Fasting for Life: Medical Proof Fasting Reduces Risk of Heart Disease, Cancer, and Diabetes

Chapter 4

WHY FASTING WORKS

To lengthen thy life, lessen thy meals.

—BENJAMIN FRANKLIN1

BEFORE I REVIEW INFORMATION ABOUT THE SPECIFIC markers of health that fasting has been shown to improve, let us pause to answer a question that may have arisen as you have read: Why does fasting have such a profound effect on human health? Scientists are still grappling with all the details of fasting to explain this. Many have offered propositions (what scientists like to call “a hypothesis”) regarding the impact of fasting on overall health. However, reviewing the available data, it appears for now that the scientific community agrees on two possible explanations:

1. The hormetic effect

2. The fact that fasting reduces oxidative damage.

The effect of hormesis

In one study published in 2008, the researcher wrote about how hormesis in aging refers to beneficial effects resulting from the cellular responses to mild, repeated stress.2 As an aging (and of course, disease) retardant, hormesis is based on the principle that repeated exposure to mild stress stimulates maintenance and repair processes.3

There is considerable evidence from highly controlled studies of laboratory animals that reduced dietary energy intake (either controlled caloric restriction or intermittent fasting) can increase the resistance of the animals’ cells to various types of stress.4

Mild stress, by the way, appears to benefit the body. For example, have you ever stopped to wonder why exercise is beneficial? Strictly speaking—at least at the biochemical level—physical activity shouldn’t be good. Why? It is a well-documented scientific fact that exercise increases the production of various potentially harmful substances in your body.5 Such substances include reactive free radicals (such as reactive oxygen species and nitrogen species), aldehydes, and acids. During exercise your metabolic rate highly increases, due to up to a twentyfold increase in mitochondrial respiration and oxidative phosphorylation (the process by which the body utilizes oxygen we breath in to break down food into energy molecules that power our being). The combined effect is that prolonged exercise results in formation and accumulation of rather harmful substances in your body.6 Yet when done moderately and intermittently, exercise produces long-term beneficial effects. What shouldn’t be a positive ends up producing a beneficial effect on the whole organism. This paradox provides a good model to explain the positive effect of fasting through hormesis.

Like exercise, fasting is what biologists call a mild stress-producing signal or stressor. According to researcher S. I. Rattan, stress may be “defined as a signal generated by any physical, chemical or biological factor (stressor), which in a living system initiates a series of events in order to counteract, adapt, and survive.”7 This general ability of a living organism to adapt to the repeated presence of a low-intensity stressor by stimulating beneficial (but counter-stressor) effects is generally known as hormesis. In healthy aging research, hormesis refers to beneficial effects resulting from cellular responses to mild, repeated stress—such as fasting.

In other words, the cascading effects you experience after fasting are hormetic, much like the benefits of exercise. Restricting the body’s caloric intake, if done mildly and repeatedly, serves as a mild “stress” to the body. In return, your body initiates a range of cellular activities to adapt to this stress. Because your body is attempting to release effects to counter this stress signal (normally a bad thing), your body ends up releasing a range of positive cellular and physiological responses. Together, they are more beneficial to the body than otherwise possible.8

If you think about it, this makes a lot of sense. Vaccines work in a similar fashion. A doctor injects you with a foreign body, such as a chemical or genetic material (known as an antigen). Because of prior studies, scientists know the antigen will cause the body’s immune system to produce certain proteins known as antibodies, which will help fight that invading enemy. Although there are substantive differences between the mechanisms of fasting and vaccination, it is still clear that the overall effect in both cases is beneficial. Is there any scientific proof to back up the claim that fasting has this kind of effect? Yes. Several studies on mice and other animals have shown that fasting helps them to survive heat stress more than those on regular meals, protecting them from damage done by toxic chemical agents.9

Scientists involved in research on healthy aging are continuing to investigate the exact mechanism by which fasting works via hormesis. Still, scientific results seem to strongly confirm the following suggestion: animals on caloric restriction consistently show elevated levels of stress-regulating hormones—glucocorticoids and particularly plasma-free corticosterone.10 Why is this important? Because mammals need glucocorticoids in order to cope with harmful environments.11 To prove that increased levels of these stress-fighting hormones are not the result of some accident, scientists have observed that fasting helps to prevent cancer in rodents. But when they surgically remove the organ that produces these stress hormones, these rodents lose the ability to prevent cancer through fasting.12 What this shows is that fasting does something to stimulate adrenaline to produce these stress-regulating hormones. There hormones then work synergistically with other physiological processes to (for example) prevent cancer.

Preventing oxidative damage

A pair of studies illustrate how fasting is further beneficial in reducing oxidative stress, which refers to the imbalance between the production of free radicals and the body’s ability to neutralize them through antioxidants. To quote the authors:

• “Caloric restriction decreases the steady-state concentration of the production of oxidative damage to proteins, DNA, and lipids.”13

• “Recent evidence suggests that antioxidant supplements (although highly recommended by the pharmaceutical industry and taken by many individuals) do not offer sufficient protection against oxidative stress, oxidative damage or increase the lifespan. The key to the future success of decreasing oxidative-stress-induced damage should thus be the suppression of oxidative damage without disrupting the well-integrated antioxidant defense network.”14

We know that high levels of reactive oxygen species—the aforementioned free radicals—in relation to antioxidant defenses play an important role in causing disease and enhancing the aging process. We also know that perhaps the best way to get all the antioxidant defenses we need is eating more vegetables and fruits. Several studies show there are numerous ingredients in fruits that not only help the body maintain the right balance between oxidants and antioxidants, but also help the body to self-renew and therefore remain healthy. In general people who eat fruits and vegetables, which are rich sources of antioxidants, tend to have a lower risk of heart disease and some neurological diseases. There is also evidence from epidemiological studies that some types of vegetables and fruits in general protect against a number of cancers.

Despite this well-documented knowledge, many Americans neglect fruits and vegetables. One published source noted that “80 percent of American children and adolescents and 68 percent of adults do not eat five portions [of fruits and vegetables] a day.”15 This study also noted the inadequate dietary intake of vitamins and minerals on one hand, and a corresponding, excessive consumption of energy-rich, micronutrient-poor, and refined foods.

Instead, too many people try to find simple alternatives—namely, synthetic antioxidants, such as vitamins C or E supplements. As a result, in an awareness and desire to decrease oxidative stress, slow the aging process, and improve our health, we consume more and more antioxidants—usually the synthetic kind. One researcher notes that supplements represent an annual market of more than $7 billion in the United States alone, and more than $30 billion worldwide.16 But the more antioxidant supplements we consume, the more it becomes apparent that nothing can take the place of fruits and vegetables. Why? Because studies prove that fruits and vegetables contain numerous antioxidants, including a complex mixture of natural substances that—when combined—provide immense benefits to the body. Here is a short list of some of these natural substances:

• Green tea, resveratrol, polyphenols, and curcumin: very good inhibitors of cell proliferation.

• Grapefruits and garlic: contain powerful inhibitors of P450.

• Flavonoids and isoflavonoids (contained in green tea and other natural plants): powerful antagonists of estrogen and inhibitors of metastases (the ability of cancer or other diseases to quickly spread from one organ or part of the body to another), and inhibitors of angiogenesis.17

Contributing to health

Together, studies suggest that these ingredients may have important contributory influence to improved cardiovascular health and decreased incidence of cancer. Both have been observed in individuals who consume a higher volume of fruits and vegetables than those who follow a traditional, meat-heavy diet.

Two studies suggest that antioxidant consumption may not be working as well as we would like for a number of reasons.18 One reason is that the body has its own well-coordinated antioxidant defense system, which allows only a certain amount of antioxidants to reach its cells. Hence, only a limited number of antioxidants consumed actually reach the body. Second, recent studies have shown that the traditional view of oxidative species and aging as being proportionally related is no longer set in stone. Yes, sustained high levels of oxidative species in the body over a long period of time play a role in causing age-associated diseases. Still, there is no conclusive study that has shown that increased antioxidant levels in the body leads to longevity. In fact, some recent studies are showing that the body does need some levels of reactive oxidants to help it maintain homeostasis.

So, if consuming more antioxidants isn’t the answer, what is? First, understand that consuming more antioxidants is only aimed at suppressing high levels of oxidants in the body. It is not a preventive measure. Many people feverishly attempt to assuage an already bad situation; ironically in many cases the body already has a way of dealing with the problem. (For example, most reactive oxygen species are short-lived and are so reactive that they must react with something quickly enough to be converted to something else.) Instead, you should focus efforts on preventive measures that do not allow introduction of extra reactive oxygen species (ROS), which disrupt the body’s balance of oxidant/antioxidant levels. The body has its own well-coordinated antioxidant defense system.

To do that, it is necessary to understand how we become exposed to ROS. Reactive oxygen species are generated in two main ways:

1. One is exposure to environmental agents that produce ROS in the body (such as smoking, UV radiation, pollutants in food and environment.)

2. The second source—and the most important one—is from the body itself, from normal mitochondrial respiration.

As noted in a recent review article: “The cells of all present aerobic organisms produce the majority of chemical energy by consuming oxygen in their mitochondria. Mitochondria are thus the main site of intracellular oxygen consumption and the main source of ROS formation. Mitochondrial ROS sources are represented by the electron transport chain and the nitric oxide synthase reaction.”19 To simplify that for the average reader, in the process of breaking down food to generate energy, the body uses oxygen we take in through respiration. In the process of doing this, oxidant species (which we now know as ROS) are generated. It is like a machine that produces good products yet also leaks oil or gas in the process. The more efficient the machine, the fewer leaks—and hence, fewer problems.

For the body, this leakage is in the form of electrons, which then react with oxygen and oxides of nitrogen to produce these toxic ROS materials. As it turns out, the more food the body has to continuously process to produce energy, the more electron leaks that occur; thus, the more reactive oxygen species produced. This means that the best way to prevent formation of ROS is to help the mitochondria (the body’s machine that helps us carry out respiration and energy production) to function efficiently.

The role of fasting

More and more studies are showing that calorie reduction helps to reduce the level of oxidative damage in the body.20 But it is also somewhat surprising to researchers that this increased level of protection from oxidative damage during CR isn’t occurring through production of more antioxidants. Instead it is now becoming increasingly clear that CR provides antioxidant protection through increased efficiency in the function of mitochondria. What this means is that when you restrict energy intake, the body generally welcomes that opportunity to help mitochondrial cells become more efficient. Studies have shown that there is less leakage of electrons in mitochondrial cells during CR. And cells are much better protected from oxidative decay. Again, this is a hormetic response to the mild stress being introduced in the system by fasting.21

In fact, after reviewing all the current approaches being used in the developed world to attenuate the effect of oxidative stress, one researcher concludes: “To date, only caloric restriction (with adequate vitamin and mineral intake) has obtained scientifically based results for the prolonging of life. It could be concluded that prevention of mitochondrial ROS generation is a more efficient approach to decreasing oxidative stress (e.g., by CR) than quenching any already formed free radicals with antioxidants, since the lifetime of most aggressive free radicals is very short (e.g., .OH) and they react with the first compound encountered (e.g., protein, DNA).”22

In other words, fasting works!