Intermittent fasting, in some form, has been a part of religious observance since ancient times. The ancient Greek Oracle at Delphi is said to have undergone purification rites, including fasting, before delivering her prophesies. Even today, Christians, Jews, and Muslims include some form of fasting or constrained consumption in their religious observances. During the month of Ramadan, Muslims fast from dawn to sunset, eating only one meal before dawn and another to break the fast at sunset. Most Christian religions observe some form of fasting or abstinence—such as abstaining from animal products or “giving up” a favorite food—during the forty days of Lent. And Jews fast from sundown on the eve of Yom Kippur, the holiest day in the Jewish calendar, until the following sundown.
What is important to note about these various observances is that they create physical deprivation that is intended and believed to increase spiritual observance. They are not meant to be easy or “fun” holidays, and the only reason that people are willing and able to comply with their restrictions is that they last only for a limited period of time.
Limiting deprivation while increasing health and longevity is also the basis for the development of what I call the “up-day, down-day diet,” which became the basis for this book. I was initially inspired to develop the diet by reading about a mouse study done in 2003 by Mark Mattson and his colleagues at the National Institute on Aging. Mattson discovered that when mice specifically bred to gorge themselves were fed every other day, they ate enough on the alternate feeding days to compensate for the fasting days and, therefore, to maintain their weight. Despite their lack of weight loss, however, their markers for longevity and resistance to brain injury were more significantly improved than those of a second group of the same breed of mice who were fed freely every day or than the markers of a third group who were given only 60 percent of their normal calorie intake on a daily basis. Those in the last group not surprisingly lost weight, and while the logical supposition would be that the thin mice would also the healthiest, that was not what Mattson found.
I was stunned by the results of this study. If the same applied to humans, it would mean that by following an alternate-day calorie reduction we would be healthier even if we were fat, thereby defying the conventional wisdom that becoming thin is the only road to optimal health.
The only problem was that I knew I wouldn’t be able to eat nothing every other day for any significant length of time. I decided that the minimum number of calories I could tolerate on the restricted days would be 20 percent of my normal calorie requirement, and I believed for a variety of reasons that this level would be low enough to trigger the health benefits seen by Mattson in his mice. On the normal eating days I would follow my regular diet, which was not always the healthiest, and I wouldn’t restrict myself in any way except that I wouldn’t overeat.
Within two weeks of putting myself on this diet, I had lost a significant amount of weight and improved my triglyceride and fasting glucose levels. I also had relief from chronic sinusitis and improvement in my arthritis symptoms. It appeared that the diet was working as I had expected it would! I began to proclaim these remarkable effects to my friends, family, and patients, and I encouraged them to try it.
At the same time, I was told by a friend that Eric Ravussin, a well-known metabolic researcher at the Pennington Biomedical Research Center in Baton Rouge, was also interested in the concept of alternate-day restriction, so I called him and described my 20 percent/100 percent diet. He responded that he believed he could go all day without eating anything and told me that he and his colleagues were in the process of setting up a three-week study during which a group of staff members at Pennington would eat nothing every other day.
Ravussin and I met a few weeks later, in September of 2003, at which time I told him of my own experience with the 20 percent/100 percent plan, as well as the results seen by the two hundred or so people to whom I had by then introduced the idea. At the time I was also developing a protocol to study the health effects as well as the weight-loss benefits of my plan specifically in a group of asthma patients. Dr. Ravussin and I shared our opinions and then independently returned to the pursuit of our separate studies.
We didn’t correspond again until the following fall, at which point I wrote to tell him that the results of our Asthma Study (which you’ll be reading more about in Chapter 4) had been extremely positive in terms of both weight loss and improvement of the participants’ asthma symptoms. In fact, no other study before or since has shown such significant improvement from any treatment modality including medications. The cherry on the cake, so to speak, was that they also reported that their mood and energy levels increased throughout the study period and their hunger levels were no worse on the restricted day than on the day they ate freely.
Ravussin responded that he and his colleagues had also completed their study, which had been accepted for publication in the American Journal of Clinical Nutrition. At that time, he sent me a copy of the manuscript and wrote in an email on September 10, 2004:
As you can see from the manuscript we obtained a significant weight loss over a short time period (3 weeks), but unlike in your experience I think that the volunteers of this study did not experience a decrease in hunger over time. I guess maybe the 20% that you allow is providing enough volume to satisfy the people.
In his paper, which was published in January of 2005, Ravussin stated that the objective of the study “was to determine whether alternate-day fasting is a feasible method of dietary restriction in non-obese humans and whether it improves known biomarkers of longevity.” He went on to say that the participants did lose weight and that they showed improvement in biomarkers of health. But the article also states that, “hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.” (Emphasis added.)
In November of 2004, my coauthor, Dr. Donald Laub, and I presented the preliminary results of our study at a national meeting of the Calorie Restriction Society. Dr. Mark Mattson, who was also at the meeting, suggested that his laboratory perform assays not available anywhere except at a research center, on the frozen samples we had collected, and subsequently he collaborated with us on the first published article about the 20 percent/100 percent diet, which appeared in the peer-reviewed journal Free Radical Biology and Medicine.
Up to that time, the only study of alternate-day calorie restriction with good nutrition and without total fasting with human beings as its subjects had been conducted in Spain in 1956 by Dr. Eduardo Arias Vallejo. The participants were a group of healthy men and women over the age of sixty-five who were living in an old-age home in Madrid. Vallejo’s work had always been considered by later authors to consist of an overall calorie restriction of 35 percent, meaning that the amount the participants ate on their “normal” eating days did not fully compensate for those they lacked on the restricted days. However, as you’ll read in Chapter 3, when my colleagues and I revisited the data, we were able to show that (not unlike Mattson’s fat mice) Vallejo’s participants were eating more than normal on the days when they were allowed to eat freely. On restricted days, they were consuming roughly 50 percent of their normal calories, and on the unrestricted days they were eating about 150 percent. And yet, also like Mattson’s mice, their diet reduced their risk of serious illness and death by about one-half as compared to those in the control group. This validated my hypothesis that eating more calories than required on one day and fewer than required the next day in a repeating pattern over a period of time provides very significant health benefits even without weight loss.
In fact, at the time I was working on the first edition of this book, the wide range of health benefits to be gained from alternate-day dieting were not widely recognized by the general public even though they were becoming increasingly clear within the scientific community. For example, at about the same time Ravussin and I were completing our studies, Marc Hellerstein, an endocrinologist and researcher at the University of California at Berkeley, and his colleagues were finding that alternate-day calorie restriction could likely reduce the risk for cancer in mice. Donald Laub and I visited Dr. Hellerstein, who had already heard about our 20 percent/100 percent protocol from Eric Ravussin, and discussed our own ongoing findings.
In terms of studying the value for humans of alternate-day restriction without total fasting, I was something of a trailblazer. In August of 2003, I filed a provisional patent for my diet in order to establish a priority date for describing the 20 percent/100 percent pattern, the expected benefits, and the various permutations we have developed since that time. At that point, there had been no publications describing this pattern and virtually all the studies of intermittent fasting, with the exception of Ravussin’s, were being done on rodents, for at least a couple of good reasons. First of all, it’s much more difficult to get approval for a human study than it is for an animal study, and second, unless the humans are in a closely controlled environment, it’s hard to monitor their degree of compliance with the program. A mouse in a cage can eat only what and when you feed it; a human surrounded by supermarkets, restaurants, and street vendors has food available on a daily basis virtually around the clock.
Basically, to develop this diet, I was extrapolating from animal studies and using my understanding of human nature to determine what I thought would be a degree of restriction people would be willing to tolerate that would still provide them with the many health benefits proven in animals. What I arrived at is the diet in this book.
The first two weeks of the Alternate-Day Diet are the most restrictive, allowing only 20 percent of normal calorie intake in the form of a meal replacement shake on alternate days. At that level you will jump-start the health-promoting metabolic changes of the program and also lose significant weight, as did the participants in my Asthma Study. After that, you can start to eat “real food” on the restricted days and can increase your intake to as much as 50 percent of normal caloric needs. The reasons for this are twofold: I believe that almost everyone will find it tolerable, and it has been well established that this level of restriction will both provide the health benefits of alternate-day fasting and also allow for weight maintenance. It is the level that I have maintained for myself.
Of course, if your goal after two weeks is still to lose more weight, the fewer calories you eat on your restricting day, the more weight you’re likely to lose—if for no other reason than that you’ll be less likely to unthinkingly compensate or even overcompensate for the calorie deficit on the days you eat freely.
Ten years ago, I had to make assumptions and test their validity by applying them in the real world. Since the initial publication of The Alternate-Day Diet in 2008, however, other researchers have been validating and duplicating my findings. To date, there has been nothing to alter or invalidate any of the initial assumptions I made all those years ago, nor has there been any significant addition to the underlying science.
What has changed is that the public has now become very aware of the irrefutable benefits of intermittent calorie restriction, and various media have trumpeted the virtues of one version or another of the Alternate-Day Diet as if it were just born yesterday—not unlike the working actor who, after years in the trenches, is suddenly declared an overnight success. One version, for example, suggests restricting for two days and eating normally five days a week. While other forms of intermittent calorie restriction undoubtedly do have benefits, there is no doubt that the pattern I initially conceived remains the most effective.
In terms of validation, one recent study is particularly significant. David Sinclair and his colleagues at Harvard Medical School have now proved beyond any doubt Sinclair’s earlier assertion that resveratrol, a compound found in grapes and red wine, improves health and slows the aging process by activating a gene called SIRT1, which is also activated by alternate-day calorie restriction. In Chapter 5, you’ll be reading about the mechanism through which SIRT1 is activated and about Sinclair’s initial research. For the last several years that research has been criticized and repudiated in studies done by drug companies and in other laboratories. Dr. Sinclair has persisted, however, and has now demonstrated beyond question that not only does the activation of SIRT1 set in motion the amazing effects of alternate-day calorie restriction but also that resveratrol can produce the same results. In the history of human scientific research, there has been no other natural mechanism whose discovery is remotely comparable to the potential benefits of activating SIRT1.
Sinclair is now working on developing a synthetic form of resveratrol. If and when that happens, we may have a way to both prolong health and cure obesity simply by taking a pill. That day is still far in the future, however, and in the meantime the most effective and tolerable way for us food-loving humans to stay young and healthy is to follow the Alternate-Day Diet.