 diabetes, etc.). I also neglected to discuss the additional benefits of Mediterranean diet to human health. Hopefully, these will be subjects of future posts.

Actionables

It has been proposed that limiting the food and drink intake to 6-10 hours a day may have the same benefits as any longer-term fasting regimen. In practice, this means that one could fast  from early dinner till late breakfast next day, or skip breakfast or dinner. 

PS:
A later post also explores this topic.
 

New News on The Red Meat/Processed Meat Cancer Risk

There is a well-established link between consumption of processed meat and cancer risk, particularly risk for colorectal cancer. Now, the link has been made more explicit, with the World Health Organization (WHO) stating that these foodstuffs can cause cancer, based on an evidence review by 22 scientists, the details of which were published in the journal, The Lancet. The link between consumption of red meat and cancer was less clear, but is considered probable.

This story has gotten a lot of press in the popular media. See here and also here and also here. A summary from these stories is:

The World Health Organization has deemed that processed meats — such as bacon, sausages and hot dogs — cause cancer.

In addition, the WHO says red meats including beef, pork, veal and lamb are "probably carcinogenic" to people.

A group of 22 scientists reviewed the evidence linking red meat and processed meat consumption to cancer, and concluded that eating processed meats regularly increases the risk of colorectal cancer. Their evidence review is explained in an article published in The Lancet.
 
The conclusion puts processed meats in the same category of cancer risk as tobacco smoking and asbestos. But this does not mean that they are equally dangerous, says the International Agency for Research on Cancer (IARC) — the agency within the WHO that sets the classifications. And it's important to note that even things such as aloe vera are on the list of possible carcinogens.

In a Q & A released by the IARC, the agency says that "eating meat has known health benefits," but also points out that the cancer risk increases with the amount of meat consumed. As we've reported, studies show that the heaviest meat eaters tend to have the highest risk.

The IARC says high-temperature cooking methods (such as cooking meat in direct contact with a flame) produce more carcinogenic compounds. However, the group says that therewere not enough data "to reach a conclusion about whether the way meat is cooked affects the risk of cancer."

Susan Gapstur of the American Cancer Society (ACS) says the society recommends "consuming a healthy diet with an emphasis on plant foods and limiting consumption of processed meat and red meat."

The recommendation, Gapstur tells The Salt, is based on research. For instance, a systematic literature review on colorectal cancer published in 2011 by the World Cancer Research Fund found a statistically significant, 16-percent increased risk of colorectal cancer associated with each 100 grams of red and processed meat consumed. As the ACS points out, this is an amount of meat roughly equivalent in size to a deck of cards.

There is of course controversy, some of which comes from groups labeled “a powerful lobbying industry.” Thus:

…the panel decision was not unanimous, and is expected to face criticism within the United States, where processed and red meat still forms the base of most meals, and is backed by a powerful lobbying industry.

The National Cattleman’s Beef Association, the national trade association that represents U.S. cattle producers, put out a press release soon after the WHO announcement that — not surprisingly — questions the findings. “Most scientists agree that it is unrealistic to isolate a single food as a cause of cancer from a complex dietary pattern further confounded by lifestyle and environmental factors,” the association says in the release.

“The available scientific evidence simply does not support a causal relationship between red or processed meat and any type of cancer,” Shalene McNeill, executive director of human nutrition at the National Cattlemen’s Beef Association said in the release.

In addition, more critical comments are:

"Scientific evidence shows cancer is a complex disease not caused by single foods and that a balanced diet and healthy lifestyle choices are essential to good health," writes Barry Carpenter, president of the North American Meat Institute, in a statement on the new WHO classification.

Carpenter says it's important to put this new classification in context. "IARC's panel was given the basic task of looking at hazards that meat could pose at some level, under circumstance, but was not asked to consider any off-setting benefits, like the nutrition that meat delivers or the implications of drastically reducing or removing meat from the diet altogether," the statement concludes.

I myself would trust more the scientists performing the evidence study, and the physician making the recommendations, than groups that have a vested economic interest in meat consumption, particularly consumption of red meat.

I myself eat red meat rarely, getting the vast bulk of my animal protein intake from chicken, turkey, fish, eggs, and dairy (all in moderation). As far as processed meat, I may have a breakfast sandwich a couple of times per month that has turkey sausage, but that’s it. My typical everyday diet does not include red or processed meat.

In my opinion, the wise choice is moderation. Eating red meat every day, or even multiple times per week, is in my opinion unwise given these data. Eating processed meat, such as bacon and lunch meats, more often than a few times per month is also unwise.

Note that cancer risk is directly related to the amount of these meats consumed. Keep in mind also that the definition of “processed meat” varies. Some would consider canned fish (tuna, salmon, etc.) to be “processed meat.” I eat those frequently; obviously I am not putting them in the same category as stereotypical processed meat like bacon or ham. Others specifically exclude canned tuna or salmon from the list, as I do, since the canning process, and addition of minimal amounts of salt, is not equivalent to the smoking, curing, or salting processes used for the foods typically considered “processed meats.” And of course, fish meat is not considered “meat” per se in the sense used by nutritionists, who focus on the flesh of land animals and birds.

Therefore, canned fish (in water, not oil!) should be considered different from eating a slab of bacon; eating such fish is considered healthy (but note certain types of tuna can have higher levels of mercury).

Update: list of red and processed meat.
Actionables: Eat less red meat and processed meat.

Fructose - Your Foe

We all know that sugar is bad for us. This is why the World Health Organization recommends us to limit our sugar (sucrose) intake to six teaspoons a day. But did you know that fructose, one of the individual types of sugar, is toxic for you? You may not be aware that you consume fructose every day. It is present in regular sugar “sucrose” (composed by glucose and fructose at a ratio of 1:1); however, its main source in the diet is the omnipresent high fructose corn syrup. This “syrup” is added to almost everything: from soft drinks, candy, bread, to tomato soup and ketchup. It is even in some potato and macaroni salads in the neighborhood deli. The fruit juices also contain considerable levels of fructose.
 
Whereas the sugar glucose is used as an energy source by every single cell in the body, fructose is not. Be aware, however, that excess of glucose intake could be converted into fructose in the body. Unlike glucose, fructose can be utilized only by liver cells, where fructose processing results in increased levels of the toxic uric acid and fat. Thus, excess of fructose intake from the diet results in excess fat in the liver (and “fatty liver” disease) and excess fat circulating in the blood. The increased fat in the blood accumulates in the body, and leads to obesity, cardiovascular (heart) diseases, and type 2 diabetes. In fact, fructose is the main culprit for metabolic syndrome, the condition in which high blood pressure, high blood sugar, excess body fat around the waist, and high cholesterol levels co-occur.


Actionable

• Read the ingredients of each food product in your refrigerator and pantry. If “high fructose corn syrup” is one of the ingredients, discard the product. Stop buying such products.

• Stop drinking soft drinks and fruit juices. Instead, eat fruit and drink water.

• Do not allow your children to drink anything else but water and plain milk.

• Laugh with this Coca Cola video. Coca Cola is one of the companies that have drowned us in drinks with high fructose corn syrup and sugar.

• Next time you want to eat out, think twice: do you know what is in your meal? The only way to be sure is to cook it yourself. Learn how to cook with these affordable recipes from the free Good and Cheap cookbook.

• If you do eat out and you are served in a plate larger than 9 inches in diameter, chances are that there is too much food. Eat only half of the meal and take the other half home.

An ounce of prevention is worth a pound of cure

Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory, 2014

Ben Franklin’s statement, “An ounce of prevention is worth a pound of cure”, is particularly true in times of scarce funds and crisis.  We have both on our hands: the country is struggling financially and it has an obesity crisis that projects itself into a health care crisis. Watch the most comprehensive account of the obesity epidemic in the HBO documentary The Weight of The Nation. Currently, 34.9% or 78.6 million of U.S. adults are obese and approximately the same number of people are overweight.  According to the Trust for America’s Health, by 2030 obesity-related health care costs may exceed $195 billion. This calculation is based upon the health care cost of obesity-related type 2 diabetes, coronary heart disease and stroke, and cancer.  Although the connection between the first two chronic diseases and obesity is well known, not too many of us associate obesity with cancer; however, obesity is an established risk factor for at least ten types of cancer. 

As obesity becomes prevalent in our country, we begin to face its terrifying consequences even among the young.  Historically associated with old age, colorectal cancer is now on the rise among people younger than 50 years of age. A strong warning comes from the finding that in the past 35 years, colorectal cancer incidence has increased among 20- to 34-year olds, and if the trend continues, there will be up to a 90% increase in colon cancer incidence, and 124.2% increase in rectal cancer incidence, in this age group by 2030. Consider that cancer usually takes years to establish; in the case of colorectal cancer, it is believed that it takes at least 10 years for the malignancy to develop. If we do simple math, for 20- to 34-year olds to be diagnosed with colorectal cancer means that the development of cancer started when the individuals were 10 to 24-years old. 

Why is the initiation of malignancy occurring at this young age? Why was not this happening 35 years ago? The dramatic shift in age of diagnosis is likely due to the increasing obesity among children (aged 6 to 11) and adolescents (aged 12 to 19).  What we eat and how much we move accounts for obesity. It is also likely that the biggest culprit in these past 35 years has been the change in the food industry, as discussed by Dr. Robert Lustig.  Since immediate government-initiated steps to revamp the food industry are not in sight, we, the consumers, should be aware of how to protect ourselves and our children from becoming overweight and obese.  There are four simple recommendations against childhood obesity, and these should be publicized by all of us. Being knowledgeable about food will not only save our money, but it will also save our lives.  Be informed, be in charge of your life.

Fat Mice Get Bigger Tumors

It is well known that obesity increases the risk for various forms of cancer.  A National Cancer Institute fact sheet on the obesity-cancer link provides useful information on this topic, as does another information source from Cancer Research UK.

Mouse models of human cancer are often used to investigate the mechanisms of the human disease. A recent paper in the journal Oncotarget (free online) demonstrates that even in mice, obesity due to a high fat diet increases the development of cancer, in this case, colon cancer.  Thus, colon cancer cells injected into the mice resulted in larger tumors when the mice were fed a high fat diet.  The abstract of the paper is as follows:

There are an increasing number of reports on obesity being a key risk factor for the development of colon cancer. Our goal in this study was to explore the metabolic networks and molecular signaling pathways linking obesity, adipose tissue and colon cancer. Using in-vivo experiments, we found that mice fed a high-fat diet (HFD) and injected with MC38 colon cancer cells develop significantly larger tumors than their counterparts fed a control diet. In ex-vivo experiments, MC38 and CT26 colon cancer cells exposed to conditioned media (CM) from the adipose tissue of HFD-fed mice demonstrated significantly lower oxygen consumption rate as well as lower maximal oxygen consumption rate after carbonyl cyanide-4-trifluoromethoxy-phenylhydrazone treatment. In addition, in-vitro assays showed downregulated expression of mitochondrial genes in colon cancer cells exposed to CM prepared from the visceral fat of HFD-fed mice or to leptin. Interestingly, leptin levels detected in the media of adipose tissue explants co-cultured with MC38 cancer cells were higher than in adipose tissue explants cultures, indicating cross talk between the adipose tissue and the cancer cells. Salient findings of the present study demonstrate that this crosstalk is mediated at least partially by the JNK/STAT3-signaling pathway.

Mitochondria are the “powerhouse of the cell,” responsible for generating most of the ATP that provides the “chemical energy” the cells require, and mitochondria are involved in other important processes, such as programmed cell death. This paper shows that diet-derived obesity causes the mitochondria to malfunction and this contributes to increased tumor formation.  An important cell signaling pathway called JNK/STA3 is apparently involved in the association between obesity and cancer in these over-fed mice. The authors conclude:

We conclude from this study that (i) obesity induces mitochondrial dysfunction, promoting cancer in several organs adjacent to the visceral fat, such as the colon, and (ii) inhibition of the JNK/STAT3-signaling pathway in colon cancer cells seems to be critical for reestablishing mitochondrial function and overcoming the glycolytic phenotype. We assume that this signaling pathway may be partly responsible for the relation between obesity–leptin-induced mitochondrial dysfunction and colon cancer.

What does this mean for the typical person, who may not be familiar with all the scientific jargon used? This paper is yet more evidence of the serious damage done to the organism by diet-induced obesity, damaging the mitochondria and affecting signaling in many cells, and these negative effects contribute to cancer development. What is happening in these mice likely occurs in people as well. Losing weight to transition to a more normal BMI – and optimally, never becoming obese to begin with – must rank as one of the most important things you can do for your health. And of course, the benefits are not only restricted to cancer, but to cardiovascular diseases, metabolic diseases (e.g., diabetes), and much more.

The mice in this study didn’t have a choice about their obesity, they do not have the capacity to understand the diet they were given, and the effects that diet had on their bodies. We in contrast do understand and do have a choice, and we need to choose wisely.