At first blush, when I heard about the fad of intermittent fasting as a way to lose weight, improve one’s health, and prolong life—the latter being a major concern for Silicon Valley mega-billionaires—I was skeptical. When it comes to weight loss, isn’t it calories in minus calories out that determines your net gain or loss? Elementary, my dear Watson, the second law of thermodynamics is totally immutable and completely resistant to attempts to apply “alternative facts”. And yet, hope springs eternal.
Attempts to find chinks in the armor of the laws of physics (perpetual motion machines), chemistry (make gold out of lead, or mercury, or…you name it), biochemistry/physiology (dietary fads), have been an integral part of human history since antiquity. This is not to diminish the great benefits these attempts have brought to humanity. They have, in fact, served to confirm, again and again, the validity of the laws of nature discovered by science.
The theory behind intermittent dieting
A common argument used by proponents of intermittent diet is that “it makes evolutionary sense.” It roughly goes along these lines: Since the genus Homo evolved over 2 million years ago, we were largely hunters-gatherers. When the band had a successful hunt, it meant a day or two of feasting on a calorie-rich meat diet. But when the feast was over, it meant surviving on calorie-poor wild cereals, roots, and berries. That, in turn, led over the years to biochemical/metabolic adaptation, through the process of natural selection, that maximized our survival capacity in such uncertain food supply circumstances.
Let’s dissect the argument. What are the adaptations the pro-fasters are talking about? Our carbohydrate, fat, and protein metabolic pathways are the same as those of chimps, gorillas, and bonobos, our closest relatives who did not have to adapt to intermittent disruptions of calorie supply. There is an important adaptation that impacts results of fasting, however. Fasting lowers our metabolic rate precisely because our metabolism is geared to conserve energy related to an uneven supply of calories. The problem is that actually works in opposite direction of the desire of intermittent dieters to burn more calories.
To invoke the hunter-gatherer paradigm is a bit problematic on its face. Since humans invented agriculture about 10,000 years ago, the supply of calories became much more predictable and plentiful. We haven’t lost our metabolic adaptation of conservation of energy, but we got progressively more plump (think of Rubens’ women), and recently even obese (picture any street in the industrialized world). Physiologically, it means that our metabolic set point is probably higher than in the good old days of hunting-gathering, and the hormones geared to maintain homeostasis (physiological stability, or maintenance of the status quo) will resist mightily any change in the metabolic set point, which anyone who ever dieted knows too well.
There is another complication in comparisons with hunter-gatherer metabolism theory. It is amply documented that gut flora plays a crucial role in the metabolic fate of nutrients. Here is the rub: Obesity causes a radical change in the gut flora. And the new flora actually promotes further obesity. Hunters-gatherers probably did not have this problem.
Now let’s look at the scientific evidence
An interesting angle of looking at the problem of intermittent feeding/fasting was employed by Panda and his colleagues, of the Salk Institute. Most of our bodily functions throughout the day are controlled by a master pacemaker situated in a brain structure called the SCN (for supra chiasmatic nucleus). This pacemaker gets neural signals from the eyes and is, thus, controlled primarily by the light/dark periods. But in a similar arrangement to our Federal system, every organ has its own sub-pacemaker, designed to serve the specific requirements of that organ.
In the liver, Panda et al. found that when they withheld food from mice for 24 hours, 90% of the genes that are under the circadian regulation of the clock ceased to function. Not surprisingly, since one would expect the major metabolic organ to be controlled by the supply of food. On the other hand, let mice eat a high-fat diet 24 hours a day and all the genes under the control of the liver circadian pacemaker get activated around the clock. Unsurprisingly, the mice became obese. This explains the mechanism of feeding/fasting on the molecular level. But to definitively settle the question of the benefits obtained by intermittent fasting, there is no substitute for well-designed studies in humans.
The human experience
One of the most consistent advocates of intermittent fasting for weight loss is nutrition researcher Krysta Varady, of the University of Illinois, Chicago. She published widely on the subject and summarized her research in a popular book, The Every-Other-Day Diet, with the tagline: 4 weeks, 12 pounds, 2 sizes. It also includes recipes to accomplish the goal. But to Dr. Varady’s credit, she also ran a critical experiment: A well-controlled study in humans. In a paper published recently in JAMA, her group reported of a study of 100 obese participants (86 women, 14 men) who were randomized to 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating “feast days”), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.
So, in addition to being randomized and well-controlled, it lasted 1 year, unlike those short-term hit-and-run studies. And the results?
Here are the authors’ conclusions:
“Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs. daily calorie restriction.”
In an interview for The Scientist magazine, Varady says that intermittent diets work not because of some speculative evolutionary adaptation or complicated genetic/molecular mechanism, but “it’s just tricking your mind and body into eating less, and because you’re losing weight, you’re getting all the metabolic benefits.” In other words, better compliance through mind tricks, although her JAMA study actually said that it “did not produce superior adherence”.
No matter, there is a lot to be admired here. Here is a scientist who devoted her career to proving the benefits of intermittent diets, but had the courage to run the definitive experiment, and the intellectual integrity to state the facts, however inconvenient. So much of it is lacking in our political life nowadays.
You make us proud Professor Varady. Bravo!