Is Intermittent Fasting as effective as Calorie Restriction ?

Real Life Extension: Caloric Restriction or Intermittent Fasting? Written by Tim Ferriss Topics: Physical Performance

Can you slow the sands of time? The research say yes… but what’s the best option?

In recent years, caloric restriction (CR) has been demonstrated to increase lab rat lifespans more than 20%. “Intermittent fasting” (IF), a much lesser-known and more lifestyle-friendly alternative, has shown results that even surpass CR in some respects.

Following up on the popularity of his last post on this blog (The Science of Fat-Loss: Why a Calorie Isn’t Always a Calorie), Dr. Eades examines these two options and his personal experiments with both.

If you want to live longer, this two-part article is an excellent place to start for avoiding common mistakes, pain and wasted effort.

Dr. Eades:

How would you like it if I told you there was a way to eat pretty much anything and everything you wanted to eat and still maintain your health? Or better yet, what if I told you that you could eat pretty much anything and everything you wanted and even improve your health? Would you be interested?…

There is a way to reduce blood sugar, improve insulin sensitivity, reduce blood pressure, increase HDL levels, get rid of diabetes, live a lot longer, and still be able to lose a little weight. All without giving up the foods you love. And without having to eat those foods in tiny amounts. Sounds like a late-night infomercial gimmick, but it isn’t.

When I wrote those words as the lede to an article about a year and a half ago, the idea of intermittent fasting was limited mainly to research scientists and faddists. But a number of studies had been published – primarily on rodents – showing that intermittent fasting led to a host of benefits that not even caloric restriction could claim.

And these weren’t studies published by no-name scientists laboring in backwater research departments. The lead author on many of these papers was Mark P. Mattson, Ph.D, the Chief of the Laboratory of Neurosciences and Chief of the Cellular and Molecular Neurosciences Section of the National Institute on Aging, a division of the National Institutes of Health. People were starting to take notice.

Before the work on intermittent fasting, the only real strategy for extending the lives of laboratory animals was caloric restriction (CR). If rats or mice or even primates had their calories restricted by 30-40 percent as compared to those fed ad libitum ["at pleasure" = as much as they want] they lived 20-30 percent longer. These studies are typically done by dividing genetically similar animals into two groups, then giving one group all the food it can eat in a day. Researchers measure the food consumed, then reduce it by 30-40 percent and give to the other group the next day. Each day this drill is repeated with the calorically restricted group getting a reduced amount of food compared to what the other group got the day before.

These CR verses ad libitum-fed studies almost uniformly demonstrate an increase in longevity in the CR animals. The CR animals not only live 30 percent or so longer, they don’t develop cancers, diabetes, heart disease, or obesity. And these animals have low blood sugar levels, low insulin levels, good insulin sensitivity, low blood pressure and are, in general, much healthier physically than their ad libitum fed counterparts. But not so psychologically.

As we saw in the Keys semi-starvation study, caloric restriction isn’t much fun for humans, and it apparently isn’t all that much fun for the animals undergoing it either. When rats live out their ratty lives calorically restricted in their cages, they seem to show signs of depression and irritability. Primates do as well. If primates don’t get enough cholesterol, they can actually become violent. But they do live longer. Even though CR has never been proven in humans, based on lab animal experience it does work. So, if you’re willing to put up with irritability, hostility and depression, it might be worth cutting your calories by 30 percent for the rest of your long, healthy miserable life.

But could there be a better way?

An enterprising scientist decided to try a little twist on the CR experiment. He divided the genetically-similar animals into two groups, fed one group all it wanted and measured the intake, then fed the other group all it wanted – except every other day instead of daily. When the intake of the group fed every other day was measured, it turned out that that group – the intermittently fasted group – ate just about double on the eat days, so that overall both groups consumed the same amount of food. Animals in the one group at X amount of food per day while the animals in the other group ate 2X amount of food every other day. So both groups ate the same number of calories but the commonality ended there.

The intermittently fasted group of animals despite consuming the same number of calories as the ad libitum fed group enjoyed all the health and longevity benefits of calorically restricted animals. In essence, they got their cake and ate it, too. They got all the benefits of CR plus some without the CR.

Intermittent fasting (IF) reduced oxidative stress, made the animals more resistant to acute stress in general, reduced blood pressure, reduced blood sugar, improved insulin sensitivity, reduced the incidence of cancer, diabetes, and heart disease, and improved cognitive ability. But IF did even more. Animals that were intermittently fasted greatly increased the amount of brain-derived neurotrophic factor (BDNF) relative to CR animals. CR animals don’t produce much more BDNF than do ad libitum fed animals.

BDNF, as its name implies, is a substance that increases the growth of new nerve cells in the brain, but it does much more than that. BDNF is neuroprotective against stress and toxic insults to the brain and is somehow–no one yet knows how, exactly–involved in the insulin sensitivity/glucose regulating mechanism. Infusing BDNF into animals increases their insulin sensitivity and makes them lose weight. Humans with greater levels of BDNF have lower levels of depression. BDNF given to depressed humans reduces their depression. And increased levels of BDNF improve cognitive ability. In short, you want as much BDNF as you can get, and with IF you – if you’re a lab animal at least – can get a lot.

As the animal study data poured in, a few researchers began tentatively studying human subjects. A few studies appeared in the literature, and all showed positive benefits to humans who intermittently fasted. In none of the studies did subjects go completely without food for a day – most had one meal per day or ate ad libitum one day and reduced consumption markedly the next.

Even some academic physicians (including Don Laub, my old mentor when I did a plastic surgery rotation at Stanford) put themselves on a modified version of an IF and wrote about it the the journal Medical Hypothesis. Since May 2003, these folks have been on a version of the IF in which they consume about 20-50 percent of their estimated daily energy requirements on the fast day and eat whatever they want on the non-fast days.

Since starting their regimen they have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette’s, Meniere’s) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes.

It all sounded good. But before I try anything out of the ordinary, and certainly before I suggest it to any of my own patients or readers, I view the idea through the lens of natural selection. In other words, I ask myself if the regimen in question would have been congruent with our Paleolithic heritage. If so, I move forward. If not, I take a long, hard look at all the biochemistry, physiology and pharmacology involved before I make any sort of recommendation.

In viewing IF through the lens of natural selection I came to the conclusion that IF was probably the way Paleolithic man ate. We modern humans have become acculturated to the three square meals per day regimen. Animals in the wild, particularly carnivorous animals, don’t eat thrice per day; they eat when they make a kill. I would imagine that Paleolithic man did the same. If I had to make an intelligent guess, I would say that Paleolithic man probably ate once per day or maybe even twice every three days. In data gathered from humans still living in non-Westernized cultures in the last century, it appears that they would gorge after a kill and sleep and lay around doing not much of anything for the next day or so. When these folks got hungry, they went out and hunted and started the cycle again.

If you accept, as I do, that the Paleolithic diet is the optimal diet for modern man due to our evolved physiologies, then you should probably also buy into the idea that a meal timing schedule more like that of Paleolithic man would provide benefit as well.

With this in mind, I recruited my wife into the process and we went on an intermittent fast . It wasn’t all that difficult, but I can tell you that the non-eating days were long. And the eating days were spent eating and dreading the non-eating day soon to follow.

After a few weeks, it dawned on me that we weren’t really following the same IF that all the lab animals were. The lab animals got food for 24 hours then went without for 24 hours. We, on the other hand, got food for about 16 hours (the waking hours) then went without for about 32 hours (8 hours sleeping, 16 hours awake and the next 8 hours sleeping). We decided to modify our fasting strategy…

We fooled around with a number of different eat-fast-eat regimens and came up with something that works pretty well. We set up our cutoff time as 6 PM. On the day we started, we ate until 6 PM, then fasted until 6 PM the next day. On the next day we ate supper right after 6 PM and ate breakfast and lunch (and a few snacks) the next day until 6 PM when we started fasting again.

The advantage of this regimen is that we were able to eat every day. One day we would get supper–the next day we would get breakfast and lunch. On no days would we go entirely without food. This schedule worked the best for us.

The big surprise in the whole process was how easy the whole thing was. We realized that intermittent fasting and dieting had opposing attributes and disadvantages. Diets are easy in the contemplation, difficult in the execution. IF is just the opposite – it’s difficult in the contemplation but easy in the execution. Here’s what I mean.

Most of us have contemplated going on a diet. When we find a diet that appeals to us, it seems as if it will be a breeze to do. But when we get into the nitty gritty of it, it becomes tough. For example, I stay on a low-carb diet almost all the time. But if I think about going on a low-fat diet, it looks easy. I think about bagels, whole wheat bread and jelly, mashed potatoes, corn, bananas by the dozen, etc. – all of which sound appealing. But were I to embark on such a low-fat diet I would soon tire of it and wish I could have meat and eggs. So a diet is easy in contemplation, but not so easy in the long-term execution.

Intermittent fasting is hard in the contemplation, of that there is no doubt. “You go without food for 24 hours?” people would ask, incredulously when we explained what we were doing. “I could never do that.” But once started, it’s a snap. No worries about what and where to eat for one or two out of the three meals per day. It’s a great liberation. Your food expenditures plummet. And you’re not particularly hungry. You’re either eating until 6 PM or you’ve got a meal waiting at 6 PM, so though it’s tough to overcome the idea of going without food, once you begin the regimen, nothing could be easier.

My wife and I fooled around with our regimen for a few weeks here and there just to prove to ourselves that we could live with it and that it was a doable strategy for just about anyone. We ultimately drifted back to our normal low-carb existence just because it seemed to work better with our schedules. It seemed that we always ended up with some kind of dinner engagement on the nights we were supposed to be fasting, necessitating a change in our fasting schedule.

Over the period that we followed the various IF regimens we lost a couple of pounds (we really didn’t have much weight to lose, nor did we have health problems that needed fixing) because, unlike the rodents, we couldn’t eat twice as much during the eating days as we would have eaten were we not fasting. We didn’t check any lab work to see if any values had changed. We weren’t doing a hard-core study; we were simply evaluating IF as a practical means for humans to use to improve their health.

I then wrote a blog post about IF that became the most commented post on my blog. It seems that the idea of IF had struck a chord with a lot of people, many of whom took up the torch and started IFing.

People started commenting that they were doing great on the IF. Some were losing weight, but others weren’t. Or if they were, they were losing much less than they thought they should be losing given the caloric reduction. As I mentioned, it seems that humans have a difficult time doubling up on calories on eat days, so in most humans an IF is also a reduced-calorie diet. And humans, it appeared, weren’t losing as much as their reduction in calories would predict. Reports started popping up on low-carb bulletin boards describing how blood sugar levels had gone up in people IFing and how some people had seen their blood pressure go up.

Like many of my readers, the research community had jumped on the IF bandwagon as well. And, in a similar fashion, the results were not all positive. Papers appeared showing that subjects IFing, or even regularly skipping a couple of meals per day, were developing insulin resistance, impaired glucose tolerance, elevated blood pressure, and decreased thermogenesis. Even Mark Mattson published a couple of human studies, including a randomized crossover designed experiment that showing the above disorders in women who ate the same number of calories in one meal per day as opposed to three meals per day.

I must hasten to add that the loss of insulin sensitivity, the impaired glucose tolerance and high blood pressure did not reach major levels. But they were significantly more pronounced than the same measures in the same subjects consuming the same number of calories divided into three meals instead of just one. The finding that troubles me the most, however, is the decrease in thermogenesis found under iso-caloric conditions. Said decrease in thermogenesis can only be worse in a true, real-world, intermittent fast in which the calories are typically lower than usual.

The decreased thermogenesis explains why the IF doesn’t work particularly well as a weight-loss regimen even though in most cases it is a reduced calorie diet [see the "the real science of fat-loss: why a calorie isn't always a calorie" post for more on this phenomenon]. The subjects in these studies who consumed only one meal per day had reduced thermogenesis even while consuming the same number of calories that they did when eating three times per day. Imagine the reduction in thermogenesis if the calories were reduced as well as they are in most IF regimens.

The energy balance equation states that the change in weight equals calories in minus calories out.

Δ Wt = kcal in – kcal out

Many people think that the items on the right side of that equation are independent variables. In other words, if kcal in decreases weight will be lost because kcal out stays the same. But it doesn’t work that way because those terms aren’t independent variables – they are dependent variables. If kcal in goes down, often kcal out goes down as well to compensate. If people increase kcal out by exercising, they end up increasing kcal in because they eat more. It’s called working up an appetite. And since exercise doesn’t burn a whole lot more calories than simply sitting on one’s butt, it doesn’t take a lot of food to compensate. This effect is called adaptive thermogenesis. (Here is a full text article that goes into depth regarding the mechanisms involved.)

IF fasting, by significantly decreasing thermogenesis, decreases kcal out because our thermogenesis is what burns a whole lot of our calories. If the kcal in are decreased by the IF and the kcal out are decreased by the diminished thermogenesis brought about by the IF, it’s no wonder the IF doesn’t result in a lot of weight loss for most people.

The one question that remains unanswered is whether or not the intermittent fast followed in a low-carbohydrate way will lead to these same problems. To me, that point is kind of moot. Why? Because I looked at the IF as a strategy that allowed me to eat a lot of high carb foods that I would normally avoid and not pay the health consequences for it. If I’m going to limit myself to low-carb foods, why go on the IF? I can get the same results just following a regular, whole-food, low-carb diet without having to eat only every other day.

It’s looking like the intermittent fast is another of those ideas in science that looks good in animal studies then not so good in human studies, proving once again that rats and mice aren’t simply furry little humans. And it appears – for humans, at least – that the intermittent fast is indeed beginning to look like the reality of a late-night gimmicky infomercial: long on promises, short on delivery. I suspect that it is also a cautionary tale about the applicability of caloric restriction studies to humans.

Sorry to be the bearer of bad news, but that’s the way science sometimes works. Lab results and reality are often two different animals.

Guest writer biography: Dr. Michael Eades is one of the best-known bariatric (obesity treatment) doctors in the US and was the first doctor to introduce insulin resistance to the mainstream via his books, including the national best seller Protein Power.…