Fasting for Life: Medical Proof Fasting Reduces Risk of Heart Disease, Cancer, and Diabetes - Francis E. Umesiri (2016)

Part 1. The Science of Fasting

Chapter 3. SCIENTIFICALLY SPEAKING

Fasting is the greatest remedy—the physician within.

—PHILIPPUS PARACELSUS, MD (1493–1541)

ONE OF THE THREE FATHERS OF WESTERN MEDICINE1

FASTING REFERS TO THE TERM I INTRODUCED IN chapter 2: caloric restriction or intermittent fasting. For those involved in research on successful aging and dietary impact on health, fasting for improved health and longevity means controlled reduction of dietary energy intake of an individual (or animal, in animal model studies) by 20 to 40 percent of customary intake.

I have chosen to call this caloric reduction, or fasting for short. For the purpose of this discussion, and in accurate reflection of the decades of scientific research done in this area, CR means a reduction in energy intake without lowering the nutritional value the body needs.

Scientists generally classify calorie reduction in three broad categories:

1. Caloric restriction, the sustained 20 to 40 percent reduction just mentioned.

2. Alternate-day fasting, also known as intermittent fasting. As the name implies, this is a situation where one eats normally one day, and the next day either reduces intake or eliminates food altogether. This is an alternative to CR, since scientists believe that for many people, continuous sustained CR is stressful and may not prove feasible in the long run. Hence, they expect the process of alternating fasting with normal meals to be more sustainable.

3. Dietary restriction (DR). This is a situation where one or more macronutrient components (such as proteins or carbohydrates) are reduced without significant reduction in total caloric intake. An interesting result has emerged from DR research. While carbohydrate and lipid restriction do not offer any significant health or life span benefits in measurable health biomarkers, protein reduction increases life span in animal studies by as much as 20 percent.2 Specifically this benefit is believed to be mainly due to reduction in one protein-rich amino acid called methionine. While studies in this area are ongoing, what they should do is serve as a check on the wanton pursuit of every weight-loss craze that comes along. Long-term health and the delay of age-associated diseases are more important than short-lived weight control. Having the discipline to say no to food intermittently may be a much better approach in the long run.

Reduced energy intake

No matter what category or label scientists give it, the point is clear: reduction in calorie intake can literally save your life. The willingness and ability to adopt a lifestyle change that reduces your overall energy intake while maintaining adequate nutrient intake is key to delaying major diseases and ensuring a healthy, happy life.

For some people, being able to fast two or three times a week may work. I have friends who fast from morning until 6:00 p.m. every Monday, Wednesday, and Friday. You notice that this is similar to what anti-aging scientists call alternate-day fasting. You may begin by fasting only on Fridays. That is a start—an important one that could boost your health.

I started by fasting every Friday and Sunday for several years. Later I fasted every Sunday, plus three other days of complete fasting during that month. Today I basically do more of what researchers call calorie restriction. I have reduced my overall energy intake by about 30 percent. One week of every month I follow a restricted diet where I eat only fruits and vegetables (and sometimes nuts) until 7:00 p.m. and then enjoy a full meal for dinner.

Magic health pill?

Due to the challenge of self-discipline involved in following a calorie-restricted lifestyle, some scientists are also testing certain chemical compounds for their ability to extend life span or induce delays of age-associated diseases. Some of these—specifically a nutrient material called resveratrol and a drug called rapamycin—have been shown to mimic to some extent the health benefits of fasting.3 As a result, there are efforts now to develop some of these as alternatives to calorie reduction. After all, “Take a pill a day and live longer” appears to be a much more attractive promise than disciplining our behavior and reducing calorie intake.

However, as we have seen with every man-made drug ever invented, no drug can replace the behavioral component of health determination. Choosing a fasted lifestyle that works for you may require diligence, planning, and consistency. Ultimately, though, science has shown that a healthy lifestyle, including a fasted lifestyle, works over the long-term. The powerful benefits of hormesis and reduced oxidative stress that stem from calorie reduction will be difficult to replace with a pill. To be sure, the time may come when we need to take some of these pills to augment the health benefits, but they likely are not sufficient to replace calorie reduction—think obesity and associated diabetes, cancer, and cardiovascular complications. In the long run calorie reduction is the only method that makes sense, medically speaking.

Proof it works

After reviewing several scientific publications—both original research and review articles—I have reached a simple but profound conclusion: there is sufficient scientific evidence to take fasting seriously at a personal level. Given what we know today about the effects of fasting or calorie reduction on health and the aging process, it is surprising that many individuals remain unaware of this simple, free, and natural approach to improving health. Realizing the benefits of calorie restriction isn’t magic, but an idea grounded in science. Numerous scientific studies reveal this works on mice, monkeys, and human beings.

While scientists sometimes get lured away by the attractive, esoteric nature of scientific pursuits, it is so easy to forget that real people’s lives are at stake. So, let us leave scientists to continue their study and debate about whether CR can extend human life. While we don’t know that for certain, most credible studies show that CR improves most important biomarkers of health. They range from reduced adiposity (namely, obesity) to cardiovascular (heart health) biomarkers. In the rest of this chapter I will provide an overview of some of the many studies showing the benefits of calorie reduction on primates and on humans. (In later chapters I will discuss in detail the effects of fasting on reducing your risk for specific diseases, such as diabetes, cardiovascular disease, and Alzheimer’s disease.)

These results demand immediate action from everyone. They call us to not only take action, but also to help our loved ones do the same. In developed countries we are literally eating ourselves to an early grave. Most religions teach moderation and call for periods of fasting to train oneself to refrain from self-indulgence and connect with a larger perspective on life. However, my discussion of fasting is aimed at showing its benefits, whether you are a person of faith or no faith. For all the talk about the so-called dichotomy between religion and science, it seems that fasting presents one of those rare opportunities where religion and science seem to agree. Whether motivated by faith or by health, the important thing is that careful scientific studies now show that the age-old practice of fasting regularly does have a profound, long-range positive influence on our health.

As you review the following research summaries, I will hope it will inspire you to draw up a plan of action. Life is too short to eat your way to a premature death. There is more you are called to be and to do. You may not have all the time in the world to visit the gym every day; the kind of job you have may necessitate not being as physically active as you would like. (Still, you should strive to exercise regularly and be as physically active as possible for your circumstances.) However, no matter how intense your desk-bound work schedule or flexibility to work in visits to the gym or health club, you can eat less. Fasting intermittently while still getting adequate nourishment is something everyone can do.

Clinical studies on primates

In the July 2009 edition of Science a group of biomedical research scientists from the Wisconsin National Primate Research Center at the University of Wisconsin published the results of a twenty-year study aimed at investigating the effect of calorie reduction on rhesus monkeys.4 The significance of this report: for the first time it demonstrated the effect of prolonged fasting on primates, the closest species to humans. Even though scientists were convinced from extended research that caloric restriction does increase health span and life span in lower animals, they weren’t quite sure if this was the case with primates and humans. They wanted to test this hypothesis with primates.

After two decades of study involving monkeys kept at moderate CR, R. J. Colman and his coworkers learned that animals on CR lived longer than those on a regular diet—80 percent survived with a restricted regimen, compared to only 50 percent of those on a normal diet. Perhaps even more importantly they also discovered CR significantly lowered the incidence of age-associated diseases in those monkeys kept on a regular fasting diet, compared to those fed normally. Specifically the results showed that incidence of diabetes, cardiovascular disease, cancer, and brain atrophy were significantly reduced in animals that fasted. After careful examination of their data, here is one of these scientists’ conclusions: “Given the obvious parallels between rhesus monkey and human, the beneficial effects of CR may also occur in humans.”5 This prediction is supported by studies of people on long-term CR, who show fewer signs of cardiovascular aging. Later I will examine in detail the positive effects of fasting on diabetes, cancer, and heart attack incidence.

Human studies

The Okinawan connection

Okinawa is a Japanese island located in the Pacific Ocean roughly four hundred miles south of the rest of Japan. For many years scientists have observed that people living on this small, somewhat isolated island have the longest life expectancy of any group of people—both in Japan and the rest of the world. The Okinawan people also show the lowest risk for major age-associated diseases.6 For a long time this puzzled scientists, who wanted to know what was responsible for this remarkable phenomenon, especially among older generations.

In 2007 a team of biomedical researchers from the United States and Japan published the first-ever comprehensive, epidemiological studies on the Okinawan phenomenon.7 Among other things, they set out to confirm whether Okinawans indeed live longer, healthier lives than most other people groups around the world. They also set out to investigate the dietary regimen of older Okinawans to ascertain if caloric restriction played a role in their healthy aging and prolonged life span. Their results, published in the Annals of the New York Academy of Sciences, suggest that the answer to both questions is “yes.”

For example, they learned that the average diet of senior Okinawans (especially until the 1960s) averaged about 11 percent fewer calories than Japan’s national average. They also found out that the average diet of Okinawans consisted of vegetable-laden, low-calorie meals, such as sweet potatoes and green and yellow vegetables. Equally notable: how their natural diets were rich in vitamins C and E, folate, and vitamin B6 (as much as 289 percent, 190 percent, 295 percent, and 221 percent higher, respectively, than the daily recommended intake). In simple terms the Okinawan people live longer and healthier lives because—among other factors—they practice calorie restriction as part of normal life.

Human experiment

Dr. Roy Walford and a team of scientists from the Department of Pathology and Department of Surgery and Neurology at the University of California at Los Angeles (UCLA) School of Medicine published a number of reports on a two-year-experiment. As part of other goals of the Biosphere 2 project, they conducted tests on human beings to test the effects of calorie restriction on humans—perhaps the longest-running of such tests on people.8 The results were published in a number of reputable journals.

Four men and four women ranging in age from twenty-seven to sixty-seven lived in a closed ecological space called Biosphere 2, located near Tucson, Arizona. These eight people agreed to live together and grow virtually all their food inside this biospace for two years. Water and nearly all air and organic matter were recycled inside this living space for that span of time. Because they were constrained to this space and had to grow their own food, there was only so much available. Consequently, by default, they had to adapt to a restricted caloric intake for those two years. However, although their diet consisted of fewer calories, it was still rich in nutrients. At the end of the experiment the men showed an average weight loss of 18 percent, while the women sustained an average 10 percent decrease in weight.

In terms of health, these scientists observed the same kind of health benefits that CR has always conferred on rodents and other animals—improved health, slowed aging process, and lower incidence of disease. The scientists took blood samples from these humans before, during, and after those two years. Then they analyzed them for health biomarkers that are standard in the biomedical field, such as glucose, blood lipid, glycosylated hemoglobin, and insulin. The summary of these tests showed that fasting has the same beneficial effect on humans as observed previously on other vertebrates.

Controlled clinical study

It is possible to dismiss the Okinawa epidemiological study as merely observational. Certainly, while such studies provide a valuable insight to the role of caloric restriction in healthy aging, it is no doubt limited in the conclusions we can draw from that. This is why a group of medical researchers from reputable medical research centers across the country have since embarked on the first-ever comprehensive, randomized clinical trial to test the effects of caloric restriction on human health—and possibly on longevity.

The Comprehensive Assessment of the Long-Term Effects of Reducing Intake of Energy (CALERIE) is sponsored by the National Institutes of Health (NIH). This is currently the largest and most trusted study on the role of calorie restriction on human health. When the NIH commissioned this study, one of its major goals was to investigate whether fasting can actually prolong human life. Since almost all other studies on lower animals had shown that fasting tended to prolong life span, they wanted to determine if this could be true for humans.

Phase 1 of this study has concluded. This phase of the study showed that fasting does improve important biomarkers of health, some of which will be discussed shortly. In fact, spurred by promising results from phase 1 trials, this study has now progressed to phase 2.9 The second phase, currently in data collection and analysis stage, is aimed at validating and confirming earlier results, by extending fasting period and adopting uniform testing parameters across all clinical sites. While the question of whether fasting extends life span for humans remains rather inconclusive, these NIH-sponsored studies indicate that fasting does improve health span. These studies show that fasting reduces the risk for various life-threatening diseases, as well as improving biomarkers of health. Many of the scientists involved in the first phase of this study have published their results. Below is a brief summary of some of their findings as published in peer-reviewed journals, along with the results of other related studies. I am using the article headlines to provide you with a quick picture of their conclusions, even if you don’t read the full summary (feel free to check these articles for yourself).

• “Caloric restriction improves memory in elderly humans.”

Scientists from Germany set out to test if caloric restriction, which has improved cognition in lower animals, could be beneficial for cognitive function in elderly humans. The result of their study was published in the Proceedings of the National Academy of Science.10 Their conclusion? They found a significant increase in verbal memory scores for those with restricted calorie intake (a mean increase of 20 percent, P < 0.001). And this improved verbal memory ability correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein. This was most pronounced in participants who adhered closely to the restricted diet. This study effectively demonstrates the beneficial effects of scientific fasting on memory performance in healthy elderly people.

• “Caloric restriction alone and with exercise improves CVD in healthy non-obese individuals.”

This is the headline on the article published by Michael Lefevre and coworkers in 2009 as part of the CALERIE project.11 I will still discuss this article in more detail due to the significant findings it made regarding the effects of fasting on the heart. The purpose of their study was to determine the effect of fasting (caloric restriction) for six months with or without exercise on cardiovascular disease (CVD) risk factors. Based on that, they made a ten-year estimate of CVD risk in healthy non-obese men and women. After careful analysis of their data, their conclusion was that—considering positive changes in lipid and blood pressure observed in those who fasted—caloric restriction with or without exercise favorably reduces risk for CVD, even in already healthy non-obese individuals, especially if that fasting induces weight loss as well.

• “The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the CALERIE Trial of Human Caloric Restriction.”

Many believe that decreasing oxidative stress and increasing antioxidant defense may be one mechanism by which fasting increases health span. So a group of researchers at the Human Nutrition Research Center on Aging at Tufts University in Boston decided to study whether fasting (10 percent or 30 percent CR) helps to increase the human body’s antioxidative defense.12 The results of their six-month study appeared in 2011. Their conclusion was that short-term caloric restriction in moderately overweight people results in some positive biomarkers of antioxidant defense.

• “Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.”

The goal of this study was to investigate the effect of prolonged calorie restriction on biomarkers of longevity or markers of oxidative stress, or reduction on metabolic rate beyond that expected from reduced metabolic mass in humans (12.5 percent CR with about 12.5 percent increase in exercise also). Their conclusion was that two negative biomarkers of longevity—fasting insulin level and body temperature—were favorably reduced by prolonged caloric restriction, demonstrating the health benefits of fasting.13

• “Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans.”

Caloric restriction without malnutrition is known to lower free radical production by the mitochondria. In order to determine if CR lowers free radical production by the mitochondria in humans, a group of scientists (as part of the CALERIE team) undertook a clinical randomized trial involving healthy humans. Those who participated in CR, with or without exercise, had increased expression of genes encoding proteins involved in mitochondrial function. This study showed that there is an increase in muscle mitochondrial DNA and a corresponding decrease in both body oxygen consumption and DNA damage.14

What this means is that fasting improves mitochondrial function—the energy driving cells—in non-obese people. You may wonder about the relevance of improved mitochondrial function on good health and healthy aging. According to the mitochondrial theory of aging, free electrons are often produced as a by-product of aerobic respiration (within the mitochondria). The problem with these free electrons is that they tend to convert oxygen to highly reactive oxygen species (oxygen radicals). These are capable of reacting with and damaging proteins, lipids, and DNA molecules. If this continues over a long period of time, damage accumulates slowly, leading to early incidence of age-associated diseases, such as cancer and others.

• “Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, Beta-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects.”

The purpose of this study was to determine the effect of fasting on insulin sensitivity, fat cell size, etc., in healthy overweight humans.15 The scientific community accepts as fact that large adipocytes (fat cells) often lead to insulin resistance, through large deposits of fats in abdominal cavity and around the liver. What these scientists found was that fasting alone or with exercise reverses this trend. What does this mean to the layperson? Simply that fasting dissolves fat and improves your sensitivity to insulin, thereby reducing your chances of contracting type 2 diabetes and other medical conditions.