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.